New signals of a potential additive benefit from the nonsteroidal mineralocorticoid antagonist finerenone (Kerendia) and a sodium-glucose transporter 2 inhibitor in patients with type 2 diabetes and chronic kidney disease (CKD) emerged in a follow-up report from the FIDELITY analysis, which combined data from more than 13,000 patients who received finerenone in either of the two pivotal trials with the agent.

The analysis showed that the 877 patients enrolled in either the FIDELIO DKD or FIGARO DKD trials taking an SGLT2 inhibitor at baseline had a 37% relative reduction in their urinary albumin-to-creatinine ratio (UACR), compared with placebo-treated patients after a median of 3 years on treatment.

Among the remaining 12,149 patients who did not receive an SGLT2 inhibitor, finerenone cut the average UACR by 32%, compared with placebo, said Peter Rossing, DMSc, MD, who presented the findings on Feb. 27 at the World Congress of Nephrology 2022 in Kuala Lumpur, Malaysia.

Primary endpoint results for FIDELIO-DKD and FIGARO-DKD also suggest similar additive effects of finerenone plus an SGLT2 inhibitor.

Results of the composite renal endpoint in each study – progression to kidney failure, renal death, or at least a 57% decline in estimated glomerular filtration rate (eGFR) from baseline – showed a 58% relative risk reduction in patients who received agents from both drug classes and a 20% relative risk reduction in those who only received finerenone, a between-group difference that was not significant.

For the composite cardiovascular event endpoint – cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure – the rate fell by 37%, compared with placebo, in patients who also received an SGLT2 inhibitor, and by 13%, compared with placebo, in those who received finerenone but no SGLT2 inhibitor, also a difference that was not significant.

‘A lot of interest in finerenone’ in U.S.

“The benefits of finerenone on cardiovascular and kidney outcomes were consistent, irrespective of SGLT2 inhibitor use at baseline,” concluded Dr. Rossing, professor and head of research at the Steno Diabetes Center in Copenhagen.

The new findings are a “suggestion that the two classes might be additive [in their effects], but more data are needed,” Dr. Rossing said during his presentation.

But he cautioned that in both pivotal trials randomization did not consider SGLT2 inhibitor use. All patients in the two trials were already receiving a renin-angiotensin system (RAS) inhibitor as background treatment, either an ACE inhibitor or angiotensin-receptor blocker.

The consequence of treatment with finerenone combined with an SGLT2 inhibitor is of growing importance because “an SGLT2 inhibitor is now recommended in most guidelines” for the type of patients enrolled in the two finerenone trials, explained Dr. Rossing.

He also noted that the first guideline to recommend routine use of finerenone in indicated patients appeared recently in the annual update to Standards of Medical Care in Diabetes – 2022 published by the American Diabetes Association.

The 2022 Standards states: “In patients with CKD who are at increased risk for cardiovascular events or CKD progression or are unable to use an SGLT2 inhibitor, a nonsteroidal mineralocorticoid receptor antagonist (finerenone) is recommended to reduce CKD progression and cardiovascular events.”

Results from FIDELIO-DKD, reported in the New England Journal of Medicine in 2020, and the main study, FIGARO-DKD, published in the same journal in 2021, led the Food and Drug Administration to approve finerenone in July 2021 to slow the progression of renal disease in patients with type 2 diabetes and CKD.

“My impression is that in the United States there is a lot of interest in finerenone,” Dr. Rossing said during the discussion following his presentation.

Finerenone has also been recently approved in the European Union.
 

‘Consistent’ benefits irrespective of SGLT2 inhibitors

“The cardiovascular and kidney benefits of finerenone were consistent irrespective of SGLT2 inhibitor use. This is definitely interesting and warrants a randomized controlled trial” to examine the relationship in a more rigorous way, commented Tejas Desai, MD, a nephrologist with the Department of Veterans Affairs, Charlotte, N.C.

That study, CONFIDENCE, is on its way, Dr. Rossing said during his talk. The randomized phase 2 trial has a planned enrollment of 800 patients with type 2 diabetes and CKD and three treatment groups: finerenone plus placebo, the SGLT2 inhibitor empagliflozin (Jardiance) plus placebo, or finerenone plus empagliflozin. The study will launch later in 2022 and has a planned completion date of late 2023.

“SGLT2 inhibitors, compared with finerenone, is where all of this is headed. We need a large trial that adjudicates the best medication to use with a RAS inhibitor,” Dr. Desai said in an interview.

The new analyses from the combined FIDELITY study expand on a previous report presented at the 2021 annual congress of the European Society of Cardiology and published in the European Heart Journal.
 

‘Impressive’ effect on cardiovascular events

The main findings from FIDELITY presented in those earlier reports, in 13,026 patients, showed there was a significant 14% relative reduction in the composite cardiovascular endpoint with finerenone, compared with placebo, during a median 3 years of follow-up.

The same report documented, in the total combined cohort, a significant 23% relative reduction in the composite renal endpoint in those taking finerenone compared with placebo.

“Reducing the risk of cardiovascular endpoints by a relative 14% is impressive,” and the time course showed a “relatively quick onset of action,” Dr. Desai noted.

He also characterized the enrolled patients, which included many with stage 3 or 4 CKD, as “not the sickest population of patients with CKD,” but rather “relatively healthier patients with CKD.”

Dr. Desai also downplayed the importance of the observed reduction in UACR associated with finerenone in FIDELITY.

“UACR is a surrogate marker. Results from many studies have shown improvements in UACR only to not show protection against falls in eGFR rate,” Dr. Desai said.

He was also reassured by the low incidence of hyperkalemia that led to discontinuation, which occurred in 1.7% of patients taking finerenone and in 0.6% of those taking placebo.

The types of patients enrolled in FIDELIO-DKD and FIGARO-DKD, who did not have eGFR rates below 25 mL/min per 1.73 m², are not particularly susceptible to this adverse effect, he said, noting, “I’m not overly concerned with hyperkalemia in this CKD population.

“I’m more concerned about [hyperkalemia in] patients with CKD and an eGFR of less than 25 mL/min per 1.73 m², but this was less than 1% of the enrolled population,” Dr. Desai observed.

FIDELIO-DKD, FIGARO-DKD, and FIDELITY were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Rossing reported being a consultant for Bayer and other drug companies, and receiving research funding from AstraZeneca and Novo Nordisk. Dr. Desai reported no relevant financial relationships.

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

New signals of a potential additive benefit from the nonsteroidal mineralocorticoid antagonist finerenone (Kerendia) and a sodium-glucose transporter 2 inhibitor in patients with type 2 diabetes and chronic kidney disease (CKD) emerged in a follow-up report from the FIDELITY analysis, which combined data from more than 13,000 patients who received finerenone in either of the two pivotal trials with the agent.

The analysis showed that the 877 patients enrolled in either the FIDELIO DKD or FIGARO DKD trials taking an SGLT2 inhibitor at baseline had a 37% relative reduction in their urinary albumin-to-creatinine ratio (UACR), compared with placebo-treated patients after a median of 3 years on treatment.

Among the remaining 12,149 patients who did not receive an SGLT2 inhibitor, finerenone cut the average UACR by 32%, compared with placebo, said Peter Rossing, DMSc, MD, who presented the findings on Feb. 27 at the World Congress of Nephrology 2022 in Kuala Lumpur, Malaysia.

Primary endpoint results for FIDELIO-DKD and FIGARO-DKD also suggest similar additive effects of finerenone plus an SGLT2 inhibitor.

Results of the composite renal endpoint in each study – progression to kidney failure, renal death, or at least a 57% decline in estimated glomerular filtration rate (eGFR) from baseline – showed a 58% relative risk reduction in patients who received agents from both drug classes and a 20% relative risk reduction in those who only received finerenone, a between-group difference that was not significant.

For the composite cardiovascular event endpoint – cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure – the rate fell by 37%, compared with placebo, in patients who also received an SGLT2 inhibitor, and by 13%, compared with placebo, in those who received finerenone but no SGLT2 inhibitor, also a difference that was not significant.

‘A lot of interest in finerenone’ in U.S.

“The benefits of finerenone on cardiovascular and kidney outcomes were consistent, irrespective of SGLT2 inhibitor use at baseline,” concluded Dr. Rossing, professor and head of research at the Steno Diabetes Center in Copenhagen.

The new findings are a “suggestion that the two classes might be additive [in their effects], but more data are needed,” Dr. Rossing said during his presentation.

But he cautioned that in both pivotal trials randomization did not consider SGLT2 inhibitor use. All patients in the two trials were already receiving a renin-angiotensin system (RAS) inhibitor as background treatment, either an ACE inhibitor or angiotensin-receptor blocker.

The consequence of treatment with finerenone combined with an SGLT2 inhibitor is of growing importance because “an SGLT2 inhibitor is now recommended in most guidelines” for the type of patients enrolled in the two finerenone trials, explained Dr. Rossing.

He also noted that the first guideline to recommend routine use of finerenone in indicated patients appeared recently in the annual update to Standards of Medical Care in Diabetes – 2022 published by the American Diabetes Association.

The 2022 Standards states: “In patients with CKD who are at increased risk for cardiovascular events or CKD progression or are unable to use an SGLT2 inhibitor, a nonsteroidal mineralocorticoid receptor antagonist (finerenone) is recommended to reduce CKD progression and cardiovascular events.”

Results from FIDELIO-DKD, reported in the New England Journal of Medicine in 2020, and the main study, FIGARO-DKD, published in the same journal in 2021, led the Food and Drug Administration to approve finerenone in July 2021 to slow the progression of renal disease in patients with type 2 diabetes and CKD.

“My impression is that in the United States there is a lot of interest in finerenone,” Dr. Rossing said during the discussion following his presentation.

Finerenone has also been recently approved in the European Union.
 

‘Consistent’ benefits irrespective of SGLT2 inhibitors

“The cardiovascular and kidney benefits of finerenone were consistent irrespective of SGLT2 inhibitor use. This is definitely interesting and warrants a randomized controlled trial” to examine the relationship in a more rigorous way, commented Tejas Desai, MD, a nephrologist with the Department of Veterans Affairs, Charlotte, N.C.

That study, CONFIDENCE, is on its way, Dr. Rossing said during his talk. The randomized phase 2 trial has a planned enrollment of 800 patients with type 2 diabetes and CKD and three treatment groups: finerenone plus placebo, the SGLT2 inhibitor empagliflozin (Jardiance) plus placebo, or finerenone plus empagliflozin. The study will launch later in 2022 and has a planned completion date of late 2023.

“SGLT2 inhibitors, compared with finerenone, is where all of this is headed. We need a large trial that adjudicates the best medication to use with a RAS inhibitor,” Dr. Desai said in an interview.

The new analyses from the combined FIDELITY study expand on a previous report presented at the 2021 annual congress of the European Society of Cardiology and published in the European Heart Journal.
 

‘Impressive’ effect on cardiovascular events

The main findings from FIDELITY presented in those earlier reports, in 13,026 patients, showed there was a significant 14% relative reduction in the composite cardiovascular endpoint with finerenone, compared with placebo, during a median 3 years of follow-up.

The same report documented, in the total combined cohort, a significant 23% relative reduction in the composite renal endpoint in those taking finerenone compared with placebo.

“Reducing the risk of cardiovascular endpoints by a relative 14% is impressive,” and the time course showed a “relatively quick onset of action,” Dr. Desai noted.

He also characterized the enrolled patients, which included many with stage 3 or 4 CKD, as “not the sickest population of patients with CKD,” but rather “relatively healthier patients with CKD.”

Dr. Desai also downplayed the importance of the observed reduction in UACR associated with finerenone in FIDELITY.

“UACR is a surrogate marker. Results from many studies have shown improvements in UACR only to not show protection against falls in eGFR rate,” Dr. Desai said.

He was also reassured by the low incidence of hyperkalemia that led to discontinuation, which occurred in 1.7% of patients taking finerenone and in 0.6% of those taking placebo.

The types of patients enrolled in FIDELIO-DKD and FIGARO-DKD, who did not have eGFR rates below 25 mL/min per 1.73 m², are not particularly susceptible to this adverse effect, he said, noting, “I’m not overly concerned with hyperkalemia in this CKD population.

“I’m more concerned about [hyperkalemia in] patients with CKD and an eGFR of less than 25 mL/min per 1.73 m², but this was less than 1% of the enrolled population,” Dr. Desai observed.

FIDELIO-DKD, FIGARO-DKD, and FIDELITY were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Rossing reported being a consultant for Bayer and other drug companies, and receiving research funding from AstraZeneca and Novo Nordisk. Dr. Desai reported no relevant financial relationships.

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

New signals of a potential additive benefit from the nonsteroidal mineralocorticoid antagonist finerenone (Kerendia) and a sodium-glucose transporter 2 inhibitor in patients with type 2 diabetes and chronic kidney disease (CKD) emerged in a follow-up report from the FIDELITY analysis, which combined data from more than 13,000 patients who received finerenone in either of the two pivotal trials with the agent.

The analysis showed that the 877 patients enrolled in either the FIDELIO DKD or FIGARO DKD trials taking an SGLT2 inhibitor at baseline had a 37% relative reduction in their urinary albumin-to-creatinine ratio (UACR), compared with placebo-treated patients after a median of 3 years on treatment.

Among the remaining 12,149 patients who did not receive an SGLT2 inhibitor, finerenone cut the average UACR by 32%, compared with placebo, said Peter Rossing, DMSc, MD, who presented the findings on Feb. 27 at the World Congress of Nephrology 2022 in Kuala Lumpur, Malaysia.

Primary endpoint results for FIDELIO-DKD and FIGARO-DKD also suggest similar additive effects of finerenone plus an SGLT2 inhibitor.

Results of the composite renal endpoint in each study – progression to kidney failure, renal death, or at least a 57% decline in estimated glomerular filtration rate (eGFR) from baseline – showed a 58% relative risk reduction in patients who received agents from both drug classes and a 20% relative risk reduction in those who only received finerenone, a between-group difference that was not significant.

For the composite cardiovascular event endpoint – cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure – the rate fell by 37%, compared with placebo, in patients who also received an SGLT2 inhibitor, and by 13%, compared with placebo, in those who received finerenone but no SGLT2 inhibitor, also a difference that was not significant.

‘A lot of interest in finerenone’ in U.S.

“The benefits of finerenone on cardiovascular and kidney outcomes were consistent, irrespective of SGLT2 inhibitor use at baseline,” concluded Dr. Rossing, professor and head of research at the Steno Diabetes Center in Copenhagen.

The new findings are a “suggestion that the two classes might be additive [in their effects], but more data are needed,” Dr. Rossing said during his presentation.

But he cautioned that in both pivotal trials randomization did not consider SGLT2 inhibitor use. All patients in the two trials were already receiving a renin-angiotensin system (RAS) inhibitor as background treatment, either an ACE inhibitor or angiotensin-receptor blocker.

The consequence of treatment with finerenone combined with an SGLT2 inhibitor is of growing importance because “an SGLT2 inhibitor is now recommended in most guidelines” for the type of patients enrolled in the two finerenone trials, explained Dr. Rossing.

He also noted that the first guideline to recommend routine use of finerenone in indicated patients appeared recently in the annual update to Standards of Medical Care in Diabetes – 2022 published by the American Diabetes Association.

The 2022 Standards states: “In patients with CKD who are at increased risk for cardiovascular events or CKD progression or are unable to use an SGLT2 inhibitor, a nonsteroidal mineralocorticoid receptor antagonist (finerenone) is recommended to reduce CKD progression and cardiovascular events.”

Results from FIDELIO-DKD, reported in the New England Journal of Medicine in 2020, and the main study, FIGARO-DKD, published in the same journal in 2021, led the Food and Drug Administration to approve finerenone in July 2021 to slow the progression of renal disease in patients with type 2 diabetes and CKD.

“My impression is that in the United States there is a lot of interest in finerenone,” Dr. Rossing said during the discussion following his presentation.

Finerenone has also been recently approved in the European Union.
 

‘Consistent’ benefits irrespective of SGLT2 inhibitors

“The cardiovascular and kidney benefits of finerenone were consistent irrespective of SGLT2 inhibitor use. This is definitely interesting and warrants a randomized controlled trial” to examine the relationship in a more rigorous way, commented Tejas Desai, MD, a nephrologist with the Department of Veterans Affairs, Charlotte, N.C.

That study, CONFIDENCE, is on its way, Dr. Rossing said during his talk. The randomized phase 2 trial has a planned enrollment of 800 patients with type 2 diabetes and CKD and three treatment groups: finerenone plus placebo, the SGLT2 inhibitor empagliflozin (Jardiance) plus placebo, or finerenone plus empagliflozin. The study will launch later in 2022 and has a planned completion date of late 2023.

“SGLT2 inhibitors, compared with finerenone, is where all of this is headed. We need a large trial that adjudicates the best medication to use with a RAS inhibitor,” Dr. Desai said in an interview.

The new analyses from the combined FIDELITY study expand on a previous report presented at the 2021 annual congress of the European Society of Cardiology and published in the European Heart Journal.
 

‘Impressive’ effect on cardiovascular events

The main findings from FIDELITY presented in those earlier reports, in 13,026 patients, showed there was a significant 14% relative reduction in the composite cardiovascular endpoint with finerenone, compared with placebo, during a median 3 years of follow-up.

The same report documented, in the total combined cohort, a significant 23% relative reduction in the composite renal endpoint in those taking finerenone compared with placebo.

“Reducing the risk of cardiovascular endpoints by a relative 14% is impressive,” and the time course showed a “relatively quick onset of action,” Dr. Desai noted.

He also characterized the enrolled patients, which included many with stage 3 or 4 CKD, as “not the sickest population of patients with CKD,” but rather “relatively healthier patients with CKD.”

Dr. Desai also downplayed the importance of the observed reduction in UACR associated with finerenone in FIDELITY.

“UACR is a surrogate marker. Results from many studies have shown improvements in UACR only to not show protection against falls in eGFR rate,” Dr. Desai said.

He was also reassured by the low incidence of hyperkalemia that led to discontinuation, which occurred in 1.7% of patients taking finerenone and in 0.6% of those taking placebo.

The types of patients enrolled in FIDELIO-DKD and FIGARO-DKD, who did not have eGFR rates below 25 mL/min per 1.73 m², are not particularly susceptible to this adverse effect, he said, noting, “I’m not overly concerned with hyperkalemia in this CKD population.

“I’m more concerned about [hyperkalemia in] patients with CKD and an eGFR of less than 25 mL/min per 1.73 m², but this was less than 1% of the enrolled population,” Dr. Desai observed.

FIDELIO-DKD, FIGARO-DKD, and FIDELITY were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Rossing reported being a consultant for Bayer and other drug companies, and receiving research funding from AstraZeneca and Novo Nordisk. Dr. Desai reported no relevant financial relationships.

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

A single injection of the experimental agent nirsevimab ahead of respiratory syncytial virus (RSV) season protects healthy infants from lower respiratory tract infections associated with the pathogen, according to the results of a phase 3 study.

A previously published trial showed that a single dose of nirsevimab was effective in preterm infants. The ability to protect all babies from RSV, which causes bronchiolitis and pneumonia and is a leading cause of hospitalization for this age group, “would be a paradigm shift in the approach to this disease,” William Muller, MD, PhD, of the Lurie Children’s Hospital of Chicago and a coauthor of the study, said in a statement.

The primary endpoint of the study was medically attended lower respiratory tract infections linked to RSV. The single injection of nirsevimab was associated with a 74.5% reduction in such infections (P < .001), according to Dr. Muller’s group, who published their findings March 2 in the New England Journal of Medicine.

Nirsevimab, a monoclonal antibody to the RSV fusion protein being developed by AstraZeneca and Sanofi, has an extended half-life, which may allow one dose to confer protection throughout a season. The only approved option to prevent RSV, palivizumab (Synagis), is used for high-risk infants, and five injections are needed to cover a viral season.
 

Nearly 1,500 infants in more than 20 countries studied

To assess the effectiveness of nirsevimab in late-preterm and term infants, investigators at 160 sites randomly assigned 1,490 babies born at a gestational age of at least 35 weeks to receive an intramuscular injection of nirsevimab or placebo.

During the 150 days after injection, medically attended RSV-associated lower respiratory tract infections occurred in 12 of 994 infants who received nirsevimab, compared with 25 of 496 babies who received placebo (1.2% vs. 5%).

Six of 994 infants who received nirsevimab were hospitalized for RSV-associated lower respiratory tract infections, compared with 8 of 496 infants in the placebo group (0.6% vs. 1.6%; P = .07). The proportion of children hospitalized for any respiratory illness as a result of RSV was 0.9% among those who received nirsevimab, compared with 2.2% among those who received placebo.

Serious adverse events occurred in 6.8% of the nirsevimab group and 7.3% of the placebo group. None of these events, including three deaths in the nirsevimab group, was considered related to nirsevimab or placebo, according to the researchers. One infant who received nirsevimab had a generalized macular rash without systemic features that did not require treatment and resolved in 20 days, they said.

Antidrug antibodies were detected in 6.1% of the nirsevimab group and in 1.1% of the placebo group. These antidrug antibodies tended to develop later and did not affect nirsevimab pharmacokinetics during the RSV season, the researchers reported. How they might affect subsequent doses of nirsevimab is not known, they added.

In a separate report in the journal, researcher Joseph Domachowske, MD, SUNY Upstate Medical University, Syracuse, New York, and colleagues described safety results from an ongoing study of nirsevimab that includes infants with congenital heart disease, chronic lung disease, and prematurity.

In this trial, infants received nirsevimab or palivizumab, and the treatments appeared to have similar safety profiles, the authors reported.

Other approaches to RSV protection include passive antibodies acquired from maternal vaccination in pregnancy and active vaccination of infants.

The publication follows news last month that GlaxoSmithKline is pausing a maternal RSV vaccine trial, which “had the same goal of protecting babies against severe RSV infection,” said Louis Bont, MD, PhD, with University Medical Center Utrecht, the Netherlands.

RSV infection is one of the deadliest diseases during infancy, and the nirsevimab trial, conducted in more than 20 countries, is “gamechanging,” Dr. Bont told this news organization. Still, researchers will need to monitor for RSV resistance to this treatment, he said.

Whether nirsevimab prevents the development of reactive airway disease and asthma is another open question, he said.

“Finally, we need to keep in mind that RSV mortality is almost limited to the developing world, and it is unlikely that this novel drug will become available to these countries in the coming years,” Dr. Bont said. “Nevertheless, nirsevimab has the potential to seriously decrease the annual overwhelming number of RSV infected babies.”

Nirsevimab may have advantages in low- and middle-income countries, including its potential to be incorporated into established immunization programs and to be given seasonally, said Amy Sarah Ginsburg, MD, MPH, of the University of Washington, Seattle. “However, cost remains a significant factor, as does susceptibility to pathogen escape,” she said.

MedImmune/AstraZeneca and Sanofi funded the nirsevimab studies. UMC Utrecht has received research grants and fees for advisory work from AstraZeneca for RSV-related work by Bont.

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

A single injection of the experimental agent nirsevimab ahead of respiratory syncytial virus (RSV) season protects healthy infants from lower respiratory tract infections associated with the pathogen, according to the results of a phase 3 study.

A previously published trial showed that a single dose of nirsevimab was effective in preterm infants. The ability to protect all babies from RSV, which causes bronchiolitis and pneumonia and is a leading cause of hospitalization for this age group, “would be a paradigm shift in the approach to this disease,” William Muller, MD, PhD, of the Lurie Children’s Hospital of Chicago and a coauthor of the study, said in a statement.

The primary endpoint of the study was medically attended lower respiratory tract infections linked to RSV. The single injection of nirsevimab was associated with a 74.5% reduction in such infections (P < .001), according to Dr. Muller’s group, who published their findings March 2 in the New England Journal of Medicine.

Nirsevimab, a monoclonal antibody to the RSV fusion protein being developed by AstraZeneca and Sanofi, has an extended half-life, which may allow one dose to confer protection throughout a season. The only approved option to prevent RSV, palivizumab (Synagis), is used for high-risk infants, and five injections are needed to cover a viral season.
 

Nearly 1,500 infants in more than 20 countries studied

To assess the effectiveness of nirsevimab in late-preterm and term infants, investigators at 160 sites randomly assigned 1,490 babies born at a gestational age of at least 35 weeks to receive an intramuscular injection of nirsevimab or placebo.

During the 150 days after injection, medically attended RSV-associated lower respiratory tract infections occurred in 12 of 994 infants who received nirsevimab, compared with 25 of 496 babies who received placebo (1.2% vs. 5%).

Six of 994 infants who received nirsevimab were hospitalized for RSV-associated lower respiratory tract infections, compared with 8 of 496 infants in the placebo group (0.6% vs. 1.6%; P = .07). The proportion of children hospitalized for any respiratory illness as a result of RSV was 0.9% among those who received nirsevimab, compared with 2.2% among those who received placebo.

Serious adverse events occurred in 6.8% of the nirsevimab group and 7.3% of the placebo group. None of these events, including three deaths in the nirsevimab group, was considered related to nirsevimab or placebo, according to the researchers. One infant who received nirsevimab had a generalized macular rash without systemic features that did not require treatment and resolved in 20 days, they said.

Antidrug antibodies were detected in 6.1% of the nirsevimab group and in 1.1% of the placebo group. These antidrug antibodies tended to develop later and did not affect nirsevimab pharmacokinetics during the RSV season, the researchers reported. How they might affect subsequent doses of nirsevimab is not known, they added.

In a separate report in the journal, researcher Joseph Domachowske, MD, SUNY Upstate Medical University, Syracuse, New York, and colleagues described safety results from an ongoing study of nirsevimab that includes infants with congenital heart disease, chronic lung disease, and prematurity.

In this trial, infants received nirsevimab or palivizumab, and the treatments appeared to have similar safety profiles, the authors reported.

Other approaches to RSV protection include passive antibodies acquired from maternal vaccination in pregnancy and active vaccination of infants.

The publication follows news last month that GlaxoSmithKline is pausing a maternal RSV vaccine trial, which “had the same goal of protecting babies against severe RSV infection,” said Louis Bont, MD, PhD, with University Medical Center Utrecht, the Netherlands.

RSV infection is one of the deadliest diseases during infancy, and the nirsevimab trial, conducted in more than 20 countries, is “gamechanging,” Dr. Bont told this news organization. Still, researchers will need to monitor for RSV resistance to this treatment, he said.

Whether nirsevimab prevents the development of reactive airway disease and asthma is another open question, he said.

“Finally, we need to keep in mind that RSV mortality is almost limited to the developing world, and it is unlikely that this novel drug will become available to these countries in the coming years,” Dr. Bont said. “Nevertheless, nirsevimab has the potential to seriously decrease the annual overwhelming number of RSV infected babies.”

Nirsevimab may have advantages in low- and middle-income countries, including its potential to be incorporated into established immunization programs and to be given seasonally, said Amy Sarah Ginsburg, MD, MPH, of the University of Washington, Seattle. “However, cost remains a significant factor, as does susceptibility to pathogen escape,” she said.

MedImmune/AstraZeneca and Sanofi funded the nirsevimab studies. UMC Utrecht has received research grants and fees for advisory work from AstraZeneca for RSV-related work by Bont.

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

A single injection of the experimental agent nirsevimab ahead of respiratory syncytial virus (RSV) season protects healthy infants from lower respiratory tract infections associated with the pathogen, according to the results of a phase 3 study.

A previously published trial showed that a single dose of nirsevimab was effective in preterm infants. The ability to protect all babies from RSV, which causes bronchiolitis and pneumonia and is a leading cause of hospitalization for this age group, “would be a paradigm shift in the approach to this disease,” William Muller, MD, PhD, of the Lurie Children’s Hospital of Chicago and a coauthor of the study, said in a statement.

The primary endpoint of the study was medically attended lower respiratory tract infections linked to RSV. The single injection of nirsevimab was associated with a 74.5% reduction in such infections (P < .001), according to Dr. Muller’s group, who published their findings March 2 in the New England Journal of Medicine.

Nirsevimab, a monoclonal antibody to the RSV fusion protein being developed by AstraZeneca and Sanofi, has an extended half-life, which may allow one dose to confer protection throughout a season. The only approved option to prevent RSV, palivizumab (Synagis), is used for high-risk infants, and five injections are needed to cover a viral season.
 

Nearly 1,500 infants in more than 20 countries studied

To assess the effectiveness of nirsevimab in late-preterm and term infants, investigators at 160 sites randomly assigned 1,490 babies born at a gestational age of at least 35 weeks to receive an intramuscular injection of nirsevimab or placebo.

During the 150 days after injection, medically attended RSV-associated lower respiratory tract infections occurred in 12 of 994 infants who received nirsevimab, compared with 25 of 496 babies who received placebo (1.2% vs. 5%).

Six of 994 infants who received nirsevimab were hospitalized for RSV-associated lower respiratory tract infections, compared with 8 of 496 infants in the placebo group (0.6% vs. 1.6%; P = .07). The proportion of children hospitalized for any respiratory illness as a result of RSV was 0.9% among those who received nirsevimab, compared with 2.2% among those who received placebo.

Serious adverse events occurred in 6.8% of the nirsevimab group and 7.3% of the placebo group. None of these events, including three deaths in the nirsevimab group, was considered related to nirsevimab or placebo, according to the researchers. One infant who received nirsevimab had a generalized macular rash without systemic features that did not require treatment and resolved in 20 days, they said.

Antidrug antibodies were detected in 6.1% of the nirsevimab group and in 1.1% of the placebo group. These antidrug antibodies tended to develop later and did not affect nirsevimab pharmacokinetics during the RSV season, the researchers reported. How they might affect subsequent doses of nirsevimab is not known, they added.

In a separate report in the journal, researcher Joseph Domachowske, MD, SUNY Upstate Medical University, Syracuse, New York, and colleagues described safety results from an ongoing study of nirsevimab that includes infants with congenital heart disease, chronic lung disease, and prematurity.

In this trial, infants received nirsevimab or palivizumab, and the treatments appeared to have similar safety profiles, the authors reported.

Other approaches to RSV protection include passive antibodies acquired from maternal vaccination in pregnancy and active vaccination of infants.

The publication follows news last month that GlaxoSmithKline is pausing a maternal RSV vaccine trial, which “had the same goal of protecting babies against severe RSV infection,” said Louis Bont, MD, PhD, with University Medical Center Utrecht, the Netherlands.

RSV infection is one of the deadliest diseases during infancy, and the nirsevimab trial, conducted in more than 20 countries, is “gamechanging,” Dr. Bont told this news organization. Still, researchers will need to monitor for RSV resistance to this treatment, he said.

Whether nirsevimab prevents the development of reactive airway disease and asthma is another open question, he said.

“Finally, we need to keep in mind that RSV mortality is almost limited to the developing world, and it is unlikely that this novel drug will become available to these countries in the coming years,” Dr. Bont said. “Nevertheless, nirsevimab has the potential to seriously decrease the annual overwhelming number of RSV infected babies.”

Nirsevimab may have advantages in low- and middle-income countries, including its potential to be incorporated into established immunization programs and to be given seasonally, said Amy Sarah Ginsburg, MD, MPH, of the University of Washington, Seattle. “However, cost remains a significant factor, as does susceptibility to pathogen escape,” she said.

MedImmune/AstraZeneca and Sanofi funded the nirsevimab studies. UMC Utrecht has received research grants and fees for advisory work from AstraZeneca for RSV-related work by Bont.

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

Children who are diagnosed with inflammatory bowel disease (IBD) are more than twice as likely to develop cancer, especially gastrointestinal cancer, later in life compared with the general pediatric population, a new meta-analysis suggests.

Although the overall incidence rate of cancer in this population is low, “we found a 2.4-fold increase in the relative rate of cancer among patients with pediatric-onset IBD compared with the general pediatric population, primarily associated with an increased rate of gastrointestinal cancers,” wrote senior author Tine Jess, MD, DMSci, Aalborg University, Copenhagen, and colleagues.

The study was published online March 1 in JAMA Network Open.

Previous research indicates that IBD is associated with an increased risk for colon, small bowel, and other types of cancer in adults, but the risk among children with IBD is not well understood.

In the current analysis, Dr. Jess and colleagues examined five population-based studies from North America and Europe, which included more than 19,800 participants with pediatric-onset IBD. Of these participants, 715 were later diagnosed with cancer.

Overall, the risk for cancer among individuals with pediatric-onset IBD was 2.4-fold higher than that of their peers without IBD, but those rates varied by IBD subtype. Those with Crohn’s disease, for instance, were about two times more likely to develop cancer, while those with ulcerative colitis were 2.6 times more likely to develop cancer later.

Two studies included in the meta-analysis broke down results by sex and found that the risk for cancer was higher among male versus female patients (pooled relative rates [pRR], 3.23 in men and 2.45 in women).

These two studies also calculated the risk for cancer by exposure to thiopurines. Patients receiving these immunosuppressive drugs had an increased relative rate of cancer (pRR, 2.09). Although numerically higher, this rate was not statistically higher compared with patients not exposed to the drugs (pRR, 1.82).

When looking at risk by cancer site, the authors consistently observed the highest relative rates for gastrointestinal cancers. Specifically, the investigators calculated a 55-fold increased risk for liver cancer (pRR, 55.4), followed by a 20-fold increased risk for colorectal cancer (pRR, 20.2), and a 16-fold increased risk for small bowel cancer (pRR, 16.2).

Despite such high estimates for gastrointestinal cancers, “this risk corresponds to a mean incidence rate of 0.3 cases of liver cancer, 0.6 cases of colorectal cancer, and 0.1 cases of small bowel cancer per 1,000 person-years in this population,” the authors noted.

In other words, “the overall incidence rate of cancer in this population is low,” at less than 3.3 cases per 1,000 person-years, the authors concluded.

Relative rates of extraintestinal cancers were even lower, with the highest risks for nonmelanoma skin cancer (pRR, 3.62), lymphoid cancer (pRR, 3.10), and melanoma (pRR, 2.05).

The authors suggest that identifying variables that might reduce cancer risk in pediatric patients who develop IBD could better shape management and prevention strategies.

CRC screening guidelines already recommend that children undergo a colonoscopy 6-8 years after being diagnosed with colitis extending beyond the rectum. Annual colonoscopy is also recommended for patients with primary sclerosing cholangitis from the time of diagnosis and annual screening for skin cancer is recommended for all patients with IBD.

The investigators further suggest that because ongoing inflammation is an important risk factor for cancer, early and adequate control of inflammation could be critical in the prevention of long-term complications.

The study was supported by a grant from the Danish National Research Foundation. Dr. Jess and coauthors Rahma Elmahdi, MD, Camilla Lemser, and Kristine Allin, MD, reported receiving grants from the Danish National Research Foundation National Center of Excellence during the conduct of the study. Coauthor Manasi Agrawal, MD, reported receiving grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study.

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

Children who are diagnosed with inflammatory bowel disease (IBD) are more than twice as likely to develop cancer, especially gastrointestinal cancer, later in life compared with the general pediatric population, a new meta-analysis suggests.

Although the overall incidence rate of cancer in this population is low, “we found a 2.4-fold increase in the relative rate of cancer among patients with pediatric-onset IBD compared with the general pediatric population, primarily associated with an increased rate of gastrointestinal cancers,” wrote senior author Tine Jess, MD, DMSci, Aalborg University, Copenhagen, and colleagues.

The study was published online March 1 in JAMA Network Open.

Previous research indicates that IBD is associated with an increased risk for colon, small bowel, and other types of cancer in adults, but the risk among children with IBD is not well understood.

In the current analysis, Dr. Jess and colleagues examined five population-based studies from North America and Europe, which included more than 19,800 participants with pediatric-onset IBD. Of these participants, 715 were later diagnosed with cancer.

Overall, the risk for cancer among individuals with pediatric-onset IBD was 2.4-fold higher than that of their peers without IBD, but those rates varied by IBD subtype. Those with Crohn’s disease, for instance, were about two times more likely to develop cancer, while those with ulcerative colitis were 2.6 times more likely to develop cancer later.

Two studies included in the meta-analysis broke down results by sex and found that the risk for cancer was higher among male versus female patients (pooled relative rates [pRR], 3.23 in men and 2.45 in women).

These two studies also calculated the risk for cancer by exposure to thiopurines. Patients receiving these immunosuppressive drugs had an increased relative rate of cancer (pRR, 2.09). Although numerically higher, this rate was not statistically higher compared with patients not exposed to the drugs (pRR, 1.82).

When looking at risk by cancer site, the authors consistently observed the highest relative rates for gastrointestinal cancers. Specifically, the investigators calculated a 55-fold increased risk for liver cancer (pRR, 55.4), followed by a 20-fold increased risk for colorectal cancer (pRR, 20.2), and a 16-fold increased risk for small bowel cancer (pRR, 16.2).

Despite such high estimates for gastrointestinal cancers, “this risk corresponds to a mean incidence rate of 0.3 cases of liver cancer, 0.6 cases of colorectal cancer, and 0.1 cases of small bowel cancer per 1,000 person-years in this population,” the authors noted.

In other words, “the overall incidence rate of cancer in this population is low,” at less than 3.3 cases per 1,000 person-years, the authors concluded.

Relative rates of extraintestinal cancers were even lower, with the highest risks for nonmelanoma skin cancer (pRR, 3.62), lymphoid cancer (pRR, 3.10), and melanoma (pRR, 2.05).

The authors suggest that identifying variables that might reduce cancer risk in pediatric patients who develop IBD could better shape management and prevention strategies.

CRC screening guidelines already recommend that children undergo a colonoscopy 6-8 years after being diagnosed with colitis extending beyond the rectum. Annual colonoscopy is also recommended for patients with primary sclerosing cholangitis from the time of diagnosis and annual screening for skin cancer is recommended for all patients with IBD.

The investigators further suggest that because ongoing inflammation is an important risk factor for cancer, early and adequate control of inflammation could be critical in the prevention of long-term complications.

The study was supported by a grant from the Danish National Research Foundation. Dr. Jess and coauthors Rahma Elmahdi, MD, Camilla Lemser, and Kristine Allin, MD, reported receiving grants from the Danish National Research Foundation National Center of Excellence during the conduct of the study. Coauthor Manasi Agrawal, MD, reported receiving grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study.

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

Children who are diagnosed with inflammatory bowel disease (IBD) are more than twice as likely to develop cancer, especially gastrointestinal cancer, later in life compared with the general pediatric population, a new meta-analysis suggests.

Although the overall incidence rate of cancer in this population is low, “we found a 2.4-fold increase in the relative rate of cancer among patients with pediatric-onset IBD compared with the general pediatric population, primarily associated with an increased rate of gastrointestinal cancers,” wrote senior author Tine Jess, MD, DMSci, Aalborg University, Copenhagen, and colleagues.

The study was published online March 1 in JAMA Network Open.

Previous research indicates that IBD is associated with an increased risk for colon, small bowel, and other types of cancer in adults, but the risk among children with IBD is not well understood.

In the current analysis, Dr. Jess and colleagues examined five population-based studies from North America and Europe, which included more than 19,800 participants with pediatric-onset IBD. Of these participants, 715 were later diagnosed with cancer.

Overall, the risk for cancer among individuals with pediatric-onset IBD was 2.4-fold higher than that of their peers without IBD, but those rates varied by IBD subtype. Those with Crohn’s disease, for instance, were about two times more likely to develop cancer, while those with ulcerative colitis were 2.6 times more likely to develop cancer later.

Two studies included in the meta-analysis broke down results by sex and found that the risk for cancer was higher among male versus female patients (pooled relative rates [pRR], 3.23 in men and 2.45 in women).

These two studies also calculated the risk for cancer by exposure to thiopurines. Patients receiving these immunosuppressive drugs had an increased relative rate of cancer (pRR, 2.09). Although numerically higher, this rate was not statistically higher compared with patients not exposed to the drugs (pRR, 1.82).

When looking at risk by cancer site, the authors consistently observed the highest relative rates for gastrointestinal cancers. Specifically, the investigators calculated a 55-fold increased risk for liver cancer (pRR, 55.4), followed by a 20-fold increased risk for colorectal cancer (pRR, 20.2), and a 16-fold increased risk for small bowel cancer (pRR, 16.2).

Despite such high estimates for gastrointestinal cancers, “this risk corresponds to a mean incidence rate of 0.3 cases of liver cancer, 0.6 cases of colorectal cancer, and 0.1 cases of small bowel cancer per 1,000 person-years in this population,” the authors noted.

In other words, “the overall incidence rate of cancer in this population is low,” at less than 3.3 cases per 1,000 person-years, the authors concluded.

Relative rates of extraintestinal cancers were even lower, with the highest risks for nonmelanoma skin cancer (pRR, 3.62), lymphoid cancer (pRR, 3.10), and melanoma (pRR, 2.05).

The authors suggest that identifying variables that might reduce cancer risk in pediatric patients who develop IBD could better shape management and prevention strategies.

CRC screening guidelines already recommend that children undergo a colonoscopy 6-8 years after being diagnosed with colitis extending beyond the rectum. Annual colonoscopy is also recommended for patients with primary sclerosing cholangitis from the time of diagnosis and annual screening for skin cancer is recommended for all patients with IBD.

The investigators further suggest that because ongoing inflammation is an important risk factor for cancer, early and adequate control of inflammation could be critical in the prevention of long-term complications.

The study was supported by a grant from the Danish National Research Foundation. Dr. Jess and coauthors Rahma Elmahdi, MD, Camilla Lemser, and Kristine Allin, MD, reported receiving grants from the Danish National Research Foundation National Center of Excellence during the conduct of the study. Coauthor Manasi Agrawal, MD, reported receiving grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study.

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

Many emergency departments are currently unable to provide care for geriatric patients that meets best practices and guidelines recommended by several major medical organizations, but a panel discussion in 2021 at the American Academy of Emergency Medicine’s Scientific Assembly identified three areas in which realistic improvements might be achieved.

In an article published online in the Journal of Emergency Medicine, Richard D. Shih, MD, of Florida Atlantic University, Boca Raton, and colleagues synthesized the presentation and discussion of an expert panel on the topic of the GED guidelines and the current realities of patient care.

The Geriatric Emergency Department (GED) Guidelines, published in 2014 in Annals of Emergency Medicine, were endorsed by the American College of Emergency Physicians, American Geriatrics Society, Emergency Nurses Association, and Society for Academic Emergency Medicine.

“With the substantial challenges in providing guideline-recommended care in EDs, this article will explore three high-impact GED clinical conditions to highlight guideline recommendations, challenges, and opportunities, and discuss realistically achievable expectations for non–GED-accredited institutions,” the authors wrote. The article addressed the ED patient with delirium, the ED fall patient, and the ED patient with polypharmacy.
 

Geriatric patients and delirium

When delirium in older adults is not identified in the ED, the patient’s 6-month mortality rate significantly increases, but few EDs have delirium screening protocols, the authors said. Challenges included the time and money needed to educate staff, on top of multiple mandatory training requirements on other topics. Delirium screening in the clinical setting also requires personnel to conduct assessments, and time to document symptoms and screening results in medical records.

“Perhaps the highest priority challenge for delirium experts is to evaluate and publish effective delirium intervention strategies because current evidence is completely lacking for ED-based delirium prevention or treatment,” they said. In the meantime, developing outcome measures for quality improvement of delirium care will require institutional support as well as education.
 

Geriatric patients and falls

Approximately one third of community-dwelling adults older than 65 years suffer falls, but data suggest that fewer than half of these individuals report falls to their doctors. “Older adults who present to an ED after a fall have an approximately 30% greater risk of functional decline and depression at 6 months after the event,” the authors noted.

The GED guidelines call for a comprehensive approach to evaluating and managing falls in older adults, but many of these “are untested in the ED,” the authors said. The recommended protocol includes an initial assessment of fall risk, followed by, for those at low risk, tailored recommendations for education and the use of community resources. Additional recommendations for those at high risk of falls include multifactorial assessment of modifiable risk factors, including peripheral neuropathy, balance/gait assessment, and medication review.

However, this best practice workflow is beyond the resource capacity of most EDs, the authors noted. “When ED resources are insufficient to support best practices, the care should focus on educating patients and caregivers about the significance of a fall event, providing educational materials (e.g., [the Centers for Disease Control and Prevention’s] STEADI materials), and assessing safety with respect to mobility for immediate return to the home environment and follow-up with a PCP.”
 

Geriatric patients and polypharmacy

Polypharmacy is common among older adults by virtue of their greater number of illnesses and comorbid conditions, and polypharmacy also has been associated with more adverse drug reactions, the authors said. The AGS Beers Criteria identifies medications associated with adverse drug reactions, but it is not practical for use in a busy ED setting. Instead, the authors suggested a more practical approach of focusing on a smaller list of common medications that tend to cause the adverse events that may result in ED visits.

“Perhaps targeting patients on multiple (three or more) psychoactive medications, drugs that can cause hypotension, or hypoglycemics could not only be done quickly, but identify patients in whom deprescribing should be considered in the ED,” the authors wrote. Deprescribing is a complicated process, however, and may be more effective when done via the patient’s primary care provider or in a geriatric consultation.

The GED Guidelines highlighted the specific needs of the geriatric population in the ED, the authors said. Widespread implementation remains a challenge, but many organizations provide resources to help improve care of geriatric patients in the ED and beyond.

In particular, the Geriatric Emergency Care Applied Research Network and Geriatric Emergency Department Collaborative provide funding opportunities, updated and focused published reviews, and webinars (some including free continuing medical education) for the entire health care team, including hospital administrators, the authors said.
 

Article brings attention to clinical realities

“The reality is that the overwhelming majority of emergency departments in the United States, if not globally, are simply not equipped – operationally or financially – to meet the rigorous standards that are required to fulfill the goals of operating an accredited geriatric ED,” Robert D. Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, said in an interview.

“Drawing attention to this important gap in accreditation is critical to not only inform hospitals, health care providers and stakeholders, but the public, patients, and their families about the important work that needs to be done to better equip all EDs with the proper tools and educational approaches to more effectively care for the geriatric community,” Dr. Glatter emphasized.

“There are currently three tiers of accreditation, with level 1 being the highest,” he explained, but there are only 100 geriatric ED accreditation-certified hospitals across the United States.

“I am not surprised at all by the challenges of implementing current GED guidelines,” said Dr. Glatter. “It comes down to operational and budget considerations, which ultimately compete with many other departments and regulatory constraints in any given hospital.”

However, “the bottom line is that such guidelines are designed with patient safety in mind, making them important issues in the eyes of any hospital administrator looking to improve outcomes and reduce medicolegal risk or exposure impacting geriatric patients in the emergency department,” he noted. 

Ultimately, guideline adherence “comes down to budget decisions, and where hospitals must invest their money to meet the bottom line,” said Dr. Glatter. “Making modifications to hospital infrastructure and architecture to accommodate geriatric patients may not be the top priority of hospital administrators when confronted with multiple competing interests. But, if it impacts patient safety, the decision to invest in structural and operational improvements may certainly have additional and important considerations.

“Until Medicare, or even the Joint Commission on Accreditation of Hospitals, adopts geriatric guidelines in emergency departments as a requirement for accreditation, there may not be adequate incentives in place currently to satisfy the intent of having a rigorous set of guidelines in the first place,” Dr. Glatter added. 

Despite the limitations of applying the current guidelines, there are some steps hospitals can take, said Dr. Glatter. “They can institute new measures in a graded fashion, with the goal of taking the important steps to satisfy at least some components of the guidelines. Attention to details can go a long way, such as rails in bathrooms, better lighting, and treads on floors that may reduce the risk of falls in the ED itself.

“Attention to fall prevention by assessing contributors including polypharmacy, gait instability, and quality of footwear can impact risk of future ED visits. Having incentives in place by Medicare or JACO may force the hand of hospital administrators to comply with geriatric guidelines and place emphasis on compliance,” noted Dr. Glatter.

More research is needed that “looks at costs of implementing geriatric guidelines in typical community and academic EDs and how this impacts key metrics such as length of stay, effect on reimbursement per ICD-10 code, and savings, if any, realized in reduced malpractice claims related to missed diagnoses (such as delirium), injuries, (patient falls), or medical misadventures due to polypharmacy,” he said.

The article received no outside funding. The authors disclosed no relevant financial relationships. Dr. Glatter disclosed no relevant financial relationships, and serves on the advisory board of Medscape Emergency Medicine.

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

Many emergency departments are currently unable to provide care for geriatric patients that meets best practices and guidelines recommended by several major medical organizations, but a panel discussion in 2021 at the American Academy of Emergency Medicine’s Scientific Assembly identified three areas in which realistic improvements might be achieved.

In an article published online in the Journal of Emergency Medicine, Richard D. Shih, MD, of Florida Atlantic University, Boca Raton, and colleagues synthesized the presentation and discussion of an expert panel on the topic of the GED guidelines and the current realities of patient care.

The Geriatric Emergency Department (GED) Guidelines, published in 2014 in Annals of Emergency Medicine, were endorsed by the American College of Emergency Physicians, American Geriatrics Society, Emergency Nurses Association, and Society for Academic Emergency Medicine.

“With the substantial challenges in providing guideline-recommended care in EDs, this article will explore three high-impact GED clinical conditions to highlight guideline recommendations, challenges, and opportunities, and discuss realistically achievable expectations for non–GED-accredited institutions,” the authors wrote. The article addressed the ED patient with delirium, the ED fall patient, and the ED patient with polypharmacy.
 

Geriatric patients and delirium

When delirium in older adults is not identified in the ED, the patient’s 6-month mortality rate significantly increases, but few EDs have delirium screening protocols, the authors said. Challenges included the time and money needed to educate staff, on top of multiple mandatory training requirements on other topics. Delirium screening in the clinical setting also requires personnel to conduct assessments, and time to document symptoms and screening results in medical records.

“Perhaps the highest priority challenge for delirium experts is to evaluate and publish effective delirium intervention strategies because current evidence is completely lacking for ED-based delirium prevention or treatment,” they said. In the meantime, developing outcome measures for quality improvement of delirium care will require institutional support as well as education.
 

Geriatric patients and falls

Approximately one third of community-dwelling adults older than 65 years suffer falls, but data suggest that fewer than half of these individuals report falls to their doctors. “Older adults who present to an ED after a fall have an approximately 30% greater risk of functional decline and depression at 6 months after the event,” the authors noted.

The GED guidelines call for a comprehensive approach to evaluating and managing falls in older adults, but many of these “are untested in the ED,” the authors said. The recommended protocol includes an initial assessment of fall risk, followed by, for those at low risk, tailored recommendations for education and the use of community resources. Additional recommendations for those at high risk of falls include multifactorial assessment of modifiable risk factors, including peripheral neuropathy, balance/gait assessment, and medication review.

However, this best practice workflow is beyond the resource capacity of most EDs, the authors noted. “When ED resources are insufficient to support best practices, the care should focus on educating patients and caregivers about the significance of a fall event, providing educational materials (e.g., [the Centers for Disease Control and Prevention’s] STEADI materials), and assessing safety with respect to mobility for immediate return to the home environment and follow-up with a PCP.”
 

Geriatric patients and polypharmacy

Polypharmacy is common among older adults by virtue of their greater number of illnesses and comorbid conditions, and polypharmacy also has been associated with more adverse drug reactions, the authors said. The AGS Beers Criteria identifies medications associated with adverse drug reactions, but it is not practical for use in a busy ED setting. Instead, the authors suggested a more practical approach of focusing on a smaller list of common medications that tend to cause the adverse events that may result in ED visits.

“Perhaps targeting patients on multiple (three or more) psychoactive medications, drugs that can cause hypotension, or hypoglycemics could not only be done quickly, but identify patients in whom deprescribing should be considered in the ED,” the authors wrote. Deprescribing is a complicated process, however, and may be more effective when done via the patient’s primary care provider or in a geriatric consultation.

The GED Guidelines highlighted the specific needs of the geriatric population in the ED, the authors said. Widespread implementation remains a challenge, but many organizations provide resources to help improve care of geriatric patients in the ED and beyond.

In particular, the Geriatric Emergency Care Applied Research Network and Geriatric Emergency Department Collaborative provide funding opportunities, updated and focused published reviews, and webinars (some including free continuing medical education) for the entire health care team, including hospital administrators, the authors said.
 

Article brings attention to clinical realities

“The reality is that the overwhelming majority of emergency departments in the United States, if not globally, are simply not equipped – operationally or financially – to meet the rigorous standards that are required to fulfill the goals of operating an accredited geriatric ED,” Robert D. Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, said in an interview.

“Drawing attention to this important gap in accreditation is critical to not only inform hospitals, health care providers and stakeholders, but the public, patients, and their families about the important work that needs to be done to better equip all EDs with the proper tools and educational approaches to more effectively care for the geriatric community,” Dr. Glatter emphasized.

“There are currently three tiers of accreditation, with level 1 being the highest,” he explained, but there are only 100 geriatric ED accreditation-certified hospitals across the United States.

“I am not surprised at all by the challenges of implementing current GED guidelines,” said Dr. Glatter. “It comes down to operational and budget considerations, which ultimately compete with many other departments and regulatory constraints in any given hospital.”

However, “the bottom line is that such guidelines are designed with patient safety in mind, making them important issues in the eyes of any hospital administrator looking to improve outcomes and reduce medicolegal risk or exposure impacting geriatric patients in the emergency department,” he noted. 

Ultimately, guideline adherence “comes down to budget decisions, and where hospitals must invest their money to meet the bottom line,” said Dr. Glatter. “Making modifications to hospital infrastructure and architecture to accommodate geriatric patients may not be the top priority of hospital administrators when confronted with multiple competing interests. But, if it impacts patient safety, the decision to invest in structural and operational improvements may certainly have additional and important considerations.

“Until Medicare, or even the Joint Commission on Accreditation of Hospitals, adopts geriatric guidelines in emergency departments as a requirement for accreditation, there may not be adequate incentives in place currently to satisfy the intent of having a rigorous set of guidelines in the first place,” Dr. Glatter added. 

Despite the limitations of applying the current guidelines, there are some steps hospitals can take, said Dr. Glatter. “They can institute new measures in a graded fashion, with the goal of taking the important steps to satisfy at least some components of the guidelines. Attention to details can go a long way, such as rails in bathrooms, better lighting, and treads on floors that may reduce the risk of falls in the ED itself.

“Attention to fall prevention by assessing contributors including polypharmacy, gait instability, and quality of footwear can impact risk of future ED visits. Having incentives in place by Medicare or JACO may force the hand of hospital administrators to comply with geriatric guidelines and place emphasis on compliance,” noted Dr. Glatter.

More research is needed that “looks at costs of implementing geriatric guidelines in typical community and academic EDs and how this impacts key metrics such as length of stay, effect on reimbursement per ICD-10 code, and savings, if any, realized in reduced malpractice claims related to missed diagnoses (such as delirium), injuries, (patient falls), or medical misadventures due to polypharmacy,” he said.

The article received no outside funding. The authors disclosed no relevant financial relationships. Dr. Glatter disclosed no relevant financial relationships, and serves on the advisory board of Medscape Emergency Medicine.

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

Many emergency departments are currently unable to provide care for geriatric patients that meets best practices and guidelines recommended by several major medical organizations, but a panel discussion in 2021 at the American Academy of Emergency Medicine’s Scientific Assembly identified three areas in which realistic improvements might be achieved.

In an article published online in the Journal of Emergency Medicine, Richard D. Shih, MD, of Florida Atlantic University, Boca Raton, and colleagues synthesized the presentation and discussion of an expert panel on the topic of the GED guidelines and the current realities of patient care.

The Geriatric Emergency Department (GED) Guidelines, published in 2014 in Annals of Emergency Medicine, were endorsed by the American College of Emergency Physicians, American Geriatrics Society, Emergency Nurses Association, and Society for Academic Emergency Medicine.

“With the substantial challenges in providing guideline-recommended care in EDs, this article will explore three high-impact GED clinical conditions to highlight guideline recommendations, challenges, and opportunities, and discuss realistically achievable expectations for non–GED-accredited institutions,” the authors wrote. The article addressed the ED patient with delirium, the ED fall patient, and the ED patient with polypharmacy.
 

Geriatric patients and delirium

When delirium in older adults is not identified in the ED, the patient’s 6-month mortality rate significantly increases, but few EDs have delirium screening protocols, the authors said. Challenges included the time and money needed to educate staff, on top of multiple mandatory training requirements on other topics. Delirium screening in the clinical setting also requires personnel to conduct assessments, and time to document symptoms and screening results in medical records.

“Perhaps the highest priority challenge for delirium experts is to evaluate and publish effective delirium intervention strategies because current evidence is completely lacking for ED-based delirium prevention or treatment,” they said. In the meantime, developing outcome measures for quality improvement of delirium care will require institutional support as well as education.
 

Geriatric patients and falls

Approximately one third of community-dwelling adults older than 65 years suffer falls, but data suggest that fewer than half of these individuals report falls to their doctors. “Older adults who present to an ED after a fall have an approximately 30% greater risk of functional decline and depression at 6 months after the event,” the authors noted.

The GED guidelines call for a comprehensive approach to evaluating and managing falls in older adults, but many of these “are untested in the ED,” the authors said. The recommended protocol includes an initial assessment of fall risk, followed by, for those at low risk, tailored recommendations for education and the use of community resources. Additional recommendations for those at high risk of falls include multifactorial assessment of modifiable risk factors, including peripheral neuropathy, balance/gait assessment, and medication review.

However, this best practice workflow is beyond the resource capacity of most EDs, the authors noted. “When ED resources are insufficient to support best practices, the care should focus on educating patients and caregivers about the significance of a fall event, providing educational materials (e.g., [the Centers for Disease Control and Prevention’s] STEADI materials), and assessing safety with respect to mobility for immediate return to the home environment and follow-up with a PCP.”
 

Geriatric patients and polypharmacy

Polypharmacy is common among older adults by virtue of their greater number of illnesses and comorbid conditions, and polypharmacy also has been associated with more adverse drug reactions, the authors said. The AGS Beers Criteria identifies medications associated with adverse drug reactions, but it is not practical for use in a busy ED setting. Instead, the authors suggested a more practical approach of focusing on a smaller list of common medications that tend to cause the adverse events that may result in ED visits.

“Perhaps targeting patients on multiple (three or more) psychoactive medications, drugs that can cause hypotension, or hypoglycemics could not only be done quickly, but identify patients in whom deprescribing should be considered in the ED,” the authors wrote. Deprescribing is a complicated process, however, and may be more effective when done via the patient’s primary care provider or in a geriatric consultation.

The GED Guidelines highlighted the specific needs of the geriatric population in the ED, the authors said. Widespread implementation remains a challenge, but many organizations provide resources to help improve care of geriatric patients in the ED and beyond.

In particular, the Geriatric Emergency Care Applied Research Network and Geriatric Emergency Department Collaborative provide funding opportunities, updated and focused published reviews, and webinars (some including free continuing medical education) for the entire health care team, including hospital administrators, the authors said.
 

Article brings attention to clinical realities

“The reality is that the overwhelming majority of emergency departments in the United States, if not globally, are simply not equipped – operationally or financially – to meet the rigorous standards that are required to fulfill the goals of operating an accredited geriatric ED,” Robert D. Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, said in an interview.

“Drawing attention to this important gap in accreditation is critical to not only inform hospitals, health care providers and stakeholders, but the public, patients, and their families about the important work that needs to be done to better equip all EDs with the proper tools and educational approaches to more effectively care for the geriatric community,” Dr. Glatter emphasized.

“There are currently three tiers of accreditation, with level 1 being the highest,” he explained, but there are only 100 geriatric ED accreditation-certified hospitals across the United States.

“I am not surprised at all by the challenges of implementing current GED guidelines,” said Dr. Glatter. “It comes down to operational and budget considerations, which ultimately compete with many other departments and regulatory constraints in any given hospital.”

However, “the bottom line is that such guidelines are designed with patient safety in mind, making them important issues in the eyes of any hospital administrator looking to improve outcomes and reduce medicolegal risk or exposure impacting geriatric patients in the emergency department,” he noted. 

Ultimately, guideline adherence “comes down to budget decisions, and where hospitals must invest their money to meet the bottom line,” said Dr. Glatter. “Making modifications to hospital infrastructure and architecture to accommodate geriatric patients may not be the top priority of hospital administrators when confronted with multiple competing interests. But, if it impacts patient safety, the decision to invest in structural and operational improvements may certainly have additional and important considerations.

“Until Medicare, or even the Joint Commission on Accreditation of Hospitals, adopts geriatric guidelines in emergency departments as a requirement for accreditation, there may not be adequate incentives in place currently to satisfy the intent of having a rigorous set of guidelines in the first place,” Dr. Glatter added. 

Despite the limitations of applying the current guidelines, there are some steps hospitals can take, said Dr. Glatter. “They can institute new measures in a graded fashion, with the goal of taking the important steps to satisfy at least some components of the guidelines. Attention to details can go a long way, such as rails in bathrooms, better lighting, and treads on floors that may reduce the risk of falls in the ED itself.

“Attention to fall prevention by assessing contributors including polypharmacy, gait instability, and quality of footwear can impact risk of future ED visits. Having incentives in place by Medicare or JACO may force the hand of hospital administrators to comply with geriatric guidelines and place emphasis on compliance,” noted Dr. Glatter.

More research is needed that “looks at costs of implementing geriatric guidelines in typical community and academic EDs and how this impacts key metrics such as length of stay, effect on reimbursement per ICD-10 code, and savings, if any, realized in reduced malpractice claims related to missed diagnoses (such as delirium), injuries, (patient falls), or medical misadventures due to polypharmacy,” he said.

The article received no outside funding. The authors disclosed no relevant financial relationships. Dr. Glatter disclosed no relevant financial relationships, and serves on the advisory board of Medscape Emergency Medicine.

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

PHOENIX – New results from a separate, larger phase 3 trial confirm the benefits of dupilumab (Dupixent) in adults and adolescents with eosinophilic esophagitis (EoE), showing that weekly injections of the biologic sent 59% of EoE patients into disease remission after 24 weeks. The late-breaking data on Part B of the LIBERTY EoE TREET study drew a standing-room-only crowd at the American Academy of Allergy, Asthma and Immunology (AAAAI) annual meeting.

EoE is a chronic, progressive, type 2 inflammatory disease resulting from esophageal build-up of eosinophils, which injures the tissue and leads to swallowing difficulties. Dupilumab, a monoclonal antibody that blocks type 2 immune responses, is currently approved to treat poorly controlled atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.

Dupilumab also showed benefits in patients with hard-to-treat EoE in a phase 3 trial (LIBERTY EoE TREET 28-week extension of Part A), reported by Medscape Medical News in October from the American College of Gastroenterology (ACG) annual meeting.

Part B enrolled 159 EoE patients 12 years or older and tested the efficacy and safety of weekly 300 mg dupilumab versus placebo injections for 24 weeks. More than half of the participants had previously tried swallowed topical corticosteroids, and about 30% were on a food elimination diet. (Generally, corticosteroids and elimination diets are about 70% effective in EoE.)

Compared with placebo, 6 months of weekly dupilumab reduced eosinophils in the esophagus and produced statistically significant and clinically meaningful improvements in the ability to swallow.

Treated participants saw a 64% reduction in disease symptoms (23.8-point improvement on the self-reported Dysphagia Symptom Questionnaire [DSQ]), compared with 41% reduction (13.9 point DSQ improvement) in the placebo group. 

Histologically, dupilumab reduced peak eosinophil counts to 6 or lower in 59% of patients, whereas only 6% achieved disease remission on placebo.

On safety, dupilumab was generally well tolerated. The most common treatment adverse events were injection site reactions (occurring in about 20% of both groups) or injection site erythema (occurring in 10% of treated patients and 11.5% of placebo patients).

“These results replicate those in Part A in a larger sample size,” Marc Rothenberg, MD, PhD, director of the division of allergy and immunology at Cincinnati Children’s Hospital Medical Center, noted in a prerecorded presentation.

Based on the phase 3 data, dupilumab seems “effective for patients who may have no other options for managing their EoE,” Brian Schroer, MD, director of allergy and immunology at Akron (Ohio) Children’s Hospital, said in an interview. Dr. Schroer expects EoE cases to rise as more food allergy patients begin oral immunotherapy (OIT), where studies have shown EoE as a side effect in about 4% of patients undergoing OIT.

In a live Q&A following the prerecorded talk, Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, told attendees that data from Part B’s second arm, which tested dupilumab injections given every other week, have not yet been presented. So far, histological results in this arm look identical to those of patients who received weekly dupilumab, though symptoms “did not meet statistical significance,” he said. “I think we’re going to have much more detail about those results at some conferences to come in the spring.”

LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon and Dr. Rothenberg reported numerous conflicts of interest. Dr. Schroer has received consulting fees from Sanofi and Ready, Set, Food.

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

PHOENIX – New results from a separate, larger phase 3 trial confirm the benefits of dupilumab (Dupixent) in adults and adolescents with eosinophilic esophagitis (EoE), showing that weekly injections of the biologic sent 59% of EoE patients into disease remission after 24 weeks. The late-breaking data on Part B of the LIBERTY EoE TREET study drew a standing-room-only crowd at the American Academy of Allergy, Asthma and Immunology (AAAAI) annual meeting.

EoE is a chronic, progressive, type 2 inflammatory disease resulting from esophageal build-up of eosinophils, which injures the tissue and leads to swallowing difficulties. Dupilumab, a monoclonal antibody that blocks type 2 immune responses, is currently approved to treat poorly controlled atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.

Dupilumab also showed benefits in patients with hard-to-treat EoE in a phase 3 trial (LIBERTY EoE TREET 28-week extension of Part A), reported by Medscape Medical News in October from the American College of Gastroenterology (ACG) annual meeting.

Part B enrolled 159 EoE patients 12 years or older and tested the efficacy and safety of weekly 300 mg dupilumab versus placebo injections for 24 weeks. More than half of the participants had previously tried swallowed topical corticosteroids, and about 30% were on a food elimination diet. (Generally, corticosteroids and elimination diets are about 70% effective in EoE.)

Compared with placebo, 6 months of weekly dupilumab reduced eosinophils in the esophagus and produced statistically significant and clinically meaningful improvements in the ability to swallow.

Treated participants saw a 64% reduction in disease symptoms (23.8-point improvement on the self-reported Dysphagia Symptom Questionnaire [DSQ]), compared with 41% reduction (13.9 point DSQ improvement) in the placebo group. 

Histologically, dupilumab reduced peak eosinophil counts to 6 or lower in 59% of patients, whereas only 6% achieved disease remission on placebo.

On safety, dupilumab was generally well tolerated. The most common treatment adverse events were injection site reactions (occurring in about 20% of both groups) or injection site erythema (occurring in 10% of treated patients and 11.5% of placebo patients).

“These results replicate those in Part A in a larger sample size,” Marc Rothenberg, MD, PhD, director of the division of allergy and immunology at Cincinnati Children’s Hospital Medical Center, noted in a prerecorded presentation.

Based on the phase 3 data, dupilumab seems “effective for patients who may have no other options for managing their EoE,” Brian Schroer, MD, director of allergy and immunology at Akron (Ohio) Children’s Hospital, said in an interview. Dr. Schroer expects EoE cases to rise as more food allergy patients begin oral immunotherapy (OIT), where studies have shown EoE as a side effect in about 4% of patients undergoing OIT.

In a live Q&A following the prerecorded talk, Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, told attendees that data from Part B’s second arm, which tested dupilumab injections given every other week, have not yet been presented. So far, histological results in this arm look identical to those of patients who received weekly dupilumab, though symptoms “did not meet statistical significance,” he said. “I think we’re going to have much more detail about those results at some conferences to come in the spring.”

LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon and Dr. Rothenberg reported numerous conflicts of interest. Dr. Schroer has received consulting fees from Sanofi and Ready, Set, Food.

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

PHOENIX – New results from a separate, larger phase 3 trial confirm the benefits of dupilumab (Dupixent) in adults and adolescents with eosinophilic esophagitis (EoE), showing that weekly injections of the biologic sent 59% of EoE patients into disease remission after 24 weeks. The late-breaking data on Part B of the LIBERTY EoE TREET study drew a standing-room-only crowd at the American Academy of Allergy, Asthma and Immunology (AAAAI) annual meeting.

EoE is a chronic, progressive, type 2 inflammatory disease resulting from esophageal build-up of eosinophils, which injures the tissue and leads to swallowing difficulties. Dupilumab, a monoclonal antibody that blocks type 2 immune responses, is currently approved to treat poorly controlled atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.

Dupilumab also showed benefits in patients with hard-to-treat EoE in a phase 3 trial (LIBERTY EoE TREET 28-week extension of Part A), reported by Medscape Medical News in October from the American College of Gastroenterology (ACG) annual meeting.

Part B enrolled 159 EoE patients 12 years or older and tested the efficacy and safety of weekly 300 mg dupilumab versus placebo injections for 24 weeks. More than half of the participants had previously tried swallowed topical corticosteroids, and about 30% were on a food elimination diet. (Generally, corticosteroids and elimination diets are about 70% effective in EoE.)

Compared with placebo, 6 months of weekly dupilumab reduced eosinophils in the esophagus and produced statistically significant and clinically meaningful improvements in the ability to swallow.

Treated participants saw a 64% reduction in disease symptoms (23.8-point improvement on the self-reported Dysphagia Symptom Questionnaire [DSQ]), compared with 41% reduction (13.9 point DSQ improvement) in the placebo group. 

Histologically, dupilumab reduced peak eosinophil counts to 6 or lower in 59% of patients, whereas only 6% achieved disease remission on placebo.

On safety, dupilumab was generally well tolerated. The most common treatment adverse events were injection site reactions (occurring in about 20% of both groups) or injection site erythema (occurring in 10% of treated patients and 11.5% of placebo patients).

“These results replicate those in Part A in a larger sample size,” Marc Rothenberg, MD, PhD, director of the division of allergy and immunology at Cincinnati Children’s Hospital Medical Center, noted in a prerecorded presentation.

Based on the phase 3 data, dupilumab seems “effective for patients who may have no other options for managing their EoE,” Brian Schroer, MD, director of allergy and immunology at Akron (Ohio) Children’s Hospital, said in an interview. Dr. Schroer expects EoE cases to rise as more food allergy patients begin oral immunotherapy (OIT), where studies have shown EoE as a side effect in about 4% of patients undergoing OIT.

In a live Q&A following the prerecorded talk, Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, told attendees that data from Part B’s second arm, which tested dupilumab injections given every other week, have not yet been presented. So far, histological results in this arm look identical to those of patients who received weekly dupilumab, though symptoms “did not meet statistical significance,” he said. “I think we’re going to have much more detail about those results at some conferences to come in the spring.”

LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon and Dr. Rothenberg reported numerous conflicts of interest. Dr. Schroer has received consulting fees from Sanofi and Ready, Set, Food.

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.

As one of 4 statutory missions, the US Department of Veterans Affairs (VA) educates and trains health professionals to enhance the quality of and timely access to care provided to veterans within the Veterans Health Administration (VHA). To achieve its mission to educate, the VA has conducted health professions education and training in partnership with affiliated US academic institutions for the past 76 years in accordance with the landmark 1946 Policy Memorandum No. 2.^1,2

Despite its long-term success affiliating with medical schools, VA has continued to be challenged by physician staff shortages with wide variability in the number and specialty of available health care professionals across facilities.^3,4 A 2020 VA Office of Inspector General report on VHA occupational staffing shortages concluded that numerous physician specialties were difficult to recruit due to a lack of qualified applicants, noncompetitive salary, and less desirable geographic locations.³

Federal health professions scholarship programs and loan repayment programs have long been used to address physician shortages.⁴ Focusing on physician shortages in underserved areas in the US, the Emergency Health Personnel Act of 1970 and its subsequent amendments paved the way for various federal medical school scholarship and loan repayment programs.⁵ Similarly, physician shortages in the armed forces were mitigated through the Uniformed Services Health Professions Revitalization Act of 1972 (USHPRA).^6,7

In 2018, Congress passed the VA MISSION (Maintaining Internal Systems and Strengthening Integrated Outside Networks) Act, which included sections designed to alleviate physician shortages in the VHA.⁸ These sections authorized scholarships similar to those offered by the US Department of Defense (DoD) and loan repayment programs. Section 301 created the Health Professions Scholarship Program (HPSP), which offers scholarships for physicians and dentists. Section 302 increased the maximum debt reduction through the Education Debt Reduction Program (EDRP). Section 303 authorizes the Specialty Education Loan Repayment Program (SELRP), which provides for repayment of educational loans for physicians in specialties deemed necessary for VA. Finally, Section 304 created the Veterans Healing Veterans (VHV), a pilot scholarship specifically for veteran medical students.
 

Program Characteristics

Health Professions Scholarship

The VA HPSP is a program for physicians and dentists that extends from 2020 to 2033. The HPSP funds the costs of tuition, fees, and provides a stipend with a service obligation of 18 months for each year of support. The program is authorized for 10 years and must provide a minimum of 50 scholarships annually for physicians or dentists based on VHA needs. Applications are screened based on criteria that include a commitment to rural or underserved populations, veteran status, grade point average, essays, and letters of recommendation. Although the minimum required number of scholarships annually is 50, VA anticipates providing 1000 scholarships over 10 years with an aim to significantly increase the number physicians at VHA facilities (Table 1).

Veterans Healing Veterans

Implemented in 2020, the VHV was a 1-year pilot program. It offered scholarships to 2 veterans attending medical school at each of the 5 Teague-Cranston and the 4 Historically Black College and University (HBCU) medical schools (Table 2). The intent of the program was to determine the feasibility of increasing the pool of veteran physicians at VHA. Eligible applicants were notified of the scholarship opportunity through the American Medical College Application Service or through the medical school. Applicants must have separated from military service within the preceding 10 years of being admitted to medical school. In exchange for full tuition, fees, a monthly stipend, and rotation travel costs, the recipients accepted a 4-year clinical service obligation at VA facilities after completing their residency training.

Specialty Education Loan Repayment

The SELRP is a loan repayment program available to recently graduated physicians. Applicants must have graduated from an accredited medical or osteopathic school, matched to an accredited residency program and be ≥ 2 years from completion of residency. The specialties qualifying for SELRP are determined through an analysis of succession planning by the VA Office of Workforce Management and Consulting and change based on VA physician workforce needs. The SELRP provides loan repayment in the amount of $40,000 per year for up to 4 years, with a service obligation of 1 year for each $40,000 of support. In April 2021, VA began accepting applications from the eligible specialties of family medicine, internal medicine, gastroenterology, psychiatry, emergency medicine, and geriatrics.

Education Debt Reduction

The EDRP offers debt relief to clinicians in the most difficult to recruit professions, including physicians (generalists and specialists), registered nurses, licensed practical nurses, social workers, and psychologists. The list of difficult to recruit positions is developed annually by VA facilities. Annual reimbursements through the program may be used for tuition and expenses, such as fees, books, supplies, equipment, and other materials. In 2018, through the MISSION Act Section 302, the annual loan repayment was increased from $24,000 to $40,000, and the maximum level of support was increased from $120,000 to $200,000 over 5 years. Recipients receive reimbursement for loan repayment at the end of each year or service period and recipients are not required to remain in VA for 5 years.

Program Results

Health Professions Scholarship

For academic years 2020/2021 and 2021/2022, 126 HPSP applications from both allopathic and osteopathic schools were submitted and 51 scholarships were awarded (Table 3). Assuming an average residency length of 4 years, VHA estimates that these awards will yield 204 service-year equivalents by 2029.

Veterans Healing Veterans

In the VHV program, scholarship recipients came from 5 Teague-Cranston schools; 2 at University of South Carolina, 2 at East Tennessee State University, 2 at Wright State University, 1 at Texas A&M College of Medicine, 1 at Marshall University; and 3 HBCUs; 2 at Howard University, 1 at Morehouse School of Medicine and 1 at Meharry Medical College. The Charles R. Drew University of Medicine and Science did not nominate any students for the scholarship. Assuming all recipients complete postgraduate training, the VHV scholarship program will provide an additional 12 veteran physicians to serve at VA for at least 4 years each (48 service years).

Specialty Education Loan Repayment

Fourteen applicants have been approved, including 5 in psychiatry, 4 in family medicine, 3 in internal medicine, 1 in emergency medicine, and 1 in geriatrics. The mean loan repayment is anticipated to be $110,000 and equating to 38.5 VA service years or a mean of 2.3 years of service obligation per individual for the first cohort. The program has no termination date, and with continued funding, VA anticipates granting 100 loan repayments annually.

Education Debt Reduction

Since 2018, 1,546 VA physicians have received EDRP awards. Due to the increased reimbursement provided through the MISSION Act, average physician award amounts have increased from $96,090 in 2018 to $142,557 in 2019 and $148,302 in 2020.

Conclusions

The VA physician scholarship and loan repayment programs outlined in the MISSION Act build on the success of existing federal scholarship programs by providing opportunities for physician trainees to alleviate educational debt and explore a VA health professions career.

Looking ahead, VA must focus on measuring the success of the MISSION scholarship and loan repayment programs by tracking rates of acceptance and student graduation, residency and fellowship completion, and placement in VA medical facilities—both for the service obligation and future employment. Ultimately, the total impact on VA staffing, especially at rural and underresourced sites, will determine the success of the MISSION programs.

As one of 4 statutory missions, the US Department of Veterans Affairs (VA) educates and trains health professionals to enhance the quality of and timely access to care provided to veterans within the Veterans Health Administration (VHA). To achieve its mission to educate, the VA has conducted health professions education and training in partnership with affiliated US academic institutions for the past 76 years in accordance with the landmark 1946 Policy Memorandum No. 2.^1,2

Despite its long-term success affiliating with medical schools, VA has continued to be challenged by physician staff shortages with wide variability in the number and specialty of available health care professionals across facilities.^3,4 A 2020 VA Office of Inspector General report on VHA occupational staffing shortages concluded that numerous physician specialties were difficult to recruit due to a lack of qualified applicants, noncompetitive salary, and less desirable geographic locations.³

Federal health professions scholarship programs and loan repayment programs have long been used to address physician shortages.⁴ Focusing on physician shortages in underserved areas in the US, the Emergency Health Personnel Act of 1970 and its subsequent amendments paved the way for various federal medical school scholarship and loan repayment programs.⁵ Similarly, physician shortages in the armed forces were mitigated through the Uniformed Services Health Professions Revitalization Act of 1972 (USHPRA).^6,7

In 2018, Congress passed the VA MISSION (Maintaining Internal Systems and Strengthening Integrated Outside Networks) Act, which included sections designed to alleviate physician shortages in the VHA.⁸ These sections authorized scholarships similar to those offered by the US Department of Defense (DoD) and loan repayment programs. Section 301 created the Health Professions Scholarship Program (HPSP), which offers scholarships for physicians and dentists. Section 302 increased the maximum debt reduction through the Education Debt Reduction Program (EDRP). Section 303 authorizes the Specialty Education Loan Repayment Program (SELRP), which provides for repayment of educational loans for physicians in specialties deemed necessary for VA. Finally, Section 304 created the Veterans Healing Veterans (VHV), a pilot scholarship specifically for veteran medical students.
 

Program Characteristics

Health Professions Scholarship

The VA HPSP is a program for physicians and dentists that extends from 2020 to 2033. The HPSP funds the costs of tuition, fees, and provides a stipend with a service obligation of 18 months for each year of support. The program is authorized for 10 years and must provide a minimum of 50 scholarships annually for physicians or dentists based on VHA needs. Applications are screened based on criteria that include a commitment to rural or underserved populations, veteran status, grade point average, essays, and letters of recommendation. Although the minimum required number of scholarships annually is 50, VA anticipates providing 1000 scholarships over 10 years with an aim to significantly increase the number physicians at VHA facilities (Table 1).

Veterans Healing Veterans

Implemented in 2020, the VHV was a 1-year pilot program. It offered scholarships to 2 veterans attending medical school at each of the 5 Teague-Cranston and the 4 Historically Black College and University (HBCU) medical schools (Table 2). The intent of the program was to determine the feasibility of increasing the pool of veteran physicians at VHA. Eligible applicants were notified of the scholarship opportunity through the American Medical College Application Service or through the medical school. Applicants must have separated from military service within the preceding 10 years of being admitted to medical school. In exchange for full tuition, fees, a monthly stipend, and rotation travel costs, the recipients accepted a 4-year clinical service obligation at VA facilities after completing their residency training.

Specialty Education Loan Repayment

The SELRP is a loan repayment program available to recently graduated physicians. Applicants must have graduated from an accredited medical or osteopathic school, matched to an accredited residency program and be ≥ 2 years from completion of residency. The specialties qualifying for SELRP are determined through an analysis of succession planning by the VA Office of Workforce Management and Consulting and change based on VA physician workforce needs. The SELRP provides loan repayment in the amount of $40,000 per year for up to 4 years, with a service obligation of 1 year for each $40,000 of support. In April 2021, VA began accepting applications from the eligible specialties of family medicine, internal medicine, gastroenterology, psychiatry, emergency medicine, and geriatrics.

Education Debt Reduction

The EDRP offers debt relief to clinicians in the most difficult to recruit professions, including physicians (generalists and specialists), registered nurses, licensed practical nurses, social workers, and psychologists. The list of difficult to recruit positions is developed annually by VA facilities. Annual reimbursements through the program may be used for tuition and expenses, such as fees, books, supplies, equipment, and other materials. In 2018, through the MISSION Act Section 302, the annual loan repayment was increased from $24,000 to $40,000, and the maximum level of support was increased from $120,000 to $200,000 over 5 years. Recipients receive reimbursement for loan repayment at the end of each year or service period and recipients are not required to remain in VA for 5 years.

Program Results

Health Professions Scholarship

For academic years 2020/2021 and 2021/2022, 126 HPSP applications from both allopathic and osteopathic schools were submitted and 51 scholarships were awarded (Table 3). Assuming an average residency length of 4 years, VHA estimates that these awards will yield 204 service-year equivalents by 2029.

Veterans Healing Veterans

In the VHV program, scholarship recipients came from 5 Teague-Cranston schools; 2 at University of South Carolina, 2 at East Tennessee State University, 2 at Wright State University, 1 at Texas A&M College of Medicine, 1 at Marshall University; and 3 HBCUs; 2 at Howard University, 1 at Morehouse School of Medicine and 1 at Meharry Medical College. The Charles R. Drew University of Medicine and Science did not nominate any students for the scholarship. Assuming all recipients complete postgraduate training, the VHV scholarship program will provide an additional 12 veteran physicians to serve at VA for at least 4 years each (48 service years).

Specialty Education Loan Repayment

Fourteen applicants have been approved, including 5 in psychiatry, 4 in family medicine, 3 in internal medicine, 1 in emergency medicine, and 1 in geriatrics. The mean loan repayment is anticipated to be $110,000 and equating to 38.5 VA service years or a mean of 2.3 years of service obligation per individual for the first cohort. The program has no termination date, and with continued funding, VA anticipates granting 100 loan repayments annually.

Education Debt Reduction

Since 2018, 1,546 VA physicians have received EDRP awards. Due to the increased reimbursement provided through the MISSION Act, average physician award amounts have increased from $96,090 in 2018 to $142,557 in 2019 and $148,302 in 2020.

Conclusions

The VA physician scholarship and loan repayment programs outlined in the MISSION Act build on the success of existing federal scholarship programs by providing opportunities for physician trainees to alleviate educational debt and explore a VA health professions career.

Looking ahead, VA must focus on measuring the success of the MISSION scholarship and loan repayment programs by tracking rates of acceptance and student graduation, residency and fellowship completion, and placement in VA medical facilities—both for the service obligation and future employment. Ultimately, the total impact on VA staffing, especially at rural and underresourced sites, will determine the success of the MISSION programs.

As one of 4 statutory missions, the US Department of Veterans Affairs (VA) educates and trains health professionals to enhance the quality of and timely access to care provided to veterans within the Veterans Health Administration (VHA). To achieve its mission to educate, the VA has conducted health professions education and training in partnership with affiliated US academic institutions for the past 76 years in accordance with the landmark 1946 Policy Memorandum No. 2.^1,2

Despite its long-term success affiliating with medical schools, VA has continued to be challenged by physician staff shortages with wide variability in the number and specialty of available health care professionals across facilities.^3,4 A 2020 VA Office of Inspector General report on VHA occupational staffing shortages concluded that numerous physician specialties were difficult to recruit due to a lack of qualified applicants, noncompetitive salary, and less desirable geographic locations.³

Federal health professions scholarship programs and loan repayment programs have long been used to address physician shortages.⁴ Focusing on physician shortages in underserved areas in the US, the Emergency Health Personnel Act of 1970 and its subsequent amendments paved the way for various federal medical school scholarship and loan repayment programs.⁵ Similarly, physician shortages in the armed forces were mitigated through the Uniformed Services Health Professions Revitalization Act of 1972 (USHPRA).^6,7

In 2018, Congress passed the VA MISSION (Maintaining Internal Systems and Strengthening Integrated Outside Networks) Act, which included sections designed to alleviate physician shortages in the VHA.⁸ These sections authorized scholarships similar to those offered by the US Department of Defense (DoD) and loan repayment programs. Section 301 created the Health Professions Scholarship Program (HPSP), which offers scholarships for physicians and dentists. Section 302 increased the maximum debt reduction through the Education Debt Reduction Program (EDRP). Section 303 authorizes the Specialty Education Loan Repayment Program (SELRP), which provides for repayment of educational loans for physicians in specialties deemed necessary for VA. Finally, Section 304 created the Veterans Healing Veterans (VHV), a pilot scholarship specifically for veteran medical students.
 

Program Characteristics

Health Professions Scholarship

The VA HPSP is a program for physicians and dentists that extends from 2020 to 2033. The HPSP funds the costs of tuition, fees, and provides a stipend with a service obligation of 18 months for each year of support. The program is authorized for 10 years and must provide a minimum of 50 scholarships annually for physicians or dentists based on VHA needs. Applications are screened based on criteria that include a commitment to rural or underserved populations, veteran status, grade point average, essays, and letters of recommendation. Although the minimum required number of scholarships annually is 50, VA anticipates providing 1000 scholarships over 10 years with an aim to significantly increase the number physicians at VHA facilities (Table 1).

Veterans Healing Veterans

Implemented in 2020, the VHV was a 1-year pilot program. It offered scholarships to 2 veterans attending medical school at each of the 5 Teague-Cranston and the 4 Historically Black College and University (HBCU) medical schools (Table 2). The intent of the program was to determine the feasibility of increasing the pool of veteran physicians at VHA. Eligible applicants were notified of the scholarship opportunity through the American Medical College Application Service or through the medical school. Applicants must have separated from military service within the preceding 10 years of being admitted to medical school. In exchange for full tuition, fees, a monthly stipend, and rotation travel costs, the recipients accepted a 4-year clinical service obligation at VA facilities after completing their residency training.

Specialty Education Loan Repayment

The SELRP is a loan repayment program available to recently graduated physicians. Applicants must have graduated from an accredited medical or osteopathic school, matched to an accredited residency program and be ≥ 2 years from completion of residency. The specialties qualifying for SELRP are determined through an analysis of succession planning by the VA Office of Workforce Management and Consulting and change based on VA physician workforce needs. The SELRP provides loan repayment in the amount of $40,000 per year for up to 4 years, with a service obligation of 1 year for each $40,000 of support. In April 2021, VA began accepting applications from the eligible specialties of family medicine, internal medicine, gastroenterology, psychiatry, emergency medicine, and geriatrics.

Education Debt Reduction

The EDRP offers debt relief to clinicians in the most difficult to recruit professions, including physicians (generalists and specialists), registered nurses, licensed practical nurses, social workers, and psychologists. The list of difficult to recruit positions is developed annually by VA facilities. Annual reimbursements through the program may be used for tuition and expenses, such as fees, books, supplies, equipment, and other materials. In 2018, through the MISSION Act Section 302, the annual loan repayment was increased from $24,000 to $40,000, and the maximum level of support was increased from $120,000 to $200,000 over 5 years. Recipients receive reimbursement for loan repayment at the end of each year or service period and recipients are not required to remain in VA for 5 years.

Program Results

Health Professions Scholarship

For academic years 2020/2021 and 2021/2022, 126 HPSP applications from both allopathic and osteopathic schools were submitted and 51 scholarships were awarded (Table 3). Assuming an average residency length of 4 years, VHA estimates that these awards will yield 204 service-year equivalents by 2029.

Veterans Healing Veterans

In the VHV program, scholarship recipients came from 5 Teague-Cranston schools; 2 at University of South Carolina, 2 at East Tennessee State University, 2 at Wright State University, 1 at Texas A&M College of Medicine, 1 at Marshall University; and 3 HBCUs; 2 at Howard University, 1 at Morehouse School of Medicine and 1 at Meharry Medical College. The Charles R. Drew University of Medicine and Science did not nominate any students for the scholarship. Assuming all recipients complete postgraduate training, the VHV scholarship program will provide an additional 12 veteran physicians to serve at VA for at least 4 years each (48 service years).

Specialty Education Loan Repayment

Fourteen applicants have been approved, including 5 in psychiatry, 4 in family medicine, 3 in internal medicine, 1 in emergency medicine, and 1 in geriatrics. The mean loan repayment is anticipated to be $110,000 and equating to 38.5 VA service years or a mean of 2.3 years of service obligation per individual for the first cohort. The program has no termination date, and with continued funding, VA anticipates granting 100 loan repayments annually.

Education Debt Reduction

Since 2018, 1,546 VA physicians have received EDRP awards. Due to the increased reimbursement provided through the MISSION Act, average physician award amounts have increased from $96,090 in 2018 to $142,557 in 2019 and $148,302 in 2020.

Conclusions

The VA physician scholarship and loan repayment programs outlined in the MISSION Act build on the success of existing federal scholarship programs by providing opportunities for physician trainees to alleviate educational debt and explore a VA health professions career.

Looking ahead, VA must focus on measuring the success of the MISSION scholarship and loan repayment programs by tracking rates of acceptance and student graduation, residency and fellowship completion, and placement in VA medical facilities—both for the service obligation and future employment. Ultimately, the total impact on VA staffing, especially at rural and underresourced sites, will determine the success of the MISSION programs.