Since 2008, suicide has ranked as the tenth leading cause of death for all ages in the US, with rates of suicide continuing to rise.^1-3 Suicide is even more urgent to address in veteran populations. The age- and sex-adjusted suicide rate in 2017 was more than 1.5 times greater for veterans than it was for nonveteran adults.² Of importance, rates of suicide are increasing at a faster rate in veterans who are not connected to Veterans Health Administration (VHA) care.^4,5 These at-risk veterans include individuals who are eligible for VHA care yet have not had a VHA appointment within the year before death; veterans who may be ineligible to receive VHA care due to complex rules set by legislation; and veterans who are eligible but not enrolled in VHA care. Notably, between 2005 and 2016, the number of veterans not enrolled in VHA care rose more quickly than did the number of veterans enrolled in VHA care.^5,6 Thus, to impact the high veteran suicide rates, an emergent challenge for VHA is to prevent suicide among unenrolled veterans and veterans receiving community care, while continuing to increase access to mental health services for veterans enrolled in VHA health care.

In response to the high rates of veteran suicide deaths, the US Department of Veterans Affairs (VA) has developed a broad, multicomponent suicide prevention program that is unparalleled in private US health care systems.^4,7 Suicide prevention efforts are led and implemented by both the VHA National Center for Patient Safety and the VHA Office of Mental Health and Suicide Prevention. Program components are numerous and multifaceted, falling within the broad promotion and prevention strategies outlined by the National Academy of Medicine (NAM).^1,8-11 The NAM continuum of prevention model encompassing multiple strategies is also referred to as the Universal, Selective, Indicated (USI) Model.^7,8,10 The VHA suicide prevention program contains a wide spread of program components, making it both comprehensive and innovative (Table 1).

Although significant momentum and progress has been made within the VHA, policy set by legislation has historically limited access to VHA health care services to VHA-eligible veterans. This is particularly concerning given the rising suicide rates among veterans not engaged in VHA care.² Adding to this complexity, recent legislation has increased veterans’ access to non-VHA health care, in addition to their existing access through Medicare, Medicaid, and other health care programs.^12-14 Best practices for suicide prevention are not often implemented in the private sector; thus, these systems are ill prepared to adequately meet the suicide prevention care needs of veterans.^4,15-18 Furthermore, VHA and non-VHA services generally are not well coordinated, and private sector health care providers (HCPs) are not required to complete a commensurate level of suicide prevention training as are VHA HCPs.^16-18 Most non-VHA HCPs do not receive military cultural competence training.¹⁹ These issues create a significant gap in suicide prevention services and may contribute to the increases in suicide rates in veterans who do not receive VHA care. Thus, changes in policy to increase access through private sector care may have paradoxical effects on veteran suicide deaths. To impact the veteran suicide rate, VHA must develop and disseminate best practices for veterans who use non-VHA services.

A Roadmap to Suicide Prevention

There is significant momentum at the federal level regarding this issue. The President’s Roadmap to Empower Veterans and End the National Tragedy of Suicide (Executive Order 13,861) directs the VHA to work closely with community organizations to improve veteran suicide prevention.²⁰ The VHA and partners, such as the Substance Abuse and Mental Health Services Administration (SAMHSA), are bridging this gap with collaborative efforts that increase suicide prevention resources for veterans living in the community through programs such as the Governor’s Challenges to Prevent Suicide Among Service Members, Veterans, and their Families. These programs intend to empower communities to develop statewide, strategic action plans to prevent veteran suicide.^7,21-24

In addition to partnerships, VHA has built other aspects of outreach and intervention into its programming. A key VHA initiative is to “know all veterans” by committing to identifying and reaching out to all veterans who may be at risk for suicide.²² The VHA has committed to offering “emergency stabilization care for former service members who present at the facility with an emergent mental health need” regardless of eligibility.²⁵ The intent is to provide temporary emergent mental health care to veterans who are otherwise ineligible for care, such as those who were discharged under other-than-honorable conditions while the VHA determines eligibility status.²⁶ However, veterans must meet certain criteria, and there is a limit on services.

Although services are being expanded to reach veterans who do not access VHA health care, how to best implement these new directives with regard to suicide prevention is unclear. Strategic development and innovations to expand suicide prevention care to veterans outside the current reach of VHA are desperately needed.

Program Overview 

VHA Patient Safety Center of Inquiry-Suicide Prevention Collaborative (PSCI-SPC), funded by the VHA National Center for Patient Safety, aims to help fill the gap in community-based suicide prevention for veterans. PSCI-SPC is located within the VHA Rocky Mountain Mental Illness Research, Education, and Clinical Center in Aurora, Colorado. The overarching mission of PSCI-SPC is to develop, implement, and evaluate practical solutions to reduce suicide among veterans not receiving VHA care. PSCI-SPC serves as a national clinical innovation and dissemination center for best practices in suicide prevention for organizations that serve veterans who receive care in the community. PSCI-SPC creates products to support dissemination of these practices to other VAMCs and works to ensure these programs are sustainable. PSCI-SPC focuses on 3 primary objectives. All PSCI-SPC projects are currently underway.

Objective 1: Growing a Community Learning Collaborative

Acknowledging that nearly two-thirds of veterans who die by suicide do not use VHA services, PSCI-SPC aims to reduce suicide among all veterans by expanding the reach of best practices for suicide prevention to veterans who receive myriad services in the community.²⁷ Community organizations are defined here as organizations that may in some way serve, interact with, or work with veterans, and/or employ veterans. Examples include non-VHA health care systems, public services such as police and fire departments, nonprofit organizations, mental health clinics, and veterans’ courts. As veterans increasingly seek health care and other services within their communities, the success of suicide prevention will be influenced by the capability of non-VHA public and private organizations. Objective 1, therefore, seeks to develop a VHA-community collaborative that can be leveraged to improve systems of suicide prevention.

Current programs in the VHA have focused on implementation of suicide prevention awareness and prevention education campaigns instead of grassroots partnerships that are intended to be sustainable. Additionally, these programs typically lack the capacity and systems to sustain numerous meaningful community partnerships. Traditionally, community organizations have been hesitant to partner with government agencies, such as the VHA, due to histories of institutional mistrust and bureaucracy.²⁸

The PSCI-SPC model for developing a VHA-community collaborative partnership draws from the tradition of community-based participatory research. The best community-based participatory research practices are to build on strengths and resources within the local community; develop collaborative, equitable partnerships that involve an empowering and power-sharing process; foster colearning, heuristics, and capacity building among partners; and focus on systems development using an iterative process. These practices also are consistent with the literature on learning collaboratives.^29-31

The premise for a learning collaborative is to bridge the gap between knowledge and practice in health care.³¹ Figure 1 depicts how this collaborative was developed, and how it supports Objectives 2 and 3. To achieve Objective 1, we developed a VHA-learning collaborative of 13 influential community partners in the Denver and Colorado Springs region of Colorado. The VHA team consists of a learning collaborative leader, a program manager, and a program support assistant. The principal investigator attends and contributes to all meetings. Learning collaborative partners include a university psychology clinic that focuses on veterans’ care, 3 veterans service organizations, a mental health private practice, a university school of nursing, a community mental health center, veterans’ courts, and 5 city departments.

Objective 2: Implementation Toolkit

The second PSCI-SPC objective is to develop a toolkit for the implementation of best practices within a VHA-community suicide prevention learning collaborative. Lessons from the development of a successful suicide prevention learning collaborative will be shared through an online guide that other VHA facilities can use to support similar collaborative efforts within their communities. The toolkit will be disseminated across the VHA to assist suicide prevention coordinators and other staff in developing a suicide prevention learning collaborative at their facilities.

PSCI-SPC uses the Zero Suicide framework and the VA/US Department of Defense (DoD) Clinical Practice Guideline for the Assessment and Management of Patients at Risk for Suicide as models for preventing suicide in veterans not enrolled in VHA care.^11,32 This implementation toolkit focuses on how to implement suicide prevention best practices into organizations that serve veterans. This toolkit differs from clinical practice guidelines in that it focuses on implementation strategies to promote success and effectively address challenges.

In order to provide a menu of available options for the learning collaborative and resulting toolkit, PSCI-SPC uses a logic model to compare the components of the VHA suicide prevention program, as well as other similar veteran and military suicide prevention programs.^{7,12,14,21,33,34} These programs are categorized into 2 types of prevention frameworks, the USI model as described above, and the SAMHSA Strategic Prevention Framework (Table 2).³⁵ The SAMHSA framework was designed to promote mental health and prevent substance abuse, yet the derived classification is also applicable to suicide prevention programs.³⁵ The results of the logic model comparison form the basis of the best practice interventions for the learning collaborative and initial toolkit. In addition to the best practice interventions, the toolkit consists of documents describing how to develop a veteran suicide prevention learning collaborative, as well as tools for learning collaborative members. Current tool development includes workbooks to guide collaborative members through the implementation process, guides for community organizations in implementing suicide prevention screening and risk assessment, a standard operating procedure for suicide prevention in a veterans court, and peer support training for veteran suicide prevention.

Objective 3: High-Risk Veterans Not Receiving VHA Care

Although veterans not receiving VHA care account for a number of veteran deaths by suicide, we are not aware of any current VHA programs that provide temporary psychotherapy and intensive case management to at-risk veterans ineligible for VHA care who are in need of immediate care while an appropriate permanent community placement is identified. In the current system, veterans in the community can present to VHA suicide prevention services through several different systems, including referrals to VHA and the Veterans Crisis Line (VCL). However, a portion of VCL calls are from veterans whose VHA eligibility is unknown or who are ineligible for services. If veterans are at imminent risk for suicide, emergency care is coordinated for them. However, if veterans are not at imminent suicide risk they are referred to the local suicide prevention coordinator and instructed to independently work toward determining their VHA eligibility.

It is currently unknown how many veterans follow through with these instructions. Nonetheless, if veterans are deemed eligible, they may present to VHA to obtain a same-day appointment. If not eligible, a suicide prevention coordinator may give them the phone number of a community referral. However, this practice is not standardized across VA medical centers, and the provided resources are up to the suicide prevention coordinator to research. Additionally, when a VHA suicide prevention coordinator leaves the position, knowledge of these community resources and rapport with community HCPs are often lost, leaving the next coordinator to develop these again, which reduces the efficiency and effectiveness of limited resources. It is also unknown how many veterans complete this contact and receive evidence-based treatment following referral. This is a complex system to navigate, particularly when at risk for suicide and in need of immediate but not emergency services.

Suicide prevention in such circumstances may be improved by adapting current suicide prevention practices, including evidence-based interventions, and the new VHA intensive case management program,^11,36 within a Zero Suicide framework. PSCI-SPC has developed a brief intervention to transition ineligible veterans to permanent community treatment and provide them with additional resources to meet their varied needs. The brief 1 to 3 session intervention combines practices from brief cognitive behavioral therapy (BCBT) for suicide prevention, crisis response planning (CRP), and intensive case management within a Zero Suicide framework. Both the 2019 VA/DoD suicide prevention clinical practice guidelines and Zero Suicide recommend using cognitive behavioral therapy (CBT)-based interventions for suicide prevention.^11,32 These interventions are packaged into a single intervention delivered by a PSCI-SPC therapist, typically a licensed clinical social worker, a licensed clinical psychologist, or an unlicensed psychologist under the supervision of a licensed clinical psychologist.

BCBT is one type of CBT that has shown initial efficacy in reducing suicide attempts.³⁷ BCBT reduces the risk for suicide attempts both at the conclusion of treatment and at 24-month follow-up.³⁷ BCBT is boiled down to its most essential components so it can be delivered in a distilled format. An essential element of BCBT that will remain is the CRP. A CRP^11,37,38 entails collaboratively identifying effective, appropriate coping strategies and specific individuals to contact during a crisis. CRPs demonstrated efficacy as a stand-alone intervention to existing suicide prevention methods in a randomized clinical trial, such that individuals who received CRP had faster reductions in suicidal ideation and were 76% less likely to make a suicide attempt during the 6-month follow-up period.³⁹ These results demonstrate that use of a CRP is connected to a decrease in suicidal behavior among suicidal patients.

The VHA has developed and is piloting a new initiative focused on restructuring its intensive case management services. RACETIME to Integrated Care (eg, Risk stratification, Assessment of complexity, Coordinator of lead assignment, Evaluate whole health needs, Trusting partnerships, Integrate care, Monitor progress, Experience of the veteran and employee) is a framework that assists VHA case managers in transitioning from a traditional case management mind-set to a more integrated and holistic method of care.³⁶ RACETIME intensive case management practices will be incorporated into the intervention. However, RACETIME focuses on case management internally to the VHA. A modification for this treatment will be to focus on intensive case management from a mental health perspective and connecting to external community resources. Community referrals are mapped within a structured process and stored on a shared drive. This improves continuity between suicide prevention coordinators when they leave for a new position.

This intervention is conducted within a Zero Suicide framework. Pertinent to PSCI-SPC innovation to enhance care for non-VHA veterans is the care transitions element within the Zero Suicide framework, which has developed comprehensive suicide prevention guidance, including a pathway to care.³² This pathway refers a process to conduct follow-up supportive contacts that are tracked and recorded.

The PSCI-SPC pilot program incorporates the elements of CRP and brief CBT within a Zero Suicide framework. The PSCI-SPC team is developing and testing a protocol for providing brief treatment and community referrals to ineligible veterans that integrates these programming elements (Figure 2). A PSCI-SPC social worker will coordinate with the eligibility office to determine VHA eligibility. Ineligible veterans are referred to community partners and nonenrolled, eligible veterans are linked to VHA HCPs if they desire. These transitions will be coordinated, closely monitored, and verified. The PSCI-SPC team receives referrals from the VCL and other VHA programs that are in contact with ineligible veterans. Other program eligibility criteria include meeting 1 of 3 criteria: (1) a lifetime suicide attempt; (2) suicidal ideation in the past 6 months; or (3) a current mental health disorder. At the outset of the program, it is explained that the purpose of the intervention is to provide short-term, transitional services to assist the veteran in attaining a permanent mental health placement.

Discussion

Improving suicide prevention for veterans who receive non-VHA health care is essential to significantly reduce veteran suicide rates. For the past decade, VHA suicide prevention initiatives have largely focused on veterans eligible for care, although the fastest increase in veteran suicide rates has occurred among veterans not connected to VHA services. Currently, if a veteran is deemed ineligible for care, it is up to the veteran to find other health care services in his or her community. There is not always a clear next step for the veteran to take, nor clear guidance provided to the VHA registration staff to assist with this care transition. This is particularly concerning for veterans at high risk for suicide as this could further thwart the veteran’s sense of belongingness and increase perceived burdensomeness, both suicide risk factors, and discourage them from attaining help.⁴⁰ Overall, while the VHA has successfully implemented diverse suicide prevention initiatives and services, the need for continued system improvement focused on non-VHA veterans remains. PSCI-SPC was developed for this purpose.

By creating a collaborative that will connect VHA and community organizations, there will be better utilization of resources and more appropriate referrals throughout systems that interact with veterans. Sharing suicide prevention best practices between VHA and community partners is expected to increase access to mental health treatment to all veterans. Finally, by allowing best practices for suicide prevention in the VHA to serve as a guide in the development of best practices for suicide prevention between the VHA and the local health and behavioral health care community, PSCI-SPC will create a new suicide prevention intervention for veterans with mental health needs. Through these initiatives, PSCI-SPC will support providers’ and concerned citizens’ efforts to ensure that fewer veterans fall through the cracks of disjointed systems and will promote healthier communities where, regardless of VHA enrollment status, veterans receive suicide prevention care.

Conclusions

PSCI-SPC is a novel center for the innovation and dissemination of the nation’s best practices in suicide prevention for veterans who are ineligible for or otherwise not engaged in VHA services and who turn to their community for health care. PSCI-SPC not only seeks to create, develop, and measure various solutions to reduce suicide among veterans who receive non-VHA care, but also seeks to facilitate the overall quality of existing practices for suicide prevention and care coordination for enrolled veterans who use community resources. By bridging the gap between the VHA, civilian health care systems, and other community partners striving to prevent veteran suicides, we can create better access to care and a more seamless path of communication among these important entities that impact the lives of our veterans daily

Since 2008, suicide has ranked as the tenth leading cause of death for all ages in the US, with rates of suicide continuing to rise.^1-3 Suicide is even more urgent to address in veteran populations. The age- and sex-adjusted suicide rate in 2017 was more than 1.5 times greater for veterans than it was for nonveteran adults.² Of importance, rates of suicide are increasing at a faster rate in veterans who are not connected to Veterans Health Administration (VHA) care.^4,5 These at-risk veterans include individuals who are eligible for VHA care yet have not had a VHA appointment within the year before death; veterans who may be ineligible to receive VHA care due to complex rules set by legislation; and veterans who are eligible but not enrolled in VHA care. Notably, between 2005 and 2016, the number of veterans not enrolled in VHA care rose more quickly than did the number of veterans enrolled in VHA care.^5,6 Thus, to impact the high veteran suicide rates, an emergent challenge for VHA is to prevent suicide among unenrolled veterans and veterans receiving community care, while continuing to increase access to mental health services for veterans enrolled in VHA health care.

In response to the high rates of veteran suicide deaths, the US Department of Veterans Affairs (VA) has developed a broad, multicomponent suicide prevention program that is unparalleled in private US health care systems.^4,7 Suicide prevention efforts are led and implemented by both the VHA National Center for Patient Safety and the VHA Office of Mental Health and Suicide Prevention. Program components are numerous and multifaceted, falling within the broad promotion and prevention strategies outlined by the National Academy of Medicine (NAM).^1,8-11 The NAM continuum of prevention model encompassing multiple strategies is also referred to as the Universal, Selective, Indicated (USI) Model.^7,8,10 The VHA suicide prevention program contains a wide spread of program components, making it both comprehensive and innovative (Table 1).

Although significant momentum and progress has been made within the VHA, policy set by legislation has historically limited access to VHA health care services to VHA-eligible veterans. This is particularly concerning given the rising suicide rates among veterans not engaged in VHA care.² Adding to this complexity, recent legislation has increased veterans’ access to non-VHA health care, in addition to their existing access through Medicare, Medicaid, and other health care programs.^12-14 Best practices for suicide prevention are not often implemented in the private sector; thus, these systems are ill prepared to adequately meet the suicide prevention care needs of veterans.^4,15-18 Furthermore, VHA and non-VHA services generally are not well coordinated, and private sector health care providers (HCPs) are not required to complete a commensurate level of suicide prevention training as are VHA HCPs.^16-18 Most non-VHA HCPs do not receive military cultural competence training.¹⁹ These issues create a significant gap in suicide prevention services and may contribute to the increases in suicide rates in veterans who do not receive VHA care. Thus, changes in policy to increase access through private sector care may have paradoxical effects on veteran suicide deaths. To impact the veteran suicide rate, VHA must develop and disseminate best practices for veterans who use non-VHA services.

A Roadmap to Suicide Prevention

There is significant momentum at the federal level regarding this issue. The President’s Roadmap to Empower Veterans and End the National Tragedy of Suicide (Executive Order 13,861) directs the VHA to work closely with community organizations to improve veteran suicide prevention.²⁰ The VHA and partners, such as the Substance Abuse and Mental Health Services Administration (SAMHSA), are bridging this gap with collaborative efforts that increase suicide prevention resources for veterans living in the community through programs such as the Governor’s Challenges to Prevent Suicide Among Service Members, Veterans, and their Families. These programs intend to empower communities to develop statewide, strategic action plans to prevent veteran suicide.^7,21-24

In addition to partnerships, VHA has built other aspects of outreach and intervention into its programming. A key VHA initiative is to “know all veterans” by committing to identifying and reaching out to all veterans who may be at risk for suicide.²² The VHA has committed to offering “emergency stabilization care for former service members who present at the facility with an emergent mental health need” regardless of eligibility.²⁵ The intent is to provide temporary emergent mental health care to veterans who are otherwise ineligible for care, such as those who were discharged under other-than-honorable conditions while the VHA determines eligibility status.²⁶ However, veterans must meet certain criteria, and there is a limit on services.

Although services are being expanded to reach veterans who do not access VHA health care, how to best implement these new directives with regard to suicide prevention is unclear. Strategic development and innovations to expand suicide prevention care to veterans outside the current reach of VHA are desperately needed.

Program Overview 

VHA Patient Safety Center of Inquiry-Suicide Prevention Collaborative (PSCI-SPC), funded by the VHA National Center for Patient Safety, aims to help fill the gap in community-based suicide prevention for veterans. PSCI-SPC is located within the VHA Rocky Mountain Mental Illness Research, Education, and Clinical Center in Aurora, Colorado. The overarching mission of PSCI-SPC is to develop, implement, and evaluate practical solutions to reduce suicide among veterans not receiving VHA care. PSCI-SPC serves as a national clinical innovation and dissemination center for best practices in suicide prevention for organizations that serve veterans who receive care in the community. PSCI-SPC creates products to support dissemination of these practices to other VAMCs and works to ensure these programs are sustainable. PSCI-SPC focuses on 3 primary objectives. All PSCI-SPC projects are currently underway.

Objective 1: Growing a Community Learning Collaborative

Acknowledging that nearly two-thirds of veterans who die by suicide do not use VHA services, PSCI-SPC aims to reduce suicide among all veterans by expanding the reach of best practices for suicide prevention to veterans who receive myriad services in the community.²⁷ Community organizations are defined here as organizations that may in some way serve, interact with, or work with veterans, and/or employ veterans. Examples include non-VHA health care systems, public services such as police and fire departments, nonprofit organizations, mental health clinics, and veterans’ courts. As veterans increasingly seek health care and other services within their communities, the success of suicide prevention will be influenced by the capability of non-VHA public and private organizations. Objective 1, therefore, seeks to develop a VHA-community collaborative that can be leveraged to improve systems of suicide prevention.

Current programs in the VHA have focused on implementation of suicide prevention awareness and prevention education campaigns instead of grassroots partnerships that are intended to be sustainable. Additionally, these programs typically lack the capacity and systems to sustain numerous meaningful community partnerships. Traditionally, community organizations have been hesitant to partner with government agencies, such as the VHA, due to histories of institutional mistrust and bureaucracy.²⁸

The PSCI-SPC model for developing a VHA-community collaborative partnership draws from the tradition of community-based participatory research. The best community-based participatory research practices are to build on strengths and resources within the local community; develop collaborative, equitable partnerships that involve an empowering and power-sharing process; foster colearning, heuristics, and capacity building among partners; and focus on systems development using an iterative process. These practices also are consistent with the literature on learning collaboratives.^29-31

The premise for a learning collaborative is to bridge the gap between knowledge and practice in health care.³¹ Figure 1 depicts how this collaborative was developed, and how it supports Objectives 2 and 3. To achieve Objective 1, we developed a VHA-learning collaborative of 13 influential community partners in the Denver and Colorado Springs region of Colorado. The VHA team consists of a learning collaborative leader, a program manager, and a program support assistant. The principal investigator attends and contributes to all meetings. Learning collaborative partners include a university psychology clinic that focuses on veterans’ care, 3 veterans service organizations, a mental health private practice, a university school of nursing, a community mental health center, veterans’ courts, and 5 city departments.

Objective 2: Implementation Toolkit

The second PSCI-SPC objective is to develop a toolkit for the implementation of best practices within a VHA-community suicide prevention learning collaborative. Lessons from the development of a successful suicide prevention learning collaborative will be shared through an online guide that other VHA facilities can use to support similar collaborative efforts within their communities. The toolkit will be disseminated across the VHA to assist suicide prevention coordinators and other staff in developing a suicide prevention learning collaborative at their facilities.

PSCI-SPC uses the Zero Suicide framework and the VA/US Department of Defense (DoD) Clinical Practice Guideline for the Assessment and Management of Patients at Risk for Suicide as models for preventing suicide in veterans not enrolled in VHA care.^11,32 This implementation toolkit focuses on how to implement suicide prevention best practices into organizations that serve veterans. This toolkit differs from clinical practice guidelines in that it focuses on implementation strategies to promote success and effectively address challenges.

In order to provide a menu of available options for the learning collaborative and resulting toolkit, PSCI-SPC uses a logic model to compare the components of the VHA suicide prevention program, as well as other similar veteran and military suicide prevention programs.^{7,12,14,21,33,34} These programs are categorized into 2 types of prevention frameworks, the USI model as described above, and the SAMHSA Strategic Prevention Framework (Table 2).³⁵ The SAMHSA framework was designed to promote mental health and prevent substance abuse, yet the derived classification is also applicable to suicide prevention programs.³⁵ The results of the logic model comparison form the basis of the best practice interventions for the learning collaborative and initial toolkit. In addition to the best practice interventions, the toolkit consists of documents describing how to develop a veteran suicide prevention learning collaborative, as well as tools for learning collaborative members. Current tool development includes workbooks to guide collaborative members through the implementation process, guides for community organizations in implementing suicide prevention screening and risk assessment, a standard operating procedure for suicide prevention in a veterans court, and peer support training for veteran suicide prevention.

Objective 3: High-Risk Veterans Not Receiving VHA Care

Although veterans not receiving VHA care account for a number of veteran deaths by suicide, we are not aware of any current VHA programs that provide temporary psychotherapy and intensive case management to at-risk veterans ineligible for VHA care who are in need of immediate care while an appropriate permanent community placement is identified. In the current system, veterans in the community can present to VHA suicide prevention services through several different systems, including referrals to VHA and the Veterans Crisis Line (VCL). However, a portion of VCL calls are from veterans whose VHA eligibility is unknown or who are ineligible for services. If veterans are at imminent risk for suicide, emergency care is coordinated for them. However, if veterans are not at imminent suicide risk they are referred to the local suicide prevention coordinator and instructed to independently work toward determining their VHA eligibility.

It is currently unknown how many veterans follow through with these instructions. Nonetheless, if veterans are deemed eligible, they may present to VHA to obtain a same-day appointment. If not eligible, a suicide prevention coordinator may give them the phone number of a community referral. However, this practice is not standardized across VA medical centers, and the provided resources are up to the suicide prevention coordinator to research. Additionally, when a VHA suicide prevention coordinator leaves the position, knowledge of these community resources and rapport with community HCPs are often lost, leaving the next coordinator to develop these again, which reduces the efficiency and effectiveness of limited resources. It is also unknown how many veterans complete this contact and receive evidence-based treatment following referral. This is a complex system to navigate, particularly when at risk for suicide and in need of immediate but not emergency services.

Suicide prevention in such circumstances may be improved by adapting current suicide prevention practices, including evidence-based interventions, and the new VHA intensive case management program,^11,36 within a Zero Suicide framework. PSCI-SPC has developed a brief intervention to transition ineligible veterans to permanent community treatment and provide them with additional resources to meet their varied needs. The brief 1 to 3 session intervention combines practices from brief cognitive behavioral therapy (BCBT) for suicide prevention, crisis response planning (CRP), and intensive case management within a Zero Suicide framework. Both the 2019 VA/DoD suicide prevention clinical practice guidelines and Zero Suicide recommend using cognitive behavioral therapy (CBT)-based interventions for suicide prevention.^11,32 These interventions are packaged into a single intervention delivered by a PSCI-SPC therapist, typically a licensed clinical social worker, a licensed clinical psychologist, or an unlicensed psychologist under the supervision of a licensed clinical psychologist.

BCBT is one type of CBT that has shown initial efficacy in reducing suicide attempts.³⁷ BCBT reduces the risk for suicide attempts both at the conclusion of treatment and at 24-month follow-up.³⁷ BCBT is boiled down to its most essential components so it can be delivered in a distilled format. An essential element of BCBT that will remain is the CRP. A CRP^11,37,38 entails collaboratively identifying effective, appropriate coping strategies and specific individuals to contact during a crisis. CRPs demonstrated efficacy as a stand-alone intervention to existing suicide prevention methods in a randomized clinical trial, such that individuals who received CRP had faster reductions in suicidal ideation and were 76% less likely to make a suicide attempt during the 6-month follow-up period.³⁹ These results demonstrate that use of a CRP is connected to a decrease in suicidal behavior among suicidal patients.

The VHA has developed and is piloting a new initiative focused on restructuring its intensive case management services. RACETIME to Integrated Care (eg, Risk stratification, Assessment of complexity, Coordinator of lead assignment, Evaluate whole health needs, Trusting partnerships, Integrate care, Monitor progress, Experience of the veteran and employee) is a framework that assists VHA case managers in transitioning from a traditional case management mind-set to a more integrated and holistic method of care.³⁶ RACETIME intensive case management practices will be incorporated into the intervention. However, RACETIME focuses on case management internally to the VHA. A modification for this treatment will be to focus on intensive case management from a mental health perspective and connecting to external community resources. Community referrals are mapped within a structured process and stored on a shared drive. This improves continuity between suicide prevention coordinators when they leave for a new position.

This intervention is conducted within a Zero Suicide framework. Pertinent to PSCI-SPC innovation to enhance care for non-VHA veterans is the care transitions element within the Zero Suicide framework, which has developed comprehensive suicide prevention guidance, including a pathway to care.³² This pathway refers a process to conduct follow-up supportive contacts that are tracked and recorded.

The PSCI-SPC pilot program incorporates the elements of CRP and brief CBT within a Zero Suicide framework. The PSCI-SPC team is developing and testing a protocol for providing brief treatment and community referrals to ineligible veterans that integrates these programming elements (Figure 2). A PSCI-SPC social worker will coordinate with the eligibility office to determine VHA eligibility. Ineligible veterans are referred to community partners and nonenrolled, eligible veterans are linked to VHA HCPs if they desire. These transitions will be coordinated, closely monitored, and verified. The PSCI-SPC team receives referrals from the VCL and other VHA programs that are in contact with ineligible veterans. Other program eligibility criteria include meeting 1 of 3 criteria: (1) a lifetime suicide attempt; (2) suicidal ideation in the past 6 months; or (3) a current mental health disorder. At the outset of the program, it is explained that the purpose of the intervention is to provide short-term, transitional services to assist the veteran in attaining a permanent mental health placement.

Discussion

Improving suicide prevention for veterans who receive non-VHA health care is essential to significantly reduce veteran suicide rates. For the past decade, VHA suicide prevention initiatives have largely focused on veterans eligible for care, although the fastest increase in veteran suicide rates has occurred among veterans not connected to VHA services. Currently, if a veteran is deemed ineligible for care, it is up to the veteran to find other health care services in his or her community. There is not always a clear next step for the veteran to take, nor clear guidance provided to the VHA registration staff to assist with this care transition. This is particularly concerning for veterans at high risk for suicide as this could further thwart the veteran’s sense of belongingness and increase perceived burdensomeness, both suicide risk factors, and discourage them from attaining help.⁴⁰ Overall, while the VHA has successfully implemented diverse suicide prevention initiatives and services, the need for continued system improvement focused on non-VHA veterans remains. PSCI-SPC was developed for this purpose.

By creating a collaborative that will connect VHA and community organizations, there will be better utilization of resources and more appropriate referrals throughout systems that interact with veterans. Sharing suicide prevention best practices between VHA and community partners is expected to increase access to mental health treatment to all veterans. Finally, by allowing best practices for suicide prevention in the VHA to serve as a guide in the development of best practices for suicide prevention between the VHA and the local health and behavioral health care community, PSCI-SPC will create a new suicide prevention intervention for veterans with mental health needs. Through these initiatives, PSCI-SPC will support providers’ and concerned citizens’ efforts to ensure that fewer veterans fall through the cracks of disjointed systems and will promote healthier communities where, regardless of VHA enrollment status, veterans receive suicide prevention care.

Conclusions

PSCI-SPC is a novel center for the innovation and dissemination of the nation’s best practices in suicide prevention for veterans who are ineligible for or otherwise not engaged in VHA services and who turn to their community for health care. PSCI-SPC not only seeks to create, develop, and measure various solutions to reduce suicide among veterans who receive non-VHA care, but also seeks to facilitate the overall quality of existing practices for suicide prevention and care coordination for enrolled veterans who use community resources. By bridging the gap between the VHA, civilian health care systems, and other community partners striving to prevent veteran suicides, we can create better access to care and a more seamless path of communication among these important entities that impact the lives of our veterans daily

Since 2008, suicide has ranked as the tenth leading cause of death for all ages in the US, with rates of suicide continuing to rise.^1-3 Suicide is even more urgent to address in veteran populations. The age- and sex-adjusted suicide rate in 2017 was more than 1.5 times greater for veterans than it was for nonveteran adults.² Of importance, rates of suicide are increasing at a faster rate in veterans who are not connected to Veterans Health Administration (VHA) care.^4,5 These at-risk veterans include individuals who are eligible for VHA care yet have not had a VHA appointment within the year before death; veterans who may be ineligible to receive VHA care due to complex rules set by legislation; and veterans who are eligible but not enrolled in VHA care. Notably, between 2005 and 2016, the number of veterans not enrolled in VHA care rose more quickly than did the number of veterans enrolled in VHA care.^5,6 Thus, to impact the high veteran suicide rates, an emergent challenge for VHA is to prevent suicide among unenrolled veterans and veterans receiving community care, while continuing to increase access to mental health services for veterans enrolled in VHA health care.

In response to the high rates of veteran suicide deaths, the US Department of Veterans Affairs (VA) has developed a broad, multicomponent suicide prevention program that is unparalleled in private US health care systems.^4,7 Suicide prevention efforts are led and implemented by both the VHA National Center for Patient Safety and the VHA Office of Mental Health and Suicide Prevention. Program components are numerous and multifaceted, falling within the broad promotion and prevention strategies outlined by the National Academy of Medicine (NAM).^1,8-11 The NAM continuum of prevention model encompassing multiple strategies is also referred to as the Universal, Selective, Indicated (USI) Model.^7,8,10 The VHA suicide prevention program contains a wide spread of program components, making it both comprehensive and innovative (Table 1).

Although significant momentum and progress has been made within the VHA, policy set by legislation has historically limited access to VHA health care services to VHA-eligible veterans. This is particularly concerning given the rising suicide rates among veterans not engaged in VHA care.² Adding to this complexity, recent legislation has increased veterans’ access to non-VHA health care, in addition to their existing access through Medicare, Medicaid, and other health care programs.^12-14 Best practices for suicide prevention are not often implemented in the private sector; thus, these systems are ill prepared to adequately meet the suicide prevention care needs of veterans.^4,15-18 Furthermore, VHA and non-VHA services generally are not well coordinated, and private sector health care providers (HCPs) are not required to complete a commensurate level of suicide prevention training as are VHA HCPs.^16-18 Most non-VHA HCPs do not receive military cultural competence training.¹⁹ These issues create a significant gap in suicide prevention services and may contribute to the increases in suicide rates in veterans who do not receive VHA care. Thus, changes in policy to increase access through private sector care may have paradoxical effects on veteran suicide deaths. To impact the veteran suicide rate, VHA must develop and disseminate best practices for veterans who use non-VHA services.

A Roadmap to Suicide Prevention

There is significant momentum at the federal level regarding this issue. The President’s Roadmap to Empower Veterans and End the National Tragedy of Suicide (Executive Order 13,861) directs the VHA to work closely with community organizations to improve veteran suicide prevention.²⁰ The VHA and partners, such as the Substance Abuse and Mental Health Services Administration (SAMHSA), are bridging this gap with collaborative efforts that increase suicide prevention resources for veterans living in the community through programs such as the Governor’s Challenges to Prevent Suicide Among Service Members, Veterans, and their Families. These programs intend to empower communities to develop statewide, strategic action plans to prevent veteran suicide.^7,21-24

In addition to partnerships, VHA has built other aspects of outreach and intervention into its programming. A key VHA initiative is to “know all veterans” by committing to identifying and reaching out to all veterans who may be at risk for suicide.²² The VHA has committed to offering “emergency stabilization care for former service members who present at the facility with an emergent mental health need” regardless of eligibility.²⁵ The intent is to provide temporary emergent mental health care to veterans who are otherwise ineligible for care, such as those who were discharged under other-than-honorable conditions while the VHA determines eligibility status.²⁶ However, veterans must meet certain criteria, and there is a limit on services.

Although services are being expanded to reach veterans who do not access VHA health care, how to best implement these new directives with regard to suicide prevention is unclear. Strategic development and innovations to expand suicide prevention care to veterans outside the current reach of VHA are desperately needed.

Program Overview 

VHA Patient Safety Center of Inquiry-Suicide Prevention Collaborative (PSCI-SPC), funded by the VHA National Center for Patient Safety, aims to help fill the gap in community-based suicide prevention for veterans. PSCI-SPC is located within the VHA Rocky Mountain Mental Illness Research, Education, and Clinical Center in Aurora, Colorado. The overarching mission of PSCI-SPC is to develop, implement, and evaluate practical solutions to reduce suicide among veterans not receiving VHA care. PSCI-SPC serves as a national clinical innovation and dissemination center for best practices in suicide prevention for organizations that serve veterans who receive care in the community. PSCI-SPC creates products to support dissemination of these practices to other VAMCs and works to ensure these programs are sustainable. PSCI-SPC focuses on 3 primary objectives. All PSCI-SPC projects are currently underway.

Objective 1: Growing a Community Learning Collaborative

Acknowledging that nearly two-thirds of veterans who die by suicide do not use VHA services, PSCI-SPC aims to reduce suicide among all veterans by expanding the reach of best practices for suicide prevention to veterans who receive myriad services in the community.²⁷ Community organizations are defined here as organizations that may in some way serve, interact with, or work with veterans, and/or employ veterans. Examples include non-VHA health care systems, public services such as police and fire departments, nonprofit organizations, mental health clinics, and veterans’ courts. As veterans increasingly seek health care and other services within their communities, the success of suicide prevention will be influenced by the capability of non-VHA public and private organizations. Objective 1, therefore, seeks to develop a VHA-community collaborative that can be leveraged to improve systems of suicide prevention.

Current programs in the VHA have focused on implementation of suicide prevention awareness and prevention education campaigns instead of grassroots partnerships that are intended to be sustainable. Additionally, these programs typically lack the capacity and systems to sustain numerous meaningful community partnerships. Traditionally, community organizations have been hesitant to partner with government agencies, such as the VHA, due to histories of institutional mistrust and bureaucracy.²⁸

The PSCI-SPC model for developing a VHA-community collaborative partnership draws from the tradition of community-based participatory research. The best community-based participatory research practices are to build on strengths and resources within the local community; develop collaborative, equitable partnerships that involve an empowering and power-sharing process; foster colearning, heuristics, and capacity building among partners; and focus on systems development using an iterative process. These practices also are consistent with the literature on learning collaboratives.^29-31

The premise for a learning collaborative is to bridge the gap between knowledge and practice in health care.³¹ Figure 1 depicts how this collaborative was developed, and how it supports Objectives 2 and 3. To achieve Objective 1, we developed a VHA-learning collaborative of 13 influential community partners in the Denver and Colorado Springs region of Colorado. The VHA team consists of a learning collaborative leader, a program manager, and a program support assistant. The principal investigator attends and contributes to all meetings. Learning collaborative partners include a university psychology clinic that focuses on veterans’ care, 3 veterans service organizations, a mental health private practice, a university school of nursing, a community mental health center, veterans’ courts, and 5 city departments.

Objective 2: Implementation Toolkit

The second PSCI-SPC objective is to develop a toolkit for the implementation of best practices within a VHA-community suicide prevention learning collaborative. Lessons from the development of a successful suicide prevention learning collaborative will be shared through an online guide that other VHA facilities can use to support similar collaborative efforts within their communities. The toolkit will be disseminated across the VHA to assist suicide prevention coordinators and other staff in developing a suicide prevention learning collaborative at their facilities.

PSCI-SPC uses the Zero Suicide framework and the VA/US Department of Defense (DoD) Clinical Practice Guideline for the Assessment and Management of Patients at Risk for Suicide as models for preventing suicide in veterans not enrolled in VHA care.^11,32 This implementation toolkit focuses on how to implement suicide prevention best practices into organizations that serve veterans. This toolkit differs from clinical practice guidelines in that it focuses on implementation strategies to promote success and effectively address challenges.

In order to provide a menu of available options for the learning collaborative and resulting toolkit, PSCI-SPC uses a logic model to compare the components of the VHA suicide prevention program, as well as other similar veteran and military suicide prevention programs.^{7,12,14,21,33,34} These programs are categorized into 2 types of prevention frameworks, the USI model as described above, and the SAMHSA Strategic Prevention Framework (Table 2).³⁵ The SAMHSA framework was designed to promote mental health and prevent substance abuse, yet the derived classification is also applicable to suicide prevention programs.³⁵ The results of the logic model comparison form the basis of the best practice interventions for the learning collaborative and initial toolkit. In addition to the best practice interventions, the toolkit consists of documents describing how to develop a veteran suicide prevention learning collaborative, as well as tools for learning collaborative members. Current tool development includes workbooks to guide collaborative members through the implementation process, guides for community organizations in implementing suicide prevention screening and risk assessment, a standard operating procedure for suicide prevention in a veterans court, and peer support training for veteran suicide prevention.

Objective 3: High-Risk Veterans Not Receiving VHA Care

Although veterans not receiving VHA care account for a number of veteran deaths by suicide, we are not aware of any current VHA programs that provide temporary psychotherapy and intensive case management to at-risk veterans ineligible for VHA care who are in need of immediate care while an appropriate permanent community placement is identified. In the current system, veterans in the community can present to VHA suicide prevention services through several different systems, including referrals to VHA and the Veterans Crisis Line (VCL). However, a portion of VCL calls are from veterans whose VHA eligibility is unknown or who are ineligible for services. If veterans are at imminent risk for suicide, emergency care is coordinated for them. However, if veterans are not at imminent suicide risk they are referred to the local suicide prevention coordinator and instructed to independently work toward determining their VHA eligibility.

It is currently unknown how many veterans follow through with these instructions. Nonetheless, if veterans are deemed eligible, they may present to VHA to obtain a same-day appointment. If not eligible, a suicide prevention coordinator may give them the phone number of a community referral. However, this practice is not standardized across VA medical centers, and the provided resources are up to the suicide prevention coordinator to research. Additionally, when a VHA suicide prevention coordinator leaves the position, knowledge of these community resources and rapport with community HCPs are often lost, leaving the next coordinator to develop these again, which reduces the efficiency and effectiveness of limited resources. It is also unknown how many veterans complete this contact and receive evidence-based treatment following referral. This is a complex system to navigate, particularly when at risk for suicide and in need of immediate but not emergency services.

Suicide prevention in such circumstances may be improved by adapting current suicide prevention practices, including evidence-based interventions, and the new VHA intensive case management program,^11,36 within a Zero Suicide framework. PSCI-SPC has developed a brief intervention to transition ineligible veterans to permanent community treatment and provide them with additional resources to meet their varied needs. The brief 1 to 3 session intervention combines practices from brief cognitive behavioral therapy (BCBT) for suicide prevention, crisis response planning (CRP), and intensive case management within a Zero Suicide framework. Both the 2019 VA/DoD suicide prevention clinical practice guidelines and Zero Suicide recommend using cognitive behavioral therapy (CBT)-based interventions for suicide prevention.^11,32 These interventions are packaged into a single intervention delivered by a PSCI-SPC therapist, typically a licensed clinical social worker, a licensed clinical psychologist, or an unlicensed psychologist under the supervision of a licensed clinical psychologist.

BCBT is one type of CBT that has shown initial efficacy in reducing suicide attempts.³⁷ BCBT reduces the risk for suicide attempts both at the conclusion of treatment and at 24-month follow-up.³⁷ BCBT is boiled down to its most essential components so it can be delivered in a distilled format. An essential element of BCBT that will remain is the CRP. A CRP^11,37,38 entails collaboratively identifying effective, appropriate coping strategies and specific individuals to contact during a crisis. CRPs demonstrated efficacy as a stand-alone intervention to existing suicide prevention methods in a randomized clinical trial, such that individuals who received CRP had faster reductions in suicidal ideation and were 76% less likely to make a suicide attempt during the 6-month follow-up period.³⁹ These results demonstrate that use of a CRP is connected to a decrease in suicidal behavior among suicidal patients.

The VHA has developed and is piloting a new initiative focused on restructuring its intensive case management services. RACETIME to Integrated Care (eg, Risk stratification, Assessment of complexity, Coordinator of lead assignment, Evaluate whole health needs, Trusting partnerships, Integrate care, Monitor progress, Experience of the veteran and employee) is a framework that assists VHA case managers in transitioning from a traditional case management mind-set to a more integrated and holistic method of care.³⁶ RACETIME intensive case management practices will be incorporated into the intervention. However, RACETIME focuses on case management internally to the VHA. A modification for this treatment will be to focus on intensive case management from a mental health perspective and connecting to external community resources. Community referrals are mapped within a structured process and stored on a shared drive. This improves continuity between suicide prevention coordinators when they leave for a new position.

This intervention is conducted within a Zero Suicide framework. Pertinent to PSCI-SPC innovation to enhance care for non-VHA veterans is the care transitions element within the Zero Suicide framework, which has developed comprehensive suicide prevention guidance, including a pathway to care.³² This pathway refers a process to conduct follow-up supportive contacts that are tracked and recorded.

The PSCI-SPC pilot program incorporates the elements of CRP and brief CBT within a Zero Suicide framework. The PSCI-SPC team is developing and testing a protocol for providing brief treatment and community referrals to ineligible veterans that integrates these programming elements (Figure 2). A PSCI-SPC social worker will coordinate with the eligibility office to determine VHA eligibility. Ineligible veterans are referred to community partners and nonenrolled, eligible veterans are linked to VHA HCPs if they desire. These transitions will be coordinated, closely monitored, and verified. The PSCI-SPC team receives referrals from the VCL and other VHA programs that are in contact with ineligible veterans. Other program eligibility criteria include meeting 1 of 3 criteria: (1) a lifetime suicide attempt; (2) suicidal ideation in the past 6 months; or (3) a current mental health disorder. At the outset of the program, it is explained that the purpose of the intervention is to provide short-term, transitional services to assist the veteran in attaining a permanent mental health placement.

Discussion

Improving suicide prevention for veterans who receive non-VHA health care is essential to significantly reduce veteran suicide rates. For the past decade, VHA suicide prevention initiatives have largely focused on veterans eligible for care, although the fastest increase in veteran suicide rates has occurred among veterans not connected to VHA services. Currently, if a veteran is deemed ineligible for care, it is up to the veteran to find other health care services in his or her community. There is not always a clear next step for the veteran to take, nor clear guidance provided to the VHA registration staff to assist with this care transition. This is particularly concerning for veterans at high risk for suicide as this could further thwart the veteran’s sense of belongingness and increase perceived burdensomeness, both suicide risk factors, and discourage them from attaining help.⁴⁰ Overall, while the VHA has successfully implemented diverse suicide prevention initiatives and services, the need for continued system improvement focused on non-VHA veterans remains. PSCI-SPC was developed for this purpose.

By creating a collaborative that will connect VHA and community organizations, there will be better utilization of resources and more appropriate referrals throughout systems that interact with veterans. Sharing suicide prevention best practices between VHA and community partners is expected to increase access to mental health treatment to all veterans. Finally, by allowing best practices for suicide prevention in the VHA to serve as a guide in the development of best practices for suicide prevention between the VHA and the local health and behavioral health care community, PSCI-SPC will create a new suicide prevention intervention for veterans with mental health needs. Through these initiatives, PSCI-SPC will support providers’ and concerned citizens’ efforts to ensure that fewer veterans fall through the cracks of disjointed systems and will promote healthier communities where, regardless of VHA enrollment status, veterans receive suicide prevention care.

Conclusions

PSCI-SPC is a novel center for the innovation and dissemination of the nation’s best practices in suicide prevention for veterans who are ineligible for or otherwise not engaged in VHA services and who turn to their community for health care. PSCI-SPC not only seeks to create, develop, and measure various solutions to reduce suicide among veterans who receive non-VHA care, but also seeks to facilitate the overall quality of existing practices for suicide prevention and care coordination for enrolled veterans who use community resources. By bridging the gap between the VHA, civilian health care systems, and other community partners striving to prevent veteran suicides, we can create better access to care and a more seamless path of communication among these important entities that impact the lives of our veterans daily

Atypical antipsychotic use may result in metabolic abnormalities, such as hyperglycemia, dyslipidemia, weight gain, and metabolic syndrome. These adverse effects (AEs) can cause progression to type 2 diabetes mellitus (T2DM) as well as increased risk of cardiovascular disease and cardiac mortality. Individuals diagnosed with T2DM have medical expenses that are about 2.3 times higher than individuals without diabetes.^1,2 The risk of experiencing metabolic abnormalities is likely elevated for patients who were antipsychotic-naïve prior to initiation.³

In response to an increased awareness of atypical antipsychotic-related AEs, the American Diabetes Association (ADA) and American Psychiatric Association (APA) released a consensus statement in 2004 with a metabolic monitoring protocol for patients initiating or changing to a new antipsychotic medication.⁴ Within the first year after initiation, the ADA/APA consensus statements recommends that clinicians acquire a personal and family history, weight, body mass index (BMI), waist circumference, blood pressure (BP), fasting plasma glucose, and fasting lipid profile at the initial patient visit. Patient weight is recommended to be collected at 4 weeks and again 8 weeks later. Twelve weeks after the initial visit, weight, BMI, BP, fasting plasma glucose and a fasting lipid profile are recommended to be collected and assessed for abnormalities. Weight is then recommended to be assessed every 3 months thereafter. Review of personal and family history, waist circumference, BP, and a fasting plasma glucose is recommended to occur annually. Finally, a fasting lipid profile is to be collected every 5 years.

Since the initial consensus statement release, metabolic monitoring of patients prescribed antipsychotic medications has been found to be inadequate within several large health care organizations.^5,6 Mittal and colleagues reviewed metabolic monitoring practices occurring in 32 facilities within the Veterans Health Administration (VHA) and found that monitoring practices in the first 90 days after antipsychotic initiation were largely nonadherent to the ADA/APA consensus statement recommendations.⁶ Medical staff in Veterans Integrated Service Network 21 (VISN 21) currently serve about 268,000 veterans actively receiving care across California, Nevada, and the Pacific Islands.To support veteran care in the fields of mental health and medication safety, the VISN 21 pharmacy benefits manager office created a clinical dashboard that identifies veterans who are currently prescribed an antipsychotic and have not completed at least 1 annual blood glucose test. While this dashboard is a valuable tool for tracking patient care for those who have been prescribed an antipsychotic > 1 year, it does not consider the ADA/APA recommendations for more frequent monitoring in the first year after initiation. A literature review found no citations of a systematic evaluation of adherence to ADA/APA monitoring recommendations or patient progression to T2DM in the first year after antipsychotic initiation for an antipsychotic-naïve veteran population. The goal of this quality improvement project is to assess VHA health care provider and patient adherence to the 2004 consensus statement recommendations within the first year after initiation for previously antipsychotic-naïve patients receiving an atypical antipsychotic and determine rate of progression to T2DM.

Methods

The project was reviewed by the University of Nevada-Reno Institutional Review Board and determined to be a nonresearch quality improvement project. This was a retrospective chart analysis that included patients receiving their first-ever atypical antipsychotic across 8 US Department of Veterans Affairs (VA) medical centers within VISN 21. Clinical patient data, including prescription, vital sign, and laboratory information, were extracted from the VA Corporate Data Warehouse using transact sequential query language.

Veterans were included in the final cohort if they met the following criteria: aged ≥ 18 years at antipsychotic initiation, initiated their first-ever atypical antipsychotic within the VHA between February 2014 and February 2019, continued the antipsychotic for ≥ 1 year, had a medication possession ratio (MPR) > 80%, and had previously established care within VHA as evidenced by having ≥ 1 primary care or outpatient mental health visit in the 6 months prior to initiation. The MPR is defined as the sum of the day’s supply of all dispensed medications in the project time frame divided by the total number of days in the project time frame.

Veterans were excluded if they initiated any other antipsychotic during the first course, had a prior diagnosis of T2DM, had any prior use of antidiabetic medications, or had a hemoglobin A_1c (HbA_1c) > 6.4 in the year prior to initiation.

The primary outcome was completion of all recommended metabolic monitoring time points in the first year after atypical antipsychotic initiation. The secondary outcome was incidence of T2DM as evidenced by either a HbA_1c > 6.4 or diagnosis of T2DM entered into the electronic health record. Baseline monitoring for BP, blood glucose, and lipids were considered complete if a data point was collected between 3 months prior and 1 month after atypical antipsychotic initiation. Baseline monitoring for weight was considered complete if a data point was collected between 3 months prior and 2 weeks after initiation. Follow-up monitoring for BP, blood glucose, and lipids were considered completed if a data point was collected at 3 and 12 months (mean, 1 month). Follow-up monitoring for weight was considered completed if collected at 1, 2, and 3 months (mean, 2 weeks) and at 6, 9, and 12 months (mean, 1 month). Waist circumference data and patient and family history are not collected as capturable data points. Therefore, the authors were unable to include these in the final data extraction.

Results

The final cohort consisted of 1,651 veterans who met the inclusion criteria. Overall, at antipsychotic initiation the cohort had a mean (SD) age of 55 (14.6) years, was largely male (88%), and was considered overweight with a mean (SD) BMI of 29.1 (6.4) (Table 1).

Appropriate BP monitoring was completed most often with 492 patients (30%) meeting ADA/APA recommendations followed by HbA_1c and/or blood glucose monitoring with 203 patients (12%) completing all time points. Recommended lipid monitoring was completed by 96 patients (6%). Weight monitoring was completed least often with 47 patients (3%) completing all recommended time points. Regarding completion of all metabolic monitoring time points, 3 (0.2%) patients in the final cohort were found to have completed all recommended monitoring. Ninety-nine patients (6%) were found to have progressed to T2DM as indicated by an HbA_1c > 6.4 and/or entry of a T2DM ninth or tenth edition International Statistical Classification of Diseases code into the chart (Table 2).

Discussion

No previous literature exists that reviews adherence to recommended metabolic monitoring guidance up to 1 year after antipsychotic initiation in a previously antipsychotic-naïve cohort within the VHA. Metabolic monitoring was overall incomplete with 0.2% of the cohort completing all recommended monitoring time points. Weight was the parameter that was least completed. Based on these findings, the authors concluded that efforts are needed to improve completion rates of atypical antipsychotic metabolic monitoring. In the final cohort, 6% of patients were noted to have progressed to T2DM in the first year after atypical antipsychotic initiation. The actual number of patients progressing to T2DM may be larger because not all received adequate blood glucose monitoring. For comparison, the Centers for Disease Control and Prevention released information in 2015 that stated that the US population has an annual T2DM incidence of about 1% for adults aged 45 to 64 years.⁷

We understand that individuals with mental health disorders are at increased risk of T2DM compared with that of the general population and hope that this comparison only serves to drive home the point that appropriate metabolic monitoring is vital for this subgroup. The strengths of this project include identification of an area for improvement and encouraging evidence-based monitoring. Utilization of clinical data is a cost-effective and efficient method to improve patient care.

Limitations

Limitations of this study include the data’s dependence on accuracy of entry by the end-user and a lack of available data regarding prescriptions dispensed outside of the VHA. Vital signs data may have been entered into patient notes and not documented in the vitals section of the current medical record causing the appearance of missing data. Access to VHA health services and patient adherence to follow-up appointments were not assessed in this project and could affect patient ability to complete follow-up. The final analysis included only patients who remained on 1 atypical antipsychotic for a year and were considered adherent with an MPR > 80% and did not consider less adherent patients. It is also possible that health care providers who closely monitor metabolic parameters after atypical antipsychotic initiation more frequently switch patients to an alternative atypical antipsychotic while others who monitor less also switch medications less frequently. This could lead to selection of patients with health care providers who are less adherent to metabolic monitoring recommendations.

Conclusions

As a result of this study, in VISN 21 several strategies will be implemented to improve monitoring. First, the results of this project will be shared with the subject matter experts of the VISN 21 Mental Health Task Force. This task force serves as a venue for clinicians to meet virtually, discuss clinical topics, as well as to create and distribute strategies to improve patient care. Clinicians at this forum will be encouraged to implement monitoring protocols into routine practice, share best practices with colleagues, and increase patient awareness about the importance of metabolic monitoring. Second, modifications may be applied to the electronic health record to guide metabolic monitoring order entry at the time of prescription entry, which includes development of clinical reminders and laboratory order sets. Third, the clinical data manager team may be leveraged to create an electronic report identifying patients currently receiving suboptimal monitoring in the first year after antipsychotic initiation. The patients identified in this report will be discussed at the recurring VISN 21 Mental Health Task Force meeting, and strong practices will be shared with the medical centers across VISN 21. Other strategies under consideration include requiring proof of metabolic monitoring completion prior to allowing further atypical antipsychotic refills and providing direct provider education regarding the ADA/APA metabolic monitoring recommendations via the academic detailing service in effort to standardize clinical care.

Atypical antipsychotic use may result in metabolic abnormalities, such as hyperglycemia, dyslipidemia, weight gain, and metabolic syndrome. These adverse effects (AEs) can cause progression to type 2 diabetes mellitus (T2DM) as well as increased risk of cardiovascular disease and cardiac mortality. Individuals diagnosed with T2DM have medical expenses that are about 2.3 times higher than individuals without diabetes.^1,2 The risk of experiencing metabolic abnormalities is likely elevated for patients who were antipsychotic-naïve prior to initiation.³

In response to an increased awareness of atypical antipsychotic-related AEs, the American Diabetes Association (ADA) and American Psychiatric Association (APA) released a consensus statement in 2004 with a metabolic monitoring protocol for patients initiating or changing to a new antipsychotic medication.⁴ Within the first year after initiation, the ADA/APA consensus statements recommends that clinicians acquire a personal and family history, weight, body mass index (BMI), waist circumference, blood pressure (BP), fasting plasma glucose, and fasting lipid profile at the initial patient visit. Patient weight is recommended to be collected at 4 weeks and again 8 weeks later. Twelve weeks after the initial visit, weight, BMI, BP, fasting plasma glucose and a fasting lipid profile are recommended to be collected and assessed for abnormalities. Weight is then recommended to be assessed every 3 months thereafter. Review of personal and family history, waist circumference, BP, and a fasting plasma glucose is recommended to occur annually. Finally, a fasting lipid profile is to be collected every 5 years.

Since the initial consensus statement release, metabolic monitoring of patients prescribed antipsychotic medications has been found to be inadequate within several large health care organizations.^5,6 Mittal and colleagues reviewed metabolic monitoring practices occurring in 32 facilities within the Veterans Health Administration (VHA) and found that monitoring practices in the first 90 days after antipsychotic initiation were largely nonadherent to the ADA/APA consensus statement recommendations.⁶ Medical staff in Veterans Integrated Service Network 21 (VISN 21) currently serve about 268,000 veterans actively receiving care across California, Nevada, and the Pacific Islands.To support veteran care in the fields of mental health and medication safety, the VISN 21 pharmacy benefits manager office created a clinical dashboard that identifies veterans who are currently prescribed an antipsychotic and have not completed at least 1 annual blood glucose test. While this dashboard is a valuable tool for tracking patient care for those who have been prescribed an antipsychotic > 1 year, it does not consider the ADA/APA recommendations for more frequent monitoring in the first year after initiation. A literature review found no citations of a systematic evaluation of adherence to ADA/APA monitoring recommendations or patient progression to T2DM in the first year after antipsychotic initiation for an antipsychotic-naïve veteran population. The goal of this quality improvement project is to assess VHA health care provider and patient adherence to the 2004 consensus statement recommendations within the first year after initiation for previously antipsychotic-naïve patients receiving an atypical antipsychotic and determine rate of progression to T2DM.

Methods

The project was reviewed by the University of Nevada-Reno Institutional Review Board and determined to be a nonresearch quality improvement project. This was a retrospective chart analysis that included patients receiving their first-ever atypical antipsychotic across 8 US Department of Veterans Affairs (VA) medical centers within VISN 21. Clinical patient data, including prescription, vital sign, and laboratory information, were extracted from the VA Corporate Data Warehouse using transact sequential query language.

Veterans were included in the final cohort if they met the following criteria: aged ≥ 18 years at antipsychotic initiation, initiated their first-ever atypical antipsychotic within the VHA between February 2014 and February 2019, continued the antipsychotic for ≥ 1 year, had a medication possession ratio (MPR) > 80%, and had previously established care within VHA as evidenced by having ≥ 1 primary care or outpatient mental health visit in the 6 months prior to initiation. The MPR is defined as the sum of the day’s supply of all dispensed medications in the project time frame divided by the total number of days in the project time frame.

Veterans were excluded if they initiated any other antipsychotic during the first course, had a prior diagnosis of T2DM, had any prior use of antidiabetic medications, or had a hemoglobin A_1c (HbA_1c) > 6.4 in the year prior to initiation.

The primary outcome was completion of all recommended metabolic monitoring time points in the first year after atypical antipsychotic initiation. The secondary outcome was incidence of T2DM as evidenced by either a HbA_1c > 6.4 or diagnosis of T2DM entered into the electronic health record. Baseline monitoring for BP, blood glucose, and lipids were considered complete if a data point was collected between 3 months prior and 1 month after atypical antipsychotic initiation. Baseline monitoring for weight was considered complete if a data point was collected between 3 months prior and 2 weeks after initiation. Follow-up monitoring for BP, blood glucose, and lipids were considered completed if a data point was collected at 3 and 12 months (mean, 1 month). Follow-up monitoring for weight was considered completed if collected at 1, 2, and 3 months (mean, 2 weeks) and at 6, 9, and 12 months (mean, 1 month). Waist circumference data and patient and family history are not collected as capturable data points. Therefore, the authors were unable to include these in the final data extraction.

Results

The final cohort consisted of 1,651 veterans who met the inclusion criteria. Overall, at antipsychotic initiation the cohort had a mean (SD) age of 55 (14.6) years, was largely male (88%), and was considered overweight with a mean (SD) BMI of 29.1 (6.4) (Table 1).

Appropriate BP monitoring was completed most often with 492 patients (30%) meeting ADA/APA recommendations followed by HbA_1c and/or blood glucose monitoring with 203 patients (12%) completing all time points. Recommended lipid monitoring was completed by 96 patients (6%). Weight monitoring was completed least often with 47 patients (3%) completing all recommended time points. Regarding completion of all metabolic monitoring time points, 3 (0.2%) patients in the final cohort were found to have completed all recommended monitoring. Ninety-nine patients (6%) were found to have progressed to T2DM as indicated by an HbA_1c > 6.4 and/or entry of a T2DM ninth or tenth edition International Statistical Classification of Diseases code into the chart (Table 2).

Discussion

No previous literature exists that reviews adherence to recommended metabolic monitoring guidance up to 1 year after antipsychotic initiation in a previously antipsychotic-naïve cohort within the VHA. Metabolic monitoring was overall incomplete with 0.2% of the cohort completing all recommended monitoring time points. Weight was the parameter that was least completed. Based on these findings, the authors concluded that efforts are needed to improve completion rates of atypical antipsychotic metabolic monitoring. In the final cohort, 6% of patients were noted to have progressed to T2DM in the first year after atypical antipsychotic initiation. The actual number of patients progressing to T2DM may be larger because not all received adequate blood glucose monitoring. For comparison, the Centers for Disease Control and Prevention released information in 2015 that stated that the US population has an annual T2DM incidence of about 1% for adults aged 45 to 64 years.⁷

We understand that individuals with mental health disorders are at increased risk of T2DM compared with that of the general population and hope that this comparison only serves to drive home the point that appropriate metabolic monitoring is vital for this subgroup. The strengths of this project include identification of an area for improvement and encouraging evidence-based monitoring. Utilization of clinical data is a cost-effective and efficient method to improve patient care.

Limitations

Limitations of this study include the data’s dependence on accuracy of entry by the end-user and a lack of available data regarding prescriptions dispensed outside of the VHA. Vital signs data may have been entered into patient notes and not documented in the vitals section of the current medical record causing the appearance of missing data. Access to VHA health services and patient adherence to follow-up appointments were not assessed in this project and could affect patient ability to complete follow-up. The final analysis included only patients who remained on 1 atypical antipsychotic for a year and were considered adherent with an MPR > 80% and did not consider less adherent patients. It is also possible that health care providers who closely monitor metabolic parameters after atypical antipsychotic initiation more frequently switch patients to an alternative atypical antipsychotic while others who monitor less also switch medications less frequently. This could lead to selection of patients with health care providers who are less adherent to metabolic monitoring recommendations.

Conclusions

As a result of this study, in VISN 21 several strategies will be implemented to improve monitoring. First, the results of this project will be shared with the subject matter experts of the VISN 21 Mental Health Task Force. This task force serves as a venue for clinicians to meet virtually, discuss clinical topics, as well as to create and distribute strategies to improve patient care. Clinicians at this forum will be encouraged to implement monitoring protocols into routine practice, share best practices with colleagues, and increase patient awareness about the importance of metabolic monitoring. Second, modifications may be applied to the electronic health record to guide metabolic monitoring order entry at the time of prescription entry, which includes development of clinical reminders and laboratory order sets. Third, the clinical data manager team may be leveraged to create an electronic report identifying patients currently receiving suboptimal monitoring in the first year after antipsychotic initiation. The patients identified in this report will be discussed at the recurring VISN 21 Mental Health Task Force meeting, and strong practices will be shared with the medical centers across VISN 21. Other strategies under consideration include requiring proof of metabolic monitoring completion prior to allowing further atypical antipsychotic refills and providing direct provider education regarding the ADA/APA metabolic monitoring recommendations via the academic detailing service in effort to standardize clinical care.

Atypical antipsychotic use may result in metabolic abnormalities, such as hyperglycemia, dyslipidemia, weight gain, and metabolic syndrome. These adverse effects (AEs) can cause progression to type 2 diabetes mellitus (T2DM) as well as increased risk of cardiovascular disease and cardiac mortality. Individuals diagnosed with T2DM have medical expenses that are about 2.3 times higher than individuals without diabetes.^1,2 The risk of experiencing metabolic abnormalities is likely elevated for patients who were antipsychotic-naïve prior to initiation.³

In response to an increased awareness of atypical antipsychotic-related AEs, the American Diabetes Association (ADA) and American Psychiatric Association (APA) released a consensus statement in 2004 with a metabolic monitoring protocol for patients initiating or changing to a new antipsychotic medication.⁴ Within the first year after initiation, the ADA/APA consensus statements recommends that clinicians acquire a personal and family history, weight, body mass index (BMI), waist circumference, blood pressure (BP), fasting plasma glucose, and fasting lipid profile at the initial patient visit. Patient weight is recommended to be collected at 4 weeks and again 8 weeks later. Twelve weeks after the initial visit, weight, BMI, BP, fasting plasma glucose and a fasting lipid profile are recommended to be collected and assessed for abnormalities. Weight is then recommended to be assessed every 3 months thereafter. Review of personal and family history, waist circumference, BP, and a fasting plasma glucose is recommended to occur annually. Finally, a fasting lipid profile is to be collected every 5 years.

Since the initial consensus statement release, metabolic monitoring of patients prescribed antipsychotic medications has been found to be inadequate within several large health care organizations.^5,6 Mittal and colleagues reviewed metabolic monitoring practices occurring in 32 facilities within the Veterans Health Administration (VHA) and found that monitoring practices in the first 90 days after antipsychotic initiation were largely nonadherent to the ADA/APA consensus statement recommendations.⁶ Medical staff in Veterans Integrated Service Network 21 (VISN 21) currently serve about 268,000 veterans actively receiving care across California, Nevada, and the Pacific Islands.To support veteran care in the fields of mental health and medication safety, the VISN 21 pharmacy benefits manager office created a clinical dashboard that identifies veterans who are currently prescribed an antipsychotic and have not completed at least 1 annual blood glucose test. While this dashboard is a valuable tool for tracking patient care for those who have been prescribed an antipsychotic > 1 year, it does not consider the ADA/APA recommendations for more frequent monitoring in the first year after initiation. A literature review found no citations of a systematic evaluation of adherence to ADA/APA monitoring recommendations or patient progression to T2DM in the first year after antipsychotic initiation for an antipsychotic-naïve veteran population. The goal of this quality improvement project is to assess VHA health care provider and patient adherence to the 2004 consensus statement recommendations within the first year after initiation for previously antipsychotic-naïve patients receiving an atypical antipsychotic and determine rate of progression to T2DM.

Methods

The project was reviewed by the University of Nevada-Reno Institutional Review Board and determined to be a nonresearch quality improvement project. This was a retrospective chart analysis that included patients receiving their first-ever atypical antipsychotic across 8 US Department of Veterans Affairs (VA) medical centers within VISN 21. Clinical patient data, including prescription, vital sign, and laboratory information, were extracted from the VA Corporate Data Warehouse using transact sequential query language.

Veterans were included in the final cohort if they met the following criteria: aged ≥ 18 years at antipsychotic initiation, initiated their first-ever atypical antipsychotic within the VHA between February 2014 and February 2019, continued the antipsychotic for ≥ 1 year, had a medication possession ratio (MPR) > 80%, and had previously established care within VHA as evidenced by having ≥ 1 primary care or outpatient mental health visit in the 6 months prior to initiation. The MPR is defined as the sum of the day’s supply of all dispensed medications in the project time frame divided by the total number of days in the project time frame.

Veterans were excluded if they initiated any other antipsychotic during the first course, had a prior diagnosis of T2DM, had any prior use of antidiabetic medications, or had a hemoglobin A_1c (HbA_1c) > 6.4 in the year prior to initiation.

The primary outcome was completion of all recommended metabolic monitoring time points in the first year after atypical antipsychotic initiation. The secondary outcome was incidence of T2DM as evidenced by either a HbA_1c > 6.4 or diagnosis of T2DM entered into the electronic health record. Baseline monitoring for BP, blood glucose, and lipids were considered complete if a data point was collected between 3 months prior and 1 month after atypical antipsychotic initiation. Baseline monitoring for weight was considered complete if a data point was collected between 3 months prior and 2 weeks after initiation. Follow-up monitoring for BP, blood glucose, and lipids were considered completed if a data point was collected at 3 and 12 months (mean, 1 month). Follow-up monitoring for weight was considered completed if collected at 1, 2, and 3 months (mean, 2 weeks) and at 6, 9, and 12 months (mean, 1 month). Waist circumference data and patient and family history are not collected as capturable data points. Therefore, the authors were unable to include these in the final data extraction.

Results

The final cohort consisted of 1,651 veterans who met the inclusion criteria. Overall, at antipsychotic initiation the cohort had a mean (SD) age of 55 (14.6) years, was largely male (88%), and was considered overweight with a mean (SD) BMI of 29.1 (6.4) (Table 1).

Appropriate BP monitoring was completed most often with 492 patients (30%) meeting ADA/APA recommendations followed by HbA_1c and/or blood glucose monitoring with 203 patients (12%) completing all time points. Recommended lipid monitoring was completed by 96 patients (6%). Weight monitoring was completed least often with 47 patients (3%) completing all recommended time points. Regarding completion of all metabolic monitoring time points, 3 (0.2%) patients in the final cohort were found to have completed all recommended monitoring. Ninety-nine patients (6%) were found to have progressed to T2DM as indicated by an HbA_1c > 6.4 and/or entry of a T2DM ninth or tenth edition International Statistical Classification of Diseases code into the chart (Table 2).

Discussion

No previous literature exists that reviews adherence to recommended metabolic monitoring guidance up to 1 year after antipsychotic initiation in a previously antipsychotic-naïve cohort within the VHA. Metabolic monitoring was overall incomplete with 0.2% of the cohort completing all recommended monitoring time points. Weight was the parameter that was least completed. Based on these findings, the authors concluded that efforts are needed to improve completion rates of atypical antipsychotic metabolic monitoring. In the final cohort, 6% of patients were noted to have progressed to T2DM in the first year after atypical antipsychotic initiation. The actual number of patients progressing to T2DM may be larger because not all received adequate blood glucose monitoring. For comparison, the Centers for Disease Control and Prevention released information in 2015 that stated that the US population has an annual T2DM incidence of about 1% for adults aged 45 to 64 years.⁷

We understand that individuals with mental health disorders are at increased risk of T2DM compared with that of the general population and hope that this comparison only serves to drive home the point that appropriate metabolic monitoring is vital for this subgroup. The strengths of this project include identification of an area for improvement and encouraging evidence-based monitoring. Utilization of clinical data is a cost-effective and efficient method to improve patient care.

Limitations

Limitations of this study include the data’s dependence on accuracy of entry by the end-user and a lack of available data regarding prescriptions dispensed outside of the VHA. Vital signs data may have been entered into patient notes and not documented in the vitals section of the current medical record causing the appearance of missing data. Access to VHA health services and patient adherence to follow-up appointments were not assessed in this project and could affect patient ability to complete follow-up. The final analysis included only patients who remained on 1 atypical antipsychotic for a year and were considered adherent with an MPR > 80% and did not consider less adherent patients. It is also possible that health care providers who closely monitor metabolic parameters after atypical antipsychotic initiation more frequently switch patients to an alternative atypical antipsychotic while others who monitor less also switch medications less frequently. This could lead to selection of patients with health care providers who are less adherent to metabolic monitoring recommendations.

Conclusions

As a result of this study, in VISN 21 several strategies will be implemented to improve monitoring. First, the results of this project will be shared with the subject matter experts of the VISN 21 Mental Health Task Force. This task force serves as a venue for clinicians to meet virtually, discuss clinical topics, as well as to create and distribute strategies to improve patient care. Clinicians at this forum will be encouraged to implement monitoring protocols into routine practice, share best practices with colleagues, and increase patient awareness about the importance of metabolic monitoring. Second, modifications may be applied to the electronic health record to guide metabolic monitoring order entry at the time of prescription entry, which includes development of clinical reminders and laboratory order sets. Third, the clinical data manager team may be leveraged to create an electronic report identifying patients currently receiving suboptimal monitoring in the first year after antipsychotic initiation. The patients identified in this report will be discussed at the recurring VISN 21 Mental Health Task Force meeting, and strong practices will be shared with the medical centers across VISN 21. Other strategies under consideration include requiring proof of metabolic monitoring completion prior to allowing further atypical antipsychotic refills and providing direct provider education regarding the ADA/APA metabolic monitoring recommendations via the academic detailing service in effort to standardize clinical care.

Tapinarof cream 1% applied once daily in patients with plaque psoriasis convincingly hit its primary and secondary endpoints and was well tolerated in two identical pivotal phase 3, randomized trials, Mark G. Lebwohl, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Tapinarof cream has the potential to be a first-in-class topical therapeutic aryl hydrocarbon receptor modulating agent and will provide physicians and patients with a novel nonsteroidal topical treatment option that’s effective and well tolerated,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dermavant Sciences, the company developing topical tapinarof for treatment of atopic dermatitis as well as psoriasis, announced that upon completion of an ongoing long-term extension study the company plans to file for approval of the drug for psoriasis in 2021.

The two pivotal phase 3 trials, PSOARING 1 and PSOARING 2, randomized a total of 1,025 patients with plaque psoriasis to once-daily tapinarof cream 1% or its vehicle. “This was a fairly difficult group of patients,” Dr. Lebwohl said. Roughly 80% had moderate psoriasis as defined by a baseline Physician Global Assessment (PGA) score of 3, with the remainder split evenly between mild and severe disease. Participants averaged 8% body surface area involvement. Body mass index was on average greater than 31 kg/m².

The primary efficacy endpoint was a PGA score of 0 or 1 – that is, clear or almost clear – plus at least a 2-grade improvement in PGA from baseline at week 12. This was achieved in 35.4% of patients on tapinarof cream once daily in PSOARING 1 and 40.2% in PSOARING 2, compared with 6.0% and 6.3% of vehicle-treated controls, a highly significant difference (both P < .0001).

The prespecified secondary endpoint was a 75% improvement in Psoriasis Area and Severity Index (PASI) score from baseline to week 12. The PASI 75 rates were 36.1% and 47.6% with tapinarof, significantly better than the 10.2% and 6.9% rates in controls.

The most common adverse event associated with tapinarof was folliculitis, which occurred in 20.6% of treated patients in PSOARING 1 and in 15.7% in PSOARING 2. More than 98% of cases were mild or moderate. The folliculitis led to study discontinuation in only 1.8% and 0.9% of subjects in the two trials.

The other noteworthy adverse event was contact dermatitis. It occurred in 3.8% and 4.7% of tapinarof-treated patients, again with low study discontinuation rates of 1.5% and 2.2%.

During the audience discussion, Linda Stein Gold, MD, lead investigator for PSOARING 2, was asked about this folliculitis. She said the mechanism is unclear, as is the best management. She encountered it in patients, didn’t treat it, and it went away on its own. It’s not a bacterial folliculitis; when cultured it invariably proved culture negative, she noted.

The comparative efficacy of tapinarof cream versus the potent and superpotent topical corticosteroids commonly used in the treatment of psoriasis hasn’t been evaluated in head-to-head studies. Her experience and that of the other investigators has been that tapinarof’s efficacy is comparably strong, “but we don’t have the steroid side effects,” said Dr. Stein Gold, director of dermatology clinical research at Henry Ford Health System in Detroit.

In an interview, Dr. Lebwohl said tapinarof, if approved, could help meet a major unmet need for new and better topical therapies for psoriasis.

“You keep hearing about all these biologic agents and small-molecule pills coming out, but the majority of patients still only need topical therapy,” he observed.

Moreover, even when patients with more severe disease achieve a PASI 75 or PASI 90 response with systemic therapy, they usually still need supplemental topical therapy to get them closer to the goal of clear skin.

The superpotent steroids that are the current mainstay of topical therapy come with predictable side effects that dictate a 2- to 4-week limit on their approved use. Also, they’re not supposed to be applied to the face or to intertriginous sites, including the groin, axillae, and under the breasts. In contrast, tapinarof has proved safe and effective in these sensitive areas.

Asked to predict how tapinarof is likely to be used in clinical practice, Dr. Lebwohl replied: “The efficacy was equivalent to strong topical steroids, so I think it could be used first line in place of topical steroids. And in particular, in patients with psoriasis at facial and intertriginous sites, I think an argument can be made for insisting that it be first line.”

He also expects that physicians will end up utilizing tapinarof for a varied group of steroid-responsive dermatoses beyond psoriasis and atopic dermatitis.

“It clearly reduces inflammation, which is why I would expect it would work well for those,” the dermatologist said.

The mechanism of action of tapinarof has been worked out. The drug enters the cell and binds to the aryl hydrocarbon receptor, forming a complex that enters the nucleus. There it joins with the aryl hydrocarbon receptor nuclear translocator, which regulates gene expression so as to reduce production of inflammatory cytokines while promoting an increase in skin barrier proteins, which is why tapinarof is also being developed as an atopic dermatitis therapy.

Dr. Lebwohl and Dr. Stein Gold reported receiving research funds from and serving as consultants to Dermavant Sciences as well as numerous other pharmaceutical companies.

[email protected]

Tapinarof cream 1% applied once daily in patients with plaque psoriasis convincingly hit its primary and secondary endpoints and was well tolerated in two identical pivotal phase 3, randomized trials, Mark G. Lebwohl, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Tapinarof cream has the potential to be a first-in-class topical therapeutic aryl hydrocarbon receptor modulating agent and will provide physicians and patients with a novel nonsteroidal topical treatment option that’s effective and well tolerated,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dermavant Sciences, the company developing topical tapinarof for treatment of atopic dermatitis as well as psoriasis, announced that upon completion of an ongoing long-term extension study the company plans to file for approval of the drug for psoriasis in 2021.

The two pivotal phase 3 trials, PSOARING 1 and PSOARING 2, randomized a total of 1,025 patients with plaque psoriasis to once-daily tapinarof cream 1% or its vehicle. “This was a fairly difficult group of patients,” Dr. Lebwohl said. Roughly 80% had moderate psoriasis as defined by a baseline Physician Global Assessment (PGA) score of 3, with the remainder split evenly between mild and severe disease. Participants averaged 8% body surface area involvement. Body mass index was on average greater than 31 kg/m².

The primary efficacy endpoint was a PGA score of 0 or 1 – that is, clear or almost clear – plus at least a 2-grade improvement in PGA from baseline at week 12. This was achieved in 35.4% of patients on tapinarof cream once daily in PSOARING 1 and 40.2% in PSOARING 2, compared with 6.0% and 6.3% of vehicle-treated controls, a highly significant difference (both P < .0001).

The prespecified secondary endpoint was a 75% improvement in Psoriasis Area and Severity Index (PASI) score from baseline to week 12. The PASI 75 rates were 36.1% and 47.6% with tapinarof, significantly better than the 10.2% and 6.9% rates in controls.

The most common adverse event associated with tapinarof was folliculitis, which occurred in 20.6% of treated patients in PSOARING 1 and in 15.7% in PSOARING 2. More than 98% of cases were mild or moderate. The folliculitis led to study discontinuation in only 1.8% and 0.9% of subjects in the two trials.

The other noteworthy adverse event was contact dermatitis. It occurred in 3.8% and 4.7% of tapinarof-treated patients, again with low study discontinuation rates of 1.5% and 2.2%.

During the audience discussion, Linda Stein Gold, MD, lead investigator for PSOARING 2, was asked about this folliculitis. She said the mechanism is unclear, as is the best management. She encountered it in patients, didn’t treat it, and it went away on its own. It’s not a bacterial folliculitis; when cultured it invariably proved culture negative, she noted.

The comparative efficacy of tapinarof cream versus the potent and superpotent topical corticosteroids commonly used in the treatment of psoriasis hasn’t been evaluated in head-to-head studies. Her experience and that of the other investigators has been that tapinarof’s efficacy is comparably strong, “but we don’t have the steroid side effects,” said Dr. Stein Gold, director of dermatology clinical research at Henry Ford Health System in Detroit.

In an interview, Dr. Lebwohl said tapinarof, if approved, could help meet a major unmet need for new and better topical therapies for psoriasis.

“You keep hearing about all these biologic agents and small-molecule pills coming out, but the majority of patients still only need topical therapy,” he observed.

Moreover, even when patients with more severe disease achieve a PASI 75 or PASI 90 response with systemic therapy, they usually still need supplemental topical therapy to get them closer to the goal of clear skin.

The superpotent steroids that are the current mainstay of topical therapy come with predictable side effects that dictate a 2- to 4-week limit on their approved use. Also, they’re not supposed to be applied to the face or to intertriginous sites, including the groin, axillae, and under the breasts. In contrast, tapinarof has proved safe and effective in these sensitive areas.

Asked to predict how tapinarof is likely to be used in clinical practice, Dr. Lebwohl replied: “The efficacy was equivalent to strong topical steroids, so I think it could be used first line in place of topical steroids. And in particular, in patients with psoriasis at facial and intertriginous sites, I think an argument can be made for insisting that it be first line.”

He also expects that physicians will end up utilizing tapinarof for a varied group of steroid-responsive dermatoses beyond psoriasis and atopic dermatitis.

“It clearly reduces inflammation, which is why I would expect it would work well for those,” the dermatologist said.

The mechanism of action of tapinarof has been worked out. The drug enters the cell and binds to the aryl hydrocarbon receptor, forming a complex that enters the nucleus. There it joins with the aryl hydrocarbon receptor nuclear translocator, which regulates gene expression so as to reduce production of inflammatory cytokines while promoting an increase in skin barrier proteins, which is why tapinarof is also being developed as an atopic dermatitis therapy.

Dr. Lebwohl and Dr. Stein Gold reported receiving research funds from and serving as consultants to Dermavant Sciences as well as numerous other pharmaceutical companies.

[email protected]

Tapinarof cream 1% applied once daily in patients with plaque psoriasis convincingly hit its primary and secondary endpoints and was well tolerated in two identical pivotal phase 3, randomized trials, Mark G. Lebwohl, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Tapinarof cream has the potential to be a first-in-class topical therapeutic aryl hydrocarbon receptor modulating agent and will provide physicians and patients with a novel nonsteroidal topical treatment option that’s effective and well tolerated,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dermavant Sciences, the company developing topical tapinarof for treatment of atopic dermatitis as well as psoriasis, announced that upon completion of an ongoing long-term extension study the company plans to file for approval of the drug for psoriasis in 2021.

The two pivotal phase 3 trials, PSOARING 1 and PSOARING 2, randomized a total of 1,025 patients with plaque psoriasis to once-daily tapinarof cream 1% or its vehicle. “This was a fairly difficult group of patients,” Dr. Lebwohl said. Roughly 80% had moderate psoriasis as defined by a baseline Physician Global Assessment (PGA) score of 3, with the remainder split evenly between mild and severe disease. Participants averaged 8% body surface area involvement. Body mass index was on average greater than 31 kg/m².

The primary efficacy endpoint was a PGA score of 0 or 1 – that is, clear or almost clear – plus at least a 2-grade improvement in PGA from baseline at week 12. This was achieved in 35.4% of patients on tapinarof cream once daily in PSOARING 1 and 40.2% in PSOARING 2, compared with 6.0% and 6.3% of vehicle-treated controls, a highly significant difference (both P < .0001).

The prespecified secondary endpoint was a 75% improvement in Psoriasis Area and Severity Index (PASI) score from baseline to week 12. The PASI 75 rates were 36.1% and 47.6% with tapinarof, significantly better than the 10.2% and 6.9% rates in controls.

The most common adverse event associated with tapinarof was folliculitis, which occurred in 20.6% of treated patients in PSOARING 1 and in 15.7% in PSOARING 2. More than 98% of cases were mild or moderate. The folliculitis led to study discontinuation in only 1.8% and 0.9% of subjects in the two trials.

The other noteworthy adverse event was contact dermatitis. It occurred in 3.8% and 4.7% of tapinarof-treated patients, again with low study discontinuation rates of 1.5% and 2.2%.

During the audience discussion, Linda Stein Gold, MD, lead investigator for PSOARING 2, was asked about this folliculitis. She said the mechanism is unclear, as is the best management. She encountered it in patients, didn’t treat it, and it went away on its own. It’s not a bacterial folliculitis; when cultured it invariably proved culture negative, she noted.

The comparative efficacy of tapinarof cream versus the potent and superpotent topical corticosteroids commonly used in the treatment of psoriasis hasn’t been evaluated in head-to-head studies. Her experience and that of the other investigators has been that tapinarof’s efficacy is comparably strong, “but we don’t have the steroid side effects,” said Dr. Stein Gold, director of dermatology clinical research at Henry Ford Health System in Detroit.

In an interview, Dr. Lebwohl said tapinarof, if approved, could help meet a major unmet need for new and better topical therapies for psoriasis.

“You keep hearing about all these biologic agents and small-molecule pills coming out, but the majority of patients still only need topical therapy,” he observed.

Moreover, even when patients with more severe disease achieve a PASI 75 or PASI 90 response with systemic therapy, they usually still need supplemental topical therapy to get them closer to the goal of clear skin.

The superpotent steroids that are the current mainstay of topical therapy come with predictable side effects that dictate a 2- to 4-week limit on their approved use. Also, they’re not supposed to be applied to the face or to intertriginous sites, including the groin, axillae, and under the breasts. In contrast, tapinarof has proved safe and effective in these sensitive areas.

Asked to predict how tapinarof is likely to be used in clinical practice, Dr. Lebwohl replied: “The efficacy was equivalent to strong topical steroids, so I think it could be used first line in place of topical steroids. And in particular, in patients with psoriasis at facial and intertriginous sites, I think an argument can be made for insisting that it be first line.”

He also expects that physicians will end up utilizing tapinarof for a varied group of steroid-responsive dermatoses beyond psoriasis and atopic dermatitis.

“It clearly reduces inflammation, which is why I would expect it would work well for those,” the dermatologist said.

The mechanism of action of tapinarof has been worked out. The drug enters the cell and binds to the aryl hydrocarbon receptor, forming a complex that enters the nucleus. There it joins with the aryl hydrocarbon receptor nuclear translocator, which regulates gene expression so as to reduce production of inflammatory cytokines while promoting an increase in skin barrier proteins, which is why tapinarof is also being developed as an atopic dermatitis therapy.

Dr. Lebwohl and Dr. Stein Gold reported receiving research funds from and serving as consultants to Dermavant Sciences as well as numerous other pharmaceutical companies.

[email protected]

Using principles of psychoanalysis to craft public health messaging may be a novel and effective way of increasing adherence to public health advice during the COVID-19 pandemic, experts say.

In a letter published online Oct. 19 in The Lancet, coauthors Austin Ratner, MD, and Nisarg Gandhi, believe that, as expert communicators, psychoanalysts should be part of the public health care team to help battle the pandemic.

“The idea of using psychoanalysis in a public health setting is relatively unheard of,” Ratner, the author of a book titled “The Psychoanalyst’s Aversion to Proof,” told Medscape Medical News. Ratner earned his MD at John Hopkins School of Medicine but left medicine to become an author. Gandhi is a clinical research intern at Saint Barnabas Medical Center in Livingston, New Jersey.

Psychoanalysis postulates that defense mechanisms, such as denial, may play an important role in nonadherence to public health guidance regarding the pandemic, Ratner said.

“Denial is a Freudian concept and we can see how it is rearing its ugly head in a number of prominent ways all around us, including nonadherence to medical advice regarding COVID-19, as well as climate change and politics.

“By understanding that fear and anxiety underpin a lot of denial, the psychoanalytic viewpoint can help influence public health officials in recognizing the fear and anxiety, how to talk about the threat [of the pandemic], and what can be done about it,” he added.
 

“A new partnership”

“Psychoanalysts have historically resisted collaboration with disciplines such as social and experimental psychology,” Ratner said. This “insularity” results in “lost opportunities on the path for psychoanalysis to become part of the conversation regarding mass denial and mass nonadherence to medical advice.”

He noted that change is afoot in the psychoanalytic community. The American Psychoanalytic Association (APsaA) has begun to “empower constituents” who seek greater “integration with experimental science and greater involvement with public health.”

To that end, Ratner suggests a “new partnership” between three fields that have until now been disparate: experimental psychology, public health, and psychoanalysis.

Cognitive scientists have studied and documented denial, attributing it to “anxiety’s power to compromise rational thought,” but their approach has not focused on the psychoanalytic model of denial as a defense mechanism, Ratner observed.

Mark Smaller, PhD, past president of APsaA and board member of the International Psychoanalytical Association, elaborated.

“From a psychoanalytic perspective, I am interested in how a defense mechanism functions for individuals and groups,” Smaller told Medscape Medical News.

Denial as a defense mechanism often arises, whether in individuals or groups, from a sense of helplessness, explained Smaller, who is also the chair of the department of public advocacy at APsaA.

“People can only tolerate a certain amount of helplessness – in fact, I would suggest as an analyst that helplessness is the most difficult feeling for humans to come to terms with,” he said.

Helplessness can contribute to trauma and “I think we have a mass case of traumatic helplessness in our country right now because of the pandemic.”

Some people respond to a sense of helplessness with depression or hopelessness, while others “try to integrate the impact of the pandemic by focusing on things over which they have control, like wearing a mask, social distancing, and avoiding places with large numbers of people where the virus can be easily transmitted,” said Smaller.

However, “what seems to have occurred in our country is that, although many people have focused on what we do have control of, a large segment of our population are acting as if COVID-19 doesn’t exist, and we have leadership supporting this denial,” he added.
 

Is “denial” evidence-based?

Commenting for Medscape Medical News, Richard McAnulty, PhD, associate professor of psychology at the University of North Carolina at Charlotte expressed skepticism about the psychoanalytic view of denial, and its potential role in addressing the pandemic.

“A key criticism of psychoanalytic and psychodynamic viewpoints is that many – including the concept of a subconscious mind – are theoretical, not open to empirical research, and not measurable; and one of the most fundamental requirements in science is that all your constructs are measurable.”

For this reason, this approach is “limited in usefulness, although it might be an interesting source of speculation,” said McAnulty.

Ratner disagreed, noting that there is research corroborating the existence of an unconscious mind. Noted analyst Carl Jung, Ratner pointed out, conducted “some great experiments to prove some of the central tenets of psychoanalysis using word associations.”

Jung found that, if individuals were challenged with words that evoked painful associations, it took them longer to arrive at the answer to the test. They also made more mistakes.

Jung’s research “goes back to a core idea of psychoanalysis, which is that painful or difficult thoughts and feelings get distorted, pushed out of consciousness, forgotten, delayed, or suppressed,” Ratner said. These responses might account for “what we’re seeing the U.S. that people are resorting to irrational thinking without being aware of it.”

McAnulty suggested that the psychodynamic idea of denial as a defense mechanism is not relevant to mass nonadherence to pandemic-related medical advice.

Rather, the denial stems from “schemas and belief systems about the world, how people should operate and behave, and the role of government and the medical establishment,” he said.

“When certain recommendations are discrepant with the world view, it creates dissonance or a mismatch and the person will try to reconcile the mismatch,” McAnulty continued. “One way to do that is to say that these recommendations are invalid because they violate the individual’s political beliefs, world view, or religious ideas.”

Ultimately, “it depends on how we define denial,” said McAnulty. “If it means dismissing information that doesn’t fit an existing belief system, that’s denial, but the psychodynamic meaning of ‘denial’ is much deeper than that.”

Smaller, the past president of APsaA, emphasized the importance of empathy when addressing the public. “Psychoanalysts bring empathy to irrationality. Having a psychoanalyst as a team member can help public health officials to communicate better and craft the understanding of anxiety and fear into their message.”

Ratner said he is “not proposing a simplistic silver bullet as an answer to a very complex, multifaceted problem of nonadherence to medical advice.”

Instead, he is “proposing something that hasn’t happened yet, which is more research and more conversation, with psychoanalysis as part of the conversation, because the notion of denial is so relevant, despite how many other factors are involved.”

Ratner, Gandhi, Smaller, and McAnulty have disclosed no relevant financial relationships. Ratner is the author of The Psychoanalyst’s Aversion to Proof and the medical textbook Concepts in Medical Physiology.

This article first appeared on Medscape.com.

Using principles of psychoanalysis to craft public health messaging may be a novel and effective way of increasing adherence to public health advice during the COVID-19 pandemic, experts say.

In a letter published online Oct. 19 in The Lancet, coauthors Austin Ratner, MD, and Nisarg Gandhi, believe that, as expert communicators, psychoanalysts should be part of the public health care team to help battle the pandemic.

“The idea of using psychoanalysis in a public health setting is relatively unheard of,” Ratner, the author of a book titled “The Psychoanalyst’s Aversion to Proof,” told Medscape Medical News. Ratner earned his MD at John Hopkins School of Medicine but left medicine to become an author. Gandhi is a clinical research intern at Saint Barnabas Medical Center in Livingston, New Jersey.

Psychoanalysis postulates that defense mechanisms, such as denial, may play an important role in nonadherence to public health guidance regarding the pandemic, Ratner said.

“Denial is a Freudian concept and we can see how it is rearing its ugly head in a number of prominent ways all around us, including nonadherence to medical advice regarding COVID-19, as well as climate change and politics.

“By understanding that fear and anxiety underpin a lot of denial, the psychoanalytic viewpoint can help influence public health officials in recognizing the fear and anxiety, how to talk about the threat [of the pandemic], and what can be done about it,” he added.
 

“A new partnership”

“Psychoanalysts have historically resisted collaboration with disciplines such as social and experimental psychology,” Ratner said. This “insularity” results in “lost opportunities on the path for psychoanalysis to become part of the conversation regarding mass denial and mass nonadherence to medical advice.”

He noted that change is afoot in the psychoanalytic community. The American Psychoanalytic Association (APsaA) has begun to “empower constituents” who seek greater “integration with experimental science and greater involvement with public health.”

To that end, Ratner suggests a “new partnership” between three fields that have until now been disparate: experimental psychology, public health, and psychoanalysis.

Cognitive scientists have studied and documented denial, attributing it to “anxiety’s power to compromise rational thought,” but their approach has not focused on the psychoanalytic model of denial as a defense mechanism, Ratner observed.

Mark Smaller, PhD, past president of APsaA and board member of the International Psychoanalytical Association, elaborated.

“From a psychoanalytic perspective, I am interested in how a defense mechanism functions for individuals and groups,” Smaller told Medscape Medical News.

Denial as a defense mechanism often arises, whether in individuals or groups, from a sense of helplessness, explained Smaller, who is also the chair of the department of public advocacy at APsaA.

“People can only tolerate a certain amount of helplessness – in fact, I would suggest as an analyst that helplessness is the most difficult feeling for humans to come to terms with,” he said.

Helplessness can contribute to trauma and “I think we have a mass case of traumatic helplessness in our country right now because of the pandemic.”

Some people respond to a sense of helplessness with depression or hopelessness, while others “try to integrate the impact of the pandemic by focusing on things over which they have control, like wearing a mask, social distancing, and avoiding places with large numbers of people where the virus can be easily transmitted,” said Smaller.

However, “what seems to have occurred in our country is that, although many people have focused on what we do have control of, a large segment of our population are acting as if COVID-19 doesn’t exist, and we have leadership supporting this denial,” he added.
 

Is “denial” evidence-based?

Commenting for Medscape Medical News, Richard McAnulty, PhD, associate professor of psychology at the University of North Carolina at Charlotte expressed skepticism about the psychoanalytic view of denial, and its potential role in addressing the pandemic.

“A key criticism of psychoanalytic and psychodynamic viewpoints is that many – including the concept of a subconscious mind – are theoretical, not open to empirical research, and not measurable; and one of the most fundamental requirements in science is that all your constructs are measurable.”

For this reason, this approach is “limited in usefulness, although it might be an interesting source of speculation,” said McAnulty.

Ratner disagreed, noting that there is research corroborating the existence of an unconscious mind. Noted analyst Carl Jung, Ratner pointed out, conducted “some great experiments to prove some of the central tenets of psychoanalysis using word associations.”

Jung found that, if individuals were challenged with words that evoked painful associations, it took them longer to arrive at the answer to the test. They also made more mistakes.

Jung’s research “goes back to a core idea of psychoanalysis, which is that painful or difficult thoughts and feelings get distorted, pushed out of consciousness, forgotten, delayed, or suppressed,” Ratner said. These responses might account for “what we’re seeing the U.S. that people are resorting to irrational thinking without being aware of it.”

McAnulty suggested that the psychodynamic idea of denial as a defense mechanism is not relevant to mass nonadherence to pandemic-related medical advice.

Rather, the denial stems from “schemas and belief systems about the world, how people should operate and behave, and the role of government and the medical establishment,” he said.

“When certain recommendations are discrepant with the world view, it creates dissonance or a mismatch and the person will try to reconcile the mismatch,” McAnulty continued. “One way to do that is to say that these recommendations are invalid because they violate the individual’s political beliefs, world view, or religious ideas.”

Ultimately, “it depends on how we define denial,” said McAnulty. “If it means dismissing information that doesn’t fit an existing belief system, that’s denial, but the psychodynamic meaning of ‘denial’ is much deeper than that.”

Smaller, the past president of APsaA, emphasized the importance of empathy when addressing the public. “Psychoanalysts bring empathy to irrationality. Having a psychoanalyst as a team member can help public health officials to communicate better and craft the understanding of anxiety and fear into their message.”

Ratner said he is “not proposing a simplistic silver bullet as an answer to a very complex, multifaceted problem of nonadherence to medical advice.”

Instead, he is “proposing something that hasn’t happened yet, which is more research and more conversation, with psychoanalysis as part of the conversation, because the notion of denial is so relevant, despite how many other factors are involved.”

Ratner, Gandhi, Smaller, and McAnulty have disclosed no relevant financial relationships. Ratner is the author of The Psychoanalyst’s Aversion to Proof and the medical textbook Concepts in Medical Physiology.

This article first appeared on Medscape.com.

Using principles of psychoanalysis to craft public health messaging may be a novel and effective way of increasing adherence to public health advice during the COVID-19 pandemic, experts say.

In a letter published online Oct. 19 in The Lancet, coauthors Austin Ratner, MD, and Nisarg Gandhi, believe that, as expert communicators, psychoanalysts should be part of the public health care team to help battle the pandemic.

“The idea of using psychoanalysis in a public health setting is relatively unheard of,” Ratner, the author of a book titled “The Psychoanalyst’s Aversion to Proof,” told Medscape Medical News. Ratner earned his MD at John Hopkins School of Medicine but left medicine to become an author. Gandhi is a clinical research intern at Saint Barnabas Medical Center in Livingston, New Jersey.

Psychoanalysis postulates that defense mechanisms, such as denial, may play an important role in nonadherence to public health guidance regarding the pandemic, Ratner said.

“Denial is a Freudian concept and we can see how it is rearing its ugly head in a number of prominent ways all around us, including nonadherence to medical advice regarding COVID-19, as well as climate change and politics.

“By understanding that fear and anxiety underpin a lot of denial, the psychoanalytic viewpoint can help influence public health officials in recognizing the fear and anxiety, how to talk about the threat [of the pandemic], and what can be done about it,” he added.
 

“A new partnership”

“Psychoanalysts have historically resisted collaboration with disciplines such as social and experimental psychology,” Ratner said. This “insularity” results in “lost opportunities on the path for psychoanalysis to become part of the conversation regarding mass denial and mass nonadherence to medical advice.”

He noted that change is afoot in the psychoanalytic community. The American Psychoanalytic Association (APsaA) has begun to “empower constituents” who seek greater “integration with experimental science and greater involvement with public health.”

To that end, Ratner suggests a “new partnership” between three fields that have until now been disparate: experimental psychology, public health, and psychoanalysis.

Cognitive scientists have studied and documented denial, attributing it to “anxiety’s power to compromise rational thought,” but their approach has not focused on the psychoanalytic model of denial as a defense mechanism, Ratner observed.

Mark Smaller, PhD, past president of APsaA and board member of the International Psychoanalytical Association, elaborated.

“From a psychoanalytic perspective, I am interested in how a defense mechanism functions for individuals and groups,” Smaller told Medscape Medical News.

Denial as a defense mechanism often arises, whether in individuals or groups, from a sense of helplessness, explained Smaller, who is also the chair of the department of public advocacy at APsaA.

“People can only tolerate a certain amount of helplessness – in fact, I would suggest as an analyst that helplessness is the most difficult feeling for humans to come to terms with,” he said.

Helplessness can contribute to trauma and “I think we have a mass case of traumatic helplessness in our country right now because of the pandemic.”

Some people respond to a sense of helplessness with depression or hopelessness, while others “try to integrate the impact of the pandemic by focusing on things over which they have control, like wearing a mask, social distancing, and avoiding places with large numbers of people where the virus can be easily transmitted,” said Smaller.

However, “what seems to have occurred in our country is that, although many people have focused on what we do have control of, a large segment of our population are acting as if COVID-19 doesn’t exist, and we have leadership supporting this denial,” he added.
 

Is “denial” evidence-based?

Commenting for Medscape Medical News, Richard McAnulty, PhD, associate professor of psychology at the University of North Carolina at Charlotte expressed skepticism about the psychoanalytic view of denial, and its potential role in addressing the pandemic.

“A key criticism of psychoanalytic and psychodynamic viewpoints is that many – including the concept of a subconscious mind – are theoretical, not open to empirical research, and not measurable; and one of the most fundamental requirements in science is that all your constructs are measurable.”

For this reason, this approach is “limited in usefulness, although it might be an interesting source of speculation,” said McAnulty.

Ratner disagreed, noting that there is research corroborating the existence of an unconscious mind. Noted analyst Carl Jung, Ratner pointed out, conducted “some great experiments to prove some of the central tenets of psychoanalysis using word associations.”

Jung found that, if individuals were challenged with words that evoked painful associations, it took them longer to arrive at the answer to the test. They also made more mistakes.

Jung’s research “goes back to a core idea of psychoanalysis, which is that painful or difficult thoughts and feelings get distorted, pushed out of consciousness, forgotten, delayed, or suppressed,” Ratner said. These responses might account for “what we’re seeing the U.S. that people are resorting to irrational thinking without being aware of it.”

McAnulty suggested that the psychodynamic idea of denial as a defense mechanism is not relevant to mass nonadherence to pandemic-related medical advice.

Rather, the denial stems from “schemas and belief systems about the world, how people should operate and behave, and the role of government and the medical establishment,” he said.

“When certain recommendations are discrepant with the world view, it creates dissonance or a mismatch and the person will try to reconcile the mismatch,” McAnulty continued. “One way to do that is to say that these recommendations are invalid because they violate the individual’s political beliefs, world view, or religious ideas.”

Ultimately, “it depends on how we define denial,” said McAnulty. “If it means dismissing information that doesn’t fit an existing belief system, that’s denial, but the psychodynamic meaning of ‘denial’ is much deeper than that.”

Smaller, the past president of APsaA, emphasized the importance of empathy when addressing the public. “Psychoanalysts bring empathy to irrationality. Having a psychoanalyst as a team member can help public health officials to communicate better and craft the understanding of anxiety and fear into their message.”

Ratner said he is “not proposing a simplistic silver bullet as an answer to a very complex, multifaceted problem of nonadherence to medical advice.”

Instead, he is “proposing something that hasn’t happened yet, which is more research and more conversation, with psychoanalysis as part of the conversation, because the notion of denial is so relevant, despite how many other factors are involved.”

Ratner, Gandhi, Smaller, and McAnulty have disclosed no relevant financial relationships. Ratner is the author of The Psychoanalyst’s Aversion to Proof and the medical textbook Concepts in Medical Physiology.

This article first appeared on Medscape.com.

A history of prior depressive illness conferred a sevenfold increased risk of developing treatment-limiting mood symptoms in patients on isotretinoin for acne in a large Scottish observational study, Sanaa Butt, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

© Ocskay Bence/Fotolia.com

This was, however, the sole identifiable risk factor for treatment-limiting depressive symptoms in acne patients on isotretinoin in the study of 3,151 consecutive acne patients taking isotretinoin. There was no significant difference between those who did or did not develop depression on the oral retinoid in terms of age, gender, or daily dose of the drug at the time it was discontinued.

“Depressive symptoms occurred at any time from the date of initiation of isotretinoin up to 6 months into therapy, with no identifiable peak time period,” said Dr. Butt, a dermatologist with the U.K. National Health Service Tayside district at Ninewells Hospital, Dundee, Scotland. “Lower doses appear not to be protective,” she added.

The Tayside district has a catchment of roughly 450,000 people. The local population tends to stay put because Tayside is an economically disadvantaged and remote part of Scotland. There are very few private practice dermatologists in the area, so Dr. Butt and coinvestigators are confident their observational study of NHS patients captured the great majority of isotretinoin users in northern Scotland.

The investigators utilized software to analyze the contents of more than 8,000 digitized letters exchanged between NHS Tayside dermatologists and general practitioners during 2005-2018, zeroing in on 3,151 consecutive patients on isotretinoin for acne and 158 on the drug for other conditions, most often rosacea or folliculitis. They then drilled down further through the letters, electronically searching for key words such as suicide, depression, and anxiety. In this way, they ultimately identified 30 patients who discontinued the drug because they developed depressive symptoms. All 30 were on the drug for acne.

The annual incidence of treatment-limiting depressive mood changes was 0.96%, a figure that remained steady over the 13-year study period, even though prescribing of isotretinoin increased over time. This flat incidence rate effectively rules out the potential for confounding because of assessor bias, especially since many different NHS dermatologists were prescribing the drug, Dr. Butt said.

Half of acne patients prescribed isotretinoin were female and 50% were male. And 15 cases of treatment discontinuation caused by development of depressive symptoms occurred in females, 15 in males. A history of past depressive illness was present in 9.3% of females who started on isotretinoin and in 4.5% of the males. The relative risk of treatment-limiting depressive mood changes was increased 790% among females with a prior history of depressive illness and 440% in males with such a history.

Dr. Butt reported having no financial conflicts regarding her NHS-funded study.

[email protected]

A history of prior depressive illness conferred a sevenfold increased risk of developing treatment-limiting mood symptoms in patients on isotretinoin for acne in a large Scottish observational study, Sanaa Butt, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

© Ocskay Bence/Fotolia.com

This was, however, the sole identifiable risk factor for treatment-limiting depressive symptoms in acne patients on isotretinoin in the study of 3,151 consecutive acne patients taking isotretinoin. There was no significant difference between those who did or did not develop depression on the oral retinoid in terms of age, gender, or daily dose of the drug at the time it was discontinued.

“Depressive symptoms occurred at any time from the date of initiation of isotretinoin up to 6 months into therapy, with no identifiable peak time period,” said Dr. Butt, a dermatologist with the U.K. National Health Service Tayside district at Ninewells Hospital, Dundee, Scotland. “Lower doses appear not to be protective,” she added.

The Tayside district has a catchment of roughly 450,000 people. The local population tends to stay put because Tayside is an economically disadvantaged and remote part of Scotland. There are very few private practice dermatologists in the area, so Dr. Butt and coinvestigators are confident their observational study of NHS patients captured the great majority of isotretinoin users in northern Scotland.

The investigators utilized software to analyze the contents of more than 8,000 digitized letters exchanged between NHS Tayside dermatologists and general practitioners during 2005-2018, zeroing in on 3,151 consecutive patients on isotretinoin for acne and 158 on the drug for other conditions, most often rosacea or folliculitis. They then drilled down further through the letters, electronically searching for key words such as suicide, depression, and anxiety. In this way, they ultimately identified 30 patients who discontinued the drug because they developed depressive symptoms. All 30 were on the drug for acne.

The annual incidence of treatment-limiting depressive mood changes was 0.96%, a figure that remained steady over the 13-year study period, even though prescribing of isotretinoin increased over time. This flat incidence rate effectively rules out the potential for confounding because of assessor bias, especially since many different NHS dermatologists were prescribing the drug, Dr. Butt said.

Half of acne patients prescribed isotretinoin were female and 50% were male. And 15 cases of treatment discontinuation caused by development of depressive symptoms occurred in females, 15 in males. A history of past depressive illness was present in 9.3% of females who started on isotretinoin and in 4.5% of the males. The relative risk of treatment-limiting depressive mood changes was increased 790% among females with a prior history of depressive illness and 440% in males with such a history.

Dr. Butt reported having no financial conflicts regarding her NHS-funded study.

[email protected]

A history of prior depressive illness conferred a sevenfold increased risk of developing treatment-limiting mood symptoms in patients on isotretinoin for acne in a large Scottish observational study, Sanaa Butt, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

© Ocskay Bence/Fotolia.com

This was, however, the sole identifiable risk factor for treatment-limiting depressive symptoms in acne patients on isotretinoin in the study of 3,151 consecutive acne patients taking isotretinoin. There was no significant difference between those who did or did not develop depression on the oral retinoid in terms of age, gender, or daily dose of the drug at the time it was discontinued.

“Depressive symptoms occurred at any time from the date of initiation of isotretinoin up to 6 months into therapy, with no identifiable peak time period,” said Dr. Butt, a dermatologist with the U.K. National Health Service Tayside district at Ninewells Hospital, Dundee, Scotland. “Lower doses appear not to be protective,” she added.

The Tayside district has a catchment of roughly 450,000 people. The local population tends to stay put because Tayside is an economically disadvantaged and remote part of Scotland. There are very few private practice dermatologists in the area, so Dr. Butt and coinvestigators are confident their observational study of NHS patients captured the great majority of isotretinoin users in northern Scotland.

The investigators utilized software to analyze the contents of more than 8,000 digitized letters exchanged between NHS Tayside dermatologists and general practitioners during 2005-2018, zeroing in on 3,151 consecutive patients on isotretinoin for acne and 158 on the drug for other conditions, most often rosacea or folliculitis. They then drilled down further through the letters, electronically searching for key words such as suicide, depression, and anxiety. In this way, they ultimately identified 30 patients who discontinued the drug because they developed depressive symptoms. All 30 were on the drug for acne.

The annual incidence of treatment-limiting depressive mood changes was 0.96%, a figure that remained steady over the 13-year study period, even though prescribing of isotretinoin increased over time. This flat incidence rate effectively rules out the potential for confounding because of assessor bias, especially since many different NHS dermatologists were prescribing the drug, Dr. Butt said.

Half of acne patients prescribed isotretinoin were female and 50% were male. And 15 cases of treatment discontinuation caused by development of depressive symptoms occurred in females, 15 in males. A history of past depressive illness was present in 9.3% of females who started on isotretinoin and in 4.5% of the males. The relative risk of treatment-limiting depressive mood changes was increased 790% among females with a prior history of depressive illness and 440% in males with such a history.

Dr. Butt reported having no financial conflicts regarding her NHS-funded study.

[email protected]

The Diagnosis: Monilethrix

Trichoscopy showed a beaded appearance of the hair shafts (Figure, A). Light microscopy demonstrated normal medullated nodes of hair coupled with internodal, thin, nonmedullated hair at regular intervals (Figure, B). Clinical and trichoscopic findings led to a diagnosis of monilethrix.

Monilethrix is a genetic hair disorder characterized by regular periodic thinning of the hair shafts, giving the strands a beaded appearance. The hair tends to break at these constricted parts, resulting in short hairs. Nodosities represent the normal hair shaft, whereas the constricted points are the site of the defect. The hair tends to be normal at birth and then becomes short, fragile, and brittle within months, leading to hypotrichosis, particularly on the occipital scalp.¹ Monilethrix also may involve the eyebrows and eyelashes in addition to scalp hair. Follicular hyperkeratotic papules with perifollicular erythema frequently are noted on the occipital area. Monilethrix can be inherited in an autosomal-dominant fashion with mutations involving KRT81, KRT83, and KRT86, which code for the type II hair keratins Hb1, Hb3, and Hb6, respectively. The autosomal-recessive form is caused by mutations in the DSG4 gene, coding for the desmoglein 4 protein.2 Trichoscopy or light microscopy is essential to establish a diagnosis of monilethrix. Trichoscopy is an easy and rapid tool that is utilized to illustrate the beaded appearance of the hair shafts.³ Light microscopy shows the distinctive nodes that are medullated, with a normal hair diameter alternating with the internodes, or constrictions, that are nonmedullated and represent the sites of fracture.¹ Monilethrix can improve by puberty. There is no definitive treatment; however, some patients show considerable improvement on minoxidil.⁴ Treatment with minoxidil was initiated in this patient; however, she was lost to follow-up.

Genetic hair disorders are rare and can be an isolated phenomenon or part of concurrent genetic syndromes. Therefore, thorough clinical examination of other ectodermal structures such as the nails and teeth is crucial as well as obtaining a detailed family history and review of systems to exclude other syndromes.² Hypotrichosis simplex is characterized by hair loss exclusively on the scalp, sparing other ectodermal structures and with no systemic abnormalities. Ectodermal dysplasia is a heterogeneous group of disorders affecting not only the hair but also the teeth, nails, and sweat glands.² Pili torti is another rare genetic hair disorder that is characterized by twisting of the hair fiber on its own axis. It presents clinically as sparse, depigmented, lusterless hair that is easily broken. Light microscopy demonstrates twists of hair at irregular intervals. Pili annulati is characterized by bright and dark bands when viewed with reflected light. Unlike monilethrix, there is no fragility, and the hair can grow long.⁵

The Diagnosis: Monilethrix

Trichoscopy showed a beaded appearance of the hair shafts (Figure, A). Light microscopy demonstrated normal medullated nodes of hair coupled with internodal, thin, nonmedullated hair at regular intervals (Figure, B). Clinical and trichoscopic findings led to a diagnosis of monilethrix.

Monilethrix is a genetic hair disorder characterized by regular periodic thinning of the hair shafts, giving the strands a beaded appearance. The hair tends to break at these constricted parts, resulting in short hairs. Nodosities represent the normal hair shaft, whereas the constricted points are the site of the defect. The hair tends to be normal at birth and then becomes short, fragile, and brittle within months, leading to hypotrichosis, particularly on the occipital scalp.¹ Monilethrix also may involve the eyebrows and eyelashes in addition to scalp hair. Follicular hyperkeratotic papules with perifollicular erythema frequently are noted on the occipital area. Monilethrix can be inherited in an autosomal-dominant fashion with mutations involving KRT81, KRT83, and KRT86, which code for the type II hair keratins Hb1, Hb3, and Hb6, respectively. The autosomal-recessive form is caused by mutations in the DSG4 gene, coding for the desmoglein 4 protein.2 Trichoscopy or light microscopy is essential to establish a diagnosis of monilethrix. Trichoscopy is an easy and rapid tool that is utilized to illustrate the beaded appearance of the hair shafts.³ Light microscopy shows the distinctive nodes that are medullated, with a normal hair diameter alternating with the internodes, or constrictions, that are nonmedullated and represent the sites of fracture.¹ Monilethrix can improve by puberty. There is no definitive treatment; however, some patients show considerable improvement on minoxidil.⁴ Treatment with minoxidil was initiated in this patient; however, she was lost to follow-up.

Genetic hair disorders are rare and can be an isolated phenomenon or part of concurrent genetic syndromes. Therefore, thorough clinical examination of other ectodermal structures such as the nails and teeth is crucial as well as obtaining a detailed family history and review of systems to exclude other syndromes.² Hypotrichosis simplex is characterized by hair loss exclusively on the scalp, sparing other ectodermal structures and with no systemic abnormalities. Ectodermal dysplasia is a heterogeneous group of disorders affecting not only the hair but also the teeth, nails, and sweat glands.² Pili torti is another rare genetic hair disorder that is characterized by twisting of the hair fiber on its own axis. It presents clinically as sparse, depigmented, lusterless hair that is easily broken. Light microscopy demonstrates twists of hair at irregular intervals. Pili annulati is characterized by bright and dark bands when viewed with reflected light. Unlike monilethrix, there is no fragility, and the hair can grow long.⁵

The Diagnosis: Monilethrix

Trichoscopy showed a beaded appearance of the hair shafts (Figure, A). Light microscopy demonstrated normal medullated nodes of hair coupled with internodal, thin, nonmedullated hair at regular intervals (Figure, B). Clinical and trichoscopic findings led to a diagnosis of monilethrix.

Monilethrix is a genetic hair disorder characterized by regular periodic thinning of the hair shafts, giving the strands a beaded appearance. The hair tends to break at these constricted parts, resulting in short hairs. Nodosities represent the normal hair shaft, whereas the constricted points are the site of the defect. The hair tends to be normal at birth and then becomes short, fragile, and brittle within months, leading to hypotrichosis, particularly on the occipital scalp.¹ Monilethrix also may involve the eyebrows and eyelashes in addition to scalp hair. Follicular hyperkeratotic papules with perifollicular erythema frequently are noted on the occipital area. Monilethrix can be inherited in an autosomal-dominant fashion with mutations involving KRT81, KRT83, and KRT86, which code for the type II hair keratins Hb1, Hb3, and Hb6, respectively. The autosomal-recessive form is caused by mutations in the DSG4 gene, coding for the desmoglein 4 protein.2 Trichoscopy or light microscopy is essential to establish a diagnosis of monilethrix. Trichoscopy is an easy and rapid tool that is utilized to illustrate the beaded appearance of the hair shafts.³ Light microscopy shows the distinctive nodes that are medullated, with a normal hair diameter alternating with the internodes, or constrictions, that are nonmedullated and represent the sites of fracture.¹ Monilethrix can improve by puberty. There is no definitive treatment; however, some patients show considerable improvement on minoxidil.⁴ Treatment with minoxidil was initiated in this patient; however, she was lost to follow-up.

Genetic hair disorders are rare and can be an isolated phenomenon or part of concurrent genetic syndromes. Therefore, thorough clinical examination of other ectodermal structures such as the nails and teeth is crucial as well as obtaining a detailed family history and review of systems to exclude other syndromes.² Hypotrichosis simplex is characterized by hair loss exclusively on the scalp, sparing other ectodermal structures and with no systemic abnormalities. Ectodermal dysplasia is a heterogeneous group of disorders affecting not only the hair but also the teeth, nails, and sweat glands.² Pili torti is another rare genetic hair disorder that is characterized by twisting of the hair fiber on its own axis. It presents clinically as sparse, depigmented, lusterless hair that is easily broken. Light microscopy demonstrates twists of hair at irregular intervals. Pili annulati is characterized by bright and dark bands when viewed with reflected light. Unlike monilethrix, there is no fragility, and the hair can grow long.⁵

The high price of direct-acting antiviral (DAA) oral medications has made patient access challenging despite the availability of multiple effective treatment options for hepatitis C virus (HCV). Has there been any recent progress in making these treatments more affordable to patients? 

Dr. Jakab:  Certainly. We used to have great difficulty getting these medications to our patients, regardless of whether they were covered by private insurance or through the United States Department of Veterans Affairs (VA). The last few years have been amazing, not only in terms of availability of more regimens that are equally effective in curing HCV, but also in terms of patient access. I think this is capitalism at its best. Having competition—more regimens on the market—has helped drive the prices down.

These regimens are expensive, but very few patients actually pay the sticker price because the insurance plans end up negotiating a much better fee for a preferred regimen. The reality is considerably better now than it used to be even a few years ago, with more effective regimens available, and at an affordable price.

There is not much transparency in terms of pricing, so it is usually difficult to figure it out how much one insurance plan pays versus another. From the patient's perspective the progress is visible and translated in many patients being cured from HCV.

Have any of your patients faced other treatment access challenges unrelated to financial cost?

Dr. Jakab:  Historically, when the first DAAs became available, there were certain requirements put forward by insurance companies before these medications were approved given their high price at that time. Unfortunately, some of them are still in effect.

Providers still must document their clinical evaluation and laboratory testing before these medications get approved, which is important for clinical care, but some insurance plans will only cover HCV treatment for patients with advanced (stage 3 or 4) fibrosis.

Another requirement that pains me a lot—though again, great progress has been made—has to do with sobriety for patients who use drugs or alcohol. Some plans require 3 to 6 months of sobriety, or for the patient to be connected to a substance use disorder clinic or a relapse program.

There have also been some restrictions regarding which providers could prescribe these medications. Initially this was limited to hepatology, gastroenterology, or infectious disease specialists. Given the fact that the current DAA regimens are so easy to use due to their short duration of treatment and minimal side effects, more providers are comfortable with prescribing these medications. It certainly helps that CDC recommendations support the expansion of the provider pool to include primary care providers and substance use disorder providers. Physician assistants and APRNs have been increasingly involved in prescribing these medications as well. Pharmacists help us get the approval from the insurance companies, but PharmDs also treat many HCV patients.

Certain states are ahead of others in terms of eliminating Medicaid requirements that decrease patient access to HCV medications. I am lucky to be in Connecticut, which is one of the states where Medicaid restrictions have pretty much been lifted in terms of fibrosis staging or sobriety or prescriber requirements. This progress had a lot to do with patient and provider advocacy. Back in 2015 the New Haven Legal Assistance lobbied the state’s policymakers and Medicaid leadership to change these requirements. For patients covered by commercial insurance plans there are some requirements still in place, but overall, it is much better.

I have also witnessed the revolution of HCV treatment at the VA. A few years back we were restricting the use of these medications for patients with advanced fibrosis. Now the VA has all the available medications on the formulary, and there are no restrictions in terms of fibrosis staging, or sobriety requirements.

How has your team at the West Haven VA helped patients access HCV care through collaboration with other providers?

Dr. Jakab: It has been amazing to see how innovative people can be. It is true that if there is a will, there is a way. We finally had those medications so effective in curing HCV but were faced with challenges getting them to our patients. There was a huge effort throughout the VA, which is the national leader in the treatment of HCV, with more than 100,000 veterans cured. VA Connecticut was part of the movement: we expanded our liver clinic team to include a nurse practitioner, a PharmD, RN care coordinators, and a health psychologist. This way we could help our patients overcome many psychosocial or medical barriers and get them successfully treated.

The last step was going where the patients were. We realized that some patients who would benefit from treatment would not necessarily engage with us in liver clinic, even if they kept up with seeing their primary care physician. So instead of trying to get the patients into the liver clinic, we developed a program called HELP C, which stands for “HEpatitis C Leaders in Primary Care. The purpose of the program was to educate primary care providers interested in treating HCV. We continue to provide support for them through teleconferences or being available for any questions. This way we could indirectly treat patients with HCV without having them come to the liver clinic.

We also collaborated with our colleagues from substance use disorder clinics, to make sure they are updated in terms of ease of HCV treatment and need to screen for HCV in these high-risk patients.

Is there any other action that physicians can take to help improve HCV treatment accessibility for their patients?

Dr. Jakab: Education of patients, providers and policy makers is most important, and a lot of that responsibility is on those of us who are already helping patients to get to their HCV cure. It has to do with breaking barriers. Many providers still have misconceptions, for example, when it comes to patients who are actively using drugs. They feel that we should not spend resources on these patients because of their lack of engagement in terms of treatment of their substance use disorder and risk of relapse. However, we do have data proving that even patients who are actively injecting drugs achieve a high level of compliance with medications and a high level of cure in the range of 95% or so. Having the sobriety requirement on some insurance plans is a significant barrier to treatment, and it does not help select the patients who will successfully achieve HCV cure. All patients should be treated. In fact, by focusing on this high-risk category of patients, society benefits overall because by decreasing the HCV burden, we get closer to HCV eradication.

It is also important that the providers who are interested in treating HCV get familiar with the paperwork required to get these medications approved, also partnering with subspecialty pharmacies particularly when dealing with commercial insurances. In addition, there are assistance programs for patients who do not have insurance, or they are underinsured, or they get denied by their insurance plan. At the end of the day, helping a patient to get treated is worth the extra time spent with bureaucracy.

I would also encourage providers to continue looking for innovative approaches, and to try to develop multidisciplinary programs. Care coordination—partnering with pharmacy, psychology, and social work subspecialties—is what worked best for us at the West Haven VA. We were able to treat patients that were written off many times before; patients who suffered homelessness, struggled with medication adherence for their high blood pressure, or diabetes. They were patients about whom everybody said, “You guys are crazy. They will never get the treatment completed, never mind getting cured of HCV.” But they did—so it is all about advocating for your patients and partnering with the right people.

The high price of direct-acting antiviral (DAA) oral medications has made patient access challenging despite the availability of multiple effective treatment options for hepatitis C virus (HCV). Has there been any recent progress in making these treatments more affordable to patients? 

Dr. Jakab:  Certainly. We used to have great difficulty getting these medications to our patients, regardless of whether they were covered by private insurance or through the United States Department of Veterans Affairs (VA). The last few years have been amazing, not only in terms of availability of more regimens that are equally effective in curing HCV, but also in terms of patient access. I think this is capitalism at its best. Having competition—more regimens on the market—has helped drive the prices down.

These regimens are expensive, but very few patients actually pay the sticker price because the insurance plans end up negotiating a much better fee for a preferred regimen. The reality is considerably better now than it used to be even a few years ago, with more effective regimens available, and at an affordable price.

There is not much transparency in terms of pricing, so it is usually difficult to figure it out how much one insurance plan pays versus another. From the patient's perspective the progress is visible and translated in many patients being cured from HCV.

Have any of your patients faced other treatment access challenges unrelated to financial cost?

Dr. Jakab:  Historically, when the first DAAs became available, there were certain requirements put forward by insurance companies before these medications were approved given their high price at that time. Unfortunately, some of them are still in effect.

Providers still must document their clinical evaluation and laboratory testing before these medications get approved, which is important for clinical care, but some insurance plans will only cover HCV treatment for patients with advanced (stage 3 or 4) fibrosis.

Another requirement that pains me a lot—though again, great progress has been made—has to do with sobriety for patients who use drugs or alcohol. Some plans require 3 to 6 months of sobriety, or for the patient to be connected to a substance use disorder clinic or a relapse program.

There have also been some restrictions regarding which providers could prescribe these medications. Initially this was limited to hepatology, gastroenterology, or infectious disease specialists. Given the fact that the current DAA regimens are so easy to use due to their short duration of treatment and minimal side effects, more providers are comfortable with prescribing these medications. It certainly helps that CDC recommendations support the expansion of the provider pool to include primary care providers and substance use disorder providers. Physician assistants and APRNs have been increasingly involved in prescribing these medications as well. Pharmacists help us get the approval from the insurance companies, but PharmDs also treat many HCV patients.

Certain states are ahead of others in terms of eliminating Medicaid requirements that decrease patient access to HCV medications. I am lucky to be in Connecticut, which is one of the states where Medicaid restrictions have pretty much been lifted in terms of fibrosis staging or sobriety or prescriber requirements. This progress had a lot to do with patient and provider advocacy. Back in 2015 the New Haven Legal Assistance lobbied the state’s policymakers and Medicaid leadership to change these requirements. For patients covered by commercial insurance plans there are some requirements still in place, but overall, it is much better.

I have also witnessed the revolution of HCV treatment at the VA. A few years back we were restricting the use of these medications for patients with advanced fibrosis. Now the VA has all the available medications on the formulary, and there are no restrictions in terms of fibrosis staging, or sobriety requirements.

How has your team at the West Haven VA helped patients access HCV care through collaboration with other providers?

Dr. Jakab: It has been amazing to see how innovative people can be. It is true that if there is a will, there is a way. We finally had those medications so effective in curing HCV but were faced with challenges getting them to our patients. There was a huge effort throughout the VA, which is the national leader in the treatment of HCV, with more than 100,000 veterans cured. VA Connecticut was part of the movement: we expanded our liver clinic team to include a nurse practitioner, a PharmD, RN care coordinators, and a health psychologist. This way we could help our patients overcome many psychosocial or medical barriers and get them successfully treated.

The last step was going where the patients were. We realized that some patients who would benefit from treatment would not necessarily engage with us in liver clinic, even if they kept up with seeing their primary care physician. So instead of trying to get the patients into the liver clinic, we developed a program called HELP C, which stands for “HEpatitis C Leaders in Primary Care. The purpose of the program was to educate primary care providers interested in treating HCV. We continue to provide support for them through teleconferences or being available for any questions. This way we could indirectly treat patients with HCV without having them come to the liver clinic.

We also collaborated with our colleagues from substance use disorder clinics, to make sure they are updated in terms of ease of HCV treatment and need to screen for HCV in these high-risk patients.

Is there any other action that physicians can take to help improve HCV treatment accessibility for their patients?

Dr. Jakab: Education of patients, providers and policy makers is most important, and a lot of that responsibility is on those of us who are already helping patients to get to their HCV cure. It has to do with breaking barriers. Many providers still have misconceptions, for example, when it comes to patients who are actively using drugs. They feel that we should not spend resources on these patients because of their lack of engagement in terms of treatment of their substance use disorder and risk of relapse. However, we do have data proving that even patients who are actively injecting drugs achieve a high level of compliance with medications and a high level of cure in the range of 95% or so. Having the sobriety requirement on some insurance plans is a significant barrier to treatment, and it does not help select the patients who will successfully achieve HCV cure. All patients should be treated. In fact, by focusing on this high-risk category of patients, society benefits overall because by decreasing the HCV burden, we get closer to HCV eradication.

It is also important that the providers who are interested in treating HCV get familiar with the paperwork required to get these medications approved, also partnering with subspecialty pharmacies particularly when dealing with commercial insurances. In addition, there are assistance programs for patients who do not have insurance, or they are underinsured, or they get denied by their insurance plan. At the end of the day, helping a patient to get treated is worth the extra time spent with bureaucracy.

I would also encourage providers to continue looking for innovative approaches, and to try to develop multidisciplinary programs. Care coordination—partnering with pharmacy, psychology, and social work subspecialties—is what worked best for us at the West Haven VA. We were able to treat patients that were written off many times before; patients who suffered homelessness, struggled with medication adherence for their high blood pressure, or diabetes. They were patients about whom everybody said, “You guys are crazy. They will never get the treatment completed, never mind getting cured of HCV.” But they did—so it is all about advocating for your patients and partnering with the right people.

The high price of direct-acting antiviral (DAA) oral medications has made patient access challenging despite the availability of multiple effective treatment options for hepatitis C virus (HCV). Has there been any recent progress in making these treatments more affordable to patients? 

Dr. Jakab:  Certainly. We used to have great difficulty getting these medications to our patients, regardless of whether they were covered by private insurance or through the United States Department of Veterans Affairs (VA). The last few years have been amazing, not only in terms of availability of more regimens that are equally effective in curing HCV, but also in terms of patient access. I think this is capitalism at its best. Having competition—more regimens on the market—has helped drive the prices down.

These regimens are expensive, but very few patients actually pay the sticker price because the insurance plans end up negotiating a much better fee for a preferred regimen. The reality is considerably better now than it used to be even a few years ago, with more effective regimens available, and at an affordable price.

There is not much transparency in terms of pricing, so it is usually difficult to figure it out how much one insurance plan pays versus another. From the patient's perspective the progress is visible and translated in many patients being cured from HCV.

Have any of your patients faced other treatment access challenges unrelated to financial cost?

Dr. Jakab:  Historically, when the first DAAs became available, there were certain requirements put forward by insurance companies before these medications were approved given their high price at that time. Unfortunately, some of them are still in effect.

Providers still must document their clinical evaluation and laboratory testing before these medications get approved, which is important for clinical care, but some insurance plans will only cover HCV treatment for patients with advanced (stage 3 or 4) fibrosis.

Another requirement that pains me a lot—though again, great progress has been made—has to do with sobriety for patients who use drugs or alcohol. Some plans require 3 to 6 months of sobriety, or for the patient to be connected to a substance use disorder clinic or a relapse program.

There have also been some restrictions regarding which providers could prescribe these medications. Initially this was limited to hepatology, gastroenterology, or infectious disease specialists. Given the fact that the current DAA regimens are so easy to use due to their short duration of treatment and minimal side effects, more providers are comfortable with prescribing these medications. It certainly helps that CDC recommendations support the expansion of the provider pool to include primary care providers and substance use disorder providers. Physician assistants and APRNs have been increasingly involved in prescribing these medications as well. Pharmacists help us get the approval from the insurance companies, but PharmDs also treat many HCV patients.

Certain states are ahead of others in terms of eliminating Medicaid requirements that decrease patient access to HCV medications. I am lucky to be in Connecticut, which is one of the states where Medicaid restrictions have pretty much been lifted in terms of fibrosis staging or sobriety or prescriber requirements. This progress had a lot to do with patient and provider advocacy. Back in 2015 the New Haven Legal Assistance lobbied the state’s policymakers and Medicaid leadership to change these requirements. For patients covered by commercial insurance plans there are some requirements still in place, but overall, it is much better.

I have also witnessed the revolution of HCV treatment at the VA. A few years back we were restricting the use of these medications for patients with advanced fibrosis. Now the VA has all the available medications on the formulary, and there are no restrictions in terms of fibrosis staging, or sobriety requirements.

How has your team at the West Haven VA helped patients access HCV care through collaboration with other providers?

Dr. Jakab: It has been amazing to see how innovative people can be. It is true that if there is a will, there is a way. We finally had those medications so effective in curing HCV but were faced with challenges getting them to our patients. There was a huge effort throughout the VA, which is the national leader in the treatment of HCV, with more than 100,000 veterans cured. VA Connecticut was part of the movement: we expanded our liver clinic team to include a nurse practitioner, a PharmD, RN care coordinators, and a health psychologist. This way we could help our patients overcome many psychosocial or medical barriers and get them successfully treated.

The last step was going where the patients were. We realized that some patients who would benefit from treatment would not necessarily engage with us in liver clinic, even if they kept up with seeing their primary care physician. So instead of trying to get the patients into the liver clinic, we developed a program called HELP C, which stands for “HEpatitis C Leaders in Primary Care. The purpose of the program was to educate primary care providers interested in treating HCV. We continue to provide support for them through teleconferences or being available for any questions. This way we could indirectly treat patients with HCV without having them come to the liver clinic.

We also collaborated with our colleagues from substance use disorder clinics, to make sure they are updated in terms of ease of HCV treatment and need to screen for HCV in these high-risk patients.

Is there any other action that physicians can take to help improve HCV treatment accessibility for their patients?

Dr. Jakab: Education of patients, providers and policy makers is most important, and a lot of that responsibility is on those of us who are already helping patients to get to their HCV cure. It has to do with breaking barriers. Many providers still have misconceptions, for example, when it comes to patients who are actively using drugs. They feel that we should not spend resources on these patients because of their lack of engagement in terms of treatment of their substance use disorder and risk of relapse. However, we do have data proving that even patients who are actively injecting drugs achieve a high level of compliance with medications and a high level of cure in the range of 95% or so. Having the sobriety requirement on some insurance plans is a significant barrier to treatment, and it does not help select the patients who will successfully achieve HCV cure. All patients should be treated. In fact, by focusing on this high-risk category of patients, society benefits overall because by decreasing the HCV burden, we get closer to HCV eradication.

It is also important that the providers who are interested in treating HCV get familiar with the paperwork required to get these medications approved, also partnering with subspecialty pharmacies particularly when dealing with commercial insurances. In addition, there are assistance programs for patients who do not have insurance, or they are underinsured, or they get denied by their insurance plan. At the end of the day, helping a patient to get treated is worth the extra time spent with bureaucracy.

I would also encourage providers to continue looking for innovative approaches, and to try to develop multidisciplinary programs. Care coordination—partnering with pharmacy, psychology, and social work subspecialties—is what worked best for us at the West Haven VA. We were able to treat patients that were written off many times before; patients who suffered homelessness, struggled with medication adherence for their high blood pressure, or diabetes. They were patients about whom everybody said, “You guys are crazy. They will never get the treatment completed, never mind getting cured of HCV.” But they did—so it is all about advocating for your patients and partnering with the right people.

SARS-CoV-2 infection posed increased risk for pregnant women in terms of severe disease and poor pregnancy outcomes including preterm birth, based on data from two studies published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

In a study of birth and infant outcomes, rates of preterm birth (less than 37 weeks’ gestational age) were higher among women with confirmed SARS-CoV-2 infections compared with the national average (12.9% vs. 10.2%) wrote Kate R. Woodworth, MD, and colleagues of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team.

The researchers collected information on pregnancy and infant outcomes from 16 jurisdictions through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). The study included 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29–Oct. 14, 2020.

Overall, 12.9% of the 3,912 live births with known gestational age were preterm. A total of 610 infants were tested for SARS-CoV-2, and 2.6% were positive. Most of these perinatal infections (85%) occurred among infants born to women with SARS-CoV-2 infection within 1 week of delivery.

Half of the infants with positive test results were preterm, possibly reflecting higher screening rates in the ICU, the researchers said. “These findings also support the growing evidence that although severe COVID-19 does occur in neonates the majority of term neonates experience asymptomatic infection or mild disease; however, information on long term outcomes among exposed infants is unknown.”

Address disparities that amplify risk

The study findings were limited by several factors including inconsistent symptom reporting, overrepresentation of Hispanic women, and incomplete information on pregnancy loss, Dr. Woodworth and associates noted. However, the results add to the knowledge about the impact of COVID-19 disease on pregnancy by providing a large, population-based cohort with completed pregnancy outcomes as well as infant testing.

“SET-NET will continue to follow pregnancies affected by SARS-CoV-2 through completion of pregnancy and infants until age 6 months to guide clinical and public health practice,” the researchers noted. “Longer-term investigation into solutions to alleviate underlying inequities in social determinants of health associated with disparities in maternal morbidity, mortality, and adverse pregnancy outcomes, and effectively addressing these inequities, could reduce the prevalence of conditions and experiences that might amplify risks from COVID-19,” they added.

Severe disease and death increased in pregnant women

In a second study published in the MMWR, Laura D. Zambrano, PhD, and colleagues, also of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team, compared data on 23,434 reportedly pregnant and 386,028 nonpregnant women of reproductive age (15-44 years) with confirmed and symptomatic SARS-CoV-2 infections reported to the CDC between Jan. 22, 2020, and Oct. 3, 2020.

After adjustment for age, race, and underlying medical conditions, pregnant women with COVID-19 disease were significantly more likely than were nonpregnant women to be admitted to intensive care (10.5 per 1,000 cases vs. 3.9 per 1,000 cases), to receive invasive ventilation (2.9 vs. 1.1), receive extracorporeal membrane oxygenation (0.7 vs. 0.3) and to die (1.5 vs. 1.2).

“Irrespective of pregnancy status, ICU admissions, receipt of invasive ventilation, and death occurred more often among women aged 35-44 years than among those aged 15-24 years,” Dr. Zambrano and associates noted. In addition, non-Hispanic Black and Black women comprised 14.1% of the study population but accounted for 36.6% of deaths overall (9 in pregnant women and 167 in nonpregnant women).

The findings in the study of characteristics were limited by several factors including the voluntary reporting of COVID-19 cases, potential reporting bias, and inadequate time to assess severe cases, the researchers noted. However, “data from previous influenza pandemics, including 2009 H1N1, have shown that pregnant women are at increased risk for severe outcomes including death and the absolute risks for severe outcomes were higher than in this study of COVID-19 during pregnancy.”

“Pregnant women should be informed of their risk for severe COVID-19–associated illness and the warning signs of severe COVID-19,” Dr. Zambrano and associates said. “Providers who care for pregnant women should be familiar with guidelines for medical management of COVID-19, including considerations for management of COVID-19 in pregnancy.”

More data needed for informed counseling

“It is important to conduct research trials involving pregnant women so that we have reliable data regarding outcomes with which to counsel women,” Angela Bianco, MD, a maternal fetal medicine specialist at Mount Sinai Hospital in New York, said in an interview.

“Often pregnant women are excluded from research trials, but the impact of the current public health crisis affects all persons regardless of pregnancy status,” she said.

Dr. Bianco said that she was not surprised by the findings of either study. “In fact, our own research produced similar results.”

“These recent publications found that age-matched pregnant versus nonpregnant women had more severe manifestations of COVID-19, and specifically that pregnant women had a higher risk of requiring ventilation and intensive care admission, as well as higher risk of death,” she said. “Previous studies examining the effect of other SARS viruses have demonstrated that pregnancy is associated with worse outcomes; these findings are likely attributable to the relative state of immunosuppression in pregnancy.” Also, “one of these trials found a greater risk of premature birth in women with COVID-19; this may largely be attributable to iatrogenic delivery due to maternal illness as opposed to spontaneous preterm birth,” Dr. Bianco explained.

“Data are emerging regarding the impact of SARS-CoV-2 on pregnancy outcomes, however information remains limited,” Dr. Bianco noted. “Clinicians need to make patients aware that SARS-CoV-2 infection during pregnancy is associated with a greater risk of severe illness requiring intensive care and/or ventilatory support and even death; however, the precise rates remain unknown. “COVID-19 during pregnancy may result in a preterm birth, but at this time the rate of fetal infection remains unknown,” she said. “Clinicians need to reinforce the importance of physical distancing, mask use, and proper hand hygiene, particularly in this vulnerable population.”

Dr. Bianco emphasized: “Longitudinal studies assessing the impact of SARS-CoV-2 infection at various gestational age periods are needed, as at this time most of the available data includes women with SARS-CoV-2 infection around the time of delivery. Long-term infant outcomes are needed, as well as studies assessing the risk of fetal infection.”

The studies were supported by the Centers for Disease Control and Prevention. The researchers had no financial conflicts to disclose. Dr. Bianco had no relevant financial disclosures.

SOURCE: Woodworth KR et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e2; Zambrano LD et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e3.

SARS-CoV-2 infection posed increased risk for pregnant women in terms of severe disease and poor pregnancy outcomes including preterm birth, based on data from two studies published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

In a study of birth and infant outcomes, rates of preterm birth (less than 37 weeks’ gestational age) were higher among women with confirmed SARS-CoV-2 infections compared with the national average (12.9% vs. 10.2%) wrote Kate R. Woodworth, MD, and colleagues of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team.

The researchers collected information on pregnancy and infant outcomes from 16 jurisdictions through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). The study included 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29–Oct. 14, 2020.

Overall, 12.9% of the 3,912 live births with known gestational age were preterm. A total of 610 infants were tested for SARS-CoV-2, and 2.6% were positive. Most of these perinatal infections (85%) occurred among infants born to women with SARS-CoV-2 infection within 1 week of delivery.

Half of the infants with positive test results were preterm, possibly reflecting higher screening rates in the ICU, the researchers said. “These findings also support the growing evidence that although severe COVID-19 does occur in neonates the majority of term neonates experience asymptomatic infection or mild disease; however, information on long term outcomes among exposed infants is unknown.”

Address disparities that amplify risk

The study findings were limited by several factors including inconsistent symptom reporting, overrepresentation of Hispanic women, and incomplete information on pregnancy loss, Dr. Woodworth and associates noted. However, the results add to the knowledge about the impact of COVID-19 disease on pregnancy by providing a large, population-based cohort with completed pregnancy outcomes as well as infant testing.

“SET-NET will continue to follow pregnancies affected by SARS-CoV-2 through completion of pregnancy and infants until age 6 months to guide clinical and public health practice,” the researchers noted. “Longer-term investigation into solutions to alleviate underlying inequities in social determinants of health associated with disparities in maternal morbidity, mortality, and adverse pregnancy outcomes, and effectively addressing these inequities, could reduce the prevalence of conditions and experiences that might amplify risks from COVID-19,” they added.

Severe disease and death increased in pregnant women

In a second study published in the MMWR, Laura D. Zambrano, PhD, and colleagues, also of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team, compared data on 23,434 reportedly pregnant and 386,028 nonpregnant women of reproductive age (15-44 years) with confirmed and symptomatic SARS-CoV-2 infections reported to the CDC between Jan. 22, 2020, and Oct. 3, 2020.

After adjustment for age, race, and underlying medical conditions, pregnant women with COVID-19 disease were significantly more likely than were nonpregnant women to be admitted to intensive care (10.5 per 1,000 cases vs. 3.9 per 1,000 cases), to receive invasive ventilation (2.9 vs. 1.1), receive extracorporeal membrane oxygenation (0.7 vs. 0.3) and to die (1.5 vs. 1.2).

“Irrespective of pregnancy status, ICU admissions, receipt of invasive ventilation, and death occurred more often among women aged 35-44 years than among those aged 15-24 years,” Dr. Zambrano and associates noted. In addition, non-Hispanic Black and Black women comprised 14.1% of the study population but accounted for 36.6% of deaths overall (9 in pregnant women and 167 in nonpregnant women).

The findings in the study of characteristics were limited by several factors including the voluntary reporting of COVID-19 cases, potential reporting bias, and inadequate time to assess severe cases, the researchers noted. However, “data from previous influenza pandemics, including 2009 H1N1, have shown that pregnant women are at increased risk for severe outcomes including death and the absolute risks for severe outcomes were higher than in this study of COVID-19 during pregnancy.”

“Pregnant women should be informed of their risk for severe COVID-19–associated illness and the warning signs of severe COVID-19,” Dr. Zambrano and associates said. “Providers who care for pregnant women should be familiar with guidelines for medical management of COVID-19, including considerations for management of COVID-19 in pregnancy.”

More data needed for informed counseling

“It is important to conduct research trials involving pregnant women so that we have reliable data regarding outcomes with which to counsel women,” Angela Bianco, MD, a maternal fetal medicine specialist at Mount Sinai Hospital in New York, said in an interview.

“Often pregnant women are excluded from research trials, but the impact of the current public health crisis affects all persons regardless of pregnancy status,” she said.

Dr. Bianco said that she was not surprised by the findings of either study. “In fact, our own research produced similar results.”

“These recent publications found that age-matched pregnant versus nonpregnant women had more severe manifestations of COVID-19, and specifically that pregnant women had a higher risk of requiring ventilation and intensive care admission, as well as higher risk of death,” she said. “Previous studies examining the effect of other SARS viruses have demonstrated that pregnancy is associated with worse outcomes; these findings are likely attributable to the relative state of immunosuppression in pregnancy.” Also, “one of these trials found a greater risk of premature birth in women with COVID-19; this may largely be attributable to iatrogenic delivery due to maternal illness as opposed to spontaneous preterm birth,” Dr. Bianco explained.

“Data are emerging regarding the impact of SARS-CoV-2 on pregnancy outcomes, however information remains limited,” Dr. Bianco noted. “Clinicians need to make patients aware that SARS-CoV-2 infection during pregnancy is associated with a greater risk of severe illness requiring intensive care and/or ventilatory support and even death; however, the precise rates remain unknown. “COVID-19 during pregnancy may result in a preterm birth, but at this time the rate of fetal infection remains unknown,” she said. “Clinicians need to reinforce the importance of physical distancing, mask use, and proper hand hygiene, particularly in this vulnerable population.”

Dr. Bianco emphasized: “Longitudinal studies assessing the impact of SARS-CoV-2 infection at various gestational age periods are needed, as at this time most of the available data includes women with SARS-CoV-2 infection around the time of delivery. Long-term infant outcomes are needed, as well as studies assessing the risk of fetal infection.”

The studies were supported by the Centers for Disease Control and Prevention. The researchers had no financial conflicts to disclose. Dr. Bianco had no relevant financial disclosures.

SOURCE: Woodworth KR et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e2; Zambrano LD et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e3.

SARS-CoV-2 infection posed increased risk for pregnant women in terms of severe disease and poor pregnancy outcomes including preterm birth, based on data from two studies published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

In a study of birth and infant outcomes, rates of preterm birth (less than 37 weeks’ gestational age) were higher among women with confirmed SARS-CoV-2 infections compared with the national average (12.9% vs. 10.2%) wrote Kate R. Woodworth, MD, and colleagues of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team.

The researchers collected information on pregnancy and infant outcomes from 16 jurisdictions through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). The study included 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29–Oct. 14, 2020.

Overall, 12.9% of the 3,912 live births with known gestational age were preterm. A total of 610 infants were tested for SARS-CoV-2, and 2.6% were positive. Most of these perinatal infections (85%) occurred among infants born to women with SARS-CoV-2 infection within 1 week of delivery.

Half of the infants with positive test results were preterm, possibly reflecting higher screening rates in the ICU, the researchers said. “These findings also support the growing evidence that although severe COVID-19 does occur in neonates the majority of term neonates experience asymptomatic infection or mild disease; however, information on long term outcomes among exposed infants is unknown.”

Address disparities that amplify risk

The study findings were limited by several factors including inconsistent symptom reporting, overrepresentation of Hispanic women, and incomplete information on pregnancy loss, Dr. Woodworth and associates noted. However, the results add to the knowledge about the impact of COVID-19 disease on pregnancy by providing a large, population-based cohort with completed pregnancy outcomes as well as infant testing.

“SET-NET will continue to follow pregnancies affected by SARS-CoV-2 through completion of pregnancy and infants until age 6 months to guide clinical and public health practice,” the researchers noted. “Longer-term investigation into solutions to alleviate underlying inequities in social determinants of health associated with disparities in maternal morbidity, mortality, and adverse pregnancy outcomes, and effectively addressing these inequities, could reduce the prevalence of conditions and experiences that might amplify risks from COVID-19,” they added.

Severe disease and death increased in pregnant women

In a second study published in the MMWR, Laura D. Zambrano, PhD, and colleagues, also of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team, compared data on 23,434 reportedly pregnant and 386,028 nonpregnant women of reproductive age (15-44 years) with confirmed and symptomatic SARS-CoV-2 infections reported to the CDC between Jan. 22, 2020, and Oct. 3, 2020.

After adjustment for age, race, and underlying medical conditions, pregnant women with COVID-19 disease were significantly more likely than were nonpregnant women to be admitted to intensive care (10.5 per 1,000 cases vs. 3.9 per 1,000 cases), to receive invasive ventilation (2.9 vs. 1.1), receive extracorporeal membrane oxygenation (0.7 vs. 0.3) and to die (1.5 vs. 1.2).

“Irrespective of pregnancy status, ICU admissions, receipt of invasive ventilation, and death occurred more often among women aged 35-44 years than among those aged 15-24 years,” Dr. Zambrano and associates noted. In addition, non-Hispanic Black and Black women comprised 14.1% of the study population but accounted for 36.6% of deaths overall (9 in pregnant women and 167 in nonpregnant women).

The findings in the study of characteristics were limited by several factors including the voluntary reporting of COVID-19 cases, potential reporting bias, and inadequate time to assess severe cases, the researchers noted. However, “data from previous influenza pandemics, including 2009 H1N1, have shown that pregnant women are at increased risk for severe outcomes including death and the absolute risks for severe outcomes were higher than in this study of COVID-19 during pregnancy.”

“Pregnant women should be informed of their risk for severe COVID-19–associated illness and the warning signs of severe COVID-19,” Dr. Zambrano and associates said. “Providers who care for pregnant women should be familiar with guidelines for medical management of COVID-19, including considerations for management of COVID-19 in pregnancy.”

More data needed for informed counseling

“It is important to conduct research trials involving pregnant women so that we have reliable data regarding outcomes with which to counsel women,” Angela Bianco, MD, a maternal fetal medicine specialist at Mount Sinai Hospital in New York, said in an interview.

“Often pregnant women are excluded from research trials, but the impact of the current public health crisis affects all persons regardless of pregnancy status,” she said.

Dr. Bianco said that she was not surprised by the findings of either study. “In fact, our own research produced similar results.”

“These recent publications found that age-matched pregnant versus nonpregnant women had more severe manifestations of COVID-19, and specifically that pregnant women had a higher risk of requiring ventilation and intensive care admission, as well as higher risk of death,” she said. “Previous studies examining the effect of other SARS viruses have demonstrated that pregnancy is associated with worse outcomes; these findings are likely attributable to the relative state of immunosuppression in pregnancy.” Also, “one of these trials found a greater risk of premature birth in women with COVID-19; this may largely be attributable to iatrogenic delivery due to maternal illness as opposed to spontaneous preterm birth,” Dr. Bianco explained.

“Data are emerging regarding the impact of SARS-CoV-2 on pregnancy outcomes, however information remains limited,” Dr. Bianco noted. “Clinicians need to make patients aware that SARS-CoV-2 infection during pregnancy is associated with a greater risk of severe illness requiring intensive care and/or ventilatory support and even death; however, the precise rates remain unknown. “COVID-19 during pregnancy may result in a preterm birth, but at this time the rate of fetal infection remains unknown,” she said. “Clinicians need to reinforce the importance of physical distancing, mask use, and proper hand hygiene, particularly in this vulnerable population.”

Dr. Bianco emphasized: “Longitudinal studies assessing the impact of SARS-CoV-2 infection at various gestational age periods are needed, as at this time most of the available data includes women with SARS-CoV-2 infection around the time of delivery. Long-term infant outcomes are needed, as well as studies assessing the risk of fetal infection.”

The studies were supported by the Centers for Disease Control and Prevention. The researchers had no financial conflicts to disclose. Dr. Bianco had no relevant financial disclosures.

SOURCE: Woodworth KR et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e2; Zambrano LD et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e3.

Coaching is a new topic in medicine. I first heard about coaching several years ago and met the term with skepticism. I was unsure how coaching was different than mentoring or advising and I wondered about its usefulness. However, the reason that I even started to learn about coaching was because I was struggling. I had finally arrived in my career, I had my dream job with two healthy kids, a perfect house, and good marriage. I kept hearing the refrain in my head: “Is this all there is?” I had this arrival fallacy that after all this striving and straining that I would finally be content. I felt unfulfilled and was dissatisfied with where I was that was affecting all parts of my life.

As I was wrestling with these thoughts, I had an opportunity to become a coach to residents around the country through the Association of Women Surgeons. I discussed with them what fills them up, what gets them down, how to set goals, and what their goals were for the year, as well as imposter syndrome. Impostor syndrome is defined as a pattern in which an individual doubts their accomplishments or talents and has a persistent internalized fear of being exposed as a “fraud.” Despite external evidence of their competence, those experiencing this phenomenon remain convinced that they are fooling everyone around them and do not deserve all they have achieved. Individuals incorrectly attribute their success to luck or interpret it as a result of deceiving others into thinking they are more intelligent than they perceive themselves to be. Imposter syndrome is prevalent and deep in medicine. As perfectionists, we are especially vulnerable to imposter syndrome as we set unrealistic ideals for ourselves. When we fail to reach these ideals, we feel like frauds, setting up this cycle of self-doubt that is toxic. When we feel that we can’t achieve the goals that we are striving for we will always find ourselves lacking. There is a slow, insidious erosion of self over the years. Imposter syndrome is well documented in medicine and is even felt as early as medical school.^1,2

When I began coaching these residents the most profound thing that came out of these sessions was that my life was getting better – I knew what filled me up, what got me down, what my goals were for the year, and how I still deal with imposter syndrome. Coaching gave me a framework for helping determine what I wanted for the rest of my life. As I began coaching, I started learning all the ways in which I could figure out my values, my personal and professional goals, and perhaps most importantly, my relationships with myself and others.

Another perspective on coaching is to look at a professional athlete such as Tom Brady, one of the greatest quarterbacks of all time. He has a quarterback coach. No coach is going to be a better quarterback than Tom Brady. A coach for him is to be there as an advocate, break his fundamentals down technically, and help him improve upon what he already knows. A coach also identifies strengths and weaknesses, and helps him capitalize on both by bringing awareness, reflection, accountability, and support. If world-class athletes still want and benefit from coaching in a sport they have already mastered, coaching for physicians is just another tool to help us improve our abilities in and out of medicine.

The way I visualize coaching in medicine is a conscious effort to notice and evaluate how our thoughts affect our experiences and how our perspective shows up in the results of our lives. Coaching is more encompassing than advising or mentoring. It is about examining deeply held beliefs to see if they are really serving us, if they are in line with our values and how we want to live our lives.

Coaching has also been validated in medicine in several papers. In an article by Dyrbye et al. in JAMA Internal Medicine, measures of emotional exhaustion and burnout decreased in physicians who were coached and increased in those who were not.³ In another study from this year by McGonagle et al., a randomized, controlled trial showed that primary care physicians who had sessions (as short as 6 weeks) to address burnout, psychological capital, and job satisfaction experienced an improvement in measures which persisted for 6 months after intervention.⁴ Numerous other articles in medicine also exist to demonstrate the effect of coaching on mitigating burnout at an institutional level.

Physicians are inherently driven by their love of learning. As physicians, we love getting to the root cause of any problem and coming up with creative solutions. Any challenge we have, or just wanting to improve the quality of our lives, can be addressed with coaching. As perpetual students we can use coaching to truly master ourselves.

Dr. Shah is associate professor of surgery, Rush University Medical Center, Chicago. Instagram: ami.shahmdcoaching.

References

1. Gottlieb M et al. Med Educ. 2020 Feb;54(2):116-24.

2. Villwock JA et al. Int J Med Educ. 2016 Oct 31;7:364-9.

3. Dyrbye LN et al. JAMA Intern Med. 2019 Aug 5;179(10):1406-14.

4. McGonagle AK et al. J Occup Health Psychol. 2020 Apr 16. doi: 10.1037/ocp0000180.

Coaching is a new topic in medicine. I first heard about coaching several years ago and met the term with skepticism. I was unsure how coaching was different than mentoring or advising and I wondered about its usefulness. However, the reason that I even started to learn about coaching was because I was struggling. I had finally arrived in my career, I had my dream job with two healthy kids, a perfect house, and good marriage. I kept hearing the refrain in my head: “Is this all there is?” I had this arrival fallacy that after all this striving and straining that I would finally be content. I felt unfulfilled and was dissatisfied with where I was that was affecting all parts of my life.

As I was wrestling with these thoughts, I had an opportunity to become a coach to residents around the country through the Association of Women Surgeons. I discussed with them what fills them up, what gets them down, how to set goals, and what their goals were for the year, as well as imposter syndrome. Impostor syndrome is defined as a pattern in which an individual doubts their accomplishments or talents and has a persistent internalized fear of being exposed as a “fraud.” Despite external evidence of their competence, those experiencing this phenomenon remain convinced that they are fooling everyone around them and do not deserve all they have achieved. Individuals incorrectly attribute their success to luck or interpret it as a result of deceiving others into thinking they are more intelligent than they perceive themselves to be. Imposter syndrome is prevalent and deep in medicine. As perfectionists, we are especially vulnerable to imposter syndrome as we set unrealistic ideals for ourselves. When we fail to reach these ideals, we feel like frauds, setting up this cycle of self-doubt that is toxic. When we feel that we can’t achieve the goals that we are striving for we will always find ourselves lacking. There is a slow, insidious erosion of self over the years. Imposter syndrome is well documented in medicine and is even felt as early as medical school.^1,2

When I began coaching these residents the most profound thing that came out of these sessions was that my life was getting better – I knew what filled me up, what got me down, what my goals were for the year, and how I still deal with imposter syndrome. Coaching gave me a framework for helping determine what I wanted for the rest of my life. As I began coaching, I started learning all the ways in which I could figure out my values, my personal and professional goals, and perhaps most importantly, my relationships with myself and others.

Another perspective on coaching is to look at a professional athlete such as Tom Brady, one of the greatest quarterbacks of all time. He has a quarterback coach. No coach is going to be a better quarterback than Tom Brady. A coach for him is to be there as an advocate, break his fundamentals down technically, and help him improve upon what he already knows. A coach also identifies strengths and weaknesses, and helps him capitalize on both by bringing awareness, reflection, accountability, and support. If world-class athletes still want and benefit from coaching in a sport they have already mastered, coaching for physicians is just another tool to help us improve our abilities in and out of medicine.

The way I visualize coaching in medicine is a conscious effort to notice and evaluate how our thoughts affect our experiences and how our perspective shows up in the results of our lives. Coaching is more encompassing than advising or mentoring. It is about examining deeply held beliefs to see if they are really serving us, if they are in line with our values and how we want to live our lives.

Coaching has also been validated in medicine in several papers. In an article by Dyrbye et al. in JAMA Internal Medicine, measures of emotional exhaustion and burnout decreased in physicians who were coached and increased in those who were not.³ In another study from this year by McGonagle et al., a randomized, controlled trial showed that primary care physicians who had sessions (as short as 6 weeks) to address burnout, psychological capital, and job satisfaction experienced an improvement in measures which persisted for 6 months after intervention.⁴ Numerous other articles in medicine also exist to demonstrate the effect of coaching on mitigating burnout at an institutional level.

Physicians are inherently driven by their love of learning. As physicians, we love getting to the root cause of any problem and coming up with creative solutions. Any challenge we have, or just wanting to improve the quality of our lives, can be addressed with coaching. As perpetual students we can use coaching to truly master ourselves.

Dr. Shah is associate professor of surgery, Rush University Medical Center, Chicago. Instagram: ami.shahmdcoaching.

References

1. Gottlieb M et al. Med Educ. 2020 Feb;54(2):116-24.

2. Villwock JA et al. Int J Med Educ. 2016 Oct 31;7:364-9.

3. Dyrbye LN et al. JAMA Intern Med. 2019 Aug 5;179(10):1406-14.

4. McGonagle AK et al. J Occup Health Psychol. 2020 Apr 16. doi: 10.1037/ocp0000180.

Coaching is a new topic in medicine. I first heard about coaching several years ago and met the term with skepticism. I was unsure how coaching was different than mentoring or advising and I wondered about its usefulness. However, the reason that I even started to learn about coaching was because I was struggling. I had finally arrived in my career, I had my dream job with two healthy kids, a perfect house, and good marriage. I kept hearing the refrain in my head: “Is this all there is?” I had this arrival fallacy that after all this striving and straining that I would finally be content. I felt unfulfilled and was dissatisfied with where I was that was affecting all parts of my life.

As I was wrestling with these thoughts, I had an opportunity to become a coach to residents around the country through the Association of Women Surgeons. I discussed with them what fills them up, what gets them down, how to set goals, and what their goals were for the year, as well as imposter syndrome. Impostor syndrome is defined as a pattern in which an individual doubts their accomplishments or talents and has a persistent internalized fear of being exposed as a “fraud.” Despite external evidence of their competence, those experiencing this phenomenon remain convinced that they are fooling everyone around them and do not deserve all they have achieved. Individuals incorrectly attribute their success to luck or interpret it as a result of deceiving others into thinking they are more intelligent than they perceive themselves to be. Imposter syndrome is prevalent and deep in medicine. As perfectionists, we are especially vulnerable to imposter syndrome as we set unrealistic ideals for ourselves. When we fail to reach these ideals, we feel like frauds, setting up this cycle of self-doubt that is toxic. When we feel that we can’t achieve the goals that we are striving for we will always find ourselves lacking. There is a slow, insidious erosion of self over the years. Imposter syndrome is well documented in medicine and is even felt as early as medical school.^1,2

When I began coaching these residents the most profound thing that came out of these sessions was that my life was getting better – I knew what filled me up, what got me down, what my goals were for the year, and how I still deal with imposter syndrome. Coaching gave me a framework for helping determine what I wanted for the rest of my life. As I began coaching, I started learning all the ways in which I could figure out my values, my personal and professional goals, and perhaps most importantly, my relationships with myself and others.

Another perspective on coaching is to look at a professional athlete such as Tom Brady, one of the greatest quarterbacks of all time. He has a quarterback coach. No coach is going to be a better quarterback than Tom Brady. A coach for him is to be there as an advocate, break his fundamentals down technically, and help him improve upon what he already knows. A coach also identifies strengths and weaknesses, and helps him capitalize on both by bringing awareness, reflection, accountability, and support. If world-class athletes still want and benefit from coaching in a sport they have already mastered, coaching for physicians is just another tool to help us improve our abilities in and out of medicine.

The way I visualize coaching in medicine is a conscious effort to notice and evaluate how our thoughts affect our experiences and how our perspective shows up in the results of our lives. Coaching is more encompassing than advising or mentoring. It is about examining deeply held beliefs to see if they are really serving us, if they are in line with our values and how we want to live our lives.

Coaching has also been validated in medicine in several papers. In an article by Dyrbye et al. in JAMA Internal Medicine, measures of emotional exhaustion and burnout decreased in physicians who were coached and increased in those who were not.³ In another study from this year by McGonagle et al., a randomized, controlled trial showed that primary care physicians who had sessions (as short as 6 weeks) to address burnout, psychological capital, and job satisfaction experienced an improvement in measures which persisted for 6 months after intervention.⁴ Numerous other articles in medicine also exist to demonstrate the effect of coaching on mitigating burnout at an institutional level.

Physicians are inherently driven by their love of learning. As physicians, we love getting to the root cause of any problem and coming up with creative solutions. Any challenge we have, or just wanting to improve the quality of our lives, can be addressed with coaching. As perpetual students we can use coaching to truly master ourselves.

Dr. Shah is associate professor of surgery, Rush University Medical Center, Chicago. Instagram: ami.shahmdcoaching.

References

1. Gottlieb M et al. Med Educ. 2020 Feb;54(2):116-24.

2. Villwock JA et al. Int J Med Educ. 2016 Oct 31;7:364-9.

3. Dyrbye LN et al. JAMA Intern Med. 2019 Aug 5;179(10):1406-14.

4. McGonagle AK et al. J Occup Health Psychol. 2020 Apr 16. doi: 10.1037/ocp0000180.

A gene-replacement therapy called AT132 significantly decreases dependence on a ventilator among children with X-linked myotubular myopathy, according to research presented at the 2020 CNS-ICNA Conjoint Meeting, which was held virtually this year. The treatment also appears to improve patients’ motor function significantly and help them to achieve motor milestones.

belchonock/Thinkstock

The results come from a phase 1/2 study of two doses of AT132. Three of 17 patients who received the higher dose had fatal liver dysfunction. The researchers are investigating these cases and will communicate their findings.

X-linked myotubular myopathy is a rare and often fatal neuromuscular disease. Mutations in MTM1, which encodes the myotubularin enzyme that is required for the development and function of skeletal muscle, cause the disease, which affects about one in 50,000 to one in 40,000 newborn boys. The disease is associated with profound muscle weakness and impairment of neuromuscular and respiratory function. Patients with X-linked myotubular myopathy achieve motor milestones much later or not at all, and most require a ventilator or a feeding tube. The mortality by age 18 months is approximately 50%.
 

The ASPIRO trial

Investigators theorized that muscle tissue would be an appropriate therapeutic target because it does not display dystrophic or inflammatory changes in most patients. They identified adeno-associated virus AAV8 as a potential carrier for gene therapy, since it targets skeletal muscle effectively.

Nancy L. Kuntz, MD, an attending physician at Ann and Robert H. Lurie Children’s Hospital of Chicago, and colleagues conducted the ASPIRO trial to examine AT132 as a potential treatment for X-linked myotubular myopathy. Eligible patients were younger than 5 years or had previously enrolled in a natural history study of the disease, required ventilator support at baseline, and had no clinically significant underlying liver disease. Patients were randomly assigned to 1 × 10¹⁴ vg/kg of AAT132, 3 × 10¹⁴ vg/kg of AT132, or delayed treatment. Participants assigned to delayed treatment served as the study’s control group.

The study’s primary end points were safety and change in hours of daily ventilator support from baseline to week 24 after dosing. The investigators also examined a respiratory endpoint (i.e., maximal inspiratory pressure [MIP]) and neuromuscular endpoints (i.e., motor milestones, CHOP INTEND score, and muscle biopsy).
 

Treatment improved respiratory function

As of July 28, Dr. Kuntz and colleagues had enrolled 23 patients in the trial. Six participants received the lower dose of therapy, and 17 received the higher dose. Median age was 1.7 years for the low-dose group and 2.6 years for the high-dose group.

Patients assigned to receive the higher dose of therapy received treatment more recently than the low-dose group, and not all of the former have reached 48 weeks since treatment, said Dr. Kuntz. Fewer efficacy data are thus available for the high-dose group.

Each dose of AT132 was associated with a significantly greater decrease from baseline in least squares mean daily hours of ventilator dependence, compared with the control condition. At week 48, the mean reduction was approximately 19 hours/day for patients receiving 1 × 10¹⁴ vg/kg of AAT132 and approximately 13 hours per day for patients receiving 3 × 10¹⁴ vg/kg of AT132. The investigators did not perform a statistical comparison of the two doses because of differing protocols for ventilator weaning between groups. All six patients who received the lower dose achieved ventilator independence, as did one patient who received the higher dose.

In addition, all treated patients had significantly greater increases from baseline in least squares mean MIP, compared with controls. The mean increase was 45.7 cmH₂O for the low-dose group, 46.1 cmH₂O for the high-dose group, and −8.0 cmH₂O for controls.

Before treatment, most patients had not achieved any of the motor milestones that investigators assessed. After treatment, five of six patients receiving the low dose achieved independent walking, as did one in 10 patients receiving the high dose. No controls achieved this milestone. Treated patients also had significantly greater increases from baseline in least squares mean CHOP INTEND scores, compared with controls. At least at one time point, five of six patients receiving the low dose, six of 10 patients receiving the high dose, and one control patient achieved the mean score observed in healthy infants.

Patients in both treatment arms had improvements in muscle pathology at weeks 24 and 48, including improvements in organelle localization and fiber size. In addition, patients in both treatment arms had continued detectable vector copies and myotubularin protein expression at both time points.
 

Deaths under investigation

In the low-dose group, one patient had four serious treatment-emergent adverse events, and in the high-dose group, eight patients had 27 serious treatment-emergent adverse events. The three patients in the high-dose group who developed fatal liver dysfunction were among the older, heavier patients in the study and, consequently, received among the highest total doses of treatment. These patients had evidence of likely preexisting intrahepatic cholestasis.

“This clinical trial is on hold pending discussions between regulatory agencies and the study sponsor regarding additional recruitment and the duration of follow-up,” said Dr. Kuntz.

Audentes Therapeutics, which is developing AT132, funded the trial. Dr. Kuntz had no conflicts of interest.

[email protected]

SOURCE: Bönnemann CG et al. CNS-ICNA 2020, Abstract P.62.

A gene-replacement therapy called AT132 significantly decreases dependence on a ventilator among children with X-linked myotubular myopathy, according to research presented at the 2020 CNS-ICNA Conjoint Meeting, which was held virtually this year. The treatment also appears to improve patients’ motor function significantly and help them to achieve motor milestones.

belchonock/Thinkstock

The results come from a phase 1/2 study of two doses of AT132. Three of 17 patients who received the higher dose had fatal liver dysfunction. The researchers are investigating these cases and will communicate their findings.

X-linked myotubular myopathy is a rare and often fatal neuromuscular disease. Mutations in MTM1, which encodes the myotubularin enzyme that is required for the development and function of skeletal muscle, cause the disease, which affects about one in 50,000 to one in 40,000 newborn boys. The disease is associated with profound muscle weakness and impairment of neuromuscular and respiratory function. Patients with X-linked myotubular myopathy achieve motor milestones much later or not at all, and most require a ventilator or a feeding tube. The mortality by age 18 months is approximately 50%.
 

The ASPIRO trial

Investigators theorized that muscle tissue would be an appropriate therapeutic target because it does not display dystrophic or inflammatory changes in most patients. They identified adeno-associated virus AAV8 as a potential carrier for gene therapy, since it targets skeletal muscle effectively.

Nancy L. Kuntz, MD, an attending physician at Ann and Robert H. Lurie Children’s Hospital of Chicago, and colleagues conducted the ASPIRO trial to examine AT132 as a potential treatment for X-linked myotubular myopathy. Eligible patients were younger than 5 years or had previously enrolled in a natural history study of the disease, required ventilator support at baseline, and had no clinically significant underlying liver disease. Patients were randomly assigned to 1 × 10¹⁴ vg/kg of AAT132, 3 × 10¹⁴ vg/kg of AT132, or delayed treatment. Participants assigned to delayed treatment served as the study’s control group.

The study’s primary end points were safety and change in hours of daily ventilator support from baseline to week 24 after dosing. The investigators also examined a respiratory endpoint (i.e., maximal inspiratory pressure [MIP]) and neuromuscular endpoints (i.e., motor milestones, CHOP INTEND score, and muscle biopsy).
 

Treatment improved respiratory function

As of July 28, Dr. Kuntz and colleagues had enrolled 23 patients in the trial. Six participants received the lower dose of therapy, and 17 received the higher dose. Median age was 1.7 years for the low-dose group and 2.6 years for the high-dose group.

Patients assigned to receive the higher dose of therapy received treatment more recently than the low-dose group, and not all of the former have reached 48 weeks since treatment, said Dr. Kuntz. Fewer efficacy data are thus available for the high-dose group.

Each dose of AT132 was associated with a significantly greater decrease from baseline in least squares mean daily hours of ventilator dependence, compared with the control condition. At week 48, the mean reduction was approximately 19 hours/day for patients receiving 1 × 10¹⁴ vg/kg of AAT132 and approximately 13 hours per day for patients receiving 3 × 10¹⁴ vg/kg of AT132. The investigators did not perform a statistical comparison of the two doses because of differing protocols for ventilator weaning between groups. All six patients who received the lower dose achieved ventilator independence, as did one patient who received the higher dose.

In addition, all treated patients had significantly greater increases from baseline in least squares mean MIP, compared with controls. The mean increase was 45.7 cmH₂O for the low-dose group, 46.1 cmH₂O for the high-dose group, and −8.0 cmH₂O for controls.

Before treatment, most patients had not achieved any of the motor milestones that investigators assessed. After treatment, five of six patients receiving the low dose achieved independent walking, as did one in 10 patients receiving the high dose. No controls achieved this milestone. Treated patients also had significantly greater increases from baseline in least squares mean CHOP INTEND scores, compared with controls. At least at one time point, five of six patients receiving the low dose, six of 10 patients receiving the high dose, and one control patient achieved the mean score observed in healthy infants.

Patients in both treatment arms had improvements in muscle pathology at weeks 24 and 48, including improvements in organelle localization and fiber size. In addition, patients in both treatment arms had continued detectable vector copies and myotubularin protein expression at both time points.
 

Deaths under investigation

In the low-dose group, one patient had four serious treatment-emergent adverse events, and in the high-dose group, eight patients had 27 serious treatment-emergent adverse events. The three patients in the high-dose group who developed fatal liver dysfunction were among the older, heavier patients in the study and, consequently, received among the highest total doses of treatment. These patients had evidence of likely preexisting intrahepatic cholestasis.

“This clinical trial is on hold pending discussions between regulatory agencies and the study sponsor regarding additional recruitment and the duration of follow-up,” said Dr. Kuntz.

Audentes Therapeutics, which is developing AT132, funded the trial. Dr. Kuntz had no conflicts of interest.

[email protected]

SOURCE: Bönnemann CG et al. CNS-ICNA 2020, Abstract P.62.

A gene-replacement therapy called AT132 significantly decreases dependence on a ventilator among children with X-linked myotubular myopathy, according to research presented at the 2020 CNS-ICNA Conjoint Meeting, which was held virtually this year. The treatment also appears to improve patients’ motor function significantly and help them to achieve motor milestones.

belchonock/Thinkstock

The results come from a phase 1/2 study of two doses of AT132. Three of 17 patients who received the higher dose had fatal liver dysfunction. The researchers are investigating these cases and will communicate their findings.

X-linked myotubular myopathy is a rare and often fatal neuromuscular disease. Mutations in MTM1, which encodes the myotubularin enzyme that is required for the development and function of skeletal muscle, cause the disease, which affects about one in 50,000 to one in 40,000 newborn boys. The disease is associated with profound muscle weakness and impairment of neuromuscular and respiratory function. Patients with X-linked myotubular myopathy achieve motor milestones much later or not at all, and most require a ventilator or a feeding tube. The mortality by age 18 months is approximately 50%.
 

The ASPIRO trial

Investigators theorized that muscle tissue would be an appropriate therapeutic target because it does not display dystrophic or inflammatory changes in most patients. They identified adeno-associated virus AAV8 as a potential carrier for gene therapy, since it targets skeletal muscle effectively.

Nancy L. Kuntz, MD, an attending physician at Ann and Robert H. Lurie Children’s Hospital of Chicago, and colleagues conducted the ASPIRO trial to examine AT132 as a potential treatment for X-linked myotubular myopathy. Eligible patients were younger than 5 years or had previously enrolled in a natural history study of the disease, required ventilator support at baseline, and had no clinically significant underlying liver disease. Patients were randomly assigned to 1 × 10¹⁴ vg/kg of AAT132, 3 × 10¹⁴ vg/kg of AT132, or delayed treatment. Participants assigned to delayed treatment served as the study’s control group.

The study’s primary end points were safety and change in hours of daily ventilator support from baseline to week 24 after dosing. The investigators also examined a respiratory endpoint (i.e., maximal inspiratory pressure [MIP]) and neuromuscular endpoints (i.e., motor milestones, CHOP INTEND score, and muscle biopsy).
 

Treatment improved respiratory function

As of July 28, Dr. Kuntz and colleagues had enrolled 23 patients in the trial. Six participants received the lower dose of therapy, and 17 received the higher dose. Median age was 1.7 years for the low-dose group and 2.6 years for the high-dose group.

Patients assigned to receive the higher dose of therapy received treatment more recently than the low-dose group, and not all of the former have reached 48 weeks since treatment, said Dr. Kuntz. Fewer efficacy data are thus available for the high-dose group.

Each dose of AT132 was associated with a significantly greater decrease from baseline in least squares mean daily hours of ventilator dependence, compared with the control condition. At week 48, the mean reduction was approximately 19 hours/day for patients receiving 1 × 10¹⁴ vg/kg of AAT132 and approximately 13 hours per day for patients receiving 3 × 10¹⁴ vg/kg of AT132. The investigators did not perform a statistical comparison of the two doses because of differing protocols for ventilator weaning between groups. All six patients who received the lower dose achieved ventilator independence, as did one patient who received the higher dose.

In addition, all treated patients had significantly greater increases from baseline in least squares mean MIP, compared with controls. The mean increase was 45.7 cmH₂O for the low-dose group, 46.1 cmH₂O for the high-dose group, and −8.0 cmH₂O for controls.

Before treatment, most patients had not achieved any of the motor milestones that investigators assessed. After treatment, five of six patients receiving the low dose achieved independent walking, as did one in 10 patients receiving the high dose. No controls achieved this milestone. Treated patients also had significantly greater increases from baseline in least squares mean CHOP INTEND scores, compared with controls. At least at one time point, five of six patients receiving the low dose, six of 10 patients receiving the high dose, and one control patient achieved the mean score observed in healthy infants.

Patients in both treatment arms had improvements in muscle pathology at weeks 24 and 48, including improvements in organelle localization and fiber size. In addition, patients in both treatment arms had continued detectable vector copies and myotubularin protein expression at both time points.
 

Deaths under investigation

In the low-dose group, one patient had four serious treatment-emergent adverse events, and in the high-dose group, eight patients had 27 serious treatment-emergent adverse events. The three patients in the high-dose group who developed fatal liver dysfunction were among the older, heavier patients in the study and, consequently, received among the highest total doses of treatment. These patients had evidence of likely preexisting intrahepatic cholestasis.

“This clinical trial is on hold pending discussions between regulatory agencies and the study sponsor regarding additional recruitment and the duration of follow-up,” said Dr. Kuntz.

Audentes Therapeutics, which is developing AT132, funded the trial. Dr. Kuntz had no conflicts of interest.

[email protected]

SOURCE: Bönnemann CG et al. CNS-ICNA 2020, Abstract P.62.