Federal Practitioner

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

Ahead of its official release on March 18, the new Diagnostic and Statistical Manual of Mental Disorders, which is in the form of a textbook, is already drawing some criticism.

The American Psychiatric Association’s DSM-5-TR (Text Revision) which is not a full revision, only includes one new condition, prolonged grief disorder.

It also includes symptom codes for suicidal behavior and nonsuicidal self-injury, clarifying modifications to criteria sets for more than 70 disorders, including autism spectrum disorder; changes in terminology for gender dysphoria; and a comprehensive review of the impact of racism and discrimination on the diagnosis and manifestations of mental disorders.

The Text Revision is a compilation of iterative changes that have been made online on a rolling basis since the DSM-5 was first published in 2013.

“The goal of the Text Revision was to allow a thorough revision of the text, not the criteria,” Paul Appelbaum, MD, chair of the APA’s DSM steering committee, told this news organization.

For the Text Revision, some 200 experts across a variety of APA working groups recommended changes to the text based on a comprehensive literature review, said Appelbaum, who is the Elizabeth K. Dollard Professor of Psychiatry, Medicine and Law, and director of the division of law, ethics and psychiatry at Columbia University, New York.

However, there’s not a lot that’s new, in part, because there have been few therapeutic advances.
 

Money maker?

Allen Frances, MD, chair of the DSM-4 task force and professor and chair emeritus of psychiatry at Duke University, Durham, N.C., said the APA is publishing the Text Revision “just to make money. They’re very anxious to do anything that will increase sales and having a revision forces some people, especially in institutions, to buy the book, even though it may not have anything substantive to add to the original.”

Dr. Frances told this news organization that when the APA published the first DSM in the late 1970s, “it became an instantaneous best-seller, to everyone’s surprise.”

The APA would not comment on how many of the $170 (list price) volumes it sells or how much those sales contribute to its budget.

Dr. Appelbaum acknowledged, “at any point in time, the canonical version is the online version.” However, it’s clear from DSM-5 sales “that many people still value having a hard copy of the DSM available to them.”  
 

Prolonged grief: Timely or overkill?

Persistent complex bereavement disorder (PCBD) was listed as a “condition for further study” in DSM-5. After a 2019 workshop aimed at getting consensus for diagnosis criteria, the APA board approved the new prolonged grief disorder in October 2020, and the APA assembly approved the new disorder in November 2020. 

Given the 950,000 deaths from COVID-19 over the past 2 years, inclusion of prolonged grief disorder in the DSM-5 may arrive at just the right time.

The diagnostic criteria for PCBD include:

• The development of a persistent grief response (longer than a year for adults and 6 months for children and adolescents) characterized by one or both of the following symptoms, which have been present most days to a clinically significant degree, and have occurred nearly every day for at least the last month: intense yearning/longing for the deceased person; preoccupation with thoughts or memories of the deceased person.
• Since the death, at least three symptoms present most days to a clinically significant degree, and occurring nearly every day for at least the last month, including identity disruption, marked sense of disbelief about the death, avoidance of reminders that the person is dead, intense emotional pain related to the death, difficulty reintegrating into one’s relationships and activities after the death, emotional numbness, feeling that life is meaningless as a result of the death, and intense loneliness as a result of the death.
• The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
• The duration and severity of the bereavement reaction clearly exceed expected social, cultural, or religious norms for the individual’s culture and context.
• The symptoms are not better explained by another mental disorder, such as major depressive disorder (MDD) or PTSD, and are not attributable to the physiological effects of a substance or another medical condition.

Dr. Frances said he believes creating a new diagnosis pathologizes grief. In DSM-3 and DSM-4, an exception was made under the diagnosis of MDD for individuals who had recently lost a loved one. “We wanted to have at least an opportunity for people to grieve without being stigmatized, mislabeled, and overtreated with medication.”

DSM-5 removed the bereavement exclusion. After 2 weeks, people who are grieving and have particular symptoms could receive a diagnosis of MDD, said Dr. Frances. He believes the exclusion should have been broadened to cover anyone experiencing a major loss – such as a job loss or divorce. If someone is having prolonged symptoms that interfere with functioning, they should get an MDD diagnosis.

The new disorder “doesn’t solve anything, it just adds to the confusion and stigmatization, and it’s part of a kind of creeping medical imperialization of everyday life, where everything has to have a mental disorder label,” Dr. Frances said.

However, Dr. Appelbaum countered that “the criteria for prolonged grief disorder are constructed in such a way as to make every effort to exclude people who are going through a normal grieving process.”

“Part of the purpose of the data analyses was to ensure the criteria that were adopted would, in fact, effectively distinguish between what anybody goes through, say when someone close to you dies, and this unusual prolonged grieving process without end that affects a much smaller number of people but which really can be crippling for them,” he added.

The Text Revision adds new symptom codes for suicidal behavior and nonsuicidal self-injury, which appear in the chapter, “Other Conditions That May Be a Focus of Clinical Attention,” said Dr. Appelbaum.

“Both suicidal behavior and nonsuicidal self-injury seem pretty persuasively to fall into that category – something a clinician would want to know about, pay attention to, and factor into treatment planning, although they are behaviors that cross many diagnostic categories,” he added.

Codes also provide a systematic way of ascertaining the incidence and prevalence of such behaviors, said Dr. Appelbaum.
 

Changes to gender terminology

The Text Revision also tweaks some terminology with respect to transgender individuals. The term “desired gender” is now “experienced gender”, the term “cross-sex medical procedure” is now “gender-affirming medical procedure”, and the terms “natal male/natal female” are now “individual assigned male/female at birth”.

Dr. Frances said that the existence of gender dysphoria as a diagnosis has been a matter of controversy ever since it was first included.

“The transgender community has had mixed feelings on whether there should be anything at all in the manual,” he said. On one hand is the argument that gender dysphoria should be removed because it’s not really a psychiatric issue.

“We seriously considered eliminating it altogether in DSM-4,” said Dr. Frances.

However, an argument in favor of keeping it was that if the diagnosis was removed, it would mean that people could not receive treatment. “There’s no right argument for this dilemma,” he said.

Dr. Frances, who has been a frequent critic of DSM-5, said he believes the manual continues to miss opportunities to tighten criteria for many diagnoses, including ADHD and autism spectrum disorder.

“There’s a consistent pattern of taking behaviors and symptoms of behaviors that are on the border with normality and expanding the definition of mental disorder and reducing the realm of normality,” he said.

That has consequences, Dr. Frances added. “When someone gets a diagnosis that they need to get, it’s the beginning of a much better future. When someone gets a diagnosis that’s a mislabel that they don’t need, it has all harms and no benefits. It’s stigmatizing, leads to too much treatment, the wrong treatment, and it’s much more harmful than helpful.”

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

Ahead of its official release on March 18, the new Diagnostic and Statistical Manual of Mental Disorders, which is in the form of a textbook, is already drawing some criticism.

The American Psychiatric Association’s DSM-5-TR (Text Revision) which is not a full revision, only includes one new condition, prolonged grief disorder.

It also includes symptom codes for suicidal behavior and nonsuicidal self-injury, clarifying modifications to criteria sets for more than 70 disorders, including autism spectrum disorder; changes in terminology for gender dysphoria; and a comprehensive review of the impact of racism and discrimination on the diagnosis and manifestations of mental disorders.

The Text Revision is a compilation of iterative changes that have been made online on a rolling basis since the DSM-5 was first published in 2013.

“The goal of the Text Revision was to allow a thorough revision of the text, not the criteria,” Paul Appelbaum, MD, chair of the APA’s DSM steering committee, told this news organization.

For the Text Revision, some 200 experts across a variety of APA working groups recommended changes to the text based on a comprehensive literature review, said Appelbaum, who is the Elizabeth K. Dollard Professor of Psychiatry, Medicine and Law, and director of the division of law, ethics and psychiatry at Columbia University, New York.

However, there’s not a lot that’s new, in part, because there have been few therapeutic advances.
 

Money maker?

Allen Frances, MD, chair of the DSM-4 task force and professor and chair emeritus of psychiatry at Duke University, Durham, N.C., said the APA is publishing the Text Revision “just to make money. They’re very anxious to do anything that will increase sales and having a revision forces some people, especially in institutions, to buy the book, even though it may not have anything substantive to add to the original.”

Dr. Frances told this news organization that when the APA published the first DSM in the late 1970s, “it became an instantaneous best-seller, to everyone’s surprise.”

The APA would not comment on how many of the $170 (list price) volumes it sells or how much those sales contribute to its budget.

Dr. Appelbaum acknowledged, “at any point in time, the canonical version is the online version.” However, it’s clear from DSM-5 sales “that many people still value having a hard copy of the DSM available to them.”  
 

Prolonged grief: Timely or overkill?

Persistent complex bereavement disorder (PCBD) was listed as a “condition for further study” in DSM-5. After a 2019 workshop aimed at getting consensus for diagnosis criteria, the APA board approved the new prolonged grief disorder in October 2020, and the APA assembly approved the new disorder in November 2020. 

Given the 950,000 deaths from COVID-19 over the past 2 years, inclusion of prolonged grief disorder in the DSM-5 may arrive at just the right time.

The diagnostic criteria for PCBD include:

• The development of a persistent grief response (longer than a year for adults and 6 months for children and adolescents) characterized by one or both of the following symptoms, which have been present most days to a clinically significant degree, and have occurred nearly every day for at least the last month: intense yearning/longing for the deceased person; preoccupation with thoughts or memories of the deceased person.
• Since the death, at least three symptoms present most days to a clinically significant degree, and occurring nearly every day for at least the last month, including identity disruption, marked sense of disbelief about the death, avoidance of reminders that the person is dead, intense emotional pain related to the death, difficulty reintegrating into one’s relationships and activities after the death, emotional numbness, feeling that life is meaningless as a result of the death, and intense loneliness as a result of the death.
• The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
• The duration and severity of the bereavement reaction clearly exceed expected social, cultural, or religious norms for the individual’s culture and context.
• The symptoms are not better explained by another mental disorder, such as major depressive disorder (MDD) or PTSD, and are not attributable to the physiological effects of a substance or another medical condition.

Dr. Frances said he believes creating a new diagnosis pathologizes grief. In DSM-3 and DSM-4, an exception was made under the diagnosis of MDD for individuals who had recently lost a loved one. “We wanted to have at least an opportunity for people to grieve without being stigmatized, mislabeled, and overtreated with medication.”

DSM-5 removed the bereavement exclusion. After 2 weeks, people who are grieving and have particular symptoms could receive a diagnosis of MDD, said Dr. Frances. He believes the exclusion should have been broadened to cover anyone experiencing a major loss – such as a job loss or divorce. If someone is having prolonged symptoms that interfere with functioning, they should get an MDD diagnosis.

The new disorder “doesn’t solve anything, it just adds to the confusion and stigmatization, and it’s part of a kind of creeping medical imperialization of everyday life, where everything has to have a mental disorder label,” Dr. Frances said.

However, Dr. Appelbaum countered that “the criteria for prolonged grief disorder are constructed in such a way as to make every effort to exclude people who are going through a normal grieving process.”

“Part of the purpose of the data analyses was to ensure the criteria that were adopted would, in fact, effectively distinguish between what anybody goes through, say when someone close to you dies, and this unusual prolonged grieving process without end that affects a much smaller number of people but which really can be crippling for them,” he added.

The Text Revision adds new symptom codes for suicidal behavior and nonsuicidal self-injury, which appear in the chapter, “Other Conditions That May Be a Focus of Clinical Attention,” said Dr. Appelbaum.

“Both suicidal behavior and nonsuicidal self-injury seem pretty persuasively to fall into that category – something a clinician would want to know about, pay attention to, and factor into treatment planning, although they are behaviors that cross many diagnostic categories,” he added.

Codes also provide a systematic way of ascertaining the incidence and prevalence of such behaviors, said Dr. Appelbaum.
 

Changes to gender terminology

The Text Revision also tweaks some terminology with respect to transgender individuals. The term “desired gender” is now “experienced gender”, the term “cross-sex medical procedure” is now “gender-affirming medical procedure”, and the terms “natal male/natal female” are now “individual assigned male/female at birth”.

Dr. Frances said that the existence of gender dysphoria as a diagnosis has been a matter of controversy ever since it was first included.

“The transgender community has had mixed feelings on whether there should be anything at all in the manual,” he said. On one hand is the argument that gender dysphoria should be removed because it’s not really a psychiatric issue.

“We seriously considered eliminating it altogether in DSM-4,” said Dr. Frances.

However, an argument in favor of keeping it was that if the diagnosis was removed, it would mean that people could not receive treatment. “There’s no right argument for this dilemma,” he said.

Dr. Frances, who has been a frequent critic of DSM-5, said he believes the manual continues to miss opportunities to tighten criteria for many diagnoses, including ADHD and autism spectrum disorder.

“There’s a consistent pattern of taking behaviors and symptoms of behaviors that are on the border with normality and expanding the definition of mental disorder and reducing the realm of normality,” he said.

That has consequences, Dr. Frances added. “When someone gets a diagnosis that they need to get, it’s the beginning of a much better future. When someone gets a diagnosis that’s a mislabel that they don’t need, it has all harms and no benefits. It’s stigmatizing, leads to too much treatment, the wrong treatment, and it’s much more harmful than helpful.”

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

Ahead of its official release on March 18, the new Diagnostic and Statistical Manual of Mental Disorders, which is in the form of a textbook, is already drawing some criticism.

The American Psychiatric Association’s DSM-5-TR (Text Revision) which is not a full revision, only includes one new condition, prolonged grief disorder.

It also includes symptom codes for suicidal behavior and nonsuicidal self-injury, clarifying modifications to criteria sets for more than 70 disorders, including autism spectrum disorder; changes in terminology for gender dysphoria; and a comprehensive review of the impact of racism and discrimination on the diagnosis and manifestations of mental disorders.

The Text Revision is a compilation of iterative changes that have been made online on a rolling basis since the DSM-5 was first published in 2013.

“The goal of the Text Revision was to allow a thorough revision of the text, not the criteria,” Paul Appelbaum, MD, chair of the APA’s DSM steering committee, told this news organization.

For the Text Revision, some 200 experts across a variety of APA working groups recommended changes to the text based on a comprehensive literature review, said Appelbaum, who is the Elizabeth K. Dollard Professor of Psychiatry, Medicine and Law, and director of the division of law, ethics and psychiatry at Columbia University, New York.

However, there’s not a lot that’s new, in part, because there have been few therapeutic advances.
 

Money maker?

Allen Frances, MD, chair of the DSM-4 task force and professor and chair emeritus of psychiatry at Duke University, Durham, N.C., said the APA is publishing the Text Revision “just to make money. They’re very anxious to do anything that will increase sales and having a revision forces some people, especially in institutions, to buy the book, even though it may not have anything substantive to add to the original.”

Dr. Frances told this news organization that when the APA published the first DSM in the late 1970s, “it became an instantaneous best-seller, to everyone’s surprise.”

The APA would not comment on how many of the $170 (list price) volumes it sells or how much those sales contribute to its budget.

Dr. Appelbaum acknowledged, “at any point in time, the canonical version is the online version.” However, it’s clear from DSM-5 sales “that many people still value having a hard copy of the DSM available to them.”  
 

Prolonged grief: Timely or overkill?

Persistent complex bereavement disorder (PCBD) was listed as a “condition for further study” in DSM-5. After a 2019 workshop aimed at getting consensus for diagnosis criteria, the APA board approved the new prolonged grief disorder in October 2020, and the APA assembly approved the new disorder in November 2020. 

Given the 950,000 deaths from COVID-19 over the past 2 years, inclusion of prolonged grief disorder in the DSM-5 may arrive at just the right time.

The diagnostic criteria for PCBD include:

• The development of a persistent grief response (longer than a year for adults and 6 months for children and adolescents) characterized by one or both of the following symptoms, which have been present most days to a clinically significant degree, and have occurred nearly every day for at least the last month: intense yearning/longing for the deceased person; preoccupation with thoughts or memories of the deceased person.
• Since the death, at least three symptoms present most days to a clinically significant degree, and occurring nearly every day for at least the last month, including identity disruption, marked sense of disbelief about the death, avoidance of reminders that the person is dead, intense emotional pain related to the death, difficulty reintegrating into one’s relationships and activities after the death, emotional numbness, feeling that life is meaningless as a result of the death, and intense loneliness as a result of the death.
• The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
• The duration and severity of the bereavement reaction clearly exceed expected social, cultural, or religious norms for the individual’s culture and context.
• The symptoms are not better explained by another mental disorder, such as major depressive disorder (MDD) or PTSD, and are not attributable to the physiological effects of a substance or another medical condition.

Dr. Frances said he believes creating a new diagnosis pathologizes grief. In DSM-3 and DSM-4, an exception was made under the diagnosis of MDD for individuals who had recently lost a loved one. “We wanted to have at least an opportunity for people to grieve without being stigmatized, mislabeled, and overtreated with medication.”

DSM-5 removed the bereavement exclusion. After 2 weeks, people who are grieving and have particular symptoms could receive a diagnosis of MDD, said Dr. Frances. He believes the exclusion should have been broadened to cover anyone experiencing a major loss – such as a job loss or divorce. If someone is having prolonged symptoms that interfere with functioning, they should get an MDD diagnosis.

The new disorder “doesn’t solve anything, it just adds to the confusion and stigmatization, and it’s part of a kind of creeping medical imperialization of everyday life, where everything has to have a mental disorder label,” Dr. Frances said.

However, Dr. Appelbaum countered that “the criteria for prolonged grief disorder are constructed in such a way as to make every effort to exclude people who are going through a normal grieving process.”

“Part of the purpose of the data analyses was to ensure the criteria that were adopted would, in fact, effectively distinguish between what anybody goes through, say when someone close to you dies, and this unusual prolonged grieving process without end that affects a much smaller number of people but which really can be crippling for them,” he added.

The Text Revision adds new symptom codes for suicidal behavior and nonsuicidal self-injury, which appear in the chapter, “Other Conditions That May Be a Focus of Clinical Attention,” said Dr. Appelbaum.

“Both suicidal behavior and nonsuicidal self-injury seem pretty persuasively to fall into that category – something a clinician would want to know about, pay attention to, and factor into treatment planning, although they are behaviors that cross many diagnostic categories,” he added.

Codes also provide a systematic way of ascertaining the incidence and prevalence of such behaviors, said Dr. Appelbaum.
 

Changes to gender terminology

The Text Revision also tweaks some terminology with respect to transgender individuals. The term “desired gender” is now “experienced gender”, the term “cross-sex medical procedure” is now “gender-affirming medical procedure”, and the terms “natal male/natal female” are now “individual assigned male/female at birth”.

Dr. Frances said that the existence of gender dysphoria as a diagnosis has been a matter of controversy ever since it was first included.

“The transgender community has had mixed feelings on whether there should be anything at all in the manual,” he said. On one hand is the argument that gender dysphoria should be removed because it’s not really a psychiatric issue.

“We seriously considered eliminating it altogether in DSM-4,” said Dr. Frances.

However, an argument in favor of keeping it was that if the diagnosis was removed, it would mean that people could not receive treatment. “There’s no right argument for this dilemma,” he said.

Dr. Frances, who has been a frequent critic of DSM-5, said he believes the manual continues to miss opportunities to tighten criteria for many diagnoses, including ADHD and autism spectrum disorder.

“There’s a consistent pattern of taking behaviors and symptoms of behaviors that are on the border with normality and expanding the definition of mental disorder and reducing the realm of normality,” he said.

That has consequences, Dr. Frances added. “When someone gets a diagnosis that they need to get, it’s the beginning of a much better future. When someone gets a diagnosis that’s a mislabel that they don’t need, it has all harms and no benefits. It’s stigmatizing, leads to too much treatment, the wrong treatment, and it’s much more harmful than helpful.”

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

Cirrhosis is the most common cause of ascites in the United States. In patients with compensated cirrhosis, the 10-year probability of developing ascites is 47%. Developing ascites portends a poor prognosis. Fifteen percent of patients who receive this diagnosis die within 1 year, and 44% within 5 years.¹ First-line treatment of cirrhotic ascites consists of dietary sodium restriction and diuretic therapy. Refractory ascites is defined as ascites that cannot be easily mobilized despite adhering to a dietary sodium intake of ≤ 2 g daily and daily doses of spironolactone 400 mg and furosemide 160 mg.

Patients who cannot tolerate diuretics because of complications are defined as having diuretic intractable ascites. Diuretic-induced complications include hepatic encephalopathy, renal impairment, hyponatremia, and hypo- or hyperkalemia. Because these patients are either unresponsive to or intolerant of diuretics, second-line treatments, such as regular large-volume paracentesis (LVP) or the insertion of a transjugular intrahepatic portosystemic shunt (TIPS) are needed to manage their ascites. These patients also should be considered for liver transplantation unless there is a contraindication.²

Serial LVP has been shown to be safe and effective in controlling refractory ascites.³ TIPS will decrease the need for repeated LVP in patients with refractory LVP. However, given the uncertainty as to the effect of TIPS creation on survival and the increased risk of encephalopathy, the American Association for the Study of Liver Diseases (AASLD) recommends that TIPS should be used only in those patients who cannot tolerate repeated LVP.⁴ Repeated LVP also has been shown to be safe and effective in controlling malignant ascites.^5,6

LVP can be done in different health care settings. These include the emergency department (ED), interventional radiology suite, inpatient bed, or an outpatient paracentesis clinic. There have been various descriptions of outpatient paracentesis clinics. Reports from the United Kingdom have revealed that paracenteses in these outpatient clinics can be performed safely by nurse practitioners or a liver specialist nurse, that these clinics are highly rated by the patients, and are cost effective.^7-10 Gashau and colleagues describe a clinic in Great Britain run by gastroenterology (GI) fellows using an endoscopy suite.¹¹ A nurse practitioner outpatient paracentesis clinic in the US has been described as well.¹² Grabau and colleagues present a clinic run by GI endoscopy assistants (licensed practical nurses) using a dedicated paracentesis room in the endoscopy suite.¹³ Cheng and colleagues describe an outpatient paracentesis clinic in a radiology department run by a single advanced practitioner with assistance from an ultrasound technologist.¹⁴ Wang and colleagues present outpatient paracenteses in an outpatient transitional care program by a physician or an advanced practitioner supervised by a physician.¹⁵ Sehgal and colleagues describe (in abstract) the creation of a hospitalist-run paracentesis clinic.¹⁶

Traditionally, at Veterans Affairs Pittsburgh Healthcare System (VAPHS) in Pennsylvania, if a patient needed LVP, they were admitted to a medicine bed. LVP is not done in the ED, and interventional radiology cannot accommodate the number of patients requiring LVP because of their caseload. The procedure was done by an attending hospitalist or medical residents under the supervision of an attending hospitalist. To improve patient flow and decrease the number of patients using inpatients beds, we created an outpatient paracentesis clinic in 2014. Here, we present the logistics of the clinic, patient demographics, the amount of ascites removed, and the time required to remove the ascites. As part of ongoing quality assurance, we keep track of any complications and report these as well.

Methods

The setting of the outpatient paracentesis clinic is a room in the VAPHS endoscopy suite. The clinic operates 1 half-day per week with up to 3 patients receiving a paracentesis. We use the existing logistics in the endoscopy suite. There are 1 or 2 registered nurses (RNs) who assist the physician performing the paracentesis. The proceduralist is an academic hospitalist who at the time is not on service with residents. The patients are referred to the clinic by the ED, hepatology clinic, palliative care, primary care physicians, or at hospital discharge. In the clinic consult, patients are required to have at least an estimated 3 L of ascites and systolic blood pressure (SBP) ≥ 90. The patients can eat and take medications the morning of the procedure except diuretics. Patients are checked in to the endoscopy suite and a peripheral IV is placed. Blood tests, such as a complete blood count and coagulation studies, are not checked routinely since the AASLD guidelines state that routine prophylactic use of fresh frozen plasma or platelets before paracentesis is not recommended because bleeding is uncommon.³ The proceduralist can order blood work at their discretion.

After the procedure, patients are brought to the recovery area of the endoscopy suite and discharged. The patients are discharged usually within 15 to 30 minutes from arriving in the recovery area after it is assured that the SBP is within 10% of their baseline. Patient follow-up in the outpatient paracentesis clinic is determined by the proceduralist. Most patients need regularly scheduled paracenteses depending on how quickly they reaccumulate ascites. If a patient does not need a regularly scheduled paracentesis, the proceduralist ensures that the appropriate outpatient clinic visit has been scheduled or requested.

Procedure

Informed consent is obtained, and a time-out is performed before each paracentesis. The patient is attached to a cardiac monitor and pulse oximetry as per the endoscopy suite protocol. The proceduralist does a point-of-care ultrasound to find the optimal site and marks the site of puncture. The skin around the marked site is prepared with 3 chlorhexidine gluconate 2%/isopropyl alcohol 70% applicators. A fenestrated drape is used to form a sterile field. The Avanos Paracentesis Kit is routinely used for LVP at VAPHS. Local anesthesia with 1% lidocaine is used with a 25-gauge × 1-inch needle. Deeper anesthesia is obtained with 1% lidocaine, using a 22-gauge × 1.5-inch needle, injecting and aspirating while advancing the needle until ascites is aspirated.

A 15-gauge 3.3-inch Caldwell cannula with an inner needle is inserted into the peritoneal cavity and ascites is aspirated into a syringe. The inner needle is then removed, and the Caldwell cannula is left in the peritoneal cavity and tubing with a roller clamp is attached to the cannula. The tubing is then attached to a 1-L vacuum suction bottle by the RN. We use the CareFusion PleurX drainage bottle. The proceduralist maintains sterility and assures the cannula remains in place. The RN changes the drainage bottles after being filled with 1 L of ascites.

We drain as much ascites as possible until drainage stops on its own. The cannula is then removed, and pressure is held with a gauze pad. An adhesive bandage is then placed over the site. Consistent with AASLD guideline, 25 g of IV albumin 25% is infused for every 3 L of albumin removed provided > 5 L of ascites is removed.³ The albumin is infused during the procedure and not after to limit the time of the procedure. A sample of ascites is sent for cell count with differential and culture.

Results

Between March 2014 and May 2020, 506 paracenteses were performed on 82 patients. The mean age was 66.4 years, and 80 of 82 patients were male. The etiology of the ascites is presented in the Table. Twelve percent of the patients had concomitant hepatocellular carcinoma. Data on the amount of ascites removed were available for all patients, but data on the amount of time it took to do the LVP were available for 392 of 506 paracenteses. The mean volume removed was 7.9 L (range, 0.2-22.9 L), and the mean time of the procedure was 33.3 minutes. The time of the procedure was the time difference between entering and leaving the procedure room. This does not include IV placement or the recovery area time.

There were 5 episodes of postprocedure hypotension that required IV fluid or admission. In all these events, the patients had received the appropriate amount of IV albumin. Three patients required admission, and 1 patient required IV fluid postparacentesis on 2 occasions and then was discharged home. One abdominal wall hematoma occurred. Two patients with umbilical hernias developed incarceration after the paracentesis; both required surgical repair. There were 3 episodes of leakage at the paracentesis site; a skin adhesive was used in 2 cases, and sutures were applied in the other. There were no deaths.

Possible Infections

Ascitic fluid infection is a risk for patients needing paracentesis. Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascites in the absence of a focal contiguous source. The polymorphonuclear leukocyte (PMN) count in the ascites is ≥ 250 cells/mm³ in the presence of a single organism on culture. Culture-negative neutrocytic ascites (CNNA) is an ascitic fluid PMN count ≥ 250 cells/mm³ in the absence of culture growth obtained before the administration of antibiotics. Monomicrobial nonneutrocytic bacterascites (MNB) is an ascitic fluid PMN count < 250 cells/mm³ with growth of a single organism on culture.¹⁷ There was one occasion where a patient developed symptomatic CNNA 3 days after having a therapeutic paracentesis in the clinic at which time his ascites had a normal neutrophil count and a negative culture. He presented with abdominal pain and fever 3 days later, and a diagnostic paracentesis was done in the ED. He was treated as though he had SBP and did well.

Ascites cell count and culture are routinely sent in the clinic, and 1 case of asymptomatic SBP and 3 cases of asymptomatic ascitic fluid infection variants were diagnosed. The patient with SBP grew vancomycin-resistant Enterococcus faecium in his ascites. Two cases were CNNA. These patients were admitted to the hospital and treated with IV antibiotics. One case of MNB occurred that grew Escherichia coli. The patient refused to return to the hospital for IV antibiotics and was treated with a 5-day course of oral ciprofloxacin.

Discussion

We describe an academic hospitalist–run outpatient LVP clinic where large volumes of ascites are removed efficiently and safely. The only other description of a hospitalist-run paracentesis clinic was in abstract form.¹⁶ Without the clinic, the patients would have been admitted to the hospital to get an LVP. Based on VAPHS data from fiscal year 2021, the average cost per day of a nontelemetry medicine admission was $3394. Over 74 months, 506 admissions were prevented, which averages to 82 admissions prevented per year, an approximate annual cost savings of $278,308 in the last fiscal year alone.

Possible Complications

The complications we report are congruent with those reported in the literature. Runyon reported that the rate of an abdominal wall hematoma requiring blood transfusion was 0.9%, and the rate of an abdominal wall hematoma not requiring blood transfusion was also 0.9%.¹⁸ We had 1 patient who developed an abdominal wall hematoma (0.2% of paracenteses). This patient required 4 units of packed red blood cells. The incidence of ascitic fluid leakage after paracentesis has been reported to be between 0.4% and 2.4%.¹² We had 3 episodes of leakage (0.6% of paracenteses). The Z-track technique has been purported to decrease postparacentesis leakage.² This involves creating a pathway that is nonlinear when anesthetizing the soft tissues and inserting the paracentesis needle. The Z-track technique was not used in any of the paracenteses in our clinic.

Postparacentesis hypotension has been reported to be 0.4% to 1.8%.^12,14 We report 5 episodes of hypotension (0.1% of paracenteses) of which 3 patients were admitted to the hospital. Interestingly, 4 of the 5 patients were on β-blockers. Serste and colleagues reported in a crossover trial that paracentesis-induced circulatory dysfunction (PICD) decreased from 80 to 10% when propranolol was discontinued.¹⁹ PICD is characterized by reduction of effective arterial blood volume with subsequent activation of vasoconstrictor and antinatriuretic factors that can cause rapid ascites recurrence rate, development of dilutional hyponatremia, hepatorenal syndrome, and increased mortality. IV albumin is given during LVP to prevent PICD. Discontinuing unnecessary antihypertensive medications, especially β-blockers, may mitigate postparacentesis hypotension. In a study of 515 paracenteses, De Gottardi and colleagues reported a 0.2% rate of iatrogenic percutaneous infection of ascites.²⁰ We had 1 patient return 3 days after LVP with fever, abdominal pain, and neutrocytic ascites. His blood and ascites cultures were negative. The etiology of his infected ascites could have been either a spontaneously developed CNNA infection or an iatrogenic percutaneous infection of ascites.

Two cases of incarceration and strangulation of umbilical hernias postparacentesis that required emergent surgical intervention were unanticipated complications. Incarceration of an existing umbilical hernia postparacentesis is an uncommon but serious complication of LVP described in the past in numerous case reports but whose incidence is otherwise unknown.^21-26 The fluid and pressure shifts before and after LVP are likely responsible for the hernia incarceration. When ascites is present, the umbilical hernia ring is kept patent by the pressure of the ascitic fluid, and the decrease in tension after removal of ascites may lead to decreased size of the hernia ring and trapping of contents in the hernia sac.^25-27 In most reported cases, symptoms and recognition of the incarcerated hernia have occurred within 2 days of the index paracentesis procedure. Most cases were in patients who required serial paracenteses for management of ascites and had relatively regular LVPs.

In both cases, the patients had regular visits for paracentesis, and incarceration occurred 0.5 hours postprocedure, in 1 case and 6 hours in the other. Umbilical hernias are common in patients with cirrhosis, with the prevalence approaching 20%.²⁸ The management of umbilical hernias in patients with ascites is complex and optimal guideline-based management involves elective repair when ascites is adequately controlled to prevent recurrence, with consideration of TIPS at the time of repair.³ However, patients enrolled in outpatient paracentesis clinics are unlikely to have adequate ascites control to be considered optimized for an elective repair. In addition, given the number of serial procedures that they require, it is not surprising that they may be at risk for complications that are otherwise thought to be rare. Although incarceration and strangulation of umbilical hernia is thought to be a rare complication of LVP, patients should be informed of this potential complication so that they are aware to seek medical attention should they develop signs or symptoms.

Guidelines

There are no guidelines on how much ascites can be removed and how quickly the ascites can be removed during LVP. The goal of a therapeutic paracentesis is to remove as much fluid as possible, and there are no limits on the amount that can be removed safely.¹ Concerning paracentesis flow rates, Elsabaawy and colleagues showed that ascites flow rate does not correlate with PICD. They looked at 3 groups with ascites flow rates of 80 mL/min, 180 mL/min and 270 mL/min.²⁹ We had data on the time in the procedure room in 77% of our procedures. Given our average amount of ascites removed (7.9 L) and average time in the procedure room (33.3 minutes), the average flow rate from our clinic was at least 237 mL/min (although the flow rate was likely higher because the average time from needle inserted to needle removed was < 33.3 minutes). Both the mean duration of LVP and the mean volume of ascites removed in an outpatient paracentesis clinic were reported in only 1 other study. In a study of 1100 patients, Grabau and colleagues reported the mean duration, defined as the time between when the patient entered and exited the procedure room (the same time period we reported) as 97 minutes and the mean volume of ascites removed as 8.7 L.¹³

The AASLD guidelines state that patients undergoing serial outpatient LVP should be tested only for cell count and differential without sending a bacterial culture. The reason given is that false positives may exceed true positives from ascites bacterial culture results in asymptomatic patients.³ Mohan and Venkataraman reported a 0.4% rate of SBP, 1.4% rate of CNNA, and 0.7% rate of MNB in asymptomatic patients undergoing LVP in an outpatient clinic.³⁰ We had a 0.2% rate of SBP, 0.4% rate of CNNA, and 0.2% rate of MNB. Given the low rates of SBP in outpatient paracenteses clinics, we will adopt the AASLD suggestions to only send an ascites cell count and not a culture in asymptomatic patients. Noteworthy, our patient with asymptomatic SBP grew vancomycin-resistant Enterococcus faecium, which was resistant to standard SBP antibiotic therapy. However, if ascites culture was not sent, he would have been treated with antibiotics for CNNA, and if he developed symptoms, he would have had a repeat paracentesis with cell count and culture sent.

Training

In 2015, faculty at VAPHS and the University of Pittsburgh School of Medicine designed a Mastering Paracentesis for Medical Residents course based on current guidelines on the management of ascites and published procedural guides. The course is mandatory for all postgraduate year-1 internal medicine residents and begins with 2 hours of didactic and simulation-based training with an ultrasound-compatible paracentesis mannequin. In the 3 weeks following simulation-based training, residents rotate through our outpatient paracentesis clinic and perform between 1 and 3 abdominal paracentesis procedures, receiving as-needed coaching and postprocedure feedback from faculty. Since the course’s inception, more than 150 internal medicine residents have been trained in paracentesis through our clinic.

Conclusions

We present a description of a successful outpatient paracentesis clinic at our hospital run by academic hospitalists. The clinic was created to decrease the number of admissions for LVP. We were fortunate to be able to use the GI endoscopy suite and their resources as the clinic setting. To create outpatient LVP clinics at other institutions, administrative support is essential. In conclusion, we have shown that an outpatient paracentesis clinic run by academic hospitalists can safely and quickly remove large volumes of ascites.

Cirrhosis is the most common cause of ascites in the United States. In patients with compensated cirrhosis, the 10-year probability of developing ascites is 47%. Developing ascites portends a poor prognosis. Fifteen percent of patients who receive this diagnosis die within 1 year, and 44% within 5 years.¹ First-line treatment of cirrhotic ascites consists of dietary sodium restriction and diuretic therapy. Refractory ascites is defined as ascites that cannot be easily mobilized despite adhering to a dietary sodium intake of ≤ 2 g daily and daily doses of spironolactone 400 mg and furosemide 160 mg.

Patients who cannot tolerate diuretics because of complications are defined as having diuretic intractable ascites. Diuretic-induced complications include hepatic encephalopathy, renal impairment, hyponatremia, and hypo- or hyperkalemia. Because these patients are either unresponsive to or intolerant of diuretics, second-line treatments, such as regular large-volume paracentesis (LVP) or the insertion of a transjugular intrahepatic portosystemic shunt (TIPS) are needed to manage their ascites. These patients also should be considered for liver transplantation unless there is a contraindication.²

Serial LVP has been shown to be safe and effective in controlling refractory ascites.³ TIPS will decrease the need for repeated LVP in patients with refractory LVP. However, given the uncertainty as to the effect of TIPS creation on survival and the increased risk of encephalopathy, the American Association for the Study of Liver Diseases (AASLD) recommends that TIPS should be used only in those patients who cannot tolerate repeated LVP.⁴ Repeated LVP also has been shown to be safe and effective in controlling malignant ascites.^5,6

LVP can be done in different health care settings. These include the emergency department (ED), interventional radiology suite, inpatient bed, or an outpatient paracentesis clinic. There have been various descriptions of outpatient paracentesis clinics. Reports from the United Kingdom have revealed that paracenteses in these outpatient clinics can be performed safely by nurse practitioners or a liver specialist nurse, that these clinics are highly rated by the patients, and are cost effective.^7-10 Gashau and colleagues describe a clinic in Great Britain run by gastroenterology (GI) fellows using an endoscopy suite.¹¹ A nurse practitioner outpatient paracentesis clinic in the US has been described as well.¹² Grabau and colleagues present a clinic run by GI endoscopy assistants (licensed practical nurses) using a dedicated paracentesis room in the endoscopy suite.¹³ Cheng and colleagues describe an outpatient paracentesis clinic in a radiology department run by a single advanced practitioner with assistance from an ultrasound technologist.¹⁴ Wang and colleagues present outpatient paracenteses in an outpatient transitional care program by a physician or an advanced practitioner supervised by a physician.¹⁵ Sehgal and colleagues describe (in abstract) the creation of a hospitalist-run paracentesis clinic.¹⁶

Traditionally, at Veterans Affairs Pittsburgh Healthcare System (VAPHS) in Pennsylvania, if a patient needed LVP, they were admitted to a medicine bed. LVP is not done in the ED, and interventional radiology cannot accommodate the number of patients requiring LVP because of their caseload. The procedure was done by an attending hospitalist or medical residents under the supervision of an attending hospitalist. To improve patient flow and decrease the number of patients using inpatients beds, we created an outpatient paracentesis clinic in 2014. Here, we present the logistics of the clinic, patient demographics, the amount of ascites removed, and the time required to remove the ascites. As part of ongoing quality assurance, we keep track of any complications and report these as well.

Methods

The setting of the outpatient paracentesis clinic is a room in the VAPHS endoscopy suite. The clinic operates 1 half-day per week with up to 3 patients receiving a paracentesis. We use the existing logistics in the endoscopy suite. There are 1 or 2 registered nurses (RNs) who assist the physician performing the paracentesis. The proceduralist is an academic hospitalist who at the time is not on service with residents. The patients are referred to the clinic by the ED, hepatology clinic, palliative care, primary care physicians, or at hospital discharge. In the clinic consult, patients are required to have at least an estimated 3 L of ascites and systolic blood pressure (SBP) ≥ 90. The patients can eat and take medications the morning of the procedure except diuretics. Patients are checked in to the endoscopy suite and a peripheral IV is placed. Blood tests, such as a complete blood count and coagulation studies, are not checked routinely since the AASLD guidelines state that routine prophylactic use of fresh frozen plasma or platelets before paracentesis is not recommended because bleeding is uncommon.³ The proceduralist can order blood work at their discretion.

After the procedure, patients are brought to the recovery area of the endoscopy suite and discharged. The patients are discharged usually within 15 to 30 minutes from arriving in the recovery area after it is assured that the SBP is within 10% of their baseline. Patient follow-up in the outpatient paracentesis clinic is determined by the proceduralist. Most patients need regularly scheduled paracenteses depending on how quickly they reaccumulate ascites. If a patient does not need a regularly scheduled paracentesis, the proceduralist ensures that the appropriate outpatient clinic visit has been scheduled or requested.

Procedure

Informed consent is obtained, and a time-out is performed before each paracentesis. The patient is attached to a cardiac monitor and pulse oximetry as per the endoscopy suite protocol. The proceduralist does a point-of-care ultrasound to find the optimal site and marks the site of puncture. The skin around the marked site is prepared with 3 chlorhexidine gluconate 2%/isopropyl alcohol 70% applicators. A fenestrated drape is used to form a sterile field. The Avanos Paracentesis Kit is routinely used for LVP at VAPHS. Local anesthesia with 1% lidocaine is used with a 25-gauge × 1-inch needle. Deeper anesthesia is obtained with 1% lidocaine, using a 22-gauge × 1.5-inch needle, injecting and aspirating while advancing the needle until ascites is aspirated.

A 15-gauge 3.3-inch Caldwell cannula with an inner needle is inserted into the peritoneal cavity and ascites is aspirated into a syringe. The inner needle is then removed, and the Caldwell cannula is left in the peritoneal cavity and tubing with a roller clamp is attached to the cannula. The tubing is then attached to a 1-L vacuum suction bottle by the RN. We use the CareFusion PleurX drainage bottle. The proceduralist maintains sterility and assures the cannula remains in place. The RN changes the drainage bottles after being filled with 1 L of ascites.

We drain as much ascites as possible until drainage stops on its own. The cannula is then removed, and pressure is held with a gauze pad. An adhesive bandage is then placed over the site. Consistent with AASLD guideline, 25 g of IV albumin 25% is infused for every 3 L of albumin removed provided > 5 L of ascites is removed.³ The albumin is infused during the procedure and not after to limit the time of the procedure. A sample of ascites is sent for cell count with differential and culture.

Results

Between March 2014 and May 2020, 506 paracenteses were performed on 82 patients. The mean age was 66.4 years, and 80 of 82 patients were male. The etiology of the ascites is presented in the Table. Twelve percent of the patients had concomitant hepatocellular carcinoma. Data on the amount of ascites removed were available for all patients, but data on the amount of time it took to do the LVP were available for 392 of 506 paracenteses. The mean volume removed was 7.9 L (range, 0.2-22.9 L), and the mean time of the procedure was 33.3 minutes. The time of the procedure was the time difference between entering and leaving the procedure room. This does not include IV placement or the recovery area time.

There were 5 episodes of postprocedure hypotension that required IV fluid or admission. In all these events, the patients had received the appropriate amount of IV albumin. Three patients required admission, and 1 patient required IV fluid postparacentesis on 2 occasions and then was discharged home. One abdominal wall hematoma occurred. Two patients with umbilical hernias developed incarceration after the paracentesis; both required surgical repair. There were 3 episodes of leakage at the paracentesis site; a skin adhesive was used in 2 cases, and sutures were applied in the other. There were no deaths.

Possible Infections

Ascitic fluid infection is a risk for patients needing paracentesis. Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascites in the absence of a focal contiguous source. The polymorphonuclear leukocyte (PMN) count in the ascites is ≥ 250 cells/mm³ in the presence of a single organism on culture. Culture-negative neutrocytic ascites (CNNA) is an ascitic fluid PMN count ≥ 250 cells/mm³ in the absence of culture growth obtained before the administration of antibiotics. Monomicrobial nonneutrocytic bacterascites (MNB) is an ascitic fluid PMN count < 250 cells/mm³ with growth of a single organism on culture.¹⁷ There was one occasion where a patient developed symptomatic CNNA 3 days after having a therapeutic paracentesis in the clinic at which time his ascites had a normal neutrophil count and a negative culture. He presented with abdominal pain and fever 3 days later, and a diagnostic paracentesis was done in the ED. He was treated as though he had SBP and did well.

Ascites cell count and culture are routinely sent in the clinic, and 1 case of asymptomatic SBP and 3 cases of asymptomatic ascitic fluid infection variants were diagnosed. The patient with SBP grew vancomycin-resistant Enterococcus faecium in his ascites. Two cases were CNNA. These patients were admitted to the hospital and treated with IV antibiotics. One case of MNB occurred that grew Escherichia coli. The patient refused to return to the hospital for IV antibiotics and was treated with a 5-day course of oral ciprofloxacin.

Discussion

We describe an academic hospitalist–run outpatient LVP clinic where large volumes of ascites are removed efficiently and safely. The only other description of a hospitalist-run paracentesis clinic was in abstract form.¹⁶ Without the clinic, the patients would have been admitted to the hospital to get an LVP. Based on VAPHS data from fiscal year 2021, the average cost per day of a nontelemetry medicine admission was $3394. Over 74 months, 506 admissions were prevented, which averages to 82 admissions prevented per year, an approximate annual cost savings of $278,308 in the last fiscal year alone.

Possible Complications

The complications we report are congruent with those reported in the literature. Runyon reported that the rate of an abdominal wall hematoma requiring blood transfusion was 0.9%, and the rate of an abdominal wall hematoma not requiring blood transfusion was also 0.9%.¹⁸ We had 1 patient who developed an abdominal wall hematoma (0.2% of paracenteses). This patient required 4 units of packed red blood cells. The incidence of ascitic fluid leakage after paracentesis has been reported to be between 0.4% and 2.4%.¹² We had 3 episodes of leakage (0.6% of paracenteses). The Z-track technique has been purported to decrease postparacentesis leakage.² This involves creating a pathway that is nonlinear when anesthetizing the soft tissues and inserting the paracentesis needle. The Z-track technique was not used in any of the paracenteses in our clinic.

Postparacentesis hypotension has been reported to be 0.4% to 1.8%.^12,14 We report 5 episodes of hypotension (0.1% of paracenteses) of which 3 patients were admitted to the hospital. Interestingly, 4 of the 5 patients were on β-blockers. Serste and colleagues reported in a crossover trial that paracentesis-induced circulatory dysfunction (PICD) decreased from 80 to 10% when propranolol was discontinued.¹⁹ PICD is characterized by reduction of effective arterial blood volume with subsequent activation of vasoconstrictor and antinatriuretic factors that can cause rapid ascites recurrence rate, development of dilutional hyponatremia, hepatorenal syndrome, and increased mortality. IV albumin is given during LVP to prevent PICD. Discontinuing unnecessary antihypertensive medications, especially β-blockers, may mitigate postparacentesis hypotension. In a study of 515 paracenteses, De Gottardi and colleagues reported a 0.2% rate of iatrogenic percutaneous infection of ascites.²⁰ We had 1 patient return 3 days after LVP with fever, abdominal pain, and neutrocytic ascites. His blood and ascites cultures were negative. The etiology of his infected ascites could have been either a spontaneously developed CNNA infection or an iatrogenic percutaneous infection of ascites.

Two cases of incarceration and strangulation of umbilical hernias postparacentesis that required emergent surgical intervention were unanticipated complications. Incarceration of an existing umbilical hernia postparacentesis is an uncommon but serious complication of LVP described in the past in numerous case reports but whose incidence is otherwise unknown.^21-26 The fluid and pressure shifts before and after LVP are likely responsible for the hernia incarceration. When ascites is present, the umbilical hernia ring is kept patent by the pressure of the ascitic fluid, and the decrease in tension after removal of ascites may lead to decreased size of the hernia ring and trapping of contents in the hernia sac.^25-27 In most reported cases, symptoms and recognition of the incarcerated hernia have occurred within 2 days of the index paracentesis procedure. Most cases were in patients who required serial paracenteses for management of ascites and had relatively regular LVPs.

In both cases, the patients had regular visits for paracentesis, and incarceration occurred 0.5 hours postprocedure, in 1 case and 6 hours in the other. Umbilical hernias are common in patients with cirrhosis, with the prevalence approaching 20%.²⁸ The management of umbilical hernias in patients with ascites is complex and optimal guideline-based management involves elective repair when ascites is adequately controlled to prevent recurrence, with consideration of TIPS at the time of repair.³ However, patients enrolled in outpatient paracentesis clinics are unlikely to have adequate ascites control to be considered optimized for an elective repair. In addition, given the number of serial procedures that they require, it is not surprising that they may be at risk for complications that are otherwise thought to be rare. Although incarceration and strangulation of umbilical hernia is thought to be a rare complication of LVP, patients should be informed of this potential complication so that they are aware to seek medical attention should they develop signs or symptoms.

Guidelines

There are no guidelines on how much ascites can be removed and how quickly the ascites can be removed during LVP. The goal of a therapeutic paracentesis is to remove as much fluid as possible, and there are no limits on the amount that can be removed safely.¹ Concerning paracentesis flow rates, Elsabaawy and colleagues showed that ascites flow rate does not correlate with PICD. They looked at 3 groups with ascites flow rates of 80 mL/min, 180 mL/min and 270 mL/min.²⁹ We had data on the time in the procedure room in 77% of our procedures. Given our average amount of ascites removed (7.9 L) and average time in the procedure room (33.3 minutes), the average flow rate from our clinic was at least 237 mL/min (although the flow rate was likely higher because the average time from needle inserted to needle removed was < 33.3 minutes). Both the mean duration of LVP and the mean volume of ascites removed in an outpatient paracentesis clinic were reported in only 1 other study. In a study of 1100 patients, Grabau and colleagues reported the mean duration, defined as the time between when the patient entered and exited the procedure room (the same time period we reported) as 97 minutes and the mean volume of ascites removed as 8.7 L.¹³

The AASLD guidelines state that patients undergoing serial outpatient LVP should be tested only for cell count and differential without sending a bacterial culture. The reason given is that false positives may exceed true positives from ascites bacterial culture results in asymptomatic patients.³ Mohan and Venkataraman reported a 0.4% rate of SBP, 1.4% rate of CNNA, and 0.7% rate of MNB in asymptomatic patients undergoing LVP in an outpatient clinic.³⁰ We had a 0.2% rate of SBP, 0.4% rate of CNNA, and 0.2% rate of MNB. Given the low rates of SBP in outpatient paracenteses clinics, we will adopt the AASLD suggestions to only send an ascites cell count and not a culture in asymptomatic patients. Noteworthy, our patient with asymptomatic SBP grew vancomycin-resistant Enterococcus faecium, which was resistant to standard SBP antibiotic therapy. However, if ascites culture was not sent, he would have been treated with antibiotics for CNNA, and if he developed symptoms, he would have had a repeat paracentesis with cell count and culture sent.

Training

In 2015, faculty at VAPHS and the University of Pittsburgh School of Medicine designed a Mastering Paracentesis for Medical Residents course based on current guidelines on the management of ascites and published procedural guides. The course is mandatory for all postgraduate year-1 internal medicine residents and begins with 2 hours of didactic and simulation-based training with an ultrasound-compatible paracentesis mannequin. In the 3 weeks following simulation-based training, residents rotate through our outpatient paracentesis clinic and perform between 1 and 3 abdominal paracentesis procedures, receiving as-needed coaching and postprocedure feedback from faculty. Since the course’s inception, more than 150 internal medicine residents have been trained in paracentesis through our clinic.

Conclusions

We present a description of a successful outpatient paracentesis clinic at our hospital run by academic hospitalists. The clinic was created to decrease the number of admissions for LVP. We were fortunate to be able to use the GI endoscopy suite and their resources as the clinic setting. To create outpatient LVP clinics at other institutions, administrative support is essential. In conclusion, we have shown that an outpatient paracentesis clinic run by academic hospitalists can safely and quickly remove large volumes of ascites.

Cirrhosis is the most common cause of ascites in the United States. In patients with compensated cirrhosis, the 10-year probability of developing ascites is 47%. Developing ascites portends a poor prognosis. Fifteen percent of patients who receive this diagnosis die within 1 year, and 44% within 5 years.¹ First-line treatment of cirrhotic ascites consists of dietary sodium restriction and diuretic therapy. Refractory ascites is defined as ascites that cannot be easily mobilized despite adhering to a dietary sodium intake of ≤ 2 g daily and daily doses of spironolactone 400 mg and furosemide 160 mg.

Patients who cannot tolerate diuretics because of complications are defined as having diuretic intractable ascites. Diuretic-induced complications include hepatic encephalopathy, renal impairment, hyponatremia, and hypo- or hyperkalemia. Because these patients are either unresponsive to or intolerant of diuretics, second-line treatments, such as regular large-volume paracentesis (LVP) or the insertion of a transjugular intrahepatic portosystemic shunt (TIPS) are needed to manage their ascites. These patients also should be considered for liver transplantation unless there is a contraindication.²

Serial LVP has been shown to be safe and effective in controlling refractory ascites.³ TIPS will decrease the need for repeated LVP in patients with refractory LVP. However, given the uncertainty as to the effect of TIPS creation on survival and the increased risk of encephalopathy, the American Association for the Study of Liver Diseases (AASLD) recommends that TIPS should be used only in those patients who cannot tolerate repeated LVP.⁴ Repeated LVP also has been shown to be safe and effective in controlling malignant ascites.^5,6

LVP can be done in different health care settings. These include the emergency department (ED), interventional radiology suite, inpatient bed, or an outpatient paracentesis clinic. There have been various descriptions of outpatient paracentesis clinics. Reports from the United Kingdom have revealed that paracenteses in these outpatient clinics can be performed safely by nurse practitioners or a liver specialist nurse, that these clinics are highly rated by the patients, and are cost effective.^7-10 Gashau and colleagues describe a clinic in Great Britain run by gastroenterology (GI) fellows using an endoscopy suite.¹¹ A nurse practitioner outpatient paracentesis clinic in the US has been described as well.¹² Grabau and colleagues present a clinic run by GI endoscopy assistants (licensed practical nurses) using a dedicated paracentesis room in the endoscopy suite.¹³ Cheng and colleagues describe an outpatient paracentesis clinic in a radiology department run by a single advanced practitioner with assistance from an ultrasound technologist.¹⁴ Wang and colleagues present outpatient paracenteses in an outpatient transitional care program by a physician or an advanced practitioner supervised by a physician.¹⁵ Sehgal and colleagues describe (in abstract) the creation of a hospitalist-run paracentesis clinic.¹⁶

Traditionally, at Veterans Affairs Pittsburgh Healthcare System (VAPHS) in Pennsylvania, if a patient needed LVP, they were admitted to a medicine bed. LVP is not done in the ED, and interventional radiology cannot accommodate the number of patients requiring LVP because of their caseload. The procedure was done by an attending hospitalist or medical residents under the supervision of an attending hospitalist. To improve patient flow and decrease the number of patients using inpatients beds, we created an outpatient paracentesis clinic in 2014. Here, we present the logistics of the clinic, patient demographics, the amount of ascites removed, and the time required to remove the ascites. As part of ongoing quality assurance, we keep track of any complications and report these as well.

Methods

The setting of the outpatient paracentesis clinic is a room in the VAPHS endoscopy suite. The clinic operates 1 half-day per week with up to 3 patients receiving a paracentesis. We use the existing logistics in the endoscopy suite. There are 1 or 2 registered nurses (RNs) who assist the physician performing the paracentesis. The proceduralist is an academic hospitalist who at the time is not on service with residents. The patients are referred to the clinic by the ED, hepatology clinic, palliative care, primary care physicians, or at hospital discharge. In the clinic consult, patients are required to have at least an estimated 3 L of ascites and systolic blood pressure (SBP) ≥ 90. The patients can eat and take medications the morning of the procedure except diuretics. Patients are checked in to the endoscopy suite and a peripheral IV is placed. Blood tests, such as a complete blood count and coagulation studies, are not checked routinely since the AASLD guidelines state that routine prophylactic use of fresh frozen plasma or platelets before paracentesis is not recommended because bleeding is uncommon.³ The proceduralist can order blood work at their discretion.

After the procedure, patients are brought to the recovery area of the endoscopy suite and discharged. The patients are discharged usually within 15 to 30 minutes from arriving in the recovery area after it is assured that the SBP is within 10% of their baseline. Patient follow-up in the outpatient paracentesis clinic is determined by the proceduralist. Most patients need regularly scheduled paracenteses depending on how quickly they reaccumulate ascites. If a patient does not need a regularly scheduled paracentesis, the proceduralist ensures that the appropriate outpatient clinic visit has been scheduled or requested.

Procedure

Informed consent is obtained, and a time-out is performed before each paracentesis. The patient is attached to a cardiac monitor and pulse oximetry as per the endoscopy suite protocol. The proceduralist does a point-of-care ultrasound to find the optimal site and marks the site of puncture. The skin around the marked site is prepared with 3 chlorhexidine gluconate 2%/isopropyl alcohol 70% applicators. A fenestrated drape is used to form a sterile field. The Avanos Paracentesis Kit is routinely used for LVP at VAPHS. Local anesthesia with 1% lidocaine is used with a 25-gauge × 1-inch needle. Deeper anesthesia is obtained with 1% lidocaine, using a 22-gauge × 1.5-inch needle, injecting and aspirating while advancing the needle until ascites is aspirated.

A 15-gauge 3.3-inch Caldwell cannula with an inner needle is inserted into the peritoneal cavity and ascites is aspirated into a syringe. The inner needle is then removed, and the Caldwell cannula is left in the peritoneal cavity and tubing with a roller clamp is attached to the cannula. The tubing is then attached to a 1-L vacuum suction bottle by the RN. We use the CareFusion PleurX drainage bottle. The proceduralist maintains sterility and assures the cannula remains in place. The RN changes the drainage bottles after being filled with 1 L of ascites.

We drain as much ascites as possible until drainage stops on its own. The cannula is then removed, and pressure is held with a gauze pad. An adhesive bandage is then placed over the site. Consistent with AASLD guideline, 25 g of IV albumin 25% is infused for every 3 L of albumin removed provided > 5 L of ascites is removed.³ The albumin is infused during the procedure and not after to limit the time of the procedure. A sample of ascites is sent for cell count with differential and culture.

Results

Between March 2014 and May 2020, 506 paracenteses were performed on 82 patients. The mean age was 66.4 years, and 80 of 82 patients were male. The etiology of the ascites is presented in the Table. Twelve percent of the patients had concomitant hepatocellular carcinoma. Data on the amount of ascites removed were available for all patients, but data on the amount of time it took to do the LVP were available for 392 of 506 paracenteses. The mean volume removed was 7.9 L (range, 0.2-22.9 L), and the mean time of the procedure was 33.3 minutes. The time of the procedure was the time difference between entering and leaving the procedure room. This does not include IV placement or the recovery area time.

There were 5 episodes of postprocedure hypotension that required IV fluid or admission. In all these events, the patients had received the appropriate amount of IV albumin. Three patients required admission, and 1 patient required IV fluid postparacentesis on 2 occasions and then was discharged home. One abdominal wall hematoma occurred. Two patients with umbilical hernias developed incarceration after the paracentesis; both required surgical repair. There were 3 episodes of leakage at the paracentesis site; a skin adhesive was used in 2 cases, and sutures were applied in the other. There were no deaths.

Possible Infections

Ascitic fluid infection is a risk for patients needing paracentesis. Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascites in the absence of a focal contiguous source. The polymorphonuclear leukocyte (PMN) count in the ascites is ≥ 250 cells/mm³ in the presence of a single organism on culture. Culture-negative neutrocytic ascites (CNNA) is an ascitic fluid PMN count ≥ 250 cells/mm³ in the absence of culture growth obtained before the administration of antibiotics. Monomicrobial nonneutrocytic bacterascites (MNB) is an ascitic fluid PMN count < 250 cells/mm³ with growth of a single organism on culture.¹⁷ There was one occasion where a patient developed symptomatic CNNA 3 days after having a therapeutic paracentesis in the clinic at which time his ascites had a normal neutrophil count and a negative culture. He presented with abdominal pain and fever 3 days later, and a diagnostic paracentesis was done in the ED. He was treated as though he had SBP and did well.

Ascites cell count and culture are routinely sent in the clinic, and 1 case of asymptomatic SBP and 3 cases of asymptomatic ascitic fluid infection variants were diagnosed. The patient with SBP grew vancomycin-resistant Enterococcus faecium in his ascites. Two cases were CNNA. These patients were admitted to the hospital and treated with IV antibiotics. One case of MNB occurred that grew Escherichia coli. The patient refused to return to the hospital for IV antibiotics and was treated with a 5-day course of oral ciprofloxacin.

Discussion

We describe an academic hospitalist–run outpatient LVP clinic where large volumes of ascites are removed efficiently and safely. The only other description of a hospitalist-run paracentesis clinic was in abstract form.¹⁶ Without the clinic, the patients would have been admitted to the hospital to get an LVP. Based on VAPHS data from fiscal year 2021, the average cost per day of a nontelemetry medicine admission was $3394. Over 74 months, 506 admissions were prevented, which averages to 82 admissions prevented per year, an approximate annual cost savings of $278,308 in the last fiscal year alone.

Possible Complications

The complications we report are congruent with those reported in the literature. Runyon reported that the rate of an abdominal wall hematoma requiring blood transfusion was 0.9%, and the rate of an abdominal wall hematoma not requiring blood transfusion was also 0.9%.¹⁸ We had 1 patient who developed an abdominal wall hematoma (0.2% of paracenteses). This patient required 4 units of packed red blood cells. The incidence of ascitic fluid leakage after paracentesis has been reported to be between 0.4% and 2.4%.¹² We had 3 episodes of leakage (0.6% of paracenteses). The Z-track technique has been purported to decrease postparacentesis leakage.² This involves creating a pathway that is nonlinear when anesthetizing the soft tissues and inserting the paracentesis needle. The Z-track technique was not used in any of the paracenteses in our clinic.

Postparacentesis hypotension has been reported to be 0.4% to 1.8%.^12,14 We report 5 episodes of hypotension (0.1% of paracenteses) of which 3 patients were admitted to the hospital. Interestingly, 4 of the 5 patients were on β-blockers. Serste and colleagues reported in a crossover trial that paracentesis-induced circulatory dysfunction (PICD) decreased from 80 to 10% when propranolol was discontinued.¹⁹ PICD is characterized by reduction of effective arterial blood volume with subsequent activation of vasoconstrictor and antinatriuretic factors that can cause rapid ascites recurrence rate, development of dilutional hyponatremia, hepatorenal syndrome, and increased mortality. IV albumin is given during LVP to prevent PICD. Discontinuing unnecessary antihypertensive medications, especially β-blockers, may mitigate postparacentesis hypotension. In a study of 515 paracenteses, De Gottardi and colleagues reported a 0.2% rate of iatrogenic percutaneous infection of ascites.²⁰ We had 1 patient return 3 days after LVP with fever, abdominal pain, and neutrocytic ascites. His blood and ascites cultures were negative. The etiology of his infected ascites could have been either a spontaneously developed CNNA infection or an iatrogenic percutaneous infection of ascites.

Two cases of incarceration and strangulation of umbilical hernias postparacentesis that required emergent surgical intervention were unanticipated complications. Incarceration of an existing umbilical hernia postparacentesis is an uncommon but serious complication of LVP described in the past in numerous case reports but whose incidence is otherwise unknown.^21-26 The fluid and pressure shifts before and after LVP are likely responsible for the hernia incarceration. When ascites is present, the umbilical hernia ring is kept patent by the pressure of the ascitic fluid, and the decrease in tension after removal of ascites may lead to decreased size of the hernia ring and trapping of contents in the hernia sac.^25-27 In most reported cases, symptoms and recognition of the incarcerated hernia have occurred within 2 days of the index paracentesis procedure. Most cases were in patients who required serial paracenteses for management of ascites and had relatively regular LVPs.

In both cases, the patients had regular visits for paracentesis, and incarceration occurred 0.5 hours postprocedure, in 1 case and 6 hours in the other. Umbilical hernias are common in patients with cirrhosis, with the prevalence approaching 20%.²⁸ The management of umbilical hernias in patients with ascites is complex and optimal guideline-based management involves elective repair when ascites is adequately controlled to prevent recurrence, with consideration of TIPS at the time of repair.³ However, patients enrolled in outpatient paracentesis clinics are unlikely to have adequate ascites control to be considered optimized for an elective repair. In addition, given the number of serial procedures that they require, it is not surprising that they may be at risk for complications that are otherwise thought to be rare. Although incarceration and strangulation of umbilical hernia is thought to be a rare complication of LVP, patients should be informed of this potential complication so that they are aware to seek medical attention should they develop signs or symptoms.

Guidelines

There are no guidelines on how much ascites can be removed and how quickly the ascites can be removed during LVP. The goal of a therapeutic paracentesis is to remove as much fluid as possible, and there are no limits on the amount that can be removed safely.¹ Concerning paracentesis flow rates, Elsabaawy and colleagues showed that ascites flow rate does not correlate with PICD. They looked at 3 groups with ascites flow rates of 80 mL/min, 180 mL/min and 270 mL/min.²⁹ We had data on the time in the procedure room in 77% of our procedures. Given our average amount of ascites removed (7.9 L) and average time in the procedure room (33.3 minutes), the average flow rate from our clinic was at least 237 mL/min (although the flow rate was likely higher because the average time from needle inserted to needle removed was < 33.3 minutes). Both the mean duration of LVP and the mean volume of ascites removed in an outpatient paracentesis clinic were reported in only 1 other study. In a study of 1100 patients, Grabau and colleagues reported the mean duration, defined as the time between when the patient entered and exited the procedure room (the same time period we reported) as 97 minutes and the mean volume of ascites removed as 8.7 L.¹³

The AASLD guidelines state that patients undergoing serial outpatient LVP should be tested only for cell count and differential without sending a bacterial culture. The reason given is that false positives may exceed true positives from ascites bacterial culture results in asymptomatic patients.³ Mohan and Venkataraman reported a 0.4% rate of SBP, 1.4% rate of CNNA, and 0.7% rate of MNB in asymptomatic patients undergoing LVP in an outpatient clinic.³⁰ We had a 0.2% rate of SBP, 0.4% rate of CNNA, and 0.2% rate of MNB. Given the low rates of SBP in outpatient paracenteses clinics, we will adopt the AASLD suggestions to only send an ascites cell count and not a culture in asymptomatic patients. Noteworthy, our patient with asymptomatic SBP grew vancomycin-resistant Enterococcus faecium, which was resistant to standard SBP antibiotic therapy. However, if ascites culture was not sent, he would have been treated with antibiotics for CNNA, and if he developed symptoms, he would have had a repeat paracentesis with cell count and culture sent.

Training

In 2015, faculty at VAPHS and the University of Pittsburgh School of Medicine designed a Mastering Paracentesis for Medical Residents course based on current guidelines on the management of ascites and published procedural guides. The course is mandatory for all postgraduate year-1 internal medicine residents and begins with 2 hours of didactic and simulation-based training with an ultrasound-compatible paracentesis mannequin. In the 3 weeks following simulation-based training, residents rotate through our outpatient paracentesis clinic and perform between 1 and 3 abdominal paracentesis procedures, receiving as-needed coaching and postprocedure feedback from faculty. Since the course’s inception, more than 150 internal medicine residents have been trained in paracentesis through our clinic.

Conclusions

We present a description of a successful outpatient paracentesis clinic at our hospital run by academic hospitalists. The clinic was created to decrease the number of admissions for LVP. We were fortunate to be able to use the GI endoscopy suite and their resources as the clinic setting. To create outpatient LVP clinics at other institutions, administrative support is essential. In conclusion, we have shown that an outpatient paracentesis clinic run by academic hospitalists can safely and quickly remove large volumes of ascites.

The COVID-19 pandemic has significantly impacted mental health. Adolescents, adults, and health care professionals (HCPs) report worsening mental health outcomes since the pandemic.^1-3 Anxiety rates have tripled, depression quadrupled, and substance and alcohol use also have increased.³ The World Health Organization (WHO) reported that during the COVID-19 pandemic, 93% of countries worldwide documented disruptions to mental health services.⁴ HCP shortages, worsened by the pandemic, have resulted in a mental health crisis. What can we do?

Over the past 20 years, pharmacists have assumed a more significant role in managing patients’ mental health conditions through multidisciplinary team engagement. Pharmacists’ training includes optimizing pharmacotherapy, identifying and managing adverse effects (AEs), improving medication adherence, and reducing unnecessary health care costs.⁵ Pharmacists have assumed pivotal roles in mental health management, including but not limited to screening, drug selection, medication management, and decision-making support for patients and HCPs. Pharmacist-provided services have led to improved medication therapy outcomes and patient satisfaction.⁶

According to the 2012 National Alliance on Mental Illness national survey, > 50% of patients treated for a mental health condition report having a strong relationship with their pharmacist.⁷ The US Department of Veterans Affairs (VA) has led the charge, engaging pharmacists in patient-oriented mental health care,including those specific to accessing mental health care (eg, fear of stigmatization).⁸ After obtaining a 4-year PharmD degree, psychiatric pharmacists receive additional postgraduate residency training (2 years) focused on direct patient care and then are eligible for board certification. There are about 2000 board-certified psychiatric pharmacists in the United States. Qualified psychiatric pharmacists, especially those in underresourced states, have increased the number of available patient-oriented mental health services.⁷ However, to continue expanding and improving access to care, we need more HCPs and pharmacists.

Mental health clinical pharmacy specialists (CPSs) within the VA work in a variety of settings, including but not limited to, the inpatient psychiatric unit; residential programs for posttraumatic stress disorder (PTSD) and substance misuse; as part of the Mental Health Intensive Case Management (MHICM) team; and in pain, telehealth, and other outpatient clinics. The VA’s mental health CPSs operate under an independent scope of practice (SOP) and manage a variety of mental health disorders. The SOP also allows pharmacists to independently manage medications for psychiatric conditions, request laboratory tests, and change therapy as needed based on patient response. The Table describes pharmacist-reported roles in a single VA facility in various mental health practice sites (eg, inpatient, outpatient, substance misuse). Pharmacist involvement in medication management with the interdisciplinary team improved symptoms, medication adherence, and reduced AEs for conditions such as depression.⁹

Within the VA, the outpatient mental health pharmacist works collaboratively with psychiatrists and HCPs to manage common psychiatric conditions on the phone and in person. VA pharmacists also are involved in the monitoring of patients on second-generation antipsychotics. Pharmacists assist with metabolic monitoring and assessing patients for movements disorders, using standardized rating scales. Pharmacists can manage complex psychiatric patients in collaboration with psychiatrists by providing medication management, laboratory test monitoring, medication counseling, and HCP referrals.

Pharmacists’ expertise is used in diverse ways in the VHA. At one facility, pharmacists functioned as interim prescribers when the facility experienced a turnover in behavioral health professionals. Pharmacists’ involvement decreased inappropriate use of psychiatric emergency services.¹⁰ VA pharmacists who manage patients’ mental health needs in primary care help achieve symptom improvement and medication adherence as well as lower referral rates for specialty mental health services.⁹ Pharmacist-managed electronic consult service provided a costs savings of about $40,000 a year.¹¹

Pharmacists have shown that they can expand their roles. Pharmacists are versatile HCPs, currently working and collaborating with other HCPs in various settings to provide mental health services. Health care systems need to continue to use and expand the number of pharmacists. Including pharmacists in the primary and specialty care teams can increase access to care and improve health outcomes during the pandemic and beyond. The American Association of Colleges of Pharmacy in partnership with the American Medical Association established a resource to support and guide institutions interested in embedding pharmacists into different clinical sites.¹² Opportunities for increased services by pharmacists can lead to improved outcomes, timely patient care, appropriate use of psychiatric medications and services, and cost savings.

Acknowledgments

We acknowledge the following Boise Veterans Affairs pharmacists: Paul Black, PharmD; Josh Gerving, PharmD; Kristin Helmboldt, PharmD; Samantha Patton, PharmD; Heather Walser, PharmD; and Andrea Winterswyk, PharmD, for contributing information about their practice roles and impact on patient care.

The COVID-19 pandemic has significantly impacted mental health. Adolescents, adults, and health care professionals (HCPs) report worsening mental health outcomes since the pandemic.^1-3 Anxiety rates have tripled, depression quadrupled, and substance and alcohol use also have increased.³ The World Health Organization (WHO) reported that during the COVID-19 pandemic, 93% of countries worldwide documented disruptions to mental health services.⁴ HCP shortages, worsened by the pandemic, have resulted in a mental health crisis. What can we do?

Over the past 20 years, pharmacists have assumed a more significant role in managing patients’ mental health conditions through multidisciplinary team engagement. Pharmacists’ training includes optimizing pharmacotherapy, identifying and managing adverse effects (AEs), improving medication adherence, and reducing unnecessary health care costs.⁵ Pharmacists have assumed pivotal roles in mental health management, including but not limited to screening, drug selection, medication management, and decision-making support for patients and HCPs. Pharmacist-provided services have led to improved medication therapy outcomes and patient satisfaction.⁶

According to the 2012 National Alliance on Mental Illness national survey, > 50% of patients treated for a mental health condition report having a strong relationship with their pharmacist.⁷ The US Department of Veterans Affairs (VA) has led the charge, engaging pharmacists in patient-oriented mental health care,including those specific to accessing mental health care (eg, fear of stigmatization).⁸ After obtaining a 4-year PharmD degree, psychiatric pharmacists receive additional postgraduate residency training (2 years) focused on direct patient care and then are eligible for board certification. There are about 2000 board-certified psychiatric pharmacists in the United States. Qualified psychiatric pharmacists, especially those in underresourced states, have increased the number of available patient-oriented mental health services.⁷ However, to continue expanding and improving access to care, we need more HCPs and pharmacists.

Mental health clinical pharmacy specialists (CPSs) within the VA work in a variety of settings, including but not limited to, the inpatient psychiatric unit; residential programs for posttraumatic stress disorder (PTSD) and substance misuse; as part of the Mental Health Intensive Case Management (MHICM) team; and in pain, telehealth, and other outpatient clinics. The VA’s mental health CPSs operate under an independent scope of practice (SOP) and manage a variety of mental health disorders. The SOP also allows pharmacists to independently manage medications for psychiatric conditions, request laboratory tests, and change therapy as needed based on patient response. The Table describes pharmacist-reported roles in a single VA facility in various mental health practice sites (eg, inpatient, outpatient, substance misuse). Pharmacist involvement in medication management with the interdisciplinary team improved symptoms, medication adherence, and reduced AEs for conditions such as depression.⁹

Within the VA, the outpatient mental health pharmacist works collaboratively with psychiatrists and HCPs to manage common psychiatric conditions on the phone and in person. VA pharmacists also are involved in the monitoring of patients on second-generation antipsychotics. Pharmacists assist with metabolic monitoring and assessing patients for movements disorders, using standardized rating scales. Pharmacists can manage complex psychiatric patients in collaboration with psychiatrists by providing medication management, laboratory test monitoring, medication counseling, and HCP referrals.

Pharmacists’ expertise is used in diverse ways in the VHA. At one facility, pharmacists functioned as interim prescribers when the facility experienced a turnover in behavioral health professionals. Pharmacists’ involvement decreased inappropriate use of psychiatric emergency services.¹⁰ VA pharmacists who manage patients’ mental health needs in primary care help achieve symptom improvement and medication adherence as well as lower referral rates for specialty mental health services.⁹ Pharmacist-managed electronic consult service provided a costs savings of about $40,000 a year.¹¹

Pharmacists have shown that they can expand their roles. Pharmacists are versatile HCPs, currently working and collaborating with other HCPs in various settings to provide mental health services. Health care systems need to continue to use and expand the number of pharmacists. Including pharmacists in the primary and specialty care teams can increase access to care and improve health outcomes during the pandemic and beyond. The American Association of Colleges of Pharmacy in partnership with the American Medical Association established a resource to support and guide institutions interested in embedding pharmacists into different clinical sites.¹² Opportunities for increased services by pharmacists can lead to improved outcomes, timely patient care, appropriate use of psychiatric medications and services, and cost savings.

Acknowledgments

We acknowledge the following Boise Veterans Affairs pharmacists: Paul Black, PharmD; Josh Gerving, PharmD; Kristin Helmboldt, PharmD; Samantha Patton, PharmD; Heather Walser, PharmD; and Andrea Winterswyk, PharmD, for contributing information about their practice roles and impact on patient care.

The COVID-19 pandemic has significantly impacted mental health. Adolescents, adults, and health care professionals (HCPs) report worsening mental health outcomes since the pandemic.^1-3 Anxiety rates have tripled, depression quadrupled, and substance and alcohol use also have increased.³ The World Health Organization (WHO) reported that during the COVID-19 pandemic, 93% of countries worldwide documented disruptions to mental health services.⁴ HCP shortages, worsened by the pandemic, have resulted in a mental health crisis. What can we do?

Over the past 20 years, pharmacists have assumed a more significant role in managing patients’ mental health conditions through multidisciplinary team engagement. Pharmacists’ training includes optimizing pharmacotherapy, identifying and managing adverse effects (AEs), improving medication adherence, and reducing unnecessary health care costs.⁵ Pharmacists have assumed pivotal roles in mental health management, including but not limited to screening, drug selection, medication management, and decision-making support for patients and HCPs. Pharmacist-provided services have led to improved medication therapy outcomes and patient satisfaction.⁶

According to the 2012 National Alliance on Mental Illness national survey, > 50% of patients treated for a mental health condition report having a strong relationship with their pharmacist.⁷ The US Department of Veterans Affairs (VA) has led the charge, engaging pharmacists in patient-oriented mental health care,including those specific to accessing mental health care (eg, fear of stigmatization).⁸ After obtaining a 4-year PharmD degree, psychiatric pharmacists receive additional postgraduate residency training (2 years) focused on direct patient care and then are eligible for board certification. There are about 2000 board-certified psychiatric pharmacists in the United States. Qualified psychiatric pharmacists, especially those in underresourced states, have increased the number of available patient-oriented mental health services.⁷ However, to continue expanding and improving access to care, we need more HCPs and pharmacists.

Mental health clinical pharmacy specialists (CPSs) within the VA work in a variety of settings, including but not limited to, the inpatient psychiatric unit; residential programs for posttraumatic stress disorder (PTSD) and substance misuse; as part of the Mental Health Intensive Case Management (MHICM) team; and in pain, telehealth, and other outpatient clinics. The VA’s mental health CPSs operate under an independent scope of practice (SOP) and manage a variety of mental health disorders. The SOP also allows pharmacists to independently manage medications for psychiatric conditions, request laboratory tests, and change therapy as needed based on patient response. The Table describes pharmacist-reported roles in a single VA facility in various mental health practice sites (eg, inpatient, outpatient, substance misuse). Pharmacist involvement in medication management with the interdisciplinary team improved symptoms, medication adherence, and reduced AEs for conditions such as depression.⁹

Within the VA, the outpatient mental health pharmacist works collaboratively with psychiatrists and HCPs to manage common psychiatric conditions on the phone and in person. VA pharmacists also are involved in the monitoring of patients on second-generation antipsychotics. Pharmacists assist with metabolic monitoring and assessing patients for movements disorders, using standardized rating scales. Pharmacists can manage complex psychiatric patients in collaboration with psychiatrists by providing medication management, laboratory test monitoring, medication counseling, and HCP referrals.

Pharmacists’ expertise is used in diverse ways in the VHA. At one facility, pharmacists functioned as interim prescribers when the facility experienced a turnover in behavioral health professionals. Pharmacists’ involvement decreased inappropriate use of psychiatric emergency services.¹⁰ VA pharmacists who manage patients’ mental health needs in primary care help achieve symptom improvement and medication adherence as well as lower referral rates for specialty mental health services.⁹ Pharmacist-managed electronic consult service provided a costs savings of about $40,000 a year.¹¹

Pharmacists have shown that they can expand their roles. Pharmacists are versatile HCPs, currently working and collaborating with other HCPs in various settings to provide mental health services. Health care systems need to continue to use and expand the number of pharmacists. Including pharmacists in the primary and specialty care teams can increase access to care and improve health outcomes during the pandemic and beyond. The American Association of Colleges of Pharmacy in partnership with the American Medical Association established a resource to support and guide institutions interested in embedding pharmacists into different clinical sites.¹² Opportunities for increased services by pharmacists can lead to improved outcomes, timely patient care, appropriate use of psychiatric medications and services, and cost savings.

Acknowledgments

We acknowledge the following Boise Veterans Affairs pharmacists: Paul Black, PharmD; Josh Gerving, PharmD; Kristin Helmboldt, PharmD; Samantha Patton, PharmD; Heather Walser, PharmD; and Andrea Winterswyk, PharmD, for contributing information about their practice roles and impact on patient care.

The number of opioid-related overdose deaths in the United States is estimated to have increased 6-fold over the past 2 decades.¹ In 2017, more than two-thirds of drug overdose deaths involved opioids, yielding a mortality rate of 14.9 per 100,000.² Not only does the opioid epidemic currently pose a significant public health crisis characterized by high morbidity and mortality, but it is also projected to worsen in coming years. According to Chen and colleagues, opioid overdose deaths are estimated to increase by 147% from 2015 to 2025.³ That projects almost 82,000 US deaths annually and > 700,000 deaths in this period—even before accounting for surges in opioid overdoses and opioid-related mortality coinciding with the COVID-19 pandemic.^3,4

As health systems and communities globally struggle with unprecedented losses and stressors introduced by the pandemic, emerging data warrants escalating concerns with regard to increased vulnerability to relapse and overdose among those with mental health and substance use disorders (SUDs). In a recent report, the American Medical Association estimates that opioid-related deaths have increased in more than 40 states with the COVID-19 pandemic.⁴

Veterans are twice as likely to experience a fatal opioid overdose compared with their civilian counterparts.⁵ While several risk mitigation strategies have been employed in recent years to improve opioid prescribing and safety within the US Department of Veterans Affairs (VA), veterans continue to overdose on opioids, both prescribed and obtained illicitly.⁶ Variables shown to be strongly associated with opioid overdose risk include presence of mental health disorders, SUDs, medical conditions involving impaired drug metabolism or excretion, respiratory disorders, higher doses of opioids, concomitant use of sedative medications, and history of overdose.^6-8 Many veterans struggle with chronic pain and those prescribed high doses of opioids were more likely to have comorbid pain diagnoses, mental health disorders, and SUDs.⁹ Dashboards and predictive models, such as the Stratification Tool for Opioid Risk Mitigation (STORM) and the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD), incorporate such factors to stratify overdose risk among veterans, in an effort to prioritize high-risk individuals for review and provision of care.^6,10,11 Despite recent recognition that overdose prevention likely requires a holistic approach that addresses the biopsychosocial factors contributing to opioid-related morbidity and mortality, it is unclear whether veterans are receiving adequate and appropriate treatment for contributing conditions.

There are currently no existing studies that describe health service utilization (HSU), medication interventions, and rates of opioid-related adverse events (ORAEs) among veterans after survival of a nonfatal opioid overdose (NFO). Clinical characteristics of veterans treated for opioid overdose at a VA emergency department (ED) have previously been described by Clement and Stock.¹² Despite improvements that have been made in VA opioid prescribing and safety, knowledge gaps remain with regard to best practices for opioid overdose prevention. The aim of this study was to characterize HSU and medication interventions in veterans following NFO, as well as the frequency of ORAEs after overdose. The findings of this study may aid in the identification of areas for targeted improvement in the prevention and reduction of opioid overdoses and adverse opioid-related sequelae.

Methods

This retrospective descriptive study was conducted at VA San Diego Healthcare System (VASDHCS) in California. Subjects included were veterans administered naloxone in the ED for suspected opioid overdose between July 1, 2013 and April 1, 2017. The study population was identified through data retrieved from automated drug dispensing systems, which was then confirmed through manual chart review of notes associated with the index ED visit. Inclusion criteria included documented increased respiration or responsiveness following naloxone administration. Subjects were excluded if they demonstrated lack of response to naloxone, overdosed secondary to inpatient administration of opioids, received palliative or hospice care during the study period, or were lost to follow-up.

Data were collected via retrospective chart review and included date of index ED visit, demographics, active prescriptions, urine drug screen (UDS) results, benzodiazepine (BZD) use corroborated by positive UDS or mention of BZD in index visit chart notes, whether overdose was determined to be a suicide attempt, and naloxone kit dispensing. Patient data was collected for 2 years following overdose, including: ORAEs; ED visits; hospitalizations; repeat overdoses; fatal overdose; whether subjects were still alive; follow-up visits for pain management, mental health, and addiction treatment services; and visits to the psychiatric emergency clinic. Clinical characteristics, such as mental health disorder diagnoses, SUDs, and relevant medical conditions also were collected. Statistical analysis was performed using Microsoft Excel and included only descriptive statistics.

Results

Ninety-three patients received naloxone in the VASDHCS ED. Thirty-five met inclusion criteria and were included in the primary analysis. All subjects received IV naloxone with a mean 0.8 mg IV boluses (range, 0.1-4.4 mg).

Most patients were male with a mean age of 59.8 years (Table 1). Almost all overdoses were nonintentional except for 3 suicide attempts that were reviewed by the Suicide Prevention Committee. Three patients had previously been treated for opioid overdose at the VA with a documented positive clinical response to naloxone administration.

Discussions

This retrospective study is representative of many veterans receiving VA care, despite the small sample size. Clinical characteristics observed in the study population were generally consistent with those published by Clement and Stock, including high rates of medical and psychiatric comorbidities.¹² Subjects in both studies were prescribed comparable dosages of opioids; among those prescribed opioids but not BZDs through the VA, the mean MEDD was 117 mg in our study compared with 126 mg in the Clement and Stock study. Since implementation of the Opioid Safety Initiative (OSI) in 2013, opioid prescribing practices have improved nationwide across VA facilities, including successful reduction in the numbers of patients prescribed high-dose opioids and concurrent BZDs.¹³

Despite the tools and resources available to clinicians, discontinuing opioid therapy remains a difficult process. Concerns related to mental health and/or substance-use related decompensations often exist in the setting of rapid dose reductions or abrupt discontinuation of opioids.⁶ Although less than half of patients in the present study with an active opioid prescription at time of index overdose had their opioids discontinued within 2 years, it is reassuring to note the much higher rate of those with subsequent decreases in their prescribed doses, as well as the 50% reduction in BZD coprescribing. Ultimately, these findings remain consistent with the VA goals of mitigating harm, improving opioid prescribing, and ensuring the safe use of opioid medications when clinically appropriate.

Moreover, recent evidence suggests that interventions focused solely on opioid prescribing practices are becoming increasingly limited in their impact on reducing opioid-related deaths and will likely be insufficient for addressing the opioid epidemic as it continues to evolve. According to Chen and colleagues, opioid overdose deaths are projected to increase over the next several years, while further reduction in the incidence of prescription opioid misuse is estimated to decrease overdose deaths by only 3% to 5.3%. In the context of recent surges in synthetic opioid use, it is projected that 80% of overdose deaths between 2016 and 2025 will be attributable to illicit opioids.³ Such predictions underscore the urgent need to adopt alternative approaches to risk-reducing measures and policy change.

The increased risk of mortality associated with opioid misuse and overdose is well established in the current literature. However, less is known regarding the rate of ORAEs after survival of an NFO. Olfson and colleagues sought to address this knowledge gap by characterizing mortality risks in 76,325 US adults within 1 year following NFO.¹⁴ Among their studied population, all-cause mortality occurred at a rate of 778.3 per 10,000 person-years, which was 24 times greater than that of the general population. This emphasizes the need for the optimization of mental health services, addiction treatment, and medical care for these individuals at higher risk.

Limitations

Certain factors and limitations should be considered when interpreting the results of this study. Given that the study included only veterans, factors such as the demographic and clinical characteristics more commonly observed among these patients should be taken into account and may in turn limit the generalizability of these findings to nonveteran populations. Another major limitation is the small sample size; the study period and by extension, the number of patients able to be included in the present study were restricted by the availability of retrievable data from automated drug dispensing systems. Patients without documented response to naloxone were excluded from the study due to low clinical suspicion for opioid overdose, although the possibility that the dose administered was too low to produce a robust clinical response cannot be definitively ruled out. The lack of reliable methods to capture events and overdoses treated outside of the VA may have resulted in underestimations of the true occurrence of ORAEs following NFO. Information regarding naloxone administration outside VA facilities, such as in transport to the hospital, self-reported, or bystander administration, was similarly limited by lack of reliable methods for retrieving such data and absence of documentation in VA records. Although all interventions and outcomes reported in the present study occurred within 2 years following NFO, further conclusions pertaining to the relative timing of specific interventions and ORAEs cannot be made. Lastly, this study did not investigate the direct impact of opioid risk mitigation initiatives implemented by the VA in the years coinciding with the study period.

Future Directions

Despite these limitations, an important strength of this study is its ability to identify potential areas for targeted improvement and to guide further efforts relating to the prevention of opioid overdose and opioid-related mortality among veterans. Identification of individuals at high risk for opioid overdose and misuse is an imperative first step that allows for the implementation of downstream risk-mitigating interventions. Within the VA, several tools have been developed in recent years to provide clinicians with additional resources and support in this regard.^6,15

No more than half of those diagnosed with mental health disorders and SUDs in the present study received outpatient follow-up care for these conditions within 6 months following NFO, which may suggest high rates of inadequate treatment. Given the strong association between mental health disorders, SUDs, and increased risk of overdose, increasing engagement with mental health and addiction treatment services may be paramount to preventing subsequent ORAEs, including repeat overdose.^6-9,11

Naloxone kit dispensing represents another area for targeted improvement. Interventions may include clinician education and systematic changes, such as implementing protocols that boost the likelihood of high-risk individuals being provided with naloxone at the earliest opportunity. Bystander-administered naloxone programs can also be considered for increasing naloxone access and reducing opioid-related mortality.¹⁶

Finally, despite evidence supporting the benefit of MAT in OUD treatment and reducing all-cause and opioid-related mortality after NFO, the low rates of MAT observed in this study are consistent with previous reports that these medications remain underutilized.¹⁷ Screening for OUD, in conjunction with increasing access to and utilization of OUD treatment modalities, is an established and integral component of overdose prevention efforts. For VA clinicians, the Psychotropic Drug Safety Initiative (PDSI) dashboard can be used to identify patients diagnosed with OUD who are not yet on MAT.¹⁸ Initiatives to expand MAT access through the ED have the potential to provide life-saving interventions and bridge care in the interim until patients are able to become established with a long-term health care practitioner.¹⁹

Conclusions

This is the first study to describe HSU, medication interventions, and ORAEs among veterans who survive NFO. Studies have shown that veterans with a history of NFO are at increased risk of subsequent AEs and premature death.^6,7,10,14 As such, NFOs represent crucial opportunities to identify high-risk individuals and ensure provision of adequate care. Recent data supports the development of a holistic, multimodal approach focused on adequate treatment of conditions that contribute to opioid-related risks, including mental health disorders, SUDs, pain diagnoses, and medical comorbidities.^3,14 Interventions designed to improve access, engagement, and retention in such care therefore play a pivotal role in overdose prevention and reducing mortality.

Although existing risk mitigation initiatives have improved opioid prescribing and safety within the VA, the findings of this study suggest that there remains room for improvement, and the need for well-coordinated efforts to reduce risks associated with both prescribed and illicit opioid use cannot be overstated. Rates of overdose deaths not only remain high but are projected to continue increasing in coming years, despite advances in clinical practice aimed at reducing harms associated with opioid use. The present findings aim to help identify processes with the potential to reduce rates of overdose, death, and adverse sequelae in high-risk populations. However, future studies are warranted to expand on these findings and contribute to ongoing efforts in reducing opioid-related harms and overdose deaths. This study may provide critical insight to inform further investigations to guide such interventions and highlight tools that health care facilities even outside the VA can consider implementing.

Acknowledgments

The authors would like to thank Jonathan Lacro, PharmD, BCPP, for his guidance with this important clinical topic and navigating IRB submissions.

The number of opioid-related overdose deaths in the United States is estimated to have increased 6-fold over the past 2 decades.¹ In 2017, more than two-thirds of drug overdose deaths involved opioids, yielding a mortality rate of 14.9 per 100,000.² Not only does the opioid epidemic currently pose a significant public health crisis characterized by high morbidity and mortality, but it is also projected to worsen in coming years. According to Chen and colleagues, opioid overdose deaths are estimated to increase by 147% from 2015 to 2025.³ That projects almost 82,000 US deaths annually and > 700,000 deaths in this period—even before accounting for surges in opioid overdoses and opioid-related mortality coinciding with the COVID-19 pandemic.^3,4

As health systems and communities globally struggle with unprecedented losses and stressors introduced by the pandemic, emerging data warrants escalating concerns with regard to increased vulnerability to relapse and overdose among those with mental health and substance use disorders (SUDs). In a recent report, the American Medical Association estimates that opioid-related deaths have increased in more than 40 states with the COVID-19 pandemic.⁴

Veterans are twice as likely to experience a fatal opioid overdose compared with their civilian counterparts.⁵ While several risk mitigation strategies have been employed in recent years to improve opioid prescribing and safety within the US Department of Veterans Affairs (VA), veterans continue to overdose on opioids, both prescribed and obtained illicitly.⁶ Variables shown to be strongly associated with opioid overdose risk include presence of mental health disorders, SUDs, medical conditions involving impaired drug metabolism or excretion, respiratory disorders, higher doses of opioids, concomitant use of sedative medications, and history of overdose.^6-8 Many veterans struggle with chronic pain and those prescribed high doses of opioids were more likely to have comorbid pain diagnoses, mental health disorders, and SUDs.⁹ Dashboards and predictive models, such as the Stratification Tool for Opioid Risk Mitigation (STORM) and the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD), incorporate such factors to stratify overdose risk among veterans, in an effort to prioritize high-risk individuals for review and provision of care.^6,10,11 Despite recent recognition that overdose prevention likely requires a holistic approach that addresses the biopsychosocial factors contributing to opioid-related morbidity and mortality, it is unclear whether veterans are receiving adequate and appropriate treatment for contributing conditions.

There are currently no existing studies that describe health service utilization (HSU), medication interventions, and rates of opioid-related adverse events (ORAEs) among veterans after survival of a nonfatal opioid overdose (NFO). Clinical characteristics of veterans treated for opioid overdose at a VA emergency department (ED) have previously been described by Clement and Stock.¹² Despite improvements that have been made in VA opioid prescribing and safety, knowledge gaps remain with regard to best practices for opioid overdose prevention. The aim of this study was to characterize HSU and medication interventions in veterans following NFO, as well as the frequency of ORAEs after overdose. The findings of this study may aid in the identification of areas for targeted improvement in the prevention and reduction of opioid overdoses and adverse opioid-related sequelae.

Methods

This retrospective descriptive study was conducted at VA San Diego Healthcare System (VASDHCS) in California. Subjects included were veterans administered naloxone in the ED for suspected opioid overdose between July 1, 2013 and April 1, 2017. The study population was identified through data retrieved from automated drug dispensing systems, which was then confirmed through manual chart review of notes associated with the index ED visit. Inclusion criteria included documented increased respiration or responsiveness following naloxone administration. Subjects were excluded if they demonstrated lack of response to naloxone, overdosed secondary to inpatient administration of opioids, received palliative or hospice care during the study period, or were lost to follow-up.

Data were collected via retrospective chart review and included date of index ED visit, demographics, active prescriptions, urine drug screen (UDS) results, benzodiazepine (BZD) use corroborated by positive UDS or mention of BZD in index visit chart notes, whether overdose was determined to be a suicide attempt, and naloxone kit dispensing. Patient data was collected for 2 years following overdose, including: ORAEs; ED visits; hospitalizations; repeat overdoses; fatal overdose; whether subjects were still alive; follow-up visits for pain management, mental health, and addiction treatment services; and visits to the psychiatric emergency clinic. Clinical characteristics, such as mental health disorder diagnoses, SUDs, and relevant medical conditions also were collected. Statistical analysis was performed using Microsoft Excel and included only descriptive statistics.

Results

Ninety-three patients received naloxone in the VASDHCS ED. Thirty-five met inclusion criteria and were included in the primary analysis. All subjects received IV naloxone with a mean 0.8 mg IV boluses (range, 0.1-4.4 mg).

Most patients were male with a mean age of 59.8 years (Table 1). Almost all overdoses were nonintentional except for 3 suicide attempts that were reviewed by the Suicide Prevention Committee. Three patients had previously been treated for opioid overdose at the VA with a documented positive clinical response to naloxone administration.

Discussions

This retrospective study is representative of many veterans receiving VA care, despite the small sample size. Clinical characteristics observed in the study population were generally consistent with those published by Clement and Stock, including high rates of medical and psychiatric comorbidities.¹² Subjects in both studies were prescribed comparable dosages of opioids; among those prescribed opioids but not BZDs through the VA, the mean MEDD was 117 mg in our study compared with 126 mg in the Clement and Stock study. Since implementation of the Opioid Safety Initiative (OSI) in 2013, opioid prescribing practices have improved nationwide across VA facilities, including successful reduction in the numbers of patients prescribed high-dose opioids and concurrent BZDs.¹³

Despite the tools and resources available to clinicians, discontinuing opioid therapy remains a difficult process. Concerns related to mental health and/or substance-use related decompensations often exist in the setting of rapid dose reductions or abrupt discontinuation of opioids.⁶ Although less than half of patients in the present study with an active opioid prescription at time of index overdose had their opioids discontinued within 2 years, it is reassuring to note the much higher rate of those with subsequent decreases in their prescribed doses, as well as the 50% reduction in BZD coprescribing. Ultimately, these findings remain consistent with the VA goals of mitigating harm, improving opioid prescribing, and ensuring the safe use of opioid medications when clinically appropriate.

Moreover, recent evidence suggests that interventions focused solely on opioid prescribing practices are becoming increasingly limited in their impact on reducing opioid-related deaths and will likely be insufficient for addressing the opioid epidemic as it continues to evolve. According to Chen and colleagues, opioid overdose deaths are projected to increase over the next several years, while further reduction in the incidence of prescription opioid misuse is estimated to decrease overdose deaths by only 3% to 5.3%. In the context of recent surges in synthetic opioid use, it is projected that 80% of overdose deaths between 2016 and 2025 will be attributable to illicit opioids.³ Such predictions underscore the urgent need to adopt alternative approaches to risk-reducing measures and policy change.

The increased risk of mortality associated with opioid misuse and overdose is well established in the current literature. However, less is known regarding the rate of ORAEs after survival of an NFO. Olfson and colleagues sought to address this knowledge gap by characterizing mortality risks in 76,325 US adults within 1 year following NFO.¹⁴ Among their studied population, all-cause mortality occurred at a rate of 778.3 per 10,000 person-years, which was 24 times greater than that of the general population. This emphasizes the need for the optimization of mental health services, addiction treatment, and medical care for these individuals at higher risk.

Limitations

Certain factors and limitations should be considered when interpreting the results of this study. Given that the study included only veterans, factors such as the demographic and clinical characteristics more commonly observed among these patients should be taken into account and may in turn limit the generalizability of these findings to nonveteran populations. Another major limitation is the small sample size; the study period and by extension, the number of patients able to be included in the present study were restricted by the availability of retrievable data from automated drug dispensing systems. Patients without documented response to naloxone were excluded from the study due to low clinical suspicion for opioid overdose, although the possibility that the dose administered was too low to produce a robust clinical response cannot be definitively ruled out. The lack of reliable methods to capture events and overdoses treated outside of the VA may have resulted in underestimations of the true occurrence of ORAEs following NFO. Information regarding naloxone administration outside VA facilities, such as in transport to the hospital, self-reported, or bystander administration, was similarly limited by lack of reliable methods for retrieving such data and absence of documentation in VA records. Although all interventions and outcomes reported in the present study occurred within 2 years following NFO, further conclusions pertaining to the relative timing of specific interventions and ORAEs cannot be made. Lastly, this study did not investigate the direct impact of opioid risk mitigation initiatives implemented by the VA in the years coinciding with the study period.

Future Directions

Despite these limitations, an important strength of this study is its ability to identify potential areas for targeted improvement and to guide further efforts relating to the prevention of opioid overdose and opioid-related mortality among veterans. Identification of individuals at high risk for opioid overdose and misuse is an imperative first step that allows for the implementation of downstream risk-mitigating interventions. Within the VA, several tools have been developed in recent years to provide clinicians with additional resources and support in this regard.^6,15

No more than half of those diagnosed with mental health disorders and SUDs in the present study received outpatient follow-up care for these conditions within 6 months following NFO, which may suggest high rates of inadequate treatment. Given the strong association between mental health disorders, SUDs, and increased risk of overdose, increasing engagement with mental health and addiction treatment services may be paramount to preventing subsequent ORAEs, including repeat overdose.^6-9,11

Naloxone kit dispensing represents another area for targeted improvement. Interventions may include clinician education and systematic changes, such as implementing protocols that boost the likelihood of high-risk individuals being provided with naloxone at the earliest opportunity. Bystander-administered naloxone programs can also be considered for increasing naloxone access and reducing opioid-related mortality.¹⁶

Finally, despite evidence supporting the benefit of MAT in OUD treatment and reducing all-cause and opioid-related mortality after NFO, the low rates of MAT observed in this study are consistent with previous reports that these medications remain underutilized.¹⁷ Screening for OUD, in conjunction with increasing access to and utilization of OUD treatment modalities, is an established and integral component of overdose prevention efforts. For VA clinicians, the Psychotropic Drug Safety Initiative (PDSI) dashboard can be used to identify patients diagnosed with OUD who are not yet on MAT.¹⁸ Initiatives to expand MAT access through the ED have the potential to provide life-saving interventions and bridge care in the interim until patients are able to become established with a long-term health care practitioner.¹⁹

Conclusions

This is the first study to describe HSU, medication interventions, and ORAEs among veterans who survive NFO. Studies have shown that veterans with a history of NFO are at increased risk of subsequent AEs and premature death.^6,7,10,14 As such, NFOs represent crucial opportunities to identify high-risk individuals and ensure provision of adequate care. Recent data supports the development of a holistic, multimodal approach focused on adequate treatment of conditions that contribute to opioid-related risks, including mental health disorders, SUDs, pain diagnoses, and medical comorbidities.^3,14 Interventions designed to improve access, engagement, and retention in such care therefore play a pivotal role in overdose prevention and reducing mortality.

Although existing risk mitigation initiatives have improved opioid prescribing and safety within the VA, the findings of this study suggest that there remains room for improvement, and the need for well-coordinated efforts to reduce risks associated with both prescribed and illicit opioid use cannot be overstated. Rates of overdose deaths not only remain high but are projected to continue increasing in coming years, despite advances in clinical practice aimed at reducing harms associated with opioid use. The present findings aim to help identify processes with the potential to reduce rates of overdose, death, and adverse sequelae in high-risk populations. However, future studies are warranted to expand on these findings and contribute to ongoing efforts in reducing opioid-related harms and overdose deaths. This study may provide critical insight to inform further investigations to guide such interventions and highlight tools that health care facilities even outside the VA can consider implementing.

Acknowledgments

The authors would like to thank Jonathan Lacro, PharmD, BCPP, for his guidance with this important clinical topic and navigating IRB submissions.

The number of opioid-related overdose deaths in the United States is estimated to have increased 6-fold over the past 2 decades.¹ In 2017, more than two-thirds of drug overdose deaths involved opioids, yielding a mortality rate of 14.9 per 100,000.² Not only does the opioid epidemic currently pose a significant public health crisis characterized by high morbidity and mortality, but it is also projected to worsen in coming years. According to Chen and colleagues, opioid overdose deaths are estimated to increase by 147% from 2015 to 2025.³ That projects almost 82,000 US deaths annually and > 700,000 deaths in this period—even before accounting for surges in opioid overdoses and opioid-related mortality coinciding with the COVID-19 pandemic.^3,4

As health systems and communities globally struggle with unprecedented losses and stressors introduced by the pandemic, emerging data warrants escalating concerns with regard to increased vulnerability to relapse and overdose among those with mental health and substance use disorders (SUDs). In a recent report, the American Medical Association estimates that opioid-related deaths have increased in more than 40 states with the COVID-19 pandemic.⁴

Veterans are twice as likely to experience a fatal opioid overdose compared with their civilian counterparts.⁵ While several risk mitigation strategies have been employed in recent years to improve opioid prescribing and safety within the US Department of Veterans Affairs (VA), veterans continue to overdose on opioids, both prescribed and obtained illicitly.⁶ Variables shown to be strongly associated with opioid overdose risk include presence of mental health disorders, SUDs, medical conditions involving impaired drug metabolism or excretion, respiratory disorders, higher doses of opioids, concomitant use of sedative medications, and history of overdose.^6-8 Many veterans struggle with chronic pain and those prescribed high doses of opioids were more likely to have comorbid pain diagnoses, mental health disorders, and SUDs.⁹ Dashboards and predictive models, such as the Stratification Tool for Opioid Risk Mitigation (STORM) and the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD), incorporate such factors to stratify overdose risk among veterans, in an effort to prioritize high-risk individuals for review and provision of care.^6,10,11 Despite recent recognition that overdose prevention likely requires a holistic approach that addresses the biopsychosocial factors contributing to opioid-related morbidity and mortality, it is unclear whether veterans are receiving adequate and appropriate treatment for contributing conditions.

There are currently no existing studies that describe health service utilization (HSU), medication interventions, and rates of opioid-related adverse events (ORAEs) among veterans after survival of a nonfatal opioid overdose (NFO). Clinical characteristics of veterans treated for opioid overdose at a VA emergency department (ED) have previously been described by Clement and Stock.¹² Despite improvements that have been made in VA opioid prescribing and safety, knowledge gaps remain with regard to best practices for opioid overdose prevention. The aim of this study was to characterize HSU and medication interventions in veterans following NFO, as well as the frequency of ORAEs after overdose. The findings of this study may aid in the identification of areas for targeted improvement in the prevention and reduction of opioid overdoses and adverse opioid-related sequelae.

Methods

This retrospective descriptive study was conducted at VA San Diego Healthcare System (VASDHCS) in California. Subjects included were veterans administered naloxone in the ED for suspected opioid overdose between July 1, 2013 and April 1, 2017. The study population was identified through data retrieved from automated drug dispensing systems, which was then confirmed through manual chart review of notes associated with the index ED visit. Inclusion criteria included documented increased respiration or responsiveness following naloxone administration. Subjects were excluded if they demonstrated lack of response to naloxone, overdosed secondary to inpatient administration of opioids, received palliative or hospice care during the study period, or were lost to follow-up.

Data were collected via retrospective chart review and included date of index ED visit, demographics, active prescriptions, urine drug screen (UDS) results, benzodiazepine (BZD) use corroborated by positive UDS or mention of BZD in index visit chart notes, whether overdose was determined to be a suicide attempt, and naloxone kit dispensing. Patient data was collected for 2 years following overdose, including: ORAEs; ED visits; hospitalizations; repeat overdoses; fatal overdose; whether subjects were still alive; follow-up visits for pain management, mental health, and addiction treatment services; and visits to the psychiatric emergency clinic. Clinical characteristics, such as mental health disorder diagnoses, SUDs, and relevant medical conditions also were collected. Statistical analysis was performed using Microsoft Excel and included only descriptive statistics.

Results

Ninety-three patients received naloxone in the VASDHCS ED. Thirty-five met inclusion criteria and were included in the primary analysis. All subjects received IV naloxone with a mean 0.8 mg IV boluses (range, 0.1-4.4 mg).

Most patients were male with a mean age of 59.8 years (Table 1). Almost all overdoses were nonintentional except for 3 suicide attempts that were reviewed by the Suicide Prevention Committee. Three patients had previously been treated for opioid overdose at the VA with a documented positive clinical response to naloxone administration.

Discussions

This retrospective study is representative of many veterans receiving VA care, despite the small sample size. Clinical characteristics observed in the study population were generally consistent with those published by Clement and Stock, including high rates of medical and psychiatric comorbidities.¹² Subjects in both studies were prescribed comparable dosages of opioids; among those prescribed opioids but not BZDs through the VA, the mean MEDD was 117 mg in our study compared with 126 mg in the Clement and Stock study. Since implementation of the Opioid Safety Initiative (OSI) in 2013, opioid prescribing practices have improved nationwide across VA facilities, including successful reduction in the numbers of patients prescribed high-dose opioids and concurrent BZDs.¹³

Despite the tools and resources available to clinicians, discontinuing opioid therapy remains a difficult process. Concerns related to mental health and/or substance-use related decompensations often exist in the setting of rapid dose reductions or abrupt discontinuation of opioids.⁶ Although less than half of patients in the present study with an active opioid prescription at time of index overdose had their opioids discontinued within 2 years, it is reassuring to note the much higher rate of those with subsequent decreases in their prescribed doses, as well as the 50% reduction in BZD coprescribing. Ultimately, these findings remain consistent with the VA goals of mitigating harm, improving opioid prescribing, and ensuring the safe use of opioid medications when clinically appropriate.

Moreover, recent evidence suggests that interventions focused solely on opioid prescribing practices are becoming increasingly limited in their impact on reducing opioid-related deaths and will likely be insufficient for addressing the opioid epidemic as it continues to evolve. According to Chen and colleagues, opioid overdose deaths are projected to increase over the next several years, while further reduction in the incidence of prescription opioid misuse is estimated to decrease overdose deaths by only 3% to 5.3%. In the context of recent surges in synthetic opioid use, it is projected that 80% of overdose deaths between 2016 and 2025 will be attributable to illicit opioids.³ Such predictions underscore the urgent need to adopt alternative approaches to risk-reducing measures and policy change.

The increased risk of mortality associated with opioid misuse and overdose is well established in the current literature. However, less is known regarding the rate of ORAEs after survival of an NFO. Olfson and colleagues sought to address this knowledge gap by characterizing mortality risks in 76,325 US adults within 1 year following NFO.¹⁴ Among their studied population, all-cause mortality occurred at a rate of 778.3 per 10,000 person-years, which was 24 times greater than that of the general population. This emphasizes the need for the optimization of mental health services, addiction treatment, and medical care for these individuals at higher risk.

Limitations

Certain factors and limitations should be considered when interpreting the results of this study. Given that the study included only veterans, factors such as the demographic and clinical characteristics more commonly observed among these patients should be taken into account and may in turn limit the generalizability of these findings to nonveteran populations. Another major limitation is the small sample size; the study period and by extension, the number of patients able to be included in the present study were restricted by the availability of retrievable data from automated drug dispensing systems. Patients without documented response to naloxone were excluded from the study due to low clinical suspicion for opioid overdose, although the possibility that the dose administered was too low to produce a robust clinical response cannot be definitively ruled out. The lack of reliable methods to capture events and overdoses treated outside of the VA may have resulted in underestimations of the true occurrence of ORAEs following NFO. Information regarding naloxone administration outside VA facilities, such as in transport to the hospital, self-reported, or bystander administration, was similarly limited by lack of reliable methods for retrieving such data and absence of documentation in VA records. Although all interventions and outcomes reported in the present study occurred within 2 years following NFO, further conclusions pertaining to the relative timing of specific interventions and ORAEs cannot be made. Lastly, this study did not investigate the direct impact of opioid risk mitigation initiatives implemented by the VA in the years coinciding with the study period.

Future Directions

Despite these limitations, an important strength of this study is its ability to identify potential areas for targeted improvement and to guide further efforts relating to the prevention of opioid overdose and opioid-related mortality among veterans. Identification of individuals at high risk for opioid overdose and misuse is an imperative first step that allows for the implementation of downstream risk-mitigating interventions. Within the VA, several tools have been developed in recent years to provide clinicians with additional resources and support in this regard.^6,15

No more than half of those diagnosed with mental health disorders and SUDs in the present study received outpatient follow-up care for these conditions within 6 months following NFO, which may suggest high rates of inadequate treatment. Given the strong association between mental health disorders, SUDs, and increased risk of overdose, increasing engagement with mental health and addiction treatment services may be paramount to preventing subsequent ORAEs, including repeat overdose.^6-9,11

Naloxone kit dispensing represents another area for targeted improvement. Interventions may include clinician education and systematic changes, such as implementing protocols that boost the likelihood of high-risk individuals being provided with naloxone at the earliest opportunity. Bystander-administered naloxone programs can also be considered for increasing naloxone access and reducing opioid-related mortality.¹⁶

Finally, despite evidence supporting the benefit of MAT in OUD treatment and reducing all-cause and opioid-related mortality after NFO, the low rates of MAT observed in this study are consistent with previous reports that these medications remain underutilized.¹⁷ Screening for OUD, in conjunction with increasing access to and utilization of OUD treatment modalities, is an established and integral component of overdose prevention efforts. For VA clinicians, the Psychotropic Drug Safety Initiative (PDSI) dashboard can be used to identify patients diagnosed with OUD who are not yet on MAT.¹⁸ Initiatives to expand MAT access through the ED have the potential to provide life-saving interventions and bridge care in the interim until patients are able to become established with a long-term health care practitioner.¹⁹

Conclusions

This is the first study to describe HSU, medication interventions, and ORAEs among veterans who survive NFO. Studies have shown that veterans with a history of NFO are at increased risk of subsequent AEs and premature death.^6,7,10,14 As such, NFOs represent crucial opportunities to identify high-risk individuals and ensure provision of adequate care. Recent data supports the development of a holistic, multimodal approach focused on adequate treatment of conditions that contribute to opioid-related risks, including mental health disorders, SUDs, pain diagnoses, and medical comorbidities.^3,14 Interventions designed to improve access, engagement, and retention in such care therefore play a pivotal role in overdose prevention and reducing mortality.

Although existing risk mitigation initiatives have improved opioid prescribing and safety within the VA, the findings of this study suggest that there remains room for improvement, and the need for well-coordinated efforts to reduce risks associated with both prescribed and illicit opioid use cannot be overstated. Rates of overdose deaths not only remain high but are projected to continue increasing in coming years, despite advances in clinical practice aimed at reducing harms associated with opioid use. The present findings aim to help identify processes with the potential to reduce rates of overdose, death, and adverse sequelae in high-risk populations. However, future studies are warranted to expand on these findings and contribute to ongoing efforts in reducing opioid-related harms and overdose deaths. This study may provide critical insight to inform further investigations to guide such interventions and highlight tools that health care facilities even outside the VA can consider implementing.

Acknowledgments

The authors would like to thank Jonathan Lacro, PharmD, BCPP, for his guidance with this important clinical topic and navigating IRB submissions.

Nontuberculous Mycobacterium (NTM) is a ubiquitous organism known to cause a variety of infections in susceptible hosts; however, pulmonary infection is the most common. Mycobacterium avium complex (MAC) is the most prevalent cause of NTM-related pulmonary disease (NTM-PD) and is associated with underlying structural lung disease, such as chronic obstructive pulmonary disease (COPD) and noncystic fibrosis bronchiectasis.^1-3

Diagnosis of NTM-PD requires (1) symptoms or radiographic abnormality; and (2) at least 2 sputum cultures positive with the same organism or at least 1 positive culture result on bronchoscopy (wash, lavage, or biopsy).¹ Notably, the natural history of untreated NTM-PD varies, though even mild disease may progress substantially.^4-6 Progressive disease is more likely to occur in those with a positive smear or more extensive radiographic findings at the initial diagnosis.⁷ A nationwide Medicare-based study showed that patients with NTM-PD had a higher rate of all-cause mortality than did patients without NTM-PD.⁸ In a study of 123 patients from Taiwan with MAC-PD, lack of treatment was an independent predictor of mortality.⁹ Given the risk of progressive morbidity and mortality, recent guidelines recommend initiation of a susceptibility driven, macrolide-based, 3-drug treatment regimen over watchful waiting.¹⁰

MAC-PD is increasingly recognized among US veterans.^11,12 The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in south/west Chicago serves a large, predominantly Black male population of veterans many of whom are socioeconomically underresourced, and half are aged ≥ 65 years. We observed that initiation of guideline-directed therapy in veterans with MAC-PD at JBVAMC varied among health care professionals (HCPs) in the pulmonary clinic. Therefore, the purpose of this retrospective study was to describe and compare the characteristics of veterans without HIV were diagnosed with MAC-PD and managed at JBVAMC.

Methods

The hospital microbiology department identified veterans diagnosed with NTM at JBVAMC between October 2008 and July 2019. Veterans included in the study were considered to have MAC-PD per American Thoracic Society (ATS)/Infectious Diseases Society of America (ISDA) guidelines and those diagnosed with HIV were excluded from analysis. The electronic health record (EHR) was queried for pertinent demographics, smoking history, comorbidities, and symptoms at the time of a positive mycobacterial culture. Computed tomography (CT) and pulmonary function tests (PFTs) performed within 1 year of diagnosis were included. PFTs were assessed in accordance with Global Initiative for Obstructive Lung Disease (GOLD) criteria, with normal forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) values defined as ≥ 80% and a normal FEV₁/FVC ratio defined as ≥ 70. The diffusion capacity of lung for carbon monoxide (DLCO) was assessed per 2017 European Respiratory Society (ERS) technical standards and was considered reduced if below the lower limit of normal.¹³ Information regarding treatment decisions, initiation, and cessation were collected. All-cause mortality was recorded if available in the EHR at the time of data collection.

Statistical analysis was performed using Mann-Whitney U and Fisher exact tests where appropriate. P < .05 was considered statistically significant. The study was approved by the JBVAMC Institutional Review Board.

Results

We identified 43 veterans who had a positive culture for MAC; however, only 19 veterans met the diagnostic criteria for MAC-PD and were included in the study (Table). The cohort included predominantly Black and male veterans with a median age of 74 years at time of diagnosis (range, 45-92). Sixteen veterans had underlying lung disease (84.2%), and 16 (84.2%) were current or former smokers. Common comorbidities included COPD, obstructive sleep apnea, gastroesophageal reflux disease, and lung cancer. Respiratory symptoms were reported in 17 veterans (89.5%), 15 (78.9%) had a chronic cough, and 10 (52.6%) had dyspnea. Fifteen veterans had a chest CT scan within 1 year of diagnosis: A nodular and tree-in-bud pattern was most commonly found in 13 (86.7%) of veterans. Thirteen veterans had PFTs within 1 year of MAC-PD diagnosis, of whom 6 had a restrictive pattern with percent predicted FVC < 80%, and 9 had evidence of obstruction with FEV₁/FVC < 70. DLCO was below the lower limit of normal in 18 veterans. Finally, 6 veterans were deceased at the time of the study.

Of the 19 veterans, guideline-directed, combination antimycobacterial therapy for MAC-PD was initiated in only 10 (52.6%) patients due to presence of symptoms and/or imaging abnormalities. Treatment was deferred due to improved symptoms, concern for adverse events (AEs), or lost to follow-up. Five veterans stopped treatment prematurely due to AEs, lost to follow-up, or all-cause mortality. Assessment of differences between treated and untreated groups revealed no significant difference in race, sex, age, body mass index (BMI), symptom presence, or chest CT abnormalities. There was no statistically significant difference in all-cause mortality (40% and 22.2% in treated and untreated group, respectively).

To further understand the differences of this cohort, the 13 veterans alive at time of the study were compared with the 6 who had since died of all-cause mortality. No statistically significant differences were found.

Discussion

Consistent with previous reports in the literature, veterans in our cohort were predominantly current or former smoking males with underlying COPD and bronchiectasis.^1-3,11,12 Chest CT findings varied: Most veterans presented not only with nodules and tree-in-bud opacities, but also a high frequency of fibrosis and emphysema. PFTs revealed a variety of obstruction and restrictive patterns, and most veterans had a reduced DLCO, though it is unclear whether this is reflective of underlying emphysema, fibrosis, or an alternative cardiopulmonary disease.^13,14

While underlying structural lung disease may have been a risk factor for MAC-PD in this cohort, the contribution of environmental and domiciliary factors in metropolitan Chicago neighborhoods is unknown. JBVAMC serves an underresourced population who live in the west and south Chicago neighborhoods. Household factors, ambient and indoor air pollution, and potential contamination of the water supply and surface soil may contribute to the prevalence of MAC-PD in this group.^15-19 Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.

Recent ATS, European Society of Clinical Microbiology and Infectious Diseases, and IDSA guidelines recommend combination antimycobacterial therapy for patients who meet clinical, radiographic, and microbiologic criteria for the diagnosis of MAC-PD.¹⁰ Patients who meet these diagnostic criteria, particularly patients with smear positivity or fibrocavitary disease, should be treated because of risk of unfavorable outcomes.^15,20-22 However, we found that the initiation of guideline-recommended antimycobacterial therapy in veterans without HIV with MAC-PD were inconsistent among HCPs. The reasons underlying this phenomenon were not apparent beyond cited reasons for treatment initiation or deference. Despite this inconsistency, there was no clear difference in age, BMI, symptom burden, radiographic abnormality, or all-cause mortality between treatment groups. Existing studies support slow but substantial progression of untreated MAC-PD, and while treatment prevents deterioration of the disease, it does not prevent progression of bronchiectasis.⁶ The natural history of MAC-PD in this veteran cohort has yet to be fully elucidated. Furthermore, the 50% treatment dropout rate was higher than previously reported rates (11-33%).⁵ However, the small number of veterans in this study precludes meaningful comparison with similar reports in the literature.

We did note a relatively high all-cause mortality in this cohort (n = 6, 32%); however, this rate is comparable to the all-cause mortality rate of 27% observed in a 2018 meta-analysis of 9035 patients with MAC-PD.²³ Although there was no major difference in those deceased and those alive at the time of data collection in our study, previously described predictors of mortality included male sex, advanced age, presence of fibrocavitary disease, decreased FVC, and presence of comorbidities.^8,23 Larger prospective studies evaluating veterans with MAC-PD are needed to further evaluate contributors to mortality in veterans with MAC-PD.

Limitations

The limitations of this small, single-center, retrospective study prevent a robust, generalizable comparison between groups. Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.^24-26

Conclusions

These data suggest that clinical, imaging, and treatment attributes of MAC-PD in veterans without HIV who reside in metropolitan Chicago are heterogeneous and are associated with a relatively high mortality rate. Although there was no difference in the attributes or outcomes of veterans who did and did not initiate treatment despite current recommendations, further studies are needed to better explore these relationships.

Nontuberculous Mycobacterium (NTM) is a ubiquitous organism known to cause a variety of infections in susceptible hosts; however, pulmonary infection is the most common. Mycobacterium avium complex (MAC) is the most prevalent cause of NTM-related pulmonary disease (NTM-PD) and is associated with underlying structural lung disease, such as chronic obstructive pulmonary disease (COPD) and noncystic fibrosis bronchiectasis.^1-3

Diagnosis of NTM-PD requires (1) symptoms or radiographic abnormality; and (2) at least 2 sputum cultures positive with the same organism or at least 1 positive culture result on bronchoscopy (wash, lavage, or biopsy).¹ Notably, the natural history of untreated NTM-PD varies, though even mild disease may progress substantially.^4-6 Progressive disease is more likely to occur in those with a positive smear or more extensive radiographic findings at the initial diagnosis.⁷ A nationwide Medicare-based study showed that patients with NTM-PD had a higher rate of all-cause mortality than did patients without NTM-PD.⁸ In a study of 123 patients from Taiwan with MAC-PD, lack of treatment was an independent predictor of mortality.⁹ Given the risk of progressive morbidity and mortality, recent guidelines recommend initiation of a susceptibility driven, macrolide-based, 3-drug treatment regimen over watchful waiting.¹⁰

MAC-PD is increasingly recognized among US veterans.^11,12 The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in south/west Chicago serves a large, predominantly Black male population of veterans many of whom are socioeconomically underresourced, and half are aged ≥ 65 years. We observed that initiation of guideline-directed therapy in veterans with MAC-PD at JBVAMC varied among health care professionals (HCPs) in the pulmonary clinic. Therefore, the purpose of this retrospective study was to describe and compare the characteristics of veterans without HIV were diagnosed with MAC-PD and managed at JBVAMC.

Methods

The hospital microbiology department identified veterans diagnosed with NTM at JBVAMC between October 2008 and July 2019. Veterans included in the study were considered to have MAC-PD per American Thoracic Society (ATS)/Infectious Diseases Society of America (ISDA) guidelines and those diagnosed with HIV were excluded from analysis. The electronic health record (EHR) was queried for pertinent demographics, smoking history, comorbidities, and symptoms at the time of a positive mycobacterial culture. Computed tomography (CT) and pulmonary function tests (PFTs) performed within 1 year of diagnosis were included. PFTs were assessed in accordance with Global Initiative for Obstructive Lung Disease (GOLD) criteria, with normal forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) values defined as ≥ 80% and a normal FEV₁/FVC ratio defined as ≥ 70. The diffusion capacity of lung for carbon monoxide (DLCO) was assessed per 2017 European Respiratory Society (ERS) technical standards and was considered reduced if below the lower limit of normal.¹³ Information regarding treatment decisions, initiation, and cessation were collected. All-cause mortality was recorded if available in the EHR at the time of data collection.

Statistical analysis was performed using Mann-Whitney U and Fisher exact tests where appropriate. P < .05 was considered statistically significant. The study was approved by the JBVAMC Institutional Review Board.

Results

We identified 43 veterans who had a positive culture for MAC; however, only 19 veterans met the diagnostic criteria for MAC-PD and were included in the study (Table). The cohort included predominantly Black and male veterans with a median age of 74 years at time of diagnosis (range, 45-92). Sixteen veterans had underlying lung disease (84.2%), and 16 (84.2%) were current or former smokers. Common comorbidities included COPD, obstructive sleep apnea, gastroesophageal reflux disease, and lung cancer. Respiratory symptoms were reported in 17 veterans (89.5%), 15 (78.9%) had a chronic cough, and 10 (52.6%) had dyspnea. Fifteen veterans had a chest CT scan within 1 year of diagnosis: A nodular and tree-in-bud pattern was most commonly found in 13 (86.7%) of veterans. Thirteen veterans had PFTs within 1 year of MAC-PD diagnosis, of whom 6 had a restrictive pattern with percent predicted FVC < 80%, and 9 had evidence of obstruction with FEV₁/FVC < 70. DLCO was below the lower limit of normal in 18 veterans. Finally, 6 veterans were deceased at the time of the study.

Of the 19 veterans, guideline-directed, combination antimycobacterial therapy for MAC-PD was initiated in only 10 (52.6%) patients due to presence of symptoms and/or imaging abnormalities. Treatment was deferred due to improved symptoms, concern for adverse events (AEs), or lost to follow-up. Five veterans stopped treatment prematurely due to AEs, lost to follow-up, or all-cause mortality. Assessment of differences between treated and untreated groups revealed no significant difference in race, sex, age, body mass index (BMI), symptom presence, or chest CT abnormalities. There was no statistically significant difference in all-cause mortality (40% and 22.2% in treated and untreated group, respectively).

To further understand the differences of this cohort, the 13 veterans alive at time of the study were compared with the 6 who had since died of all-cause mortality. No statistically significant differences were found.

Discussion

Consistent with previous reports in the literature, veterans in our cohort were predominantly current or former smoking males with underlying COPD and bronchiectasis.^1-3,11,12 Chest CT findings varied: Most veterans presented not only with nodules and tree-in-bud opacities, but also a high frequency of fibrosis and emphysema. PFTs revealed a variety of obstruction and restrictive patterns, and most veterans had a reduced DLCO, though it is unclear whether this is reflective of underlying emphysema, fibrosis, or an alternative cardiopulmonary disease.^13,14

While underlying structural lung disease may have been a risk factor for MAC-PD in this cohort, the contribution of environmental and domiciliary factors in metropolitan Chicago neighborhoods is unknown. JBVAMC serves an underresourced population who live in the west and south Chicago neighborhoods. Household factors, ambient and indoor air pollution, and potential contamination of the water supply and surface soil may contribute to the prevalence of MAC-PD in this group.^15-19 Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.

Recent ATS, European Society of Clinical Microbiology and Infectious Diseases, and IDSA guidelines recommend combination antimycobacterial therapy for patients who meet clinical, radiographic, and microbiologic criteria for the diagnosis of MAC-PD.¹⁰ Patients who meet these diagnostic criteria, particularly patients with smear positivity or fibrocavitary disease, should be treated because of risk of unfavorable outcomes.^15,20-22 However, we found that the initiation of guideline-recommended antimycobacterial therapy in veterans without HIV with MAC-PD were inconsistent among HCPs. The reasons underlying this phenomenon were not apparent beyond cited reasons for treatment initiation or deference. Despite this inconsistency, there was no clear difference in age, BMI, symptom burden, radiographic abnormality, or all-cause mortality between treatment groups. Existing studies support slow but substantial progression of untreated MAC-PD, and while treatment prevents deterioration of the disease, it does not prevent progression of bronchiectasis.⁶ The natural history of MAC-PD in this veteran cohort has yet to be fully elucidated. Furthermore, the 50% treatment dropout rate was higher than previously reported rates (11-33%).⁵ However, the small number of veterans in this study precludes meaningful comparison with similar reports in the literature.

We did note a relatively high all-cause mortality in this cohort (n = 6, 32%); however, this rate is comparable to the all-cause mortality rate of 27% observed in a 2018 meta-analysis of 9035 patients with MAC-PD.²³ Although there was no major difference in those deceased and those alive at the time of data collection in our study, previously described predictors of mortality included male sex, advanced age, presence of fibrocavitary disease, decreased FVC, and presence of comorbidities.^8,23 Larger prospective studies evaluating veterans with MAC-PD are needed to further evaluate contributors to mortality in veterans with MAC-PD.

Limitations

The limitations of this small, single-center, retrospective study prevent a robust, generalizable comparison between groups. Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.^24-26

Conclusions

These data suggest that clinical, imaging, and treatment attributes of MAC-PD in veterans without HIV who reside in metropolitan Chicago are heterogeneous and are associated with a relatively high mortality rate. Although there was no difference in the attributes or outcomes of veterans who did and did not initiate treatment despite current recommendations, further studies are needed to better explore these relationships.

Nontuberculous Mycobacterium (NTM) is a ubiquitous organism known to cause a variety of infections in susceptible hosts; however, pulmonary infection is the most common. Mycobacterium avium complex (MAC) is the most prevalent cause of NTM-related pulmonary disease (NTM-PD) and is associated with underlying structural lung disease, such as chronic obstructive pulmonary disease (COPD) and noncystic fibrosis bronchiectasis.^1-3

Diagnosis of NTM-PD requires (1) symptoms or radiographic abnormality; and (2) at least 2 sputum cultures positive with the same organism or at least 1 positive culture result on bronchoscopy (wash, lavage, or biopsy).¹ Notably, the natural history of untreated NTM-PD varies, though even mild disease may progress substantially.^4-6 Progressive disease is more likely to occur in those with a positive smear or more extensive radiographic findings at the initial diagnosis.⁷ A nationwide Medicare-based study showed that patients with NTM-PD had a higher rate of all-cause mortality than did patients without NTM-PD.⁸ In a study of 123 patients from Taiwan with MAC-PD, lack of treatment was an independent predictor of mortality.⁹ Given the risk of progressive morbidity and mortality, recent guidelines recommend initiation of a susceptibility driven, macrolide-based, 3-drug treatment regimen over watchful waiting.¹⁰

MAC-PD is increasingly recognized among US veterans.^11,12 The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in south/west Chicago serves a large, predominantly Black male population of veterans many of whom are socioeconomically underresourced, and half are aged ≥ 65 years. We observed that initiation of guideline-directed therapy in veterans with MAC-PD at JBVAMC varied among health care professionals (HCPs) in the pulmonary clinic. Therefore, the purpose of this retrospective study was to describe and compare the characteristics of veterans without HIV were diagnosed with MAC-PD and managed at JBVAMC.

Methods

The hospital microbiology department identified veterans diagnosed with NTM at JBVAMC between October 2008 and July 2019. Veterans included in the study were considered to have MAC-PD per American Thoracic Society (ATS)/Infectious Diseases Society of America (ISDA) guidelines and those diagnosed with HIV were excluded from analysis. The electronic health record (EHR) was queried for pertinent demographics, smoking history, comorbidities, and symptoms at the time of a positive mycobacterial culture. Computed tomography (CT) and pulmonary function tests (PFTs) performed within 1 year of diagnosis were included. PFTs were assessed in accordance with Global Initiative for Obstructive Lung Disease (GOLD) criteria, with normal forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) values defined as ≥ 80% and a normal FEV₁/FVC ratio defined as ≥ 70. The diffusion capacity of lung for carbon monoxide (DLCO) was assessed per 2017 European Respiratory Society (ERS) technical standards and was considered reduced if below the lower limit of normal.¹³ Information regarding treatment decisions, initiation, and cessation were collected. All-cause mortality was recorded if available in the EHR at the time of data collection.

Statistical analysis was performed using Mann-Whitney U and Fisher exact tests where appropriate. P < .05 was considered statistically significant. The study was approved by the JBVAMC Institutional Review Board.

Results

We identified 43 veterans who had a positive culture for MAC; however, only 19 veterans met the diagnostic criteria for MAC-PD and were included in the study (Table). The cohort included predominantly Black and male veterans with a median age of 74 years at time of diagnosis (range, 45-92). Sixteen veterans had underlying lung disease (84.2%), and 16 (84.2%) were current or former smokers. Common comorbidities included COPD, obstructive sleep apnea, gastroesophageal reflux disease, and lung cancer. Respiratory symptoms were reported in 17 veterans (89.5%), 15 (78.9%) had a chronic cough, and 10 (52.6%) had dyspnea. Fifteen veterans had a chest CT scan within 1 year of diagnosis: A nodular and tree-in-bud pattern was most commonly found in 13 (86.7%) of veterans. Thirteen veterans had PFTs within 1 year of MAC-PD diagnosis, of whom 6 had a restrictive pattern with percent predicted FVC < 80%, and 9 had evidence of obstruction with FEV₁/FVC < 70. DLCO was below the lower limit of normal in 18 veterans. Finally, 6 veterans were deceased at the time of the study.

Of the 19 veterans, guideline-directed, combination antimycobacterial therapy for MAC-PD was initiated in only 10 (52.6%) patients due to presence of symptoms and/or imaging abnormalities. Treatment was deferred due to improved symptoms, concern for adverse events (AEs), or lost to follow-up. Five veterans stopped treatment prematurely due to AEs, lost to follow-up, or all-cause mortality. Assessment of differences between treated and untreated groups revealed no significant difference in race, sex, age, body mass index (BMI), symptom presence, or chest CT abnormalities. There was no statistically significant difference in all-cause mortality (40% and 22.2% in treated and untreated group, respectively).

To further understand the differences of this cohort, the 13 veterans alive at time of the study were compared with the 6 who had since died of all-cause mortality. No statistically significant differences were found.

Discussion

Consistent with previous reports in the literature, veterans in our cohort were predominantly current or former smoking males with underlying COPD and bronchiectasis.^1-3,11,12 Chest CT findings varied: Most veterans presented not only with nodules and tree-in-bud opacities, but also a high frequency of fibrosis and emphysema. PFTs revealed a variety of obstruction and restrictive patterns, and most veterans had a reduced DLCO, though it is unclear whether this is reflective of underlying emphysema, fibrosis, or an alternative cardiopulmonary disease.^13,14

While underlying structural lung disease may have been a risk factor for MAC-PD in this cohort, the contribution of environmental and domiciliary factors in metropolitan Chicago neighborhoods is unknown. JBVAMC serves an underresourced population who live in the west and south Chicago neighborhoods. Household factors, ambient and indoor air pollution, and potential contamination of the water supply and surface soil may contribute to the prevalence of MAC-PD in this group.^15-19 Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.

Recent ATS, European Society of Clinical Microbiology and Infectious Diseases, and IDSA guidelines recommend combination antimycobacterial therapy for patients who meet clinical, radiographic, and microbiologic criteria for the diagnosis of MAC-PD.¹⁰ Patients who meet these diagnostic criteria, particularly patients with smear positivity or fibrocavitary disease, should be treated because of risk of unfavorable outcomes.^15,20-22 However, we found that the initiation of guideline-recommended antimycobacterial therapy in veterans without HIV with MAC-PD were inconsistent among HCPs. The reasons underlying this phenomenon were not apparent beyond cited reasons for treatment initiation or deference. Despite this inconsistency, there was no clear difference in age, BMI, symptom burden, radiographic abnormality, or all-cause mortality between treatment groups. Existing studies support slow but substantial progression of untreated MAC-PD, and while treatment prevents deterioration of the disease, it does not prevent progression of bronchiectasis.⁶ The natural history of MAC-PD in this veteran cohort has yet to be fully elucidated. Furthermore, the 50% treatment dropout rate was higher than previously reported rates (11-33%).⁵ However, the small number of veterans in this study precludes meaningful comparison with similar reports in the literature.

We did note a relatively high all-cause mortality in this cohort (n = 6, 32%); however, this rate is comparable to the all-cause mortality rate of 27% observed in a 2018 meta-analysis of 9035 patients with MAC-PD.²³ Although there was no major difference in those deceased and those alive at the time of data collection in our study, previously described predictors of mortality included male sex, advanced age, presence of fibrocavitary disease, decreased FVC, and presence of comorbidities.^8,23 Larger prospective studies evaluating veterans with MAC-PD are needed to further evaluate contributors to mortality in veterans with MAC-PD.

Limitations

The limitations of this small, single-center, retrospective study prevent a robust, generalizable comparison between groups. Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.^24-26

Conclusions

These data suggest that clinical, imaging, and treatment attributes of MAC-PD in veterans without HIV who reside in metropolitan Chicago are heterogeneous and are associated with a relatively high mortality rate. Although there was no difference in the attributes or outcomes of veterans who did and did not initiate treatment despite current recommendations, further studies are needed to better explore these relationships.