Clinical Review

Mr. G is a 67-year-old veteran. During the Vietnam War, he had the “most dangerous job”: helicopter door gunner and mechanic. He served in multiple combat missions and was under constant threat of attack. On returning to the U.S., he experienced anger outbursts, nightmares, hypervigilance, and urges to engage in dangerous behavior, such as driving a motorcycle more than 100 mph. Then he began abusing alcohol and drugs. Mr. G’s behavior and substance abuse eventually led to strained family relationships, termination from a high-paying job, and homelessness.

In 2001, the Washington DC VAMC homeless and substance abuse staff provided outreach and services that helped him secure permanent subsidized housing, achieve and maintain sobriety, get treatment for posttraumatic stress disorder (PTSD), and get full-time employment. Mr. G has maintained permanent supported housing status for 9 years, regained a sense of purpose, remained drug- and alcohol-free since 2001, attended a Vietnam combat PTSD support group weekly, and been an exemplary employee for 8 years.

In 2009, on any given night in the U.S., more than 75,000 veterans were without a permanent home and living on the streets, as Mr. G had been.¹ Nearly 150,000 other veterans were spending the night in an emergency shelter or transitional housing. In early 2010, the U.S. Interagency Council on Homelessness (USICH) developed a strategic plan to align federal resources toward 4 key objectives, which included preventing and ending homelessness among veterans. Since then, the most dramatic reductions in homelessness have occurred among veterans, with an overall 33% decline in chronic homelessness nationwide.

According to the U.S. Department of Housing and Urban Development (HUD), permanent housing is defined as community-based housing without a designated length of stay in which formerly homeless individuals live as independently as possible.² Under permanent housing, a program participant must be the tenant on a lease for at least 1 year, and the lease is renewable and terminable only for cause. The federal definition of the chronically homeless is a person who is homeless and lives in a place not meant for human habitation, in a safe haven, or in an emergency shelter continuously for at least 1 year; or on at least 4 separate occasions within the past 3 years; and who can be diagnosed with ≥ 1 of the following conditions: substance use disorder, serious mental illness, developmental disability as defined in section 102 of the Developmental Disabilities Assistance Bill of Rights Act of 2000 (42 U.S.C. 15002), PTSD, cognitive impairments caused by brain injury, and chronic physical illness or disability.³

Ending homelessness makes sense from a variety of perspectives. From a moral perspective, no one should experience homelessness, but this is especially true for the men and women who have served in the U.S. military. From a health care and resources perspective, homelessness is associated with poorer medical outcomes; higher medical costs for emergency department visits and hospital admissions; longer stays (often for conditions that could be treated in ambulatory settings); and increased mortality.^4-7 From a societal perspective, homelessness is associated with costs for shelters and other forms of temporary housing and with higher justice system costs stemming from police, court, and jail involvement.⁸ The higher justice system costs are in part attributable to significantly longer incarcerations for homeless persons than for demographically similar inmates who have been similarly charged but have housing.⁹ According to recent studies, significant cost reductions have been achieved by addressing homelessness and providing permanent housing, particularly for the chronically homeless with mental illness.^10-14

This article describes the efforts that have been made, through collaborations and coalitions of government and community partners, to identify and address risk factors for homelessness in Washington, DC—and ultimately to end veteran homelessness in the nation’s capitol.

Historic Perspective on Veteran Homelessness

Although the problem was first described after the Revolutionary War and again after the Civil War, homelessness among U.S. veterans has only recently been academically studied. During the colonial period, men often were promised pensions or land grants in exchange for military service. Several states failed to deliver on these promises, throwing veterans into dire financial circumstances and leaving them homeless. By the end of the Civil War, the size of the veteran population (almost 2 million, counting only those who fought for the Union), combined with an unemployment rate of 40% and economic downturns, led to thousands of veterans becoming homeless.^15,16

Homelessness among veterans continued after World War I. In 1932, more than 15,000 homeless and disabled “Bonus Army,” World War I veterans, marched on Washington to demand payment of the financial benefits promised for their military service.

Although World War II and Korean War veterans did not experience homelessness as previous veterans had, the problem resurfaced after Vietnam—the combat veterans of that war were overrepresented among the homeless.^17,18 Those at highest risk ranged from age 35 to 44 years in the early years of the all-volunteer military. It has been suggested that their increased risk may reflect social selection—volunteers for military service came from poor economic backgrounds with fewer social supports.¹⁹ A more recent study found that 3.8% of more than 300,000 Iraq and Afghanistan veterans who were followed for 5 years after military discharge experienced a homeless episode.²⁰ Female veterans similarly are overrepresented among the homeless.²¹ Female veterans represent only 1% of the overall female population, yet 3% to 4% are homeless.

Homelessness has always been a social problem, but only during the 1970s and 1980s did homelessness increase in importance—the number of visibly homeless people rose during that period—and investigators began to study and address the issue. Experts have described several factors that contributed to the increase in homelessness during that time.^22,23 First, as part of the deinstitutionalization initiative, thousands of mentally ill persons were released from state mental hospitals without a plan in place for affordable or supervised housing. Second, single-room-occupancy dwellings in poor areas, where transient single men lived, were demolished, and affordable housing options decreased. Third, economic and social changes were factors, such as a decreased need for seasonal and unskilled labor; reduced likelihood that relatives will take in homeless family members; and decriminalized public intoxication, loitering, and vagrancy. Out of these conditions came an interest in studying the causes of and risk factors for veteran homelessness and in developing a multipronged approach to end veteran homelessness.

Demographics

Nationally, veterans account for 9% of the homeless population.²⁴ Predominantly, they are single men living in urban areas—only about 9% are women—and 43% served during the Vietnam era.²⁴ Among homeless veterans, minorities are overrepresented—45% are African American or Hispanic, as contrasted with 10% and 3%, respectively, of the general population. More than two-thirds served in the military for more than 3 years, and 76% have a history of mental illness or substance abuse. Compared with the general homeless population, homeless veterans are older, better educated, more likely to have been married, and more likely to have health insurance, primarily through the VA.^24,25

The Washington, DC, metropolitan area encompasses the District of Columbia, northern Virginia, the tricounty area of southern Maryland, and Montgomery and Prince George’s counties in Maryland. Demographics for veterans in this area vary somewhat from national figures. According to the 2015 Point-in-Time survey of the homeless, veterans accounted for 5% of the homeless population (less than the national percentage). Most homeless veterans were single men (11.6% were women) and African American (65% of single adults, 85% of adults in families). Forty-five percent reported being employed and 40% had a substance use disorder or a serious mental illness. A large proportion also had at least 1 physical disability, such as hypertension, hepatitis, arthritis, diabetes mellitus, or heart disease.²⁶

Risk Factors

Multiple studies and multivariate analyses have determined that veteran status is associated with an increased risk for homelessness for both male and female veterans.²⁷ Female veterans were 3 times and male veterans 2 times more likely than nonveterans to become homeless, even when poverty, age, race, and geographic variation were controlled. A recent systematic review of U.S. veterans found that the strongest and most consistent risk factors for homelessness were substance use disorders and mental illness, particularly psychotic disorders. Posttraumatic stress disorder was not more significant than other mental conditions but it was a risk factor. Low income, unemployment, and poor money management were also factors.

Social risk factors include lack of support from family and friends. Military service with multiple deployments, transfers, and on-base housing may contribute to interruption of social support and lead to social isolation, thus increasing veterans’ risk for homelessness. Some studies have found that veterans are more likely to report physical injury or medical problems as contributing to homelessness and more likely to have 2 or more chronic medical conditions. Last, history of incarceration and adverse childhood experiences (eg, behavioral problems, family instability, foster care, childhood abuse) also have been found to be risk factors for homelessness among veterans and nonveterans alike.

Understanding these risk factors is an important step in addressing homelessness. Homelessness prevention efforts can screen for these risk factors and then intervene as quickly as possible. Access to mental health and substance abuse services, employment assistance, disability benefits and other income supports, and social services may prevent initial and subsequent episodes of homelessness. The VA, as the largest integrated health system in the U.S., is a critical safety net for low-income and disabled veterans with complex psychosocial needs. One study found access to VA service-connected pensions was protective against homelessness.²⁸

Addressing Homelessness

There are 10 USICH-recommended strategies for ending veteran homelessness (Table 1). These strategies cannot be achieved by any single federal agency or exclusively by government agencies—they require multipronged approaches and private and public partnerships. In early 2011, the staff of the Washington DC VAMC homeless program identified a single point of contact who would regularly meet with each Continuum of Care local planning body and each Public Housing Authority (PHA). This contact could identify homeless veterans regardless of the agency from which they were requesting assistance. The contact also facilitated identification of specific bottleneck issues contributing to delays in housing veterans. One such issue was that veterans were filling out application forms by themselves, and in some cases, their information was incomplete, or supporting documents (eg, government-issued IDs) were missing. The VA team adjusted the procedures to better meet veterans’ needs. Now veterans identified as meeting requirements for housing assistance are enrolled in classes in which a caseworker reviews their completed applications to ensure they are complete and supporting documents included. If an ID is needed, the caseworker facilitates the process and then submits the veteran’s application to the local PHA for processing. The result has been no returned applications.

Another issue was that in some cases a veteran spoke with the PHA and indicated interest in an apartment and only later found out that the apartment failed inspection. There would then be back-and-forth communications between PHA and landlord to have repairs made so the unit could pass inspection, which often resulted in long delays. The solution was to have a stock of preinspected housing options. The Washington DC VAMC homeless program now has a housing specialist who identifies preinspected units and can expedite the lease to a veteran. In addition, the homeless program in partnership with the PHA now sets up regular meet-and-greet events for landlords and veterans so veterans can preview available rentals.

Housing-First Model

The homeless program readily adopted the housing-first model. This model focuses on helping individuals and families access housing as quickly as possible and remain permanently housed; this assistance is not time-limited but ongoing. After housing placement, the client can choose from an array of both time-limited and long-term services, which are individualized to promote housing stability and individual well-being. Most important, housing is not contingent on compliance with services. Instead, participants must comply with a standard lease agreement and are provided the services and support that can help them do so successfully. Services are determined by completing needs assessments. In addition, as a veteran is applying for housing, a caseworker actively uses motivational interviewing techniques to enhance the likelihood that the veteran will accept services.

Providing Core Service to Veterans

In 2012, the Washington DC VAMC opened the Community Resource and Referral Center (CRRC) as a one-stop shop for homeless and at-risk veterans in need of basic, core, wraparound services through the VA. Basic services include showers, laundry facilities, and a chapel. The CRRC has onsite psychiatric services that can engage veterans in mental health and substance abuse treatment. There is also an onsite primary care team who specialize in working with the homeless and can address any acute or chronic medical problems. For veterans who want to return to employment, there is an onsite Compensated Work Therapy program, which has uniquely partnered with the VAMC as well as community partners (eg, National Archives, Smithsonian Institution, Quantico National Cemetery, Arlington National Cemetery) to offer therapeutic job experiences that often lead to gainful full-time employment.

Veterans can use an onsite computer lab to complete resumes and apply for employment online, with the assistance of veteran peer specialists and vocational rehabilitation specialists. For veterans who are unable to work, the homeless program team assists with disability applications. Social Security, Veterans Benefits Administration representatives, and Legal Aid have office hours at the CRRC to provide one-stop shopping for veterans. Additional community partnerships have led to classes to help veterans manage income effectively, and veterans are assisted with completing tax returns.

Representatives from the Veterans Justice Outreach (VJO) and Health Care for Re-entry Veterans (HCRV) programs are also onsite. The VJO program provides outreach, assessment, and case management for justice-involved veterans to prevent unnecessary criminalization of mental illness and extended incarceration. A VJO program specialist works with courts, legal representatives, and jails and acts as a liaison to engage veterans in treatment and prevent incarcerations through jail diversion strategies. The HCRV program assists incarcerated veterans with reentry into the community through outreach and prerelease assessments, and referrals and links to medical, psychiatric, and social services, including employment services on release. This program also can provide short-term case management assistance on release.

In 2013, to further the implementation of the USICH strategies in the Washington, DC, metropolitan area, 12 local government and nonprofit agencies entered into the Veterans NOW coalition (Table 2). This collaboration enabled development of a coordinated effort to identify all area veterans experiencing homelessness, regardless of which agency the veterans contacted. Further, this team set up processes to assess veterans’ housing and service needs and to match each veteran to the most appropriate housing resource. There was consensus regarding use of the Service Prioritization Decision Assistance Tool (SPDAT) as the evidence-informed approach for prioritizing client needs and identifying areas in which support is most likely needed to prevent housing instability.²⁹ More than 50 staff members at 20 different agencies in the District of Columbia have now been trained and are using this tool.

Outcomes

In 2010, the Point-in-Time count identified 718 homeless veterans in the Washington, DC, metropolitan area. By 2016, that number had dropped to 326 (55% reduction). During this same period, the number of veterans served by the Washington DC VAMC homeless program more than tripled, from 2,100 individuals in 2010 to nearly 6,400 in 2015. The coalition has housed or prevented homelessness for nearly 1,300 veterans during the past 2 years alone. Veterans were housed through multiple programs and efforts, including VA Supportive Housing (VASH), Supportive Services for Veteran Families, and Washington, DC Department of Human Services Permanent Supportive Housing. During the past year, > 60% of veterans were successfully placed in VASH housing within 90 days of application submission. Table 3 lists the national targets for assessing performance measurement and success. Not only were the various performance measure benchmarks exceeded, but more important, > 90% of veterans in VASH and Health Care for Homeless Veterans were able to keep their housing stabilized. Using SPDAT, the most chronically homeless and vulnerable were housed first, which accounts for the lower numbers of homeless Washington, DC, area veterans with substance abuse and mental health problems identified in the Point-in-Time survey.

Discussion

At the Washington DC VAMC, HCHV program staff members used evidence-based and evidence-informed tools, collaborated with community partners, and implemented recommended best practices to end veteran homelessness by 2015. Permanent supportive housing through VASH is crucial for helping veterans overcome their lack of income and in providing mechanisms for engaging in mental health and substance abuse services as well as primary care and therapeutic employment opportunities.

When former VA Secretary Eric K. Shinseki first announced the goal of ending veteran homelessness by 2015, many people questioned this goal’s attainability and feasibility. However, through the adoption of the strategies recommended by USICH, the establishment of government and community partnerships (including faith-based groups) and the implementation of programs addressing substance abuse issues, mental and physical health, income limitations, and employment, this goal now seems possible. Overall veteran homelessness decreased by 36% since 2010, and unsheltered homelessness decreased by nearly 50%.³⁰ By the end of 2015, nearly 65,000 veterans are in permanent housing nationwide, and another 8,100 are in the process of obtaining permanent supportive housing. Also, 87% of unsheltered veterans were able to move to safe housing within 30 days of engagement. Last, Supportive Services for Veteran Families was able to assist more than 156,800 individuals (single veterans as well as their children and families).

Sustainability from a national perspective also depends on continued federal funding. Mr. G, described at the beginning of this article, served his country honorably but then experienced the factors that put him at risk for homelessness. Through a veteran-centric team approach, he was able to successfully address each of these factors. As there are another 500 homeless veterans in Washington, DC, much work still needs to be done. With important collaborations and partnerships now in place, the goal of ending veteran homelessness in the District of Columbia is within sight. When homelessness is a thing of the past, we will truly be able to Welcome Home each veteran.

Mr. G is a 67-year-old veteran. During the Vietnam War, he had the “most dangerous job”: helicopter door gunner and mechanic. He served in multiple combat missions and was under constant threat of attack. On returning to the U.S., he experienced anger outbursts, nightmares, hypervigilance, and urges to engage in dangerous behavior, such as driving a motorcycle more than 100 mph. Then he began abusing alcohol and drugs. Mr. G’s behavior and substance abuse eventually led to strained family relationships, termination from a high-paying job, and homelessness.

In 2001, the Washington DC VAMC homeless and substance abuse staff provided outreach and services that helped him secure permanent subsidized housing, achieve and maintain sobriety, get treatment for posttraumatic stress disorder (PTSD), and get full-time employment. Mr. G has maintained permanent supported housing status for 9 years, regained a sense of purpose, remained drug- and alcohol-free since 2001, attended a Vietnam combat PTSD support group weekly, and been an exemplary employee for 8 years.

In 2009, on any given night in the U.S., more than 75,000 veterans were without a permanent home and living on the streets, as Mr. G had been.¹ Nearly 150,000 other veterans were spending the night in an emergency shelter or transitional housing. In early 2010, the U.S. Interagency Council on Homelessness (USICH) developed a strategic plan to align federal resources toward 4 key objectives, which included preventing and ending homelessness among veterans. Since then, the most dramatic reductions in homelessness have occurred among veterans, with an overall 33% decline in chronic homelessness nationwide.

According to the U.S. Department of Housing and Urban Development (HUD), permanent housing is defined as community-based housing without a designated length of stay in which formerly homeless individuals live as independently as possible.² Under permanent housing, a program participant must be the tenant on a lease for at least 1 year, and the lease is renewable and terminable only for cause. The federal definition of the chronically homeless is a person who is homeless and lives in a place not meant for human habitation, in a safe haven, or in an emergency shelter continuously for at least 1 year; or on at least 4 separate occasions within the past 3 years; and who can be diagnosed with ≥ 1 of the following conditions: substance use disorder, serious mental illness, developmental disability as defined in section 102 of the Developmental Disabilities Assistance Bill of Rights Act of 2000 (42 U.S.C. 15002), PTSD, cognitive impairments caused by brain injury, and chronic physical illness or disability.³

Ending homelessness makes sense from a variety of perspectives. From a moral perspective, no one should experience homelessness, but this is especially true for the men and women who have served in the U.S. military. From a health care and resources perspective, homelessness is associated with poorer medical outcomes; higher medical costs for emergency department visits and hospital admissions; longer stays (often for conditions that could be treated in ambulatory settings); and increased mortality.^4-7 From a societal perspective, homelessness is associated with costs for shelters and other forms of temporary housing and with higher justice system costs stemming from police, court, and jail involvement.⁸ The higher justice system costs are in part attributable to significantly longer incarcerations for homeless persons than for demographically similar inmates who have been similarly charged but have housing.⁹ According to recent studies, significant cost reductions have been achieved by addressing homelessness and providing permanent housing, particularly for the chronically homeless with mental illness.^10-14

This article describes the efforts that have been made, through collaborations and coalitions of government and community partners, to identify and address risk factors for homelessness in Washington, DC—and ultimately to end veteran homelessness in the nation’s capitol.

Historic Perspective on Veteran Homelessness

Although the problem was first described after the Revolutionary War and again after the Civil War, homelessness among U.S. veterans has only recently been academically studied. During the colonial period, men often were promised pensions or land grants in exchange for military service. Several states failed to deliver on these promises, throwing veterans into dire financial circumstances and leaving them homeless. By the end of the Civil War, the size of the veteran population (almost 2 million, counting only those who fought for the Union), combined with an unemployment rate of 40% and economic downturns, led to thousands of veterans becoming homeless.^15,16

Homelessness among veterans continued after World War I. In 1932, more than 15,000 homeless and disabled “Bonus Army,” World War I veterans, marched on Washington to demand payment of the financial benefits promised for their military service.

Although World War II and Korean War veterans did not experience homelessness as previous veterans had, the problem resurfaced after Vietnam—the combat veterans of that war were overrepresented among the homeless.^17,18 Those at highest risk ranged from age 35 to 44 years in the early years of the all-volunteer military. It has been suggested that their increased risk may reflect social selection—volunteers for military service came from poor economic backgrounds with fewer social supports.¹⁹ A more recent study found that 3.8% of more than 300,000 Iraq and Afghanistan veterans who were followed for 5 years after military discharge experienced a homeless episode.²⁰ Female veterans similarly are overrepresented among the homeless.²¹ Female veterans represent only 1% of the overall female population, yet 3% to 4% are homeless.

Homelessness has always been a social problem, but only during the 1970s and 1980s did homelessness increase in importance—the number of visibly homeless people rose during that period—and investigators began to study and address the issue. Experts have described several factors that contributed to the increase in homelessness during that time.^22,23 First, as part of the deinstitutionalization initiative, thousands of mentally ill persons were released from state mental hospitals without a plan in place for affordable or supervised housing. Second, single-room-occupancy dwellings in poor areas, where transient single men lived, were demolished, and affordable housing options decreased. Third, economic and social changes were factors, such as a decreased need for seasonal and unskilled labor; reduced likelihood that relatives will take in homeless family members; and decriminalized public intoxication, loitering, and vagrancy. Out of these conditions came an interest in studying the causes of and risk factors for veteran homelessness and in developing a multipronged approach to end veteran homelessness.

Demographics

Nationally, veterans account for 9% of the homeless population.²⁴ Predominantly, they are single men living in urban areas—only about 9% are women—and 43% served during the Vietnam era.²⁴ Among homeless veterans, minorities are overrepresented—45% are African American or Hispanic, as contrasted with 10% and 3%, respectively, of the general population. More than two-thirds served in the military for more than 3 years, and 76% have a history of mental illness or substance abuse. Compared with the general homeless population, homeless veterans are older, better educated, more likely to have been married, and more likely to have health insurance, primarily through the VA.^24,25

The Washington, DC, metropolitan area encompasses the District of Columbia, northern Virginia, the tricounty area of southern Maryland, and Montgomery and Prince George’s counties in Maryland. Demographics for veterans in this area vary somewhat from national figures. According to the 2015 Point-in-Time survey of the homeless, veterans accounted for 5% of the homeless population (less than the national percentage). Most homeless veterans were single men (11.6% were women) and African American (65% of single adults, 85% of adults in families). Forty-five percent reported being employed and 40% had a substance use disorder or a serious mental illness. A large proportion also had at least 1 physical disability, such as hypertension, hepatitis, arthritis, diabetes mellitus, or heart disease.²⁶

Risk Factors

Multiple studies and multivariate analyses have determined that veteran status is associated with an increased risk for homelessness for both male and female veterans.²⁷ Female veterans were 3 times and male veterans 2 times more likely than nonveterans to become homeless, even when poverty, age, race, and geographic variation were controlled. A recent systematic review of U.S. veterans found that the strongest and most consistent risk factors for homelessness were substance use disorders and mental illness, particularly psychotic disorders. Posttraumatic stress disorder was not more significant than other mental conditions but it was a risk factor. Low income, unemployment, and poor money management were also factors.

Social risk factors include lack of support from family and friends. Military service with multiple deployments, transfers, and on-base housing may contribute to interruption of social support and lead to social isolation, thus increasing veterans’ risk for homelessness. Some studies have found that veterans are more likely to report physical injury or medical problems as contributing to homelessness and more likely to have 2 or more chronic medical conditions. Last, history of incarceration and adverse childhood experiences (eg, behavioral problems, family instability, foster care, childhood abuse) also have been found to be risk factors for homelessness among veterans and nonveterans alike.

Understanding these risk factors is an important step in addressing homelessness. Homelessness prevention efforts can screen for these risk factors and then intervene as quickly as possible. Access to mental health and substance abuse services, employment assistance, disability benefits and other income supports, and social services may prevent initial and subsequent episodes of homelessness. The VA, as the largest integrated health system in the U.S., is a critical safety net for low-income and disabled veterans with complex psychosocial needs. One study found access to VA service-connected pensions was protective against homelessness.²⁸

Addressing Homelessness

There are 10 USICH-recommended strategies for ending veteran homelessness (Table 1). These strategies cannot be achieved by any single federal agency or exclusively by government agencies—they require multipronged approaches and private and public partnerships. In early 2011, the staff of the Washington DC VAMC homeless program identified a single point of contact who would regularly meet with each Continuum of Care local planning body and each Public Housing Authority (PHA). This contact could identify homeless veterans regardless of the agency from which they were requesting assistance. The contact also facilitated identification of specific bottleneck issues contributing to delays in housing veterans. One such issue was that veterans were filling out application forms by themselves, and in some cases, their information was incomplete, or supporting documents (eg, government-issued IDs) were missing. The VA team adjusted the procedures to better meet veterans’ needs. Now veterans identified as meeting requirements for housing assistance are enrolled in classes in which a caseworker reviews their completed applications to ensure they are complete and supporting documents included. If an ID is needed, the caseworker facilitates the process and then submits the veteran’s application to the local PHA for processing. The result has been no returned applications.

Another issue was that in some cases a veteran spoke with the PHA and indicated interest in an apartment and only later found out that the apartment failed inspection. There would then be back-and-forth communications between PHA and landlord to have repairs made so the unit could pass inspection, which often resulted in long delays. The solution was to have a stock of preinspected housing options. The Washington DC VAMC homeless program now has a housing specialist who identifies preinspected units and can expedite the lease to a veteran. In addition, the homeless program in partnership with the PHA now sets up regular meet-and-greet events for landlords and veterans so veterans can preview available rentals.

Housing-First Model

The homeless program readily adopted the housing-first model. This model focuses on helping individuals and families access housing as quickly as possible and remain permanently housed; this assistance is not time-limited but ongoing. After housing placement, the client can choose from an array of both time-limited and long-term services, which are individualized to promote housing stability and individual well-being. Most important, housing is not contingent on compliance with services. Instead, participants must comply with a standard lease agreement and are provided the services and support that can help them do so successfully. Services are determined by completing needs assessments. In addition, as a veteran is applying for housing, a caseworker actively uses motivational interviewing techniques to enhance the likelihood that the veteran will accept services.

Providing Core Service to Veterans

In 2012, the Washington DC VAMC opened the Community Resource and Referral Center (CRRC) as a one-stop shop for homeless and at-risk veterans in need of basic, core, wraparound services through the VA. Basic services include showers, laundry facilities, and a chapel. The CRRC has onsite psychiatric services that can engage veterans in mental health and substance abuse treatment. There is also an onsite primary care team who specialize in working with the homeless and can address any acute or chronic medical problems. For veterans who want to return to employment, there is an onsite Compensated Work Therapy program, which has uniquely partnered with the VAMC as well as community partners (eg, National Archives, Smithsonian Institution, Quantico National Cemetery, Arlington National Cemetery) to offer therapeutic job experiences that often lead to gainful full-time employment.

Veterans can use an onsite computer lab to complete resumes and apply for employment online, with the assistance of veteran peer specialists and vocational rehabilitation specialists. For veterans who are unable to work, the homeless program team assists with disability applications. Social Security, Veterans Benefits Administration representatives, and Legal Aid have office hours at the CRRC to provide one-stop shopping for veterans. Additional community partnerships have led to classes to help veterans manage income effectively, and veterans are assisted with completing tax returns.

Representatives from the Veterans Justice Outreach (VJO) and Health Care for Re-entry Veterans (HCRV) programs are also onsite. The VJO program provides outreach, assessment, and case management for justice-involved veterans to prevent unnecessary criminalization of mental illness and extended incarceration. A VJO program specialist works with courts, legal representatives, and jails and acts as a liaison to engage veterans in treatment and prevent incarcerations through jail diversion strategies. The HCRV program assists incarcerated veterans with reentry into the community through outreach and prerelease assessments, and referrals and links to medical, psychiatric, and social services, including employment services on release. This program also can provide short-term case management assistance on release.

In 2013, to further the implementation of the USICH strategies in the Washington, DC, metropolitan area, 12 local government and nonprofit agencies entered into the Veterans NOW coalition (Table 2). This collaboration enabled development of a coordinated effort to identify all area veterans experiencing homelessness, regardless of which agency the veterans contacted. Further, this team set up processes to assess veterans’ housing and service needs and to match each veteran to the most appropriate housing resource. There was consensus regarding use of the Service Prioritization Decision Assistance Tool (SPDAT) as the evidence-informed approach for prioritizing client needs and identifying areas in which support is most likely needed to prevent housing instability.²⁹ More than 50 staff members at 20 different agencies in the District of Columbia have now been trained and are using this tool.

Outcomes

In 2010, the Point-in-Time count identified 718 homeless veterans in the Washington, DC, metropolitan area. By 2016, that number had dropped to 326 (55% reduction). During this same period, the number of veterans served by the Washington DC VAMC homeless program more than tripled, from 2,100 individuals in 2010 to nearly 6,400 in 2015. The coalition has housed or prevented homelessness for nearly 1,300 veterans during the past 2 years alone. Veterans were housed through multiple programs and efforts, including VA Supportive Housing (VASH), Supportive Services for Veteran Families, and Washington, DC Department of Human Services Permanent Supportive Housing. During the past year, > 60% of veterans were successfully placed in VASH housing within 90 days of application submission. Table 3 lists the national targets for assessing performance measurement and success. Not only were the various performance measure benchmarks exceeded, but more important, > 90% of veterans in VASH and Health Care for Homeless Veterans were able to keep their housing stabilized. Using SPDAT, the most chronically homeless and vulnerable were housed first, which accounts for the lower numbers of homeless Washington, DC, area veterans with substance abuse and mental health problems identified in the Point-in-Time survey.

Discussion

At the Washington DC VAMC, HCHV program staff members used evidence-based and evidence-informed tools, collaborated with community partners, and implemented recommended best practices to end veteran homelessness by 2015. Permanent supportive housing through VASH is crucial for helping veterans overcome their lack of income and in providing mechanisms for engaging in mental health and substance abuse services as well as primary care and therapeutic employment opportunities.

When former VA Secretary Eric K. Shinseki first announced the goal of ending veteran homelessness by 2015, many people questioned this goal’s attainability and feasibility. However, through the adoption of the strategies recommended by USICH, the establishment of government and community partnerships (including faith-based groups) and the implementation of programs addressing substance abuse issues, mental and physical health, income limitations, and employment, this goal now seems possible. Overall veteran homelessness decreased by 36% since 2010, and unsheltered homelessness decreased by nearly 50%.³⁰ By the end of 2015, nearly 65,000 veterans are in permanent housing nationwide, and another 8,100 are in the process of obtaining permanent supportive housing. Also, 87% of unsheltered veterans were able to move to safe housing within 30 days of engagement. Last, Supportive Services for Veteran Families was able to assist more than 156,800 individuals (single veterans as well as their children and families).

Sustainability from a national perspective also depends on continued federal funding. Mr. G, described at the beginning of this article, served his country honorably but then experienced the factors that put him at risk for homelessness. Through a veteran-centric team approach, he was able to successfully address each of these factors. As there are another 500 homeless veterans in Washington, DC, much work still needs to be done. With important collaborations and partnerships now in place, the goal of ending veteran homelessness in the District of Columbia is within sight. When homelessness is a thing of the past, we will truly be able to Welcome Home each veteran.

Mr. G is a 67-year-old veteran. During the Vietnam War, he had the “most dangerous job”: helicopter door gunner and mechanic. He served in multiple combat missions and was under constant threat of attack. On returning to the U.S., he experienced anger outbursts, nightmares, hypervigilance, and urges to engage in dangerous behavior, such as driving a motorcycle more than 100 mph. Then he began abusing alcohol and drugs. Mr. G’s behavior and substance abuse eventually led to strained family relationships, termination from a high-paying job, and homelessness.

In 2001, the Washington DC VAMC homeless and substance abuse staff provided outreach and services that helped him secure permanent subsidized housing, achieve and maintain sobriety, get treatment for posttraumatic stress disorder (PTSD), and get full-time employment. Mr. G has maintained permanent supported housing status for 9 years, regained a sense of purpose, remained drug- and alcohol-free since 2001, attended a Vietnam combat PTSD support group weekly, and been an exemplary employee for 8 years.

In 2009, on any given night in the U.S., more than 75,000 veterans were without a permanent home and living on the streets, as Mr. G had been.¹ Nearly 150,000 other veterans were spending the night in an emergency shelter or transitional housing. In early 2010, the U.S. Interagency Council on Homelessness (USICH) developed a strategic plan to align federal resources toward 4 key objectives, which included preventing and ending homelessness among veterans. Since then, the most dramatic reductions in homelessness have occurred among veterans, with an overall 33% decline in chronic homelessness nationwide.

According to the U.S. Department of Housing and Urban Development (HUD), permanent housing is defined as community-based housing without a designated length of stay in which formerly homeless individuals live as independently as possible.² Under permanent housing, a program participant must be the tenant on a lease for at least 1 year, and the lease is renewable and terminable only for cause. The federal definition of the chronically homeless is a person who is homeless and lives in a place not meant for human habitation, in a safe haven, or in an emergency shelter continuously for at least 1 year; or on at least 4 separate occasions within the past 3 years; and who can be diagnosed with ≥ 1 of the following conditions: substance use disorder, serious mental illness, developmental disability as defined in section 102 of the Developmental Disabilities Assistance Bill of Rights Act of 2000 (42 U.S.C. 15002), PTSD, cognitive impairments caused by brain injury, and chronic physical illness or disability.³

Ending homelessness makes sense from a variety of perspectives. From a moral perspective, no one should experience homelessness, but this is especially true for the men and women who have served in the U.S. military. From a health care and resources perspective, homelessness is associated with poorer medical outcomes; higher medical costs for emergency department visits and hospital admissions; longer stays (often for conditions that could be treated in ambulatory settings); and increased mortality.^4-7 From a societal perspective, homelessness is associated with costs for shelters and other forms of temporary housing and with higher justice system costs stemming from police, court, and jail involvement.⁸ The higher justice system costs are in part attributable to significantly longer incarcerations for homeless persons than for demographically similar inmates who have been similarly charged but have housing.⁹ According to recent studies, significant cost reductions have been achieved by addressing homelessness and providing permanent housing, particularly for the chronically homeless with mental illness.^10-14

This article describes the efforts that have been made, through collaborations and coalitions of government and community partners, to identify and address risk factors for homelessness in Washington, DC—and ultimately to end veteran homelessness in the nation’s capitol.

Historic Perspective on Veteran Homelessness

Although the problem was first described after the Revolutionary War and again after the Civil War, homelessness among U.S. veterans has only recently been academically studied. During the colonial period, men often were promised pensions or land grants in exchange for military service. Several states failed to deliver on these promises, throwing veterans into dire financial circumstances and leaving them homeless. By the end of the Civil War, the size of the veteran population (almost 2 million, counting only those who fought for the Union), combined with an unemployment rate of 40% and economic downturns, led to thousands of veterans becoming homeless.^15,16

Homelessness among veterans continued after World War I. In 1932, more than 15,000 homeless and disabled “Bonus Army,” World War I veterans, marched on Washington to demand payment of the financial benefits promised for their military service.

Although World War II and Korean War veterans did not experience homelessness as previous veterans had, the problem resurfaced after Vietnam—the combat veterans of that war were overrepresented among the homeless.^17,18 Those at highest risk ranged from age 35 to 44 years in the early years of the all-volunteer military. It has been suggested that their increased risk may reflect social selection—volunteers for military service came from poor economic backgrounds with fewer social supports.¹⁹ A more recent study found that 3.8% of more than 300,000 Iraq and Afghanistan veterans who were followed for 5 years after military discharge experienced a homeless episode.²⁰ Female veterans similarly are overrepresented among the homeless.²¹ Female veterans represent only 1% of the overall female population, yet 3% to 4% are homeless.

Homelessness has always been a social problem, but only during the 1970s and 1980s did homelessness increase in importance—the number of visibly homeless people rose during that period—and investigators began to study and address the issue. Experts have described several factors that contributed to the increase in homelessness during that time.^22,23 First, as part of the deinstitutionalization initiative, thousands of mentally ill persons were released from state mental hospitals without a plan in place for affordable or supervised housing. Second, single-room-occupancy dwellings in poor areas, where transient single men lived, were demolished, and affordable housing options decreased. Third, economic and social changes were factors, such as a decreased need for seasonal and unskilled labor; reduced likelihood that relatives will take in homeless family members; and decriminalized public intoxication, loitering, and vagrancy. Out of these conditions came an interest in studying the causes of and risk factors for veteran homelessness and in developing a multipronged approach to end veteran homelessness.

Demographics

Nationally, veterans account for 9% of the homeless population.²⁴ Predominantly, they are single men living in urban areas—only about 9% are women—and 43% served during the Vietnam era.²⁴ Among homeless veterans, minorities are overrepresented—45% are African American or Hispanic, as contrasted with 10% and 3%, respectively, of the general population. More than two-thirds served in the military for more than 3 years, and 76% have a history of mental illness or substance abuse. Compared with the general homeless population, homeless veterans are older, better educated, more likely to have been married, and more likely to have health insurance, primarily through the VA.^24,25

The Washington, DC, metropolitan area encompasses the District of Columbia, northern Virginia, the tricounty area of southern Maryland, and Montgomery and Prince George’s counties in Maryland. Demographics for veterans in this area vary somewhat from national figures. According to the 2015 Point-in-Time survey of the homeless, veterans accounted for 5% of the homeless population (less than the national percentage). Most homeless veterans were single men (11.6% were women) and African American (65% of single adults, 85% of adults in families). Forty-five percent reported being employed and 40% had a substance use disorder or a serious mental illness. A large proportion also had at least 1 physical disability, such as hypertension, hepatitis, arthritis, diabetes mellitus, or heart disease.²⁶

Risk Factors

Multiple studies and multivariate analyses have determined that veteran status is associated with an increased risk for homelessness for both male and female veterans.²⁷ Female veterans were 3 times and male veterans 2 times more likely than nonveterans to become homeless, even when poverty, age, race, and geographic variation were controlled. A recent systematic review of U.S. veterans found that the strongest and most consistent risk factors for homelessness were substance use disorders and mental illness, particularly psychotic disorders. Posttraumatic stress disorder was not more significant than other mental conditions but it was a risk factor. Low income, unemployment, and poor money management were also factors.

Social risk factors include lack of support from family and friends. Military service with multiple deployments, transfers, and on-base housing may contribute to interruption of social support and lead to social isolation, thus increasing veterans’ risk for homelessness. Some studies have found that veterans are more likely to report physical injury or medical problems as contributing to homelessness and more likely to have 2 or more chronic medical conditions. Last, history of incarceration and adverse childhood experiences (eg, behavioral problems, family instability, foster care, childhood abuse) also have been found to be risk factors for homelessness among veterans and nonveterans alike.

Understanding these risk factors is an important step in addressing homelessness. Homelessness prevention efforts can screen for these risk factors and then intervene as quickly as possible. Access to mental health and substance abuse services, employment assistance, disability benefits and other income supports, and social services may prevent initial and subsequent episodes of homelessness. The VA, as the largest integrated health system in the U.S., is a critical safety net for low-income and disabled veterans with complex psychosocial needs. One study found access to VA service-connected pensions was protective against homelessness.²⁸

Addressing Homelessness

There are 10 USICH-recommended strategies for ending veteran homelessness (Table 1). These strategies cannot be achieved by any single federal agency or exclusively by government agencies—they require multipronged approaches and private and public partnerships. In early 2011, the staff of the Washington DC VAMC homeless program identified a single point of contact who would regularly meet with each Continuum of Care local planning body and each Public Housing Authority (PHA). This contact could identify homeless veterans regardless of the agency from which they were requesting assistance. The contact also facilitated identification of specific bottleneck issues contributing to delays in housing veterans. One such issue was that veterans were filling out application forms by themselves, and in some cases, their information was incomplete, or supporting documents (eg, government-issued IDs) were missing. The VA team adjusted the procedures to better meet veterans’ needs. Now veterans identified as meeting requirements for housing assistance are enrolled in classes in which a caseworker reviews their completed applications to ensure they are complete and supporting documents included. If an ID is needed, the caseworker facilitates the process and then submits the veteran’s application to the local PHA for processing. The result has been no returned applications.

Another issue was that in some cases a veteran spoke with the PHA and indicated interest in an apartment and only later found out that the apartment failed inspection. There would then be back-and-forth communications between PHA and landlord to have repairs made so the unit could pass inspection, which often resulted in long delays. The solution was to have a stock of preinspected housing options. The Washington DC VAMC homeless program now has a housing specialist who identifies preinspected units and can expedite the lease to a veteran. In addition, the homeless program in partnership with the PHA now sets up regular meet-and-greet events for landlords and veterans so veterans can preview available rentals.

Housing-First Model

The homeless program readily adopted the housing-first model. This model focuses on helping individuals and families access housing as quickly as possible and remain permanently housed; this assistance is not time-limited but ongoing. After housing placement, the client can choose from an array of both time-limited and long-term services, which are individualized to promote housing stability and individual well-being. Most important, housing is not contingent on compliance with services. Instead, participants must comply with a standard lease agreement and are provided the services and support that can help them do so successfully. Services are determined by completing needs assessments. In addition, as a veteran is applying for housing, a caseworker actively uses motivational interviewing techniques to enhance the likelihood that the veteran will accept services.

Providing Core Service to Veterans

In 2012, the Washington DC VAMC opened the Community Resource and Referral Center (CRRC) as a one-stop shop for homeless and at-risk veterans in need of basic, core, wraparound services through the VA. Basic services include showers, laundry facilities, and a chapel. The CRRC has onsite psychiatric services that can engage veterans in mental health and substance abuse treatment. There is also an onsite primary care team who specialize in working with the homeless and can address any acute or chronic medical problems. For veterans who want to return to employment, there is an onsite Compensated Work Therapy program, which has uniquely partnered with the VAMC as well as community partners (eg, National Archives, Smithsonian Institution, Quantico National Cemetery, Arlington National Cemetery) to offer therapeutic job experiences that often lead to gainful full-time employment.

Veterans can use an onsite computer lab to complete resumes and apply for employment online, with the assistance of veteran peer specialists and vocational rehabilitation specialists. For veterans who are unable to work, the homeless program team assists with disability applications. Social Security, Veterans Benefits Administration representatives, and Legal Aid have office hours at the CRRC to provide one-stop shopping for veterans. Additional community partnerships have led to classes to help veterans manage income effectively, and veterans are assisted with completing tax returns.

Representatives from the Veterans Justice Outreach (VJO) and Health Care for Re-entry Veterans (HCRV) programs are also onsite. The VJO program provides outreach, assessment, and case management for justice-involved veterans to prevent unnecessary criminalization of mental illness and extended incarceration. A VJO program specialist works with courts, legal representatives, and jails and acts as a liaison to engage veterans in treatment and prevent incarcerations through jail diversion strategies. The HCRV program assists incarcerated veterans with reentry into the community through outreach and prerelease assessments, and referrals and links to medical, psychiatric, and social services, including employment services on release. This program also can provide short-term case management assistance on release.

In 2013, to further the implementation of the USICH strategies in the Washington, DC, metropolitan area, 12 local government and nonprofit agencies entered into the Veterans NOW coalition (Table 2). This collaboration enabled development of a coordinated effort to identify all area veterans experiencing homelessness, regardless of which agency the veterans contacted. Further, this team set up processes to assess veterans’ housing and service needs and to match each veteran to the most appropriate housing resource. There was consensus regarding use of the Service Prioritization Decision Assistance Tool (SPDAT) as the evidence-informed approach for prioritizing client needs and identifying areas in which support is most likely needed to prevent housing instability.²⁹ More than 50 staff members at 20 different agencies in the District of Columbia have now been trained and are using this tool.

Outcomes

In 2010, the Point-in-Time count identified 718 homeless veterans in the Washington, DC, metropolitan area. By 2016, that number had dropped to 326 (55% reduction). During this same period, the number of veterans served by the Washington DC VAMC homeless program more than tripled, from 2,100 individuals in 2010 to nearly 6,400 in 2015. The coalition has housed or prevented homelessness for nearly 1,300 veterans during the past 2 years alone. Veterans were housed through multiple programs and efforts, including VA Supportive Housing (VASH), Supportive Services for Veteran Families, and Washington, DC Department of Human Services Permanent Supportive Housing. During the past year, > 60% of veterans were successfully placed in VASH housing within 90 days of application submission. Table 3 lists the national targets for assessing performance measurement and success. Not only were the various performance measure benchmarks exceeded, but more important, > 90% of veterans in VASH and Health Care for Homeless Veterans were able to keep their housing stabilized. Using SPDAT, the most chronically homeless and vulnerable were housed first, which accounts for the lower numbers of homeless Washington, DC, area veterans with substance abuse and mental health problems identified in the Point-in-Time survey.

Discussion

At the Washington DC VAMC, HCHV program staff members used evidence-based and evidence-informed tools, collaborated with community partners, and implemented recommended best practices to end veteran homelessness by 2015. Permanent supportive housing through VASH is crucial for helping veterans overcome their lack of income and in providing mechanisms for engaging in mental health and substance abuse services as well as primary care and therapeutic employment opportunities.

When former VA Secretary Eric K. Shinseki first announced the goal of ending veteran homelessness by 2015, many people questioned this goal’s attainability and feasibility. However, through the adoption of the strategies recommended by USICH, the establishment of government and community partnerships (including faith-based groups) and the implementation of programs addressing substance abuse issues, mental and physical health, income limitations, and employment, this goal now seems possible. Overall veteran homelessness decreased by 36% since 2010, and unsheltered homelessness decreased by nearly 50%.³⁰ By the end of 2015, nearly 65,000 veterans are in permanent housing nationwide, and another 8,100 are in the process of obtaining permanent supportive housing. Also, 87% of unsheltered veterans were able to move to safe housing within 30 days of engagement. Last, Supportive Services for Veteran Families was able to assist more than 156,800 individuals (single veterans as well as their children and families).

Sustainability from a national perspective also depends on continued federal funding. Mr. G, described at the beginning of this article, served his country honorably but then experienced the factors that put him at risk for homelessness. Through a veteran-centric team approach, he was able to successfully address each of these factors. As there are another 500 homeless veterans in Washington, DC, much work still needs to be done. With important collaborations and partnerships now in place, the goal of ending veteran homelessness in the District of Columbia is within sight. When homelessness is a thing of the past, we will truly be able to Welcome Home each veteran.

A majority of men (70%) aged ≥ 70 years report erectile dysfunction (ED) in primary care settings.¹ Further, the cost of ED medication is increasing: nationally, the VA spent $71.7 million on ED medications in 2013, triple the amount from 2006,² despite a 2011 VA mandate limiting ED medication prescriptions to 4 doses per month per veteran.³ Unfortunately, although ED is common and costly, only about 12% of men in the community report being asked about their sexual health by their primary care provider (PCP) in the past 3 years.⁴ Further, little emphasis seems to be placed on preventive care. For example, men with ED in primary care clinics are unaware of ED risk factors such as hypertension, smoking, and obesity; indeed, only 17% of a large community sample could name 1 risk factor for ED.⁵ This is problematic because diet and exercise improve erectile functioning,yet men may not realize they can reduce ED through behavioral and lifestyle change.⁶

In addition, there is little research that investigates veterans’ satisfaction with ED treatment and its effectiveness. The taboo nature of talking about erections and sexual health may partially relate to the lack of research. When surveyed, PCPs noted that they do not talk about ED routinely with patients for reasons that include time constraints, lack of experience managing sexual problems, viewing ED medication as a lifestyle drug, perceiving ED as a nonserious concern, discomfort discussing the topic for both male and female PCPs, and viewing ED discussions as the responsibility of providers of the opposite gender.^7-9

Given the dearth of ED research within the veteran population, the purpose of the current study was to (1) explore the level of treatment satisfaction of veterans prescribed an ED medication, phosphodiesterase type 5 inhibitor (PDE5); (2) assess patients’ perception of discussions with their PCPs about sexual health concerns; and (3) provide preliminary data on veterans’ knowledge of ED risk factors and identify possible areas for preventive education. This study was intended to highlight areas for further investigation to improve ED treatment satisfaction among veterans.

Methods

The authors conducted an anonymous survey with veterans who were prescribed an ED medication within the previous 12 months. In 2012, researchers obtained 8,000 names of veterans prescribed a PDE5 medication at the Clement J. Zablocki VA Medical Center (CJZVAMC) in Milwaukee, Wisconsin, and randomly selected 1,000 persons to mail a research survey to be returned anonymously. Three hundred ten surveys were returned, a 31% response rate, which was similar (32%) to a comparable large ED survey study, in which the participants were randomly selected to participate and also were not recruited by their PCP.¹⁰ Because 13 participants were excluded due to incomplete surveys or obtaining primary medical care services outside the VA, the current sample consisted of 297 participants. The CJZVAMC institutional review board approved the study in March 2013, and de-identified data were collected from March 2013 to March 2014.

The authors assessed demographics and treatment information, including whether veterans had talked with their PCP about sexual concerns.

Of the 297 participants, 55% were aged > 65 years. Racial/ethnic groups reflected the veteran population at CJZVAMC, with 78% identifying as European American, 17% as African American, 2% as Hispanic American, 2% as biracial, and 1% as Asian American or American Indian. Eighty-one percent were identified as Christian, and 10% reported no religious preference. Sixty-seven percent reported having a current sexual partner.

Measures

The International Index of Erectile Function (IIEF-5), an abridged version of a longer, 15-item instrument, was administered to assess participants’ erectile function.^11,12 The IIEF-5 consists of 5 items that ask about participants’ erectile functioning over the past 6 months. Participants responded to items on a 1 to 5 scale ranging from “almost never/never” to “almost always/always”. Items were summed to create a total score that could range from 5 to 25. Total scores reflect erectile functioning and satisfaction, with low scores indicating greater dysfunction. This measure has shown high sensitivity (.98) and specificity (.88).¹¹ Cut scores for the current study were consistent with the literature: mild ED = 17-21; mild-to-moderate ED = 12-16; moderate ED = 8-11; and severe ED = 5-7.¹³ Reliability in this sample was α = .93.

The authors were unable to find a validated measure assessing men’s knowledge of ED risk factors in the literature. Therefore, participants’ knowledge of ED risk factors was assessed using an online nonvalidated questionnaire entitled “Impotence [Erectile Dysfunction] Quiz: Test Your Medical IQ of ED” from www.emedicinehelp.com.¹³ Questions assess knowledge of specific risk factors (eg, age, obesity, depression, prostate cancer), symptoms, incidence rate, treatments, normal erectile functioning, and implications of ED. The questionnaire contains 16 items (3 true/false and 13 multiple choice items), and the total score corresponds to the percentage correct. According to the online version, the average score is 11 items correct (69%).¹³

A single item asked participants to identify behavioral changes they had tried to improve their erectile functioning. Options included taking medications at a different time, and/or decreasing tobacco, caffeine, or alcohol consumption. The Erectile Dysfunction Inventory of Treatment Satisfaction – Patient Version (EDITS) is an 11-item questionnaire administered to assess participants’ satisfaction with their medical treatment of ED.¹⁴ Items assess treatment satisfaction, ease of use, confidence in ability to perform, partner satisfaction, and naturalness of erections achieved during treatment. These items are rated on a scale ranging from 0 (dissatisfaction) to 4 (high satisfaction) and then summed, with total scores ranging from 0 (extremely dissatisfied) to 100 (extremely satisfied). The measure displayed high internal consistency (α = .90) and high test-retest reliability (r = .98).¹⁴ Several studies have used cutoff scores of 0 = very dissatisfied; 25 = dissatisfied; 50 = neither satisfied nor dissatisfied; 75 = satisfied; and 100 = very satisfied.^15,16 These cut scores and classifiers were used in the current study; reliability was α = .92.

The authors further explored reasons for veteran dissatisfaction with ED treatment by asking participants to respond to a single item: “Why are you dissatisfied with your erectile dysfunction treatment?” They could indicate that they were satisfied or circle all options for dissatisfaction that applied (“I would like to receive more pills per month,” “The treatment does not work well,” or “I want more information about erectile dysfunction and treatment”), or write in a response. The authors inquired about the number of pills prescribed to ascertain whether dissatisfaction was due to VA-specific policies vs veterans’ understanding of ED and effectiveness of treatment, which providers have more ability to improve.

In addition to the quantitative data obtained from the completed surveys, unsolicited responses from participants to the principal investigator via phone calls, and letters regarding treatment satisfaction were gathered. The second author conducted a basic exploratory content analysis of these unsolicited responses to group them into themes related to this study, such as satisfaction or dissatisfaction with ED treatment.

Results

The authors first assessed levels of ED and satisfaction with treatment in the sample. On average, participants reported mild-to-moderate erectile dysfunction (M = 13.1; SD = 5.7), which is higher than that of the general population and consistent with samples of men referred for ED treatment.^17,18 Satisfaction levels were slightly above neutral on the EDITS questionnaire (M = 58.3%; SD = 24.5). In response to a separate single-item question regarding reasons for dissatisfaction, only 6.4% of veterans reported being satisfied with their ED treatment.

According to respondents, the primary reasons for dissatisfaction were wanting more medication (46%), finding the treatment ineffective (26.7%), and desiring more information (24%). Further, ED severity was negatively correlated with satisfaction with ED treatment (r = .72, P < .01; note that higher scores correspond to less severe ED on this measure). However, despite moderate-to-low levels of satisfaction, 79.2% of patients planned to continue with their ED treatment (59.3% very likely and 19.9% moderately likely).

The authors also assessed participants’ communication with PCPs about their sexual functioning. Twenty-five percent reported not talking with their PCP about sexual concerns (despite all having been prescribed an ED medication in the past year). In this sample, talking with one’s PCP was not related to increased knowledge of ED risk factors (t [294] = .32, ns). Those who talked to their PCP tended to be less satisfied with treatment (M = 56.2; SD = 24.5) than those who did not talk to their PCP (M = 64.7; SD = 23.3; t (213) = -2.2; P = .03), likely because those who felt their treatment was working for them felt less need to talk to their provider. Indeed, those who talked to their PCP trended to have more severe levels of ED (M = 12.7; SD = 5.8) than those who did not (M = 14.2; SD = 5.3; t [285] = -1.91; P = .057; note that higher scores correspond to less severe ED on this measure). Finally, adults aged > 65 years were less likely to talk to their PCP than were younger adults (69% vs 81%); χ² (1, N = 291) = 5.57; P = .018.

Generally, the level of knowledge of ED risk factors was lower than the average of respondents to the original online survey (62% vs 69%).¹³ Younger adults were slightly more knowledgeable (M = 64%; SD = 13) than were older adults (M = 60%; SD = 15), t (288.08) = 2.01; P = .046).

Finally, most veterans reported few attempted behavioral changes to address ED, such as taking medications at a different time or decreasing use of tobacco, caffeine, or alcohol (M = 1.3; SD = 1.1). Thirty percent had not tried any behavioral changes; 34.1% tried 1 change; and 35.9% had tried more than 1 behavioral change. In contrast, 89% of participants reported using a PDE5 medication. Eight-two percent of participants reported currently receiving ED treatment of some kind; within this group, 97.4% reported currently taking a PDE5 medication. Only 2.5% of veterans reported using other kinds of treatment, such as vacuum pump, suppository, over-the-counter medication, injections, and not using a PDE5 medication, whereas 6.7% were using other kinds of treatment as well as a PDE5 medication.

In addition to the quantitative responses, 48 participants wrote unsolicited comments about their experiences with ED treatment on their returned questionnaires. The principal investigator also received 9 telephone calls from intended study participants, who provided verbal feedback regarding their experience with ED treatment. Comments unrelated to the study were eliminated, and the remaining written and verbal responses were grouped into categories to identify themes. Mirroring the quantitative results, participants providing qualitative feedback were dissatisfied with their ED treatment. Specifically, 43% of the comments consisted of complaints regarding the ineffectiveness and/or undesirable adverse effects (AEs) of ED medications and other ED treatments, including physical AEs (eg, headaches), sentiments that treatment does not feel “natural,” and dissatisfaction with the quality and length of sexual encounters despite treatment. Yet 24% of the comments entailed requests for more and/or different ED medications. Less frequent, although significant, comments related to decreased sexual interest and performance because of other medical conditions, such as pain, prostate surgery, and hypertension (15%); desire for additional information about ED treatments from health care providers (9%); use of nonpharmacologic ED interventions (eg, vacuum pump, 7%); and concerns about their partners’ level of sexual dissatisfaction as a result of their ED (7%).

Discussion

The present study examined knowledge of ED risk factors and level of satisfaction with ED treatment in a veteran population. Pharmacologic interventions comprised the most prevalent form of ED treatment. Both quantitative and qualitative results indicated areas for improvement in veteran satisfaction with ED treatment. Overall, veterans reported being neither satisfied nor dissatisfied with their current ED treatment, although very few reported being satisfied in response to a single item. The discrepancy may be related to the negative wording of the latter question (“Why are you dissatisfied with your erectile dysfunction treatment?”), which potentially biased participants’ responses. Several veterans also provided many unsolicited comments regarding areas for improvement. Despite feeling neutral to dissatisfied with treatment, 80% planned to continue with treatment. Sources of dissatisfaction included restricted access to ED medication (eg, limiting pills to 4 per month), ineffectiveness of treatment (eg, poor quality of erection, lack of climax), physical AEs, a desire for more information about ED, and psychological and relational concerns (eg, partner sexual dissatisfaction). As one veteran in his 80s lamented in describing the apparent end to his sexual life despite current ED treatment, “Is that all there is? It is the end of the road.”

The authors identified several barriers to implementing potentially beneficial interventions other than ED medications. Specifically, despite receiving long-term treatment for ED, veteran participants showed average knowledge of information related to ED risk factors. Of concern, discussing sexual health concerns with a PCP was not associated with increased knowledge of ED risk factors. This may explain the finding that veterans plan to continue with medication treatment despite feeling only neutral to dissatisfied about their current ED treatment.

Veterans who talked to their PCP about ED were less satisfied with treatment than were those who did not talk to their PCP, likely because those who felt their treatment was working for them felt less need to talk to their provider. Indeed, those who talked to their PCP tended to have more severe ED than those who did not. It may be that veterans avoid discussing ED with their PCP until they reach advanced ED when it is too late for treatment to make a difference. The principal investigator’s receipt of unsolicited telephone calls from intended study participants desiring to discuss ED—something that has not occurred during the researchers’ involvement in dozens of prior health-related studies—illustrates the importance veterans place on sexual concerns and the need to encourage discussion about the topic in the context of health care appointments. Specifically, older adults would benefit from more conversations with PCPs as they reported less knowledge of ED risk factors and fewer conversations with PCPs about sexual concerns than did younger men.

Adverse Events

Given the AEs reported by veterans and the significant cost of ED medications within the VA system,² increased use of alternative nonpharmacologic and preventive behavioral approaches would be clinically and economically beneficial. For example, in one study, men with ED who engaged in a lifestyle program that focused on weight loss, diet, and exercise were found more likely to experience improvements in erectile functioning compared with men who did not participate.⁶ Yet in the current study, 30% of participants had not attempted behavioral changes to address ED.

The VA’s Health Promotion and Disease Prevention (HPDP) Program focuses on preventive services and behavioral interventions to reduce health risks within primary care settings.¹⁹ This program may provide a framework for efforts to prevent and ameliorate ED. Specifically, coaching and education by HPDP experts could reduce PCPs’ discomfort with sexual health discussions and normalize the value of such conversations for both providers and patients. Existing HPDP behavioral interventions targeting areas such as weight loss and smoking cessation also could emphasize the potential secondary benefit of improved sexual functioning. To that end, preventive health campaigns could include sexual health and ED prevention as topics on patient education materials. Including sexual functioning on telephone or in-person prescreening questionnaires prior to routine appointments with PCPs also may facilitate destigmatization of sex as an important health topic.

Limitations

Limitations of the current study include its correlational design, which precludes conclusions regarding casual relationships among the variables in question. The authors cannot speculate about how well their sample represents the general veteran population given its low response rate (although comparable to a similar study).¹⁰ In addition, the lack of a validated measure of ED risk-factor knowledge meant reliance on an online questionnaire with unknown psychometric properties. To identify alternatives to pharmacologic treatment for ED, it would be beneficial for future research to examine the reasons for dissatisfaction among veterans, assessing satisfaction changes after implementation of behavioral and/or preventive interventions.

Conclusion

This study deepens the understanding of ED treatment efficacy among veterans in light of the paucity of available information. Overall, veterans are neutral to dissatisfied with their ED treatment, yet plan to continue it in the context of limited alternatives and possible lack of knowledge of behavioral methods shown to improve erectile functioning. Future studies that examine the reasons for continuing medication despite neutral satisfaction would help explore this finding. Based on these results, the authors recommend increased attention and discussion of sexual health during PCP visits and enhanced efforts toward using behavioral strategies to prevent and reduce ED. Encouragement from PCPs to address sexual health concerns earlier in a veteran’s treatment course—and in the context of behavioral and lifestyle change—may assist in preventing veterans’ sexual lives from prematurely reaching “the end of the road.”

Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Clement J. Zablocki VA Medical Center in Milwaukee, Wisconsin.

A majority of men (70%) aged ≥ 70 years report erectile dysfunction (ED) in primary care settings.¹ Further, the cost of ED medication is increasing: nationally, the VA spent $71.7 million on ED medications in 2013, triple the amount from 2006,² despite a 2011 VA mandate limiting ED medication prescriptions to 4 doses per month per veteran.³ Unfortunately, although ED is common and costly, only about 12% of men in the community report being asked about their sexual health by their primary care provider (PCP) in the past 3 years.⁴ Further, little emphasis seems to be placed on preventive care. For example, men with ED in primary care clinics are unaware of ED risk factors such as hypertension, smoking, and obesity; indeed, only 17% of a large community sample could name 1 risk factor for ED.⁵ This is problematic because diet and exercise improve erectile functioning,yet men may not realize they can reduce ED through behavioral and lifestyle change.⁶

In addition, there is little research that investigates veterans’ satisfaction with ED treatment and its effectiveness. The taboo nature of talking about erections and sexual health may partially relate to the lack of research. When surveyed, PCPs noted that they do not talk about ED routinely with patients for reasons that include time constraints, lack of experience managing sexual problems, viewing ED medication as a lifestyle drug, perceiving ED as a nonserious concern, discomfort discussing the topic for both male and female PCPs, and viewing ED discussions as the responsibility of providers of the opposite gender.^7-9

Given the dearth of ED research within the veteran population, the purpose of the current study was to (1) explore the level of treatment satisfaction of veterans prescribed an ED medication, phosphodiesterase type 5 inhibitor (PDE5); (2) assess patients’ perception of discussions with their PCPs about sexual health concerns; and (3) provide preliminary data on veterans’ knowledge of ED risk factors and identify possible areas for preventive education. This study was intended to highlight areas for further investigation to improve ED treatment satisfaction among veterans.

Methods

The authors conducted an anonymous survey with veterans who were prescribed an ED medication within the previous 12 months. In 2012, researchers obtained 8,000 names of veterans prescribed a PDE5 medication at the Clement J. Zablocki VA Medical Center (CJZVAMC) in Milwaukee, Wisconsin, and randomly selected 1,000 persons to mail a research survey to be returned anonymously. Three hundred ten surveys were returned, a 31% response rate, which was similar (32%) to a comparable large ED survey study, in which the participants were randomly selected to participate and also were not recruited by their PCP.¹⁰ Because 13 participants were excluded due to incomplete surveys or obtaining primary medical care services outside the VA, the current sample consisted of 297 participants. The CJZVAMC institutional review board approved the study in March 2013, and de-identified data were collected from March 2013 to March 2014.

The authors assessed demographics and treatment information, including whether veterans had talked with their PCP about sexual concerns.

Of the 297 participants, 55% were aged > 65 years. Racial/ethnic groups reflected the veteran population at CJZVAMC, with 78% identifying as European American, 17% as African American, 2% as Hispanic American, 2% as biracial, and 1% as Asian American or American Indian. Eighty-one percent were identified as Christian, and 10% reported no religious preference. Sixty-seven percent reported having a current sexual partner.

Measures

The International Index of Erectile Function (IIEF-5), an abridged version of a longer, 15-item instrument, was administered to assess participants’ erectile function.^11,12 The IIEF-5 consists of 5 items that ask about participants’ erectile functioning over the past 6 months. Participants responded to items on a 1 to 5 scale ranging from “almost never/never” to “almost always/always”. Items were summed to create a total score that could range from 5 to 25. Total scores reflect erectile functioning and satisfaction, with low scores indicating greater dysfunction. This measure has shown high sensitivity (.98) and specificity (.88).¹¹ Cut scores for the current study were consistent with the literature: mild ED = 17-21; mild-to-moderate ED = 12-16; moderate ED = 8-11; and severe ED = 5-7.¹³ Reliability in this sample was α = .93.

The authors were unable to find a validated measure assessing men’s knowledge of ED risk factors in the literature. Therefore, participants’ knowledge of ED risk factors was assessed using an online nonvalidated questionnaire entitled “Impotence [Erectile Dysfunction] Quiz: Test Your Medical IQ of ED” from www.emedicinehelp.com.¹³ Questions assess knowledge of specific risk factors (eg, age, obesity, depression, prostate cancer), symptoms, incidence rate, treatments, normal erectile functioning, and implications of ED. The questionnaire contains 16 items (3 true/false and 13 multiple choice items), and the total score corresponds to the percentage correct. According to the online version, the average score is 11 items correct (69%).¹³

A single item asked participants to identify behavioral changes they had tried to improve their erectile functioning. Options included taking medications at a different time, and/or decreasing tobacco, caffeine, or alcohol consumption. The Erectile Dysfunction Inventory of Treatment Satisfaction – Patient Version (EDITS) is an 11-item questionnaire administered to assess participants’ satisfaction with their medical treatment of ED.¹⁴ Items assess treatment satisfaction, ease of use, confidence in ability to perform, partner satisfaction, and naturalness of erections achieved during treatment. These items are rated on a scale ranging from 0 (dissatisfaction) to 4 (high satisfaction) and then summed, with total scores ranging from 0 (extremely dissatisfied) to 100 (extremely satisfied). The measure displayed high internal consistency (α = .90) and high test-retest reliability (r = .98).¹⁴ Several studies have used cutoff scores of 0 = very dissatisfied; 25 = dissatisfied; 50 = neither satisfied nor dissatisfied; 75 = satisfied; and 100 = very satisfied.^15,16 These cut scores and classifiers were used in the current study; reliability was α = .92.

The authors further explored reasons for veteran dissatisfaction with ED treatment by asking participants to respond to a single item: “Why are you dissatisfied with your erectile dysfunction treatment?” They could indicate that they were satisfied or circle all options for dissatisfaction that applied (“I would like to receive more pills per month,” “The treatment does not work well,” or “I want more information about erectile dysfunction and treatment”), or write in a response. The authors inquired about the number of pills prescribed to ascertain whether dissatisfaction was due to VA-specific policies vs veterans’ understanding of ED and effectiveness of treatment, which providers have more ability to improve.

In addition to the quantitative data obtained from the completed surveys, unsolicited responses from participants to the principal investigator via phone calls, and letters regarding treatment satisfaction were gathered. The second author conducted a basic exploratory content analysis of these unsolicited responses to group them into themes related to this study, such as satisfaction or dissatisfaction with ED treatment.

Results

The authors first assessed levels of ED and satisfaction with treatment in the sample. On average, participants reported mild-to-moderate erectile dysfunction (M = 13.1; SD = 5.7), which is higher than that of the general population and consistent with samples of men referred for ED treatment.^17,18 Satisfaction levels were slightly above neutral on the EDITS questionnaire (M = 58.3%; SD = 24.5). In response to a separate single-item question regarding reasons for dissatisfaction, only 6.4% of veterans reported being satisfied with their ED treatment.

According to respondents, the primary reasons for dissatisfaction were wanting more medication (46%), finding the treatment ineffective (26.7%), and desiring more information (24%). Further, ED severity was negatively correlated with satisfaction with ED treatment (r = .72, P < .01; note that higher scores correspond to less severe ED on this measure). However, despite moderate-to-low levels of satisfaction, 79.2% of patients planned to continue with their ED treatment (59.3% very likely and 19.9% moderately likely).

The authors also assessed participants’ communication with PCPs about their sexual functioning. Twenty-five percent reported not talking with their PCP about sexual concerns (despite all having been prescribed an ED medication in the past year). In this sample, talking with one’s PCP was not related to increased knowledge of ED risk factors (t [294] = .32, ns). Those who talked to their PCP tended to be less satisfied with treatment (M = 56.2; SD = 24.5) than those who did not talk to their PCP (M = 64.7; SD = 23.3; t (213) = -2.2; P = .03), likely because those who felt their treatment was working for them felt less need to talk to their provider. Indeed, those who talked to their PCP trended to have more severe levels of ED (M = 12.7; SD = 5.8) than those who did not (M = 14.2; SD = 5.3; t [285] = -1.91; P = .057; note that higher scores correspond to less severe ED on this measure). Finally, adults aged > 65 years were less likely to talk to their PCP than were younger adults (69% vs 81%); χ² (1, N = 291) = 5.57; P = .018.

Generally, the level of knowledge of ED risk factors was lower than the average of respondents to the original online survey (62% vs 69%).¹³ Younger adults were slightly more knowledgeable (M = 64%; SD = 13) than were older adults (M = 60%; SD = 15), t (288.08) = 2.01; P = .046).

Finally, most veterans reported few attempted behavioral changes to address ED, such as taking medications at a different time or decreasing use of tobacco, caffeine, or alcohol (M = 1.3; SD = 1.1). Thirty percent had not tried any behavioral changes; 34.1% tried 1 change; and 35.9% had tried more than 1 behavioral change. In contrast, 89% of participants reported using a PDE5 medication. Eight-two percent of participants reported currently receiving ED treatment of some kind; within this group, 97.4% reported currently taking a PDE5 medication. Only 2.5% of veterans reported using other kinds of treatment, such as vacuum pump, suppository, over-the-counter medication, injections, and not using a PDE5 medication, whereas 6.7% were using other kinds of treatment as well as a PDE5 medication.

In addition to the quantitative responses, 48 participants wrote unsolicited comments about their experiences with ED treatment on their returned questionnaires. The principal investigator also received 9 telephone calls from intended study participants, who provided verbal feedback regarding their experience with ED treatment. Comments unrelated to the study were eliminated, and the remaining written and verbal responses were grouped into categories to identify themes. Mirroring the quantitative results, participants providing qualitative feedback were dissatisfied with their ED treatment. Specifically, 43% of the comments consisted of complaints regarding the ineffectiveness and/or undesirable adverse effects (AEs) of ED medications and other ED treatments, including physical AEs (eg, headaches), sentiments that treatment does not feel “natural,” and dissatisfaction with the quality and length of sexual encounters despite treatment. Yet 24% of the comments entailed requests for more and/or different ED medications. Less frequent, although significant, comments related to decreased sexual interest and performance because of other medical conditions, such as pain, prostate surgery, and hypertension (15%); desire for additional information about ED treatments from health care providers (9%); use of nonpharmacologic ED interventions (eg, vacuum pump, 7%); and concerns about their partners’ level of sexual dissatisfaction as a result of their ED (7%).

Discussion

The present study examined knowledge of ED risk factors and level of satisfaction with ED treatment in a veteran population. Pharmacologic interventions comprised the most prevalent form of ED treatment. Both quantitative and qualitative results indicated areas for improvement in veteran satisfaction with ED treatment. Overall, veterans reported being neither satisfied nor dissatisfied with their current ED treatment, although very few reported being satisfied in response to a single item. The discrepancy may be related to the negative wording of the latter question (“Why are you dissatisfied with your erectile dysfunction treatment?”), which potentially biased participants’ responses. Several veterans also provided many unsolicited comments regarding areas for improvement. Despite feeling neutral to dissatisfied with treatment, 80% planned to continue with treatment. Sources of dissatisfaction included restricted access to ED medication (eg, limiting pills to 4 per month), ineffectiveness of treatment (eg, poor quality of erection, lack of climax), physical AEs, a desire for more information about ED, and psychological and relational concerns (eg, partner sexual dissatisfaction). As one veteran in his 80s lamented in describing the apparent end to his sexual life despite current ED treatment, “Is that all there is? It is the end of the road.”

The authors identified several barriers to implementing potentially beneficial interventions other than ED medications. Specifically, despite receiving long-term treatment for ED, veteran participants showed average knowledge of information related to ED risk factors. Of concern, discussing sexual health concerns with a PCP was not associated with increased knowledge of ED risk factors. This may explain the finding that veterans plan to continue with medication treatment despite feeling only neutral to dissatisfied about their current ED treatment.

Veterans who talked to their PCP about ED were less satisfied with treatment than were those who did not talk to their PCP, likely because those who felt their treatment was working for them felt less need to talk to their provider. Indeed, those who talked to their PCP tended to have more severe ED than those who did not. It may be that veterans avoid discussing ED with their PCP until they reach advanced ED when it is too late for treatment to make a difference. The principal investigator’s receipt of unsolicited telephone calls from intended study participants desiring to discuss ED—something that has not occurred during the researchers’ involvement in dozens of prior health-related studies—illustrates the importance veterans place on sexual concerns and the need to encourage discussion about the topic in the context of health care appointments. Specifically, older adults would benefit from more conversations with PCPs as they reported less knowledge of ED risk factors and fewer conversations with PCPs about sexual concerns than did younger men.

Adverse Events

Given the AEs reported by veterans and the significant cost of ED medications within the VA system,² increased use of alternative nonpharmacologic and preventive behavioral approaches would be clinically and economically beneficial. For example, in one study, men with ED who engaged in a lifestyle program that focused on weight loss, diet, and exercise were found more likely to experience improvements in erectile functioning compared with men who did not participate.⁶ Yet in the current study, 30% of participants had not attempted behavioral changes to address ED.

The VA’s Health Promotion and Disease Prevention (HPDP) Program focuses on preventive services and behavioral interventions to reduce health risks within primary care settings.¹⁹ This program may provide a framework for efforts to prevent and ameliorate ED. Specifically, coaching and education by HPDP experts could reduce PCPs’ discomfort with sexual health discussions and normalize the value of such conversations for both providers and patients. Existing HPDP behavioral interventions targeting areas such as weight loss and smoking cessation also could emphasize the potential secondary benefit of improved sexual functioning. To that end, preventive health campaigns could include sexual health and ED prevention as topics on patient education materials. Including sexual functioning on telephone or in-person prescreening questionnaires prior to routine appointments with PCPs also may facilitate destigmatization of sex as an important health topic.

Limitations

Limitations of the current study include its correlational design, which precludes conclusions regarding casual relationships among the variables in question. The authors cannot speculate about how well their sample represents the general veteran population given its low response rate (although comparable to a similar study).¹⁰ In addition, the lack of a validated measure of ED risk-factor knowledge meant reliance on an online questionnaire with unknown psychometric properties. To identify alternatives to pharmacologic treatment for ED, it would be beneficial for future research to examine the reasons for dissatisfaction among veterans, assessing satisfaction changes after implementation of behavioral and/or preventive interventions.

Conclusion

This study deepens the understanding of ED treatment efficacy among veterans in light of the paucity of available information. Overall, veterans are neutral to dissatisfied with their ED treatment, yet plan to continue it in the context of limited alternatives and possible lack of knowledge of behavioral methods shown to improve erectile functioning. Future studies that examine the reasons for continuing medication despite neutral satisfaction would help explore this finding. Based on these results, the authors recommend increased attention and discussion of sexual health during PCP visits and enhanced efforts toward using behavioral strategies to prevent and reduce ED. Encouragement from PCPs to address sexual health concerns earlier in a veteran’s treatment course—and in the context of behavioral and lifestyle change—may assist in preventing veterans’ sexual lives from prematurely reaching “the end of the road.”

Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Clement J. Zablocki VA Medical Center in Milwaukee, Wisconsin.

A majority of men (70%) aged ≥ 70 years report erectile dysfunction (ED) in primary care settings.¹ Further, the cost of ED medication is increasing: nationally, the VA spent $71.7 million on ED medications in 2013, triple the amount from 2006,² despite a 2011 VA mandate limiting ED medication prescriptions to 4 doses per month per veteran.³ Unfortunately, although ED is common and costly, only about 12% of men in the community report being asked about their sexual health by their primary care provider (PCP) in the past 3 years.⁴ Further, little emphasis seems to be placed on preventive care. For example, men with ED in primary care clinics are unaware of ED risk factors such as hypertension, smoking, and obesity; indeed, only 17% of a large community sample could name 1 risk factor for ED.⁵ This is problematic because diet and exercise improve erectile functioning,yet men may not realize they can reduce ED through behavioral and lifestyle change.⁶

In addition, there is little research that investigates veterans’ satisfaction with ED treatment and its effectiveness. The taboo nature of talking about erections and sexual health may partially relate to the lack of research. When surveyed, PCPs noted that they do not talk about ED routinely with patients for reasons that include time constraints, lack of experience managing sexual problems, viewing ED medication as a lifestyle drug, perceiving ED as a nonserious concern, discomfort discussing the topic for both male and female PCPs, and viewing ED discussions as the responsibility of providers of the opposite gender.^7-9

Given the dearth of ED research within the veteran population, the purpose of the current study was to (1) explore the level of treatment satisfaction of veterans prescribed an ED medication, phosphodiesterase type 5 inhibitor (PDE5); (2) assess patients’ perception of discussions with their PCPs about sexual health concerns; and (3) provide preliminary data on veterans’ knowledge of ED risk factors and identify possible areas for preventive education. This study was intended to highlight areas for further investigation to improve ED treatment satisfaction among veterans.

Methods

The authors conducted an anonymous survey with veterans who were prescribed an ED medication within the previous 12 months. In 2012, researchers obtained 8,000 names of veterans prescribed a PDE5 medication at the Clement J. Zablocki VA Medical Center (CJZVAMC) in Milwaukee, Wisconsin, and randomly selected 1,000 persons to mail a research survey to be returned anonymously. Three hundred ten surveys were returned, a 31% response rate, which was similar (32%) to a comparable large ED survey study, in which the participants were randomly selected to participate and also were not recruited by their PCP.¹⁰ Because 13 participants were excluded due to incomplete surveys or obtaining primary medical care services outside the VA, the current sample consisted of 297 participants. The CJZVAMC institutional review board approved the study in March 2013, and de-identified data were collected from March 2013 to March 2014.

The authors assessed demographics and treatment information, including whether veterans had talked with their PCP about sexual concerns.

Of the 297 participants, 55% were aged > 65 years. Racial/ethnic groups reflected the veteran population at CJZVAMC, with 78% identifying as European American, 17% as African American, 2% as Hispanic American, 2% as biracial, and 1% as Asian American or American Indian. Eighty-one percent were identified as Christian, and 10% reported no religious preference. Sixty-seven percent reported having a current sexual partner.

Measures

The International Index of Erectile Function (IIEF-5), an abridged version of a longer, 15-item instrument, was administered to assess participants’ erectile function.^11,12 The IIEF-5 consists of 5 items that ask about participants’ erectile functioning over the past 6 months. Participants responded to items on a 1 to 5 scale ranging from “almost never/never” to “almost always/always”. Items were summed to create a total score that could range from 5 to 25. Total scores reflect erectile functioning and satisfaction, with low scores indicating greater dysfunction. This measure has shown high sensitivity (.98) and specificity (.88).¹¹ Cut scores for the current study were consistent with the literature: mild ED = 17-21; mild-to-moderate ED = 12-16; moderate ED = 8-11; and severe ED = 5-7.¹³ Reliability in this sample was α = .93.

The authors were unable to find a validated measure assessing men’s knowledge of ED risk factors in the literature. Therefore, participants’ knowledge of ED risk factors was assessed using an online nonvalidated questionnaire entitled “Impotence [Erectile Dysfunction] Quiz: Test Your Medical IQ of ED” from www.emedicinehelp.com.¹³ Questions assess knowledge of specific risk factors (eg, age, obesity, depression, prostate cancer), symptoms, incidence rate, treatments, normal erectile functioning, and implications of ED. The questionnaire contains 16 items (3 true/false and 13 multiple choice items), and the total score corresponds to the percentage correct. According to the online version, the average score is 11 items correct (69%).¹³

A single item asked participants to identify behavioral changes they had tried to improve their erectile functioning. Options included taking medications at a different time, and/or decreasing tobacco, caffeine, or alcohol consumption. The Erectile Dysfunction Inventory of Treatment Satisfaction – Patient Version (EDITS) is an 11-item questionnaire administered to assess participants’ satisfaction with their medical treatment of ED.¹⁴ Items assess treatment satisfaction, ease of use, confidence in ability to perform, partner satisfaction, and naturalness of erections achieved during treatment. These items are rated on a scale ranging from 0 (dissatisfaction) to 4 (high satisfaction) and then summed, with total scores ranging from 0 (extremely dissatisfied) to 100 (extremely satisfied). The measure displayed high internal consistency (α = .90) and high test-retest reliability (r = .98).¹⁴ Several studies have used cutoff scores of 0 = very dissatisfied; 25 = dissatisfied; 50 = neither satisfied nor dissatisfied; 75 = satisfied; and 100 = very satisfied.^15,16 These cut scores and classifiers were used in the current study; reliability was α = .92.

The authors further explored reasons for veteran dissatisfaction with ED treatment by asking participants to respond to a single item: “Why are you dissatisfied with your erectile dysfunction treatment?” They could indicate that they were satisfied or circle all options for dissatisfaction that applied (“I would like to receive more pills per month,” “The treatment does not work well,” or “I want more information about erectile dysfunction and treatment”), or write in a response. The authors inquired about the number of pills prescribed to ascertain whether dissatisfaction was due to VA-specific policies vs veterans’ understanding of ED and effectiveness of treatment, which providers have more ability to improve.

In addition to the quantitative data obtained from the completed surveys, unsolicited responses from participants to the principal investigator via phone calls, and letters regarding treatment satisfaction were gathered. The second author conducted a basic exploratory content analysis of these unsolicited responses to group them into themes related to this study, such as satisfaction or dissatisfaction with ED treatment.

Results

The authors first assessed levels of ED and satisfaction with treatment in the sample. On average, participants reported mild-to-moderate erectile dysfunction (M = 13.1; SD = 5.7), which is higher than that of the general population and consistent with samples of men referred for ED treatment.^17,18 Satisfaction levels were slightly above neutral on the EDITS questionnaire (M = 58.3%; SD = 24.5). In response to a separate single-item question regarding reasons for dissatisfaction, only 6.4% of veterans reported being satisfied with their ED treatment.

According to respondents, the primary reasons for dissatisfaction were wanting more medication (46%), finding the treatment ineffective (26.7%), and desiring more information (24%). Further, ED severity was negatively correlated with satisfaction with ED treatment (r = .72, P < .01; note that higher scores correspond to less severe ED on this measure). However, despite moderate-to-low levels of satisfaction, 79.2% of patients planned to continue with their ED treatment (59.3% very likely and 19.9% moderately likely).

The authors also assessed participants’ communication with PCPs about their sexual functioning. Twenty-five percent reported not talking with their PCP about sexual concerns (despite all having been prescribed an ED medication in the past year). In this sample, talking with one’s PCP was not related to increased knowledge of ED risk factors (t [294] = .32, ns). Those who talked to their PCP tended to be less satisfied with treatment (M = 56.2; SD = 24.5) than those who did not talk to their PCP (M = 64.7; SD = 23.3; t (213) = -2.2; P = .03), likely because those who felt their treatment was working for them felt less need to talk to their provider. Indeed, those who talked to their PCP trended to have more severe levels of ED (M = 12.7; SD = 5.8) than those who did not (M = 14.2; SD = 5.3; t [285] = -1.91; P = .057; note that higher scores correspond to less severe ED on this measure). Finally, adults aged > 65 years were less likely to talk to their PCP than were younger adults (69% vs 81%); χ² (1, N = 291) = 5.57; P = .018.

Generally, the level of knowledge of ED risk factors was lower than the average of respondents to the original online survey (62% vs 69%).¹³ Younger adults were slightly more knowledgeable (M = 64%; SD = 13) than were older adults (M = 60%; SD = 15), t (288.08) = 2.01; P = .046).

Finally, most veterans reported few attempted behavioral changes to address ED, such as taking medications at a different time or decreasing use of tobacco, caffeine, or alcohol (M = 1.3; SD = 1.1). Thirty percent had not tried any behavioral changes; 34.1% tried 1 change; and 35.9% had tried more than 1 behavioral change. In contrast, 89% of participants reported using a PDE5 medication. Eight-two percent of participants reported currently receiving ED treatment of some kind; within this group, 97.4% reported currently taking a PDE5 medication. Only 2.5% of veterans reported using other kinds of treatment, such as vacuum pump, suppository, over-the-counter medication, injections, and not using a PDE5 medication, whereas 6.7% were using other kinds of treatment as well as a PDE5 medication.

In addition to the quantitative responses, 48 participants wrote unsolicited comments about their experiences with ED treatment on their returned questionnaires. The principal investigator also received 9 telephone calls from intended study participants, who provided verbal feedback regarding their experience with ED treatment. Comments unrelated to the study were eliminated, and the remaining written and verbal responses were grouped into categories to identify themes. Mirroring the quantitative results, participants providing qualitative feedback were dissatisfied with their ED treatment. Specifically, 43% of the comments consisted of complaints regarding the ineffectiveness and/or undesirable adverse effects (AEs) of ED medications and other ED treatments, including physical AEs (eg, headaches), sentiments that treatment does not feel “natural,” and dissatisfaction with the quality and length of sexual encounters despite treatment. Yet 24% of the comments entailed requests for more and/or different ED medications. Less frequent, although significant, comments related to decreased sexual interest and performance because of other medical conditions, such as pain, prostate surgery, and hypertension (15%); desire for additional information about ED treatments from health care providers (9%); use of nonpharmacologic ED interventions (eg, vacuum pump, 7%); and concerns about their partners’ level of sexual dissatisfaction as a result of their ED (7%).

Discussion

The present study examined knowledge of ED risk factors and level of satisfaction with ED treatment in a veteran population. Pharmacologic interventions comprised the most prevalent form of ED treatment. Both quantitative and qualitative results indicated areas for improvement in veteran satisfaction with ED treatment. Overall, veterans reported being neither satisfied nor dissatisfied with their current ED treatment, although very few reported being satisfied in response to a single item. The discrepancy may be related to the negative wording of the latter question (“Why are you dissatisfied with your erectile dysfunction treatment?”), which potentially biased participants’ responses. Several veterans also provided many unsolicited comments regarding areas for improvement. Despite feeling neutral to dissatisfied with treatment, 80% planned to continue with treatment. Sources of dissatisfaction included restricted access to ED medication (eg, limiting pills to 4 per month), ineffectiveness of treatment (eg, poor quality of erection, lack of climax), physical AEs, a desire for more information about ED, and psychological and relational concerns (eg, partner sexual dissatisfaction). As one veteran in his 80s lamented in describing the apparent end to his sexual life despite current ED treatment, “Is that all there is? It is the end of the road.”

The authors identified several barriers to implementing potentially beneficial interventions other than ED medications. Specifically, despite receiving long-term treatment for ED, veteran participants showed average knowledge of information related to ED risk factors. Of concern, discussing sexual health concerns with a PCP was not associated with increased knowledge of ED risk factors. This may explain the finding that veterans plan to continue with medication treatment despite feeling only neutral to dissatisfied about their current ED treatment.

Veterans who talked to their PCP about ED were less satisfied with treatment than were those who did not talk to their PCP, likely because those who felt their treatment was working for them felt less need to talk to their provider. Indeed, those who talked to their PCP tended to have more severe ED than those who did not. It may be that veterans avoid discussing ED with their PCP until they reach advanced ED when it is too late for treatment to make a difference. The principal investigator’s receipt of unsolicited telephone calls from intended study participants desiring to discuss ED—something that has not occurred during the researchers’ involvement in dozens of prior health-related studies—illustrates the importance veterans place on sexual concerns and the need to encourage discussion about the topic in the context of health care appointments. Specifically, older adults would benefit from more conversations with PCPs as they reported less knowledge of ED risk factors and fewer conversations with PCPs about sexual concerns than did younger men.

Adverse Events

Given the AEs reported by veterans and the significant cost of ED medications within the VA system,² increased use of alternative nonpharmacologic and preventive behavioral approaches would be clinically and economically beneficial. For example, in one study, men with ED who engaged in a lifestyle program that focused on weight loss, diet, and exercise were found more likely to experience improvements in erectile functioning compared with men who did not participate.⁶ Yet in the current study, 30% of participants had not attempted behavioral changes to address ED.

The VA’s Health Promotion and Disease Prevention (HPDP) Program focuses on preventive services and behavioral interventions to reduce health risks within primary care settings.¹⁹ This program may provide a framework for efforts to prevent and ameliorate ED. Specifically, coaching and education by HPDP experts could reduce PCPs’ discomfort with sexual health discussions and normalize the value of such conversations for both providers and patients. Existing HPDP behavioral interventions targeting areas such as weight loss and smoking cessation also could emphasize the potential secondary benefit of improved sexual functioning. To that end, preventive health campaigns could include sexual health and ED prevention as topics on patient education materials. Including sexual functioning on telephone or in-person prescreening questionnaires prior to routine appointments with PCPs also may facilitate destigmatization of sex as an important health topic.

Limitations

Limitations of the current study include its correlational design, which precludes conclusions regarding casual relationships among the variables in question. The authors cannot speculate about how well their sample represents the general veteran population given its low response rate (although comparable to a similar study).¹⁰ In addition, the lack of a validated measure of ED risk-factor knowledge meant reliance on an online questionnaire with unknown psychometric properties. To identify alternatives to pharmacologic treatment for ED, it would be beneficial for future research to examine the reasons for dissatisfaction among veterans, assessing satisfaction changes after implementation of behavioral and/or preventive interventions.

Conclusion

This study deepens the understanding of ED treatment efficacy among veterans in light of the paucity of available information. Overall, veterans are neutral to dissatisfied with their ED treatment, yet plan to continue it in the context of limited alternatives and possible lack of knowledge of behavioral methods shown to improve erectile functioning. Future studies that examine the reasons for continuing medication despite neutral satisfaction would help explore this finding. Based on these results, the authors recommend increased attention and discussion of sexual health during PCP visits and enhanced efforts toward using behavioral strategies to prevent and reduce ED. Encouragement from PCPs to address sexual health concerns earlier in a veteran’s treatment course—and in the context of behavioral and lifestyle change—may assist in preventing veterans’ sexual lives from prematurely reaching “the end of the road.”

Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Clement J. Zablocki VA Medical Center in Milwaukee, Wisconsin.

Multiple sclerosis (MS) is an autoimmune disorder in which the myelin of the brain and spinal cord is selectively targeted by immune-system cells. As a result, nerve transmission is disrupted, leading to a variety of unpredictable symptoms from weakness and a lack of balance to blindness and paralysis of the body. Clinically, MS can take 4 courses, including relapsing-remitting (RRMS), primary-progressive (PPMS), secondary-progressive, and progressive-relapsing.¹ At onset, 85% of diagnosed patients have RRMS, and 10% to 15% have PPMS.² If untreated, patients with RRMS become secondary-progressive, with progressive disability and indiscrete relapses.³ Hence, disease-modifying therapies are targeted toward decreasing the relapse rate as well as slowing the progression of the disease.⁴

Annually, about 16,000 veterans with MS receive health care services from the VHA.⁵ The C.W. Bill Young Bay Pines VA Healthcare System (BPVAHCS) is a level 1 facility that annually serves more than 105,000 veterans. The BPVAMC sees veterans with a wide variety of neurologic illnesses and has 5 full-time neurologists with subspecialty training. The BPVAHCS facility has outpatient clinics and a 200 inpatient bed facility. The Neurology Department sees 125 outpatients per week and consults on about 30 inpatients per week.

Methods

A retrospective review of BPVAHCS patients diagnosed with MS from January 2009 to July 2014 was performed with institutional review board approval. Patient data were collected from ICD-9-CM codes and kept confidential. A list of patients was collected from Neurology Clinic patient visits with “Multiple Sclerosis” on the problem list.

Patient medical records were reviewed to collect the following information: presence of rigorous diagnosis of MS, clinical course of MS in patient, presence or absence of disease-modifying therapy, and disease-modifying agents (DMAs) used.

Determining factors for DMA treatment included increasing tiredness, weakness, visual symptoms, and radiologic evidence (magnetic resonance imaging) of recurrent, active lesions. Each patient was examined on a case-by-case basis to assess whether or not the patient actually had MS and if so, whether they were being treated with DMAs. Only patients with RRMS were included. Patients were excluded from the study if they were deceased, not currently under BPVACHS care, or had symptoms of optic neuritis but were not fully indicative of MS. Patients with clinically isolated syndrome, probable diagnosis of MS, or PPMS also were excluded from the study.

Exclusion from this study was based on 2 additional premises. Patients were excluded if they discontinued an initial ABC (interferon beta-1a, interferon beta-1b, glatiramer acetate) due to DMA treatment relapse or adverse effects (AEs), such as injection site reactions, flulike symptoms, or depression. Additionally, patients who were not willing to take more DMA medications were excluded if they felt they were relatively stable (had infrequent relapses) and believed that additional medication was not worth the risk of potential AEs.

The study patients were seen and followed up by the neurologists. All the data for this study were based on interactions with the neurologists and not primary care providers (PCPs). Because MS treatment is complex, PCPs have little involvement in its management. The percentage of patients not on any DMAs was calculated from the list of BPVAHCS patients with RRMS.

The results were compared with a similar retrospective cohort study conducted using the Commercial Claims database and Medicare Supplemental and Coordination of Benefits database to identify individuals newly diagnosed with MS.⁶ This study was chosen because it was similar in methodology but investigated a comparable non-VA group. A 2-tailed difference between proportions test was then performed to determine whether the BPVAHCS patients with MS who were not treated with DMAs were significantly different from those from this non-VA population. Additionally, data from VA patients who were receiving DMAs were further examined and presented.

Results

At the BPVAHCS, 262 patients were diagnosed with MS and 43% were not treated with DMAs. Margolis and colleagues found that about 60% of its 11,061 newly diagnosed non-VA patients with MS remained untreated.⁶ Although the latter proportion is higher, a 2-tailed difference between proportions test indicates that the proportion of patients with MS being treated at the VA was significantly lower (P < .01).

Among the 148 patients who were diagnosed with MS and treated with DMA at BPVAHCS, 5 different DMAs were identified (Table). The most commonly prescribed regimen was glatiramer acetate, which was used by 56 of 148 patients (37.8%). Fifty-two patients (35.1%) used interferon beta-1a. Of the 2 interferon DMAs, beta-1a was twice as popular as beta-1b, which was prescribed to 22 (14.9%) of patients. Dimethyl fumarate (6.8%) and fingolimod (5.4%) were used sparingly, because they were new to the market (cost and availability also were factors). With time, increased efficacy and objective assessment of benefit in the reduction of the T2 lesion load may result in a greater use of these oral DMAs.^7–9

Based on this evaluation, 43% of patients who were diagnosed with MS were untreated at BPVAHCS. Concern over treatment AEs, the inconvenience of injectable dosing, and patients who were not 100% service-connected and lost to follow-up because of the cost may have contributed to the poor rate of treatment.

Discussion

Injected-based DMAs, such as interferon beta-1a, interferon beta-1b, and glatiramer acetate, were first introduced in the 1990s, but these proved to be inconvenient and triggered AEs, including injection site reactions. Overall, their efficacy was about 30%, with interferon beta-1a showing a 27% reduction in relapses.¹⁰ In 2010, oral DMAs, such as fingolimod, were FDA approved. These oral DMAs were a significant improvement over injectable DMAs but still had AEs. Hence, their use was restricted to neurologists by the BPVAHCS, and rightfully so.

Still, newer and more effective oral DMAs are showing promise, such as dimethyl fumarate, teriflunomide, and alemtuzumab. These new DMAs have significantly impacted the treatment of MS as they are not only easier for patients to adhere to and for neurologists to prescribe, but most significantly, have had a 50% decrease in the rate of relapse.¹⁰ Yet, the newer oral DMAs were less commonly prescribed than the older treatments at BPVAHCS.

Since this study did not demonstrate increased use of oral DMAs at the BPVAHCS, more PCP and neurologist-focused educational programs on the use of DMAs may be beneficial. Educational programs should lead to a reevaluation of patients with MS to consider oral DMAs, which offer better efficacy and fewer AEs. The newer oral DMAs have shown a higher reduction of T2 lesions, and the significantly decreased incidence of relapses in many other medical facilities is quite promising for the BPVAHCS.^7-9

The data collected at BPVAHCS were part of a quality improvement (QI) study that will be used by the Neurology Department to follow up on the patients with MS in order to implement DMA therapies. A questionnaire was developed for following up with BPVAHCS patients with MS. The primary purpose of the questionnaire is to help neurologists identify the reasons patients avoid DMA therapies and to reduce the number of BPVAHCS patients not on the most efficacious MS DMA treatment.

Conclusion

Multiple sclerosis is a disease without a cure. Current treatment strategies focus on modifying the course of the disease and managing its symptoms. However, even as promising new treatments emerge, the current literature suggests that a significant number of patients diagnosed with MS are not receiving DMAs and may not be receiving optimal treatment.¹¹

Findings from this study indicate that although DMAs are optimal for patients with MS, they may not be prescribed as frequently at BPVAHCS as they are at a non-VA care facility. It is unclear whether this finding is explained by an educational gap, clinical differences between non-VA and VA patients, organizational factors, or a combination of these variables. Further study is warranted to examine the use of DMAs among veterans with MS and factors that facilitate or impede optimal practice. The BPVAHCS will use data from this retrospective cohort study in a QI initiative for patients with MS. Findings from the QI initiative will be reported using the Standards for Quality Improvement Reporting Excellence.^12,13

Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Bay Pines VA Healthcare System.

Multiple sclerosis (MS) is an autoimmune disorder in which the myelin of the brain and spinal cord is selectively targeted by immune-system cells. As a result, nerve transmission is disrupted, leading to a variety of unpredictable symptoms from weakness and a lack of balance to blindness and paralysis of the body. Clinically, MS can take 4 courses, including relapsing-remitting (RRMS), primary-progressive (PPMS), secondary-progressive, and progressive-relapsing.¹ At onset, 85% of diagnosed patients have RRMS, and 10% to 15% have PPMS.² If untreated, patients with RRMS become secondary-progressive, with progressive disability and indiscrete relapses.³ Hence, disease-modifying therapies are targeted toward decreasing the relapse rate as well as slowing the progression of the disease.⁴

Annually, about 16,000 veterans with MS receive health care services from the VHA.⁵ The C.W. Bill Young Bay Pines VA Healthcare System (BPVAHCS) is a level 1 facility that annually serves more than 105,000 veterans. The BPVAMC sees veterans with a wide variety of neurologic illnesses and has 5 full-time neurologists with subspecialty training. The BPVAHCS facility has outpatient clinics and a 200 inpatient bed facility. The Neurology Department sees 125 outpatients per week and consults on about 30 inpatients per week.

Methods

A retrospective review of BPVAHCS patients diagnosed with MS from January 2009 to July 2014 was performed with institutional review board approval. Patient data were collected from ICD-9-CM codes and kept confidential. A list of patients was collected from Neurology Clinic patient visits with “Multiple Sclerosis” on the problem list.

Patient medical records were reviewed to collect the following information: presence of rigorous diagnosis of MS, clinical course of MS in patient, presence or absence of disease-modifying therapy, and disease-modifying agents (DMAs) used.

Determining factors for DMA treatment included increasing tiredness, weakness, visual symptoms, and radiologic evidence (magnetic resonance imaging) of recurrent, active lesions. Each patient was examined on a case-by-case basis to assess whether or not the patient actually had MS and if so, whether they were being treated with DMAs. Only patients with RRMS were included. Patients were excluded from the study if they were deceased, not currently under BPVACHS care, or had symptoms of optic neuritis but were not fully indicative of MS. Patients with clinically isolated syndrome, probable diagnosis of MS, or PPMS also were excluded from the study.

Exclusion from this study was based on 2 additional premises. Patients were excluded if they discontinued an initial ABC (interferon beta-1a, interferon beta-1b, glatiramer acetate) due to DMA treatment relapse or adverse effects (AEs), such as injection site reactions, flulike symptoms, or depression. Additionally, patients who were not willing to take more DMA medications were excluded if they felt they were relatively stable (had infrequent relapses) and believed that additional medication was not worth the risk of potential AEs.

The study patients were seen and followed up by the neurologists. All the data for this study were based on interactions with the neurologists and not primary care providers (PCPs). Because MS treatment is complex, PCPs have little involvement in its management. The percentage of patients not on any DMAs was calculated from the list of BPVAHCS patients with RRMS.

The results were compared with a similar retrospective cohort study conducted using the Commercial Claims database and Medicare Supplemental and Coordination of Benefits database to identify individuals newly diagnosed with MS.⁶ This study was chosen because it was similar in methodology but investigated a comparable non-VA group. A 2-tailed difference between proportions test was then performed to determine whether the BPVAHCS patients with MS who were not treated with DMAs were significantly different from those from this non-VA population. Additionally, data from VA patients who were receiving DMAs were further examined and presented.

Results

At the BPVAHCS, 262 patients were diagnosed with MS and 43% were not treated with DMAs. Margolis and colleagues found that about 60% of its 11,061 newly diagnosed non-VA patients with MS remained untreated.⁶ Although the latter proportion is higher, a 2-tailed difference between proportions test indicates that the proportion of patients with MS being treated at the VA was significantly lower (P < .01).

Among the 148 patients who were diagnosed with MS and treated with DMA at BPVAHCS, 5 different DMAs were identified (Table). The most commonly prescribed regimen was glatiramer acetate, which was used by 56 of 148 patients (37.8%). Fifty-two patients (35.1%) used interferon beta-1a. Of the 2 interferon DMAs, beta-1a was twice as popular as beta-1b, which was prescribed to 22 (14.9%) of patients. Dimethyl fumarate (6.8%) and fingolimod (5.4%) were used sparingly, because they were new to the market (cost and availability also were factors). With time, increased efficacy and objective assessment of benefit in the reduction of the T2 lesion load may result in a greater use of these oral DMAs.^7–9

Based on this evaluation, 43% of patients who were diagnosed with MS were untreated at BPVAHCS. Concern over treatment AEs, the inconvenience of injectable dosing, and patients who were not 100% service-connected and lost to follow-up because of the cost may have contributed to the poor rate of treatment.

Discussion

Injected-based DMAs, such as interferon beta-1a, interferon beta-1b, and glatiramer acetate, were first introduced in the 1990s, but these proved to be inconvenient and triggered AEs, including injection site reactions. Overall, their efficacy was about 30%, with interferon beta-1a showing a 27% reduction in relapses.¹⁰ In 2010, oral DMAs, such as fingolimod, were FDA approved. These oral DMAs were a significant improvement over injectable DMAs but still had AEs. Hence, their use was restricted to neurologists by the BPVAHCS, and rightfully so.

Still, newer and more effective oral DMAs are showing promise, such as dimethyl fumarate, teriflunomide, and alemtuzumab. These new DMAs have significantly impacted the treatment of MS as they are not only easier for patients to adhere to and for neurologists to prescribe, but most significantly, have had a 50% decrease in the rate of relapse.¹⁰ Yet, the newer oral DMAs were less commonly prescribed than the older treatments at BPVAHCS.

Since this study did not demonstrate increased use of oral DMAs at the BPVAHCS, more PCP and neurologist-focused educational programs on the use of DMAs may be beneficial. Educational programs should lead to a reevaluation of patients with MS to consider oral DMAs, which offer better efficacy and fewer AEs. The newer oral DMAs have shown a higher reduction of T2 lesions, and the significantly decreased incidence of relapses in many other medical facilities is quite promising for the BPVAHCS.^7-9

The data collected at BPVAHCS were part of a quality improvement (QI) study that will be used by the Neurology Department to follow up on the patients with MS in order to implement DMA therapies. A questionnaire was developed for following up with BPVAHCS patients with MS. The primary purpose of the questionnaire is to help neurologists identify the reasons patients avoid DMA therapies and to reduce the number of BPVAHCS patients not on the most efficacious MS DMA treatment.

Conclusion

Multiple sclerosis is a disease without a cure. Current treatment strategies focus on modifying the course of the disease and managing its symptoms. However, even as promising new treatments emerge, the current literature suggests that a significant number of patients diagnosed with MS are not receiving DMAs and may not be receiving optimal treatment.¹¹

Findings from this study indicate that although DMAs are optimal for patients with MS, they may not be prescribed as frequently at BPVAHCS as they are at a non-VA care facility. It is unclear whether this finding is explained by an educational gap, clinical differences between non-VA and VA patients, organizational factors, or a combination of these variables. Further study is warranted to examine the use of DMAs among veterans with MS and factors that facilitate or impede optimal practice. The BPVAHCS will use data from this retrospective cohort study in a QI initiative for patients with MS. Findings from the QI initiative will be reported using the Standards for Quality Improvement Reporting Excellence.^12,13

Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Bay Pines VA Healthcare System.

Multiple sclerosis (MS) is an autoimmune disorder in which the myelin of the brain and spinal cord is selectively targeted by immune-system cells. As a result, nerve transmission is disrupted, leading to a variety of unpredictable symptoms from weakness and a lack of balance to blindness and paralysis of the body. Clinically, MS can take 4 courses, including relapsing-remitting (RRMS), primary-progressive (PPMS), secondary-progressive, and progressive-relapsing.¹ At onset, 85% of diagnosed patients have RRMS, and 10% to 15% have PPMS.² If untreated, patients with RRMS become secondary-progressive, with progressive disability and indiscrete relapses.³ Hence, disease-modifying therapies are targeted toward decreasing the relapse rate as well as slowing the progression of the disease.⁴

Annually, about 16,000 veterans with MS receive health care services from the VHA.⁵ The C.W. Bill Young Bay Pines VA Healthcare System (BPVAHCS) is a level 1 facility that annually serves more than 105,000 veterans. The BPVAMC sees veterans with a wide variety of neurologic illnesses and has 5 full-time neurologists with subspecialty training. The BPVAHCS facility has outpatient clinics and a 200 inpatient bed facility. The Neurology Department sees 125 outpatients per week and consults on about 30 inpatients per week.

Methods

A retrospective review of BPVAHCS patients diagnosed with MS from January 2009 to July 2014 was performed with institutional review board approval. Patient data were collected from ICD-9-CM codes and kept confidential. A list of patients was collected from Neurology Clinic patient visits with “Multiple Sclerosis” on the problem list.

Patient medical records were reviewed to collect the following information: presence of rigorous diagnosis of MS, clinical course of MS in patient, presence or absence of disease-modifying therapy, and disease-modifying agents (DMAs) used.

Determining factors for DMA treatment included increasing tiredness, weakness, visual symptoms, and radiologic evidence (magnetic resonance imaging) of recurrent, active lesions. Each patient was examined on a case-by-case basis to assess whether or not the patient actually had MS and if so, whether they were being treated with DMAs. Only patients with RRMS were included. Patients were excluded from the study if they were deceased, not currently under BPVACHS care, or had symptoms of optic neuritis but were not fully indicative of MS. Patients with clinically isolated syndrome, probable diagnosis of MS, or PPMS also were excluded from the study.

Exclusion from this study was based on 2 additional premises. Patients were excluded if they discontinued an initial ABC (interferon beta-1a, interferon beta-1b, glatiramer acetate) due to DMA treatment relapse or adverse effects (AEs), such as injection site reactions, flulike symptoms, or depression. Additionally, patients who were not willing to take more DMA medications were excluded if they felt they were relatively stable (had infrequent relapses) and believed that additional medication was not worth the risk of potential AEs.

The study patients were seen and followed up by the neurologists. All the data for this study were based on interactions with the neurologists and not primary care providers (PCPs). Because MS treatment is complex, PCPs have little involvement in its management. The percentage of patients not on any DMAs was calculated from the list of BPVAHCS patients with RRMS.

The results were compared with a similar retrospective cohort study conducted using the Commercial Claims database and Medicare Supplemental and Coordination of Benefits database to identify individuals newly diagnosed with MS.⁶ This study was chosen because it was similar in methodology but investigated a comparable non-VA group. A 2-tailed difference between proportions test was then performed to determine whether the BPVAHCS patients with MS who were not treated with DMAs were significantly different from those from this non-VA population. Additionally, data from VA patients who were receiving DMAs were further examined and presented.

Results

At the BPVAHCS, 262 patients were diagnosed with MS and 43% were not treated with DMAs. Margolis and colleagues found that about 60% of its 11,061 newly diagnosed non-VA patients with MS remained untreated.⁶ Although the latter proportion is higher, a 2-tailed difference between proportions test indicates that the proportion of patients with MS being treated at the VA was significantly lower (P < .01).

Among the 148 patients who were diagnosed with MS and treated with DMA at BPVAHCS, 5 different DMAs were identified (Table). The most commonly prescribed regimen was glatiramer acetate, which was used by 56 of 148 patients (37.8%). Fifty-two patients (35.1%) used interferon beta-1a. Of the 2 interferon DMAs, beta-1a was twice as popular as beta-1b, which was prescribed to 22 (14.9%) of patients. Dimethyl fumarate (6.8%) and fingolimod (5.4%) were used sparingly, because they were new to the market (cost and availability also were factors). With time, increased efficacy and objective assessment of benefit in the reduction of the T2 lesion load may result in a greater use of these oral DMAs.^7–9

Based on this evaluation, 43% of patients who were diagnosed with MS were untreated at BPVAHCS. Concern over treatment AEs, the inconvenience of injectable dosing, and patients who were not 100% service-connected and lost to follow-up because of the cost may have contributed to the poor rate of treatment.

Discussion

Injected-based DMAs, such as interferon beta-1a, interferon beta-1b, and glatiramer acetate, were first introduced in the 1990s, but these proved to be inconvenient and triggered AEs, including injection site reactions. Overall, their efficacy was about 30%, with interferon beta-1a showing a 27% reduction in relapses.¹⁰ In 2010, oral DMAs, such as fingolimod, were FDA approved. These oral DMAs were a significant improvement over injectable DMAs but still had AEs. Hence, their use was restricted to neurologists by the BPVAHCS, and rightfully so.

Still, newer and more effective oral DMAs are showing promise, such as dimethyl fumarate, teriflunomide, and alemtuzumab. These new DMAs have significantly impacted the treatment of MS as they are not only easier for patients to adhere to and for neurologists to prescribe, but most significantly, have had a 50% decrease in the rate of relapse.¹⁰ Yet, the newer oral DMAs were less commonly prescribed than the older treatments at BPVAHCS.

Since this study did not demonstrate increased use of oral DMAs at the BPVAHCS, more PCP and neurologist-focused educational programs on the use of DMAs may be beneficial. Educational programs should lead to a reevaluation of patients with MS to consider oral DMAs, which offer better efficacy and fewer AEs. The newer oral DMAs have shown a higher reduction of T2 lesions, and the significantly decreased incidence of relapses in many other medical facilities is quite promising for the BPVAHCS.^7-9

The data collected at BPVAHCS were part of a quality improvement (QI) study that will be used by the Neurology Department to follow up on the patients with MS in order to implement DMA therapies. A questionnaire was developed for following up with BPVAHCS patients with MS. The primary purpose of the questionnaire is to help neurologists identify the reasons patients avoid DMA therapies and to reduce the number of BPVAHCS patients not on the most efficacious MS DMA treatment.

Conclusion

Multiple sclerosis is a disease without a cure. Current treatment strategies focus on modifying the course of the disease and managing its symptoms. However, even as promising new treatments emerge, the current literature suggests that a significant number of patients diagnosed with MS are not receiving DMAs and may not be receiving optimal treatment.¹¹

Findings from this study indicate that although DMAs are optimal for patients with MS, they may not be prescribed as frequently at BPVAHCS as they are at a non-VA care facility. It is unclear whether this finding is explained by an educational gap, clinical differences between non-VA and VA patients, organizational factors, or a combination of these variables. Further study is warranted to examine the use of DMAs among veterans with MS and factors that facilitate or impede optimal practice. The BPVAHCS will use data from this retrospective cohort study in a QI initiative for patients with MS. Findings from the QI initiative will be reported using the Standards for Quality Improvement Reporting Excellence.^12,13

Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Bay Pines VA Healthcare System.

The incidence of Clostridium difficile (C difficile) infection (CDI) in the U.S. has been steadily increasing. In U.S. hospitals between 1996 and 2003, the rate of CDI diagnosis doubled, and in 2011, almost half a million CDIs contributed to 29,000 deaths.^1,2 Recurrence rates after successful metronidazole or vancomycin treatment are as high as 35%.^3-5 After a second recurrence, rates are as high as 40% to 60%.⁶

Historically, CDI was almost exclusively associated with the elderly, with exposure to health care facilities, or in individuals with a history of previous antibiotic use.^1,7 Risk factors for CDI recurrence are similar, including the elderly, antibiotic use during or after initial CDI treatment, and an impaired immune response against C difficile toxins.⁸ However, more recently CDI has been linked to individuals who were previously considered low risk, including the young and previously healthy individuals without exposure to a health care environment or recent antibiotic use.⁹

Community-acquired CDIs occurring in populations previously at low risk may be due to increased virulence of the disease. A hypervirulent C difficile strain, the North American Pulsed field type 1 (NAP1)/B1/027 strain, has emerged. This strain is more resistant to fluoroquinolone antibiotics and has caused multiple CDI outbreaks in the U.S.⁷ Along with the increased rate of CDI occurrence, mortality rates due to CDI have been rising.¹⁰ Recent studies have shown increased rates of CDI recurrence and treatment failure in response to standard therapy (metronidazole or vancomycin).^11-13

To combat emerging treatment challenges of CDIs, the FDA approved a new antibiotic, fidaxomicin, for the treatment of C difficile-associated diarrhea in 2011.¹⁴ Fidaxomicin is a first-in-class macrocyclic antibiotic that has low systemic absorption, low activity against intestinal flora, and high fecal concentrations.¹⁵ Fidaxomicin also has been shown to be less likely to promote vancomycin-resistant enterococci (VRE) than does vancomycin in CDI treatment.¹⁶ Fidaxomicin is an emerging treatment strategy for CDIs, and this article reviews its role in the treatment of CDI.

CDI Standard of Therapy

Before the approval of fidaxomicin, the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America released the 2010 update to the clinical practice guidelines for the treatment of CDI. Due to initial concern that use of oral vancomycin would select for VRE, guidelines recommend oral metronidazole for mild-to-moderate disease, oral vancomycin for severe CDI, and combination therapy of oral vancomycin with or without IV metronidazole for severe, complicated CDI (disease severity is defined in the Table).^8,17

Fidaxomicin Approval

Prior to the approval of fidaxomicin for CDI in 2011, the FDA evaluated 2 noninferiority (NI) clinical trials comparing oral fidaxomicin to oral vancomycin for the treatment of CDI. Given that a clinical trial had previously demonstrated superior clinical cure rates of vancomycin over metronidazole, vancomycin was used as the comparator in the fidaxomicin NI trials.¹⁵ Louie and colleagues conducted a double-blind, randomized phase 3 trial comparing 10 days of fidaxomicin (200 mg twice daily) to vancomycin (125 mg 4 times daily) for the treatment of CDI (n = 629).³ Fidaxomicin was found to be noninferior to vancomycin for rate of clinical cure in the modified intention-to-treat (ITT) analysis (88% vs 86%, respectively) and the per-protocol analysis (92% vs 90%, respectively) with a NI margin of 10%. There were lower recurrence rates of CDI with fidaxomicin compared with that of vancomycin in the modified ITT analysis (15% vs 25%, respectively; P = .005). When infection with the NAP1/BI/027 strain was evaluated, fidaxomicin was shown to be noninferior to vancomycin for both clinical cure and recurrence rates.

The Louie and colleagues results were further validated when a second NI trial (n = 535) was published by Cornely and colleagues, which demonstrated similar clinical cure and recurrence rates with fidaxomicin compared with that of vancomycin.⁴ It is important to note that both trials used a modified ITT analysis, which included postrandomization exclusions that may have biased the results. Additionally, both trials were industry sponsored and had industry representation throughout the data collection, analysis, and manuscript preparation processes.

Use of Fidaxomicin

Fidaxomicin has been considered for use in the treatment of recurrent CDI. According to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of CDI, fidaxomicin is an option for both first and multiple recurrences (ESCMID does not recommend fidaxomicin for an initial episode of CDI). These guidelines state that either oral fidaxomicin or vancomycin for 10 days is an appropriate first recurrence treatment option. For multiple recurrences, the recommendations are oral fidaxomicin for 10 days or oral vancomycin for 10 days followed by a tapered or pulse­­d regimen.¹⁸ The IDSA C difficile treatment guidelines have not been updated since the approval of fidaxomicin and, therefore, do not contain recommendations for its use.

Given the low propensity for fidaxomicin to disrupt colonic flora, it may be hypothesized that its greatest benefit would be for use as first-line therapy in patients with a high risk of CDI recurrence prior to disruption of colonic flora with the treatment of vancomycin or metronidazole. A clinical prediction tool is needed to identify patients at high risk of CDI recurrence who would most benefit from initial fidaxomicin therapy. However, clinically relevant prediction tools are not currently used.¹⁹

Evidence exists that demonstrates the role of fidaxomicin for the treatment of recurrent CDI episodes. Cornely and colleagues pooled data from the 2 NI trials that led to the approval of fidaxomicin (n = 1,164).^3,4,20 Of these, 128 participants had a recent CDI episode prior to study enrollment. For the treatment of first recurrence, 20% of patients treated with fidaxomicin experienced a second recurrence within 28 days compared with 36% of vancomycin patients (P = .045). Similarly, fewer fidaxomicin patients experienced an early recurrence within 14 days of treatment than with vancomycin for early recurrence within 14 days of treatment (8% vs 27%, respectively; P = .003).

Limitations of Fidaxomicin

One limitation of fidaxomicin is the paucity of data existing for its use in severe, life-threatening CDI, and it is currently not recommended in this indication.¹⁸ The main limitation behind the use of fidaxomicin is cost. The average wholesale price of a 10-day course of therapy of fidaxomicin is $3,360 compared with $1,273 for vancomycin capsules, $32 for compounded vancomycin oral solution, and $21 for oral metronidazole.^21,22 Despite the price, cost-analysis studies have found that fidaxomicin compared with oral vancomycin is cost-effective for clinical cure rates and recurrences.^23,24 Fidaxomicin also was found to be cost-effective in patients with mild-to-moderate CDI and in those using concomitant antibiotics.²³ Given that 2 studies demonstrated that fidaxomicin has lower recurrence rates than that of oral vancomycin, the economical use of fidaxomicin would be of most benefit to patients at highest risk for CDI recurrence.^3,4

Conclusion

In light of increased CDI treatment failure, recurrence rates, and virulence of CDI, fidaxomicin is an emerging treatment strategy. Through 2 pivotal trials, fidaxomicin has been shown to be a safe and effective first-line agent for CDI.^3,4 New U.S. clinical guidelines for CDI are expected to be published in spring 2016, which will likely include the recommendation for fidaxomicin use in recurrent CDI. Current evidence suggests the most cost-effective use of fidaxomicin is in patients at highest risk of CDI recurrence.

The incidence of Clostridium difficile (C difficile) infection (CDI) in the U.S. has been steadily increasing. In U.S. hospitals between 1996 and 2003, the rate of CDI diagnosis doubled, and in 2011, almost half a million CDIs contributed to 29,000 deaths.^1,2 Recurrence rates after successful metronidazole or vancomycin treatment are as high as 35%.^3-5 After a second recurrence, rates are as high as 40% to 60%.⁶

Historically, CDI was almost exclusively associated with the elderly, with exposure to health care facilities, or in individuals with a history of previous antibiotic use.^1,7 Risk factors for CDI recurrence are similar, including the elderly, antibiotic use during or after initial CDI treatment, and an impaired immune response against C difficile toxins.⁸ However, more recently CDI has been linked to individuals who were previously considered low risk, including the young and previously healthy individuals without exposure to a health care environment or recent antibiotic use.⁹

Community-acquired CDIs occurring in populations previously at low risk may be due to increased virulence of the disease. A hypervirulent C difficile strain, the North American Pulsed field type 1 (NAP1)/B1/027 strain, has emerged. This strain is more resistant to fluoroquinolone antibiotics and has caused multiple CDI outbreaks in the U.S.⁷ Along with the increased rate of CDI occurrence, mortality rates due to CDI have been rising.¹⁰ Recent studies have shown increased rates of CDI recurrence and treatment failure in response to standard therapy (metronidazole or vancomycin).^11-13

To combat emerging treatment challenges of CDIs, the FDA approved a new antibiotic, fidaxomicin, for the treatment of C difficile-associated diarrhea in 2011.¹⁴ Fidaxomicin is a first-in-class macrocyclic antibiotic that has low systemic absorption, low activity against intestinal flora, and high fecal concentrations.¹⁵ Fidaxomicin also has been shown to be less likely to promote vancomycin-resistant enterococci (VRE) than does vancomycin in CDI treatment.¹⁶ Fidaxomicin is an emerging treatment strategy for CDIs, and this article reviews its role in the treatment of CDI.

CDI Standard of Therapy

Before the approval of fidaxomicin, the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America released the 2010 update to the clinical practice guidelines for the treatment of CDI. Due to initial concern that use of oral vancomycin would select for VRE, guidelines recommend oral metronidazole for mild-to-moderate disease, oral vancomycin for severe CDI, and combination therapy of oral vancomycin with or without IV metronidazole for severe, complicated CDI (disease severity is defined in the Table).^8,17

Fidaxomicin Approval

Prior to the approval of fidaxomicin for CDI in 2011, the FDA evaluated 2 noninferiority (NI) clinical trials comparing oral fidaxomicin to oral vancomycin for the treatment of CDI. Given that a clinical trial had previously demonstrated superior clinical cure rates of vancomycin over metronidazole, vancomycin was used as the comparator in the fidaxomicin NI trials.¹⁵ Louie and colleagues conducted a double-blind, randomized phase 3 trial comparing 10 days of fidaxomicin (200 mg twice daily) to vancomycin (125 mg 4 times daily) for the treatment of CDI (n = 629).³ Fidaxomicin was found to be noninferior to vancomycin for rate of clinical cure in the modified intention-to-treat (ITT) analysis (88% vs 86%, respectively) and the per-protocol analysis (92% vs 90%, respectively) with a NI margin of 10%. There were lower recurrence rates of CDI with fidaxomicin compared with that of vancomycin in the modified ITT analysis (15% vs 25%, respectively; P = .005). When infection with the NAP1/BI/027 strain was evaluated, fidaxomicin was shown to be noninferior to vancomycin for both clinical cure and recurrence rates.

The Louie and colleagues results were further validated when a second NI trial (n = 535) was published by Cornely and colleagues, which demonstrated similar clinical cure and recurrence rates with fidaxomicin compared with that of vancomycin.⁴ It is important to note that both trials used a modified ITT analysis, which included postrandomization exclusions that may have biased the results. Additionally, both trials were industry sponsored and had industry representation throughout the data collection, analysis, and manuscript preparation processes.

Use of Fidaxomicin

Fidaxomicin has been considered for use in the treatment of recurrent CDI. According to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of CDI, fidaxomicin is an option for both first and multiple recurrences (ESCMID does not recommend fidaxomicin for an initial episode of CDI). These guidelines state that either oral fidaxomicin or vancomycin for 10 days is an appropriate first recurrence treatment option. For multiple recurrences, the recommendations are oral fidaxomicin for 10 days or oral vancomycin for 10 days followed by a tapered or pulse­­d regimen.¹⁸ The IDSA C difficile treatment guidelines have not been updated since the approval of fidaxomicin and, therefore, do not contain recommendations for its use.

Given the low propensity for fidaxomicin to disrupt colonic flora, it may be hypothesized that its greatest benefit would be for use as first-line therapy in patients with a high risk of CDI recurrence prior to disruption of colonic flora with the treatment of vancomycin or metronidazole. A clinical prediction tool is needed to identify patients at high risk of CDI recurrence who would most benefit from initial fidaxomicin therapy. However, clinically relevant prediction tools are not currently used.¹⁹

Evidence exists that demonstrates the role of fidaxomicin for the treatment of recurrent CDI episodes. Cornely and colleagues pooled data from the 2 NI trials that led to the approval of fidaxomicin (n = 1,164).^3,4,20 Of these, 128 participants had a recent CDI episode prior to study enrollment. For the treatment of first recurrence, 20% of patients treated with fidaxomicin experienced a second recurrence within 28 days compared with 36% of vancomycin patients (P = .045). Similarly, fewer fidaxomicin patients experienced an early recurrence within 14 days of treatment than with vancomycin for early recurrence within 14 days of treatment (8% vs 27%, respectively; P = .003).

Limitations of Fidaxomicin

One limitation of fidaxomicin is the paucity of data existing for its use in severe, life-threatening CDI, and it is currently not recommended in this indication.¹⁸ The main limitation behind the use of fidaxomicin is cost. The average wholesale price of a 10-day course of therapy of fidaxomicin is $3,360 compared with $1,273 for vancomycin capsules, $32 for compounded vancomycin oral solution, and $21 for oral metronidazole.^21,22 Despite the price, cost-analysis studies have found that fidaxomicin compared with oral vancomycin is cost-effective for clinical cure rates and recurrences.^23,24 Fidaxomicin also was found to be cost-effective in patients with mild-to-moderate CDI and in those using concomitant antibiotics.²³ Given that 2 studies demonstrated that fidaxomicin has lower recurrence rates than that of oral vancomycin, the economical use of fidaxomicin would be of most benefit to patients at highest risk for CDI recurrence.^3,4

Conclusion

In light of increased CDI treatment failure, recurrence rates, and virulence of CDI, fidaxomicin is an emerging treatment strategy. Through 2 pivotal trials, fidaxomicin has been shown to be a safe and effective first-line agent for CDI.^3,4 New U.S. clinical guidelines for CDI are expected to be published in spring 2016, which will likely include the recommendation for fidaxomicin use in recurrent CDI. Current evidence suggests the most cost-effective use of fidaxomicin is in patients at highest risk of CDI recurrence.

The incidence of Clostridium difficile (C difficile) infection (CDI) in the U.S. has been steadily increasing. In U.S. hospitals between 1996 and 2003, the rate of CDI diagnosis doubled, and in 2011, almost half a million CDIs contributed to 29,000 deaths.^1,2 Recurrence rates after successful metronidazole or vancomycin treatment are as high as 35%.^3-5 After a second recurrence, rates are as high as 40% to 60%.⁶

Historically, CDI was almost exclusively associated with the elderly, with exposure to health care facilities, or in individuals with a history of previous antibiotic use.^1,7 Risk factors for CDI recurrence are similar, including the elderly, antibiotic use during or after initial CDI treatment, and an impaired immune response against C difficile toxins.⁸ However, more recently CDI has been linked to individuals who were previously considered low risk, including the young and previously healthy individuals without exposure to a health care environment or recent antibiotic use.⁹

Community-acquired CDIs occurring in populations previously at low risk may be due to increased virulence of the disease. A hypervirulent C difficile strain, the North American Pulsed field type 1 (NAP1)/B1/027 strain, has emerged. This strain is more resistant to fluoroquinolone antibiotics and has caused multiple CDI outbreaks in the U.S.⁷ Along with the increased rate of CDI occurrence, mortality rates due to CDI have been rising.¹⁰ Recent studies have shown increased rates of CDI recurrence and treatment failure in response to standard therapy (metronidazole or vancomycin).^11-13

To combat emerging treatment challenges of CDIs, the FDA approved a new antibiotic, fidaxomicin, for the treatment of C difficile-associated diarrhea in 2011.¹⁴ Fidaxomicin is a first-in-class macrocyclic antibiotic that has low systemic absorption, low activity against intestinal flora, and high fecal concentrations.¹⁵ Fidaxomicin also has been shown to be less likely to promote vancomycin-resistant enterococci (VRE) than does vancomycin in CDI treatment.¹⁶ Fidaxomicin is an emerging treatment strategy for CDIs, and this article reviews its role in the treatment of CDI.

CDI Standard of Therapy

Before the approval of fidaxomicin, the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America released the 2010 update to the clinical practice guidelines for the treatment of CDI. Due to initial concern that use of oral vancomycin would select for VRE, guidelines recommend oral metronidazole for mild-to-moderate disease, oral vancomycin for severe CDI, and combination therapy of oral vancomycin with or without IV metronidazole for severe, complicated CDI (disease severity is defined in the Table).^8,17

Fidaxomicin Approval

Prior to the approval of fidaxomicin for CDI in 2011, the FDA evaluated 2 noninferiority (NI) clinical trials comparing oral fidaxomicin to oral vancomycin for the treatment of CDI. Given that a clinical trial had previously demonstrated superior clinical cure rates of vancomycin over metronidazole, vancomycin was used as the comparator in the fidaxomicin NI trials.¹⁵ Louie and colleagues conducted a double-blind, randomized phase 3 trial comparing 10 days of fidaxomicin (200 mg twice daily) to vancomycin (125 mg 4 times daily) for the treatment of CDI (n = 629).³ Fidaxomicin was found to be noninferior to vancomycin for rate of clinical cure in the modified intention-to-treat (ITT) analysis (88% vs 86%, respectively) and the per-protocol analysis (92% vs 90%, respectively) with a NI margin of 10%. There were lower recurrence rates of CDI with fidaxomicin compared with that of vancomycin in the modified ITT analysis (15% vs 25%, respectively; P = .005). When infection with the NAP1/BI/027 strain was evaluated, fidaxomicin was shown to be noninferior to vancomycin for both clinical cure and recurrence rates.

The Louie and colleagues results were further validated when a second NI trial (n = 535) was published by Cornely and colleagues, which demonstrated similar clinical cure and recurrence rates with fidaxomicin compared with that of vancomycin.⁴ It is important to note that both trials used a modified ITT analysis, which included postrandomization exclusions that may have biased the results. Additionally, both trials were industry sponsored and had industry representation throughout the data collection, analysis, and manuscript preparation processes.

Use of Fidaxomicin

Fidaxomicin has been considered for use in the treatment of recurrent CDI. According to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of CDI, fidaxomicin is an option for both first and multiple recurrences (ESCMID does not recommend fidaxomicin for an initial episode of CDI). These guidelines state that either oral fidaxomicin or vancomycin for 10 days is an appropriate first recurrence treatment option. For multiple recurrences, the recommendations are oral fidaxomicin for 10 days or oral vancomycin for 10 days followed by a tapered or pulse­­d regimen.¹⁸ The IDSA C difficile treatment guidelines have not been updated since the approval of fidaxomicin and, therefore, do not contain recommendations for its use.

Given the low propensity for fidaxomicin to disrupt colonic flora, it may be hypothesized that its greatest benefit would be for use as first-line therapy in patients with a high risk of CDI recurrence prior to disruption of colonic flora with the treatment of vancomycin or metronidazole. A clinical prediction tool is needed to identify patients at high risk of CDI recurrence who would most benefit from initial fidaxomicin therapy. However, clinically relevant prediction tools are not currently used.¹⁹

Evidence exists that demonstrates the role of fidaxomicin for the treatment of recurrent CDI episodes. Cornely and colleagues pooled data from the 2 NI trials that led to the approval of fidaxomicin (n = 1,164).^3,4,20 Of these, 128 participants had a recent CDI episode prior to study enrollment. For the treatment of first recurrence, 20% of patients treated with fidaxomicin experienced a second recurrence within 28 days compared with 36% of vancomycin patients (P = .045). Similarly, fewer fidaxomicin patients experienced an early recurrence within 14 days of treatment than with vancomycin for early recurrence within 14 days of treatment (8% vs 27%, respectively; P = .003).

Limitations of Fidaxomicin

One limitation of fidaxomicin is the paucity of data existing for its use in severe, life-threatening CDI, and it is currently not recommended in this indication.¹⁸ The main limitation behind the use of fidaxomicin is cost. The average wholesale price of a 10-day course of therapy of fidaxomicin is $3,360 compared with $1,273 for vancomycin capsules, $32 for compounded vancomycin oral solution, and $21 for oral metronidazole.^21,22 Despite the price, cost-analysis studies have found that fidaxomicin compared with oral vancomycin is cost-effective for clinical cure rates and recurrences.^23,24 Fidaxomicin also was found to be cost-effective in patients with mild-to-moderate CDI and in those using concomitant antibiotics.²³ Given that 2 studies demonstrated that fidaxomicin has lower recurrence rates than that of oral vancomycin, the economical use of fidaxomicin would be of most benefit to patients at highest risk for CDI recurrence.^3,4

Conclusion

In light of increased CDI treatment failure, recurrence rates, and virulence of CDI, fidaxomicin is an emerging treatment strategy. Through 2 pivotal trials, fidaxomicin has been shown to be a safe and effective first-line agent for CDI.^3,4 New U.S. clinical guidelines for CDI are expected to be published in spring 2016, which will likely include the recommendation for fidaxomicin use in recurrent CDI. Current evidence suggests the most cost-effective use of fidaxomicin is in patients at highest risk of CDI recurrence.

For the past 40 to 50 years, the first-line treatment for high-grade cervical intraepithelial neoplasia (CIN) has been excisional procedures (including loop electrosurgical excision [LEEP], cone biopsy, cryosurgery, and laser therapy), and these treatments work well. It appears, however, that these procedures potentially can lead to preterm birth.^1–3 With results from large, comprehensive meta-analyses that control for such risk factors as smoking and other factors that could contribute to both preterm birth and high-grade CIN, we have learned that excision treatment can result in a 2% to 5% increased risk for preterm birth, depending on the size and the extent of excision performed.^1–3 The preterm birth rate in the United States is about 11.4%.⁴ With about 500,000 excisional treatments for high-grade CIN performed in the United States every year, and about 2% of preterm births caused by excisional procedures, conservatively, about 5,000 to 10,000 US preterm births are directly related to excisional procedures for high-grade CIN annually.

Clearly, excisional treatment for high-grade CIN and its connection to preterm birth adds to health care costs and long-term morbidity because babies that are born preterm potentially have diminished functionality. We need a better treatment approach other than excision to CIN, which is known to be a virally mediated disease. Consider the fact that just because excisional procedures remove potentially cancerous cells does not mean that these treatments remove the underlying reason behind the high-grade CIN—HPV. We cannot cut out a virus. Consequently, many studies have explored better-targeted therapies against high-grade CIN. Immune-based therapies, which can train a patient’s own immune system to attack HPV-infected cells, are exciting possibilities.

In this Update, I focus on 2 studies of immune-based therapies to treat cervical cancer. In addition, I discuss long-term follow-up data that are available regarding efficacy of primary HPV testing.

HPV therapeutic vaccine shows promise in RCT
_{Trimble CL, Morrow MP, Kraynyak KA, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. 2015;386(10008):2078-2088.}

While the promise of immune-based therapies to target a virally mediated disease has good scientific rationale, there have been many generally negative studies published in the past 15 years on immune-based targeted therapies. This study by Trimble and colleagues has interesting results because it is a randomized controlled trial (RCT) using a DNA vaccine delivered with a novel approach called electroporation. Electroporation generates a small electrical shot at the vaccine site that potentially increases a vaccine's DNA uptake and the patient's immune response. 

Details of the study
Women aged 18 to 55 years with HPV16- or HPV18-positive high-grade CIN from 36 academic and private gynecology practices in 7 countries were assigned in a 3:1 blinded randomization to receive vaccine (6 mg; VGX-3100) or placebo (1 mL), given intramuscularly at 0, 4, and 12 weeks. Patients were stratified by age 25 or older versus younger than 25 and by CIN2 versus CIN3. The primary efficacy endpoint was regression to CIN1 or normal pathology 36 weeks after the first vaccine dose.
 
A mandatory interim safety colposcopy was performed 12 weeks after the third vaccine dose. At 36 weeks (the primary endpoint visit), patients with colposcopic evidence of residual disease underwent standard excision (LEEP or cone). In patients with no evidence of disease, investigators could biopsy the site of the original lesions. At 40 weeks, when all patients had completed their first visit after the primary endpoint, the data were unmasked. Long-term follow-up data were collected on all patients with remaining visits. Patients and study site investigators and personnel stayed masked to treatment until study data were final.

Results indicated a significant clinical response as well as an immune response in those patients who were treated with electroporation and the vaccine versus electroporation and placebo. In the per-protocol analysis, 53 (49.5%) of 107 vaccine recipients and 11 (30.6%) of 36 placebo recipients had histopathologic regression (percentage point difference [PPD], 19.0 [95% confidence interval CI, 1.4-36.6]; P = .034) (FIGURE 1). In the modified intention-to-treat analysis, 55 (48.2%) of 114 vaccine recipients and 12 (30.0%) of 40 placebo recipients had histopathologic regression (PPD, 18.2; 95% CI, 1.3-34.4; P = .034).
 
Injection-site reactions occurred in most patients, but only erythema was significantly more common in the vaccine group than in the placebo group (PPD, 21.3 [95% CI, 5.3-37.8]; P = .007).

What this evidence means for practice
In prior studies of immunotherapies, there have not been good correlations between immune responses and clinical responses, and this is one of the important differences between this study by Trimble and colleagues and prior studies in this space. Unfortunately, immune-based therapies are a "shot in the dark," with researchers not knowing which patients may have an increased immune response but no clinical response or a clinical response but no immune response. The measured immune responses are from peripheral blood, an immune response that might not reflect the milieu of immune responses in the cervical-vaginal tract.

If perfected, technologies like these hold the promise of minimizing the amount of patients who need to undergo excisional procedures because patients' own immune systems have been trained to target HPV-infected cells. The bigger hope is that we will be able to minimize preterm births that are directly related to treatment of dysplasia.

Adoptive T-cell therapy offers targeted treatment for recurrent cervical cancer
_{Stevanovic S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 2015;33(14):1543-1550.}

Stevanovic and colleagues have been developing another immune-based therapy that has been tested for other cancers. This uses a method for generating T-cell cultures from HPV-positive cancers and selecting specific HPV oncoprotein- reactive cultures for administration to patients. Termed adoptive T-cell therapy (ACT), this targeted approach to recurrent cervical cancer is what I would consider one of the most intriguing future treatments of cervical disease. In the past, the largest barrier to an effective HPV vaccine to treat cervical cancer has been lack of clinical response to existing cytotoxic regimens. In this, albeit small, trial, investigators found a correlation between HPV reactivity and the infused T cells and objective clinical responses.

What is adoptive T-cell therapy?
ACT allows for more rigorous control over the magnitude of the targeted response than tumor vaccination treatment strategies because the T cells used for therapy are identified and selected in vitro. The cells selected are exposed to cytokines and immunomodulators that influence differentiation during priming and are expanded to large numbers. The resulting number of antigen-specific T cells produced in the peripheral blood is much greater (more than 10-fold) than that possible by current vaccine regimens alone.
 
Studies conducted by the National Cancer Institute of adoptive transfer of in vitro-selected tumor-infiltrating lymphocytes were the first to demonstrate the potential of T-cell immunotherapy to eradicate solid tumors.^5,6 Among 13 patients with melanoma, treatment with adoptive transfer of ex vivo-amplified autologous tumor-infiltrating T cells resulted in treatment response in 10 of the patients—clinical responses in 6 and mixed responses in 4.

Details of the study
This study by Stevanovic and colleagues involved 9 patients with metastatic cervical cancer who previously had received optimal recommended chemotherapy or concomitant chemoradiotherapy regimens. Patients were treated with a single infusion of tumor-infiltrating T cells specifically selected for HPV E6 and E7 reactivity (HPV-TILs). Patients received lymphocyte-depleting chemotherapy before ACT and aldesleukin chemotherapy injection after ACT.
 
In such a phase I population, one would not expect clinical responses over persistent stable disease. However, in this small trial, 2 patients had complete tumor regression and 1 patient had a partial treatment response, demonstrating that a complete response to metastatic cervical cancer can occur after a single infusion of HPV-TILs. The partial response lasted 3 months. The 2 complete responses were ongoing 22 and 15 months after treatment (FIGURE 2).
 
Editorialists point out that, only when the infusion product had reactivity against the HPV E6 and E7 peptides did the patients show objective clinical response, suggesting it was the immune response that contributed to the tumor regression.⁷ In addition, in the 3 patients with objective responses, HPV-specific T cells persisted in peripheral blood for several months.

FIGURE 2 Patients with complete tumor responses with adoptive T-cell therapy
Two patients with metastatic cervical cancer had complete tumor responses with treatment with tumor-infiltrating T cells selected for HPV E6 and E7 reactivity (HPV-TILs). Contrast-enhanced computed tomography scans obtained before treatment and at most recent follow-up for both patients. (A) First patient (patient 3) had disease involving para-aortic, bilateral hilar, subcarinal, and left iliac lymph nodes (gold arrows). Patient had no evidence of disease 22 months after treatment. (B) Second patient (patient 6) had metastatic disease in para-aortic lymph node, abdominal wall, aortocaval lymph node, left pericolic pelvic mass, and right ureteral nodule (gold arrows). Patient had no evidence of disease 15 months after treatment. (Red arrowhead indicates ureteral stent that was removed after right ureteral tumor regressed.)

Stevanovic S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells.J Clin Oncol. 2015;33(14):1543–1550. Used with permission.

What this evidence means for practice
The recent approval of bevacizumab has been a major breakthrough in the treatment of advanced and recurrent cervical cancer. Although ACT is a treatment that is in early clinical development, it is the next major advance in this area. Its promise is currently limited, as the process is cumbersome and complex, involving surgical removal of a patient's lymph nodes, culturing of the T cells from the lymph nodes, and infusing the T cells with the oncoproteins that will train those T cells to infiltrate the cancer tumor. The process is wrought with potential problems in laboratory and translational techniques. However, this group of investigators from the NCI has perfected the process of ACT, creating T cells that will target the HPV that is integrated into each cervical cancer tumor.

The patients who demonstrated good T-cell reactivity against HPV were the ones who had a treatment response, which demonstrates the targeted precision of ACT therapy. There might come a day when we can select patients with recurrent cervical cancer who are going to have T-cell reactivity, and send them for treatment to a center specialized in ACT. Typically in phase 1 trials, we are happy to see a number of patients responding with stable disease. In this trial, 2 patients had a complete response. The results demonstrated by Stevanovic and colleagues are very exciting for the future treatment of patients with cervical cancer.

Primary HPV screening shows up to 70% greater protection against invasive cervical cancer than cytology
_{Ronco G, Dillner J, Elfstrom KM; International HPV Screening Working Group. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383(9916):424-532.}

In my 2015 "Update on Cervical Disease,"⁸ I discussed the newly published interim guidance for managing abnormal screening results for cervical cancer from a collective expert panel from the American Society for Colposcopy and Cervical Pathology, Society of Gynecologic Oncology, the American College of Obstetricians and Gynecologists, and 4 more societies.⁹ The guidelines support use of HPV testing alone or with the Papanicolaou test. In 2016, follow-up data from 4 RCTs provide long-term data on the efficacy of HPV primary testing.
  
Details of the trial 
Incidence of invasive cervical cancer was the endpoint in 4 European trials comparing HPV-based with cytology-based screening. In total, 176,464 women aged 20 to 64 years were randomly assigned to either screening strategy. Median follow-up was 6.5 years (1,214,415 person-years). Using screening, pathology, and cancer registries investigators identified 107 invasive cervical carcinomas, with masked review of histologic specimens and reports.
 
Investigators calculated the rate ratios (defined as the cancer detection rate in the primary HPV testing-based versus cytology-based arms) for incidence of invasive cervical cancer. During the first 2.5 years of follow-up, detection of invasive cancer was similar between screening methods (0.79, 0.46-1.36). Thereafter, however, cumulative cancer detection was lower in the primary HPV testing-based arm (0.45; 95% CI, 0.25-0.81).

At 3.5 and 5.5 years after a negative cytology test on entry, cumulative cancer incidence was 15.4 per 10⁵ (95% CI, 7.9-27.0) and 36.0 per 10⁵ (23.2-53.5), respectively. At 3.5 and 5.5 years after a negative HPV test on entry, cumulative cancer incidence was 4.6 per 10⁵ (1.1-12.1) and 8.7 per 10⁵ (3.3-18.6), respectively (FIGURE 3).

FIGURE 3 Cumulative detection of invasive cervical carcinoma

*Observations are censored 2.5 years after CIN2 or CIN3 detection, if any. Experimental arm = primary HPV testing−based screening; control arm = cytology-based screening. Reprinted from The Lancet, 383(9916), Ronco G, Dillner J, Elfstrom KM; International HPV Screening Working Group, Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomized controlled trials, 424–532, Copyright 2014, with permission from Elsevier.   The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0.60 (95% CI, 0.40-0.89), with no heterogeneity between studies (P = .52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2.5 years of follow-up (0.79, 0.46-1.36) but was significantly lower in the experimental arm thereafter (0.45, 0.25-0.81). Among women with a negative screening test at entry, the rate ratio was 0.30 (0.15-0.60).   Ronco and colleagues concluded that primary HPV testing-based screening provides 60% to 70% greater protection against invasive cervical cancers than cytology.

What this EVIDENCE means for practice
The 4 studies in this report were completed across Europe (in England, Netherlands, Sweden, and Italy): different regions, different sites, hospitals, and screening systems. The women in Europe are not any different than the women in the United States in terms of rates of HPV and age and incidence of HPV. Therefore, these results are globally generalizable.

The US trial by Wright and colleagues10 that led to US Food and Drug Administration approval of HPV primary testing was different than this European study in that all trial sites had to perform screening in the same way. In addition, the end point was high-grade dysplasia; in this trial by Ronco and colleagues the end point is cancer. These current investigators found no difference with either screening arm in terms of detection of invasive cervical cancer. Even more interesting is that, over time, the cervical cancer rates in the primary HPV testing-based arm were much less than that in the cytology-based arm.

The real strengths of this study are the long-term follow-up and the study size. We are not likely to see validation cohorts this big again. This study demonstrates that, overall, we should be able to continue to reduce the incidence of invasive cervical cancer with a primary HPV testing-based screening strategy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

For the past 40 to 50 years, the first-line treatment for high-grade cervical intraepithelial neoplasia (CIN) has been excisional procedures (including loop electrosurgical excision [LEEP], cone biopsy, cryosurgery, and laser therapy), and these treatments work well. It appears, however, that these procedures potentially can lead to preterm birth.^1–3 With results from large, comprehensive meta-analyses that control for such risk factors as smoking and other factors that could contribute to both preterm birth and high-grade CIN, we have learned that excision treatment can result in a 2% to 5% increased risk for preterm birth, depending on the size and the extent of excision performed.^1–3 The preterm birth rate in the United States is about 11.4%.⁴ With about 500,000 excisional treatments for high-grade CIN performed in the United States every year, and about 2% of preterm births caused by excisional procedures, conservatively, about 5,000 to 10,000 US preterm births are directly related to excisional procedures for high-grade CIN annually.

Clearly, excisional treatment for high-grade CIN and its connection to preterm birth adds to health care costs and long-term morbidity because babies that are born preterm potentially have diminished functionality. We need a better treatment approach other than excision to CIN, which is known to be a virally mediated disease. Consider the fact that just because excisional procedures remove potentially cancerous cells does not mean that these treatments remove the underlying reason behind the high-grade CIN—HPV. We cannot cut out a virus. Consequently, many studies have explored better-targeted therapies against high-grade CIN. Immune-based therapies, which can train a patient’s own immune system to attack HPV-infected cells, are exciting possibilities.

In this Update, I focus on 2 studies of immune-based therapies to treat cervical cancer. In addition, I discuss long-term follow-up data that are available regarding efficacy of primary HPV testing.

HPV therapeutic vaccine shows promise in RCT
_{Trimble CL, Morrow MP, Kraynyak KA, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. 2015;386(10008):2078-2088.}

While the promise of immune-based therapies to target a virally mediated disease has good scientific rationale, there have been many generally negative studies published in the past 15 years on immune-based targeted therapies. This study by Trimble and colleagues has interesting results because it is a randomized controlled trial (RCT) using a DNA vaccine delivered with a novel approach called electroporation. Electroporation generates a small electrical shot at the vaccine site that potentially increases a vaccine's DNA uptake and the patient's immune response. 

Details of the study
Women aged 18 to 55 years with HPV16- or HPV18-positive high-grade CIN from 36 academic and private gynecology practices in 7 countries were assigned in a 3:1 blinded randomization to receive vaccine (6 mg; VGX-3100) or placebo (1 mL), given intramuscularly at 0, 4, and 12 weeks. Patients were stratified by age 25 or older versus younger than 25 and by CIN2 versus CIN3. The primary efficacy endpoint was regression to CIN1 or normal pathology 36 weeks after the first vaccine dose.
 
A mandatory interim safety colposcopy was performed 12 weeks after the third vaccine dose. At 36 weeks (the primary endpoint visit), patients with colposcopic evidence of residual disease underwent standard excision (LEEP or cone). In patients with no evidence of disease, investigators could biopsy the site of the original lesions. At 40 weeks, when all patients had completed their first visit after the primary endpoint, the data were unmasked. Long-term follow-up data were collected on all patients with remaining visits. Patients and study site investigators and personnel stayed masked to treatment until study data were final.

Results indicated a significant clinical response as well as an immune response in those patients who were treated with electroporation and the vaccine versus electroporation and placebo. In the per-protocol analysis, 53 (49.5%) of 107 vaccine recipients and 11 (30.6%) of 36 placebo recipients had histopathologic regression (percentage point difference [PPD], 19.0 [95% confidence interval CI, 1.4-36.6]; P = .034) (FIGURE 1). In the modified intention-to-treat analysis, 55 (48.2%) of 114 vaccine recipients and 12 (30.0%) of 40 placebo recipients had histopathologic regression (PPD, 18.2; 95% CI, 1.3-34.4; P = .034).
 
Injection-site reactions occurred in most patients, but only erythema was significantly more common in the vaccine group than in the placebo group (PPD, 21.3 [95% CI, 5.3-37.8]; P = .007).

What this evidence means for practice
In prior studies of immunotherapies, there have not been good correlations between immune responses and clinical responses, and this is one of the important differences between this study by Trimble and colleagues and prior studies in this space. Unfortunately, immune-based therapies are a "shot in the dark," with researchers not knowing which patients may have an increased immune response but no clinical response or a clinical response but no immune response. The measured immune responses are from peripheral blood, an immune response that might not reflect the milieu of immune responses in the cervical-vaginal tract.

If perfected, technologies like these hold the promise of minimizing the amount of patients who need to undergo excisional procedures because patients' own immune systems have been trained to target HPV-infected cells. The bigger hope is that we will be able to minimize preterm births that are directly related to treatment of dysplasia.

Adoptive T-cell therapy offers targeted treatment for recurrent cervical cancer
_{Stevanovic S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 2015;33(14):1543-1550.}

Stevanovic and colleagues have been developing another immune-based therapy that has been tested for other cancers. This uses a method for generating T-cell cultures from HPV-positive cancers and selecting specific HPV oncoprotein- reactive cultures for administration to patients. Termed adoptive T-cell therapy (ACT), this targeted approach to recurrent cervical cancer is what I would consider one of the most intriguing future treatments of cervical disease. In the past, the largest barrier to an effective HPV vaccine to treat cervical cancer has been lack of clinical response to existing cytotoxic regimens. In this, albeit small, trial, investigators found a correlation between HPV reactivity and the infused T cells and objective clinical responses.

What is adoptive T-cell therapy?
ACT allows for more rigorous control over the magnitude of the targeted response than tumor vaccination treatment strategies because the T cells used for therapy are identified and selected in vitro. The cells selected are exposed to cytokines and immunomodulators that influence differentiation during priming and are expanded to large numbers. The resulting number of antigen-specific T cells produced in the peripheral blood is much greater (more than 10-fold) than that possible by current vaccine regimens alone.
 
Studies conducted by the National Cancer Institute of adoptive transfer of in vitro-selected tumor-infiltrating lymphocytes were the first to demonstrate the potential of T-cell immunotherapy to eradicate solid tumors.^5,6 Among 13 patients with melanoma, treatment with adoptive transfer of ex vivo-amplified autologous tumor-infiltrating T cells resulted in treatment response in 10 of the patients—clinical responses in 6 and mixed responses in 4.

Details of the study
This study by Stevanovic and colleagues involved 9 patients with metastatic cervical cancer who previously had received optimal recommended chemotherapy or concomitant chemoradiotherapy regimens. Patients were treated with a single infusion of tumor-infiltrating T cells specifically selected for HPV E6 and E7 reactivity (HPV-TILs). Patients received lymphocyte-depleting chemotherapy before ACT and aldesleukin chemotherapy injection after ACT.
 
In such a phase I population, one would not expect clinical responses over persistent stable disease. However, in this small trial, 2 patients had complete tumor regression and 1 patient had a partial treatment response, demonstrating that a complete response to metastatic cervical cancer can occur after a single infusion of HPV-TILs. The partial response lasted 3 months. The 2 complete responses were ongoing 22 and 15 months after treatment (FIGURE 2).
 
Editorialists point out that, only when the infusion product had reactivity against the HPV E6 and E7 peptides did the patients show objective clinical response, suggesting it was the immune response that contributed to the tumor regression.⁷ In addition, in the 3 patients with objective responses, HPV-specific T cells persisted in peripheral blood for several months.

FIGURE 2 Patients with complete tumor responses with adoptive T-cell therapy
Two patients with metastatic cervical cancer had complete tumor responses with treatment with tumor-infiltrating T cells selected for HPV E6 and E7 reactivity (HPV-TILs). Contrast-enhanced computed tomography scans obtained before treatment and at most recent follow-up for both patients. (A) First patient (patient 3) had disease involving para-aortic, bilateral hilar, subcarinal, and left iliac lymph nodes (gold arrows). Patient had no evidence of disease 22 months after treatment. (B) Second patient (patient 6) had metastatic disease in para-aortic lymph node, abdominal wall, aortocaval lymph node, left pericolic pelvic mass, and right ureteral nodule (gold arrows). Patient had no evidence of disease 15 months after treatment. (Red arrowhead indicates ureteral stent that was removed after right ureteral tumor regressed.)

Stevanovic S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells.J Clin Oncol. 2015;33(14):1543–1550. Used with permission.

What this evidence means for practice
The recent approval of bevacizumab has been a major breakthrough in the treatment of advanced and recurrent cervical cancer. Although ACT is a treatment that is in early clinical development, it is the next major advance in this area. Its promise is currently limited, as the process is cumbersome and complex, involving surgical removal of a patient's lymph nodes, culturing of the T cells from the lymph nodes, and infusing the T cells with the oncoproteins that will train those T cells to infiltrate the cancer tumor. The process is wrought with potential problems in laboratory and translational techniques. However, this group of investigators from the NCI has perfected the process of ACT, creating T cells that will target the HPV that is integrated into each cervical cancer tumor.

The patients who demonstrated good T-cell reactivity against HPV were the ones who had a treatment response, which demonstrates the targeted precision of ACT therapy. There might come a day when we can select patients with recurrent cervical cancer who are going to have T-cell reactivity, and send them for treatment to a center specialized in ACT. Typically in phase 1 trials, we are happy to see a number of patients responding with stable disease. In this trial, 2 patients had a complete response. The results demonstrated by Stevanovic and colleagues are very exciting for the future treatment of patients with cervical cancer.

Primary HPV screening shows up to 70% greater protection against invasive cervical cancer than cytology
_{Ronco G, Dillner J, Elfstrom KM; International HPV Screening Working Group. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383(9916):424-532.}

In my 2015 "Update on Cervical Disease,"⁸ I discussed the newly published interim guidance for managing abnormal screening results for cervical cancer from a collective expert panel from the American Society for Colposcopy and Cervical Pathology, Society of Gynecologic Oncology, the American College of Obstetricians and Gynecologists, and 4 more societies.⁹ The guidelines support use of HPV testing alone or with the Papanicolaou test. In 2016, follow-up data from 4 RCTs provide long-term data on the efficacy of HPV primary testing.
  
Details of the trial 
Incidence of invasive cervical cancer was the endpoint in 4 European trials comparing HPV-based with cytology-based screening. In total, 176,464 women aged 20 to 64 years were randomly assigned to either screening strategy. Median follow-up was 6.5 years (1,214,415 person-years). Using screening, pathology, and cancer registries investigators identified 107 invasive cervical carcinomas, with masked review of histologic specimens and reports.
 
Investigators calculated the rate ratios (defined as the cancer detection rate in the primary HPV testing-based versus cytology-based arms) for incidence of invasive cervical cancer. During the first 2.5 years of follow-up, detection of invasive cancer was similar between screening methods (0.79, 0.46-1.36). Thereafter, however, cumulative cancer detection was lower in the primary HPV testing-based arm (0.45; 95% CI, 0.25-0.81).

At 3.5 and 5.5 years after a negative cytology test on entry, cumulative cancer incidence was 15.4 per 10⁵ (95% CI, 7.9-27.0) and 36.0 per 10⁵ (23.2-53.5), respectively. At 3.5 and 5.5 years after a negative HPV test on entry, cumulative cancer incidence was 4.6 per 10⁵ (1.1-12.1) and 8.7 per 10⁵ (3.3-18.6), respectively (FIGURE 3).

FIGURE 3 Cumulative detection of invasive cervical carcinoma

*Observations are censored 2.5 years after CIN2 or CIN3 detection, if any. Experimental arm = primary HPV testing−based screening; control arm = cytology-based screening. Reprinted from The Lancet, 383(9916), Ronco G, Dillner J, Elfstrom KM; International HPV Screening Working Group, Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomized controlled trials, 424–532, Copyright 2014, with permission from Elsevier.   The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0.60 (95% CI, 0.40-0.89), with no heterogeneity between studies (P = .52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2.5 years of follow-up (0.79, 0.46-1.36) but was significantly lower in the experimental arm thereafter (0.45, 0.25-0.81). Among women with a negative screening test at entry, the rate ratio was 0.30 (0.15-0.60).   Ronco and colleagues concluded that primary HPV testing-based screening provides 60% to 70% greater protection against invasive cervical cancers than cytology.

What this EVIDENCE means for practice
The 4 studies in this report were completed across Europe (in England, Netherlands, Sweden, and Italy): different regions, different sites, hospitals, and screening systems. The women in Europe are not any different than the women in the United States in terms of rates of HPV and age and incidence of HPV. Therefore, these results are globally generalizable.

The US trial by Wright and colleagues10 that led to US Food and Drug Administration approval of HPV primary testing was different than this European study in that all trial sites had to perform screening in the same way. In addition, the end point was high-grade dysplasia; in this trial by Ronco and colleagues the end point is cancer. These current investigators found no difference with either screening arm in terms of detection of invasive cervical cancer. Even more interesting is that, over time, the cervical cancer rates in the primary HPV testing-based arm were much less than that in the cytology-based arm.

The real strengths of this study are the long-term follow-up and the study size. We are not likely to see validation cohorts this big again. This study demonstrates that, overall, we should be able to continue to reduce the incidence of invasive cervical cancer with a primary HPV testing-based screening strategy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

For the past 40 to 50 years, the first-line treatment for high-grade cervical intraepithelial neoplasia (CIN) has been excisional procedures (including loop electrosurgical excision [LEEP], cone biopsy, cryosurgery, and laser therapy), and these treatments work well. It appears, however, that these procedures potentially can lead to preterm birth.^1–3 With results from large, comprehensive meta-analyses that control for such risk factors as smoking and other factors that could contribute to both preterm birth and high-grade CIN, we have learned that excision treatment can result in a 2% to 5% increased risk for preterm birth, depending on the size and the extent of excision performed.^1–3 The preterm birth rate in the United States is about 11.4%.⁴ With about 500,000 excisional treatments for high-grade CIN performed in the United States every year, and about 2% of preterm births caused by excisional procedures, conservatively, about 5,000 to 10,000 US preterm births are directly related to excisional procedures for high-grade CIN annually.

Clearly, excisional treatment for high-grade CIN and its connection to preterm birth adds to health care costs and long-term morbidity because babies that are born preterm potentially have diminished functionality. We need a better treatment approach other than excision to CIN, which is known to be a virally mediated disease. Consider the fact that just because excisional procedures remove potentially cancerous cells does not mean that these treatments remove the underlying reason behind the high-grade CIN—HPV. We cannot cut out a virus. Consequently, many studies have explored better-targeted therapies against high-grade CIN. Immune-based therapies, which can train a patient’s own immune system to attack HPV-infected cells, are exciting possibilities.

In this Update, I focus on 2 studies of immune-based therapies to treat cervical cancer. In addition, I discuss long-term follow-up data that are available regarding efficacy of primary HPV testing.

HPV therapeutic vaccine shows promise in RCT
_{Trimble CL, Morrow MP, Kraynyak KA, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. 2015;386(10008):2078-2088.}

While the promise of immune-based therapies to target a virally mediated disease has good scientific rationale, there have been many generally negative studies published in the past 15 years on immune-based targeted therapies. This study by Trimble and colleagues has interesting results because it is a randomized controlled trial (RCT) using a DNA vaccine delivered with a novel approach called electroporation. Electroporation generates a small electrical shot at the vaccine site that potentially increases a vaccine's DNA uptake and the patient's immune response. 

Details of the study
Women aged 18 to 55 years with HPV16- or HPV18-positive high-grade CIN from 36 academic and private gynecology practices in 7 countries were assigned in a 3:1 blinded randomization to receive vaccine (6 mg; VGX-3100) or placebo (1 mL), given intramuscularly at 0, 4, and 12 weeks. Patients were stratified by age 25 or older versus younger than 25 and by CIN2 versus CIN3. The primary efficacy endpoint was regression to CIN1 or normal pathology 36 weeks after the first vaccine dose.
 
A mandatory interim safety colposcopy was performed 12 weeks after the third vaccine dose. At 36 weeks (the primary endpoint visit), patients with colposcopic evidence of residual disease underwent standard excision (LEEP or cone). In patients with no evidence of disease, investigators could biopsy the site of the original lesions. At 40 weeks, when all patients had completed their first visit after the primary endpoint, the data were unmasked. Long-term follow-up data were collected on all patients with remaining visits. Patients and study site investigators and personnel stayed masked to treatment until study data were final.

Results indicated a significant clinical response as well as an immune response in those patients who were treated with electroporation and the vaccine versus electroporation and placebo. In the per-protocol analysis, 53 (49.5%) of 107 vaccine recipients and 11 (30.6%) of 36 placebo recipients had histopathologic regression (percentage point difference [PPD], 19.0 [95% confidence interval CI, 1.4-36.6]; P = .034) (FIGURE 1). In the modified intention-to-treat analysis, 55 (48.2%) of 114 vaccine recipients and 12 (30.0%) of 40 placebo recipients had histopathologic regression (PPD, 18.2; 95% CI, 1.3-34.4; P = .034).
 
Injection-site reactions occurred in most patients, but only erythema was significantly more common in the vaccine group than in the placebo group (PPD, 21.3 [95% CI, 5.3-37.8]; P = .007).

What this evidence means for practice
In prior studies of immunotherapies, there have not been good correlations between immune responses and clinical responses, and this is one of the important differences between this study by Trimble and colleagues and prior studies in this space. Unfortunately, immune-based therapies are a "shot in the dark," with researchers not knowing which patients may have an increased immune response but no clinical response or a clinical response but no immune response. The measured immune responses are from peripheral blood, an immune response that might not reflect the milieu of immune responses in the cervical-vaginal tract.

If perfected, technologies like these hold the promise of minimizing the amount of patients who need to undergo excisional procedures because patients' own immune systems have been trained to target HPV-infected cells. The bigger hope is that we will be able to minimize preterm births that are directly related to treatment of dysplasia.

Adoptive T-cell therapy offers targeted treatment for recurrent cervical cancer
_{Stevanovic S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 2015;33(14):1543-1550.}

Stevanovic and colleagues have been developing another immune-based therapy that has been tested for other cancers. This uses a method for generating T-cell cultures from HPV-positive cancers and selecting specific HPV oncoprotein- reactive cultures for administration to patients. Termed adoptive T-cell therapy (ACT), this targeted approach to recurrent cervical cancer is what I would consider one of the most intriguing future treatments of cervical disease. In the past, the largest barrier to an effective HPV vaccine to treat cervical cancer has been lack of clinical response to existing cytotoxic regimens. In this, albeit small, trial, investigators found a correlation between HPV reactivity and the infused T cells and objective clinical responses.

What is adoptive T-cell therapy?
ACT allows for more rigorous control over the magnitude of the targeted response than tumor vaccination treatment strategies because the T cells used for therapy are identified and selected in vitro. The cells selected are exposed to cytokines and immunomodulators that influence differentiation during priming and are expanded to large numbers. The resulting number of antigen-specific T cells produced in the peripheral blood is much greater (more than 10-fold) than that possible by current vaccine regimens alone.
 
Studies conducted by the National Cancer Institute of adoptive transfer of in vitro-selected tumor-infiltrating lymphocytes were the first to demonstrate the potential of T-cell immunotherapy to eradicate solid tumors.^5,6 Among 13 patients with melanoma, treatment with adoptive transfer of ex vivo-amplified autologous tumor-infiltrating T cells resulted in treatment response in 10 of the patients—clinical responses in 6 and mixed responses in 4.

Details of the study
This study by Stevanovic and colleagues involved 9 patients with metastatic cervical cancer who previously had received optimal recommended chemotherapy or concomitant chemoradiotherapy regimens. Patients were treated with a single infusion of tumor-infiltrating T cells specifically selected for HPV E6 and E7 reactivity (HPV-TILs). Patients received lymphocyte-depleting chemotherapy before ACT and aldesleukin chemotherapy injection after ACT.
 
In such a phase I population, one would not expect clinical responses over persistent stable disease. However, in this small trial, 2 patients had complete tumor regression and 1 patient had a partial treatment response, demonstrating that a complete response to metastatic cervical cancer can occur after a single infusion of HPV-TILs. The partial response lasted 3 months. The 2 complete responses were ongoing 22 and 15 months after treatment (FIGURE 2).
 
Editorialists point out that, only when the infusion product had reactivity against the HPV E6 and E7 peptides did the patients show objective clinical response, suggesting it was the immune response that contributed to the tumor regression.⁷ In addition, in the 3 patients with objective responses, HPV-specific T cells persisted in peripheral blood for several months.

FIGURE 2 Patients with complete tumor responses with adoptive T-cell therapy
Two patients with metastatic cervical cancer had complete tumor responses with treatment with tumor-infiltrating T cells selected for HPV E6 and E7 reactivity (HPV-TILs). Contrast-enhanced computed tomography scans obtained before treatment and at most recent follow-up for both patients. (A) First patient (patient 3) had disease involving para-aortic, bilateral hilar, subcarinal, and left iliac lymph nodes (gold arrows). Patient had no evidence of disease 22 months after treatment. (B) Second patient (patient 6) had metastatic disease in para-aortic lymph node, abdominal wall, aortocaval lymph node, left pericolic pelvic mass, and right ureteral nodule (gold arrows). Patient had no evidence of disease 15 months after treatment. (Red arrowhead indicates ureteral stent that was removed after right ureteral tumor regressed.)

Stevanovic S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells.J Clin Oncol. 2015;33(14):1543–1550. Used with permission.

What this evidence means for practice
The recent approval of bevacizumab has been a major breakthrough in the treatment of advanced and recurrent cervical cancer. Although ACT is a treatment that is in early clinical development, it is the next major advance in this area. Its promise is currently limited, as the process is cumbersome and complex, involving surgical removal of a patient's lymph nodes, culturing of the T cells from the lymph nodes, and infusing the T cells with the oncoproteins that will train those T cells to infiltrate the cancer tumor. The process is wrought with potential problems in laboratory and translational techniques. However, this group of investigators from the NCI has perfected the process of ACT, creating T cells that will target the HPV that is integrated into each cervical cancer tumor.

The patients who demonstrated good T-cell reactivity against HPV were the ones who had a treatment response, which demonstrates the targeted precision of ACT therapy. There might come a day when we can select patients with recurrent cervical cancer who are going to have T-cell reactivity, and send them for treatment to a center specialized in ACT. Typically in phase 1 trials, we are happy to see a number of patients responding with stable disease. In this trial, 2 patients had a complete response. The results demonstrated by Stevanovic and colleagues are very exciting for the future treatment of patients with cervical cancer.

Primary HPV screening shows up to 70% greater protection against invasive cervical cancer than cytology
_{Ronco G, Dillner J, Elfstrom KM; International HPV Screening Working Group. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383(9916):424-532.}

In my 2015 "Update on Cervical Disease,"⁸ I discussed the newly published interim guidance for managing abnormal screening results for cervical cancer from a collective expert panel from the American Society for Colposcopy and Cervical Pathology, Society of Gynecologic Oncology, the American College of Obstetricians and Gynecologists, and 4 more societies.⁹ The guidelines support use of HPV testing alone or with the Papanicolaou test. In 2016, follow-up data from 4 RCTs provide long-term data on the efficacy of HPV primary testing.
  
Details of the trial 
Incidence of invasive cervical cancer was the endpoint in 4 European trials comparing HPV-based with cytology-based screening. In total, 176,464 women aged 20 to 64 years were randomly assigned to either screening strategy. Median follow-up was 6.5 years (1,214,415 person-years). Using screening, pathology, and cancer registries investigators identified 107 invasive cervical carcinomas, with masked review of histologic specimens and reports.
 
Investigators calculated the rate ratios (defined as the cancer detection rate in the primary HPV testing-based versus cytology-based arms) for incidence of invasive cervical cancer. During the first 2.5 years of follow-up, detection of invasive cancer was similar between screening methods (0.79, 0.46-1.36). Thereafter, however, cumulative cancer detection was lower in the primary HPV testing-based arm (0.45; 95% CI, 0.25-0.81).

At 3.5 and 5.5 years after a negative cytology test on entry, cumulative cancer incidence was 15.4 per 10⁵ (95% CI, 7.9-27.0) and 36.0 per 10⁵ (23.2-53.5), respectively. At 3.5 and 5.5 years after a negative HPV test on entry, cumulative cancer incidence was 4.6 per 10⁵ (1.1-12.1) and 8.7 per 10⁵ (3.3-18.6), respectively (FIGURE 3).

FIGURE 3 Cumulative detection of invasive cervical carcinoma

*Observations are censored 2.5 years after CIN2 or CIN3 detection, if any. Experimental arm = primary HPV testing−based screening; control arm = cytology-based screening. Reprinted from The Lancet, 383(9916), Ronco G, Dillner J, Elfstrom KM; International HPV Screening Working Group, Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomized controlled trials, 424–532, Copyright 2014, with permission from Elsevier.   The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0.60 (95% CI, 0.40-0.89), with no heterogeneity between studies (P = .52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2.5 years of follow-up (0.79, 0.46-1.36) but was significantly lower in the experimental arm thereafter (0.45, 0.25-0.81). Among women with a negative screening test at entry, the rate ratio was 0.30 (0.15-0.60).   Ronco and colleagues concluded that primary HPV testing-based screening provides 60% to 70% greater protection against invasive cervical cancers than cytology.

What this EVIDENCE means for practice
The 4 studies in this report were completed across Europe (in England, Netherlands, Sweden, and Italy): different regions, different sites, hospitals, and screening systems. The women in Europe are not any different than the women in the United States in terms of rates of HPV and age and incidence of HPV. Therefore, these results are globally generalizable.

The US trial by Wright and colleagues10 that led to US Food and Drug Administration approval of HPV primary testing was different than this European study in that all trial sites had to perform screening in the same way. In addition, the end point was high-grade dysplasia; in this trial by Ronco and colleagues the end point is cancer. These current investigators found no difference with either screening arm in terms of detection of invasive cervical cancer. Even more interesting is that, over time, the cervical cancer rates in the primary HPV testing-based arm were much less than that in the cytology-based arm.

The real strengths of this study are the long-term follow-up and the study size. We are not likely to see validation cohorts this big again. This study demonstrates that, overall, we should be able to continue to reduce the incidence of invasive cervical cancer with a primary HPV testing-based screening strategy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

During its 8th annual retreat in Tempe, Arizona February 21 to 24, 2016, the Association of Academic Chairs of Emergency Medicine (AACEM) organized a panel discussion that included representatives from seven prominent EM organizations: the American Academy of Emergency Medicine (AAEM), AAEM Resident and Student Association (AAEM/RSA), American Board of Emergency Medicine (ABEM), American College of Emergency Physicians (ACEP), Council of Residency Directors in Emergency Medicine (CORD), Emergency Medicine Residents’ Association (EMRA), and Society for Academic Emergency Medicine (SAEM). Part 1 of this series (Emerg Med. 2016;48[4]:163-166), published reports from the AAEM, AAEM/RSA, ABEM, and ACEP.  Part 2, the concluding part of this series, features reports from CORD, EMRA, and SAEM.

Council of Emergency Medicine Residency Directors

Saadia Akhtar, MD, President CORD

Resident Involvement in CORD. CORD members consist of faculty of EM residency programs. Each program is allowed to have a number of representatives, including program directors, associate/assistant program directors, clerkship directors, faculty, and program coordinators. In November 2015, the membership participated in a CORD bylaws amendment voting process, which resulted in the addition of a resident as a CORD program member representative. In addition, a vote was passed to establish a resident member-at-large position on the CORD board of directors , effective for 2016 to 2017. This will be the first time that a resident will have a position as a member of the CORD board of directors. Residents also have the opportunity to join various CORD task forces, committees, and communities of practice.

Physician Resilience. CORD has a long-standing history of supporting physician well-being and resilience. Emergency physicians are at great risk for burnout and physician suicide. CORD recently established the CORD Resilience Committee. The goals of the committee are to promote a culture of wellness among educators, residents, and students, along with providing curricular resources for educators. The committee plans to establish a network for educators, residents, and students interested in advancing physician wellness. In addition, the committee will conduct research and scholarship in physician wellness.

GME Funding. CORD is actively engaged in advocating graduate medical education (GME) funding. We are educating and empowering our members on advocacy issues affecting EM medical education and developing curriculum resources on GME funding. CORD is also collaborating with other organizations with similar interests.

Free Open-Access Medical Education. CORD is invested in enhancing free open-access medical education (FOAMEd). CORD has partnered with Academic Life in Emergency Medicine (ALiEM) by creating the CORD-ALiEM Task Force. CORD has financially supported and endorsed a number of projects that are important to both organizations. The establishment of this task force has allowed CORD members to participate and offer their expertise in EM medical education.

Academic Assembly. CORD is proud to conduct its annual Academic Assembly, which incorporates a variety of educational opportunities for medical educators and residents. Attendees can participate in a number of tracks, including program leadership, best practices, and navigating the academic waters. Additional tracks for clerkship directors, residency coordinators, and residents are also offered. The conference hosts the annual semi-final Clinical Pathologic Conference Competition. The CORD Academic Assembly is an excellent platform for EM educators and future leaders of our specialty to share ideas, collaborate, network, and advance our organization.

Emergency Medicine Residents’ Association

Leonard Stallings, MD, EMRA RRC-EM Liaison

Overview. EMRA is the largest resident organization in the world, with more than 13,000 members. EMRA represents 85% of all EM residents in the world and 90% of all senior residents in Accreditation Council for Graduate Medical Education-accredited EM residency programs.

Benefits of EMRA Membership. Members receive over $200 worth of EMRA educational publications (eg, EMRA Antibiotic Guide) immediately upon joining. It offers its members opportunities to submit articles for publication in EM Resident and its monthly e-newsletter. There are numerous committees and divisions to join based on the members’ area of interest, including ultrasound, emergency medical services, and critical care. EMRA gives out approximately $70,000 worth of awards annually, including travel scholarships and local action grants for residents and students.

EMRA Chair’s Challenge. Once again, EMRA challenges all chairs of academic EM departments to support sending one or more residents to the American College of Emergency Physicians (ACEP) Leadership and Advocacy Conference May 15 to 18, 2016 in Washington, DC. Participants will be entered into a drawing for two subscriptions to Virtual ACEP 15. The goal of this conference is to highlight and advocate legislation advancing emergency care, regardless of political labels.

Strategic Plan. The EMRA Strategic Plan includes developing diverse future EMRA leaders, producing quality educational resources, remaining fiscally responsible and secure, and advancing the EMRA culture of innovation.

Society for Academic Emergency Medicine

Deborah B. Diercks, MD, President SAEM

New Chief Executive Officer (CEO). In the summer of 2015, SAEM was pleased to announce the hiring of Megan Schagrin, MBA, CAE, as the new CEO of SAEM. Ms Schagrin has extensive experience serving in leadership positions at several medical nonprofit organizations, most recently at the American College of Chest Physicians. Over the last 9 months, Ms Schagrin has transformed the staff of SAEM by adding needed expertise, setting high expectations, and providing the support needed for existing staff to meet its maximal potential. This includes leading SAEM into a new office headquarters later this year.

Implementation of a New Strategic Plan. SAEM completed a new strategic plan in early 2015. This plan focuses on four key areas: member and leader development, medical education, research and research grants, and virtual relevance. Under the guidance of our new CEO, we have established programs and metrics to reach our goals in each of these areas.

Updates on Our Journal Plus One. In January 2016, our journal, Academic Emergency Medicine (AEM), named a new editor-in-chief, Jeffrey A. Kline, MD. Dr Kline has worked diligently to establish an editorial board, increase the journal’s virtual presence, and develop new content. In addition, in early 2017, AEM will launch a second journal: Academic Emergency Medicine Education and Training. This quarterly journal will be led by Editor Susan Promes, MD. AEM Education and Training will begin accepting high-quality education and research submissions in August 2016.

Refinement of our Annual Meeting. This year’s SAEM annual meeting will have a more focused format. To elevate the visibility of the best research and didactics in EM, the program committee, under the guidance of Ali Raja, MD, limited the number of accepted abstracts and didactic sessions. This will allow increased participation and engagement in these events and improve networking at the 2016 Annual Meeting, which will be held in New Orleans, May 10 to 13, 2016.

Editor’s Note: Physician wellness, continuing medical education, and increased resident involvement were some of the recurring themes of this panel discussion. For reports from the AAEM, AAEM/RSA, ABEM, and ACEP, see part 1 of this article in Emergency Medicine April 2016 (http://bit.ly/1VhZSKn). In an upcoming we will publish updates from the American College of Osteopathic Emergency Physicians and the American Osteopathic Board of Emergency Medicine.

Have a comment or question about this article? Let us know: [email protected].

During its 8th annual retreat in Tempe, Arizona February 21 to 24, 2016, the Association of Academic Chairs of Emergency Medicine (AACEM) organized a panel discussion that included representatives from seven prominent EM organizations: the American Academy of Emergency Medicine (AAEM), AAEM Resident and Student Association (AAEM/RSA), American Board of Emergency Medicine (ABEM), American College of Emergency Physicians (ACEP), Council of Residency Directors in Emergency Medicine (CORD), Emergency Medicine Residents’ Association (EMRA), and Society for Academic Emergency Medicine (SAEM). Part 1 of this series (Emerg Med. 2016;48[4]:163-166), published reports from the AAEM, AAEM/RSA, ABEM, and ACEP.  Part 2, the concluding part of this series, features reports from CORD, EMRA, and SAEM.

Council of Emergency Medicine Residency Directors

Saadia Akhtar, MD, President CORD

Resident Involvement in CORD. CORD members consist of faculty of EM residency programs. Each program is allowed to have a number of representatives, including program directors, associate/assistant program directors, clerkship directors, faculty, and program coordinators. In November 2015, the membership participated in a CORD bylaws amendment voting process, which resulted in the addition of a resident as a CORD program member representative. In addition, a vote was passed to establish a resident member-at-large position on the CORD board of directors , effective for 2016 to 2017. This will be the first time that a resident will have a position as a member of the CORD board of directors. Residents also have the opportunity to join various CORD task forces, committees, and communities of practice.

Physician Resilience. CORD has a long-standing history of supporting physician well-being and resilience. Emergency physicians are at great risk for burnout and physician suicide. CORD recently established the CORD Resilience Committee. The goals of the committee are to promote a culture of wellness among educators, residents, and students, along with providing curricular resources for educators. The committee plans to establish a network for educators, residents, and students interested in advancing physician wellness. In addition, the committee will conduct research and scholarship in physician wellness.

GME Funding. CORD is actively engaged in advocating graduate medical education (GME) funding. We are educating and empowering our members on advocacy issues affecting EM medical education and developing curriculum resources on GME funding. CORD is also collaborating with other organizations with similar interests.

Free Open-Access Medical Education. CORD is invested in enhancing free open-access medical education (FOAMEd). CORD has partnered with Academic Life in Emergency Medicine (ALiEM) by creating the CORD-ALiEM Task Force. CORD has financially supported and endorsed a number of projects that are important to both organizations. The establishment of this task force has allowed CORD members to participate and offer their expertise in EM medical education.

Academic Assembly. CORD is proud to conduct its annual Academic Assembly, which incorporates a variety of educational opportunities for medical educators and residents. Attendees can participate in a number of tracks, including program leadership, best practices, and navigating the academic waters. Additional tracks for clerkship directors, residency coordinators, and residents are also offered. The conference hosts the annual semi-final Clinical Pathologic Conference Competition. The CORD Academic Assembly is an excellent platform for EM educators and future leaders of our specialty to share ideas, collaborate, network, and advance our organization.

Emergency Medicine Residents’ Association

Leonard Stallings, MD, EMRA RRC-EM Liaison

Overview. EMRA is the largest resident organization in the world, with more than 13,000 members. EMRA represents 85% of all EM residents in the world and 90% of all senior residents in Accreditation Council for Graduate Medical Education-accredited EM residency programs.

Benefits of EMRA Membership. Members receive over $200 worth of EMRA educational publications (eg, EMRA Antibiotic Guide) immediately upon joining. It offers its members opportunities to submit articles for publication in EM Resident and its monthly e-newsletter. There are numerous committees and divisions to join based on the members’ area of interest, including ultrasound, emergency medical services, and critical care. EMRA gives out approximately $70,000 worth of awards annually, including travel scholarships and local action grants for residents and students.

EMRA Chair’s Challenge. Once again, EMRA challenges all chairs of academic EM departments to support sending one or more residents to the American College of Emergency Physicians (ACEP) Leadership and Advocacy Conference May 15 to 18, 2016 in Washington, DC. Participants will be entered into a drawing for two subscriptions to Virtual ACEP 15. The goal of this conference is to highlight and advocate legislation advancing emergency care, regardless of political labels.

Strategic Plan. The EMRA Strategic Plan includes developing diverse future EMRA leaders, producing quality educational resources, remaining fiscally responsible and secure, and advancing the EMRA culture of innovation.

Society for Academic Emergency Medicine

Deborah B. Diercks, MD, President SAEM

New Chief Executive Officer (CEO). In the summer of 2015, SAEM was pleased to announce the hiring of Megan Schagrin, MBA, CAE, as the new CEO of SAEM. Ms Schagrin has extensive experience serving in leadership positions at several medical nonprofit organizations, most recently at the American College of Chest Physicians. Over the last 9 months, Ms Schagrin has transformed the staff of SAEM by adding needed expertise, setting high expectations, and providing the support needed for existing staff to meet its maximal potential. This includes leading SAEM into a new office headquarters later this year.

Implementation of a New Strategic Plan. SAEM completed a new strategic plan in early 2015. This plan focuses on four key areas: member and leader development, medical education, research and research grants, and virtual relevance. Under the guidance of our new CEO, we have established programs and metrics to reach our goals in each of these areas.

Updates on Our Journal Plus One. In January 2016, our journal, Academic Emergency Medicine (AEM), named a new editor-in-chief, Jeffrey A. Kline, MD. Dr Kline has worked diligently to establish an editorial board, increase the journal’s virtual presence, and develop new content. In addition, in early 2017, AEM will launch a second journal: Academic Emergency Medicine Education and Training. This quarterly journal will be led by Editor Susan Promes, MD. AEM Education and Training will begin accepting high-quality education and research submissions in August 2016.

Refinement of our Annual Meeting. This year’s SAEM annual meeting will have a more focused format. To elevate the visibility of the best research and didactics in EM, the program committee, under the guidance of Ali Raja, MD, limited the number of accepted abstracts and didactic sessions. This will allow increased participation and engagement in these events and improve networking at the 2016 Annual Meeting, which will be held in New Orleans, May 10 to 13, 2016.

Editor’s Note: Physician wellness, continuing medical education, and increased resident involvement were some of the recurring themes of this panel discussion. For reports from the AAEM, AAEM/RSA, ABEM, and ACEP, see part 1 of this article in Emergency Medicine April 2016 (http://bit.ly/1VhZSKn). In an upcoming we will publish updates from the American College of Osteopathic Emergency Physicians and the American Osteopathic Board of Emergency Medicine.

Have a comment or question about this article? Let us know: [email protected].

During its 8th annual retreat in Tempe, Arizona February 21 to 24, 2016, the Association of Academic Chairs of Emergency Medicine (AACEM) organized a panel discussion that included representatives from seven prominent EM organizations: the American Academy of Emergency Medicine (AAEM), AAEM Resident and Student Association (AAEM/RSA), American Board of Emergency Medicine (ABEM), American College of Emergency Physicians (ACEP), Council of Residency Directors in Emergency Medicine (CORD), Emergency Medicine Residents’ Association (EMRA), and Society for Academic Emergency Medicine (SAEM). Part 1 of this series (Emerg Med. 2016;48[4]:163-166), published reports from the AAEM, AAEM/RSA, ABEM, and ACEP.  Part 2, the concluding part of this series, features reports from CORD, EMRA, and SAEM.

Council of Emergency Medicine Residency Directors

Saadia Akhtar, MD, President CORD

Resident Involvement in CORD. CORD members consist of faculty of EM residency programs. Each program is allowed to have a number of representatives, including program directors, associate/assistant program directors, clerkship directors, faculty, and program coordinators. In November 2015, the membership participated in a CORD bylaws amendment voting process, which resulted in the addition of a resident as a CORD program member representative. In addition, a vote was passed to establish a resident member-at-large position on the CORD board of directors , effective for 2016 to 2017. This will be the first time that a resident will have a position as a member of the CORD board of directors. Residents also have the opportunity to join various CORD task forces, committees, and communities of practice.

Physician Resilience. CORD has a long-standing history of supporting physician well-being and resilience. Emergency physicians are at great risk for burnout and physician suicide. CORD recently established the CORD Resilience Committee. The goals of the committee are to promote a culture of wellness among educators, residents, and students, along with providing curricular resources for educators. The committee plans to establish a network for educators, residents, and students interested in advancing physician wellness. In addition, the committee will conduct research and scholarship in physician wellness.

GME Funding. CORD is actively engaged in advocating graduate medical education (GME) funding. We are educating and empowering our members on advocacy issues affecting EM medical education and developing curriculum resources on GME funding. CORD is also collaborating with other organizations with similar interests.

Free Open-Access Medical Education. CORD is invested in enhancing free open-access medical education (FOAMEd). CORD has partnered with Academic Life in Emergency Medicine (ALiEM) by creating the CORD-ALiEM Task Force. CORD has financially supported and endorsed a number of projects that are important to both organizations. The establishment of this task force has allowed CORD members to participate and offer their expertise in EM medical education.

Academic Assembly. CORD is proud to conduct its annual Academic Assembly, which incorporates a variety of educational opportunities for medical educators and residents. Attendees can participate in a number of tracks, including program leadership, best practices, and navigating the academic waters. Additional tracks for clerkship directors, residency coordinators, and residents are also offered. The conference hosts the annual semi-final Clinical Pathologic Conference Competition. The CORD Academic Assembly is an excellent platform for EM educators and future leaders of our specialty to share ideas, collaborate, network, and advance our organization.

Emergency Medicine Residents’ Association

Leonard Stallings, MD, EMRA RRC-EM Liaison

Overview. EMRA is the largest resident organization in the world, with more than 13,000 members. EMRA represents 85% of all EM residents in the world and 90% of all senior residents in Accreditation Council for Graduate Medical Education-accredited EM residency programs.

Benefits of EMRA Membership. Members receive over $200 worth of EMRA educational publications (eg, EMRA Antibiotic Guide) immediately upon joining. It offers its members opportunities to submit articles for publication in EM Resident and its monthly e-newsletter. There are numerous committees and divisions to join based on the members’ area of interest, including ultrasound, emergency medical services, and critical care. EMRA gives out approximately $70,000 worth of awards annually, including travel scholarships and local action grants for residents and students.

EMRA Chair’s Challenge. Once again, EMRA challenges all chairs of academic EM departments to support sending one or more residents to the American College of Emergency Physicians (ACEP) Leadership and Advocacy Conference May 15 to 18, 2016 in Washington, DC. Participants will be entered into a drawing for two subscriptions to Virtual ACEP 15. The goal of this conference is to highlight and advocate legislation advancing emergency care, regardless of political labels.

Strategic Plan. The EMRA Strategic Plan includes developing diverse future EMRA leaders, producing quality educational resources, remaining fiscally responsible and secure, and advancing the EMRA culture of innovation.

Society for Academic Emergency Medicine

Deborah B. Diercks, MD, President SAEM

New Chief Executive Officer (CEO). In the summer of 2015, SAEM was pleased to announce the hiring of Megan Schagrin, MBA, CAE, as the new CEO of SAEM. Ms Schagrin has extensive experience serving in leadership positions at several medical nonprofit organizations, most recently at the American College of Chest Physicians. Over the last 9 months, Ms Schagrin has transformed the staff of SAEM by adding needed expertise, setting high expectations, and providing the support needed for existing staff to meet its maximal potential. This includes leading SAEM into a new office headquarters later this year.

Implementation of a New Strategic Plan. SAEM completed a new strategic plan in early 2015. This plan focuses on four key areas: member and leader development, medical education, research and research grants, and virtual relevance. Under the guidance of our new CEO, we have established programs and metrics to reach our goals in each of these areas.

Updates on Our Journal Plus One. In January 2016, our journal, Academic Emergency Medicine (AEM), named a new editor-in-chief, Jeffrey A. Kline, MD. Dr Kline has worked diligently to establish an editorial board, increase the journal’s virtual presence, and develop new content. In addition, in early 2017, AEM will launch a second journal: Academic Emergency Medicine Education and Training. This quarterly journal will be led by Editor Susan Promes, MD. AEM Education and Training will begin accepting high-quality education and research submissions in August 2016.

Refinement of our Annual Meeting. This year’s SAEM annual meeting will have a more focused format. To elevate the visibility of the best research and didactics in EM, the program committee, under the guidance of Ali Raja, MD, limited the number of accepted abstracts and didactic sessions. This will allow increased participation and engagement in these events and improve networking at the 2016 Annual Meeting, which will be held in New Orleans, May 10 to 13, 2016.

Editor’s Note: Physician wellness, continuing medical education, and increased resident involvement were some of the recurring themes of this panel discussion. For reports from the AAEM, AAEM/RSA, ABEM, and ACEP, see part 1 of this article in Emergency Medicine April 2016 (http://bit.ly/1VhZSKn). In an upcoming we will publish updates from the American College of Osteopathic Emergency Physicians and the American Osteopathic Board of Emergency Medicine.

Have a comment or question about this article? Let us know: [email protected].