Catatonia is a psychomotor syndrome identified by its clinical phenotype. Unlike common psychiatric syndromes such as major depression that are characterized by self-report of symptoms, catatonia is identified chiefly by empirically evaluated signs on clinical evaluation. Its signs are recognized through observation, physical examination, or elicitation by clinical maneuvers or the presentation of stimuli. However, catatonia is often overlooked even though its clinical signs are often visibly apparent, including to the casual observer.

Why is catatonia underdiagnosed? A key modifiable factor appears to be a prevalent misunderstanding over what catatonia looks like.¹ We have sought to address this in a few ways.

First identified was the need for comprehensive educational resources on how to assess for and recognize catatonia. Using the Bush-Francis Catatonia Rating Scale – the most widely used scale for catatonia in both research and clinical settings and the most cited publication in the catatonia literature– our team developed the BFCRS Training Manual and Coding Guide.^2,3 This manual expands on the definitions of each BFCRS item based on how it was originally operationalized by the scale’s authors. Subsequently, we created a comprehensive set of educational resources including videos illustrating how to assess for catatonia, a video for each of the 23 items on the BFCRS, and self-assessment tools. All resources are freely available online at https://bfcrs.urmc.edu.⁴

Through this project it became apparent that there are many discrepancies across the field regarding the phenotype of catatonia. Specifically, a recent review inspired by this project set about to characterize the scope of distinctions across diagnostic systems and rating scales.⁵ For instance, each diagnostic system and rating scale includes a unique set of signs, approaches diagnostic thresholds differently, and often operationalizes clinical features in ways that lead either to criterion overlap (for example, combativeness would be scored both as combativeness and agitation on ICD-11) or contradictions with other systems or scales (for example, varied definitions of waxy flexibility). In the face of so many inconsistencies, what is a clinician to do? What follows is a discussion of how to apply the insights from this recent review in clinical and research settings.

Starting with DSM-5-TR and ICD-11 – the current editions of the two leading diagnostic systems – one might ask: How do they compare?^6,7 Overall, these two systems are broadly aligned in terms of the catatonic syndrome. Both systems identify individual clinical signs (as opposed to symptom complexes). Both require three features as a diagnostic threshold. Most of the same clinical signs are included in both systems, and the definitions of individual items are largely equivalent. Additionally, both systems allow for diagnosis of catatonia in association with psychiatric and medical conditions and include a category for unspecified catatonia.

Despite these core agreements, though, there are several important distinctions. First, whereas all 12 signs included in DSM-5-TR count toward an ICD-11 catatonia diagnosis, the opposite cannot be said. ICD-11 includes several features that are not in DSM-5-TR: rigidity, verbigeration, withdrawal, staring, ambitendency, impulsivity, and combativeness. Next, autonomic abnormality, which signifies the most severe type of catatonia called malignant catatonia, is included as a potential comorbidity in ICD-11 but not mentioned in DSM-5-TR. Third, ICD-11 includes a separate diagnosis for substance-induced catatonia, whereas this condition would be diagnosed as unspecified catatonia in DSM-5-TR.

There are also elements missing from both systems. The most notable of these is that neither system specifies the period over which findings must be present for diagnosis. By clinical convention, the practical definition of 24 hours is appropriate in most instances. The clinical features identified during direct evaluation are usually sufficient for diagnosis, but additional signs observed or documented over the prior 24 hours should be incorporated as part of the clinical evaluation. Another distinction is how to handle clinical features before and after lorazepam challenge. As noted in the BFCRS Training Manual, it would be appropriate to compare “state assessments” (that is, restricted to features identified only during direct, in-person assessment) from before and after lorazepam administration to document improvement.⁴

Whereas DSM-5-TR and ICD-11 are broadly in agreement, comparing these systems with catatonia rating scales reveals many sources of potential confusion, but also concrete guidance on operationalizing individual items.⁵ How exactly should each of catatonia’s clinical signs be defined? Descriptions differ, and thresholds of duration and frequency vary considerably across scales. As a result, clinicians who use different scales and then convert these results to diagnostic criteria are liable to come to different clinical conclusions. For instance, both echophenomena and negativism must be elicited more than five times to be scored per Northoff,⁸ but even a single convincing instance of either would be scored on the BFCRS as “occasional.”²

Such discrepancies are important because, whereas the psychometric properties of several catatonia scales have been documented, there are no analogous studies on the DSM-5-TR and ICD-11 criteria. Therefore, it is essential for clinicians and researchers to document how diagnostic criteria have been operationalized. The most practical and evidence-based way to do this is to use a clinically validated scale and convert these to diagnostic criteria, yet in doing so a few modifications will be necessary.

Of the available clinical scales, the BFCRS is best positioned for clinical use. The BFCRS has been validated clinically and has good reliability, detailed item definitions and audiovisual examples available. In addition, it is the only scale with a published semistructured evaluation (see initial paper and Training Manual), which takes about 5 minutes.2,4 In terms of utility, all 12 signs included by DSM-5-TR are among the first 14 items on the BFCRS, which constitutes a standalone tool known as the Bush-Francis Catatonia Screening Instrument (BFCSI, see Table).

Many fundamental questions remain about catatonia,but the importance of a shared understanding of its clinical features is clear.⁹ Catatonia should be on the differential whenever a patient exhibits a markedly altered level of activity or grossly abnormal behavior, especially when inappropriate to context. We encourage readers to familiarize themselves with the phenotype of catatonia through online educational resources⁴ because the optimal care of patients with catatonia requires – at a minimum – that we know what we’re looking for.

Dr. Oldham is assistant professor of psychiatry at the University of Rochester (N.Y.) Medical Center. Dr. Francis is professor of psychiatry at Penn State University, Hershey. The authors declare no relevant conflicts of interest. Funding for the educational project hosted at https://bfcrs.urmc.edu was provided by the department of psychiatry at the University of Rochester Medical Center. Dr. Oldham is currently supported by a K23 career development award from the National Institute on Aging (AG072383). The educational resources referenced in this piece could not have been created were it not for the intellectual and thespian collaboration of Joshua R. Wortzel, MD, who is currently a fellow in child and adolescent psychiatry at Brown University, Providence, R.I. The authors are also indebted to Hochang B. Lee, MD, for his gracious support of this project.

References

1. Wortzel JR et al. J Clin Psychiatry. 2021 Aug 17;82(5):21m14025. doi: 10.4088/JCP.21m14025.

2. Bush G et al. Acta Psychiatr Scand. 1996 Feb;93(2):129-36. doi: 10.1111/j.1600-0447.1996.tb09814.x.

3. Weleff J et al. J Acad Consult Liaison Psychiatry. 2023 Jan-Feb;64(1):13-27. doi:10.1016/j.jaclp.2022.07.002.

4. Oldham MA et al. Bush-Francis Catatonia Rating Scale Assessment Resources. University of Rochester Medical Center, Department of Psychiatry. https://bfcrs.urmc.edu.

5. Oldham MA. Schizophr Res. 2022 Aug 19;S0920-9964(22)00294-8. doi: 10.1016/j.schres.2022.08.002.

6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR. Washington, D.C.: American Psychiatric Association Publishing, 2022.

7. World Health Organization. ICD-11 for Mortality and Morbidity Stastistics. 2022. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/486722075.

8. Northoff G et al. Mov Disord. May 1999;14(3):404-16. doi: 10.1002/1531-8257(199905)14:3<404::AID-MDS1004>3.0.CO;2-5.

9. Walther S et al. The Lancet Psychiatry. 2019 Jul;6(7):610-9. doi: 10.1016/S2215-0366(18)30474-7.

Catatonia is a psychomotor syndrome identified by its clinical phenotype. Unlike common psychiatric syndromes such as major depression that are characterized by self-report of symptoms, catatonia is identified chiefly by empirically evaluated signs on clinical evaluation. Its signs are recognized through observation, physical examination, or elicitation by clinical maneuvers or the presentation of stimuli. However, catatonia is often overlooked even though its clinical signs are often visibly apparent, including to the casual observer.

Why is catatonia underdiagnosed? A key modifiable factor appears to be a prevalent misunderstanding over what catatonia looks like.¹ We have sought to address this in a few ways.

First identified was the need for comprehensive educational resources on how to assess for and recognize catatonia. Using the Bush-Francis Catatonia Rating Scale – the most widely used scale for catatonia in both research and clinical settings and the most cited publication in the catatonia literature– our team developed the BFCRS Training Manual and Coding Guide.^2,3 This manual expands on the definitions of each BFCRS item based on how it was originally operationalized by the scale’s authors. Subsequently, we created a comprehensive set of educational resources including videos illustrating how to assess for catatonia, a video for each of the 23 items on the BFCRS, and self-assessment tools. All resources are freely available online at https://bfcrs.urmc.edu.⁴

Through this project it became apparent that there are many discrepancies across the field regarding the phenotype of catatonia. Specifically, a recent review inspired by this project set about to characterize the scope of distinctions across diagnostic systems and rating scales.⁵ For instance, each diagnostic system and rating scale includes a unique set of signs, approaches diagnostic thresholds differently, and often operationalizes clinical features in ways that lead either to criterion overlap (for example, combativeness would be scored both as combativeness and agitation on ICD-11) or contradictions with other systems or scales (for example, varied definitions of waxy flexibility). In the face of so many inconsistencies, what is a clinician to do? What follows is a discussion of how to apply the insights from this recent review in clinical and research settings.

Starting with DSM-5-TR and ICD-11 – the current editions of the two leading diagnostic systems – one might ask: How do they compare?^6,7 Overall, these two systems are broadly aligned in terms of the catatonic syndrome. Both systems identify individual clinical signs (as opposed to symptom complexes). Both require three features as a diagnostic threshold. Most of the same clinical signs are included in both systems, and the definitions of individual items are largely equivalent. Additionally, both systems allow for diagnosis of catatonia in association with psychiatric and medical conditions and include a category for unspecified catatonia.

Despite these core agreements, though, there are several important distinctions. First, whereas all 12 signs included in DSM-5-TR count toward an ICD-11 catatonia diagnosis, the opposite cannot be said. ICD-11 includes several features that are not in DSM-5-TR: rigidity, verbigeration, withdrawal, staring, ambitendency, impulsivity, and combativeness. Next, autonomic abnormality, which signifies the most severe type of catatonia called malignant catatonia, is included as a potential comorbidity in ICD-11 but not mentioned in DSM-5-TR. Third, ICD-11 includes a separate diagnosis for substance-induced catatonia, whereas this condition would be diagnosed as unspecified catatonia in DSM-5-TR.

There are also elements missing from both systems. The most notable of these is that neither system specifies the period over which findings must be present for diagnosis. By clinical convention, the practical definition of 24 hours is appropriate in most instances. The clinical features identified during direct evaluation are usually sufficient for diagnosis, but additional signs observed or documented over the prior 24 hours should be incorporated as part of the clinical evaluation. Another distinction is how to handle clinical features before and after lorazepam challenge. As noted in the BFCRS Training Manual, it would be appropriate to compare “state assessments” (that is, restricted to features identified only during direct, in-person assessment) from before and after lorazepam administration to document improvement.⁴

Whereas DSM-5-TR and ICD-11 are broadly in agreement, comparing these systems with catatonia rating scales reveals many sources of potential confusion, but also concrete guidance on operationalizing individual items.⁵ How exactly should each of catatonia’s clinical signs be defined? Descriptions differ, and thresholds of duration and frequency vary considerably across scales. As a result, clinicians who use different scales and then convert these results to diagnostic criteria are liable to come to different clinical conclusions. For instance, both echophenomena and negativism must be elicited more than five times to be scored per Northoff,⁸ but even a single convincing instance of either would be scored on the BFCRS as “occasional.”²

Such discrepancies are important because, whereas the psychometric properties of several catatonia scales have been documented, there are no analogous studies on the DSM-5-TR and ICD-11 criteria. Therefore, it is essential for clinicians and researchers to document how diagnostic criteria have been operationalized. The most practical and evidence-based way to do this is to use a clinically validated scale and convert these to diagnostic criteria, yet in doing so a few modifications will be necessary.

Of the available clinical scales, the BFCRS is best positioned for clinical use. The BFCRS has been validated clinically and has good reliability, detailed item definitions and audiovisual examples available. In addition, it is the only scale with a published semistructured evaluation (see initial paper and Training Manual), which takes about 5 minutes.2,4 In terms of utility, all 12 signs included by DSM-5-TR are among the first 14 items on the BFCRS, which constitutes a standalone tool known as the Bush-Francis Catatonia Screening Instrument (BFCSI, see Table).

Many fundamental questions remain about catatonia,but the importance of a shared understanding of its clinical features is clear.⁹ Catatonia should be on the differential whenever a patient exhibits a markedly altered level of activity or grossly abnormal behavior, especially when inappropriate to context. We encourage readers to familiarize themselves with the phenotype of catatonia through online educational resources⁴ because the optimal care of patients with catatonia requires – at a minimum – that we know what we’re looking for.

Dr. Oldham is assistant professor of psychiatry at the University of Rochester (N.Y.) Medical Center. Dr. Francis is professor of psychiatry at Penn State University, Hershey. The authors declare no relevant conflicts of interest. Funding for the educational project hosted at https://bfcrs.urmc.edu was provided by the department of psychiatry at the University of Rochester Medical Center. Dr. Oldham is currently supported by a K23 career development award from the National Institute on Aging (AG072383). The educational resources referenced in this piece could not have been created were it not for the intellectual and thespian collaboration of Joshua R. Wortzel, MD, who is currently a fellow in child and adolescent psychiatry at Brown University, Providence, R.I. The authors are also indebted to Hochang B. Lee, MD, for his gracious support of this project.

References

1. Wortzel JR et al. J Clin Psychiatry. 2021 Aug 17;82(5):21m14025. doi: 10.4088/JCP.21m14025.

2. Bush G et al. Acta Psychiatr Scand. 1996 Feb;93(2):129-36. doi: 10.1111/j.1600-0447.1996.tb09814.x.

3. Weleff J et al. J Acad Consult Liaison Psychiatry. 2023 Jan-Feb;64(1):13-27. doi:10.1016/j.jaclp.2022.07.002.

4. Oldham MA et al. Bush-Francis Catatonia Rating Scale Assessment Resources. University of Rochester Medical Center, Department of Psychiatry. https://bfcrs.urmc.edu.

5. Oldham MA. Schizophr Res. 2022 Aug 19;S0920-9964(22)00294-8. doi: 10.1016/j.schres.2022.08.002.

6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR. Washington, D.C.: American Psychiatric Association Publishing, 2022.

7. World Health Organization. ICD-11 for Mortality and Morbidity Stastistics. 2022. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/486722075.

8. Northoff G et al. Mov Disord. May 1999;14(3):404-16. doi: 10.1002/1531-8257(199905)14:3<404::AID-MDS1004>3.0.CO;2-5.

9. Walther S et al. The Lancet Psychiatry. 2019 Jul;6(7):610-9. doi: 10.1016/S2215-0366(18)30474-7.

Catatonia is a psychomotor syndrome identified by its clinical phenotype. Unlike common psychiatric syndromes such as major depression that are characterized by self-report of symptoms, catatonia is identified chiefly by empirically evaluated signs on clinical evaluation. Its signs are recognized through observation, physical examination, or elicitation by clinical maneuvers or the presentation of stimuli. However, catatonia is often overlooked even though its clinical signs are often visibly apparent, including to the casual observer.

Why is catatonia underdiagnosed? A key modifiable factor appears to be a prevalent misunderstanding over what catatonia looks like.¹ We have sought to address this in a few ways.

First identified was the need for comprehensive educational resources on how to assess for and recognize catatonia. Using the Bush-Francis Catatonia Rating Scale – the most widely used scale for catatonia in both research and clinical settings and the most cited publication in the catatonia literature– our team developed the BFCRS Training Manual and Coding Guide.^2,3 This manual expands on the definitions of each BFCRS item based on how it was originally operationalized by the scale’s authors. Subsequently, we created a comprehensive set of educational resources including videos illustrating how to assess for catatonia, a video for each of the 23 items on the BFCRS, and self-assessment tools. All resources are freely available online at https://bfcrs.urmc.edu.⁴

Through this project it became apparent that there are many discrepancies across the field regarding the phenotype of catatonia. Specifically, a recent review inspired by this project set about to characterize the scope of distinctions across diagnostic systems and rating scales.⁵ For instance, each diagnostic system and rating scale includes a unique set of signs, approaches diagnostic thresholds differently, and often operationalizes clinical features in ways that lead either to criterion overlap (for example, combativeness would be scored both as combativeness and agitation on ICD-11) or contradictions with other systems or scales (for example, varied definitions of waxy flexibility). In the face of so many inconsistencies, what is a clinician to do? What follows is a discussion of how to apply the insights from this recent review in clinical and research settings.

Starting with DSM-5-TR and ICD-11 – the current editions of the two leading diagnostic systems – one might ask: How do they compare?^6,7 Overall, these two systems are broadly aligned in terms of the catatonic syndrome. Both systems identify individual clinical signs (as opposed to symptom complexes). Both require three features as a diagnostic threshold. Most of the same clinical signs are included in both systems, and the definitions of individual items are largely equivalent. Additionally, both systems allow for diagnosis of catatonia in association with psychiatric and medical conditions and include a category for unspecified catatonia.

Despite these core agreements, though, there are several important distinctions. First, whereas all 12 signs included in DSM-5-TR count toward an ICD-11 catatonia diagnosis, the opposite cannot be said. ICD-11 includes several features that are not in DSM-5-TR: rigidity, verbigeration, withdrawal, staring, ambitendency, impulsivity, and combativeness. Next, autonomic abnormality, which signifies the most severe type of catatonia called malignant catatonia, is included as a potential comorbidity in ICD-11 but not mentioned in DSM-5-TR. Third, ICD-11 includes a separate diagnosis for substance-induced catatonia, whereas this condition would be diagnosed as unspecified catatonia in DSM-5-TR.

There are also elements missing from both systems. The most notable of these is that neither system specifies the period over which findings must be present for diagnosis. By clinical convention, the practical definition of 24 hours is appropriate in most instances. The clinical features identified during direct evaluation are usually sufficient for diagnosis, but additional signs observed or documented over the prior 24 hours should be incorporated as part of the clinical evaluation. Another distinction is how to handle clinical features before and after lorazepam challenge. As noted in the BFCRS Training Manual, it would be appropriate to compare “state assessments” (that is, restricted to features identified only during direct, in-person assessment) from before and after lorazepam administration to document improvement.⁴

Whereas DSM-5-TR and ICD-11 are broadly in agreement, comparing these systems with catatonia rating scales reveals many sources of potential confusion, but also concrete guidance on operationalizing individual items.⁵ How exactly should each of catatonia’s clinical signs be defined? Descriptions differ, and thresholds of duration and frequency vary considerably across scales. As a result, clinicians who use different scales and then convert these results to diagnostic criteria are liable to come to different clinical conclusions. For instance, both echophenomena and negativism must be elicited more than five times to be scored per Northoff,⁸ but even a single convincing instance of either would be scored on the BFCRS as “occasional.”²

Such discrepancies are important because, whereas the psychometric properties of several catatonia scales have been documented, there are no analogous studies on the DSM-5-TR and ICD-11 criteria. Therefore, it is essential for clinicians and researchers to document how diagnostic criteria have been operationalized. The most practical and evidence-based way to do this is to use a clinically validated scale and convert these to diagnostic criteria, yet in doing so a few modifications will be necessary.

Of the available clinical scales, the BFCRS is best positioned for clinical use. The BFCRS has been validated clinically and has good reliability, detailed item definitions and audiovisual examples available. In addition, it is the only scale with a published semistructured evaluation (see initial paper and Training Manual), which takes about 5 minutes.2,4 In terms of utility, all 12 signs included by DSM-5-TR are among the first 14 items on the BFCRS, which constitutes a standalone tool known as the Bush-Francis Catatonia Screening Instrument (BFCSI, see Table).

Many fundamental questions remain about catatonia,but the importance of a shared understanding of its clinical features is clear.⁹ Catatonia should be on the differential whenever a patient exhibits a markedly altered level of activity or grossly abnormal behavior, especially when inappropriate to context. We encourage readers to familiarize themselves with the phenotype of catatonia through online educational resources⁴ because the optimal care of patients with catatonia requires – at a minimum – that we know what we’re looking for.

Dr. Oldham is assistant professor of psychiatry at the University of Rochester (N.Y.) Medical Center. Dr. Francis is professor of psychiatry at Penn State University, Hershey. The authors declare no relevant conflicts of interest. Funding for the educational project hosted at https://bfcrs.urmc.edu was provided by the department of psychiatry at the University of Rochester Medical Center. Dr. Oldham is currently supported by a K23 career development award from the National Institute on Aging (AG072383). The educational resources referenced in this piece could not have been created were it not for the intellectual and thespian collaboration of Joshua R. Wortzel, MD, who is currently a fellow in child and adolescent psychiatry at Brown University, Providence, R.I. The authors are also indebted to Hochang B. Lee, MD, for his gracious support of this project.

References

1. Wortzel JR et al. J Clin Psychiatry. 2021 Aug 17;82(5):21m14025. doi: 10.4088/JCP.21m14025.

2. Bush G et al. Acta Psychiatr Scand. 1996 Feb;93(2):129-36. doi: 10.1111/j.1600-0447.1996.tb09814.x.

3. Weleff J et al. J Acad Consult Liaison Psychiatry. 2023 Jan-Feb;64(1):13-27. doi:10.1016/j.jaclp.2022.07.002.

4. Oldham MA et al. Bush-Francis Catatonia Rating Scale Assessment Resources. University of Rochester Medical Center, Department of Psychiatry. https://bfcrs.urmc.edu.

5. Oldham MA. Schizophr Res. 2022 Aug 19;S0920-9964(22)00294-8. doi: 10.1016/j.schres.2022.08.002.

6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR. Washington, D.C.: American Psychiatric Association Publishing, 2022.

7. World Health Organization. ICD-11 for Mortality and Morbidity Stastistics. 2022. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/486722075.

8. Northoff G et al. Mov Disord. May 1999;14(3):404-16. doi: 10.1002/1531-8257(199905)14:3<404::AID-MDS1004>3.0.CO;2-5.

9. Walther S et al. The Lancet Psychiatry. 2019 Jul;6(7):610-9. doi: 10.1016/S2215-0366(18)30474-7.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

Migraine is a condition that particularly affects the population of reproductive-aged women. A significant amount of the literature discusses the effect of estrogen as a migraine trigger and specifically migraine with aura as a vascular risk factor. One topic that is not discussed in the literature is whether migraine could be a risk for miscarriage, also known as spontaneous abortion. The National Institutes of Health (NIH)-funded study by Crowe and colleagues looks at this risk, especially as it relates to the frequency of migraine, the use of acute migraine medications, and caffeine intake.

This was a broad study, including nearly 2000 patients with migraine, and was a continuation of a prior ongoing NIH-funded epidemiologic study. The initial study enrolled nearly 8000 participants, all of whom were women aged 21-45 years, were in a pregnancy planning stage, and were followed for up to 12 months or until a reported pregnancy. Questionnaires were given preconception, as well as early in pregnancy (defined as 8-9 weeks' gestation), and late in pregnancy (defined as 32 weeks' gestation).

During this study 19% of pregnancies ended in spontaneous abortion. A history of migraine preconception was not associated with spontaneous abortion risk on the basis of hazard ratios. There was a slight risk in those taking some migraine medication daily, either prophylactic or analgesic. Frequency of migraine itself was not noted as a risk for spontaneous abortion.

It is necessary that this important study be followed by further investigations looking at specific medication classes and their potential risk for spontaneous abortion. Migraine itself does not appear to be a risk for miscarriage; however, there remains the possibility that some preventive or acute medications may elevate this risk. At the current moment, there is not enough information to draw a conclusion. All clinicians who treat people with migraine, particularly women who are in their reproductive years, should continue to have conversations regarding pregnancy planning and the adjustment of both preventive and acute medications prior to conception.

Neck pain is a common comorbidity of both chronic and acute migraine, and botulinum toxin is a US Food and Drug Administration–approved treatment both for chronic migraine and certain painful neck conditions, including cervical dystonia. Migraine itself can be a disabling condition; when migraine is combined with other painful comorbidities the likelihood of disability becomes increased significantly. The standard PREEMPT protocol for botulinum toxin injection in chronic migraine of 155 units includes a number of injections in the trapezius and cervical paraspinal muscles. Many clinicians will give additional injections into these muscles and other areas around the neck, specifically targeting areas of neck and shoulder spasm and tenderness. Onan and colleagues investigated the quality of life and disability scores of patients who received these additional injections.

This was an open study, in which participants were given an additional 30 units of botulinum toxin into the general neck areas in a follow-the-pain protocol. The authors, used as a primary outcome, the reduction in the Migraine Disability Assessment (MIDAS) and Neck Disability Index (NDI) scores at 4 weeks and 3 months. The secondary outcome was the Headache Impact Test (HIT-6) score. An objective assessment of neck mobility or a quantification of trigger points were not calculated.

All scores, both the primary and secondary outcomes, were significantly decreased, and quality of life was also noted to be significantly improved with these additional injections. Most clinicians receive a 200-unit vial of botulinum toxin for each of their chronic migraine protocol injections. There is a growing body of evidence to argue that the additional units of botulinum toxin significantly improve outcomes, both regarding headache and neck pain. This study argues for delivering these additional injections of botulinum toxin, especially when neck pain is more prominent.

Much has been written about diet triggers and migraine recently. There has been some evidence for specific diet changes, ie, the addition of foods or nutrients that can be helpful or preventive for migraine. There is some evidence for the addition of omega-3 fatty acids. Huang and He investigated the effect of a high fiber diet on migraine frequency and severity.

This was a cross-sectional study involving data collected from the NIH/Centers for Disease Control and Prevention–sponsored National Health and Nutrition Examination Survey trial from 1999 to 2004. In the studied population, severe headache and migraine was present in approximately 20%, and dietary fiber intake was delineated on the basis of whether it was more than or less than 100 g/d. This study assessed dietary intake of fiber, via a 24-hour dietary recall that was conducted by trained interviewers during two interviews conducted over the course of 2 years.

A total of 12,000 participants were included in the study. There was a significant decrease in migraine severity between those with a higher and lower dietary fiber intake. The incidence of severe headache or migraine, as defined by frequency and severity, decreased in participants who had a dietary fiber intake > 100 g/d. The authors found that for every 10 g/d increase in dietary fiber intake, the prevalence of severe headache or migraine decreased by approximately 11%.

Although much has been written about the association between diet and migraine, most of the literature focuses on the avoidance of specific dietary triggers. A different consideration now exists, one that will likely increase compliance with dietary recommendations. Specifically, people treating patients with migraine can make recommendations regarding dietary changes that focus on adding specific healthy foods or other changes that can actually be associated with improving migraine frequency long-term. Recommending healthy fats, such as omega-3 fatty acids, and high fiber should be done for nearly all patients with migraine.

Migraine is a condition that particularly affects the population of reproductive-aged women. A significant amount of the literature discusses the effect of estrogen as a migraine trigger and specifically migraine with aura as a vascular risk factor. One topic that is not discussed in the literature is whether migraine could be a risk for miscarriage, also known as spontaneous abortion. The National Institutes of Health (NIH)-funded study by Crowe and colleagues looks at this risk, especially as it relates to the frequency of migraine, the use of acute migraine medications, and caffeine intake.

This was a broad study, including nearly 2000 patients with migraine, and was a continuation of a prior ongoing NIH-funded epidemiologic study. The initial study enrolled nearly 8000 participants, all of whom were women aged 21-45 years, were in a pregnancy planning stage, and were followed for up to 12 months or until a reported pregnancy. Questionnaires were given preconception, as well as early in pregnancy (defined as 8-9 weeks' gestation), and late in pregnancy (defined as 32 weeks' gestation).

During this study 19% of pregnancies ended in spontaneous abortion. A history of migraine preconception was not associated with spontaneous abortion risk on the basis of hazard ratios. There was a slight risk in those taking some migraine medication daily, either prophylactic or analgesic. Frequency of migraine itself was not noted as a risk for spontaneous abortion.

It is necessary that this important study be followed by further investigations looking at specific medication classes and their potential risk for spontaneous abortion. Migraine itself does not appear to be a risk for miscarriage; however, there remains the possibility that some preventive or acute medications may elevate this risk. At the current moment, there is not enough information to draw a conclusion. All clinicians who treat people with migraine, particularly women who are in their reproductive years, should continue to have conversations regarding pregnancy planning and the adjustment of both preventive and acute medications prior to conception.

Neck pain is a common comorbidity of both chronic and acute migraine, and botulinum toxin is a US Food and Drug Administration–approved treatment both for chronic migraine and certain painful neck conditions, including cervical dystonia. Migraine itself can be a disabling condition; when migraine is combined with other painful comorbidities the likelihood of disability becomes increased significantly. The standard PREEMPT protocol for botulinum toxin injection in chronic migraine of 155 units includes a number of injections in the trapezius and cervical paraspinal muscles. Many clinicians will give additional injections into these muscles and other areas around the neck, specifically targeting areas of neck and shoulder spasm and tenderness. Onan and colleagues investigated the quality of life and disability scores of patients who received these additional injections.

This was an open study, in which participants were given an additional 30 units of botulinum toxin into the general neck areas in a follow-the-pain protocol. The authors, used as a primary outcome, the reduction in the Migraine Disability Assessment (MIDAS) and Neck Disability Index (NDI) scores at 4 weeks and 3 months. The secondary outcome was the Headache Impact Test (HIT-6) score. An objective assessment of neck mobility or a quantification of trigger points were not calculated.

All scores, both the primary and secondary outcomes, were significantly decreased, and quality of life was also noted to be significantly improved with these additional injections. Most clinicians receive a 200-unit vial of botulinum toxin for each of their chronic migraine protocol injections. There is a growing body of evidence to argue that the additional units of botulinum toxin significantly improve outcomes, both regarding headache and neck pain. This study argues for delivering these additional injections of botulinum toxin, especially when neck pain is more prominent.

Much has been written about diet triggers and migraine recently. There has been some evidence for specific diet changes, ie, the addition of foods or nutrients that can be helpful or preventive for migraine. There is some evidence for the addition of omega-3 fatty acids. Huang and He investigated the effect of a high fiber diet on migraine frequency and severity.

This was a cross-sectional study involving data collected from the NIH/Centers for Disease Control and Prevention–sponsored National Health and Nutrition Examination Survey trial from 1999 to 2004. In the studied population, severe headache and migraine was present in approximately 20%, and dietary fiber intake was delineated on the basis of whether it was more than or less than 100 g/d. This study assessed dietary intake of fiber, via a 24-hour dietary recall that was conducted by trained interviewers during two interviews conducted over the course of 2 years.

A total of 12,000 participants were included in the study. There was a significant decrease in migraine severity between those with a higher and lower dietary fiber intake. The incidence of severe headache or migraine, as defined by frequency and severity, decreased in participants who had a dietary fiber intake > 100 g/d. The authors found that for every 10 g/d increase in dietary fiber intake, the prevalence of severe headache or migraine decreased by approximately 11%.

Although much has been written about the association between diet and migraine, most of the literature focuses on the avoidance of specific dietary triggers. A different consideration now exists, one that will likely increase compliance with dietary recommendations. Specifically, people treating patients with migraine can make recommendations regarding dietary changes that focus on adding specific healthy foods or other changes that can actually be associated with improving migraine frequency long-term. Recommending healthy fats, such as omega-3 fatty acids, and high fiber should be done for nearly all patients with migraine.

Migraine is a condition that particularly affects the population of reproductive-aged women. A significant amount of the literature discusses the effect of estrogen as a migraine trigger and specifically migraine with aura as a vascular risk factor. One topic that is not discussed in the literature is whether migraine could be a risk for miscarriage, also known as spontaneous abortion. The National Institutes of Health (NIH)-funded study by Crowe and colleagues looks at this risk, especially as it relates to the frequency of migraine, the use of acute migraine medications, and caffeine intake.

This was a broad study, including nearly 2000 patients with migraine, and was a continuation of a prior ongoing NIH-funded epidemiologic study. The initial study enrolled nearly 8000 participants, all of whom were women aged 21-45 years, were in a pregnancy planning stage, and were followed for up to 12 months or until a reported pregnancy. Questionnaires were given preconception, as well as early in pregnancy (defined as 8-9 weeks' gestation), and late in pregnancy (defined as 32 weeks' gestation).

During this study 19% of pregnancies ended in spontaneous abortion. A history of migraine preconception was not associated with spontaneous abortion risk on the basis of hazard ratios. There was a slight risk in those taking some migraine medication daily, either prophylactic or analgesic. Frequency of migraine itself was not noted as a risk for spontaneous abortion.

It is necessary that this important study be followed by further investigations looking at specific medication classes and their potential risk for spontaneous abortion. Migraine itself does not appear to be a risk for miscarriage; however, there remains the possibility that some preventive or acute medications may elevate this risk. At the current moment, there is not enough information to draw a conclusion. All clinicians who treat people with migraine, particularly women who are in their reproductive years, should continue to have conversations regarding pregnancy planning and the adjustment of both preventive and acute medications prior to conception.

Neck pain is a common comorbidity of both chronic and acute migraine, and botulinum toxin is a US Food and Drug Administration–approved treatment both for chronic migraine and certain painful neck conditions, including cervical dystonia. Migraine itself can be a disabling condition; when migraine is combined with other painful comorbidities the likelihood of disability becomes increased significantly. The standard PREEMPT protocol for botulinum toxin injection in chronic migraine of 155 units includes a number of injections in the trapezius and cervical paraspinal muscles. Many clinicians will give additional injections into these muscles and other areas around the neck, specifically targeting areas of neck and shoulder spasm and tenderness. Onan and colleagues investigated the quality of life and disability scores of patients who received these additional injections.

This was an open study, in which participants were given an additional 30 units of botulinum toxin into the general neck areas in a follow-the-pain protocol. The authors, used as a primary outcome, the reduction in the Migraine Disability Assessment (MIDAS) and Neck Disability Index (NDI) scores at 4 weeks and 3 months. The secondary outcome was the Headache Impact Test (HIT-6) score. An objective assessment of neck mobility or a quantification of trigger points were not calculated.

All scores, both the primary and secondary outcomes, were significantly decreased, and quality of life was also noted to be significantly improved with these additional injections. Most clinicians receive a 200-unit vial of botulinum toxin for each of their chronic migraine protocol injections. There is a growing body of evidence to argue that the additional units of botulinum toxin significantly improve outcomes, both regarding headache and neck pain. This study argues for delivering these additional injections of botulinum toxin, especially when neck pain is more prominent.

Much has been written about diet triggers and migraine recently. There has been some evidence for specific diet changes, ie, the addition of foods or nutrients that can be helpful or preventive for migraine. There is some evidence for the addition of omega-3 fatty acids. Huang and He investigated the effect of a high fiber diet on migraine frequency and severity.

This was a cross-sectional study involving data collected from the NIH/Centers for Disease Control and Prevention–sponsored National Health and Nutrition Examination Survey trial from 1999 to 2004. In the studied population, severe headache and migraine was present in approximately 20%, and dietary fiber intake was delineated on the basis of whether it was more than or less than 100 g/d. This study assessed dietary intake of fiber, via a 24-hour dietary recall that was conducted by trained interviewers during two interviews conducted over the course of 2 years.

A total of 12,000 participants were included in the study. There was a significant decrease in migraine severity between those with a higher and lower dietary fiber intake. The incidence of severe headache or migraine, as defined by frequency and severity, decreased in participants who had a dietary fiber intake > 100 g/d. The authors found that for every 10 g/d increase in dietary fiber intake, the prevalence of severe headache or migraine decreased by approximately 11%.

Although much has been written about the association between diet and migraine, most of the literature focuses on the avoidance of specific dietary triggers. A different consideration now exists, one that will likely increase compliance with dietary recommendations. Specifically, people treating patients with migraine can make recommendations regarding dietary changes that focus on adding specific healthy foods or other changes that can actually be associated with improving migraine frequency long-term. Recommending healthy fats, such as omega-3 fatty acids, and high fiber should be done for nearly all patients with migraine.

The recent debate about how best to address the growing epidemic of obesity in children and adolescents has pitted different professional organizations against each other. While there is little controversy that both obesity and eating disorders represent important public health concerns, each deserving of clinical attention, how best to address one without worsening the other has been the crux of the discussion.

Sparking the dispute was a recent publication from the American Academy of Pediatrics that outlines the scope of the obesity problem and makes specific recommendations for assessment and treatment.¹ The ambitious 100-page document, with 801 citations, puts new emphasis on the medical and psychological costs associated with obesity and advocates that pediatric primary care clinicians be more assertive in its treatment. While the guidelines certainly don’t urge the use of medications or surgery options as first-line treatment, the new recommendations do put them on the table as options.

In response, the Academy of Eating Disorders issued a public statement outlining several concerns regarding these guidelines that centered around a lack of a detailed plan to screen and address eating disorders; concerns that pediatricians don’t have the level of training and “skills” to conduct these conversations with patients and families with enough sensitivity; and worries about the premature use of antiobesity medications and surgeries in this population.²

It is fair to say that the critique was sharply worded, invoking physicians’ Hippocratic oath, criticizing their training, and suggesting that the guidelines could be biased by pharmaceutical industry influence (of note, the authors of the guidelines reported no ties to any pharmaceutical company). The AED urged that the guidelines be “revised” after consultation with other groups, including them.

Not unexpectedly, this response, especially coming from a group whose leadership and members are primarily nonphysicians, triggered its own sharp rebukes, including a recent commentary that counter-accused some of the eating disorder clinicians of being more concerned with their pet diets than actual health improvements.³

After everyone takes some deep breaths, it’s worth looking to see if there is some middle ground to explore here. The AAP document, to my reading, shows some important acknowledgments of the stigma associated with being overweight, even coming from pediatricians themselves. One passage reads, “Pediatricians and other PHCPs [primary health care providers] have been – and remain – a source of weight bias. They first need to uncover and address their own attitudes regarding children with obesity. Understanding weight stigma and bias, and learning how to reduce it in the clinical setting, sets the stage for productive discussions and improved relationships between families and pediatricians or other PHCPs.”

The guidelines also include some suggestions for how to talk to youth and families about obesity in less stigmatizing ways and offer a fairly lengthy summary of motivational interviewing techniques as they might apply to obesity discussions and lifestyle change. There is also a section on the interface between obesity and eating disorders with suggestions for further reading on their assessment and management.⁴

Indeed, research has looked specifically at how to minimize the triggering of eating disorders when addressing weight problems, a concern that has been raised by pediatricians themselves as documented in a qualitative study that also invoked the “do no harm” principle.⁵ One study asked more than 2,000 teens about how various conversations about weight affected their behavior.⁶ A main finding from that study was that conversations that focused on healthy eating rather than weight per se were less likely to be associated with unhealthy weight control behaviors. This message was emphasized in a publication that came from the AAP itself; it addresses the interaction between eating disorders and obesity.⁷ Strangely, however, the suggestion to try to minimize the focus on weight in discussions with patients isn’t well emphasized in the publication.

Overall, though, the AAP guidelines offer a well-informed and balanced approach to helping overweight youth. Pediatricians and other pediatric primary care clinicians are frequently called upon to engage in extremely sensitive and difficult discussions with patients and families on a wide variety of topics and most do so quite skillfully, especially when given the proper time and tools. While it is an area in which many of us, including mental health professionals, could do better, it’s no surprise that the AED’s disparaging of pediatricians’ communication competence came off as insulting. Similarly, productive dialogue would be likely enhanced if both sides avoided unfounded speculation about bias and motive and worked from a good faith perspective that all of us are engaged in this important discussion because of a desire to improve the lives of kids.

From my reading, it is quite a stretch to conclude that this document is urging a hasty and financially driven descent into GLP-1 analogues and bariatric surgery. That said, this wouldn’t be the first time a professional organization issues detailed, thoughtful, and nuanced care guidelines only to have them “condensed” within the practical confines of a busy office practice. Leaders would do well to remember that there remains much work to do to empower clinicians to be able to follow these guidelines as intended.
 

Dr. Rettew is a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland. His latest book is “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood.”

References

1. Hampl SE et al. Pediatrics. 2023;151(2):e2022060640.

2. Academy of Eating Disorders. Jan. 26, 2023. Accessed February 2, 2023. Available at The Academy for Eating Disorders Releases a Statement on the Recent American Academy of Pediatrics Clinical Practice Guideline for Weight-Related Care: First, Do No Harm (newswise.com).

3. Freedhoff Y. MDedge Pediatrics 2023. Available at https://www.mdedge.com/pediatrics/article/260894/obesity/weight-bias-affects-views-kids-obesity-recommendations?channel=52.

4. Hornberger LL, Lane MA et al. Pediatrics. 2021;147(1):e202004027989.

5. Loth KA, Lebow J et al. Global Pediatric Health. 2021;8:1-9.

6. Berge JM et al. JAMA Pediatrics. 2013;167(8):746-53.

7. Golden NH et al. Pediatrics. 2016;138(3):e20161649.

The recent debate about how best to address the growing epidemic of obesity in children and adolescents has pitted different professional organizations against each other. While there is little controversy that both obesity and eating disorders represent important public health concerns, each deserving of clinical attention, how best to address one without worsening the other has been the crux of the discussion.

Sparking the dispute was a recent publication from the American Academy of Pediatrics that outlines the scope of the obesity problem and makes specific recommendations for assessment and treatment.¹ The ambitious 100-page document, with 801 citations, puts new emphasis on the medical and psychological costs associated with obesity and advocates that pediatric primary care clinicians be more assertive in its treatment. While the guidelines certainly don’t urge the use of medications or surgery options as first-line treatment, the new recommendations do put them on the table as options.

In response, the Academy of Eating Disorders issued a public statement outlining several concerns regarding these guidelines that centered around a lack of a detailed plan to screen and address eating disorders; concerns that pediatricians don’t have the level of training and “skills” to conduct these conversations with patients and families with enough sensitivity; and worries about the premature use of antiobesity medications and surgeries in this population.²

It is fair to say that the critique was sharply worded, invoking physicians’ Hippocratic oath, criticizing their training, and suggesting that the guidelines could be biased by pharmaceutical industry influence (of note, the authors of the guidelines reported no ties to any pharmaceutical company). The AED urged that the guidelines be “revised” after consultation with other groups, including them.

Not unexpectedly, this response, especially coming from a group whose leadership and members are primarily nonphysicians, triggered its own sharp rebukes, including a recent commentary that counter-accused some of the eating disorder clinicians of being more concerned with their pet diets than actual health improvements.³

After everyone takes some deep breaths, it’s worth looking to see if there is some middle ground to explore here. The AAP document, to my reading, shows some important acknowledgments of the stigma associated with being overweight, even coming from pediatricians themselves. One passage reads, “Pediatricians and other PHCPs [primary health care providers] have been – and remain – a source of weight bias. They first need to uncover and address their own attitudes regarding children with obesity. Understanding weight stigma and bias, and learning how to reduce it in the clinical setting, sets the stage for productive discussions and improved relationships between families and pediatricians or other PHCPs.”

The guidelines also include some suggestions for how to talk to youth and families about obesity in less stigmatizing ways and offer a fairly lengthy summary of motivational interviewing techniques as they might apply to obesity discussions and lifestyle change. There is also a section on the interface between obesity and eating disorders with suggestions for further reading on their assessment and management.⁴

Indeed, research has looked specifically at how to minimize the triggering of eating disorders when addressing weight problems, a concern that has been raised by pediatricians themselves as documented in a qualitative study that also invoked the “do no harm” principle.⁵ One study asked more than 2,000 teens about how various conversations about weight affected their behavior.⁶ A main finding from that study was that conversations that focused on healthy eating rather than weight per se were less likely to be associated with unhealthy weight control behaviors. This message was emphasized in a publication that came from the AAP itself; it addresses the interaction between eating disorders and obesity.⁷ Strangely, however, the suggestion to try to minimize the focus on weight in discussions with patients isn’t well emphasized in the publication.

Overall, though, the AAP guidelines offer a well-informed and balanced approach to helping overweight youth. Pediatricians and other pediatric primary care clinicians are frequently called upon to engage in extremely sensitive and difficult discussions with patients and families on a wide variety of topics and most do so quite skillfully, especially when given the proper time and tools. While it is an area in which many of us, including mental health professionals, could do better, it’s no surprise that the AED’s disparaging of pediatricians’ communication competence came off as insulting. Similarly, productive dialogue would be likely enhanced if both sides avoided unfounded speculation about bias and motive and worked from a good faith perspective that all of us are engaged in this important discussion because of a desire to improve the lives of kids.

From my reading, it is quite a stretch to conclude that this document is urging a hasty and financially driven descent into GLP-1 analogues and bariatric surgery. That said, this wouldn’t be the first time a professional organization issues detailed, thoughtful, and nuanced care guidelines only to have them “condensed” within the practical confines of a busy office practice. Leaders would do well to remember that there remains much work to do to empower clinicians to be able to follow these guidelines as intended.
 

Dr. Rettew is a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland. His latest book is “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood.”

References

1. Hampl SE et al. Pediatrics. 2023;151(2):e2022060640.

2. Academy of Eating Disorders. Jan. 26, 2023. Accessed February 2, 2023. Available at The Academy for Eating Disorders Releases a Statement on the Recent American Academy of Pediatrics Clinical Practice Guideline for Weight-Related Care: First, Do No Harm (newswise.com).

3. Freedhoff Y. MDedge Pediatrics 2023. Available at https://www.mdedge.com/pediatrics/article/260894/obesity/weight-bias-affects-views-kids-obesity-recommendations?channel=52.

4. Hornberger LL, Lane MA et al. Pediatrics. 2021;147(1):e202004027989.

5. Loth KA, Lebow J et al. Global Pediatric Health. 2021;8:1-9.

6. Berge JM et al. JAMA Pediatrics. 2013;167(8):746-53.

7. Golden NH et al. Pediatrics. 2016;138(3):e20161649.

The recent debate about how best to address the growing epidemic of obesity in children and adolescents has pitted different professional organizations against each other. While there is little controversy that both obesity and eating disorders represent important public health concerns, each deserving of clinical attention, how best to address one without worsening the other has been the crux of the discussion.

Sparking the dispute was a recent publication from the American Academy of Pediatrics that outlines the scope of the obesity problem and makes specific recommendations for assessment and treatment.¹ The ambitious 100-page document, with 801 citations, puts new emphasis on the medical and psychological costs associated with obesity and advocates that pediatric primary care clinicians be more assertive in its treatment. While the guidelines certainly don’t urge the use of medications or surgery options as first-line treatment, the new recommendations do put them on the table as options.

In response, the Academy of Eating Disorders issued a public statement outlining several concerns regarding these guidelines that centered around a lack of a detailed plan to screen and address eating disorders; concerns that pediatricians don’t have the level of training and “skills” to conduct these conversations with patients and families with enough sensitivity; and worries about the premature use of antiobesity medications and surgeries in this population.²

It is fair to say that the critique was sharply worded, invoking physicians’ Hippocratic oath, criticizing their training, and suggesting that the guidelines could be biased by pharmaceutical industry influence (of note, the authors of the guidelines reported no ties to any pharmaceutical company). The AED urged that the guidelines be “revised” after consultation with other groups, including them.

Not unexpectedly, this response, especially coming from a group whose leadership and members are primarily nonphysicians, triggered its own sharp rebukes, including a recent commentary that counter-accused some of the eating disorder clinicians of being more concerned with their pet diets than actual health improvements.³

After everyone takes some deep breaths, it’s worth looking to see if there is some middle ground to explore here. The AAP document, to my reading, shows some important acknowledgments of the stigma associated with being overweight, even coming from pediatricians themselves. One passage reads, “Pediatricians and other PHCPs [primary health care providers] have been – and remain – a source of weight bias. They first need to uncover and address their own attitudes regarding children with obesity. Understanding weight stigma and bias, and learning how to reduce it in the clinical setting, sets the stage for productive discussions and improved relationships between families and pediatricians or other PHCPs.”

The guidelines also include some suggestions for how to talk to youth and families about obesity in less stigmatizing ways and offer a fairly lengthy summary of motivational interviewing techniques as they might apply to obesity discussions and lifestyle change. There is also a section on the interface between obesity and eating disorders with suggestions for further reading on their assessment and management.⁴

Indeed, research has looked specifically at how to minimize the triggering of eating disorders when addressing weight problems, a concern that has been raised by pediatricians themselves as documented in a qualitative study that also invoked the “do no harm” principle.⁵ One study asked more than 2,000 teens about how various conversations about weight affected their behavior.⁶ A main finding from that study was that conversations that focused on healthy eating rather than weight per se were less likely to be associated with unhealthy weight control behaviors. This message was emphasized in a publication that came from the AAP itself; it addresses the interaction between eating disorders and obesity.⁷ Strangely, however, the suggestion to try to minimize the focus on weight in discussions with patients isn’t well emphasized in the publication.

Overall, though, the AAP guidelines offer a well-informed and balanced approach to helping overweight youth. Pediatricians and other pediatric primary care clinicians are frequently called upon to engage in extremely sensitive and difficult discussions with patients and families on a wide variety of topics and most do so quite skillfully, especially when given the proper time and tools. While it is an area in which many of us, including mental health professionals, could do better, it’s no surprise that the AED’s disparaging of pediatricians’ communication competence came off as insulting. Similarly, productive dialogue would be likely enhanced if both sides avoided unfounded speculation about bias and motive and worked from a good faith perspective that all of us are engaged in this important discussion because of a desire to improve the lives of kids.

From my reading, it is quite a stretch to conclude that this document is urging a hasty and financially driven descent into GLP-1 analogues and bariatric surgery. That said, this wouldn’t be the first time a professional organization issues detailed, thoughtful, and nuanced care guidelines only to have them “condensed” within the practical confines of a busy office practice. Leaders would do well to remember that there remains much work to do to empower clinicians to be able to follow these guidelines as intended.
 

Dr. Rettew is a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland. His latest book is “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood.”

References

1. Hampl SE et al. Pediatrics. 2023;151(2):e2022060640.

2. Academy of Eating Disorders. Jan. 26, 2023. Accessed February 2, 2023. Available at The Academy for Eating Disorders Releases a Statement on the Recent American Academy of Pediatrics Clinical Practice Guideline for Weight-Related Care: First, Do No Harm (newswise.com).

3. Freedhoff Y. MDedge Pediatrics 2023. Available at https://www.mdedge.com/pediatrics/article/260894/obesity/weight-bias-affects-views-kids-obesity-recommendations?channel=52.

4. Hornberger LL, Lane MA et al. Pediatrics. 2021;147(1):e202004027989.

5. Loth KA, Lebow J et al. Global Pediatric Health. 2021;8:1-9.

6. Berge JM et al. JAMA Pediatrics. 2013;167(8):746-53.

7. Golden NH et al. Pediatrics. 2016;138(3):e20161649.

Here we are, 1 month into the new year, and it already feels like my time as President of the American College of Chest Physicians will pass too quickly. One of my goals is to share some thoughts on issues important to our profession by contributing quarterly to CHEST Physician. CHEST has always been like an extended family to me, and I look forward to having this regular touchpoint with all of you.

For my first written contribution, I want to focus on the future of medicine through medical education and involvement in professional associations because I am, at heart, a medical educator.

During my address at the CHEST Annual Meeting 2022, I spoke on how CHEST provided me with networking, mentoring, and volunteer opportunities that were critical in advancing my career. Those same opportunities should be extended to everyone in pulmonary, critical care, and sleep medicine – whether a current member or prospective member.
 

Lighting a fire

Attending my first CHEST Annual Meeting was possible due to my nomination for a leadership development course. The connections I made during the meeting really lit a fire within me. We need to engage with early career clinicians and provide them the same exposure and encouragement that I received.

To instill this fire in the next generation, I encourage each of our established members, years (or decades) into their careers, to pass along their expertise to someone who is just starting out, whether it be a trainee or a junior faculty member. If this applies to you: encourage a new attending who has never been to a CHEST event to attend with you; invite a fellow or resident to submit an abstract or case report to the journal CHEST® with your oversight; or simply volunteer to speak at your medical school or residency program about why you chose PCCM and the career it has given you.

Think back to when you were embarking on your journey toward where you are now – what would it have meant to be able to get career advice or even just a friendly conversation started with someone at your current level?
 

CHEST offerings and accreditations

Beyond bringing someone to a CHEST Annual Meeting – which you should definitely do – work with your learners at medical schools and residency programs to expose them to CHEST much earlier in their careers. The Trainings and Transitions Committee is an excellent resource to guide newer clinicians and can provide a vital source of encouragement and support. If your institution doesn’t have a simulation learning center or if it has limited offerings, the hands-on learning opportunities offered at CHEST headquarters may be a fit. Accredited by the Society for Simulation in Healthcare (SSH) and the Accreditation Council for Continuing Medical Education (ACCME), CHEST currently offers 24 courses with four new courses planned for 2023 in a wide variety of areas, including courses on ultrasound and bronchoscopy.

There are so many ways to introduce early career clinicians to CHEST, and it can begin with one personal outreach. If you are working on a project for CHEST right now, consider inviting an early career clinician to join you on it – this may be the opportunity that will change their career. It did for me.

As medical professionals, each of us plays an important role in the future of medicine, and the CHEST organization can bring us together to strengthen our impact.

If you are interested in brainstorming ideas for how to engage your medical students, residents, or fellows, please feel free to contact me or anyone at CHEST to help create a plan.

I look forward to the next time we connect.

Doreen J. Addrizzo-Harris, MD, FCCP

CHEST President

Here we are, 1 month into the new year, and it already feels like my time as President of the American College of Chest Physicians will pass too quickly. One of my goals is to share some thoughts on issues important to our profession by contributing quarterly to CHEST Physician. CHEST has always been like an extended family to me, and I look forward to having this regular touchpoint with all of you.

For my first written contribution, I want to focus on the future of medicine through medical education and involvement in professional associations because I am, at heart, a medical educator.

During my address at the CHEST Annual Meeting 2022, I spoke on how CHEST provided me with networking, mentoring, and volunteer opportunities that were critical in advancing my career. Those same opportunities should be extended to everyone in pulmonary, critical care, and sleep medicine – whether a current member or prospective member.
 

Lighting a fire

Attending my first CHEST Annual Meeting was possible due to my nomination for a leadership development course. The connections I made during the meeting really lit a fire within me. We need to engage with early career clinicians and provide them the same exposure and encouragement that I received.

To instill this fire in the next generation, I encourage each of our established members, years (or decades) into their careers, to pass along their expertise to someone who is just starting out, whether it be a trainee or a junior faculty member. If this applies to you: encourage a new attending who has never been to a CHEST event to attend with you; invite a fellow or resident to submit an abstract or case report to the journal CHEST® with your oversight; or simply volunteer to speak at your medical school or residency program about why you chose PCCM and the career it has given you.

Think back to when you were embarking on your journey toward where you are now – what would it have meant to be able to get career advice or even just a friendly conversation started with someone at your current level?
 

CHEST offerings and accreditations

Beyond bringing someone to a CHEST Annual Meeting – which you should definitely do – work with your learners at medical schools and residency programs to expose them to CHEST much earlier in their careers. The Trainings and Transitions Committee is an excellent resource to guide newer clinicians and can provide a vital source of encouragement and support. If your institution doesn’t have a simulation learning center or if it has limited offerings, the hands-on learning opportunities offered at CHEST headquarters may be a fit. Accredited by the Society for Simulation in Healthcare (SSH) and the Accreditation Council for Continuing Medical Education (ACCME), CHEST currently offers 24 courses with four new courses planned for 2023 in a wide variety of areas, including courses on ultrasound and bronchoscopy.

There are so many ways to introduce early career clinicians to CHEST, and it can begin with one personal outreach. If you are working on a project for CHEST right now, consider inviting an early career clinician to join you on it – this may be the opportunity that will change their career. It did for me.

As medical professionals, each of us plays an important role in the future of medicine, and the CHEST organization can bring us together to strengthen our impact.

If you are interested in brainstorming ideas for how to engage your medical students, residents, or fellows, please feel free to contact me or anyone at CHEST to help create a plan.

I look forward to the next time we connect.

Doreen J. Addrizzo-Harris, MD, FCCP

CHEST President

Here we are, 1 month into the new year, and it already feels like my time as President of the American College of Chest Physicians will pass too quickly. One of my goals is to share some thoughts on issues important to our profession by contributing quarterly to CHEST Physician. CHEST has always been like an extended family to me, and I look forward to having this regular touchpoint with all of you.

For my first written contribution, I want to focus on the future of medicine through medical education and involvement in professional associations because I am, at heart, a medical educator.

During my address at the CHEST Annual Meeting 2022, I spoke on how CHEST provided me with networking, mentoring, and volunteer opportunities that were critical in advancing my career. Those same opportunities should be extended to everyone in pulmonary, critical care, and sleep medicine – whether a current member or prospective member.
 

Lighting a fire

Attending my first CHEST Annual Meeting was possible due to my nomination for a leadership development course. The connections I made during the meeting really lit a fire within me. We need to engage with early career clinicians and provide them the same exposure and encouragement that I received.

To instill this fire in the next generation, I encourage each of our established members, years (or decades) into their careers, to pass along their expertise to someone who is just starting out, whether it be a trainee or a junior faculty member. If this applies to you: encourage a new attending who has never been to a CHEST event to attend with you; invite a fellow or resident to submit an abstract or case report to the journal CHEST® with your oversight; or simply volunteer to speak at your medical school or residency program about why you chose PCCM and the career it has given you.

Think back to when you were embarking on your journey toward where you are now – what would it have meant to be able to get career advice or even just a friendly conversation started with someone at your current level?
 

CHEST offerings and accreditations

Beyond bringing someone to a CHEST Annual Meeting – which you should definitely do – work with your learners at medical schools and residency programs to expose them to CHEST much earlier in their careers. The Trainings and Transitions Committee is an excellent resource to guide newer clinicians and can provide a vital source of encouragement and support. If your institution doesn’t have a simulation learning center or if it has limited offerings, the hands-on learning opportunities offered at CHEST headquarters may be a fit. Accredited by the Society for Simulation in Healthcare (SSH) and the Accreditation Council for Continuing Medical Education (ACCME), CHEST currently offers 24 courses with four new courses planned for 2023 in a wide variety of areas, including courses on ultrasound and bronchoscopy.

There are so many ways to introduce early career clinicians to CHEST, and it can begin with one personal outreach. If you are working on a project for CHEST right now, consider inviting an early career clinician to join you on it – this may be the opportunity that will change their career. It did for me.

As medical professionals, each of us plays an important role in the future of medicine, and the CHEST organization can bring us together to strengthen our impact.

If you are interested in brainstorming ideas for how to engage your medical students, residents, or fellows, please feel free to contact me or anyone at CHEST to help create a plan.

I look forward to the next time we connect.

Doreen J. Addrizzo-Harris, MD, FCCP

CHEST President

HMG-CoA reductase inhibitors (statins) have been shown to effectively reduce low-density lipoprotein cholesterol (LDL-C) as well as morbidity and mortality in patients who have either atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD.^1-12 However, research shows that up to 20% of patients are unable to tolerate statin therapy due to muscle-related adverse events (AEs).¹³ This presents a substantial clinical challenge, as current management strategies for patients with statin-associated muscle symptoms, such as intermittent administration of statins and ezetimibe, seldom achieve the > 50% LDL-C reduction recommended by the 2018 American Heart Association/American College of Cardiology Clinical Practice Guidelines.¹⁴ Additionally, statin-intolerant patients who have antihyperlipidemic medication lowered or discontinued are at an increased risk of future cardiovascular events.¹⁵ Observational data also show that about 70% of adult patients (primarily with genetic lipid disorders such as heterozygous familial hypercholesterolemia) do not achieve an LDL-C level < 100 mg/dL despite treatment with maximum doses of statins with or without ezetimibe.^16,17

PCSK9 inhibitors (PCSK9i) have robust efficacy data to support use in patients who do not meet their LDL-C goal despite maximally tolerated lipid therapy.¹⁴ However, long-term safety data for PCSK9i are not as robust as its efficacy data. Specifically, safety data relating to muscle-related AEs, which are the most widely recognized AE associated with statins, have only been reported in a few clinical trials with varying incidence rates, levels of significance, and relatively small study populations. Furthermore, the real-world prevalence of muscle-related PCSK9i AEs is unknown. Clinical guidance for management strategies for muscle-related AEs associated with PCSK9i is largely lacking. For this study, muscle-related AEs were defined as any new or unusual muscle soreness, weakness, cramping, aches, and stiffness that persists, is generally bilateral, and typically affects the large muscles. It is important to note, that muscle-related AEs associated with statins, ezetimibe, and PCSK9i can be attributed to the nocebo effect.

According to the prescribing information for alirocumab and evolocumab, myalgia, muscle spasms, and musculoskeletal pain each occurred in < 5% of the study populations.^18,19 From these data, muscle-related PCSK9i AEs are thought to be relatively rare, based on the ODYSSEY-OUTCOME and FOURIER trials, which did not enroll statin-intolerant patients.^20,21 However, currently available safety data from 3 small, randomized clinical trials specifically in statin-intolerant patients taking a PCSK9i suggest that muscle-related AEs occur at a rate of 12.2% to 32.5% and discontinuation rates varied from 0% to 15.9%.^22-25 As the incidence rates of muscle-related AEs in the prescribing information and clinical trials varied widely, this study will provide quantitative data on the percentage of patients that developed muscle-related PCSK9i AEs in a veteran population to help shed light on a topic that is not well studied.

Methods

This was a single-center, retrospective chart review of patients prescribed a PCSK9i between December 1, 2017, and September 1, 2021, and were managed in a pharmacy-led patient aligned care team (PACT) clinic at the Wilkes-Barre US Department of Veterans Affairs (VA) Medical Center (WBVAMC) in Pennsylvania. This study was approved by the Coatesville VA Medical Center Institutional Review Board, which oversees research conducted at WBVAMC. Veterans aged ≥ 18 years were included in the study. Patients were excluded if they had a history of serious hypersensitivity reaction to a PCSK9i or rhabdomyolysis or did not meet the VA criteria for use.²⁶

The primary outcome was the percentage of patients who developed a muscle-related AE while on a PCSK9i in a PACT clinic. Data were further analyzed based on patients who (1) tolerated a full PCSK9i dose; (2) tolerated alternative PCSK9i following initial intolerance; (3) required a PCSK9i dose reduction, or (4) discontinued PCSK9i. A secondary outcome was the percentage of statin- and/or ezetimibe-intolerant patients in these 4 groups. Another secondary outcome was the management strategies taken for patients who were on a reduced (monthly) dose of PCSK9i who did not reach their LDL-C goal. Management strategies that were assessed included restarting weekly statin, restarting weekly ezetimibe, increasing the dose of the same PCSK9i administered monthly, and switching to an alternative PCSK9i.

Data were collected using the VA Computerized Patient Record System (CPRS) and stored in a secure, locked spreadsheet. Baseline patient demographic characteristics collected included age (at PCSK9i start); sex; race; and PCSK9i name, dose, and frequency. We recorded when a patient switched PCSK9i, whether or not it was due to a muscle-related AE, and the name of the original PCSK9i. Also collected were lipid therapy intolerances prior to PCSK9i initiation (ie, intolerance to statin, ezetimibe, or both).

Patients were considered statin intolerant due to a muscle-related AE in accordance with the VA PCSK9i Criteria for Use, which requires trial of at least 3 statins, one of which was trialed at the lowest dosage approved by the US Food and Drug Administration (FDA) and resulted in intolerable skeletal muscle AEs that worsened during treatment and resolved when the statin was stopped. For our study purposes, patients taking alternative day dosing of statins due to muscle-related AEs (ie, 2- or 3-times weekly dosing) were not considered statin intolerant; however, patients taking once-weekly statin dosing were considered statin intolerant. Patients were considered ezetimibe intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when ezetimibe was stopped. Patients were considered PCSK9i intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when the PCSK9i was stopped. Patients with non–muscle-related intolerances to statins, ezetimibe, and PCSK9i were not considered statin, ezetimibe, and PCSK9i intolerant.

Alirocumab was initiated at 75 mg subcutaneous (SQ) once every 2 weeks or evolocumab 140 mg SQ once every 2 weeks in our study. The protocol allowed for a dose reduction of alirocumab 75 mg SQ once monthly if a patient experienced AEs, but this dose reduction strategy was not used for any patients on evolocumab in this study. Of note, alirocumab 75 mg SQ once monthly is not an FDA-approved dosing strategy. However, it is similar in concept to the alternative statin dosing (ie, alternate day dosing, once-weekly dosing) and may avoid the need to discontinue PCSK9i therapy altogether.

A review of the CPRS also documented whether a muscle-related AE occurred while the patient was on a PCSK9i (if yes, the specific AE was recorded), the result of PCSK9i therapy (tolerated full dose, required a dose reduction, switched medication, or discontinued), and management strategies taken for patients who did not meet their LDL-C goal while on a reduced (monthly) PCSK9i dose. Prior lipid therapy intolerances, PCSK9i-related AEs, results of PCSK9i therapy, and management strategies for patients who did not meet LDL-C goal while on a reduced PCSK9i dose were obtained by reviewing the PACT pharmacist’s clinic notes and assessment, along with clinic notes and medication history listed within the CPRS.

Statistical Analysis

Descriptive statistics were used for the demographic characteristics of study patients. The primary outcome was calculated as a binary measure (yes/no) of whether the patient developed a muscle-related AE while on a PCSK9i. The secondary outcome of statin, ezetimibe, or statin and ezetimibe intolerances in subgroups also was calculated as a binary measure.

Results

For the study, 156 charts were reviewed and 137 patients were included (Figure).

For the secondary results, 4 patients (2.9%) tolerated an alternate PCSK9i (evolocumab 140 mg SQ every 2 weeks) after initial intolerance to PCSK9i, 16 (11.7%) required a dose reduction, and 6 (4.4%) discontinued PCSK9i due to a muscle-related AE.

Discussion

This retrospective study found 17.5% of patients experienced muscle-related PCSK9i AEs. These occurred at a higher rate than reported in the prescribing information (< 5%) and were similar to the incidence rates reported in the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE clinical trials (12.0%-32.5%), which is what we hypothesized.^18,19,22-25 It is important to note that the incidence rates of muscle-related AEs reported in the prescribing information for alirocumab and evolocumab were based on trials that did not include statin- and/or ezetimibe-intolerant patients; whereas many patients in our study and patients in the clinical trials were statin and/or ezetimibe intolerant.

Additionally, a new study by Donald and colleagues found an incidence rate of 32% to 36% for muscle-related PCSK9i AEs.²⁷ Collectively, the data from clinical trials and our study indicate that patients with prior intolerances to statin and/or ezetimibe appear to have a higher likelihood of developing a muscle-related PCSK9i intolerance. In our study, 23 of 24 patients who developed a muscle-related PCSK9i AE had a prior history of statin and/or ezetimibe intolerances. This should alert clinicians prescribing PCSK9i in patients with a history of statin and/or ezetimibe intolerance to counsel their patients on the possibility of muscle-related PCSK9i AEs and management strategies. However, it is important to note that there was a substantial number of patients in our study who were statin and/or ezetimibe intolerant due to a prior muscle-related AE who tolerated the full dose of PCSK9i.

To our knowledge, this was the first trial to evaluate muscle-related PCSK9i AEs in a veteran population. Additionally, our study appears to be the first to use 2 PCSK9i dosing strategies that are not FDA approved: Dose reduction for patients who experienced a muscle-related AE on alirocumab 75 mg SQ every 2 weeks and dose escalation for patients who did not meet their LDL-C goal on alirocumab 75 mg SQ monthly following an initial intolerance to 2-week dosing. The dose-reduction strategy allowed patients who experienced a muscle-related AE to alirocumab 75 mg to reduce administration from every 2 weeks to monthly.

This strategy was only performed with alirocumab, the preferred PCSK9i at WBVAMC, but the same dose-reduction strategy can theoretically be used with evolocumab as well. Reduced monthly dosing of alirocumab allowed patients with a prior intolerance to remain on a lower dosage without discontinuation. This is important because as noted by Myers and colleagues, individuals without access to PCSK9i were found to have a significantly higher incidence ratio of cardiovascular events compared with those taking PCSK9i.¹⁵ Also of note, > 30% of patients on the reduced monthly dose of alirocumab still met their LDL-C goal. Therefore, using this dose-reduction strategy (instead of patients discontinuing therapy altogether due to a muscle-related intolerance) can lessen the risk of major adverse cardiovascular events (MACE) as well as mitigate muscle-related AEs that occurred while on 2-week PCSK9i dosing regimens. While we acknowledge that this reduced monthly dose of either alirocumab or evolocumab is not FDA approved, it is similar to alternative statin dosing that also is not FDA approved but may minimize the need to discontinue PCSK9i therapy. It would be beneficial if these dosing strategies were investigated by future research.

The dose-escalation strategy for patients who did not meet their LDL-C goal while on the reduced, monthly dose of alirocumab also was unique. Alirocumab was increased from 75 mg SQ once monthly to 150 mg SQ once monthly. Interestingly, we found that through the end of the chart review period, all patients tolerated the increase well, despite having an initial muscle-related AE to alirocumab 75 mg every 2 weeks, which is the same total monthly dosage. This approach is similar to that of once-weekly statin dosing or a drug holiday and may be explained by the long half-life of PCSK9i. Regardless of the mechanism, this finding suggests that an increased monthly dose of PCSK9i is a potential alternative for patients who cannot tolerate the FDA-approved dose. However, the ability for patients to achieve goal LDL-C on the monthly dosage requires future study.

Limitations

The results of this study should be considered with the following limitations. First, this was a retrospective chart review performed over a prespecified period. Any muscle-related AEs or LDL-C lowering effects from PCSK9i that occurred outside the review period were not captured. Our study was small and only included 137 patients, though it was similar in size to the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE trials.^22-24 Additionally, the study was primarily composed of White men and may not be representative of other populations. Some muscle-related PCSK9i AEs may be attributed to the nocebo. Last, our study did not capture patients on a PCSK9i who were not followed in the PACT clinic.

Conclusions

We found that muscle-related PCSK9i AEs occurred at a similar rate as those reported in previous clinical trials and exceeded the incidence rate reported in the prescribing information for alirocumab and evolocumab. It appears that patients who have a prior muscle-related intolerance to a statin and/or ezetimibe had a higher likelihood of developing a muscle-related PCSK9i AE. In our study, only 1 patient developed a muscle-related PCSK9i AE who did not have a prior history of muscle-related intolerance to either a statin or ezetimibe. However, in our study, a substantial percentage of patients with statin and/or ezetimibe intolerances tolerated the full PCSK9i dose well, proving that PCSK9i are still a reasonable alternative for patients with prior intolerances to statins and/or ezetimibe.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the US Department of Veterans Affairs Medical Center, Wilkes-Barre, Pennsylvania.

HMG-CoA reductase inhibitors (statins) have been shown to effectively reduce low-density lipoprotein cholesterol (LDL-C) as well as morbidity and mortality in patients who have either atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD.^1-12 However, research shows that up to 20% of patients are unable to tolerate statin therapy due to muscle-related adverse events (AEs).¹³ This presents a substantial clinical challenge, as current management strategies for patients with statin-associated muscle symptoms, such as intermittent administration of statins and ezetimibe, seldom achieve the > 50% LDL-C reduction recommended by the 2018 American Heart Association/American College of Cardiology Clinical Practice Guidelines.¹⁴ Additionally, statin-intolerant patients who have antihyperlipidemic medication lowered or discontinued are at an increased risk of future cardiovascular events.¹⁵ Observational data also show that about 70% of adult patients (primarily with genetic lipid disorders such as heterozygous familial hypercholesterolemia) do not achieve an LDL-C level < 100 mg/dL despite treatment with maximum doses of statins with or without ezetimibe.^16,17

PCSK9 inhibitors (PCSK9i) have robust efficacy data to support use in patients who do not meet their LDL-C goal despite maximally tolerated lipid therapy.¹⁴ However, long-term safety data for PCSK9i are not as robust as its efficacy data. Specifically, safety data relating to muscle-related AEs, which are the most widely recognized AE associated with statins, have only been reported in a few clinical trials with varying incidence rates, levels of significance, and relatively small study populations. Furthermore, the real-world prevalence of muscle-related PCSK9i AEs is unknown. Clinical guidance for management strategies for muscle-related AEs associated with PCSK9i is largely lacking. For this study, muscle-related AEs were defined as any new or unusual muscle soreness, weakness, cramping, aches, and stiffness that persists, is generally bilateral, and typically affects the large muscles. It is important to note, that muscle-related AEs associated with statins, ezetimibe, and PCSK9i can be attributed to the nocebo effect.

According to the prescribing information for alirocumab and evolocumab, myalgia, muscle spasms, and musculoskeletal pain each occurred in < 5% of the study populations.^18,19 From these data, muscle-related PCSK9i AEs are thought to be relatively rare, based on the ODYSSEY-OUTCOME and FOURIER trials, which did not enroll statin-intolerant patients.^20,21 However, currently available safety data from 3 small, randomized clinical trials specifically in statin-intolerant patients taking a PCSK9i suggest that muscle-related AEs occur at a rate of 12.2% to 32.5% and discontinuation rates varied from 0% to 15.9%.^22-25 As the incidence rates of muscle-related AEs in the prescribing information and clinical trials varied widely, this study will provide quantitative data on the percentage of patients that developed muscle-related PCSK9i AEs in a veteran population to help shed light on a topic that is not well studied.

Methods

This was a single-center, retrospective chart review of patients prescribed a PCSK9i between December 1, 2017, and September 1, 2021, and were managed in a pharmacy-led patient aligned care team (PACT) clinic at the Wilkes-Barre US Department of Veterans Affairs (VA) Medical Center (WBVAMC) in Pennsylvania. This study was approved by the Coatesville VA Medical Center Institutional Review Board, which oversees research conducted at WBVAMC. Veterans aged ≥ 18 years were included in the study. Patients were excluded if they had a history of serious hypersensitivity reaction to a PCSK9i or rhabdomyolysis or did not meet the VA criteria for use.²⁶

The primary outcome was the percentage of patients who developed a muscle-related AE while on a PCSK9i in a PACT clinic. Data were further analyzed based on patients who (1) tolerated a full PCSK9i dose; (2) tolerated alternative PCSK9i following initial intolerance; (3) required a PCSK9i dose reduction, or (4) discontinued PCSK9i. A secondary outcome was the percentage of statin- and/or ezetimibe-intolerant patients in these 4 groups. Another secondary outcome was the management strategies taken for patients who were on a reduced (monthly) dose of PCSK9i who did not reach their LDL-C goal. Management strategies that were assessed included restarting weekly statin, restarting weekly ezetimibe, increasing the dose of the same PCSK9i administered monthly, and switching to an alternative PCSK9i.

Data were collected using the VA Computerized Patient Record System (CPRS) and stored in a secure, locked spreadsheet. Baseline patient demographic characteristics collected included age (at PCSK9i start); sex; race; and PCSK9i name, dose, and frequency. We recorded when a patient switched PCSK9i, whether or not it was due to a muscle-related AE, and the name of the original PCSK9i. Also collected were lipid therapy intolerances prior to PCSK9i initiation (ie, intolerance to statin, ezetimibe, or both).

Patients were considered statin intolerant due to a muscle-related AE in accordance with the VA PCSK9i Criteria for Use, which requires trial of at least 3 statins, one of which was trialed at the lowest dosage approved by the US Food and Drug Administration (FDA) and resulted in intolerable skeletal muscle AEs that worsened during treatment and resolved when the statin was stopped. For our study purposes, patients taking alternative day dosing of statins due to muscle-related AEs (ie, 2- or 3-times weekly dosing) were not considered statin intolerant; however, patients taking once-weekly statin dosing were considered statin intolerant. Patients were considered ezetimibe intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when ezetimibe was stopped. Patients were considered PCSK9i intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when the PCSK9i was stopped. Patients with non–muscle-related intolerances to statins, ezetimibe, and PCSK9i were not considered statin, ezetimibe, and PCSK9i intolerant.

Alirocumab was initiated at 75 mg subcutaneous (SQ) once every 2 weeks or evolocumab 140 mg SQ once every 2 weeks in our study. The protocol allowed for a dose reduction of alirocumab 75 mg SQ once monthly if a patient experienced AEs, but this dose reduction strategy was not used for any patients on evolocumab in this study. Of note, alirocumab 75 mg SQ once monthly is not an FDA-approved dosing strategy. However, it is similar in concept to the alternative statin dosing (ie, alternate day dosing, once-weekly dosing) and may avoid the need to discontinue PCSK9i therapy altogether.

A review of the CPRS also documented whether a muscle-related AE occurred while the patient was on a PCSK9i (if yes, the specific AE was recorded), the result of PCSK9i therapy (tolerated full dose, required a dose reduction, switched medication, or discontinued), and management strategies taken for patients who did not meet their LDL-C goal while on a reduced (monthly) PCSK9i dose. Prior lipid therapy intolerances, PCSK9i-related AEs, results of PCSK9i therapy, and management strategies for patients who did not meet LDL-C goal while on a reduced PCSK9i dose were obtained by reviewing the PACT pharmacist’s clinic notes and assessment, along with clinic notes and medication history listed within the CPRS.

Statistical Analysis

Descriptive statistics were used for the demographic characteristics of study patients. The primary outcome was calculated as a binary measure (yes/no) of whether the patient developed a muscle-related AE while on a PCSK9i. The secondary outcome of statin, ezetimibe, or statin and ezetimibe intolerances in subgroups also was calculated as a binary measure.

Results

For the study, 156 charts were reviewed and 137 patients were included (Figure).

For the secondary results, 4 patients (2.9%) tolerated an alternate PCSK9i (evolocumab 140 mg SQ every 2 weeks) after initial intolerance to PCSK9i, 16 (11.7%) required a dose reduction, and 6 (4.4%) discontinued PCSK9i due to a muscle-related AE.

Discussion

This retrospective study found 17.5% of patients experienced muscle-related PCSK9i AEs. These occurred at a higher rate than reported in the prescribing information (< 5%) and were similar to the incidence rates reported in the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE clinical trials (12.0%-32.5%), which is what we hypothesized.^18,19,22-25 It is important to note that the incidence rates of muscle-related AEs reported in the prescribing information for alirocumab and evolocumab were based on trials that did not include statin- and/or ezetimibe-intolerant patients; whereas many patients in our study and patients in the clinical trials were statin and/or ezetimibe intolerant.

Additionally, a new study by Donald and colleagues found an incidence rate of 32% to 36% for muscle-related PCSK9i AEs.²⁷ Collectively, the data from clinical trials and our study indicate that patients with prior intolerances to statin and/or ezetimibe appear to have a higher likelihood of developing a muscle-related PCSK9i intolerance. In our study, 23 of 24 patients who developed a muscle-related PCSK9i AE had a prior history of statin and/or ezetimibe intolerances. This should alert clinicians prescribing PCSK9i in patients with a history of statin and/or ezetimibe intolerance to counsel their patients on the possibility of muscle-related PCSK9i AEs and management strategies. However, it is important to note that there was a substantial number of patients in our study who were statin and/or ezetimibe intolerant due to a prior muscle-related AE who tolerated the full dose of PCSK9i.

To our knowledge, this was the first trial to evaluate muscle-related PCSK9i AEs in a veteran population. Additionally, our study appears to be the first to use 2 PCSK9i dosing strategies that are not FDA approved: Dose reduction for patients who experienced a muscle-related AE on alirocumab 75 mg SQ every 2 weeks and dose escalation for patients who did not meet their LDL-C goal on alirocumab 75 mg SQ monthly following an initial intolerance to 2-week dosing. The dose-reduction strategy allowed patients who experienced a muscle-related AE to alirocumab 75 mg to reduce administration from every 2 weeks to monthly.

This strategy was only performed with alirocumab, the preferred PCSK9i at WBVAMC, but the same dose-reduction strategy can theoretically be used with evolocumab as well. Reduced monthly dosing of alirocumab allowed patients with a prior intolerance to remain on a lower dosage without discontinuation. This is important because as noted by Myers and colleagues, individuals without access to PCSK9i were found to have a significantly higher incidence ratio of cardiovascular events compared with those taking PCSK9i.¹⁵ Also of note, > 30% of patients on the reduced monthly dose of alirocumab still met their LDL-C goal. Therefore, using this dose-reduction strategy (instead of patients discontinuing therapy altogether due to a muscle-related intolerance) can lessen the risk of major adverse cardiovascular events (MACE) as well as mitigate muscle-related AEs that occurred while on 2-week PCSK9i dosing regimens. While we acknowledge that this reduced monthly dose of either alirocumab or evolocumab is not FDA approved, it is similar to alternative statin dosing that also is not FDA approved but may minimize the need to discontinue PCSK9i therapy. It would be beneficial if these dosing strategies were investigated by future research.

The dose-escalation strategy for patients who did not meet their LDL-C goal while on the reduced, monthly dose of alirocumab also was unique. Alirocumab was increased from 75 mg SQ once monthly to 150 mg SQ once monthly. Interestingly, we found that through the end of the chart review period, all patients tolerated the increase well, despite having an initial muscle-related AE to alirocumab 75 mg every 2 weeks, which is the same total monthly dosage. This approach is similar to that of once-weekly statin dosing or a drug holiday and may be explained by the long half-life of PCSK9i. Regardless of the mechanism, this finding suggests that an increased monthly dose of PCSK9i is a potential alternative for patients who cannot tolerate the FDA-approved dose. However, the ability for patients to achieve goal LDL-C on the monthly dosage requires future study.

Limitations

The results of this study should be considered with the following limitations. First, this was a retrospective chart review performed over a prespecified period. Any muscle-related AEs or LDL-C lowering effects from PCSK9i that occurred outside the review period were not captured. Our study was small and only included 137 patients, though it was similar in size to the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE trials.^22-24 Additionally, the study was primarily composed of White men and may not be representative of other populations. Some muscle-related PCSK9i AEs may be attributed to the nocebo. Last, our study did not capture patients on a PCSK9i who were not followed in the PACT clinic.

Conclusions

We found that muscle-related PCSK9i AEs occurred at a similar rate as those reported in previous clinical trials and exceeded the incidence rate reported in the prescribing information for alirocumab and evolocumab. It appears that patients who have a prior muscle-related intolerance to a statin and/or ezetimibe had a higher likelihood of developing a muscle-related PCSK9i AE. In our study, only 1 patient developed a muscle-related PCSK9i AE who did not have a prior history of muscle-related intolerance to either a statin or ezetimibe. However, in our study, a substantial percentage of patients with statin and/or ezetimibe intolerances tolerated the full PCSK9i dose well, proving that PCSK9i are still a reasonable alternative for patients with prior intolerances to statins and/or ezetimibe.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the US Department of Veterans Affairs Medical Center, Wilkes-Barre, Pennsylvania.

HMG-CoA reductase inhibitors (statins) have been shown to effectively reduce low-density lipoprotein cholesterol (LDL-C) as well as morbidity and mortality in patients who have either atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD.^1-12 However, research shows that up to 20% of patients are unable to tolerate statin therapy due to muscle-related adverse events (AEs).¹³ This presents a substantial clinical challenge, as current management strategies for patients with statin-associated muscle symptoms, such as intermittent administration of statins and ezetimibe, seldom achieve the > 50% LDL-C reduction recommended by the 2018 American Heart Association/American College of Cardiology Clinical Practice Guidelines.¹⁴ Additionally, statin-intolerant patients who have antihyperlipidemic medication lowered or discontinued are at an increased risk of future cardiovascular events.¹⁵ Observational data also show that about 70% of adult patients (primarily with genetic lipid disorders such as heterozygous familial hypercholesterolemia) do not achieve an LDL-C level < 100 mg/dL despite treatment with maximum doses of statins with or without ezetimibe.^16,17

PCSK9 inhibitors (PCSK9i) have robust efficacy data to support use in patients who do not meet their LDL-C goal despite maximally tolerated lipid therapy.¹⁴ However, long-term safety data for PCSK9i are not as robust as its efficacy data. Specifically, safety data relating to muscle-related AEs, which are the most widely recognized AE associated with statins, have only been reported in a few clinical trials with varying incidence rates, levels of significance, and relatively small study populations. Furthermore, the real-world prevalence of muscle-related PCSK9i AEs is unknown. Clinical guidance for management strategies for muscle-related AEs associated with PCSK9i is largely lacking. For this study, muscle-related AEs were defined as any new or unusual muscle soreness, weakness, cramping, aches, and stiffness that persists, is generally bilateral, and typically affects the large muscles. It is important to note, that muscle-related AEs associated with statins, ezetimibe, and PCSK9i can be attributed to the nocebo effect.

According to the prescribing information for alirocumab and evolocumab, myalgia, muscle spasms, and musculoskeletal pain each occurred in < 5% of the study populations.^18,19 From these data, muscle-related PCSK9i AEs are thought to be relatively rare, based on the ODYSSEY-OUTCOME and FOURIER trials, which did not enroll statin-intolerant patients.^20,21 However, currently available safety data from 3 small, randomized clinical trials specifically in statin-intolerant patients taking a PCSK9i suggest that muscle-related AEs occur at a rate of 12.2% to 32.5% and discontinuation rates varied from 0% to 15.9%.^22-25 As the incidence rates of muscle-related AEs in the prescribing information and clinical trials varied widely, this study will provide quantitative data on the percentage of patients that developed muscle-related PCSK9i AEs in a veteran population to help shed light on a topic that is not well studied.

Methods

This was a single-center, retrospective chart review of patients prescribed a PCSK9i between December 1, 2017, and September 1, 2021, and were managed in a pharmacy-led patient aligned care team (PACT) clinic at the Wilkes-Barre US Department of Veterans Affairs (VA) Medical Center (WBVAMC) in Pennsylvania. This study was approved by the Coatesville VA Medical Center Institutional Review Board, which oversees research conducted at WBVAMC. Veterans aged ≥ 18 years were included in the study. Patients were excluded if they had a history of serious hypersensitivity reaction to a PCSK9i or rhabdomyolysis or did not meet the VA criteria for use.²⁶

The primary outcome was the percentage of patients who developed a muscle-related AE while on a PCSK9i in a PACT clinic. Data were further analyzed based on patients who (1) tolerated a full PCSK9i dose; (2) tolerated alternative PCSK9i following initial intolerance; (3) required a PCSK9i dose reduction, or (4) discontinued PCSK9i. A secondary outcome was the percentage of statin- and/or ezetimibe-intolerant patients in these 4 groups. Another secondary outcome was the management strategies taken for patients who were on a reduced (monthly) dose of PCSK9i who did not reach their LDL-C goal. Management strategies that were assessed included restarting weekly statin, restarting weekly ezetimibe, increasing the dose of the same PCSK9i administered monthly, and switching to an alternative PCSK9i.

Data were collected using the VA Computerized Patient Record System (CPRS) and stored in a secure, locked spreadsheet. Baseline patient demographic characteristics collected included age (at PCSK9i start); sex; race; and PCSK9i name, dose, and frequency. We recorded when a patient switched PCSK9i, whether or not it was due to a muscle-related AE, and the name of the original PCSK9i. Also collected were lipid therapy intolerances prior to PCSK9i initiation (ie, intolerance to statin, ezetimibe, or both).

Patients were considered statin intolerant due to a muscle-related AE in accordance with the VA PCSK9i Criteria for Use, which requires trial of at least 3 statins, one of which was trialed at the lowest dosage approved by the US Food and Drug Administration (FDA) and resulted in intolerable skeletal muscle AEs that worsened during treatment and resolved when the statin was stopped. For our study purposes, patients taking alternative day dosing of statins due to muscle-related AEs (ie, 2- or 3-times weekly dosing) were not considered statin intolerant; however, patients taking once-weekly statin dosing were considered statin intolerant. Patients were considered ezetimibe intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when ezetimibe was stopped. Patients were considered PCSK9i intolerant due to a muscle-related AE if the intolerance was due to skeletal muscle concerns that worsened during treatment and resolved when the PCSK9i was stopped. Patients with non–muscle-related intolerances to statins, ezetimibe, and PCSK9i were not considered statin, ezetimibe, and PCSK9i intolerant.

Alirocumab was initiated at 75 mg subcutaneous (SQ) once every 2 weeks or evolocumab 140 mg SQ once every 2 weeks in our study. The protocol allowed for a dose reduction of alirocumab 75 mg SQ once monthly if a patient experienced AEs, but this dose reduction strategy was not used for any patients on evolocumab in this study. Of note, alirocumab 75 mg SQ once monthly is not an FDA-approved dosing strategy. However, it is similar in concept to the alternative statin dosing (ie, alternate day dosing, once-weekly dosing) and may avoid the need to discontinue PCSK9i therapy altogether.

A review of the CPRS also documented whether a muscle-related AE occurred while the patient was on a PCSK9i (if yes, the specific AE was recorded), the result of PCSK9i therapy (tolerated full dose, required a dose reduction, switched medication, or discontinued), and management strategies taken for patients who did not meet their LDL-C goal while on a reduced (monthly) PCSK9i dose. Prior lipid therapy intolerances, PCSK9i-related AEs, results of PCSK9i therapy, and management strategies for patients who did not meet LDL-C goal while on a reduced PCSK9i dose were obtained by reviewing the PACT pharmacist’s clinic notes and assessment, along with clinic notes and medication history listed within the CPRS.

Statistical Analysis

Descriptive statistics were used for the demographic characteristics of study patients. The primary outcome was calculated as a binary measure (yes/no) of whether the patient developed a muscle-related AE while on a PCSK9i. The secondary outcome of statin, ezetimibe, or statin and ezetimibe intolerances in subgroups also was calculated as a binary measure.

Results

For the study, 156 charts were reviewed and 137 patients were included (Figure).

For the secondary results, 4 patients (2.9%) tolerated an alternate PCSK9i (evolocumab 140 mg SQ every 2 weeks) after initial intolerance to PCSK9i, 16 (11.7%) required a dose reduction, and 6 (4.4%) discontinued PCSK9i due to a muscle-related AE.

Discussion

This retrospective study found 17.5% of patients experienced muscle-related PCSK9i AEs. These occurred at a higher rate than reported in the prescribing information (< 5%) and were similar to the incidence rates reported in the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE clinical trials (12.0%-32.5%), which is what we hypothesized.^18,19,22-25 It is important to note that the incidence rates of muscle-related AEs reported in the prescribing information for alirocumab and evolocumab were based on trials that did not include statin- and/or ezetimibe-intolerant patients; whereas many patients in our study and patients in the clinical trials were statin and/or ezetimibe intolerant.

Additionally, a new study by Donald and colleagues found an incidence rate of 32% to 36% for muscle-related PCSK9i AEs.²⁷ Collectively, the data from clinical trials and our study indicate that patients with prior intolerances to statin and/or ezetimibe appear to have a higher likelihood of developing a muscle-related PCSK9i intolerance. In our study, 23 of 24 patients who developed a muscle-related PCSK9i AE had a prior history of statin and/or ezetimibe intolerances. This should alert clinicians prescribing PCSK9i in patients with a history of statin and/or ezetimibe intolerance to counsel their patients on the possibility of muscle-related PCSK9i AEs and management strategies. However, it is important to note that there was a substantial number of patients in our study who were statin and/or ezetimibe intolerant due to a prior muscle-related AE who tolerated the full dose of PCSK9i.

To our knowledge, this was the first trial to evaluate muscle-related PCSK9i AEs in a veteran population. Additionally, our study appears to be the first to use 2 PCSK9i dosing strategies that are not FDA approved: Dose reduction for patients who experienced a muscle-related AE on alirocumab 75 mg SQ every 2 weeks and dose escalation for patients who did not meet their LDL-C goal on alirocumab 75 mg SQ monthly following an initial intolerance to 2-week dosing. The dose-reduction strategy allowed patients who experienced a muscle-related AE to alirocumab 75 mg to reduce administration from every 2 weeks to monthly.

This strategy was only performed with alirocumab, the preferred PCSK9i at WBVAMC, but the same dose-reduction strategy can theoretically be used with evolocumab as well. Reduced monthly dosing of alirocumab allowed patients with a prior intolerance to remain on a lower dosage without discontinuation. This is important because as noted by Myers and colleagues, individuals without access to PCSK9i were found to have a significantly higher incidence ratio of cardiovascular events compared with those taking PCSK9i.¹⁵ Also of note, > 30% of patients on the reduced monthly dose of alirocumab still met their LDL-C goal. Therefore, using this dose-reduction strategy (instead of patients discontinuing therapy altogether due to a muscle-related intolerance) can lessen the risk of major adverse cardiovascular events (MACE) as well as mitigate muscle-related AEs that occurred while on 2-week PCSK9i dosing regimens. While we acknowledge that this reduced monthly dose of either alirocumab or evolocumab is not FDA approved, it is similar to alternative statin dosing that also is not FDA approved but may minimize the need to discontinue PCSK9i therapy. It would be beneficial if these dosing strategies were investigated by future research.

The dose-escalation strategy for patients who did not meet their LDL-C goal while on the reduced, monthly dose of alirocumab also was unique. Alirocumab was increased from 75 mg SQ once monthly to 150 mg SQ once monthly. Interestingly, we found that through the end of the chart review period, all patients tolerated the increase well, despite having an initial muscle-related AE to alirocumab 75 mg every 2 weeks, which is the same total monthly dosage. This approach is similar to that of once-weekly statin dosing or a drug holiday and may be explained by the long half-life of PCSK9i. Regardless of the mechanism, this finding suggests that an increased monthly dose of PCSK9i is a potential alternative for patients who cannot tolerate the FDA-approved dose. However, the ability for patients to achieve goal LDL-C on the monthly dosage requires future study.

Limitations

The results of this study should be considered with the following limitations. First, this was a retrospective chart review performed over a prespecified period. Any muscle-related AEs or LDL-C lowering effects from PCSK9i that occurred outside the review period were not captured. Our study was small and only included 137 patients, though it was similar in size to the GAUSS-2, GAUSS-3, and ODYSSEY-ALTERNATIVE trials.^22-24 Additionally, the study was primarily composed of White men and may not be representative of other populations. Some muscle-related PCSK9i AEs may be attributed to the nocebo. Last, our study did not capture patients on a PCSK9i who were not followed in the PACT clinic.

Conclusions

We found that muscle-related PCSK9i AEs occurred at a similar rate as those reported in previous clinical trials and exceeded the incidence rate reported in the prescribing information for alirocumab and evolocumab. It appears that patients who have a prior muscle-related intolerance to a statin and/or ezetimibe had a higher likelihood of developing a muscle-related PCSK9i AE. In our study, only 1 patient developed a muscle-related PCSK9i AE who did not have a prior history of muscle-related intolerance to either a statin or ezetimibe. However, in our study, a substantial percentage of patients with statin and/or ezetimibe intolerances tolerated the full PCSK9i dose well, proving that PCSK9i are still a reasonable alternative for patients with prior intolerances to statins and/or ezetimibe.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the US Department of Veterans Affairs Medical Center, Wilkes-Barre, Pennsylvania.

Growing up I can remember my father telling stories of service members in the medical battalion he commanded in World War II (WWII) who after the war with his encouragement and their GI Bill educational benefits went to school to become doctors, nurses, and dentists. They were among the 2,300,000 veterans who attended US colleges and universities through the Servicemen’s Readjustment Act passed in 1944. The American Legion navigated the bill through the twists and turns of congressional support, and it was one of their leaders who invented the catchy GI Bill shorthand.²

As with most political legislation, there were mixed motives driving passage of the act, and like many policies in America, the primary impetus was economic. While the war was raging overseas, at home the US Department of Labor predicted that by the war’s end, 16 million service members would be jobless. Apprehensive about the prospect of yet another financial depression, in 1943 a White House agency recommended that the federal government fund education and training for the individuals who had served during the war.²

While troops stormed the beaches of Normandy, wartime President Franklin D. Roosevelt (FDR) signed the bill that delivered not only educational and training opportunities for service members and veterans, but also funded home loans and US Department of Veterans Affairs (VA) hospitals. The bill was practical in that it provided not only tuition, but also books, supplies, a living stipend, and counseling for the students. The bill technically expired in 1956, but a series of extensions and expansions has been true to the original intention to offer those who served their nation in the military a better life as citizens.

Articles describing the impact of the GI Bill use terms like life changing and transformative.^3,4 Our contemporary culture makes it difficult to imagine how out of reach a college education was for the generation that fought WWII. Universities were primarily for the rich and connected, the powerful and privileged. Were it not for the upward social mobility the GI Bill propelled, the American dream would not have become a reality for many farmers, small town merchants, and factory workers. The GI Bill though could not by itself ensure equity. The systemic racism endemic in the United States and among the elected representatives who debated the bill resulted in many Black service members especially in the South being denied entrance to institutions of higher learning.⁵ Despite this invidious discrimination, the bill was a profound effort to help many other service members to successfully reintegrate into the society they had preserved and defended.⁴

“With the signing of this bill, a well-rounded program of special veterans’ benefits is nearly completed,” FDR said, capturing its noble intent: “It gives emphatic notice to the men and women in our armed forces that the American people do not intend to let them down.”⁶

Regrettably, we have not kept FDR’s pledge. Now unscrupulous businesses are preying on the aspirations of military personnel and veterans for an education and thwarting their ability to seek gainful employment. For more than a decade, respected news media have reported that for-profit universities were exploiting service members trying to improve their lives through obtaining a college education via the GI Bill.⁷ The sad irony is that what enabled the exploitation to occur was a major expansion of the benefits under the Post-9/11 GI Bill. This version granted educational funding to any individual who had served on active duty for 90 days or more after September 10, 2001.⁸ Federal law prohibits for-profit educational institutions from receiving more than 90% of their total revenue from federal student aid. A loophole in the law enabled these institutions to categorize GI Bill funding as private not government dollars. Bad old American greed drove these for-profit colleges and universities to aggressively recruit veterans who trusted in the good faith of the academic institutions. Once the GI Bill monies were exhausted, veterans had already invested so much time and energy in a degree or certificate, the schools could persuade them to take out student loans with the promise of job placement assistance that never materialized. They took advantage of the veterans’ hopes to fatten their own bottom line in the face of declining enrolments.⁹ Journalists, government, think tank reports, and even a documentary described the tragic stories of service members left unemployed with immense debt and degrees that to many of them were now worthless.¹⁰

After years of reporters exposing the scam and politically thwarted efforts to stop it, Congress and President Biden closed what was known as the 90/10 loophole. This ended the weaponization of education it had promoted. In October 2022, the US Department of Education announced its final rule to prohibit the widespread educational fraud that had betrayed so many veterans and service members, which Secretary Dennis McDonough described as “abuse.”¹¹Some readers may wonder why I have devoted an editorial to a topic that seems somewhat distant from the health care that is the primary domain of Federal Practitioner. It happens that education is in closer proximity to health for our patients than many of us might have realized. A 2018 Military Medicine study found that veterans who took advantage of the educational opportunities of the GI Bill had better health and reduced smoking, among other benefits.¹² This connection between health and education should serve as a source of pride for all of us in federal practice as we are part of organizations that affirm the holistic concept of health that embraces not just medicine but education, housing, and other services essential for comprehensive well-being.

Growing up I can remember my father telling stories of service members in the medical battalion he commanded in World War II (WWII) who after the war with his encouragement and their GI Bill educational benefits went to school to become doctors, nurses, and dentists. They were among the 2,300,000 veterans who attended US colleges and universities through the Servicemen’s Readjustment Act passed in 1944. The American Legion navigated the bill through the twists and turns of congressional support, and it was one of their leaders who invented the catchy GI Bill shorthand.²

As with most political legislation, there were mixed motives driving passage of the act, and like many policies in America, the primary impetus was economic. While the war was raging overseas, at home the US Department of Labor predicted that by the war’s end, 16 million service members would be jobless. Apprehensive about the prospect of yet another financial depression, in 1943 a White House agency recommended that the federal government fund education and training for the individuals who had served during the war.²

While troops stormed the beaches of Normandy, wartime President Franklin D. Roosevelt (FDR) signed the bill that delivered not only educational and training opportunities for service members and veterans, but also funded home loans and US Department of Veterans Affairs (VA) hospitals. The bill was practical in that it provided not only tuition, but also books, supplies, a living stipend, and counseling for the students. The bill technically expired in 1956, but a series of extensions and expansions has been true to the original intention to offer those who served their nation in the military a better life as citizens.

Articles describing the impact of the GI Bill use terms like life changing and transformative.^3,4 Our contemporary culture makes it difficult to imagine how out of reach a college education was for the generation that fought WWII. Universities were primarily for the rich and connected, the powerful and privileged. Were it not for the upward social mobility the GI Bill propelled, the American dream would not have become a reality for many farmers, small town merchants, and factory workers. The GI Bill though could not by itself ensure equity. The systemic racism endemic in the United States and among the elected representatives who debated the bill resulted in many Black service members especially in the South being denied entrance to institutions of higher learning.⁵ Despite this invidious discrimination, the bill was a profound effort to help many other service members to successfully reintegrate into the society they had preserved and defended.⁴

“With the signing of this bill, a well-rounded program of special veterans’ benefits is nearly completed,” FDR said, capturing its noble intent: “It gives emphatic notice to the men and women in our armed forces that the American people do not intend to let them down.”⁶

Regrettably, we have not kept FDR’s pledge. Now unscrupulous businesses are preying on the aspirations of military personnel and veterans for an education and thwarting their ability to seek gainful employment. For more than a decade, respected news media have reported that for-profit universities were exploiting service members trying to improve their lives through obtaining a college education via the GI Bill.⁷ The sad irony is that what enabled the exploitation to occur was a major expansion of the benefits under the Post-9/11 GI Bill. This version granted educational funding to any individual who had served on active duty for 90 days or more after September 10, 2001.⁸ Federal law prohibits for-profit educational institutions from receiving more than 90% of their total revenue from federal student aid. A loophole in the law enabled these institutions to categorize GI Bill funding as private not government dollars. Bad old American greed drove these for-profit colleges and universities to aggressively recruit veterans who trusted in the good faith of the academic institutions. Once the GI Bill monies were exhausted, veterans had already invested so much time and energy in a degree or certificate, the schools could persuade them to take out student loans with the promise of job placement assistance that never materialized. They took advantage of the veterans’ hopes to fatten their own bottom line in the face of declining enrolments.⁹ Journalists, government, think tank reports, and even a documentary described the tragic stories of service members left unemployed with immense debt and degrees that to many of them were now worthless.¹⁰

After years of reporters exposing the scam and politically thwarted efforts to stop it, Congress and President Biden closed what was known as the 90/10 loophole. This ended the weaponization of education it had promoted. In October 2022, the US Department of Education announced its final rule to prohibit the widespread educational fraud that had betrayed so many veterans and service members, which Secretary Dennis McDonough described as “abuse.”¹¹Some readers may wonder why I have devoted an editorial to a topic that seems somewhat distant from the health care that is the primary domain of Federal Practitioner. It happens that education is in closer proximity to health for our patients than many of us might have realized. A 2018 Military Medicine study found that veterans who took advantage of the educational opportunities of the GI Bill had better health and reduced smoking, among other benefits.¹² This connection between health and education should serve as a source of pride for all of us in federal practice as we are part of organizations that affirm the holistic concept of health that embraces not just medicine but education, housing, and other services essential for comprehensive well-being.

Growing up I can remember my father telling stories of service members in the medical battalion he commanded in World War II (WWII) who after the war with his encouragement and their GI Bill educational benefits went to school to become doctors, nurses, and dentists. They were among the 2,300,000 veterans who attended US colleges and universities through the Servicemen’s Readjustment Act passed in 1944. The American Legion navigated the bill through the twists and turns of congressional support, and it was one of their leaders who invented the catchy GI Bill shorthand.²

As with most political legislation, there were mixed motives driving passage of the act, and like many policies in America, the primary impetus was economic. While the war was raging overseas, at home the US Department of Labor predicted that by the war’s end, 16 million service members would be jobless. Apprehensive about the prospect of yet another financial depression, in 1943 a White House agency recommended that the federal government fund education and training for the individuals who had served during the war.²

While troops stormed the beaches of Normandy, wartime President Franklin D. Roosevelt (FDR) signed the bill that delivered not only educational and training opportunities for service members and veterans, but also funded home loans and US Department of Veterans Affairs (VA) hospitals. The bill was practical in that it provided not only tuition, but also books, supplies, a living stipend, and counseling for the students. The bill technically expired in 1956, but a series of extensions and expansions has been true to the original intention to offer those who served their nation in the military a better life as citizens.

Articles describing the impact of the GI Bill use terms like life changing and transformative.^3,4 Our contemporary culture makes it difficult to imagine how out of reach a college education was for the generation that fought WWII. Universities were primarily for the rich and connected, the powerful and privileged. Were it not for the upward social mobility the GI Bill propelled, the American dream would not have become a reality for many farmers, small town merchants, and factory workers. The GI Bill though could not by itself ensure equity. The systemic racism endemic in the United States and among the elected representatives who debated the bill resulted in many Black service members especially in the South being denied entrance to institutions of higher learning.⁵ Despite this invidious discrimination, the bill was a profound effort to help many other service members to successfully reintegrate into the society they had preserved and defended.⁴

“With the signing of this bill, a well-rounded program of special veterans’ benefits is nearly completed,” FDR said, capturing its noble intent: “It gives emphatic notice to the men and women in our armed forces that the American people do not intend to let them down.”⁶

Regrettably, we have not kept FDR’s pledge. Now unscrupulous businesses are preying on the aspirations of military personnel and veterans for an education and thwarting their ability to seek gainful employment. For more than a decade, respected news media have reported that for-profit universities were exploiting service members trying to improve their lives through obtaining a college education via the GI Bill.⁷ The sad irony is that what enabled the exploitation to occur was a major expansion of the benefits under the Post-9/11 GI Bill. This version granted educational funding to any individual who had served on active duty for 90 days or more after September 10, 2001.⁸ Federal law prohibits for-profit educational institutions from receiving more than 90% of their total revenue from federal student aid. A loophole in the law enabled these institutions to categorize GI Bill funding as private not government dollars. Bad old American greed drove these for-profit colleges and universities to aggressively recruit veterans who trusted in the good faith of the academic institutions. Once the GI Bill monies were exhausted, veterans had already invested so much time and energy in a degree or certificate, the schools could persuade them to take out student loans with the promise of job placement assistance that never materialized. They took advantage of the veterans’ hopes to fatten their own bottom line in the face of declining enrolments.⁹ Journalists, government, think tank reports, and even a documentary described the tragic stories of service members left unemployed with immense debt and degrees that to many of them were now worthless.¹⁰

After years of reporters exposing the scam and politically thwarted efforts to stop it, Congress and President Biden closed what was known as the 90/10 loophole. This ended the weaponization of education it had promoted. In October 2022, the US Department of Education announced its final rule to prohibit the widespread educational fraud that had betrayed so many veterans and service members, which Secretary Dennis McDonough described as “abuse.”¹¹Some readers may wonder why I have devoted an editorial to a topic that seems somewhat distant from the health care that is the primary domain of Federal Practitioner. It happens that education is in closer proximity to health for our patients than many of us might have realized. A 2018 Military Medicine study found that veterans who took advantage of the educational opportunities of the GI Bill had better health and reduced smoking, among other benefits.¹² This connection between health and education should serve as a source of pride for all of us in federal practice as we are part of organizations that affirm the holistic concept of health that embraces not just medicine but education, housing, and other services essential for comprehensive well-being.

Veterans who interact with the criminal justice system (ie, justice-involved veterans) have heightened rates of mental health and psychosocial needs, including posttraumatic stress disorder (PTSD), substance use disorder, depression, suicidal ideation and attempt, and homelessness.^1,2 Alongside these criminogenic risk factors, recidivism is common among justice-involved veterans: About 70% of incarcerated veterans disclosed at least one prior incarceration.³

To address the complex interplay of psychosocial factors, mental health concerns, and justice involvement among veterans, veterans treatment courts (VTCs) emerged as an alternative to incarceration.⁴ VTC participation often consists of integrated treatment and rehabilitative services (eg, vocational training, health care), ongoing monitoring for substance use, graduated responses to address treatment adherence, and ongoing communication with the judge and legal counsel.⁴

A primary aim of these courts is to address psychosocial needs believed to underlie criminal behavior, thus reducing risk of recidivism and promoting successful recovery and community integration for eligible veterans. To do so, VTCs collaborate with community-based and/or US Department of Veterans Affairs services, such as the Veterans Justice Outreach program (VJO). VJO specialists identify and refer justice-involved veterans to Veterans Health Administration (VHA) and community care and serve as a liaison between VTC staff and VHA health care professionals (HCPs).⁵

VTC outcome studies highlight the importance of not only diverting veterans to problem-solving courts, but also ensuring their optimal participation. Successful graduates of VTC programs demonstrate significant improvements in mental health symptoms, life satisfaction, and social support, as well as lower rates of law enforcement interactions.^6,7 However, less is known about supporting those veterans who have difficulty engaging in VTCs and either discontinue participation or require lengthier periods of participation to meet court graduation requirements.⁸ One possibility to improve engagement among these veterans is to enhance court practices to best meet their needs.

In addition to delivering treatment, VHA mental health professionals may serve a critical interdisciplinary role by lending expertise to support VTC practices. For example, equipping court professionals with clinical knowledge and skills related to motivation may strengthen the staff’s interactions with participants, enabling them to address barriers as they arise and to facilitate veterans’ treatment adherence. Additionally, responsiveness to the impact of trauma exposure, which is common among this population, may prove important as related symptoms can affect veterans’ engagement, receptivity, and behavior in court settings. Indeed, prior examinations of justice-involved veterans have found trauma exposure rates ranging from 60% to 90% and PTSD rates ranging from 27% to 40%.^1,2 Notably, involvement with the justice system (eg, incarceration) may itself further increase risk of trauma exposure (eg, experiencing a physical or sexual assault in prison) or exacerbate existing PTSD.⁹ Nonetheless, whereas many drug courts and domestic violence courts have been established, problem-solving courts with a specialized focus on trauma exposure remain rare, suggesting a potential gap in court training.

VHA HCPs have the potential to facilitate justice-involved veterans’ successful court and treatment participation by coordinating with VJO specialists to provide training and consultation to the courts. Supporting efforts to effectively and responsively address criminogenic risk (eg, mental health) in VTC settings may in turn reduce the likelihood of recidivism.¹⁰ Given the elevated rates of trauma exposure among justice-involved veterans and the relative lack of trauma-focused VTCs, we developed a trauma-informed training for VTC professionals that centered on related clinical presentations of justice-involved veterans and frequently occurring challenges in the context of court participation.

Program Development

This educational program aimed to (1) provide psychoeducation on trauma exposure, PTSD, and existing evidence-based treatments; (2) present clinical considerations for justice-involved veterans related to trauma exposure and/or PTSD; and (3) introduce skills to facilitate effective communication and trauma-informed care practices among professionals working with veterans in a treatment court.

Prior to piloting the program, we conducted a needs assessment with VTC professionals and identified relevant theoretical constructs and brief interventions for inclusion in the training. Additionally, given the dearth of prior research on mental health education for VTCs, the team consulted with the developers of PTSD 101, a VHA workshop for veterans’ families that promotes psychoeducation, support, and effective communication.¹¹ Doing so informed approaches to delivering education to nonclinical audiences that interact with veterans with histories of trauma exposure. As this was a program development project, it was determined to be exempt from institutional review board review.

Needs Assessment

In the initial stages of development, local VJO specialists identified regional VTCs and facilitated introductions to these courts. Two of the 3 Rocky Mountain region VTCs that were contacted expressed interest in receiving trauma-informed training. Based on preliminary interest, the facilitators conducted a needs assessment with VJO and VTC staff from these 2 courts to capture requests for specific content and past experiences with other mental health trainings.

Guided by the focus group model, the needs assessments took place during three 1-hour meetings with VJO specialists and a 1-hour meeting with VJO specialists, VTC professionals, and community-based clinical partners.¹² Additionally, attending a VTC graduation and court session allowed for observations of court practices and interactions with veterans. A total of 13 professionals (judges, court coordinators, case managers, peer mentors, VJO specialists, and clinicians who specialize in substance use disorder and intimate partner violence) participated in the needs assessments.

The most critical need identified by court professionals was a focus on how to apply knowledge about trauma and PTSD to interactions with justice-involved veterans. This was reportedly absent from prior training sessions the courts had received. Both Rocky Mountain region VTCs expressed a strong interest in and openness to adapting practices based on research and practice recommendations. Additional requests that emerged included a refresher on psychoeducation related to trauma and how to address the personal impact of working with this population (eg, compassion fatigue).

Training Components

Based on the needs identified by VTC professionals and informed by consultation with the developers of PTSD 101,

Fostering court familiarity with cognitive processing therapy and prolonged exposure may bolster veteran engagement in treatment through regular reinforcement of skills and concepts introduced in therapy. This may prove particularly salient given the limited engagement with mental health treatment and elevated dropout rates from PTSD treatment among the general veteran population.^15,16

Exercises and metaphors were used to illustrate concepts in multiple ways. For example, training attendees engaged in a “stop, drop, and roll” thought exercise in which they were asked to brainstorm behavioral reactions to catching on fire. This exercise illustrated the tendency for individuals to revert to common yet unhelpful attempts at problem solving (eg, running due to panic, which would exacerbate the fire), particularly in crisis and without prior education regarding adaptive ways to respond. Attendee-generated examples, such as running, were used to demonstrate the importance of practicing and reinforcing skill development prior to a crisis, to ensure proficiency and optimal response. Additionally, in prompting consideration of one’s response tendencies, this exercise may engender empathy and understanding for veterans.

Skills training. Efforts to promote veteran engagement in court, facilitate motivation and readiness for change, and address barriers that arise (eg, distress associated with court appearances) may support successful and timely graduation. As such, skills training constituted the largest component of the training and drew from observations of court practices and the VTCs’ identified challenges. Consistent with the project’s aims and reported needs of the court, skills that target common presentations following trauma exposure (eg, avoidance, hypervigilance) were prioritized for this pilot training. Strategies included brief interventions from dialectical behavior therapy, acceptance and commitment therapy, and motivational interviewing to strengthen the support provided by staff to veterans and address their needs (Table 2).

Training attendees also participated in exercises to reiterate skills. For example, attendees completed an ambivalence matrix using an audience-identified common behavior that is difficult to change (eg, heavy alcohol use as a coping mechanism for distress).

Attendees engaged in an exercise that involved identifying unhelpful thoughts and behaviors, targets for validation, and veteran strengths from a hypothetical case vignette. This vignette involved a VTC participant who initially engaged effectively but began to demonstrate difficulty appropriately engaging in court and mental health treatment as well as challenging interactions with VTC staff (eg, raised voice during court sessions, not respecting communication boundaries).

Pilot Test

Based on scheduling parameters communicated by court coordinators, the pilot training was designed as a presentation during times reserved for court staffing meetings. To accommodate court preferences due to the COVID-19 pandemic, one 90-minute training was conducted virtually in March 2022, and the other training was conducted in person in April 2022 for 2 hours. The trainings were facilitated by 2 VHA clinical psychologists and included the judge, court coordinator, VJO specialist, peer mentors, case managers, probation/parole officers, and community-based HCPs who partner with the court (eg, social workers, psychologists). About 12 to 15 professionals attended each training session.

Feedback

Feedback was solicited from attendees via an anonymous online survey. Seven participants completed the survey; the response rate of about 20% was consistent with those observed for other surveys of court professionals.²⁰ Many attendees also provided feedback directly to the facilitators. Feedback highlighted that the skills-based components not only were perceived as most helpful but also notably distinguished this training. “What set this training apart from other training events was the practical applications,” one attendee noted. “It was not just information or education, both instructors did an incredible job of explaining exactly how we could apply the knowledge they were sharing. They did this in such a way that it was easy to understand and apply.”

Specific skills were consistently identified as helpful, including managing intense emotions, addressing ambivalence, and approaching sanctions and rewards. Additionally, employing a less formal approach to the training, with relatable overviews of concepts and immediate responsiveness to requests for expansion on a topic, was perceived as a unique benefit: Another attendee appreciated that “It was beneficial to sit around a table with a less formal presentation and be able to ask questions.” This approach seemed particularly well suited for the program’s cross-disciplinary audience. Attendees reported that they valued the relatively limited focus on DSM-5 criteria. Attendees emphasized that education specific to veterans on evidence-based PTSD treatments, psychoeducation, and avoidance was very helpful. Respondents also recommended that the training be lengthened to a daylong workshop to accommodate greater opportunity to practice skills and consultation.

The consultation portion of the training provided insight into additional areas of importance to incorporate into future iterations. Identified needs included appropriate and realistic boundary setting (eg, addressing disruptions in the courtroom), suggestions for improving and expanding homework assigned by the court, and ways to address concerns about PTSD treatment shared by veterans in court (eg, attributing substance use relapses to the intensiveness of trauma-focused treatment vs lack of familiarity with alternate coping skills). Additionally, the VTC professionals’ desire to support mental health professionals’ work with veterans was clearly evident, highlighting the bidirectional value of interdisciplinary collaboration between VHA mental health professionals and VTC professionals.

Discussion

A trauma-informed training was developed and delivered to 2 VTCs in the Rocky Mountain region with the goal of providing relevant psychoeducation and introducing skills to bolster court practices that address veteran needs. Psychoeducational components of the training that were particularly well received and prompted significant participant engagement included discussions and examples of avoidance, levels of validation, language to facilitate motivation and address barriers, mechanisms underlying treatment, and potential functions underlying limited veteran treatment engagement. Distress tolerance, approaches to sanctions and rewards, and use of ambivalence matrices to guide motivation were identified as particularly helpful skills.

The pilot phase of this trauma-informed training provided valuable insights into developing mental health trainings for VTCs. Specifically, VTCs may benefit from the expertise of VHA HCPs and are particularly interested in learning brief skills to improve their practices. The usefulness of such trainings may be bolstered by efforts to form relationships with the court to identify their perceived needs and employing an iterative process that is responsive to feedback both during and after the training. Last, each stage of this project was strengthened by collaboration with VJO specialists, highlighting the importance of future collaboration between VJO and VHA mental health clinics to further support justice-involved veterans. For example, VJO specialists were instrumental in identifying training needs related to veterans’ clinical presentations in court, facilitating introductions to local VTCs, and helping to address barriers to piloting, like scheduling.

Modifications and Future Directions

The insights gained through the process of training design, delivery, and feedback inform future development of this training. Based on the feedback received, subsequent versions of the training may be expanded into a half- or full-day workshop to allow for adequate time for skills training and feedback, as well as consultation. Doing so will enable facilitators to further foster attendees’ familiarity with and confidence in their ability to use these skills. Furthermore, the consultation portion of this training revealed areas that may benefit from greater attention, including how to address challenging interactions in court (eg, addressing gender dynamics between court professionals and participants) and better support veterans who are having difficulty engaging in mental health treatment (eg, courts’ observation of high rates of dropout around the third or fourth session of evidence-based treatment for PTSD). Last, all attendees who responded to the survey expressed interest in a brief resource guide based on the training, emphasizing the need for ready access to key skills and concepts to support the use of strategies learned.

An additional future aim of this project is to conduct a more thorough evaluation of the needs and outcomes related to this trauma-informed training for VTC professionals. With the rapid growth of VTCs nationwide, relatively little examination of court processes and practices has occurred, and there is a lack of research on the development or effectiveness of mental health trainings provided to VTCs.²¹ Therefore, we intend to conduct larger scale qualitative interviews with court personnel and VJO specialists to obtain a clearer understanding of the needs related to skills-based training and gaps in psychoeducation. These comprehensive needs assessments may also capture common comorbidities that were not incorporated into the pilot training (eg, substance use disorders) but may be important training targets for court professionals. This information will be used to inform subsequent expansion and adaptation of the training into a longer workshop. Program evaluation will be conducted via survey-based feedback on perceived usefulness of the workshop and self-report of confidence in and use of strategies to improve court practices. Furthermore, efforts to obtain veteran outcome data, such as treatment engagement and successful participation in VTC, may be pursued.

Limitations

This training development and pilot project provided valuable foundational information regarding a largely unexamined component of treatment courts—the benefit of skills-based trainings to facilitate court practices related to justice-involved veterans. However, it is worth noting that survey responses were limited; thus, the feedback received may not reflect all attendees’ perceptions. Additionally, because both training sessions were conducted solely with 2 courts in the Rocky Mountain area, feedback may be limited to the needs of this geographic region.

Conclusions

A trauma-informed training was developed for VTCs to facilitate relevant understanding of justice-involved veterans’ needs and presentations in court, introduce skills to address challenges that arise (eg, motivation, emotional dysregulation), and provide interdisciplinary support to court professionals. This training was an important step toward fostering strong collaborations between VHA HCPs and community-based veterans courts, and feedback received during development and following implementation highlighted the perceived need for a skills-based approach to such trainings. Further program development and evaluation can strengthen this training and provide a foundation for dissemination to a broader scope of VTCs, with the goal of reducing recidivism risk among justice-involved veterans by promoting effective engagement in problem-solving court.

Veterans who interact with the criminal justice system (ie, justice-involved veterans) have heightened rates of mental health and psychosocial needs, including posttraumatic stress disorder (PTSD), substance use disorder, depression, suicidal ideation and attempt, and homelessness.^1,2 Alongside these criminogenic risk factors, recidivism is common among justice-involved veterans: About 70% of incarcerated veterans disclosed at least one prior incarceration.³

To address the complex interplay of psychosocial factors, mental health concerns, and justice involvement among veterans, veterans treatment courts (VTCs) emerged as an alternative to incarceration.⁴ VTC participation often consists of integrated treatment and rehabilitative services (eg, vocational training, health care), ongoing monitoring for substance use, graduated responses to address treatment adherence, and ongoing communication with the judge and legal counsel.⁴

A primary aim of these courts is to address psychosocial needs believed to underlie criminal behavior, thus reducing risk of recidivism and promoting successful recovery and community integration for eligible veterans. To do so, VTCs collaborate with community-based and/or US Department of Veterans Affairs services, such as the Veterans Justice Outreach program (VJO). VJO specialists identify and refer justice-involved veterans to Veterans Health Administration (VHA) and community care and serve as a liaison between VTC staff and VHA health care professionals (HCPs).⁵

VTC outcome studies highlight the importance of not only diverting veterans to problem-solving courts, but also ensuring their optimal participation. Successful graduates of VTC programs demonstrate significant improvements in mental health symptoms, life satisfaction, and social support, as well as lower rates of law enforcement interactions.^6,7 However, less is known about supporting those veterans who have difficulty engaging in VTCs and either discontinue participation or require lengthier periods of participation to meet court graduation requirements.⁸ One possibility to improve engagement among these veterans is to enhance court practices to best meet their needs.

In addition to delivering treatment, VHA mental health professionals may serve a critical interdisciplinary role by lending expertise to support VTC practices. For example, equipping court professionals with clinical knowledge and skills related to motivation may strengthen the staff’s interactions with participants, enabling them to address barriers as they arise and to facilitate veterans’ treatment adherence. Additionally, responsiveness to the impact of trauma exposure, which is common among this population, may prove important as related symptoms can affect veterans’ engagement, receptivity, and behavior in court settings. Indeed, prior examinations of justice-involved veterans have found trauma exposure rates ranging from 60% to 90% and PTSD rates ranging from 27% to 40%.^1,2 Notably, involvement with the justice system (eg, incarceration) may itself further increase risk of trauma exposure (eg, experiencing a physical or sexual assault in prison) or exacerbate existing PTSD.⁹ Nonetheless, whereas many drug courts and domestic violence courts have been established, problem-solving courts with a specialized focus on trauma exposure remain rare, suggesting a potential gap in court training.

VHA HCPs have the potential to facilitate justice-involved veterans’ successful court and treatment participation by coordinating with VJO specialists to provide training and consultation to the courts. Supporting efforts to effectively and responsively address criminogenic risk (eg, mental health) in VTC settings may in turn reduce the likelihood of recidivism.¹⁰ Given the elevated rates of trauma exposure among justice-involved veterans and the relative lack of trauma-focused VTCs, we developed a trauma-informed training for VTC professionals that centered on related clinical presentations of justice-involved veterans and frequently occurring challenges in the context of court participation.

Program Development

This educational program aimed to (1) provide psychoeducation on trauma exposure, PTSD, and existing evidence-based treatments; (2) present clinical considerations for justice-involved veterans related to trauma exposure and/or PTSD; and (3) introduce skills to facilitate effective communication and trauma-informed care practices among professionals working with veterans in a treatment court.

Prior to piloting the program, we conducted a needs assessment with VTC professionals and identified relevant theoretical constructs and brief interventions for inclusion in the training. Additionally, given the dearth of prior research on mental health education for VTCs, the team consulted with the developers of PTSD 101, a VHA workshop for veterans’ families that promotes psychoeducation, support, and effective communication.¹¹ Doing so informed approaches to delivering education to nonclinical audiences that interact with veterans with histories of trauma exposure. As this was a program development project, it was determined to be exempt from institutional review board review.

Needs Assessment

In the initial stages of development, local VJO specialists identified regional VTCs and facilitated introductions to these courts. Two of the 3 Rocky Mountain region VTCs that were contacted expressed interest in receiving trauma-informed training. Based on preliminary interest, the facilitators conducted a needs assessment with VJO and VTC staff from these 2 courts to capture requests for specific content and past experiences with other mental health trainings.

Guided by the focus group model, the needs assessments took place during three 1-hour meetings with VJO specialists and a 1-hour meeting with VJO specialists, VTC professionals, and community-based clinical partners.¹² Additionally, attending a VTC graduation and court session allowed for observations of court practices and interactions with veterans. A total of 13 professionals (judges, court coordinators, case managers, peer mentors, VJO specialists, and clinicians who specialize in substance use disorder and intimate partner violence) participated in the needs assessments.

The most critical need identified by court professionals was a focus on how to apply knowledge about trauma and PTSD to interactions with justice-involved veterans. This was reportedly absent from prior training sessions the courts had received. Both Rocky Mountain region VTCs expressed a strong interest in and openness to adapting practices based on research and practice recommendations. Additional requests that emerged included a refresher on psychoeducation related to trauma and how to address the personal impact of working with this population (eg, compassion fatigue).

Training Components

Based on the needs identified by VTC professionals and informed by consultation with the developers of PTSD 101,

Fostering court familiarity with cognitive processing therapy and prolonged exposure may bolster veteran engagement in treatment through regular reinforcement of skills and concepts introduced in therapy. This may prove particularly salient given the limited engagement with mental health treatment and elevated dropout rates from PTSD treatment among the general veteran population.^15,16

Exercises and metaphors were used to illustrate concepts in multiple ways. For example, training attendees engaged in a “stop, drop, and roll” thought exercise in which they were asked to brainstorm behavioral reactions to catching on fire. This exercise illustrated the tendency for individuals to revert to common yet unhelpful attempts at problem solving (eg, running due to panic, which would exacerbate the fire), particularly in crisis and without prior education regarding adaptive ways to respond. Attendee-generated examples, such as running, were used to demonstrate the importance of practicing and reinforcing skill development prior to a crisis, to ensure proficiency and optimal response. Additionally, in prompting consideration of one’s response tendencies, this exercise may engender empathy and understanding for veterans.

Skills training. Efforts to promote veteran engagement in court, facilitate motivation and readiness for change, and address barriers that arise (eg, distress associated with court appearances) may support successful and timely graduation. As such, skills training constituted the largest component of the training and drew from observations of court practices and the VTCs’ identified challenges. Consistent with the project’s aims and reported needs of the court, skills that target common presentations following trauma exposure (eg, avoidance, hypervigilance) were prioritized for this pilot training. Strategies included brief interventions from dialectical behavior therapy, acceptance and commitment therapy, and motivational interviewing to strengthen the support provided by staff to veterans and address their needs (Table 2).

Training attendees also participated in exercises to reiterate skills. For example, attendees completed an ambivalence matrix using an audience-identified common behavior that is difficult to change (eg, heavy alcohol use as a coping mechanism for distress).

Attendees engaged in an exercise that involved identifying unhelpful thoughts and behaviors, targets for validation, and veteran strengths from a hypothetical case vignette. This vignette involved a VTC participant who initially engaged effectively but began to demonstrate difficulty appropriately engaging in court and mental health treatment as well as challenging interactions with VTC staff (eg, raised voice during court sessions, not respecting communication boundaries).

Pilot Test

Based on scheduling parameters communicated by court coordinators, the pilot training was designed as a presentation during times reserved for court staffing meetings. To accommodate court preferences due to the COVID-19 pandemic, one 90-minute training was conducted virtually in March 2022, and the other training was conducted in person in April 2022 for 2 hours. The trainings were facilitated by 2 VHA clinical psychologists and included the judge, court coordinator, VJO specialist, peer mentors, case managers, probation/parole officers, and community-based HCPs who partner with the court (eg, social workers, psychologists). About 12 to 15 professionals attended each training session.

Feedback

Feedback was solicited from attendees via an anonymous online survey. Seven participants completed the survey; the response rate of about 20% was consistent with those observed for other surveys of court professionals.²⁰ Many attendees also provided feedback directly to the facilitators. Feedback highlighted that the skills-based components not only were perceived as most helpful but also notably distinguished this training. “What set this training apart from other training events was the practical applications,” one attendee noted. “It was not just information or education, both instructors did an incredible job of explaining exactly how we could apply the knowledge they were sharing. They did this in such a way that it was easy to understand and apply.”

Specific skills were consistently identified as helpful, including managing intense emotions, addressing ambivalence, and approaching sanctions and rewards. Additionally, employing a less formal approach to the training, with relatable overviews of concepts and immediate responsiveness to requests for expansion on a topic, was perceived as a unique benefit: Another attendee appreciated that “It was beneficial to sit around a table with a less formal presentation and be able to ask questions.” This approach seemed particularly well suited for the program’s cross-disciplinary audience. Attendees reported that they valued the relatively limited focus on DSM-5 criteria. Attendees emphasized that education specific to veterans on evidence-based PTSD treatments, psychoeducation, and avoidance was very helpful. Respondents also recommended that the training be lengthened to a daylong workshop to accommodate greater opportunity to practice skills and consultation.

The consultation portion of the training provided insight into additional areas of importance to incorporate into future iterations. Identified needs included appropriate and realistic boundary setting (eg, addressing disruptions in the courtroom), suggestions for improving and expanding homework assigned by the court, and ways to address concerns about PTSD treatment shared by veterans in court (eg, attributing substance use relapses to the intensiveness of trauma-focused treatment vs lack of familiarity with alternate coping skills). Additionally, the VTC professionals’ desire to support mental health professionals’ work with veterans was clearly evident, highlighting the bidirectional value of interdisciplinary collaboration between VHA mental health professionals and VTC professionals.

Discussion

A trauma-informed training was developed and delivered to 2 VTCs in the Rocky Mountain region with the goal of providing relevant psychoeducation and introducing skills to bolster court practices that address veteran needs. Psychoeducational components of the training that were particularly well received and prompted significant participant engagement included discussions and examples of avoidance, levels of validation, language to facilitate motivation and address barriers, mechanisms underlying treatment, and potential functions underlying limited veteran treatment engagement. Distress tolerance, approaches to sanctions and rewards, and use of ambivalence matrices to guide motivation were identified as particularly helpful skills.

The pilot phase of this trauma-informed training provided valuable insights into developing mental health trainings for VTCs. Specifically, VTCs may benefit from the expertise of VHA HCPs and are particularly interested in learning brief skills to improve their practices. The usefulness of such trainings may be bolstered by efforts to form relationships with the court to identify their perceived needs and employing an iterative process that is responsive to feedback both during and after the training. Last, each stage of this project was strengthened by collaboration with VJO specialists, highlighting the importance of future collaboration between VJO and VHA mental health clinics to further support justice-involved veterans. For example, VJO specialists were instrumental in identifying training needs related to veterans’ clinical presentations in court, facilitating introductions to local VTCs, and helping to address barriers to piloting, like scheduling.

Modifications and Future Directions

The insights gained through the process of training design, delivery, and feedback inform future development of this training. Based on the feedback received, subsequent versions of the training may be expanded into a half- or full-day workshop to allow for adequate time for skills training and feedback, as well as consultation. Doing so will enable facilitators to further foster attendees’ familiarity with and confidence in their ability to use these skills. Furthermore, the consultation portion of this training revealed areas that may benefit from greater attention, including how to address challenging interactions in court (eg, addressing gender dynamics between court professionals and participants) and better support veterans who are having difficulty engaging in mental health treatment (eg, courts’ observation of high rates of dropout around the third or fourth session of evidence-based treatment for PTSD). Last, all attendees who responded to the survey expressed interest in a brief resource guide based on the training, emphasizing the need for ready access to key skills and concepts to support the use of strategies learned.

An additional future aim of this project is to conduct a more thorough evaluation of the needs and outcomes related to this trauma-informed training for VTC professionals. With the rapid growth of VTCs nationwide, relatively little examination of court processes and practices has occurred, and there is a lack of research on the development or effectiveness of mental health trainings provided to VTCs.²¹ Therefore, we intend to conduct larger scale qualitative interviews with court personnel and VJO specialists to obtain a clearer understanding of the needs related to skills-based training and gaps in psychoeducation. These comprehensive needs assessments may also capture common comorbidities that were not incorporated into the pilot training (eg, substance use disorders) but may be important training targets for court professionals. This information will be used to inform subsequent expansion and adaptation of the training into a longer workshop. Program evaluation will be conducted via survey-based feedback on perceived usefulness of the workshop and self-report of confidence in and use of strategies to improve court practices. Furthermore, efforts to obtain veteran outcome data, such as treatment engagement and successful participation in VTC, may be pursued.

Limitations

This training development and pilot project provided valuable foundational information regarding a largely unexamined component of treatment courts—the benefit of skills-based trainings to facilitate court practices related to justice-involved veterans. However, it is worth noting that survey responses were limited; thus, the feedback received may not reflect all attendees’ perceptions. Additionally, because both training sessions were conducted solely with 2 courts in the Rocky Mountain area, feedback may be limited to the needs of this geographic region.

Conclusions

A trauma-informed training was developed for VTCs to facilitate relevant understanding of justice-involved veterans’ needs and presentations in court, introduce skills to address challenges that arise (eg, motivation, emotional dysregulation), and provide interdisciplinary support to court professionals. This training was an important step toward fostering strong collaborations between VHA HCPs and community-based veterans courts, and feedback received during development and following implementation highlighted the perceived need for a skills-based approach to such trainings. Further program development and evaluation can strengthen this training and provide a foundation for dissemination to a broader scope of VTCs, with the goal of reducing recidivism risk among justice-involved veterans by promoting effective engagement in problem-solving court.

Veterans who interact with the criminal justice system (ie, justice-involved veterans) have heightened rates of mental health and psychosocial needs, including posttraumatic stress disorder (PTSD), substance use disorder, depression, suicidal ideation and attempt, and homelessness.^1,2 Alongside these criminogenic risk factors, recidivism is common among justice-involved veterans: About 70% of incarcerated veterans disclosed at least one prior incarceration.³

To address the complex interplay of psychosocial factors, mental health concerns, and justice involvement among veterans, veterans treatment courts (VTCs) emerged as an alternative to incarceration.⁴ VTC participation often consists of integrated treatment and rehabilitative services (eg, vocational training, health care), ongoing monitoring for substance use, graduated responses to address treatment adherence, and ongoing communication with the judge and legal counsel.⁴

A primary aim of these courts is to address psychosocial needs believed to underlie criminal behavior, thus reducing risk of recidivism and promoting successful recovery and community integration for eligible veterans. To do so, VTCs collaborate with community-based and/or US Department of Veterans Affairs services, such as the Veterans Justice Outreach program (VJO). VJO specialists identify and refer justice-involved veterans to Veterans Health Administration (VHA) and community care and serve as a liaison between VTC staff and VHA health care professionals (HCPs).⁵

VTC outcome studies highlight the importance of not only diverting veterans to problem-solving courts, but also ensuring their optimal participation. Successful graduates of VTC programs demonstrate significant improvements in mental health symptoms, life satisfaction, and social support, as well as lower rates of law enforcement interactions.^6,7 However, less is known about supporting those veterans who have difficulty engaging in VTCs and either discontinue participation or require lengthier periods of participation to meet court graduation requirements.⁸ One possibility to improve engagement among these veterans is to enhance court practices to best meet their needs.

In addition to delivering treatment, VHA mental health professionals may serve a critical interdisciplinary role by lending expertise to support VTC practices. For example, equipping court professionals with clinical knowledge and skills related to motivation may strengthen the staff’s interactions with participants, enabling them to address barriers as they arise and to facilitate veterans’ treatment adherence. Additionally, responsiveness to the impact of trauma exposure, which is common among this population, may prove important as related symptoms can affect veterans’ engagement, receptivity, and behavior in court settings. Indeed, prior examinations of justice-involved veterans have found trauma exposure rates ranging from 60% to 90% and PTSD rates ranging from 27% to 40%.^1,2 Notably, involvement with the justice system (eg, incarceration) may itself further increase risk of trauma exposure (eg, experiencing a physical or sexual assault in prison) or exacerbate existing PTSD.⁹ Nonetheless, whereas many drug courts and domestic violence courts have been established, problem-solving courts with a specialized focus on trauma exposure remain rare, suggesting a potential gap in court training.

VHA HCPs have the potential to facilitate justice-involved veterans’ successful court and treatment participation by coordinating with VJO specialists to provide training and consultation to the courts. Supporting efforts to effectively and responsively address criminogenic risk (eg, mental health) in VTC settings may in turn reduce the likelihood of recidivism.¹⁰ Given the elevated rates of trauma exposure among justice-involved veterans and the relative lack of trauma-focused VTCs, we developed a trauma-informed training for VTC professionals that centered on related clinical presentations of justice-involved veterans and frequently occurring challenges in the context of court participation.

Program Development

This educational program aimed to (1) provide psychoeducation on trauma exposure, PTSD, and existing evidence-based treatments; (2) present clinical considerations for justice-involved veterans related to trauma exposure and/or PTSD; and (3) introduce skills to facilitate effective communication and trauma-informed care practices among professionals working with veterans in a treatment court.

Prior to piloting the program, we conducted a needs assessment with VTC professionals and identified relevant theoretical constructs and brief interventions for inclusion in the training. Additionally, given the dearth of prior research on mental health education for VTCs, the team consulted with the developers of PTSD 101, a VHA workshop for veterans’ families that promotes psychoeducation, support, and effective communication.¹¹ Doing so informed approaches to delivering education to nonclinical audiences that interact with veterans with histories of trauma exposure. As this was a program development project, it was determined to be exempt from institutional review board review.

Needs Assessment

In the initial stages of development, local VJO specialists identified regional VTCs and facilitated introductions to these courts. Two of the 3 Rocky Mountain region VTCs that were contacted expressed interest in receiving trauma-informed training. Based on preliminary interest, the facilitators conducted a needs assessment with VJO and VTC staff from these 2 courts to capture requests for specific content and past experiences with other mental health trainings.

Guided by the focus group model, the needs assessments took place during three 1-hour meetings with VJO specialists and a 1-hour meeting with VJO specialists, VTC professionals, and community-based clinical partners.¹² Additionally, attending a VTC graduation and court session allowed for observations of court practices and interactions with veterans. A total of 13 professionals (judges, court coordinators, case managers, peer mentors, VJO specialists, and clinicians who specialize in substance use disorder and intimate partner violence) participated in the needs assessments.

The most critical need identified by court professionals was a focus on how to apply knowledge about trauma and PTSD to interactions with justice-involved veterans. This was reportedly absent from prior training sessions the courts had received. Both Rocky Mountain region VTCs expressed a strong interest in and openness to adapting practices based on research and practice recommendations. Additional requests that emerged included a refresher on psychoeducation related to trauma and how to address the personal impact of working with this population (eg, compassion fatigue).

Training Components

Based on the needs identified by VTC professionals and informed by consultation with the developers of PTSD 101,

Fostering court familiarity with cognitive processing therapy and prolonged exposure may bolster veteran engagement in treatment through regular reinforcement of skills and concepts introduced in therapy. This may prove particularly salient given the limited engagement with mental health treatment and elevated dropout rates from PTSD treatment among the general veteran population.^15,16

Exercises and metaphors were used to illustrate concepts in multiple ways. For example, training attendees engaged in a “stop, drop, and roll” thought exercise in which they were asked to brainstorm behavioral reactions to catching on fire. This exercise illustrated the tendency for individuals to revert to common yet unhelpful attempts at problem solving (eg, running due to panic, which would exacerbate the fire), particularly in crisis and without prior education regarding adaptive ways to respond. Attendee-generated examples, such as running, were used to demonstrate the importance of practicing and reinforcing skill development prior to a crisis, to ensure proficiency and optimal response. Additionally, in prompting consideration of one’s response tendencies, this exercise may engender empathy and understanding for veterans.

Skills training. Efforts to promote veteran engagement in court, facilitate motivation and readiness for change, and address barriers that arise (eg, distress associated with court appearances) may support successful and timely graduation. As such, skills training constituted the largest component of the training and drew from observations of court practices and the VTCs’ identified challenges. Consistent with the project’s aims and reported needs of the court, skills that target common presentations following trauma exposure (eg, avoidance, hypervigilance) were prioritized for this pilot training. Strategies included brief interventions from dialectical behavior therapy, acceptance and commitment therapy, and motivational interviewing to strengthen the support provided by staff to veterans and address their needs (Table 2).

Training attendees also participated in exercises to reiterate skills. For example, attendees completed an ambivalence matrix using an audience-identified common behavior that is difficult to change (eg, heavy alcohol use as a coping mechanism for distress).

Attendees engaged in an exercise that involved identifying unhelpful thoughts and behaviors, targets for validation, and veteran strengths from a hypothetical case vignette. This vignette involved a VTC participant who initially engaged effectively but began to demonstrate difficulty appropriately engaging in court and mental health treatment as well as challenging interactions with VTC staff (eg, raised voice during court sessions, not respecting communication boundaries).

Pilot Test

Based on scheduling parameters communicated by court coordinators, the pilot training was designed as a presentation during times reserved for court staffing meetings. To accommodate court preferences due to the COVID-19 pandemic, one 90-minute training was conducted virtually in March 2022, and the other training was conducted in person in April 2022 for 2 hours. The trainings were facilitated by 2 VHA clinical psychologists and included the judge, court coordinator, VJO specialist, peer mentors, case managers, probation/parole officers, and community-based HCPs who partner with the court (eg, social workers, psychologists). About 12 to 15 professionals attended each training session.

Feedback

Feedback was solicited from attendees via an anonymous online survey. Seven participants completed the survey; the response rate of about 20% was consistent with those observed for other surveys of court professionals.²⁰ Many attendees also provided feedback directly to the facilitators. Feedback highlighted that the skills-based components not only were perceived as most helpful but also notably distinguished this training. “What set this training apart from other training events was the practical applications,” one attendee noted. “It was not just information or education, both instructors did an incredible job of explaining exactly how we could apply the knowledge they were sharing. They did this in such a way that it was easy to understand and apply.”

Specific skills were consistently identified as helpful, including managing intense emotions, addressing ambivalence, and approaching sanctions and rewards. Additionally, employing a less formal approach to the training, with relatable overviews of concepts and immediate responsiveness to requests for expansion on a topic, was perceived as a unique benefit: Another attendee appreciated that “It was beneficial to sit around a table with a less formal presentation and be able to ask questions.” This approach seemed particularly well suited for the program’s cross-disciplinary audience. Attendees reported that they valued the relatively limited focus on DSM-5 criteria. Attendees emphasized that education specific to veterans on evidence-based PTSD treatments, psychoeducation, and avoidance was very helpful. Respondents also recommended that the training be lengthened to a daylong workshop to accommodate greater opportunity to practice skills and consultation.

The consultation portion of the training provided insight into additional areas of importance to incorporate into future iterations. Identified needs included appropriate and realistic boundary setting (eg, addressing disruptions in the courtroom), suggestions for improving and expanding homework assigned by the court, and ways to address concerns about PTSD treatment shared by veterans in court (eg, attributing substance use relapses to the intensiveness of trauma-focused treatment vs lack of familiarity with alternate coping skills). Additionally, the VTC professionals’ desire to support mental health professionals’ work with veterans was clearly evident, highlighting the bidirectional value of interdisciplinary collaboration between VHA mental health professionals and VTC professionals.

Discussion

A trauma-informed training was developed and delivered to 2 VTCs in the Rocky Mountain region with the goal of providing relevant psychoeducation and introducing skills to bolster court practices that address veteran needs. Psychoeducational components of the training that were particularly well received and prompted significant participant engagement included discussions and examples of avoidance, levels of validation, language to facilitate motivation and address barriers, mechanisms underlying treatment, and potential functions underlying limited veteran treatment engagement. Distress tolerance, approaches to sanctions and rewards, and use of ambivalence matrices to guide motivation were identified as particularly helpful skills.

The pilot phase of this trauma-informed training provided valuable insights into developing mental health trainings for VTCs. Specifically, VTCs may benefit from the expertise of VHA HCPs and are particularly interested in learning brief skills to improve their practices. The usefulness of such trainings may be bolstered by efforts to form relationships with the court to identify their perceived needs and employing an iterative process that is responsive to feedback both during and after the training. Last, each stage of this project was strengthened by collaboration with VJO specialists, highlighting the importance of future collaboration between VJO and VHA mental health clinics to further support justice-involved veterans. For example, VJO specialists were instrumental in identifying training needs related to veterans’ clinical presentations in court, facilitating introductions to local VTCs, and helping to address barriers to piloting, like scheduling.

Modifications and Future Directions

The insights gained through the process of training design, delivery, and feedback inform future development of this training. Based on the feedback received, subsequent versions of the training may be expanded into a half- or full-day workshop to allow for adequate time for skills training and feedback, as well as consultation. Doing so will enable facilitators to further foster attendees’ familiarity with and confidence in their ability to use these skills. Furthermore, the consultation portion of this training revealed areas that may benefit from greater attention, including how to address challenging interactions in court (eg, addressing gender dynamics between court professionals and participants) and better support veterans who are having difficulty engaging in mental health treatment (eg, courts’ observation of high rates of dropout around the third or fourth session of evidence-based treatment for PTSD). Last, all attendees who responded to the survey expressed interest in a brief resource guide based on the training, emphasizing the need for ready access to key skills and concepts to support the use of strategies learned.

An additional future aim of this project is to conduct a more thorough evaluation of the needs and outcomes related to this trauma-informed training for VTC professionals. With the rapid growth of VTCs nationwide, relatively little examination of court processes and practices has occurred, and there is a lack of research on the development or effectiveness of mental health trainings provided to VTCs.²¹ Therefore, we intend to conduct larger scale qualitative interviews with court personnel and VJO specialists to obtain a clearer understanding of the needs related to skills-based training and gaps in psychoeducation. These comprehensive needs assessments may also capture common comorbidities that were not incorporated into the pilot training (eg, substance use disorders) but may be important training targets for court professionals. This information will be used to inform subsequent expansion and adaptation of the training into a longer workshop. Program evaluation will be conducted via survey-based feedback on perceived usefulness of the workshop and self-report of confidence in and use of strategies to improve court practices. Furthermore, efforts to obtain veteran outcome data, such as treatment engagement and successful participation in VTC, may be pursued.

Limitations

This training development and pilot project provided valuable foundational information regarding a largely unexamined component of treatment courts—the benefit of skills-based trainings to facilitate court practices related to justice-involved veterans. However, it is worth noting that survey responses were limited; thus, the feedback received may not reflect all attendees’ perceptions. Additionally, because both training sessions were conducted solely with 2 courts in the Rocky Mountain area, feedback may be limited to the needs of this geographic region.

Conclusions

A trauma-informed training was developed for VTCs to facilitate relevant understanding of justice-involved veterans’ needs and presentations in court, introduce skills to address challenges that arise (eg, motivation, emotional dysregulation), and provide interdisciplinary support to court professionals. This training was an important step toward fostering strong collaborations between VHA HCPs and community-based veterans courts, and feedback received during development and following implementation highlighted the perceived need for a skills-based approach to such trainings. Further program development and evaluation can strengthen this training and provide a foundation for dissemination to a broader scope of VTCs, with the goal of reducing recidivism risk among justice-involved veterans by promoting effective engagement in problem-solving court.

Aspirin is an antiplatelet agent that binds irreversibly to COX-1 and COX-2 enzymes, which results in decreased prostaglandin and thromboxane A2 production and inhibition of platelet aggregation. Aspirin often is used for its antipyretic, analgesic, and antiplatelet properties. Its use in cardiovascular disease (CVD) has been studied extensively over the past few decades, and recent data are changing the framework for aspirin use in primary prevention of atherosclerotic cardiovascular disease (ASCVD). Primary prevention refers to efforts to prevent the incidence of cardiovascular events, whereas secondary prevention refers to efforts to prevent a cardiovascular event after one has occurred.¹ This differentiation is important as it guides the course of treatment.

Three trials published in 2018 evaluated aspirin use in primary prevention of ASCVD. The ASCEND trial evaluated aspirin use for primary prevention of ASCVD in patients with diabetes mellitus (DM). This study concluded that although aspirin prevented serious vascular events in patients with DM, the benefit observed was largely counteracted by the bleeding hazard.² The ARRIVE trial evaluated aspirin use for primary prevention in patients with a moderate CVD risk. The study concluded that aspirin use in patients at moderate risk of CVD could not be assessed due to the low incidence rate of CVD; however, the study concluded that aspirin did not reduce the incidence of cardiovascular events for patients at low CVD risk and that aspirin caused more mild gastrointestinal bleeds compared with placebo.³ The ASPREE trial evaluated aspirin use for primary prevention in patients aged > 70 years to determine whether its use prolonged a healthy lifespan. This trial concluded that patients who received daily aspirin were at a higher risk of major hemorrhage and that aspirin did not diminish CVD risk compared with placebo.⁴

These studies led to a paradigm shift in therapy to reevaluate aspirin use for primary prevention. Current indications for aspirin include secondary prevention of ASCVD (ie, myocardial infarction [MI], coronary artery bypass graft, transient ischemic attack [TIA], and stroke), venous thromboembolism prophylaxis in the setting of orthopedic surgery, or valvular disease with replacement and analgesia. It is important to note that certain clinical circumstances may warrant aspirin use for primary prevention of ASCVD on a patient-specific basis, and this decision should be made using a risk/benefit analysis with the patient.

In April 2022, the US Preventive Services Task Force (USPSTF) recommended against using low-dose aspirin for primary prevention of ASCVD in individuals aged ≥ 60 years. The USPSTF noted that for patients who have a ≥ 10%, 10-year CVD risk, the decision to initiate aspirin should be based on a risk/benefit discussion and may be beneficial in certain patient populations.⁵A 2019 National Heart, Lung, and Blood Institute survey found that 29 million Americans used aspirin for primary prevention of ASCVD, and 6.6 million of these Americans used aspirin for primary prevention without the recommendation of a health care professional (HCP). Almost half of these individuals were aged > 70 years and, therefore, at an increased risk for bleeding.⁶ With the recent studies and changes in guidelines highlighting a higher risk rather than benefit with the use of aspirin for primary prevention, the current use of aspirin for primary prevention in the United States needs to be readdressed.

HCPs should assess the appropriateness of aspirin use in their patients to ensure that the risks of aspirin do not outweigh the benefits. Pharmacists can play a vital role in the assessment of aspirin for primary prevention during patient visits and make recommendations to primary care practitioners to deprescribe aspirin when appropriate.

Methods

The objective of this study was to evaluate the appropriateness of aspirin therapy in patient aligned care team (PACT) clinics at the Captain James A. Lovell Federal Health Care Center (FHCC) in North Chicago, Illinois. The PACT clinics are a category of clinics that include all the primary care clinics at FHCC.

The primary outcome of this study was to determine the percentage of patients inappropriately on aspirin therapy. To assess the inappropriate use of aspirin, relevant history of ASCVD was collected. Patients were divided into 3 groups: those with a history of ASCVD, those with no risk factors or history of ASCVD, and those with risk factors and no history of ASCVD. Patients were then categorized for their indication for aspirin use, which included either primary or secondary prevention of ASCVD. Patients were categorized into the primary prevention group if they had no history of ASCVD, whereas patients with a history of ASCVD were placed into the secondary prevention group.

ASCVD was defined as patients with acute coronary syndrome (ACS), history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral artery disease (PAD), including aortic aneurysm (all with an atherosclerotic origin). Possible ASCVD risk was defined as patients with DM with a major risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, chronic kidney disease [CKD]/albuminuria) or patients diagnosed with coronary artery disease without an event. The percentage of patients followed by a PACT pharmacist, the number of pharmacist follow-up visits during the study period, and the date of the first 81-mg aspirin pharmacy order that was filled at FHCC were also collected.

The secondary outcome of this study focused on patients who were using aspirin for primary prevention and assessed potential reasons that may warrant deprescribing aspirin therapy. One reason for deprescribing is that aspirin may not be indicated for some patients, including those with DM without cardiovascular complications, patients aged > 70 years, and/or patients with CKD (defined as estimated glomerular filtration rate < 60 mL/min). Another reason for deprescribing is contraindication, which included patients with coagulopathy, thrombocytopenia (defined as platelet count < 150,000 mL), a history of gastrointestinal bleeding, peptic ulcer disease or other major bleeds, and/or consistent use of medications that increase bleeding risk (such as nonsteroidal anti-inflammatory agents, steroids, or anticoagulants) for > 14 days.

The safety outcome of this study assessed bleeding events while on aspirin therapy. All patients were categorized depending on if they had a major, minor, or no bleeding event while on aspirin therapy. Hemorrhagic stroke, symptomatic intracranial bleeding, bleeds located in other critical sites or organs (intracranial, intraspinal, intraocular, retroperitoneal, intra‐articular or pericardial), bleeds causing hemodynamic instability requiring vasopressors, bleeds causing a > 2 g/dL hemoglobin drop since initiation of aspirin therapy, severe extracranial bleeding requiring transfusion or hospitalization, fatal bleeding, or bleeds requiring > 2 units of red blood cell transfusion were considered major bleeding events. Minor bleeding events were any events that did not meet the criteria for major bleeding, including bruising, bleeding gums, epistaxis, hemorrhoidal bleeds, and bleeding that did not require intervention or treatment.⁷

Patients were included if they were aged > 18 years, had an active prescription for 81-mg aspirin tablet on September 30, 2021, and were seen in FHCC PACT clinics or at affiliated community-based outpatient centers. Other doses of aspirin were excluded as the 81-mg dose is the standard dose for primary prevention of ASCVD in the United States. US Department of Defense patients, home-based primary care patients, and community living center patients were excluded in this study. Patients with an aspirin prescription from a non–US Department of Veterans Affairs (VA) facility and patients on aspirin for reasons other than cardiovascular protection (such as pain, fever, etc) also were excluded from this study.

Data were collected from the FHCC electronic health record. A list was generated to include all active prescriptions for aspirin filled at FHCC as of September 30, 2021. Data were reviewed before this date to capture primary and secondary outcomes. No information was gathered from the chart after that date. This project was approved by the Edward Hines, Jr. VA Hospital Institutional Review Board. The primary and secondary outcomes were reported using descriptive statistics.

Results

This study reviewed 140 patient records and 105 patients met inclusion criteria.

For the primary endpoint, 53 patients (50%) were on aspirin for secondary prevention and 52 (50%) were on aspirin for primary prevention. Of the 105 patients included in the study, 31 (30%) had a possible ASCVD risk and were taking aspirin for primary prevention, while 21 (20%) had no ASCVD and were taking aspirin for primary prevention. Of the 52 patients on aspirin for primary prevention, 31 patients (60%) had a possible risk for ASCVD. Of the 52 patients in the primary prevention group, 15 (29%) were followed by a pharmacist, and the average number of follow-up appointments was 4.

The secondary endpoint focused on patients taking aspirin for primary prevention and the factors that may warrant deprescribing aspirin. Of the 52 patients on aspirin for primary prevention, 25 patients were aged > 70 years, 15 patients were concurrently taking medications that may increase bleeding risk,

Discussion

The majority of patients in this study were on aspirin appropriately. Indications deemed appropriate for aspirin therapy include secondary prevention and primary prevention with a possible ASCVD risk. About 20% of the total patient population in this study was taking aspirin for primary prevention with no ASCVD risk. For these patients, the risk of bleeding likely outweighs the benefits of aspirin therapy as patients are at low risk for ASCVD; therefore, aspirin therapy is likely inappropriate in this patient population. These patients may be unnecessarily at an increased risk for bleeding and may benefit from deprescribing aspirin. For the safety of patients, HCPs should be continuously assessing the appropriateness of aspirin for primary prevention and deprescribing when necessary.

About one-third of the patients using aspirin for primary prevention were followed by a pharmacist. Pharmacists can play a key role in deprescribing aspirin for primary prevention when aspirin use is deemed inappropriate. About 30% of the total patient population in this study was on aspirin for primary prevention with possible ASCVD risk. This patient population may benefit from aspirin therapy as they are at a higher risk for ASCVD. For these patients, a risk/benefit discussion is necessary to determine the appropriateness of aspirin for primary prevention. This risk/benefit discussion should be a continuous conversation between patients and HCPs as different factors such as age and changes in comorbid conditions and medications may increase bleeding risk.

The secondary endpoint focused on patients taking aspirin for primary prevention and the factors that may warrant deprescribing aspirin. The most common factors seen in this study included patients who were aged > 70 years, patients who were concurrently taking medications that may increase bleeding risk, and patients with CKD. All of these factors increase bleeding risk, making the risks potentially outweigh the benefits of aspirin for primary prevention. These factors should be the primary focus when assessing patients on aspirin for primary prevention to promote deprescribing aspirin if deemed appropriate as they were the most prevalent in this study.

The safety endpoints focused on bleeding events as a whole as well as the bleeding events seen in the primary prevention group. There were 2 major bleeding events and 20 minor bleeding events in the primary prevention group. The number of bleeding events both major and minor further shows the need for a continuous risk/benefit discussion between patients and HCPs on continued aspirin use for primary prevention. The bleeding risk with aspirin is prevalent. HCPs should continue to assess for factors that increase the bleeding risk that may warrant deprescribing aspirin to prevent future bleeding events in this patient population.

Strengths and Limitations

As there have been recent updates to guidelines on the use of aspirin for primary prevention, a strength of this study is that it evaluates a topic that is relevant in health care. Another strength of this study is that it focuses on specific patient factors that HCPs can assess when determining whether aspirin for primary prevention is appropriate in their patients. These specific patient factors can also be used as a guide to help HCPs deprescribe aspirin for primary prevention when appropriate.

One of the limitations of this study is that bleeding events that occurred outside of the FHCC were unable to be assessed unless the HCP specifically commented on the bleeding event in the chart. This could potentially underestimate the bleeding events seen in this study. Another limitation is that the bleeding risk for patients who were not on aspirin was not assessed. There was no comparison group to ascertain whether the bleeding risk was higher in the aspirin group compared with a no aspirin group. However, many of the major clinical trials saw an increased risk of bleeding in the aspirin group compared with placebo.

Conclusions

Aspirin therapy for secondary prevention remains an important part of treatment. Aspirin therapy for primary prevention may be appropriate for patients with a possible ASCVD risk. The therapy may be inappropriate in cases where patients have an increased bleeding risk and low or no ASCVD risk. It is important to continuously assess the need for aspirin therapy for patients in the setting of primary prevention. Common factors seen in this study to warrant deprescribing aspirin for primary prevention include patients aged > 70 years, concurrent use of medications that increase bleeding risk, and patients with CKD. By assessing ASCVD risk as well as bleeding risk and having a risk/benefit discussion between the HCP and patient, aspirin used for primary prevention can be appropriately deprescribed when the risks of bleeding outweigh the benefits.

Acknowledgments

The authors thank the Captain James A. Lovell Federal Health Care Center research committee (Hong-Yen Vi, PharmD, BCPS; Shaiza Khan, PharmD, BCPS; Yinka Alaka, BPharm, PharmD; Jennifer Kwon, PharmD, BCOP) and coinvestigator Aeman Choudhury, PharmD, BCPS, BCACP.

Aspirin is an antiplatelet agent that binds irreversibly to COX-1 and COX-2 enzymes, which results in decreased prostaglandin and thromboxane A2 production and inhibition of platelet aggregation. Aspirin often is used for its antipyretic, analgesic, and antiplatelet properties. Its use in cardiovascular disease (CVD) has been studied extensively over the past few decades, and recent data are changing the framework for aspirin use in primary prevention of atherosclerotic cardiovascular disease (ASCVD). Primary prevention refers to efforts to prevent the incidence of cardiovascular events, whereas secondary prevention refers to efforts to prevent a cardiovascular event after one has occurred.¹ This differentiation is important as it guides the course of treatment.

Three trials published in 2018 evaluated aspirin use in primary prevention of ASCVD. The ASCEND trial evaluated aspirin use for primary prevention of ASCVD in patients with diabetes mellitus (DM). This study concluded that although aspirin prevented serious vascular events in patients with DM, the benefit observed was largely counteracted by the bleeding hazard.² The ARRIVE trial evaluated aspirin use for primary prevention in patients with a moderate CVD risk. The study concluded that aspirin use in patients at moderate risk of CVD could not be assessed due to the low incidence rate of CVD; however, the study concluded that aspirin did not reduce the incidence of cardiovascular events for patients at low CVD risk and that aspirin caused more mild gastrointestinal bleeds compared with placebo.³ The ASPREE trial evaluated aspirin use for primary prevention in patients aged > 70 years to determine whether its use prolonged a healthy lifespan. This trial concluded that patients who received daily aspirin were at a higher risk of major hemorrhage and that aspirin did not diminish CVD risk compared with placebo.⁴

These studies led to a paradigm shift in therapy to reevaluate aspirin use for primary prevention. Current indications for aspirin include secondary prevention of ASCVD (ie, myocardial infarction [MI], coronary artery bypass graft, transient ischemic attack [TIA], and stroke), venous thromboembolism prophylaxis in the setting of orthopedic surgery, or valvular disease with replacement and analgesia. It is important to note that certain clinical circumstances may warrant aspirin use for primary prevention of ASCVD on a patient-specific basis, and this decision should be made using a risk/benefit analysis with the patient.

In April 2022, the US Preventive Services Task Force (USPSTF) recommended against using low-dose aspirin for primary prevention of ASCVD in individuals aged ≥ 60 years. The USPSTF noted that for patients who have a ≥ 10%, 10-year CVD risk, the decision to initiate aspirin should be based on a risk/benefit discussion and may be beneficial in certain patient populations.⁵A 2019 National Heart, Lung, and Blood Institute survey found that 29 million Americans used aspirin for primary prevention of ASCVD, and 6.6 million of these Americans used aspirin for primary prevention without the recommendation of a health care professional (HCP). Almost half of these individuals were aged > 70 years and, therefore, at an increased risk for bleeding.⁶ With the recent studies and changes in guidelines highlighting a higher risk rather than benefit with the use of aspirin for primary prevention, the current use of aspirin for primary prevention in the United States needs to be readdressed.

HCPs should assess the appropriateness of aspirin use in their patients to ensure that the risks of aspirin do not outweigh the benefits. Pharmacists can play a vital role in the assessment of aspirin for primary prevention during patient visits and make recommendations to primary care practitioners to deprescribe aspirin when appropriate.

Methods

The objective of this study was to evaluate the appropriateness of aspirin therapy in patient aligned care team (PACT) clinics at the Captain James A. Lovell Federal Health Care Center (FHCC) in North Chicago, Illinois. The PACT clinics are a category of clinics that include all the primary care clinics at FHCC.

The primary outcome of this study was to determine the percentage of patients inappropriately on aspirin therapy. To assess the inappropriate use of aspirin, relevant history of ASCVD was collected. Patients were divided into 3 groups: those with a history of ASCVD, those with no risk factors or history of ASCVD, and those with risk factors and no history of ASCVD. Patients were then categorized for their indication for aspirin use, which included either primary or secondary prevention of ASCVD. Patients were categorized into the primary prevention group if they had no history of ASCVD, whereas patients with a history of ASCVD were placed into the secondary prevention group.

ASCVD was defined as patients with acute coronary syndrome (ACS), history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral artery disease (PAD), including aortic aneurysm (all with an atherosclerotic origin). Possible ASCVD risk was defined as patients with DM with a major risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, chronic kidney disease [CKD]/albuminuria) or patients diagnosed with coronary artery disease without an event. The percentage of patients followed by a PACT pharmacist, the number of pharmacist follow-up visits during the study period, and the date of the first 81-mg aspirin pharmacy order that was filled at FHCC were also collected.

The secondary outcome of this study focused on patients who were using aspirin for primary prevention and assessed potential reasons that may warrant deprescribing aspirin therapy. One reason for deprescribing is that aspirin may not be indicated for some patients, including those with DM without cardiovascular complications, patients aged > 70 years, and/or patients with CKD (defined as estimated glomerular filtration rate < 60 mL/min). Another reason for deprescribing is contraindication, which included patients with coagulopathy, thrombocytopenia (defined as platelet count < 150,000 mL), a history of gastrointestinal bleeding, peptic ulcer disease or other major bleeds, and/or consistent use of medications that increase bleeding risk (such as nonsteroidal anti-inflammatory agents, steroids, or anticoagulants) for > 14 days.

The safety outcome of this study assessed bleeding events while on aspirin therapy. All patients were categorized depending on if they had a major, minor, or no bleeding event while on aspirin therapy. Hemorrhagic stroke, symptomatic intracranial bleeding, bleeds located in other critical sites or organs (intracranial, intraspinal, intraocular, retroperitoneal, intra‐articular or pericardial), bleeds causing hemodynamic instability requiring vasopressors, bleeds causing a > 2 g/dL hemoglobin drop since initiation of aspirin therapy, severe extracranial bleeding requiring transfusion or hospitalization, fatal bleeding, or bleeds requiring > 2 units of red blood cell transfusion were considered major bleeding events. Minor bleeding events were any events that did not meet the criteria for major bleeding, including bruising, bleeding gums, epistaxis, hemorrhoidal bleeds, and bleeding that did not require intervention or treatment.⁷

Patients were included if they were aged > 18 years, had an active prescription for 81-mg aspirin tablet on September 30, 2021, and were seen in FHCC PACT clinics or at affiliated community-based outpatient centers. Other doses of aspirin were excluded as the 81-mg dose is the standard dose for primary prevention of ASCVD in the United States. US Department of Defense patients, home-based primary care patients, and community living center patients were excluded in this study. Patients with an aspirin prescription from a non–US Department of Veterans Affairs (VA) facility and patients on aspirin for reasons other than cardiovascular protection (such as pain, fever, etc) also were excluded from this study.

Data were collected from the FHCC electronic health record. A list was generated to include all active prescriptions for aspirin filled at FHCC as of September 30, 2021. Data were reviewed before this date to capture primary and secondary outcomes. No information was gathered from the chart after that date. This project was approved by the Edward Hines, Jr. VA Hospital Institutional Review Board. The primary and secondary outcomes were reported using descriptive statistics.

Results

This study reviewed 140 patient records and 105 patients met inclusion criteria.

For the primary endpoint, 53 patients (50%) were on aspirin for secondary prevention and 52 (50%) were on aspirin for primary prevention. Of the 105 patients included in the study, 31 (30%) had a possible ASCVD risk and were taking aspirin for primary prevention, while 21 (20%) had no ASCVD and were taking aspirin for primary prevention. Of the 52 patients on aspirin for primary prevention, 31 patients (60%) had a possible risk for ASCVD. Of the 52 patients in the primary prevention group, 15 (29%) were followed by a pharmacist, and the average number of follow-up appointments was 4.

The secondary endpoint focused on patients taking aspirin for primary prevention and the factors that may warrant deprescribing aspirin. Of the 52 patients on aspirin for primary prevention, 25 patients were aged > 70 years, 15 patients were concurrently taking medications that may increase bleeding risk,

Discussion

The majority of patients in this study were on aspirin appropriately. Indications deemed appropriate for aspirin therapy include secondary prevention and primary prevention with a possible ASCVD risk. About 20% of the total patient population in this study was taking aspirin for primary prevention with no ASCVD risk. For these patients, the risk of bleeding likely outweighs the benefits of aspirin therapy as patients are at low risk for ASCVD; therefore, aspirin therapy is likely inappropriate in this patient population. These patients may be unnecessarily at an increased risk for bleeding and may benefit from deprescribing aspirin. For the safety of patients, HCPs should be continuously assessing the appropriateness of aspirin for primary prevention and deprescribing when necessary.

About one-third of the patients using aspirin for primary prevention were followed by a pharmacist. Pharmacists can play a key role in deprescribing aspirin for primary prevention when aspirin use is deemed inappropriate. About 30% of the total patient population in this study was on aspirin for primary prevention with possible ASCVD risk. This patient population may benefit from aspirin therapy as they are at a higher risk for ASCVD. For these patients, a risk/benefit discussion is necessary to determine the appropriateness of aspirin for primary prevention. This risk/benefit discussion should be a continuous conversation between patients and HCPs as different factors such as age and changes in comorbid conditions and medications may increase bleeding risk.

The secondary endpoint focused on patients taking aspirin for primary prevention and the factors that may warrant deprescribing aspirin. The most common factors seen in this study included patients who were aged > 70 years, patients who were concurrently taking medications that may increase bleeding risk, and patients with CKD. All of these factors increase bleeding risk, making the risks potentially outweigh the benefits of aspirin for primary prevention. These factors should be the primary focus when assessing patients on aspirin for primary prevention to promote deprescribing aspirin if deemed appropriate as they were the most prevalent in this study.

The safety endpoints focused on bleeding events as a whole as well as the bleeding events seen in the primary prevention group. There were 2 major bleeding events and 20 minor bleeding events in the primary prevention group. The number of bleeding events both major and minor further shows the need for a continuous risk/benefit discussion between patients and HCPs on continued aspirin use for primary prevention. The bleeding risk with aspirin is prevalent. HCPs should continue to assess for factors that increase the bleeding risk that may warrant deprescribing aspirin to prevent future bleeding events in this patient population.

Strengths and Limitations

As there have been recent updates to guidelines on the use of aspirin for primary prevention, a strength of this study is that it evaluates a topic that is relevant in health care. Another strength of this study is that it focuses on specific patient factors that HCPs can assess when determining whether aspirin for primary prevention is appropriate in their patients. These specific patient factors can also be used as a guide to help HCPs deprescribe aspirin for primary prevention when appropriate.

One of the limitations of this study is that bleeding events that occurred outside of the FHCC were unable to be assessed unless the HCP specifically commented on the bleeding event in the chart. This could potentially underestimate the bleeding events seen in this study. Another limitation is that the bleeding risk for patients who were not on aspirin was not assessed. There was no comparison group to ascertain whether the bleeding risk was higher in the aspirin group compared with a no aspirin group. However, many of the major clinical trials saw an increased risk of bleeding in the aspirin group compared with placebo.

Conclusions

Aspirin therapy for secondary prevention remains an important part of treatment. Aspirin therapy for primary prevention may be appropriate for patients with a possible ASCVD risk. The therapy may be inappropriate in cases where patients have an increased bleeding risk and low or no ASCVD risk. It is important to continuously assess the need for aspirin therapy for patients in the setting of primary prevention. Common factors seen in this study to warrant deprescribing aspirin for primary prevention include patients aged > 70 years, concurrent use of medications that increase bleeding risk, and patients with CKD. By assessing ASCVD risk as well as bleeding risk and having a risk/benefit discussion between the HCP and patient, aspirin used for primary prevention can be appropriately deprescribed when the risks of bleeding outweigh the benefits.

Acknowledgments

The authors thank the Captain James A. Lovell Federal Health Care Center research committee (Hong-Yen Vi, PharmD, BCPS; Shaiza Khan, PharmD, BCPS; Yinka Alaka, BPharm, PharmD; Jennifer Kwon, PharmD, BCOP) and coinvestigator Aeman Choudhury, PharmD, BCPS, BCACP.

Aspirin is an antiplatelet agent that binds irreversibly to COX-1 and COX-2 enzymes, which results in decreased prostaglandin and thromboxane A2 production and inhibition of platelet aggregation. Aspirin often is used for its antipyretic, analgesic, and antiplatelet properties. Its use in cardiovascular disease (CVD) has been studied extensively over the past few decades, and recent data are changing the framework for aspirin use in primary prevention of atherosclerotic cardiovascular disease (ASCVD). Primary prevention refers to efforts to prevent the incidence of cardiovascular events, whereas secondary prevention refers to efforts to prevent a cardiovascular event after one has occurred.¹ This differentiation is important as it guides the course of treatment.

Three trials published in 2018 evaluated aspirin use in primary prevention of ASCVD. The ASCEND trial evaluated aspirin use for primary prevention of ASCVD in patients with diabetes mellitus (DM). This study concluded that although aspirin prevented serious vascular events in patients with DM, the benefit observed was largely counteracted by the bleeding hazard.² The ARRIVE trial evaluated aspirin use for primary prevention in patients with a moderate CVD risk. The study concluded that aspirin use in patients at moderate risk of CVD could not be assessed due to the low incidence rate of CVD; however, the study concluded that aspirin did not reduce the incidence of cardiovascular events for patients at low CVD risk and that aspirin caused more mild gastrointestinal bleeds compared with placebo.³ The ASPREE trial evaluated aspirin use for primary prevention in patients aged > 70 years to determine whether its use prolonged a healthy lifespan. This trial concluded that patients who received daily aspirin were at a higher risk of major hemorrhage and that aspirin did not diminish CVD risk compared with placebo.⁴

These studies led to a paradigm shift in therapy to reevaluate aspirin use for primary prevention. Current indications for aspirin include secondary prevention of ASCVD (ie, myocardial infarction [MI], coronary artery bypass graft, transient ischemic attack [TIA], and stroke), venous thromboembolism prophylaxis in the setting of orthopedic surgery, or valvular disease with replacement and analgesia. It is important to note that certain clinical circumstances may warrant aspirin use for primary prevention of ASCVD on a patient-specific basis, and this decision should be made using a risk/benefit analysis with the patient.

In April 2022, the US Preventive Services Task Force (USPSTF) recommended against using low-dose aspirin for primary prevention of ASCVD in individuals aged ≥ 60 years. The USPSTF noted that for patients who have a ≥ 10%, 10-year CVD risk, the decision to initiate aspirin should be based on a risk/benefit discussion and may be beneficial in certain patient populations.⁵A 2019 National Heart, Lung, and Blood Institute survey found that 29 million Americans used aspirin for primary prevention of ASCVD, and 6.6 million of these Americans used aspirin for primary prevention without the recommendation of a health care professional (HCP). Almost half of these individuals were aged > 70 years and, therefore, at an increased risk for bleeding.⁶ With the recent studies and changes in guidelines highlighting a higher risk rather than benefit with the use of aspirin for primary prevention, the current use of aspirin for primary prevention in the United States needs to be readdressed.

HCPs should assess the appropriateness of aspirin use in their patients to ensure that the risks of aspirin do not outweigh the benefits. Pharmacists can play a vital role in the assessment of aspirin for primary prevention during patient visits and make recommendations to primary care practitioners to deprescribe aspirin when appropriate.

Methods

The objective of this study was to evaluate the appropriateness of aspirin therapy in patient aligned care team (PACT) clinics at the Captain James A. Lovell Federal Health Care Center (FHCC) in North Chicago, Illinois. The PACT clinics are a category of clinics that include all the primary care clinics at FHCC.

The primary outcome of this study was to determine the percentage of patients inappropriately on aspirin therapy. To assess the inappropriate use of aspirin, relevant history of ASCVD was collected. Patients were divided into 3 groups: those with a history of ASCVD, those with no risk factors or history of ASCVD, and those with risk factors and no history of ASCVD. Patients were then categorized for their indication for aspirin use, which included either primary or secondary prevention of ASCVD. Patients were categorized into the primary prevention group if they had no history of ASCVD, whereas patients with a history of ASCVD were placed into the secondary prevention group.

ASCVD was defined as patients with acute coronary syndrome (ACS), history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral artery disease (PAD), including aortic aneurysm (all with an atherosclerotic origin). Possible ASCVD risk was defined as patients with DM with a major risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, chronic kidney disease [CKD]/albuminuria) or patients diagnosed with coronary artery disease without an event. The percentage of patients followed by a PACT pharmacist, the number of pharmacist follow-up visits during the study period, and the date of the first 81-mg aspirin pharmacy order that was filled at FHCC were also collected.

The secondary outcome of this study focused on patients who were using aspirin for primary prevention and assessed potential reasons that may warrant deprescribing aspirin therapy. One reason for deprescribing is that aspirin may not be indicated for some patients, including those with DM without cardiovascular complications, patients aged > 70 years, and/or patients with CKD (defined as estimated glomerular filtration rate < 60 mL/min). Another reason for deprescribing is contraindication, which included patients with coagulopathy, thrombocytopenia (defined as platelet count < 150,000 mL), a history of gastrointestinal bleeding, peptic ulcer disease or other major bleeds, and/or consistent use of medications that increase bleeding risk (such as nonsteroidal anti-inflammatory agents, steroids, or anticoagulants) for > 14 days.

The safety outcome of this study assessed bleeding events while on aspirin therapy. All patients were categorized depending on if they had a major, minor, or no bleeding event while on aspirin therapy. Hemorrhagic stroke, symptomatic intracranial bleeding, bleeds located in other critical sites or organs (intracranial, intraspinal, intraocular, retroperitoneal, intra‐articular or pericardial), bleeds causing hemodynamic instability requiring vasopressors, bleeds causing a > 2 g/dL hemoglobin drop since initiation of aspirin therapy, severe extracranial bleeding requiring transfusion or hospitalization, fatal bleeding, or bleeds requiring > 2 units of red blood cell transfusion were considered major bleeding events. Minor bleeding events were any events that did not meet the criteria for major bleeding, including bruising, bleeding gums, epistaxis, hemorrhoidal bleeds, and bleeding that did not require intervention or treatment.⁷

Patients were included if they were aged > 18 years, had an active prescription for 81-mg aspirin tablet on September 30, 2021, and were seen in FHCC PACT clinics or at affiliated community-based outpatient centers. Other doses of aspirin were excluded as the 81-mg dose is the standard dose for primary prevention of ASCVD in the United States. US Department of Defense patients, home-based primary care patients, and community living center patients were excluded in this study. Patients with an aspirin prescription from a non–US Department of Veterans Affairs (VA) facility and patients on aspirin for reasons other than cardiovascular protection (such as pain, fever, etc) also were excluded from this study.

Data were collected from the FHCC electronic health record. A list was generated to include all active prescriptions for aspirin filled at FHCC as of September 30, 2021. Data were reviewed before this date to capture primary and secondary outcomes. No information was gathered from the chart after that date. This project was approved by the Edward Hines, Jr. VA Hospital Institutional Review Board. The primary and secondary outcomes were reported using descriptive statistics.

Results

This study reviewed 140 patient records and 105 patients met inclusion criteria.

For the primary endpoint, 53 patients (50%) were on aspirin for secondary prevention and 52 (50%) were on aspirin for primary prevention. Of the 105 patients included in the study, 31 (30%) had a possible ASCVD risk and were taking aspirin for primary prevention, while 21 (20%) had no ASCVD and were taking aspirin for primary prevention. Of the 52 patients on aspirin for primary prevention, 31 patients (60%) had a possible risk for ASCVD. Of the 52 patients in the primary prevention group, 15 (29%) were followed by a pharmacist, and the average number of follow-up appointments was 4.

The secondary endpoint focused on patients taking aspirin for primary prevention and the factors that may warrant deprescribing aspirin. Of the 52 patients on aspirin for primary prevention, 25 patients were aged > 70 years, 15 patients were concurrently taking medications that may increase bleeding risk,

Discussion

The majority of patients in this study were on aspirin appropriately. Indications deemed appropriate for aspirin therapy include secondary prevention and primary prevention with a possible ASCVD risk. About 20% of the total patient population in this study was taking aspirin for primary prevention with no ASCVD risk. For these patients, the risk of bleeding likely outweighs the benefits of aspirin therapy as patients are at low risk for ASCVD; therefore, aspirin therapy is likely inappropriate in this patient population. These patients may be unnecessarily at an increased risk for bleeding and may benefit from deprescribing aspirin. For the safety of patients, HCPs should be continuously assessing the appropriateness of aspirin for primary prevention and deprescribing when necessary.

About one-third of the patients using aspirin for primary prevention were followed by a pharmacist. Pharmacists can play a key role in deprescribing aspirin for primary prevention when aspirin use is deemed inappropriate. About 30% of the total patient population in this study was on aspirin for primary prevention with possible ASCVD risk. This patient population may benefit from aspirin therapy as they are at a higher risk for ASCVD. For these patients, a risk/benefit discussion is necessary to determine the appropriateness of aspirin for primary prevention. This risk/benefit discussion should be a continuous conversation between patients and HCPs as different factors such as age and changes in comorbid conditions and medications may increase bleeding risk.

The secondary endpoint focused on patients taking aspirin for primary prevention and the factors that may warrant deprescribing aspirin. The most common factors seen in this study included patients who were aged > 70 years, patients who were concurrently taking medications that may increase bleeding risk, and patients with CKD. All of these factors increase bleeding risk, making the risks potentially outweigh the benefits of aspirin for primary prevention. These factors should be the primary focus when assessing patients on aspirin for primary prevention to promote deprescribing aspirin if deemed appropriate as they were the most prevalent in this study.

The safety endpoints focused on bleeding events as a whole as well as the bleeding events seen in the primary prevention group. There were 2 major bleeding events and 20 minor bleeding events in the primary prevention group. The number of bleeding events both major and minor further shows the need for a continuous risk/benefit discussion between patients and HCPs on continued aspirin use for primary prevention. The bleeding risk with aspirin is prevalent. HCPs should continue to assess for factors that increase the bleeding risk that may warrant deprescribing aspirin to prevent future bleeding events in this patient population.

Strengths and Limitations

As there have been recent updates to guidelines on the use of aspirin for primary prevention, a strength of this study is that it evaluates a topic that is relevant in health care. Another strength of this study is that it focuses on specific patient factors that HCPs can assess when determining whether aspirin for primary prevention is appropriate in their patients. These specific patient factors can also be used as a guide to help HCPs deprescribe aspirin for primary prevention when appropriate.

One of the limitations of this study is that bleeding events that occurred outside of the FHCC were unable to be assessed unless the HCP specifically commented on the bleeding event in the chart. This could potentially underestimate the bleeding events seen in this study. Another limitation is that the bleeding risk for patients who were not on aspirin was not assessed. There was no comparison group to ascertain whether the bleeding risk was higher in the aspirin group compared with a no aspirin group. However, many of the major clinical trials saw an increased risk of bleeding in the aspirin group compared with placebo.

Conclusions

Aspirin therapy for secondary prevention remains an important part of treatment. Aspirin therapy for primary prevention may be appropriate for patients with a possible ASCVD risk. The therapy may be inappropriate in cases where patients have an increased bleeding risk and low or no ASCVD risk. It is important to continuously assess the need for aspirin therapy for patients in the setting of primary prevention. Common factors seen in this study to warrant deprescribing aspirin for primary prevention include patients aged > 70 years, concurrent use of medications that increase bleeding risk, and patients with CKD. By assessing ASCVD risk as well as bleeding risk and having a risk/benefit discussion between the HCP and patient, aspirin used for primary prevention can be appropriately deprescribed when the risks of bleeding outweigh the benefits.

Acknowledgments

The authors thank the Captain James A. Lovell Federal Health Care Center research committee (Hong-Yen Vi, PharmD, BCPS; Shaiza Khan, PharmD, BCPS; Yinka Alaka, BPharm, PharmD; Jennifer Kwon, PharmD, BCOP) and coinvestigator Aeman Choudhury, PharmD, BCPS, BCACP.