Original Research

Veterans with psychiatric disabilities who are found incompetent to manage their finances are assigned trustees to directly receive and disburse their disability funds. The term representative payee refers to trustees assigned by the Social Security Administration (SSA), and the term for those assigned by the Veterans Benefits Administration (VBA) is fiduciaries. The generic term trustee will be used when referring to an individual responsible for managing another person’s benefits, regardless of the source of those benefits.

Because a trustee assignment is associated with the loss of legal rights and personal autonomy, the clinical utility of appointing trustees has been extensively researched.^1-7 However, almost all the literature on trustees for adults with psychiatric disabilities has focused on services within the civilian sector, whereas little is known about military veterans with similar arrangements.

Veterans with psychiatric disabilities face challenges in managing money on a daily basis. Like other individuals with serious mental illnesses, they may have limitations in basic monetary skills associated with mild to severe cognitive deficits, experience difficulties in budgeting finances, and have impulsive spending habits during periods of acute psychosis, mania, or depression. Unlike civilians with severe mental illness, veterans are able to receive disability benefits from both the VBA and the SSA, thus having the potential for substantially greater income than is typical among nonveterans with psychiatric disabilities.

This increased income can increase veterans’ risk of debt through increased capacity to obtain credit cards and other unsecured loans as well as make them more vulnerable to financial exploitation and victimization. Veterans with incomes from both VBA and SSA face the added complication of dealing with 2 distinct, ever-changing, and often difficult-to-navigate benefit systems.

This article compares the VBA fiduciary program with the better-known SSA representative payment program, then discusses in detail the fiduciary program administered by the VBA, highlighting areas of particular relevance to clinicians, and ends with a review of the published literature on the VBA fiduciary program for individuals with severe mental illness.

Federal Trustee Programs

The magnitude of the 2 main federal trustee systems is remarkable. In 2010, 1.5 million adult beneficiaries who received Supplemental Security Income (SSI) had representative payees responsible for managing about $4 billion per month.^8,9 Likewise, in 2010, almost 100,000 individuals receiving VBA benefits had fiduciaries responsible for overseeing about $100 million per month in disability compensation or pension benefits.¹⁰

The SSA has a single arrangement for provision of representative payee services in which the payee assignment can be indefinite, the responsibility for modification of the arrangement lies with the beneficiary, and oversight is minimal in both policy and practice.⁹ In contrast, the VBA, which oversees veterans’ pensions and disability benefits, administers several fiduciary arrangements that range in permanency and level of oversight (Table).

Permanent fiduciary appointments can be either federal or court appointed. Federal fiduciaries manage only VBA-appointed benefits, whereas court-appointed trustees (also known as guardians, fiduciaries, conservators, or curators, depending on the state) are appointed by the state to supervise all the financial assets of an incompetent beneficiary, potentially including both VBA and SSA benefits. Court-appointed trustees are usually designated when broader trust powers are needed to protect the beneficiary’s interests.¹¹

A final VBA fiduciary arrangement is called a Supervised Direct Payment. The payment is made directly to a veteran with periodic supervision by a field examiner who assesses the veteran’s use of funds. This arrangement is used when a veteran has future potential to be deemed competent and released from VBA supervision. It allows the veteran a trial period of managing her/his funds generally for about a year but no longer than 36 months before transitioning to direct pay.¹¹

Unlike SSA, which compensates total disability only, VBA has a rating system that estimates the degree to which a veteran is disabled and grants disability compensation accordingly.¹² In 2009, the average monthly payment for all SSA recipients of SSI was $474; the average monthly payment for all recipients of disability benefits from VBA in that year was $925.^13,14 For 2009, the federal maximum a SSA recipient could receive was only $674, although this could be supplemented by state funds. On the other hand, there is no set maximum for veterans’ benefits, which are determined through a formula that includes both percentage disability and number of dependents.^12,13 In 2011, the average monthly payment for disabled veterans with fiduciaries was $2,540 per month.¹² In a study of 49 veterans with trustees, the mean benefit from VBA was twice that of the SSA.¹⁵

Because VBA benefits are typically higher than those from SSA and because veterans can receive both SSA and VBA benefits, disabled veterans tend to have higher incomes than do civilians receiving disability benefits. Veterans also may receive lump sum payouts for past benefits, which can be substantial (often $20,000 to $40,000 and sometimes up to $100,000).¹⁶ For these reasons, identifying individuals who need a fiduciary and overseeing the management of funds once a fiduciary is assigned are critical.

Referral and Evaluation

The process through which a civilian SSA beneficiary is referred and evaluated for a representative payee is arguably less rigorous than is the referral of a veteran for the VBA fiduciary program. In the former, the treating clinician’s response to a single question, “In your opinion, is the beneficiary capable of managing his/her funds?” on the application for disability benefits often serves as the impetus for payee assignment.

In the latter, the VBA uses a rating agency to make determinations of a veteran’s capacity to handle VBA benefits either after receiving a request for such a determination or after receiving notice that a state court has determined the person is incompetent and/or has appointed a guardian to the person. The Code of Federal Regulations defines the criteria for finding a veteran with a psychiatric disability incompetent to manage his or her finances as follows: “a mentally incompetent person is one who because of injury or disease lacks the mental capacity to contract or to manage his or her own affairs, including disbursement of funds without limitation.”¹⁷ As such, if a veteran with mental illness is to be assigned a fiduciary, there needs to be evidence that the mental illness causes financial incompetence.

To assign a fiduciary, multiple sources of evidence are considered in demonstrating behaviors indicating financial incapacity. To illustrate, in Sanders v Principi, the VBA reviewed a veteran’s psychiatric history and weighed the opinion of a psychiatrist that the veteran’s mental illness was in remission against the opinion of family members that the veteran did not possess the ability to “conduct business transactions as his cognitive skills were severely impaired.”¹⁸

The VBA is expected to conduct a thorough review of the record and provide reasoned analysis in support of its conclusions, as discussed in Sims v Nicholson.¹⁹ The Sims court asserted that to render its decision, the VBA can consider a wide array of information sources, including field examination reports, private psychiatric examinations, medical examiners’ reports, and private physicians. Veterans are informed of the reasons behind the need for a fiduciary, which less commonly occurs in assigning representative payees in the SSA. Although the documented policy for evaluating and determining need for a fiduciary is impressive in its rigor, it is unknown to what extent these standards are put into actual practice.

For health care clinicians, deciding when to request formal assessment by the VBA rating agency of a veteran’s capacity to manage benefits can be challenging to both clinical judgment and to the therapeutic relationship. Although clinicians such as primary care providers, nurses, social workers, and case managers often hear information from the veteran and his/her family about the veteran’s day-to-day management of funds, most of these providers are not necessarily qualified to make a formal assessment of financial capacity.

Black and colleagues developed a measure to assess money mismanagement in a population composed primarily of veterans.²⁰ Although this measure was correlated with client Global Assessment of Functioning scores and client-rated assessment of money mismanagement, it was not correlated with clinician judgment of the individual’s inability to manage funds. Rosen and colleagues similarly found that clinician assessment of whether a veteran would benefit from a trustee arrangement was not associated with the veteran meeting more stringent objective criteria, such as evidence that mismanagement of funds had resulted in the veteran’s inability to meet basic needs or had substantially harmed the veteran.²¹ Recognizing that their clinical judgment has limitations without external guidance, clinicians may postpone referral, particularly if there is also concern that the veteran may misunderstand the referral decision as a personal judgment, possibly impairing future relationships with the clinician or clinical team.

One option a clinician can consider prior to an official request to the VBA rating agency is to refer the veteran to a trained neuropsychologist for a financial capacity evaluation. The information obtained normally includes a detailed clinical interview, standardized performance measures, and neuropsychological testing.²² This evaluation may allow the clinician to feel more confident about his/her decision and provide a nonjudgmental way of initiating discussion with the veteran. Clinicians may also want to discuss the situation with staff of the Fiduciary Program prior to making a referral. The VBA website (http://benefits.va.gov/fiduciary) provides information about the fiduciary process, including regional contact information for fiduciary services, which clinicians and family members may find useful.

The Fiduciary Role

Once an individual has been determined to need a formal trustee, the decision of who will assume this role differs for SSA and VBA systems. Whereas over 70% of SSA-appointed representative payees for individuals are family members, the majority of fiduciaries for veterans are attorneys or paralegals.^23,24 The ultimate designation of a trustee can have critical consequences for both beneficiaries and their families. Some studies have shown that people with psychiatric disabilities who are financially dependent on family members are significantly more likely to be aggressive and even violent toward those family members, with a greater elevated risk of conflict if the disabled person has more education, or even better money management skills, than the assigned family trustee.^25-27 Although there are fewer family fiduciaries in the VBA system, it is still possible that veterans with psychiatric disabilities will have these conflicts.

The significant amount of money veterans receive may put them at higher risk for financial exploitation. Given that the VBA disability payment is a reliable source of income and that many veterans with psychiatric disabilities live in environments of lower socioeconomic status, the veteran with a psychiatric disability may be especially vulnerable to financial manipulation. In an environment where many individuals have limited monetary resources, experience financial strain, and are frequently unemployed, it is unsurprising that, at best, family and friends may seek help and assistance from the veteran, and at worst, may maliciously exploit him or her. As a disinterested third party, it can be helpful for the clinician to explore potential disparities between veterans’ disability benefits and the income of individuals with whom the veteran resides.

Additionally, the amount of compensation fiduciaries can receive for their role can be significant. Fiduciaries can receive up to 4% of the yearly VBA benefits of a veteran for whom they are managing money, although family members and court-appointed fiduciaries are not allowed to receive such a commission without a special exception.¹¹ Because large retroactive payments may be disbursed all at once, 4% of the total can be substantial.¹⁶

Unsurprisingly, the VBA fiduciary system suffers from a certain amount of fraud, prompting recent efforts in Congress to investigate the program more closely.²⁸ Particular concern has been expressed by the House Committee on Veterans Affairs about misuse of funds by so-called professional fiduciaries who provide services for multiple veterans.²⁹ Recent audits estimated that over $400 million in payments and estates were at risk for misuse and over $80 million might be subject to fraud.¹⁶ Until 2004, there was no policy in place to replace a veteran’s funds if those funds had been misused by her/his fiduciary.³⁰ However, this was corrected when Congress passed the Veterans Benefits Improvement Act, and the VBA now reissues benefits if they were misused and the VBA was found negligent in its monitoring of the fiduciary.³¹ Unfortunately, it is also the VBA that makes the determination of negligence, raising concerns about conflict of interest.

Clinicians may contact their VBA Regional Office to request an evaluation of a veteran’s situation if they have concerns about the fiduciary arrangement, either based on their own observations or on complaints received from the veteran. A field examiner is required to investigate concerns about misuse of veteran funds.¹¹

Fiduciary Oversight

The SSA has been criticized for its lack of close oversight of representative payees. In a recent report on the SSA representative payee program, the evaluators noted, “More broadly, the [SSA] program does not require careful accounting and reporting by payees, nor does the current system appear to be useful in detecting possible misuse of benefits by payees.”⁹

In contrast, the VBA fiduciary program has designated field examiners who play a role in the initial competence determination, fiduciary arrangement and selection, and oversight of the fiduciary arrangement. Once the VBA has been alerted that a veteran may require a fiduciary, a field examiner is dispatched to observe the individual’s living conditions, fund requirements, and capacity to handle benefits.11 After the initial contact, the field examiner makes a recommendation of the appropriate financial arrangement and prospective fiduciary.

Regardless of the type of fiduciary arrangement in place, the field examiner makes periodic follow-up visits to the beneficiary based on the individual situation. The minimum frequency of required contacts is at least once per year.¹¹ However, visits can occur as infrequently as 36 months in particular situations (Table). During follow-up visits, the field examiner evaluates the beneficiary’s welfare, the performance of the fiduciary, the use of funds, the competency of the beneficiary, and the necessity to continue the fiduciary relationship.¹¹

Although detailed oversight of fiduciaries is technically required, there are a limited number of field examiners to provide that oversight. In 2006, caseloads for field examiners ranged from 132 to 592 cases per employee.Recent auditing showed that programs with the highest staff case loads also had the highest number of deficiencies, suggesting that some field examiners may be unable to provide sufficient oversight to all their clients.¹⁶ The effectiveness of field examiners may suffer when they are responsible for very high numbers of veterans.¹⁶ Improving oversight of fiduciaries is a stated goal of the VA Office of Inspector General, although increasing the number of field examiners is not mentioned as a means to achieve this goal.³²

The SSA does not systematically assess whether a beneficiary is able to resume control over his or her finances. Responsibility lies with the beneficiary to initiate a request to become his/her own payee by demonstrating ability to care for self by means of any evidence, including providing a doctor’s statement or an official copy of a court order. The SSA further cautions beneficiaries who are considering submitting proof of their capability to manage their money as a result of improvement in their condition that, “If SSA believes your condition has improved to the point that you no longer need a payee, we may reevaluate your eligibility for disability payments.”³³ This may discourage beneficiaries from attempting to rescind the payeeship, as they potentially risk losing their disability benefits as well.

In contrast, VBA requires regular assessment by a field examiner for continuation of the fiduciary arrangement.¹¹ It is possible to rescind this arrangement if the veteran is found to be competent to handle his/her own funds, understands his/her financial situation, is applying funds to his/her needs appropriately, and would not benefit from further VBA supervision. Additionally, a trial period of limited fund disbursement for 3 to 5 months can be recommended in order to determine how well the veteran manages his/her money. This is commonly done when there are substantial amounts of money being held in trust for the veteran.¹¹

Trustee Effectiveness

Considerable research has examined the effectiveness of the SSA representative payee program as well as potential benefits and risks to the payee. For example, in beneficiaries with psychiatric disabilities, payees can be instrumental in promoting residential stability, basic health care, and psychiatric treatment engagement.⁶ In addition, representative payeeship has been shown to be associated with reduced hospitalization, victimization, and homelessness.^34,35 Finally, research has found better treatment adherence among consumers with payees compared with those without.⁵

On the other hand, risks noted in some studies suggest payeeship may be used coercively, thwart self-determination, and increase conflict.²⁵ Additionally, payeeship was not associated with a differential reduction in substance use compared with SSA beneficiaries without a payee, nor did it have any effect on clinical outcomes.^36-38 These studies may or may not be applicable to the veteran population: Few studies of SSA payeeship include veterans, and there are no studies examining the effectiveness of the VBA fiduciary program exclusively.

Conrad and colleagues reported on a randomized trial of a community trustee and case management program integrated with psychiatric care provided by the VHA.⁴ Twelve-month outcomes favored the use of the more integrated program, which showed a reduction in substance use, money mismanagement, and days homeless, along with an increased quality of life. However, the study did not distinguish between funding source (VBA, SSA, or both) and trustee status (SSA representative payee or VBA fiduciary). A voluntary program in which veterans worked with money managers who helped them manage funds and held their check books/bank cards also resulted in some improvement in substance use and money management, but this program did not involve either the formal SSA payee or VBA fiduciary systems.³⁹

Although there is a perception that fiduciaries are unwanted impositions on individuals with mental illness, many veterans who have difficulty managing their money seem to want assistance. In one study, nearly 75% of the veterans interviewed agreed with the statement, “Someone who would give me advice around my funds would be helpful to me.” Thirty-four percent agreed with the statement, “Someone who would receive my check and control my funds would be helpful to me,” and 22% reported that they thought a money manager would have helped prevent their hospitalization.⁴⁰ Additionally, veterans who had payees reported generally high levels of satisfaction and trust with their payee, as well as low feelings of coercion.¹⁵ Although similarities with the SSA system may allow some generalizing of findings across SSA and VBA, significant differences in how the programs are administered and the amount of money at stake justify independent evaluation of the VBA fiduciary program.

Conclusion

Veterans with psychiatric disabilities who are deemed incompetent to manage their finances are typically assigned a trustee to disperse disability funds. Both the VBA and SSA provide disability compensation and have a process for providing formal money management services for those determined to be financially incapacitated. However, these 2 federal programs are complex and have many differences.

Clinicians may come into contact with these programs when referring a veteran for services or when a veteran complains about their existing services. The decision of when to refer a veteran for evaluation for a fiduciary is challenging. Once a veteran is referred to the VBA rating agency, the VBA completes a more formalized evaluation to determine whether the beneficiary meets the criteria for a fiduciary. The VBA also has outlined more rigorous ongoing assessment requirements than has the SSA and has designated field examiners to complete these; however, in practice, field examiner heavy case-loads may make it more challenging for the VBA to achieve this rigor.

The VBA provides a formal means of evaluating a veteran’s ability to manage his or her funds through Supervised Direct Payment, which can allow a veteran to demonstrate the ability to manage money and thus end a fiduciary relationship that is no longer needed. In contrast, SSA has no formal evaluation program. Additionally, requesting an end to a payeeship for SSA funds can potentially trigger the loss of benefits, discouraging recipients from ever managing their money independently again.

Ultimately, assigning a fiduciary involves a complex decision weighing values of autonomy (veteran’s freedom to manage his or her own money) and social welfare (veteran’s safety if genuinely vulnerable to financial exploitation).

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Veterans with psychiatric disabilities who are found incompetent to manage their finances are assigned trustees to directly receive and disburse their disability funds. The term representative payee refers to trustees assigned by the Social Security Administration (SSA), and the term for those assigned by the Veterans Benefits Administration (VBA) is fiduciaries. The generic term trustee will be used when referring to an individual responsible for managing another person’s benefits, regardless of the source of those benefits.

Because a trustee assignment is associated with the loss of legal rights and personal autonomy, the clinical utility of appointing trustees has been extensively researched.^1-7 However, almost all the literature on trustees for adults with psychiatric disabilities has focused on services within the civilian sector, whereas little is known about military veterans with similar arrangements.

Veterans with psychiatric disabilities face challenges in managing money on a daily basis. Like other individuals with serious mental illnesses, they may have limitations in basic monetary skills associated with mild to severe cognitive deficits, experience difficulties in budgeting finances, and have impulsive spending habits during periods of acute psychosis, mania, or depression. Unlike civilians with severe mental illness, veterans are able to receive disability benefits from both the VBA and the SSA, thus having the potential for substantially greater income than is typical among nonveterans with psychiatric disabilities.

This increased income can increase veterans’ risk of debt through increased capacity to obtain credit cards and other unsecured loans as well as make them more vulnerable to financial exploitation and victimization. Veterans with incomes from both VBA and SSA face the added complication of dealing with 2 distinct, ever-changing, and often difficult-to-navigate benefit systems.

This article compares the VBA fiduciary program with the better-known SSA representative payment program, then discusses in detail the fiduciary program administered by the VBA, highlighting areas of particular relevance to clinicians, and ends with a review of the published literature on the VBA fiduciary program for individuals with severe mental illness.

Federal Trustee Programs

The magnitude of the 2 main federal trustee systems is remarkable. In 2010, 1.5 million adult beneficiaries who received Supplemental Security Income (SSI) had representative payees responsible for managing about $4 billion per month.^8,9 Likewise, in 2010, almost 100,000 individuals receiving VBA benefits had fiduciaries responsible for overseeing about $100 million per month in disability compensation or pension benefits.¹⁰

The SSA has a single arrangement for provision of representative payee services in which the payee assignment can be indefinite, the responsibility for modification of the arrangement lies with the beneficiary, and oversight is minimal in both policy and practice.⁹ In contrast, the VBA, which oversees veterans’ pensions and disability benefits, administers several fiduciary arrangements that range in permanency and level of oversight (Table).

Permanent fiduciary appointments can be either federal or court appointed. Federal fiduciaries manage only VBA-appointed benefits, whereas court-appointed trustees (also known as guardians, fiduciaries, conservators, or curators, depending on the state) are appointed by the state to supervise all the financial assets of an incompetent beneficiary, potentially including both VBA and SSA benefits. Court-appointed trustees are usually designated when broader trust powers are needed to protect the beneficiary’s interests.¹¹

A final VBA fiduciary arrangement is called a Supervised Direct Payment. The payment is made directly to a veteran with periodic supervision by a field examiner who assesses the veteran’s use of funds. This arrangement is used when a veteran has future potential to be deemed competent and released from VBA supervision. It allows the veteran a trial period of managing her/his funds generally for about a year but no longer than 36 months before transitioning to direct pay.¹¹

Unlike SSA, which compensates total disability only, VBA has a rating system that estimates the degree to which a veteran is disabled and grants disability compensation accordingly.¹² In 2009, the average monthly payment for all SSA recipients of SSI was $474; the average monthly payment for all recipients of disability benefits from VBA in that year was $925.^13,14 For 2009, the federal maximum a SSA recipient could receive was only $674, although this could be supplemented by state funds. On the other hand, there is no set maximum for veterans’ benefits, which are determined through a formula that includes both percentage disability and number of dependents.^12,13 In 2011, the average monthly payment for disabled veterans with fiduciaries was $2,540 per month.¹² In a study of 49 veterans with trustees, the mean benefit from VBA was twice that of the SSA.¹⁵

Because VBA benefits are typically higher than those from SSA and because veterans can receive both SSA and VBA benefits, disabled veterans tend to have higher incomes than do civilians receiving disability benefits. Veterans also may receive lump sum payouts for past benefits, which can be substantial (often $20,000 to $40,000 and sometimes up to $100,000).¹⁶ For these reasons, identifying individuals who need a fiduciary and overseeing the management of funds once a fiduciary is assigned are critical.

Referral and Evaluation

The process through which a civilian SSA beneficiary is referred and evaluated for a representative payee is arguably less rigorous than is the referral of a veteran for the VBA fiduciary program. In the former, the treating clinician’s response to a single question, “In your opinion, is the beneficiary capable of managing his/her funds?” on the application for disability benefits often serves as the impetus for payee assignment.

In the latter, the VBA uses a rating agency to make determinations of a veteran’s capacity to handle VBA benefits either after receiving a request for such a determination or after receiving notice that a state court has determined the person is incompetent and/or has appointed a guardian to the person. The Code of Federal Regulations defines the criteria for finding a veteran with a psychiatric disability incompetent to manage his or her finances as follows: “a mentally incompetent person is one who because of injury or disease lacks the mental capacity to contract or to manage his or her own affairs, including disbursement of funds without limitation.”¹⁷ As such, if a veteran with mental illness is to be assigned a fiduciary, there needs to be evidence that the mental illness causes financial incompetence.

To assign a fiduciary, multiple sources of evidence are considered in demonstrating behaviors indicating financial incapacity. To illustrate, in Sanders v Principi, the VBA reviewed a veteran’s psychiatric history and weighed the opinion of a psychiatrist that the veteran’s mental illness was in remission against the opinion of family members that the veteran did not possess the ability to “conduct business transactions as his cognitive skills were severely impaired.”¹⁸

The VBA is expected to conduct a thorough review of the record and provide reasoned analysis in support of its conclusions, as discussed in Sims v Nicholson.¹⁹ The Sims court asserted that to render its decision, the VBA can consider a wide array of information sources, including field examination reports, private psychiatric examinations, medical examiners’ reports, and private physicians. Veterans are informed of the reasons behind the need for a fiduciary, which less commonly occurs in assigning representative payees in the SSA. Although the documented policy for evaluating and determining need for a fiduciary is impressive in its rigor, it is unknown to what extent these standards are put into actual practice.

For health care clinicians, deciding when to request formal assessment by the VBA rating agency of a veteran’s capacity to manage benefits can be challenging to both clinical judgment and to the therapeutic relationship. Although clinicians such as primary care providers, nurses, social workers, and case managers often hear information from the veteran and his/her family about the veteran’s day-to-day management of funds, most of these providers are not necessarily qualified to make a formal assessment of financial capacity.

Black and colleagues developed a measure to assess money mismanagement in a population composed primarily of veterans.²⁰ Although this measure was correlated with client Global Assessment of Functioning scores and client-rated assessment of money mismanagement, it was not correlated with clinician judgment of the individual’s inability to manage funds. Rosen and colleagues similarly found that clinician assessment of whether a veteran would benefit from a trustee arrangement was not associated with the veteran meeting more stringent objective criteria, such as evidence that mismanagement of funds had resulted in the veteran’s inability to meet basic needs or had substantially harmed the veteran.²¹ Recognizing that their clinical judgment has limitations without external guidance, clinicians may postpone referral, particularly if there is also concern that the veteran may misunderstand the referral decision as a personal judgment, possibly impairing future relationships with the clinician or clinical team.

One option a clinician can consider prior to an official request to the VBA rating agency is to refer the veteran to a trained neuropsychologist for a financial capacity evaluation. The information obtained normally includes a detailed clinical interview, standardized performance measures, and neuropsychological testing.²² This evaluation may allow the clinician to feel more confident about his/her decision and provide a nonjudgmental way of initiating discussion with the veteran. Clinicians may also want to discuss the situation with staff of the Fiduciary Program prior to making a referral. The VBA website (http://benefits.va.gov/fiduciary) provides information about the fiduciary process, including regional contact information for fiduciary services, which clinicians and family members may find useful.

The Fiduciary Role

Once an individual has been determined to need a formal trustee, the decision of who will assume this role differs for SSA and VBA systems. Whereas over 70% of SSA-appointed representative payees for individuals are family members, the majority of fiduciaries for veterans are attorneys or paralegals.^23,24 The ultimate designation of a trustee can have critical consequences for both beneficiaries and their families. Some studies have shown that people with psychiatric disabilities who are financially dependent on family members are significantly more likely to be aggressive and even violent toward those family members, with a greater elevated risk of conflict if the disabled person has more education, or even better money management skills, than the assigned family trustee.^25-27 Although there are fewer family fiduciaries in the VBA system, it is still possible that veterans with psychiatric disabilities will have these conflicts.

The significant amount of money veterans receive may put them at higher risk for financial exploitation. Given that the VBA disability payment is a reliable source of income and that many veterans with psychiatric disabilities live in environments of lower socioeconomic status, the veteran with a psychiatric disability may be especially vulnerable to financial manipulation. In an environment where many individuals have limited monetary resources, experience financial strain, and are frequently unemployed, it is unsurprising that, at best, family and friends may seek help and assistance from the veteran, and at worst, may maliciously exploit him or her. As a disinterested third party, it can be helpful for the clinician to explore potential disparities between veterans’ disability benefits and the income of individuals with whom the veteran resides.

Additionally, the amount of compensation fiduciaries can receive for their role can be significant. Fiduciaries can receive up to 4% of the yearly VBA benefits of a veteran for whom they are managing money, although family members and court-appointed fiduciaries are not allowed to receive such a commission without a special exception.¹¹ Because large retroactive payments may be disbursed all at once, 4% of the total can be substantial.¹⁶

Unsurprisingly, the VBA fiduciary system suffers from a certain amount of fraud, prompting recent efforts in Congress to investigate the program more closely.²⁸ Particular concern has been expressed by the House Committee on Veterans Affairs about misuse of funds by so-called professional fiduciaries who provide services for multiple veterans.²⁹ Recent audits estimated that over $400 million in payments and estates were at risk for misuse and over $80 million might be subject to fraud.¹⁶ Until 2004, there was no policy in place to replace a veteran’s funds if those funds had been misused by her/his fiduciary.³⁰ However, this was corrected when Congress passed the Veterans Benefits Improvement Act, and the VBA now reissues benefits if they were misused and the VBA was found negligent in its monitoring of the fiduciary.³¹ Unfortunately, it is also the VBA that makes the determination of negligence, raising concerns about conflict of interest.

Clinicians may contact their VBA Regional Office to request an evaluation of a veteran’s situation if they have concerns about the fiduciary arrangement, either based on their own observations or on complaints received from the veteran. A field examiner is required to investigate concerns about misuse of veteran funds.¹¹

Fiduciary Oversight

The SSA has been criticized for its lack of close oversight of representative payees. In a recent report on the SSA representative payee program, the evaluators noted, “More broadly, the [SSA] program does not require careful accounting and reporting by payees, nor does the current system appear to be useful in detecting possible misuse of benefits by payees.”⁹

In contrast, the VBA fiduciary program has designated field examiners who play a role in the initial competence determination, fiduciary arrangement and selection, and oversight of the fiduciary arrangement. Once the VBA has been alerted that a veteran may require a fiduciary, a field examiner is dispatched to observe the individual’s living conditions, fund requirements, and capacity to handle benefits.11 After the initial contact, the field examiner makes a recommendation of the appropriate financial arrangement and prospective fiduciary.

Regardless of the type of fiduciary arrangement in place, the field examiner makes periodic follow-up visits to the beneficiary based on the individual situation. The minimum frequency of required contacts is at least once per year.¹¹ However, visits can occur as infrequently as 36 months in particular situations (Table). During follow-up visits, the field examiner evaluates the beneficiary’s welfare, the performance of the fiduciary, the use of funds, the competency of the beneficiary, and the necessity to continue the fiduciary relationship.¹¹

Although detailed oversight of fiduciaries is technically required, there are a limited number of field examiners to provide that oversight. In 2006, caseloads for field examiners ranged from 132 to 592 cases per employee.Recent auditing showed that programs with the highest staff case loads also had the highest number of deficiencies, suggesting that some field examiners may be unable to provide sufficient oversight to all their clients.¹⁶ The effectiveness of field examiners may suffer when they are responsible for very high numbers of veterans.¹⁶ Improving oversight of fiduciaries is a stated goal of the VA Office of Inspector General, although increasing the number of field examiners is not mentioned as a means to achieve this goal.³²

The SSA does not systematically assess whether a beneficiary is able to resume control over his or her finances. Responsibility lies with the beneficiary to initiate a request to become his/her own payee by demonstrating ability to care for self by means of any evidence, including providing a doctor’s statement or an official copy of a court order. The SSA further cautions beneficiaries who are considering submitting proof of their capability to manage their money as a result of improvement in their condition that, “If SSA believes your condition has improved to the point that you no longer need a payee, we may reevaluate your eligibility for disability payments.”³³ This may discourage beneficiaries from attempting to rescind the payeeship, as they potentially risk losing their disability benefits as well.

In contrast, VBA requires regular assessment by a field examiner for continuation of the fiduciary arrangement.¹¹ It is possible to rescind this arrangement if the veteran is found to be competent to handle his/her own funds, understands his/her financial situation, is applying funds to his/her needs appropriately, and would not benefit from further VBA supervision. Additionally, a trial period of limited fund disbursement for 3 to 5 months can be recommended in order to determine how well the veteran manages his/her money. This is commonly done when there are substantial amounts of money being held in trust for the veteran.¹¹

Trustee Effectiveness

Considerable research has examined the effectiveness of the SSA representative payee program as well as potential benefits and risks to the payee. For example, in beneficiaries with psychiatric disabilities, payees can be instrumental in promoting residential stability, basic health care, and psychiatric treatment engagement.⁶ In addition, representative payeeship has been shown to be associated with reduced hospitalization, victimization, and homelessness.^34,35 Finally, research has found better treatment adherence among consumers with payees compared with those without.⁵

On the other hand, risks noted in some studies suggest payeeship may be used coercively, thwart self-determination, and increase conflict.²⁵ Additionally, payeeship was not associated with a differential reduction in substance use compared with SSA beneficiaries without a payee, nor did it have any effect on clinical outcomes.^36-38 These studies may or may not be applicable to the veteran population: Few studies of SSA payeeship include veterans, and there are no studies examining the effectiveness of the VBA fiduciary program exclusively.

Conrad and colleagues reported on a randomized trial of a community trustee and case management program integrated with psychiatric care provided by the VHA.⁴ Twelve-month outcomes favored the use of the more integrated program, which showed a reduction in substance use, money mismanagement, and days homeless, along with an increased quality of life. However, the study did not distinguish between funding source (VBA, SSA, or both) and trustee status (SSA representative payee or VBA fiduciary). A voluntary program in which veterans worked with money managers who helped them manage funds and held their check books/bank cards also resulted in some improvement in substance use and money management, but this program did not involve either the formal SSA payee or VBA fiduciary systems.³⁹

Although there is a perception that fiduciaries are unwanted impositions on individuals with mental illness, many veterans who have difficulty managing their money seem to want assistance. In one study, nearly 75% of the veterans interviewed agreed with the statement, “Someone who would give me advice around my funds would be helpful to me.” Thirty-four percent agreed with the statement, “Someone who would receive my check and control my funds would be helpful to me,” and 22% reported that they thought a money manager would have helped prevent their hospitalization.⁴⁰ Additionally, veterans who had payees reported generally high levels of satisfaction and trust with their payee, as well as low feelings of coercion.¹⁵ Although similarities with the SSA system may allow some generalizing of findings across SSA and VBA, significant differences in how the programs are administered and the amount of money at stake justify independent evaluation of the VBA fiduciary program.

Conclusion

Veterans with psychiatric disabilities who are deemed incompetent to manage their finances are typically assigned a trustee to disperse disability funds. Both the VBA and SSA provide disability compensation and have a process for providing formal money management services for those determined to be financially incapacitated. However, these 2 federal programs are complex and have many differences.

Clinicians may come into contact with these programs when referring a veteran for services or when a veteran complains about their existing services. The decision of when to refer a veteran for evaluation for a fiduciary is challenging. Once a veteran is referred to the VBA rating agency, the VBA completes a more formalized evaluation to determine whether the beneficiary meets the criteria for a fiduciary. The VBA also has outlined more rigorous ongoing assessment requirements than has the SSA and has designated field examiners to complete these; however, in practice, field examiner heavy case-loads may make it more challenging for the VBA to achieve this rigor.

The VBA provides a formal means of evaluating a veteran’s ability to manage his or her funds through Supervised Direct Payment, which can allow a veteran to demonstrate the ability to manage money and thus end a fiduciary relationship that is no longer needed. In contrast, SSA has no formal evaluation program. Additionally, requesting an end to a payeeship for SSA funds can potentially trigger the loss of benefits, discouraging recipients from ever managing their money independently again.

Ultimately, assigning a fiduciary involves a complex decision weighing values of autonomy (veteran’s freedom to manage his or her own money) and social welfare (veteran’s safety if genuinely vulnerable to financial exploitation).

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Veterans with psychiatric disabilities who are found incompetent to manage their finances are assigned trustees to directly receive and disburse their disability funds. The term representative payee refers to trustees assigned by the Social Security Administration (SSA), and the term for those assigned by the Veterans Benefits Administration (VBA) is fiduciaries. The generic term trustee will be used when referring to an individual responsible for managing another person’s benefits, regardless of the source of those benefits.

Because a trustee assignment is associated with the loss of legal rights and personal autonomy, the clinical utility of appointing trustees has been extensively researched.^1-7 However, almost all the literature on trustees for adults with psychiatric disabilities has focused on services within the civilian sector, whereas little is known about military veterans with similar arrangements.

Veterans with psychiatric disabilities face challenges in managing money on a daily basis. Like other individuals with serious mental illnesses, they may have limitations in basic monetary skills associated with mild to severe cognitive deficits, experience difficulties in budgeting finances, and have impulsive spending habits during periods of acute psychosis, mania, or depression. Unlike civilians with severe mental illness, veterans are able to receive disability benefits from both the VBA and the SSA, thus having the potential for substantially greater income than is typical among nonveterans with psychiatric disabilities.

This increased income can increase veterans’ risk of debt through increased capacity to obtain credit cards and other unsecured loans as well as make them more vulnerable to financial exploitation and victimization. Veterans with incomes from both VBA and SSA face the added complication of dealing with 2 distinct, ever-changing, and often difficult-to-navigate benefit systems.

This article compares the VBA fiduciary program with the better-known SSA representative payment program, then discusses in detail the fiduciary program administered by the VBA, highlighting areas of particular relevance to clinicians, and ends with a review of the published literature on the VBA fiduciary program for individuals with severe mental illness.

Federal Trustee Programs

The magnitude of the 2 main federal trustee systems is remarkable. In 2010, 1.5 million adult beneficiaries who received Supplemental Security Income (SSI) had representative payees responsible for managing about $4 billion per month.^8,9 Likewise, in 2010, almost 100,000 individuals receiving VBA benefits had fiduciaries responsible for overseeing about $100 million per month in disability compensation or pension benefits.¹⁰

The SSA has a single arrangement for provision of representative payee services in which the payee assignment can be indefinite, the responsibility for modification of the arrangement lies with the beneficiary, and oversight is minimal in both policy and practice.⁹ In contrast, the VBA, which oversees veterans’ pensions and disability benefits, administers several fiduciary arrangements that range in permanency and level of oversight (Table).

Permanent fiduciary appointments can be either federal or court appointed. Federal fiduciaries manage only VBA-appointed benefits, whereas court-appointed trustees (also known as guardians, fiduciaries, conservators, or curators, depending on the state) are appointed by the state to supervise all the financial assets of an incompetent beneficiary, potentially including both VBA and SSA benefits. Court-appointed trustees are usually designated when broader trust powers are needed to protect the beneficiary’s interests.¹¹

A final VBA fiduciary arrangement is called a Supervised Direct Payment. The payment is made directly to a veteran with periodic supervision by a field examiner who assesses the veteran’s use of funds. This arrangement is used when a veteran has future potential to be deemed competent and released from VBA supervision. It allows the veteran a trial period of managing her/his funds generally for about a year but no longer than 36 months before transitioning to direct pay.¹¹

Unlike SSA, which compensates total disability only, VBA has a rating system that estimates the degree to which a veteran is disabled and grants disability compensation accordingly.¹² In 2009, the average monthly payment for all SSA recipients of SSI was $474; the average monthly payment for all recipients of disability benefits from VBA in that year was $925.^13,14 For 2009, the federal maximum a SSA recipient could receive was only $674, although this could be supplemented by state funds. On the other hand, there is no set maximum for veterans’ benefits, which are determined through a formula that includes both percentage disability and number of dependents.^12,13 In 2011, the average monthly payment for disabled veterans with fiduciaries was $2,540 per month.¹² In a study of 49 veterans with trustees, the mean benefit from VBA was twice that of the SSA.¹⁵

Because VBA benefits are typically higher than those from SSA and because veterans can receive both SSA and VBA benefits, disabled veterans tend to have higher incomes than do civilians receiving disability benefits. Veterans also may receive lump sum payouts for past benefits, which can be substantial (often $20,000 to $40,000 and sometimes up to $100,000).¹⁶ For these reasons, identifying individuals who need a fiduciary and overseeing the management of funds once a fiduciary is assigned are critical.

Referral and Evaluation

The process through which a civilian SSA beneficiary is referred and evaluated for a representative payee is arguably less rigorous than is the referral of a veteran for the VBA fiduciary program. In the former, the treating clinician’s response to a single question, “In your opinion, is the beneficiary capable of managing his/her funds?” on the application for disability benefits often serves as the impetus for payee assignment.

In the latter, the VBA uses a rating agency to make determinations of a veteran’s capacity to handle VBA benefits either after receiving a request for such a determination or after receiving notice that a state court has determined the person is incompetent and/or has appointed a guardian to the person. The Code of Federal Regulations defines the criteria for finding a veteran with a psychiatric disability incompetent to manage his or her finances as follows: “a mentally incompetent person is one who because of injury or disease lacks the mental capacity to contract or to manage his or her own affairs, including disbursement of funds without limitation.”¹⁷ As such, if a veteran with mental illness is to be assigned a fiduciary, there needs to be evidence that the mental illness causes financial incompetence.

To assign a fiduciary, multiple sources of evidence are considered in demonstrating behaviors indicating financial incapacity. To illustrate, in Sanders v Principi, the VBA reviewed a veteran’s psychiatric history and weighed the opinion of a psychiatrist that the veteran’s mental illness was in remission against the opinion of family members that the veteran did not possess the ability to “conduct business transactions as his cognitive skills were severely impaired.”¹⁸

The VBA is expected to conduct a thorough review of the record and provide reasoned analysis in support of its conclusions, as discussed in Sims v Nicholson.¹⁹ The Sims court asserted that to render its decision, the VBA can consider a wide array of information sources, including field examination reports, private psychiatric examinations, medical examiners’ reports, and private physicians. Veterans are informed of the reasons behind the need for a fiduciary, which less commonly occurs in assigning representative payees in the SSA. Although the documented policy for evaluating and determining need for a fiduciary is impressive in its rigor, it is unknown to what extent these standards are put into actual practice.

For health care clinicians, deciding when to request formal assessment by the VBA rating agency of a veteran’s capacity to manage benefits can be challenging to both clinical judgment and to the therapeutic relationship. Although clinicians such as primary care providers, nurses, social workers, and case managers often hear information from the veteran and his/her family about the veteran’s day-to-day management of funds, most of these providers are not necessarily qualified to make a formal assessment of financial capacity.

Black and colleagues developed a measure to assess money mismanagement in a population composed primarily of veterans.²⁰ Although this measure was correlated with client Global Assessment of Functioning scores and client-rated assessment of money mismanagement, it was not correlated with clinician judgment of the individual’s inability to manage funds. Rosen and colleagues similarly found that clinician assessment of whether a veteran would benefit from a trustee arrangement was not associated with the veteran meeting more stringent objective criteria, such as evidence that mismanagement of funds had resulted in the veteran’s inability to meet basic needs or had substantially harmed the veteran.²¹ Recognizing that their clinical judgment has limitations without external guidance, clinicians may postpone referral, particularly if there is also concern that the veteran may misunderstand the referral decision as a personal judgment, possibly impairing future relationships with the clinician or clinical team.

One option a clinician can consider prior to an official request to the VBA rating agency is to refer the veteran to a trained neuropsychologist for a financial capacity evaluation. The information obtained normally includes a detailed clinical interview, standardized performance measures, and neuropsychological testing.²² This evaluation may allow the clinician to feel more confident about his/her decision and provide a nonjudgmental way of initiating discussion with the veteran. Clinicians may also want to discuss the situation with staff of the Fiduciary Program prior to making a referral. The VBA website (http://benefits.va.gov/fiduciary) provides information about the fiduciary process, including regional contact information for fiduciary services, which clinicians and family members may find useful.

The Fiduciary Role

Once an individual has been determined to need a formal trustee, the decision of who will assume this role differs for SSA and VBA systems. Whereas over 70% of SSA-appointed representative payees for individuals are family members, the majority of fiduciaries for veterans are attorneys or paralegals.^23,24 The ultimate designation of a trustee can have critical consequences for both beneficiaries and their families. Some studies have shown that people with psychiatric disabilities who are financially dependent on family members are significantly more likely to be aggressive and even violent toward those family members, with a greater elevated risk of conflict if the disabled person has more education, or even better money management skills, than the assigned family trustee.^25-27 Although there are fewer family fiduciaries in the VBA system, it is still possible that veterans with psychiatric disabilities will have these conflicts.

The significant amount of money veterans receive may put them at higher risk for financial exploitation. Given that the VBA disability payment is a reliable source of income and that many veterans with psychiatric disabilities live in environments of lower socioeconomic status, the veteran with a psychiatric disability may be especially vulnerable to financial manipulation. In an environment where many individuals have limited monetary resources, experience financial strain, and are frequently unemployed, it is unsurprising that, at best, family and friends may seek help and assistance from the veteran, and at worst, may maliciously exploit him or her. As a disinterested third party, it can be helpful for the clinician to explore potential disparities between veterans’ disability benefits and the income of individuals with whom the veteran resides.

Additionally, the amount of compensation fiduciaries can receive for their role can be significant. Fiduciaries can receive up to 4% of the yearly VBA benefits of a veteran for whom they are managing money, although family members and court-appointed fiduciaries are not allowed to receive such a commission without a special exception.¹¹ Because large retroactive payments may be disbursed all at once, 4% of the total can be substantial.¹⁶

Unsurprisingly, the VBA fiduciary system suffers from a certain amount of fraud, prompting recent efforts in Congress to investigate the program more closely.²⁸ Particular concern has been expressed by the House Committee on Veterans Affairs about misuse of funds by so-called professional fiduciaries who provide services for multiple veterans.²⁹ Recent audits estimated that over $400 million in payments and estates were at risk for misuse and over $80 million might be subject to fraud.¹⁶ Until 2004, there was no policy in place to replace a veteran’s funds if those funds had been misused by her/his fiduciary.³⁰ However, this was corrected when Congress passed the Veterans Benefits Improvement Act, and the VBA now reissues benefits if they were misused and the VBA was found negligent in its monitoring of the fiduciary.³¹ Unfortunately, it is also the VBA that makes the determination of negligence, raising concerns about conflict of interest.

Clinicians may contact their VBA Regional Office to request an evaluation of a veteran’s situation if they have concerns about the fiduciary arrangement, either based on their own observations or on complaints received from the veteran. A field examiner is required to investigate concerns about misuse of veteran funds.¹¹

Fiduciary Oversight

The SSA has been criticized for its lack of close oversight of representative payees. In a recent report on the SSA representative payee program, the evaluators noted, “More broadly, the [SSA] program does not require careful accounting and reporting by payees, nor does the current system appear to be useful in detecting possible misuse of benefits by payees.”⁹

In contrast, the VBA fiduciary program has designated field examiners who play a role in the initial competence determination, fiduciary arrangement and selection, and oversight of the fiduciary arrangement. Once the VBA has been alerted that a veteran may require a fiduciary, a field examiner is dispatched to observe the individual’s living conditions, fund requirements, and capacity to handle benefits.11 After the initial contact, the field examiner makes a recommendation of the appropriate financial arrangement and prospective fiduciary.

Regardless of the type of fiduciary arrangement in place, the field examiner makes periodic follow-up visits to the beneficiary based on the individual situation. The minimum frequency of required contacts is at least once per year.¹¹ However, visits can occur as infrequently as 36 months in particular situations (Table). During follow-up visits, the field examiner evaluates the beneficiary’s welfare, the performance of the fiduciary, the use of funds, the competency of the beneficiary, and the necessity to continue the fiduciary relationship.¹¹

Although detailed oversight of fiduciaries is technically required, there are a limited number of field examiners to provide that oversight. In 2006, caseloads for field examiners ranged from 132 to 592 cases per employee.Recent auditing showed that programs with the highest staff case loads also had the highest number of deficiencies, suggesting that some field examiners may be unable to provide sufficient oversight to all their clients.¹⁶ The effectiveness of field examiners may suffer when they are responsible for very high numbers of veterans.¹⁶ Improving oversight of fiduciaries is a stated goal of the VA Office of Inspector General, although increasing the number of field examiners is not mentioned as a means to achieve this goal.³²

The SSA does not systematically assess whether a beneficiary is able to resume control over his or her finances. Responsibility lies with the beneficiary to initiate a request to become his/her own payee by demonstrating ability to care for self by means of any evidence, including providing a doctor’s statement or an official copy of a court order. The SSA further cautions beneficiaries who are considering submitting proof of their capability to manage their money as a result of improvement in their condition that, “If SSA believes your condition has improved to the point that you no longer need a payee, we may reevaluate your eligibility for disability payments.”³³ This may discourage beneficiaries from attempting to rescind the payeeship, as they potentially risk losing their disability benefits as well.

In contrast, VBA requires regular assessment by a field examiner for continuation of the fiduciary arrangement.¹¹ It is possible to rescind this arrangement if the veteran is found to be competent to handle his/her own funds, understands his/her financial situation, is applying funds to his/her needs appropriately, and would not benefit from further VBA supervision. Additionally, a trial period of limited fund disbursement for 3 to 5 months can be recommended in order to determine how well the veteran manages his/her money. This is commonly done when there are substantial amounts of money being held in trust for the veteran.¹¹

Trustee Effectiveness

Considerable research has examined the effectiveness of the SSA representative payee program as well as potential benefits and risks to the payee. For example, in beneficiaries with psychiatric disabilities, payees can be instrumental in promoting residential stability, basic health care, and psychiatric treatment engagement.⁶ In addition, representative payeeship has been shown to be associated with reduced hospitalization, victimization, and homelessness.^34,35 Finally, research has found better treatment adherence among consumers with payees compared with those without.⁵

On the other hand, risks noted in some studies suggest payeeship may be used coercively, thwart self-determination, and increase conflict.²⁵ Additionally, payeeship was not associated with a differential reduction in substance use compared with SSA beneficiaries without a payee, nor did it have any effect on clinical outcomes.^36-38 These studies may or may not be applicable to the veteran population: Few studies of SSA payeeship include veterans, and there are no studies examining the effectiveness of the VBA fiduciary program exclusively.

Conrad and colleagues reported on a randomized trial of a community trustee and case management program integrated with psychiatric care provided by the VHA.⁴ Twelve-month outcomes favored the use of the more integrated program, which showed a reduction in substance use, money mismanagement, and days homeless, along with an increased quality of life. However, the study did not distinguish between funding source (VBA, SSA, or both) and trustee status (SSA representative payee or VBA fiduciary). A voluntary program in which veterans worked with money managers who helped them manage funds and held their check books/bank cards also resulted in some improvement in substance use and money management, but this program did not involve either the formal SSA payee or VBA fiduciary systems.³⁹

Although there is a perception that fiduciaries are unwanted impositions on individuals with mental illness, many veterans who have difficulty managing their money seem to want assistance. In one study, nearly 75% of the veterans interviewed agreed with the statement, “Someone who would give me advice around my funds would be helpful to me.” Thirty-four percent agreed with the statement, “Someone who would receive my check and control my funds would be helpful to me,” and 22% reported that they thought a money manager would have helped prevent their hospitalization.⁴⁰ Additionally, veterans who had payees reported generally high levels of satisfaction and trust with their payee, as well as low feelings of coercion.¹⁵ Although similarities with the SSA system may allow some generalizing of findings across SSA and VBA, significant differences in how the programs are administered and the amount of money at stake justify independent evaluation of the VBA fiduciary program.

Conclusion

Veterans with psychiatric disabilities who are deemed incompetent to manage their finances are typically assigned a trustee to disperse disability funds. Both the VBA and SSA provide disability compensation and have a process for providing formal money management services for those determined to be financially incapacitated. However, these 2 federal programs are complex and have many differences.

Clinicians may come into contact with these programs when referring a veteran for services or when a veteran complains about their existing services. The decision of when to refer a veteran for evaluation for a fiduciary is challenging. Once a veteran is referred to the VBA rating agency, the VBA completes a more formalized evaluation to determine whether the beneficiary meets the criteria for a fiduciary. The VBA also has outlined more rigorous ongoing assessment requirements than has the SSA and has designated field examiners to complete these; however, in practice, field examiner heavy case-loads may make it more challenging for the VBA to achieve this rigor.

The VBA provides a formal means of evaluating a veteran’s ability to manage his or her funds through Supervised Direct Payment, which can allow a veteran to demonstrate the ability to manage money and thus end a fiduciary relationship that is no longer needed. In contrast, SSA has no formal evaluation program. Additionally, requesting an end to a payeeship for SSA funds can potentially trigger the loss of benefits, discouraging recipients from ever managing their money independently again.

Ultimately, assigning a fiduciary involves a complex decision weighing values of autonomy (veteran’s freedom to manage his or her own money) and social welfare (veteran’s safety if genuinely vulnerable to financial exploitation).

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The Congressionally Directed Medical Research Programs (CDMRP), an office within the U.S. Army Medical Research and Materiel Command, has executed funding for research in 18 biomedical programs (Table). These programs touch the lives of service members, veterans, family members, and the general public. A partnership with the military, government, scientific community, survivors, patients, and their family members brings together spheres of stakeholders that typically might not otherwise collaborate and enables the CDMRP to complement other sources of research funding while focusing on research most directly relevant to each disease, condition, or injury.

The CDMRP began in 1992 when the breast cancer advocacy community launched a grassroots effort to raise public awareness of the need for increased federal funding for breast cancer research. These advocates requested from Congress additional research funding to support innovative, high-impact research where the government was willing to take a risk to leapfrog the field forward. In response, Congress added funds to the DoD budget for breast cancer research, and the Breast Cancer Research Program (BCRP) was established with a fiscal year (FY) 1992 congressional appropriation.

The CDMRP brought a flexible, efficient way of managing research and was enthusiastic about the advocates’ desire to have a voice in setting research priorities. Since the initial appropriation, advocates representing breast cancer, ovarian cancer, prostate cancer, neurofibromatosis, and a wide range of other diseases, conditions, and injuries have demonstrated the need to Congress to appropriate funds for their respective causes.

There are several features that differentiate the CDMRP from other funding agencies. The most significant differences follow:

1. The CDMRP funds innovative  high-risk/high-gain research focused on the disease, condition, or injury as specified in congressional language;
2. Unlike other agencies, the CDMRP integrates patients, survivors, family members, or caregivers of a person living with the disease, condition, or injury into every aspect of the program management cycle; and
3. Every year the CDMRP programs develop a new investment strategy and release award mechanisms based on the most critical needs and scientific gaps.

These features ensure that the research funded in each program is relevant and has a high potential for impact in the patient community. 

Funding and Science Management

Funding for the programs managed by the CDMRP does not appear as part of the DoD core funding in the president’s budget; instead, Congress assesses the needs of its constituents and adds funding to the DoD budget, designated specifically to meet those needs on an annual basis. Management of the CDMRP is funded entirely out of the annual appropriation, and there is no financial burden to the DoD. Unlike other federally funded agencies that receive funding in the president’s budget every FY, each CDMRP program develops an investment strategy based on a single yearly congressional appropriation.

Full project funding is obligated at the start from the single FY appropriation, ensuring multiyear research projects are not at funding risk. This method is in contrast to other agencies, which fund projects in budget years and may fund only a percentage of previously committed levels or cut the length of time for funding, depending on varying budget year funding policies.

Each CDMRP research program is managed by a multidisciplinary team and includes an external advisory board composed of world-renowned expert scientists, clinicians, and survivors from the DoD, National Institutes of Health (NIH), Centers for Disease Control and Prevention, VA, as well as academia and industry. Each research program has a vision/mission that is focused on ending or curing that disease, condition, or injury, ameliorating its consequences, or having a major impact on the quality of life of its survivors. Establishing a vision is the first major milestone in program execution, which enables each program to develop its individual investment strategy.

When establishing the investment strategy, each program evaluates the funding landscape by comparing research portfolios and award mechanisms within the organization as well as with other federal and nonfederal agencies. For some of the CDMRP-managed programs, such as the Peer Reviewed Orthopaedic Research Program, the Spinal Cord Injury Research Program, and the Psychological Health/Traumatic Brain Injury Research Program, topic areas are aligned with the Defense Health Program (DHP) Defense Medical Research and Development Program (DMRDP). The appropriate DHP Joint Program Committee provides guidance on military-relevant research priorities and uses oversight of all core and congressional special interest research efforts across the DoD services to complement and leverage projects with CDMRP funding.

Establishment of each program’s vision and investment strategy leads to the development of Program Announcements (PAs), which describe the intent of each award mechanism in order to solicit research applications aimed at making a significant and nonincremental impact. The PAs for each program as well as links to application submission are made available on the CDMRP webpage (http://cdmrp.army.mil/funding/prgdefault.shtml).

Emphasized in CDMRP research opportunities are the specific needs of its advocacy communities. The CDMRP recognizes the value of firsthand experience with each of the targeted diseases, conditions, and injuries and has been a leader in integrating consumers (defined as a patient, survivor, family member, or caregiver of a person living with the disease, condition, or injury) into every aspect of a program’s execution. The value of consumer involvement is derived from each individual’s firsthand experience. This approach adds a perspective, passion, and sense of urgency, which ensures that the human dimension is incorporated in each program’s policy, investment strategy, and research focus. Consumers vote side by side with scientists and clinicians on advisory boards for each of the programs, and they have since the inception of the CDMRP.

Each research application must have an impact statement describing how the proposed research, if successful, will transform an aspect of the understanding, prevention, detection, and/or treatment of the respective program area; ie, have an impact on the consumer community. The impact of the proposed research is a critical determinant of the funding recommendation.

Each research program’s investment strategy and associated award mechanisms provide the framework and direction necessary to most effectively invest the congressional appropriation. Operationally, the CDMRP monitors for potentially similar approaches in research at many milestones in its science management model to ensure that the CDMRP-funded research is synergistic and harmonizing, not duplicative of other federal and nonfederal sources of funding.

At the time of proposal submission, a comprehensive list of current and pending funding support for the principal investigator (PI) and all key personnel must be submitted. During the review process, peer reviewers who have extensive knowledge of the subject consult the pending and existing support documentation to ensure the research is complementary to what is already being investigated in the field. This ensures that the proposals recommended for funding are synergistic and contribute to the substantiation of data relevant to clinical decisions. After a project has been recommended for funding, the CDMRP scientific officers (ie, scientific technical advisors) check all available sources to ensure that the project to be funded is complementary to ongoing research. Last, during the period of performance, details about funding applied for and/or new funding obtained is required in the annual technical progress reports. Through this science management model, CDMRP ensures that funded research is complementary and able to innovatively fill gaps in the biomedical research pipeline. 

Biomedical Funding

Most diseases, conditions, and injuries are complex, and finding a cure for them requires problem solving from multiple disciplines and approaches as well as validation of research results. Prior to the fielding and clinical application of knowledge and products, research spans a continuum from discovery to clinical trials. As shown in Figure 1, novel award mechanisms developed by the CDMRP programs facilitate the success of this research continuum and innovatively complement traditional research funding agencies, such as the NIH. The intent of each award mechanism is designed to solicit research proposals focused on the needs of the patient community and how they relate to the vision of the program.

The Research Continuum

Some CDMRP programs provide support along the entire continuum of research. Other programs, with less mature research fields, focus on funding more basic research. There are also CDMRP programs that place emphasis on clinical and advanced development research. Each program’s annual investment strategy and choice of award mechanisms is based on the needs of the patient and research communities, gaps in research, and other barriers to progress in curing, rehabilitating, or eliminating the disease, condition, or injury.

Fostering the Development of Ideas

Since its inception in 1992, the DoD BCRP has sought to fund innovative, ground-breaking research by encouraging “outside the box” thinking and fostering creative collaborations that have the potential to have a high impact toward the eradication of this disease. The BCRP has a proven history of developing novel award mechanisms to foster new approaches in research. For example, the Idea Award was developed in the initial years of the BCRP to support novel research with little or no preliminary data that could ultimately lead to a critical discovery or advancement in breast cancer research. At that time, such high-risk, but potentially high-reward research was determined to be significantly underfunded by existing agencies and was thus identified as a gap in funding. Several major advancements in breast cancer, including the development of trastuzumab, testing of sentinel lymph node biopsy, and discovery of BRCA2 and PTEN gene mutations, were supported in part with funding from the BCRP.

The Idea Award mechanism has been adopted by other CDMRP programs to introduce new paradigms, challenge current paradigms, or look at existing problems from new perspectives in other disease- or condition-focused research. To support the exploration of highly innovative, untested concepts or theories, the BCRP and the Prostate Cancer Research Program (PCRP) developed other award mechanisms known as the Concept Award and the Exploration-Hypothesis Development Award, respectively.

These award mechanisms supporting early concepts and ideas provided complementary and multiple approaches to the most traditional and well-known grant program: the NIH R01 (Research Project Grant Program). In general, an R01 award requires preliminary data, supports the next logical or incremental step, is knowledge focused, has no specific program requirements, and is not focused on a single disease or condition. One of the hallmarks of this type of early idea award was that the preliminary data could then be used to submit a research proposal to an NIH-like R01 award mechanism.

A recent survey of Idea Awards offered by the BCRP from 2006 to 2011 indicated that > 40% of awardees successfully obtained other sources of funding, more than half coming from the NIH. The NIH Common Fund, established in 2006, led to the creation of a high-risk/high-reward program with the Transformative Research Award, which is focused on innovation and challenging existing paradigms, unlike the R01 mechanism. This indicates that although other agencies have developed award mechanisms supporting pilot and feasibility studies (eg, R21 awards–Exploratory/Developmental Research Grant) and high-risk/high-reward research (eg, Transformative Research Award), CDMRP’s creation of these mechanisms has transformed biomedical research and remains an important vehicle in the idea development funding pipeline.

Facilitating Collaborative Partnerships

Many funding agencies have recognized that research collaborations are important for investigating the increasing complexity of disease, conditions, and injuries. The CDMRP-managed BCRP, Ovarian Cancer Research Program(OCRP), and PCRP created collaborative award mechanisms (eg, the Synergistic Idea Award) in which one research project is submitted by multiple investigators whose combined resources are leveraged and their expertise synergized to better address a research question. A unique aspect of these collaborative award mechanisms is that all the investigators (appropriately called partners) receive an individual award, not a subaward, incentivizing investigators to develop partnerships that might not otherwise be formed.

Rewarding Science Teams

Recognizing that research collaborations are important in investigating the increasing complexity of disease and injuries, several of the CDMRP research programs have developed team science award mechanisms. Using the Manhattan Project as a successful example of bringing together the most talented scientists to conduct research and development simultaneously to quickly solve a common problem, the CDMRP Neurofibromatosis Research Program developed a consortium award mechanism to establish consortia of exceptional investigators to conceive, develop, and conduct collaborative pilot, phase 1, and phase 2 clinical evaluations. To the authors’ knowledge, this is the largest dedicated effort in neurofibromatosis research to date. This mechanism has been adopted by several other CDMRP programs to focus on multidisciplinary approaches with investigators from multiple institutions, to address high-impact research ideas or unmet needs.

The PCRP used this framework to support the infrastructure necessary for a consortium consisting of 13 major U.S. cancer centers (Prostate Cancer Clinical Trials Consortium [PCCTC]) to rapidly execute early-phase clinical trials of therapeutic agents. The PCCTC consortium now conducts about 25% of all early-phase U.S. clinical trials for prostate cancer and has dramatically impacted the speed at which new options for therapy are available to patients. For example, the drug abiraterone acetate was brought through clinical testing in half the time typically required and represents a new option in the treatment of metastatic prostate cancer. In addition, the PCCTC also brought MDV3100, another therapy for advanced disease, rapidly through all phases of clinical testing.

The Lung Cancer Research Program (LCRP) used the consortium award mechanism to create a unique, early detection clinical consortium that includes 4 academic organizations, 4 military treatment facilities, and 7 VA facilities to focus on characterizing, developing, and/or improving early detection modalities for lung cancer. The BCRP has recently introduced the Multi-Team and Transformative Vision Award mechanisms to support innovative teams of scientists, clinicians, and breast cancer survivors, patients, family members, and persons affected by and/or at risk of breast cancer to work together toward making breakthroughs that may have a revolutionary impact in breast cancer prevention or treatment.

Collectively, these team science mechanisms facilitate the exchange of ideas and bring together individuals with special knowledge and skills needed to sustain cross-fertilization. Such collaborations can unravel complex phenomena and significantly accelerate progress, thus shrinking the pipeline of traditional reductionist approaches to novel discoveries and outcomes.

Encouraging Visionary Individuals

The BCRP has developed a series of award mechanisms that seek to identify and fund individuals with potential for, or a history of, extraordinary innovation and creativity at varying career stages, from predoctoral training through established investigators. The BCRP Era of Hope Scholar (EOHS) Award supports early-career researchers who are the best and brightest in their field(s) and therefore have a high potential for innovation in breast cancer research.

While demonstrated experience in forming effective partnerships and collaborations is a requirement, experience in breast cancer is not, encouraging applicants to challenge current dogma and look beyond tradition and convention already established in the field. The unique intent of this mechanism changed the way innovative science is reviewed, since the individual young investigator, rather than the project, is the central feature of this award. The BCRP Innovator Award supports established, visionary individuals, who have demonstrated creativity, innovative work, and leadership in any field. This mechanism also broke new ground by providing individuals with the funding and freedom to pursue their most novel, visionary, high-risk ideas that could ultimately lead to ending disease.

CDMRP programs uniquely address clinical/translational research by focusing on critical needs and specific gaps within a particular disease, condition, or injury rather than a broad investment in general translational research.

Dr. Greg Hannon of Cold Spring Harbor Laboratory received a BCRP New Investigator Award in FY 1995 and was one of the first recipients of the Innovator Award in FY 2001, making scientific breakthroughs in understanding the mechanisms of RNA interference. He is currently applying these discoveries to the identification of new therapeutic targets for breast cancer. By funding such individuals at different stages of their research career, the BCRP has provided the foundation for many of today’s leading breast cancer researchers. Moreover, innovative researchers, such as Dr. Hannon, have moved from other fields into the breast cancer field as a result of BCRP funding.

Another investigator who transitioned into distinct disease fields as a result of CDMRP funding is. From 2002 to 2007, Dr. Chinnaiyan received funding from the PCRP and made a paradigm-shifting discovery and identified multiple recurrent gene fusions in human prostate cancers. Dr. Chinnaiyan had not worked in prostate cancer before embarking on his groundbreaking studies and is now a leader in that field. In 2007, Dr. Chinnaiyan had a vision that characterization of recurrent gene fusions within human breast cancers could lead to the identification of new biomarkers and therapeutic targets for this disease. He was awarded the BCRP EOHS Award and went on to make an exciting discovery of 2 novel recurrent and actionable gene fusions in breast cancer, the results of which were published in 2011.¹

Within the CDMRP, the OCRP has adopted the Innovator Award mechanism to attract visionary individuals from any field of research to focus their creativity, innovation, and leadership on ovarian cancer research. Through the use of this mechanism, this program has been successful in funding several noncancer scientists, including engineers, to help solve biomedical problems in the field. Six years after the initial release by CDMRP, the NIH introduced the Director’s New Innovator Award and the Pioneer Award. This CDMRP novel mechanism seems to have transformed funding strategies by encouraging innovative individuals to provide solutions to the toughest medical challenges.

Translation of Science to the Clinic

A critical component in the research continuum is the translation of promising lead agents to clinical trials. The CDMRP programs uniquely address clinical/translational research by focusing on critical needs and specific gaps within a particular disease, condition, or injury rather than a broad investment in general translational research. For example, the PCRP Laboratory-Clinical Transition Award mechanism supports product-driven preclinical studies of promising lead agents or medical devices that have the potential to revolutionize prostate cancer clinical care. For this award mechanism, lead agent development projects generate preclinical data to be used for an FDA investigational device exemption application and/or current Good Manufacturing Practice production of a medical device.

Preclinical Awards

The CDMRP Amyotrophic Lateral Sclerosis (ALS) Research Program focuses on the preclinical development of new therapies using the Therapeutic Development Award mechanism, which is product-driven and supports preclinical assessment of therapeutics, and the Therapeutic Idea Award mechanism, which promotes new ideas for novel therapeutics. This preclinical focus on therapeutic development compliments that of the National Institute of Neurological Disorders and Stroke (NINDS), the major NIH funder of ALS research, which concentrates primarily on funding basic and clinical research.

The CDMRP Gulf War Illness (GWI) Research Program created a unique award mechanism, the Innovative Treatment Evaluation Award, to support the early systematic evaluation of innovative treatment interventions that can provide proof of principle data for broader efficacy trials. The only other major funder of GWI research is the VA Office of Research and Development, which relies on the individual research interests of its intramural investigators.

In support of the 2012 Presidential Executive Order, the DoD and VA devoted > $100 million to fund 2 new consortia aimed at improving diagnosis and treatment of mild traumatic brain injury and posttraumatic stress disorder (PTSD). The Consortium to Alleviate PTSD and the Chronic Effects of Neurotrauma Consortium are jointly managed by the VA and CDMRP on behalf of the DoD and bring together leading scientists and clinicians devoted to the health and welfare of our nation’s service members and veterans. Consortium efforts are expected to have an emphasis toward translational/clinical work.

The OCRP developed the Translational Research Partnership Award mechanism to move an observation from the laboratory into clinical application for ovarian cancer. The novelty of this award is that one partner in the collaboration is required to be a laboratory scientist and the other is required to be a clinician. This award mechanism has been adopted by several other CDMRP research programs; a comparable mechanism has not been offered by other funding agencies.

The Peer Reviewed Orthopaedic Research Program (PRORP) is the only major funding source dedicated to research in combat and combat-related orthopedic injuries, the largest source of long-term morbidity for injured military personnel. The PRORP crafts investment strategies to address these challenges using award mechanisms such as the Technology Development, Translational Partnership, and the Clinical Trial awards, which emphasize clinical and mature translational research. While industry, including pharmaceutical, biotechnology, and medical device firms, remains the largest funder of clinical trial research, the CDMRP’s niche in this arena is the ability to encourage preventive or therapeutic interventions that are in line with the priorities of the communities affected by the disease.

Training and Career Development

Training the next generation of scientists in both basic and clinical research is instrumental for the advancement of biomedical research. The career development pipeline traditionally proceeds from predoctoral through postdoctoral training to the new or junior faculty level investigator (Figure 2). The CDMRP offers pre- and postdoctoral training award mechanisms in which the research is disease- or condition-specific, and the trainee is named as the principal investigator, thereby providing the trainee with his or her first source of research funding.

The BCRP Postdoctoral Award mechanism is unique in that it provides funding for the research in addition to stipend support. The trainee is expected to have discretion over management of the award, thus providing valuable training as a researcher. In addition to recent doctoral graduates, many CDMRP training mechanisms support recent medical graduates and encourage the training of physician-scientists. For example, the Prostate Cancer Research Program (PCRP) supports the training of physicians with clinical duties for a career in prostate cancer research through the physician Research Training Award. At the time of application, the PI must be in the last year of medical residency, must designate a mentor with an established research program, and institutions must provide at least 40% protection of the PI’s time for research.

The PRORP offers a career development award in which active-duty military researchers, physical therapists, occupational therapists, or physician-scientists with < 8 years of clinical or postdoctoral research experience (excluding clinical residency or medical fellowship training) are eligible to apply. The LCRP has offered a promising clinician research award supporting the training of MDs or MD/PhDs with clinical duties and/or responsibilities that are within 5 years of a professional appointment. Each of these physician training mechanisms not only provide support at an early career stage to investigators at DoD or other clinical sites, but also enable physicians to have a career at the forefront of research and clinical practice.

In 2002, the NIH observed that the percentage of competing NIH grants awarded to investigators aged ≤ 35 years declined from 23% in 1980 to < 4% in 2002. To support these young investigators, the NIH introduced the Pathway to Independence Award mechanism, providing several years of mentored support for promising postdoctoral scientists followed by several years of independent support. More recently, the NIH has focused on new investigators by offering more R01 awards to this group. Because securing early concept funding helps pave the way for the larger R01 grant application, increasing the support for early investigators is important for creating a critical threshold of scientists with exceptional talent.

The CDMRP New Investigator Award programs are intended to support scientists in the early stages of their careers through the continued development of promising independent investigators and/or the transition of established investigators. Each of the CDMRP programs has developed variations of the New Investigator Award to meet the goals of the disease- or condition-specific program. The OCRP Ovarian Cancer Academy, which includes both medical doctors and PhD scientists, is one of the more recent and innovative New Investigator Award mechanisms. This academy is an interactive virtual research and training platform that provides intensive mentoring, national networking, and a peer group for junior faculty in a collaborative and interactive environment. Taken together, the CDMRP programs offer unique award mechanisms to support researchers at critical junctures in their careers. The unique qualities and competitiveness of the CDMRP’s disease/condition-focused training awards have supported the early-career foundation for many of today’s leading researchers.

Conclusions

Congressionally Directed Medical Research Programs complement other federal and nonfederal sources of biomedical research funding and fill important research gaps through an evaluation of the funding landscape, identification of research gaps, and development of novel award mechanisms. The integration of survivors, patients, and their family members ensures that every aspect of the program management cycle balances scientific expertise with human perspective and has high impact on the patient community.

As new needs emerge, each research program designs an investment strategy to target areas most critically in need. The subsequent release of novel award mechanisms focuses research and enables an acceleration of science and/or leading researchers to the patient’s bedside. The CDMRP-funded discoveries have contributed to the development of new therapeutics, new diagnostics, and to changes in the standard of care exemplifying significant clinical impact and the innovative nature of these Congressional Special Interest Medical Research Programs.

To learn more about CDMRP or to receive funding notifications by e-mail, please visit http://cdmrp.army.mil.

Acknowledgments
The authors gratefully note the CDMRP Program Evaluation Steering Committee for critical review of the manuscript. Also acknowledged are CDMRP staff at large and Dr. Lisa Kinnard for support in this project.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The Congressionally Directed Medical Research Programs (CDMRP), an office within the U.S. Army Medical Research and Materiel Command, has executed funding for research in 18 biomedical programs (Table). These programs touch the lives of service members, veterans, family members, and the general public. A partnership with the military, government, scientific community, survivors, patients, and their family members brings together spheres of stakeholders that typically might not otherwise collaborate and enables the CDMRP to complement other sources of research funding while focusing on research most directly relevant to each disease, condition, or injury.

The CDMRP began in 1992 when the breast cancer advocacy community launched a grassroots effort to raise public awareness of the need for increased federal funding for breast cancer research. These advocates requested from Congress additional research funding to support innovative, high-impact research where the government was willing to take a risk to leapfrog the field forward. In response, Congress added funds to the DoD budget for breast cancer research, and the Breast Cancer Research Program (BCRP) was established with a fiscal year (FY) 1992 congressional appropriation.

The CDMRP brought a flexible, efficient way of managing research and was enthusiastic about the advocates’ desire to have a voice in setting research priorities. Since the initial appropriation, advocates representing breast cancer, ovarian cancer, prostate cancer, neurofibromatosis, and a wide range of other diseases, conditions, and injuries have demonstrated the need to Congress to appropriate funds for their respective causes.

There are several features that differentiate the CDMRP from other funding agencies. The most significant differences follow:

1. The CDMRP funds innovative  high-risk/high-gain research focused on the disease, condition, or injury as specified in congressional language;
2. Unlike other agencies, the CDMRP integrates patients, survivors, family members, or caregivers of a person living with the disease, condition, or injury into every aspect of the program management cycle; and
3. Every year the CDMRP programs develop a new investment strategy and release award mechanisms based on the most critical needs and scientific gaps.

These features ensure that the research funded in each program is relevant and has a high potential for impact in the patient community. 

Funding and Science Management

Funding for the programs managed by the CDMRP does not appear as part of the DoD core funding in the president’s budget; instead, Congress assesses the needs of its constituents and adds funding to the DoD budget, designated specifically to meet those needs on an annual basis. Management of the CDMRP is funded entirely out of the annual appropriation, and there is no financial burden to the DoD. Unlike other federally funded agencies that receive funding in the president’s budget every FY, each CDMRP program develops an investment strategy based on a single yearly congressional appropriation.

Full project funding is obligated at the start from the single FY appropriation, ensuring multiyear research projects are not at funding risk. This method is in contrast to other agencies, which fund projects in budget years and may fund only a percentage of previously committed levels or cut the length of time for funding, depending on varying budget year funding policies.

Each CDMRP research program is managed by a multidisciplinary team and includes an external advisory board composed of world-renowned expert scientists, clinicians, and survivors from the DoD, National Institutes of Health (NIH), Centers for Disease Control and Prevention, VA, as well as academia and industry. Each research program has a vision/mission that is focused on ending or curing that disease, condition, or injury, ameliorating its consequences, or having a major impact on the quality of life of its survivors. Establishing a vision is the first major milestone in program execution, which enables each program to develop its individual investment strategy.

When establishing the investment strategy, each program evaluates the funding landscape by comparing research portfolios and award mechanisms within the organization as well as with other federal and nonfederal agencies. For some of the CDMRP-managed programs, such as the Peer Reviewed Orthopaedic Research Program, the Spinal Cord Injury Research Program, and the Psychological Health/Traumatic Brain Injury Research Program, topic areas are aligned with the Defense Health Program (DHP) Defense Medical Research and Development Program (DMRDP). The appropriate DHP Joint Program Committee provides guidance on military-relevant research priorities and uses oversight of all core and congressional special interest research efforts across the DoD services to complement and leverage projects with CDMRP funding.

Establishment of each program’s vision and investment strategy leads to the development of Program Announcements (PAs), which describe the intent of each award mechanism in order to solicit research applications aimed at making a significant and nonincremental impact. The PAs for each program as well as links to application submission are made available on the CDMRP webpage (http://cdmrp.army.mil/funding/prgdefault.shtml).

Emphasized in CDMRP research opportunities are the specific needs of its advocacy communities. The CDMRP recognizes the value of firsthand experience with each of the targeted diseases, conditions, and injuries and has been a leader in integrating consumers (defined as a patient, survivor, family member, or caregiver of a person living with the disease, condition, or injury) into every aspect of a program’s execution. The value of consumer involvement is derived from each individual’s firsthand experience. This approach adds a perspective, passion, and sense of urgency, which ensures that the human dimension is incorporated in each program’s policy, investment strategy, and research focus. Consumers vote side by side with scientists and clinicians on advisory boards for each of the programs, and they have since the inception of the CDMRP.

Each research application must have an impact statement describing how the proposed research, if successful, will transform an aspect of the understanding, prevention, detection, and/or treatment of the respective program area; ie, have an impact on the consumer community. The impact of the proposed research is a critical determinant of the funding recommendation.

Each research program’s investment strategy and associated award mechanisms provide the framework and direction necessary to most effectively invest the congressional appropriation. Operationally, the CDMRP monitors for potentially similar approaches in research at many milestones in its science management model to ensure that the CDMRP-funded research is synergistic and harmonizing, not duplicative of other federal and nonfederal sources of funding.

At the time of proposal submission, a comprehensive list of current and pending funding support for the principal investigator (PI) and all key personnel must be submitted. During the review process, peer reviewers who have extensive knowledge of the subject consult the pending and existing support documentation to ensure the research is complementary to what is already being investigated in the field. This ensures that the proposals recommended for funding are synergistic and contribute to the substantiation of data relevant to clinical decisions. After a project has been recommended for funding, the CDMRP scientific officers (ie, scientific technical advisors) check all available sources to ensure that the project to be funded is complementary to ongoing research. Last, during the period of performance, details about funding applied for and/or new funding obtained is required in the annual technical progress reports. Through this science management model, CDMRP ensures that funded research is complementary and able to innovatively fill gaps in the biomedical research pipeline. 

Biomedical Funding

Most diseases, conditions, and injuries are complex, and finding a cure for them requires problem solving from multiple disciplines and approaches as well as validation of research results. Prior to the fielding and clinical application of knowledge and products, research spans a continuum from discovery to clinical trials. As shown in Figure 1, novel award mechanisms developed by the CDMRP programs facilitate the success of this research continuum and innovatively complement traditional research funding agencies, such as the NIH. The intent of each award mechanism is designed to solicit research proposals focused on the needs of the patient community and how they relate to the vision of the program.

The Research Continuum

Some CDMRP programs provide support along the entire continuum of research. Other programs, with less mature research fields, focus on funding more basic research. There are also CDMRP programs that place emphasis on clinical and advanced development research. Each program’s annual investment strategy and choice of award mechanisms is based on the needs of the patient and research communities, gaps in research, and other barriers to progress in curing, rehabilitating, or eliminating the disease, condition, or injury.

Fostering the Development of Ideas

Since its inception in 1992, the DoD BCRP has sought to fund innovative, ground-breaking research by encouraging “outside the box” thinking and fostering creative collaborations that have the potential to have a high impact toward the eradication of this disease. The BCRP has a proven history of developing novel award mechanisms to foster new approaches in research. For example, the Idea Award was developed in the initial years of the BCRP to support novel research with little or no preliminary data that could ultimately lead to a critical discovery or advancement in breast cancer research. At that time, such high-risk, but potentially high-reward research was determined to be significantly underfunded by existing agencies and was thus identified as a gap in funding. Several major advancements in breast cancer, including the development of trastuzumab, testing of sentinel lymph node biopsy, and discovery of BRCA2 and PTEN gene mutations, were supported in part with funding from the BCRP.

The Idea Award mechanism has been adopted by other CDMRP programs to introduce new paradigms, challenge current paradigms, or look at existing problems from new perspectives in other disease- or condition-focused research. To support the exploration of highly innovative, untested concepts or theories, the BCRP and the Prostate Cancer Research Program (PCRP) developed other award mechanisms known as the Concept Award and the Exploration-Hypothesis Development Award, respectively.

These award mechanisms supporting early concepts and ideas provided complementary and multiple approaches to the most traditional and well-known grant program: the NIH R01 (Research Project Grant Program). In general, an R01 award requires preliminary data, supports the next logical or incremental step, is knowledge focused, has no specific program requirements, and is not focused on a single disease or condition. One of the hallmarks of this type of early idea award was that the preliminary data could then be used to submit a research proposal to an NIH-like R01 award mechanism.

A recent survey of Idea Awards offered by the BCRP from 2006 to 2011 indicated that > 40% of awardees successfully obtained other sources of funding, more than half coming from the NIH. The NIH Common Fund, established in 2006, led to the creation of a high-risk/high-reward program with the Transformative Research Award, which is focused on innovation and challenging existing paradigms, unlike the R01 mechanism. This indicates that although other agencies have developed award mechanisms supporting pilot and feasibility studies (eg, R21 awards–Exploratory/Developmental Research Grant) and high-risk/high-reward research (eg, Transformative Research Award), CDMRP’s creation of these mechanisms has transformed biomedical research and remains an important vehicle in the idea development funding pipeline.

Facilitating Collaborative Partnerships

Many funding agencies have recognized that research collaborations are important for investigating the increasing complexity of disease, conditions, and injuries. The CDMRP-managed BCRP, Ovarian Cancer Research Program(OCRP), and PCRP created collaborative award mechanisms (eg, the Synergistic Idea Award) in which one research project is submitted by multiple investigators whose combined resources are leveraged and their expertise synergized to better address a research question. A unique aspect of these collaborative award mechanisms is that all the investigators (appropriately called partners) receive an individual award, not a subaward, incentivizing investigators to develop partnerships that might not otherwise be formed.

Rewarding Science Teams

Recognizing that research collaborations are important in investigating the increasing complexity of disease and injuries, several of the CDMRP research programs have developed team science award mechanisms. Using the Manhattan Project as a successful example of bringing together the most talented scientists to conduct research and development simultaneously to quickly solve a common problem, the CDMRP Neurofibromatosis Research Program developed a consortium award mechanism to establish consortia of exceptional investigators to conceive, develop, and conduct collaborative pilot, phase 1, and phase 2 clinical evaluations. To the authors’ knowledge, this is the largest dedicated effort in neurofibromatosis research to date. This mechanism has been adopted by several other CDMRP programs to focus on multidisciplinary approaches with investigators from multiple institutions, to address high-impact research ideas or unmet needs.

The PCRP used this framework to support the infrastructure necessary for a consortium consisting of 13 major U.S. cancer centers (Prostate Cancer Clinical Trials Consortium [PCCTC]) to rapidly execute early-phase clinical trials of therapeutic agents. The PCCTC consortium now conducts about 25% of all early-phase U.S. clinical trials for prostate cancer and has dramatically impacted the speed at which new options for therapy are available to patients. For example, the drug abiraterone acetate was brought through clinical testing in half the time typically required and represents a new option in the treatment of metastatic prostate cancer. In addition, the PCCTC also brought MDV3100, another therapy for advanced disease, rapidly through all phases of clinical testing.

The Lung Cancer Research Program (LCRP) used the consortium award mechanism to create a unique, early detection clinical consortium that includes 4 academic organizations, 4 military treatment facilities, and 7 VA facilities to focus on characterizing, developing, and/or improving early detection modalities for lung cancer. The BCRP has recently introduced the Multi-Team and Transformative Vision Award mechanisms to support innovative teams of scientists, clinicians, and breast cancer survivors, patients, family members, and persons affected by and/or at risk of breast cancer to work together toward making breakthroughs that may have a revolutionary impact in breast cancer prevention or treatment.

Collectively, these team science mechanisms facilitate the exchange of ideas and bring together individuals with special knowledge and skills needed to sustain cross-fertilization. Such collaborations can unravel complex phenomena and significantly accelerate progress, thus shrinking the pipeline of traditional reductionist approaches to novel discoveries and outcomes.

Encouraging Visionary Individuals

The BCRP has developed a series of award mechanisms that seek to identify and fund individuals with potential for, or a history of, extraordinary innovation and creativity at varying career stages, from predoctoral training through established investigators. The BCRP Era of Hope Scholar (EOHS) Award supports early-career researchers who are the best and brightest in their field(s) and therefore have a high potential for innovation in breast cancer research.

While demonstrated experience in forming effective partnerships and collaborations is a requirement, experience in breast cancer is not, encouraging applicants to challenge current dogma and look beyond tradition and convention already established in the field. The unique intent of this mechanism changed the way innovative science is reviewed, since the individual young investigator, rather than the project, is the central feature of this award. The BCRP Innovator Award supports established, visionary individuals, who have demonstrated creativity, innovative work, and leadership in any field. This mechanism also broke new ground by providing individuals with the funding and freedom to pursue their most novel, visionary, high-risk ideas that could ultimately lead to ending disease.

CDMRP programs uniquely address clinical/translational research by focusing on critical needs and specific gaps within a particular disease, condition, or injury rather than a broad investment in general translational research.

Dr. Greg Hannon of Cold Spring Harbor Laboratory received a BCRP New Investigator Award in FY 1995 and was one of the first recipients of the Innovator Award in FY 2001, making scientific breakthroughs in understanding the mechanisms of RNA interference. He is currently applying these discoveries to the identification of new therapeutic targets for breast cancer. By funding such individuals at different stages of their research career, the BCRP has provided the foundation for many of today’s leading breast cancer researchers. Moreover, innovative researchers, such as Dr. Hannon, have moved from other fields into the breast cancer field as a result of BCRP funding.

Another investigator who transitioned into distinct disease fields as a result of CDMRP funding is. From 2002 to 2007, Dr. Chinnaiyan received funding from the PCRP and made a paradigm-shifting discovery and identified multiple recurrent gene fusions in human prostate cancers. Dr. Chinnaiyan had not worked in prostate cancer before embarking on his groundbreaking studies and is now a leader in that field. In 2007, Dr. Chinnaiyan had a vision that characterization of recurrent gene fusions within human breast cancers could lead to the identification of new biomarkers and therapeutic targets for this disease. He was awarded the BCRP EOHS Award and went on to make an exciting discovery of 2 novel recurrent and actionable gene fusions in breast cancer, the results of which were published in 2011.¹

Within the CDMRP, the OCRP has adopted the Innovator Award mechanism to attract visionary individuals from any field of research to focus their creativity, innovation, and leadership on ovarian cancer research. Through the use of this mechanism, this program has been successful in funding several noncancer scientists, including engineers, to help solve biomedical problems in the field. Six years after the initial release by CDMRP, the NIH introduced the Director’s New Innovator Award and the Pioneer Award. This CDMRP novel mechanism seems to have transformed funding strategies by encouraging innovative individuals to provide solutions to the toughest medical challenges.

Translation of Science to the Clinic

A critical component in the research continuum is the translation of promising lead agents to clinical trials. The CDMRP programs uniquely address clinical/translational research by focusing on critical needs and specific gaps within a particular disease, condition, or injury rather than a broad investment in general translational research. For example, the PCRP Laboratory-Clinical Transition Award mechanism supports product-driven preclinical studies of promising lead agents or medical devices that have the potential to revolutionize prostate cancer clinical care. For this award mechanism, lead agent development projects generate preclinical data to be used for an FDA investigational device exemption application and/or current Good Manufacturing Practice production of a medical device.

Preclinical Awards

The CDMRP Amyotrophic Lateral Sclerosis (ALS) Research Program focuses on the preclinical development of new therapies using the Therapeutic Development Award mechanism, which is product-driven and supports preclinical assessment of therapeutics, and the Therapeutic Idea Award mechanism, which promotes new ideas for novel therapeutics. This preclinical focus on therapeutic development compliments that of the National Institute of Neurological Disorders and Stroke (NINDS), the major NIH funder of ALS research, which concentrates primarily on funding basic and clinical research.

The CDMRP Gulf War Illness (GWI) Research Program created a unique award mechanism, the Innovative Treatment Evaluation Award, to support the early systematic evaluation of innovative treatment interventions that can provide proof of principle data for broader efficacy trials. The only other major funder of GWI research is the VA Office of Research and Development, which relies on the individual research interests of its intramural investigators.

In support of the 2012 Presidential Executive Order, the DoD and VA devoted > $100 million to fund 2 new consortia aimed at improving diagnosis and treatment of mild traumatic brain injury and posttraumatic stress disorder (PTSD). The Consortium to Alleviate PTSD and the Chronic Effects of Neurotrauma Consortium are jointly managed by the VA and CDMRP on behalf of the DoD and bring together leading scientists and clinicians devoted to the health and welfare of our nation’s service members and veterans. Consortium efforts are expected to have an emphasis toward translational/clinical work.

The OCRP developed the Translational Research Partnership Award mechanism to move an observation from the laboratory into clinical application for ovarian cancer. The novelty of this award is that one partner in the collaboration is required to be a laboratory scientist and the other is required to be a clinician. This award mechanism has been adopted by several other CDMRP research programs; a comparable mechanism has not been offered by other funding agencies.

The Peer Reviewed Orthopaedic Research Program (PRORP) is the only major funding source dedicated to research in combat and combat-related orthopedic injuries, the largest source of long-term morbidity for injured military personnel. The PRORP crafts investment strategies to address these challenges using award mechanisms such as the Technology Development, Translational Partnership, and the Clinical Trial awards, which emphasize clinical and mature translational research. While industry, including pharmaceutical, biotechnology, and medical device firms, remains the largest funder of clinical trial research, the CDMRP’s niche in this arena is the ability to encourage preventive or therapeutic interventions that are in line with the priorities of the communities affected by the disease.

Training and Career Development

Training the next generation of scientists in both basic and clinical research is instrumental for the advancement of biomedical research. The career development pipeline traditionally proceeds from predoctoral through postdoctoral training to the new or junior faculty level investigator (Figure 2). The CDMRP offers pre- and postdoctoral training award mechanisms in which the research is disease- or condition-specific, and the trainee is named as the principal investigator, thereby providing the trainee with his or her first source of research funding.

The BCRP Postdoctoral Award mechanism is unique in that it provides funding for the research in addition to stipend support. The trainee is expected to have discretion over management of the award, thus providing valuable training as a researcher. In addition to recent doctoral graduates, many CDMRP training mechanisms support recent medical graduates and encourage the training of physician-scientists. For example, the Prostate Cancer Research Program (PCRP) supports the training of physicians with clinical duties for a career in prostate cancer research through the physician Research Training Award. At the time of application, the PI must be in the last year of medical residency, must designate a mentor with an established research program, and institutions must provide at least 40% protection of the PI’s time for research.

The PRORP offers a career development award in which active-duty military researchers, physical therapists, occupational therapists, or physician-scientists with < 8 years of clinical or postdoctoral research experience (excluding clinical residency or medical fellowship training) are eligible to apply. The LCRP has offered a promising clinician research award supporting the training of MDs or MD/PhDs with clinical duties and/or responsibilities that are within 5 years of a professional appointment. Each of these physician training mechanisms not only provide support at an early career stage to investigators at DoD or other clinical sites, but also enable physicians to have a career at the forefront of research and clinical practice.

In 2002, the NIH observed that the percentage of competing NIH grants awarded to investigators aged ≤ 35 years declined from 23% in 1980 to < 4% in 2002. To support these young investigators, the NIH introduced the Pathway to Independence Award mechanism, providing several years of mentored support for promising postdoctoral scientists followed by several years of independent support. More recently, the NIH has focused on new investigators by offering more R01 awards to this group. Because securing early concept funding helps pave the way for the larger R01 grant application, increasing the support for early investigators is important for creating a critical threshold of scientists with exceptional talent.

The CDMRP New Investigator Award programs are intended to support scientists in the early stages of their careers through the continued development of promising independent investigators and/or the transition of established investigators. Each of the CDMRP programs has developed variations of the New Investigator Award to meet the goals of the disease- or condition-specific program. The OCRP Ovarian Cancer Academy, which includes both medical doctors and PhD scientists, is one of the more recent and innovative New Investigator Award mechanisms. This academy is an interactive virtual research and training platform that provides intensive mentoring, national networking, and a peer group for junior faculty in a collaborative and interactive environment. Taken together, the CDMRP programs offer unique award mechanisms to support researchers at critical junctures in their careers. The unique qualities and competitiveness of the CDMRP’s disease/condition-focused training awards have supported the early-career foundation for many of today’s leading researchers.

Conclusions

Congressionally Directed Medical Research Programs complement other federal and nonfederal sources of biomedical research funding and fill important research gaps through an evaluation of the funding landscape, identification of research gaps, and development of novel award mechanisms. The integration of survivors, patients, and their family members ensures that every aspect of the program management cycle balances scientific expertise with human perspective and has high impact on the patient community.

As new needs emerge, each research program designs an investment strategy to target areas most critically in need. The subsequent release of novel award mechanisms focuses research and enables an acceleration of science and/or leading researchers to the patient’s bedside. The CDMRP-funded discoveries have contributed to the development of new therapeutics, new diagnostics, and to changes in the standard of care exemplifying significant clinical impact and the innovative nature of these Congressional Special Interest Medical Research Programs.

To learn more about CDMRP or to receive funding notifications by e-mail, please visit http://cdmrp.army.mil.

Acknowledgments
The authors gratefully note the CDMRP Program Evaluation Steering Committee for critical review of the manuscript. Also acknowledged are CDMRP staff at large and Dr. Lisa Kinnard for support in this project.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The Congressionally Directed Medical Research Programs (CDMRP), an office within the U.S. Army Medical Research and Materiel Command, has executed funding for research in 18 biomedical programs (Table). These programs touch the lives of service members, veterans, family members, and the general public. A partnership with the military, government, scientific community, survivors, patients, and their family members brings together spheres of stakeholders that typically might not otherwise collaborate and enables the CDMRP to complement other sources of research funding while focusing on research most directly relevant to each disease, condition, or injury.

The CDMRP began in 1992 when the breast cancer advocacy community launched a grassroots effort to raise public awareness of the need for increased federal funding for breast cancer research. These advocates requested from Congress additional research funding to support innovative, high-impact research where the government was willing to take a risk to leapfrog the field forward. In response, Congress added funds to the DoD budget for breast cancer research, and the Breast Cancer Research Program (BCRP) was established with a fiscal year (FY) 1992 congressional appropriation.

The CDMRP brought a flexible, efficient way of managing research and was enthusiastic about the advocates’ desire to have a voice in setting research priorities. Since the initial appropriation, advocates representing breast cancer, ovarian cancer, prostate cancer, neurofibromatosis, and a wide range of other diseases, conditions, and injuries have demonstrated the need to Congress to appropriate funds for their respective causes.

There are several features that differentiate the CDMRP from other funding agencies. The most significant differences follow:

1. The CDMRP funds innovative  high-risk/high-gain research focused on the disease, condition, or injury as specified in congressional language;
2. Unlike other agencies, the CDMRP integrates patients, survivors, family members, or caregivers of a person living with the disease, condition, or injury into every aspect of the program management cycle; and
3. Every year the CDMRP programs develop a new investment strategy and release award mechanisms based on the most critical needs and scientific gaps.

These features ensure that the research funded in each program is relevant and has a high potential for impact in the patient community. 

Funding and Science Management

Funding for the programs managed by the CDMRP does not appear as part of the DoD core funding in the president’s budget; instead, Congress assesses the needs of its constituents and adds funding to the DoD budget, designated specifically to meet those needs on an annual basis. Management of the CDMRP is funded entirely out of the annual appropriation, and there is no financial burden to the DoD. Unlike other federally funded agencies that receive funding in the president’s budget every FY, each CDMRP program develops an investment strategy based on a single yearly congressional appropriation.

Full project funding is obligated at the start from the single FY appropriation, ensuring multiyear research projects are not at funding risk. This method is in contrast to other agencies, which fund projects in budget years and may fund only a percentage of previously committed levels or cut the length of time for funding, depending on varying budget year funding policies.

Each CDMRP research program is managed by a multidisciplinary team and includes an external advisory board composed of world-renowned expert scientists, clinicians, and survivors from the DoD, National Institutes of Health (NIH), Centers for Disease Control and Prevention, VA, as well as academia and industry. Each research program has a vision/mission that is focused on ending or curing that disease, condition, or injury, ameliorating its consequences, or having a major impact on the quality of life of its survivors. Establishing a vision is the first major milestone in program execution, which enables each program to develop its individual investment strategy.

When establishing the investment strategy, each program evaluates the funding landscape by comparing research portfolios and award mechanisms within the organization as well as with other federal and nonfederal agencies. For some of the CDMRP-managed programs, such as the Peer Reviewed Orthopaedic Research Program, the Spinal Cord Injury Research Program, and the Psychological Health/Traumatic Brain Injury Research Program, topic areas are aligned with the Defense Health Program (DHP) Defense Medical Research and Development Program (DMRDP). The appropriate DHP Joint Program Committee provides guidance on military-relevant research priorities and uses oversight of all core and congressional special interest research efforts across the DoD services to complement and leverage projects with CDMRP funding.

Establishment of each program’s vision and investment strategy leads to the development of Program Announcements (PAs), which describe the intent of each award mechanism in order to solicit research applications aimed at making a significant and nonincremental impact. The PAs for each program as well as links to application submission are made available on the CDMRP webpage (http://cdmrp.army.mil/funding/prgdefault.shtml).

Emphasized in CDMRP research opportunities are the specific needs of its advocacy communities. The CDMRP recognizes the value of firsthand experience with each of the targeted diseases, conditions, and injuries and has been a leader in integrating consumers (defined as a patient, survivor, family member, or caregiver of a person living with the disease, condition, or injury) into every aspect of a program’s execution. The value of consumer involvement is derived from each individual’s firsthand experience. This approach adds a perspective, passion, and sense of urgency, which ensures that the human dimension is incorporated in each program’s policy, investment strategy, and research focus. Consumers vote side by side with scientists and clinicians on advisory boards for each of the programs, and they have since the inception of the CDMRP.

Each research application must have an impact statement describing how the proposed research, if successful, will transform an aspect of the understanding, prevention, detection, and/or treatment of the respective program area; ie, have an impact on the consumer community. The impact of the proposed research is a critical determinant of the funding recommendation.

Each research program’s investment strategy and associated award mechanisms provide the framework and direction necessary to most effectively invest the congressional appropriation. Operationally, the CDMRP monitors for potentially similar approaches in research at many milestones in its science management model to ensure that the CDMRP-funded research is synergistic and harmonizing, not duplicative of other federal and nonfederal sources of funding.

At the time of proposal submission, a comprehensive list of current and pending funding support for the principal investigator (PI) and all key personnel must be submitted. During the review process, peer reviewers who have extensive knowledge of the subject consult the pending and existing support documentation to ensure the research is complementary to what is already being investigated in the field. This ensures that the proposals recommended for funding are synergistic and contribute to the substantiation of data relevant to clinical decisions. After a project has been recommended for funding, the CDMRP scientific officers (ie, scientific technical advisors) check all available sources to ensure that the project to be funded is complementary to ongoing research. Last, during the period of performance, details about funding applied for and/or new funding obtained is required in the annual technical progress reports. Through this science management model, CDMRP ensures that funded research is complementary and able to innovatively fill gaps in the biomedical research pipeline. 

Biomedical Funding

Most diseases, conditions, and injuries are complex, and finding a cure for them requires problem solving from multiple disciplines and approaches as well as validation of research results. Prior to the fielding and clinical application of knowledge and products, research spans a continuum from discovery to clinical trials. As shown in Figure 1, novel award mechanisms developed by the CDMRP programs facilitate the success of this research continuum and innovatively complement traditional research funding agencies, such as the NIH. The intent of each award mechanism is designed to solicit research proposals focused on the needs of the patient community and how they relate to the vision of the program.

The Research Continuum

Some CDMRP programs provide support along the entire continuum of research. Other programs, with less mature research fields, focus on funding more basic research. There are also CDMRP programs that place emphasis on clinical and advanced development research. Each program’s annual investment strategy and choice of award mechanisms is based on the needs of the patient and research communities, gaps in research, and other barriers to progress in curing, rehabilitating, or eliminating the disease, condition, or injury.

Fostering the Development of Ideas

Since its inception in 1992, the DoD BCRP has sought to fund innovative, ground-breaking research by encouraging “outside the box” thinking and fostering creative collaborations that have the potential to have a high impact toward the eradication of this disease. The BCRP has a proven history of developing novel award mechanisms to foster new approaches in research. For example, the Idea Award was developed in the initial years of the BCRP to support novel research with little or no preliminary data that could ultimately lead to a critical discovery or advancement in breast cancer research. At that time, such high-risk, but potentially high-reward research was determined to be significantly underfunded by existing agencies and was thus identified as a gap in funding. Several major advancements in breast cancer, including the development of trastuzumab, testing of sentinel lymph node biopsy, and discovery of BRCA2 and PTEN gene mutations, were supported in part with funding from the BCRP.

The Idea Award mechanism has been adopted by other CDMRP programs to introduce new paradigms, challenge current paradigms, or look at existing problems from new perspectives in other disease- or condition-focused research. To support the exploration of highly innovative, untested concepts or theories, the BCRP and the Prostate Cancer Research Program (PCRP) developed other award mechanisms known as the Concept Award and the Exploration-Hypothesis Development Award, respectively.

These award mechanisms supporting early concepts and ideas provided complementary and multiple approaches to the most traditional and well-known grant program: the NIH R01 (Research Project Grant Program). In general, an R01 award requires preliminary data, supports the next logical or incremental step, is knowledge focused, has no specific program requirements, and is not focused on a single disease or condition. One of the hallmarks of this type of early idea award was that the preliminary data could then be used to submit a research proposal to an NIH-like R01 award mechanism.

A recent survey of Idea Awards offered by the BCRP from 2006 to 2011 indicated that > 40% of awardees successfully obtained other sources of funding, more than half coming from the NIH. The NIH Common Fund, established in 2006, led to the creation of a high-risk/high-reward program with the Transformative Research Award, which is focused on innovation and challenging existing paradigms, unlike the R01 mechanism. This indicates that although other agencies have developed award mechanisms supporting pilot and feasibility studies (eg, R21 awards–Exploratory/Developmental Research Grant) and high-risk/high-reward research (eg, Transformative Research Award), CDMRP’s creation of these mechanisms has transformed biomedical research and remains an important vehicle in the idea development funding pipeline.

Facilitating Collaborative Partnerships

Many funding agencies have recognized that research collaborations are important for investigating the increasing complexity of disease, conditions, and injuries. The CDMRP-managed BCRP, Ovarian Cancer Research Program(OCRP), and PCRP created collaborative award mechanisms (eg, the Synergistic Idea Award) in which one research project is submitted by multiple investigators whose combined resources are leveraged and their expertise synergized to better address a research question. A unique aspect of these collaborative award mechanisms is that all the investigators (appropriately called partners) receive an individual award, not a subaward, incentivizing investigators to develop partnerships that might not otherwise be formed.

Rewarding Science Teams

Recognizing that research collaborations are important in investigating the increasing complexity of disease and injuries, several of the CDMRP research programs have developed team science award mechanisms. Using the Manhattan Project as a successful example of bringing together the most talented scientists to conduct research and development simultaneously to quickly solve a common problem, the CDMRP Neurofibromatosis Research Program developed a consortium award mechanism to establish consortia of exceptional investigators to conceive, develop, and conduct collaborative pilot, phase 1, and phase 2 clinical evaluations. To the authors’ knowledge, this is the largest dedicated effort in neurofibromatosis research to date. This mechanism has been adopted by several other CDMRP programs to focus on multidisciplinary approaches with investigators from multiple institutions, to address high-impact research ideas or unmet needs.

The PCRP used this framework to support the infrastructure necessary for a consortium consisting of 13 major U.S. cancer centers (Prostate Cancer Clinical Trials Consortium [PCCTC]) to rapidly execute early-phase clinical trials of therapeutic agents. The PCCTC consortium now conducts about 25% of all early-phase U.S. clinical trials for prostate cancer and has dramatically impacted the speed at which new options for therapy are available to patients. For example, the drug abiraterone acetate was brought through clinical testing in half the time typically required and represents a new option in the treatment of metastatic prostate cancer. In addition, the PCCTC also brought MDV3100, another therapy for advanced disease, rapidly through all phases of clinical testing.

The Lung Cancer Research Program (LCRP) used the consortium award mechanism to create a unique, early detection clinical consortium that includes 4 academic organizations, 4 military treatment facilities, and 7 VA facilities to focus on characterizing, developing, and/or improving early detection modalities for lung cancer. The BCRP has recently introduced the Multi-Team and Transformative Vision Award mechanisms to support innovative teams of scientists, clinicians, and breast cancer survivors, patients, family members, and persons affected by and/or at risk of breast cancer to work together toward making breakthroughs that may have a revolutionary impact in breast cancer prevention or treatment.

Collectively, these team science mechanisms facilitate the exchange of ideas and bring together individuals with special knowledge and skills needed to sustain cross-fertilization. Such collaborations can unravel complex phenomena and significantly accelerate progress, thus shrinking the pipeline of traditional reductionist approaches to novel discoveries and outcomes.

Encouraging Visionary Individuals

The BCRP has developed a series of award mechanisms that seek to identify and fund individuals with potential for, or a history of, extraordinary innovation and creativity at varying career stages, from predoctoral training through established investigators. The BCRP Era of Hope Scholar (EOHS) Award supports early-career researchers who are the best and brightest in their field(s) and therefore have a high potential for innovation in breast cancer research.

While demonstrated experience in forming effective partnerships and collaborations is a requirement, experience in breast cancer is not, encouraging applicants to challenge current dogma and look beyond tradition and convention already established in the field. The unique intent of this mechanism changed the way innovative science is reviewed, since the individual young investigator, rather than the project, is the central feature of this award. The BCRP Innovator Award supports established, visionary individuals, who have demonstrated creativity, innovative work, and leadership in any field. This mechanism also broke new ground by providing individuals with the funding and freedom to pursue their most novel, visionary, high-risk ideas that could ultimately lead to ending disease.

CDMRP programs uniquely address clinical/translational research by focusing on critical needs and specific gaps within a particular disease, condition, or injury rather than a broad investment in general translational research.

Dr. Greg Hannon of Cold Spring Harbor Laboratory received a BCRP New Investigator Award in FY 1995 and was one of the first recipients of the Innovator Award in FY 2001, making scientific breakthroughs in understanding the mechanisms of RNA interference. He is currently applying these discoveries to the identification of new therapeutic targets for breast cancer. By funding such individuals at different stages of their research career, the BCRP has provided the foundation for many of today’s leading breast cancer researchers. Moreover, innovative researchers, such as Dr. Hannon, have moved from other fields into the breast cancer field as a result of BCRP funding.

Another investigator who transitioned into distinct disease fields as a result of CDMRP funding is. From 2002 to 2007, Dr. Chinnaiyan received funding from the PCRP and made a paradigm-shifting discovery and identified multiple recurrent gene fusions in human prostate cancers. Dr. Chinnaiyan had not worked in prostate cancer before embarking on his groundbreaking studies and is now a leader in that field. In 2007, Dr. Chinnaiyan had a vision that characterization of recurrent gene fusions within human breast cancers could lead to the identification of new biomarkers and therapeutic targets for this disease. He was awarded the BCRP EOHS Award and went on to make an exciting discovery of 2 novel recurrent and actionable gene fusions in breast cancer, the results of which were published in 2011.¹

Within the CDMRP, the OCRP has adopted the Innovator Award mechanism to attract visionary individuals from any field of research to focus their creativity, innovation, and leadership on ovarian cancer research. Through the use of this mechanism, this program has been successful in funding several noncancer scientists, including engineers, to help solve biomedical problems in the field. Six years after the initial release by CDMRP, the NIH introduced the Director’s New Innovator Award and the Pioneer Award. This CDMRP novel mechanism seems to have transformed funding strategies by encouraging innovative individuals to provide solutions to the toughest medical challenges.

Translation of Science to the Clinic

A critical component in the research continuum is the translation of promising lead agents to clinical trials. The CDMRP programs uniquely address clinical/translational research by focusing on critical needs and specific gaps within a particular disease, condition, or injury rather than a broad investment in general translational research. For example, the PCRP Laboratory-Clinical Transition Award mechanism supports product-driven preclinical studies of promising lead agents or medical devices that have the potential to revolutionize prostate cancer clinical care. For this award mechanism, lead agent development projects generate preclinical data to be used for an FDA investigational device exemption application and/or current Good Manufacturing Practice production of a medical device.

Preclinical Awards

The CDMRP Amyotrophic Lateral Sclerosis (ALS) Research Program focuses on the preclinical development of new therapies using the Therapeutic Development Award mechanism, which is product-driven and supports preclinical assessment of therapeutics, and the Therapeutic Idea Award mechanism, which promotes new ideas for novel therapeutics. This preclinical focus on therapeutic development compliments that of the National Institute of Neurological Disorders and Stroke (NINDS), the major NIH funder of ALS research, which concentrates primarily on funding basic and clinical research.

The CDMRP Gulf War Illness (GWI) Research Program created a unique award mechanism, the Innovative Treatment Evaluation Award, to support the early systematic evaluation of innovative treatment interventions that can provide proof of principle data for broader efficacy trials. The only other major funder of GWI research is the VA Office of Research and Development, which relies on the individual research interests of its intramural investigators.

In support of the 2012 Presidential Executive Order, the DoD and VA devoted > $100 million to fund 2 new consortia aimed at improving diagnosis and treatment of mild traumatic brain injury and posttraumatic stress disorder (PTSD). The Consortium to Alleviate PTSD and the Chronic Effects of Neurotrauma Consortium are jointly managed by the VA and CDMRP on behalf of the DoD and bring together leading scientists and clinicians devoted to the health and welfare of our nation’s service members and veterans. Consortium efforts are expected to have an emphasis toward translational/clinical work.

The OCRP developed the Translational Research Partnership Award mechanism to move an observation from the laboratory into clinical application for ovarian cancer. The novelty of this award is that one partner in the collaboration is required to be a laboratory scientist and the other is required to be a clinician. This award mechanism has been adopted by several other CDMRP research programs; a comparable mechanism has not been offered by other funding agencies.

The Peer Reviewed Orthopaedic Research Program (PRORP) is the only major funding source dedicated to research in combat and combat-related orthopedic injuries, the largest source of long-term morbidity for injured military personnel. The PRORP crafts investment strategies to address these challenges using award mechanisms such as the Technology Development, Translational Partnership, and the Clinical Trial awards, which emphasize clinical and mature translational research. While industry, including pharmaceutical, biotechnology, and medical device firms, remains the largest funder of clinical trial research, the CDMRP’s niche in this arena is the ability to encourage preventive or therapeutic interventions that are in line with the priorities of the communities affected by the disease.

Training and Career Development

Training the next generation of scientists in both basic and clinical research is instrumental for the advancement of biomedical research. The career development pipeline traditionally proceeds from predoctoral through postdoctoral training to the new or junior faculty level investigator (Figure 2). The CDMRP offers pre- and postdoctoral training award mechanisms in which the research is disease- or condition-specific, and the trainee is named as the principal investigator, thereby providing the trainee with his or her first source of research funding.

The BCRP Postdoctoral Award mechanism is unique in that it provides funding for the research in addition to stipend support. The trainee is expected to have discretion over management of the award, thus providing valuable training as a researcher. In addition to recent doctoral graduates, many CDMRP training mechanisms support recent medical graduates and encourage the training of physician-scientists. For example, the Prostate Cancer Research Program (PCRP) supports the training of physicians with clinical duties for a career in prostate cancer research through the physician Research Training Award. At the time of application, the PI must be in the last year of medical residency, must designate a mentor with an established research program, and institutions must provide at least 40% protection of the PI’s time for research.

The PRORP offers a career development award in which active-duty military researchers, physical therapists, occupational therapists, or physician-scientists with < 8 years of clinical or postdoctoral research experience (excluding clinical residency or medical fellowship training) are eligible to apply. The LCRP has offered a promising clinician research award supporting the training of MDs or MD/PhDs with clinical duties and/or responsibilities that are within 5 years of a professional appointment. Each of these physician training mechanisms not only provide support at an early career stage to investigators at DoD or other clinical sites, but also enable physicians to have a career at the forefront of research and clinical practice.

In 2002, the NIH observed that the percentage of competing NIH grants awarded to investigators aged ≤ 35 years declined from 23% in 1980 to < 4% in 2002. To support these young investigators, the NIH introduced the Pathway to Independence Award mechanism, providing several years of mentored support for promising postdoctoral scientists followed by several years of independent support. More recently, the NIH has focused on new investigators by offering more R01 awards to this group. Because securing early concept funding helps pave the way for the larger R01 grant application, increasing the support for early investigators is important for creating a critical threshold of scientists with exceptional talent.

The CDMRP New Investigator Award programs are intended to support scientists in the early stages of their careers through the continued development of promising independent investigators and/or the transition of established investigators. Each of the CDMRP programs has developed variations of the New Investigator Award to meet the goals of the disease- or condition-specific program. The OCRP Ovarian Cancer Academy, which includes both medical doctors and PhD scientists, is one of the more recent and innovative New Investigator Award mechanisms. This academy is an interactive virtual research and training platform that provides intensive mentoring, national networking, and a peer group for junior faculty in a collaborative and interactive environment. Taken together, the CDMRP programs offer unique award mechanisms to support researchers at critical junctures in their careers. The unique qualities and competitiveness of the CDMRP’s disease/condition-focused training awards have supported the early-career foundation for many of today’s leading researchers.

Conclusions

Congressionally Directed Medical Research Programs complement other federal and nonfederal sources of biomedical research funding and fill important research gaps through an evaluation of the funding landscape, identification of research gaps, and development of novel award mechanisms. The integration of survivors, patients, and their family members ensures that every aspect of the program management cycle balances scientific expertise with human perspective and has high impact on the patient community.

As new needs emerge, each research program designs an investment strategy to target areas most critically in need. The subsequent release of novel award mechanisms focuses research and enables an acceleration of science and/or leading researchers to the patient’s bedside. The CDMRP-funded discoveries have contributed to the development of new therapeutics, new diagnostics, and to changes in the standard of care exemplifying significant clinical impact and the innovative nature of these Congressional Special Interest Medical Research Programs.

To learn more about CDMRP or to receive funding notifications by e-mail, please visit http://cdmrp.army.mil.

Acknowledgments
The authors gratefully note the CDMRP Program Evaluation Steering Committee for critical review of the manuscript. Also acknowledged are CDMRP staff at large and Dr. Lisa Kinnard for support in this project.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Emotional stress can induce different responses in the body, particularly in the cardiovascular system. Apical ballooning syndrome (ABS), also known as takotsubo cardiomyopathy and broken heart syndrome, is a transient cardiomyopathy that mimics an acute myocardial infarction (AMI). Dote and colleagues first described this transient entity in Japan in the early 1990s.¹ A case review series reported that 57.2% of patients were Asian, 40% were white.² Mean patient age was 67 years, although cases of ABS have occurred in children and young adults.^3,4

The term tako-tsubo means “octopus trap,” which is the morphology that the left ventricle resembles during systole in patients with this syndrome.⁵ The pathophysiology of ABS is thought to be mediated by a catecholamine surge. The presentation of ABS is indistinguishable from an AMI. The majority of patients present with angina-like chest pain, ischemic changes on an electrocardiogram (ECG), pulmonary edema, and elevation of cardiac enzymes. Apical ballooning syndrome is accompanied by reversible left ventricular apical ballooning in the absence of angiographically significant coronary artery disease.

Typically, echocardiographic findings show a left ventricle with preserved function in the basal segments, moderate-to-severe dysfunction in the mid portion of the left ventricle, and hypokinesis, akinesis, or dyskinesis in the apex. A unique but not exclusive feature of this syndrome is the occurrence of a preceding emotional trigger, usually sudden or unexpected. Most patients are initially treated for an AMI until angiography can rule out coronary obstruction. After several weeks, the left ventricular systolic function usually returns to normal.

Case Presentation

A 49-year-old woman with a history of arterial hypertension, fibromyalgia, peptic ulcer disease, and major depressive disorder with multiple admissions to the psychiatric ward (last admission was 4 weeks prior to the current presentation) presented to the emergency department, reporting severe retrosternal, oppressive chest pain with 9/10 intensity and 3 hours’ duration. The pain was associated with nausea, vomiting, diaphoresis, and palpitations. She reported no previous episodes of exertional angina, fever, illicit drug use, recent illness, or travel. She also reported no prodromal symptoms.

Her initial vital signs were essentially unremarkable, except for mild hypertension (148/84 mm Hg). The physical examination showed an anxious patient in acute distress due to chest pain. A cardiovascular examination revealed a regular heart rate and rhythm, no audible murmurs or gallops, no jugular vein distention, clear breath sounds, and no peripheral edema. The rest of the examination was otherwise unremarkable. An initial 12-lead ECG showed a normal sinus rhythm without any ST-T changes (Figure 1).

The initial cardiac markers were elevated (troponin T 0.36 ng/mL, CK-MB 4.51 ng/mL), as were NT-proBNP levels (1,057 pg/mL). The rest of the laboratory results were essentially unremarkable. The patient was started on aspirin, clopidogrel, enoxaparin, eptifibatide, and IV nitrates. She was admitted to the coronary care unit with a diagnostic impression of non-ST elevation MI. Despite medical management, the patient’s chest pain persisted for several hours from her initial presentation. A repeated 12-lead ECG revealed new borderline (1-1.5 mm) ST segment elevation in V2-V3, suggestive of possible myocardial injury (Figure 2).

A bedside echocardiogram revealed severe wall motion abnor malities, ranging from hypokinesia to dyskinesia of all mid-to-distal left ventricular wall segments with sparing of the basal segment (Figure 3). The estimated left ventricular ejection fraction was 40% to 45%.

In view of these findings, the patient was taken to the catheterization laboratory for emergent coronary angiography, which ruled out significant obstructive coronary disease (Figure 4).

Left ventriculography in right and left anterior oblique projections revealed significant wall motion abnormalities of the mid-to-distal anterolateral and inferior wall segments, sparing the basal and apical segments, giving the appearance of ballooning in systole (Figure 5). The diagnosis of ABS involving the mid ventricular walls was explored.

Subsequent sets of cardiac enzymes at 4 and 8 hours after arrival remained elevated, with a maximum troponin T 0.55 and CK-MB of 11.19. Repeated 12-lead ECG 24 hours post coronary angiography revealed anterolateral T wave inversion (Figure 6).

Noncontrast enhanced cardiac magnetic resonance imaging (MRI) (Figure 7) performed 5 days later revealed wall motion abnormalities highly suggestive of ABS, supporting previous echocardiographic and ventriculography findings. Unfortunately, contrast-enhanced phase for evaluation of delayed enhancement could not be completed, because the patient did not continue the study.

Toxicology tests were negative for sympathomimetic drugs. Metanephrine levels were within the normal range. Viral titers for cytomegalovirus and coxsackie virus also were negative. Inflammatory markers were mildly elevated (erythrocyte sedimentation rate, 22 mm/h; C-reactive protein, 4.2 mg/L).

The patient was treated with supportive care, psychotropic therapy, angiotensin-converting enzyme inhibitor (ACE-I), and beta blocker therapy. Within 9 days, NT-proBNP levels normalized (from peak 8,834 pg/mL to 191.5 pg/mL).

Six weeks later, an echocardiogram confirmed resolution of wall motion abnormalities (Figure 8). Follow-up cardiac MRI showed complete resolution of segmental wall motion abnormalities and the apical ballooning, normal wall thickness, and absent delayed enhancement (Figure 9). These findings further supported the diagnosis of ABS and excluded MI and myocarditis.

Discussion

What is striking about takotsubo cardiomyopathy is that the clinical presentation resembles an AMI. Several studies have reported that 1.7% to 2.2% of patients who had suspected acute coronary syndrome were subsequently diagnosed with takotsubo cardiomyopathy.^6-8 Nearly 90% of reported cases involved postmenopausal women, and this may be related to loss of the cardioprotective effect of estrogen.^5,9

A preceding stressful emotional or physical event is usually identified in about two-thirds of the patients with ABS.⁹ Most common emotional triggers are death of a relative or friend, broken relationships, assaults, and rapes, among others. Physical triggers include severe sepsis, shock, acute respiratory failure, seizures, and intracranial bleeds. Sometimes a specific trigger cannot be identified from the history, but the absence of an emotional or physical trigger does not exclude the diagnosis.

Although the exact pathogenesis of ABS remains unclear, it is likely that multiple factors are involved. Some of the suggested mechanisms are high levels of catecholamines, multivessel epicardial spasm, or coronary microvascular dysfunction.⁴ The catecholamine hypothesis has been supported by the finding that several patients with pheochromocytoma and subarachnoid hemorrhage also present with high levels of catecholamine and a cardiomyopathy resembling ABS. Furthermore, ABS has been reported in patients on catecholamine infusions and those treated with agents that inhibit reuptake of catecholamines.⁵

The presence of multivessel coronary spasm was suggested by early small studies in Japan, but more recent case series have not validated this hypothesis.⁵ The microvascular dysfunction hypothesis is supported by the presence of myocardial ischemia, diagnosed by ECG changes and elevated troponins, in the absence of significant coronary disease. However, it remains unclear whether this is a primary mechanism or a manifestation of a primary process.⁴ Microvascular dysfunction may be more likely related to impairment of myocardial relaxation with extramural coronary compression.

Signs and symptoms of ABS mimic those of AMI, with angina-like chest pain as the main presenting symptom in about 50% of cases.¹⁰ Other symptoms include dyspnea and less commonly, syncope or sudden cardiac death. Decompensated left heart failure occurs in 50% of patients, with severe hemodynamic compromise and cardiogenic shock not being uncommon. Other complications that may occur are tachyarrhythmias (atrial or ventricular) and ventricular thromboembolism.⁴

Common ECG changes in ABS include precordial ST segment elevations, symmetric T wave inversions, and nonspecific T wave changes.^4,10 QT interval prolongation may be seen during the first days. Transient pathologic Q waves may be seen at presentation or afterward. These ECG changes tend to revert after weeks or months of presentation.

Elevation of cardiac biomarkers is usually present in laboratory data. Levels peak at 24 hours, and the degree of elevation is usually less than that seen in patients with an AMI.¹⁰ Most important, the degree of cardiac biomarker elevation is disproportionately low for the extent of involved coronary territory and left ventricular dysfunction. Other laboratory tests that are frequently altered are the BNP and pro-BNP levels, which are usually elevated due to transient left ventricular dysfunction. C-reactive protein elevates in most patients and indicates the presence of an acute inflammatory response.

Early coronary angiography should be performed in all patients with ABS to rule out the presence of a significant obstructive coronary lesion. Patients with ABS often have luminal irregularities or normal coronary vessels. However, concomitant obstructive coronary lesions may be found, especially in elderly patients.

The hallmark of ABS is a characteristic transient contractility abnormality of the left ventricle causing ballooning of the apex, which can be detected on left ventricular angiography or echocardiography. There are 3 distinct variants of ABS, according to the left ventricular myocardial wall segments involved.¹⁰ The classic form of takotsubo is characterized by hypokinesis, dyskinesis, or akinesis of the middle and apical segments of the left ventricle. The basal segment is usually spared and may be hyperdynamic. In the midventricular or apical sparing variant, the wall motion abnormalities are restricted to the midventricular segments, and apical contraction is preserved. This case resembles the atypical variant, because the midventricular segments were affected, whereas apical and basal regions were preserved. A rare variant of takotsubo exists with hypokinesis or akinesis of the base and preserved apical function.

Besides ABS and AMI, an important entity to consider in the differential diagnosis of transient wall motion abnormalities is regional myocarditis. Viral titers are helpful in excluding this condition. Furthermore, prolonged recovery is more commonly seen in myocarditis compared with ABS. Imaging studies are particularly helpful in this scenario.

Cardiac MRI demonstrates the wall motion abnormalities or apical ballooning typical for this condition and can differentiate ABS from myocarditis or MI. It is known that delayed myocardial enhancement is seen with myocardial fibrosis. Typically in ischemic cardiomyopathy, there is wall thinning with associated delayed enhancement that extends from the subendocardium to the epicardium (from 0%-90% of wall thickness) of a particular vascular territory. In myocarditis, the enhancement is usually seen in the involved intramyocardial (mesocardium) region, and the pattern is patchy. In ABS, the delayed enhancement is absent, because there is no fibrosis in the area of regional wall motion abnormalities, and wall thickness is usually normal.^9,10

No evidence-based guidelines for treating ABS are currently available. Most patients are initially treated with antiplatelets/anticoagulant therapy, nitrates, and diuretics if the patient presents with heart failure. Patients should be admitted to an intensive care unit for close cardiac monitoring. Once ABS is diagnosed and significant coronary stenosis is excluded, patients should receive standard supportive care and optimal neurohormonal therapy. This should include beta blocker or combined alpha/beta blocker agents, an ACE-I or angiotensin receptor blocker, and diuretics if appropriate. Once left ventricular function (LVF) is recovered, therapy with inhibitors of the renin-angiotensin system may be discontinued, but patients should remain on long-term alpha or beta blocker therapy, because the sympathetic blockade provided by these agents may prevent recurrences of this disease.¹⁰

Prognosis is generally favorable, and most patients recover to normal LVF over weeks to months. It is important to assess the LVF 4 to 6 weeks after the patient is discharged to confirm the diagnosis of ABS. Recurrence may occur in up to 9% of cases.¹⁰ Long-term mortality is similar compared with the age-matched general population.

Conclusion

Apical ballooning syndrome is a relatively novel cardiomyopathy that has gained important attention among the cardiovascular community, mostly because its clinical presentation mimics that of an acute coronary syndrome. Awareness of this entity will result in a more focused diagnosis and appropriate treatment. Managing both cardiac and emotional components of this disease will have a permanent impact in the reversibility and secondary prevention of this cardiomyopathy.

Acknowledgments
Special thanks to the Radiology Service at the VA Caribbean Healthcare System, in particular Dr. Frances Aulet for interpretation of the cardiac MRI results and assistance with MRI images.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Emotional stress can induce different responses in the body, particularly in the cardiovascular system. Apical ballooning syndrome (ABS), also known as takotsubo cardiomyopathy and broken heart syndrome, is a transient cardiomyopathy that mimics an acute myocardial infarction (AMI). Dote and colleagues first described this transient entity in Japan in the early 1990s.¹ A case review series reported that 57.2% of patients were Asian, 40% were white.² Mean patient age was 67 years, although cases of ABS have occurred in children and young adults.^3,4

The term tako-tsubo means “octopus trap,” which is the morphology that the left ventricle resembles during systole in patients with this syndrome.⁵ The pathophysiology of ABS is thought to be mediated by a catecholamine surge. The presentation of ABS is indistinguishable from an AMI. The majority of patients present with angina-like chest pain, ischemic changes on an electrocardiogram (ECG), pulmonary edema, and elevation of cardiac enzymes. Apical ballooning syndrome is accompanied by reversible left ventricular apical ballooning in the absence of angiographically significant coronary artery disease.

Typically, echocardiographic findings show a left ventricle with preserved function in the basal segments, moderate-to-severe dysfunction in the mid portion of the left ventricle, and hypokinesis, akinesis, or dyskinesis in the apex. A unique but not exclusive feature of this syndrome is the occurrence of a preceding emotional trigger, usually sudden or unexpected. Most patients are initially treated for an AMI until angiography can rule out coronary obstruction. After several weeks, the left ventricular systolic function usually returns to normal.

Case Presentation

A 49-year-old woman with a history of arterial hypertension, fibromyalgia, peptic ulcer disease, and major depressive disorder with multiple admissions to the psychiatric ward (last admission was 4 weeks prior to the current presentation) presented to the emergency department, reporting severe retrosternal, oppressive chest pain with 9/10 intensity and 3 hours’ duration. The pain was associated with nausea, vomiting, diaphoresis, and palpitations. She reported no previous episodes of exertional angina, fever, illicit drug use, recent illness, or travel. She also reported no prodromal symptoms.

Her initial vital signs were essentially unremarkable, except for mild hypertension (148/84 mm Hg). The physical examination showed an anxious patient in acute distress due to chest pain. A cardiovascular examination revealed a regular heart rate and rhythm, no audible murmurs or gallops, no jugular vein distention, clear breath sounds, and no peripheral edema. The rest of the examination was otherwise unremarkable. An initial 12-lead ECG showed a normal sinus rhythm without any ST-T changes (Figure 1).

The initial cardiac markers were elevated (troponin T 0.36 ng/mL, CK-MB 4.51 ng/mL), as were NT-proBNP levels (1,057 pg/mL). The rest of the laboratory results were essentially unremarkable. The patient was started on aspirin, clopidogrel, enoxaparin, eptifibatide, and IV nitrates. She was admitted to the coronary care unit with a diagnostic impression of non-ST elevation MI. Despite medical management, the patient’s chest pain persisted for several hours from her initial presentation. A repeated 12-lead ECG revealed new borderline (1-1.5 mm) ST segment elevation in V2-V3, suggestive of possible myocardial injury (Figure 2).

A bedside echocardiogram revealed severe wall motion abnor malities, ranging from hypokinesia to dyskinesia of all mid-to-distal left ventricular wall segments with sparing of the basal segment (Figure 3). The estimated left ventricular ejection fraction was 40% to 45%.

In view of these findings, the patient was taken to the catheterization laboratory for emergent coronary angiography, which ruled out significant obstructive coronary disease (Figure 4).

Left ventriculography in right and left anterior oblique projections revealed significant wall motion abnormalities of the mid-to-distal anterolateral and inferior wall segments, sparing the basal and apical segments, giving the appearance of ballooning in systole (Figure 5). The diagnosis of ABS involving the mid ventricular walls was explored.

Subsequent sets of cardiac enzymes at 4 and 8 hours after arrival remained elevated, with a maximum troponin T 0.55 and CK-MB of 11.19. Repeated 12-lead ECG 24 hours post coronary angiography revealed anterolateral T wave inversion (Figure 6).

Noncontrast enhanced cardiac magnetic resonance imaging (MRI) (Figure 7) performed 5 days later revealed wall motion abnormalities highly suggestive of ABS, supporting previous echocardiographic and ventriculography findings. Unfortunately, contrast-enhanced phase for evaluation of delayed enhancement could not be completed, because the patient did not continue the study.

Toxicology tests were negative for sympathomimetic drugs. Metanephrine levels were within the normal range. Viral titers for cytomegalovirus and coxsackie virus also were negative. Inflammatory markers were mildly elevated (erythrocyte sedimentation rate, 22 mm/h; C-reactive protein, 4.2 mg/L).

The patient was treated with supportive care, psychotropic therapy, angiotensin-converting enzyme inhibitor (ACE-I), and beta blocker therapy. Within 9 days, NT-proBNP levels normalized (from peak 8,834 pg/mL to 191.5 pg/mL).

Six weeks later, an echocardiogram confirmed resolution of wall motion abnormalities (Figure 8). Follow-up cardiac MRI showed complete resolution of segmental wall motion abnormalities and the apical ballooning, normal wall thickness, and absent delayed enhancement (Figure 9). These findings further supported the diagnosis of ABS and excluded MI and myocarditis.

Discussion

What is striking about takotsubo cardiomyopathy is that the clinical presentation resembles an AMI. Several studies have reported that 1.7% to 2.2% of patients who had suspected acute coronary syndrome were subsequently diagnosed with takotsubo cardiomyopathy.^6-8 Nearly 90% of reported cases involved postmenopausal women, and this may be related to loss of the cardioprotective effect of estrogen.^5,9

A preceding stressful emotional or physical event is usually identified in about two-thirds of the patients with ABS.⁹ Most common emotional triggers are death of a relative or friend, broken relationships, assaults, and rapes, among others. Physical triggers include severe sepsis, shock, acute respiratory failure, seizures, and intracranial bleeds. Sometimes a specific trigger cannot be identified from the history, but the absence of an emotional or physical trigger does not exclude the diagnosis.

Although the exact pathogenesis of ABS remains unclear, it is likely that multiple factors are involved. Some of the suggested mechanisms are high levels of catecholamines, multivessel epicardial spasm, or coronary microvascular dysfunction.⁴ The catecholamine hypothesis has been supported by the finding that several patients with pheochromocytoma and subarachnoid hemorrhage also present with high levels of catecholamine and a cardiomyopathy resembling ABS. Furthermore, ABS has been reported in patients on catecholamine infusions and those treated with agents that inhibit reuptake of catecholamines.⁵

The presence of multivessel coronary spasm was suggested by early small studies in Japan, but more recent case series have not validated this hypothesis.⁵ The microvascular dysfunction hypothesis is supported by the presence of myocardial ischemia, diagnosed by ECG changes and elevated troponins, in the absence of significant coronary disease. However, it remains unclear whether this is a primary mechanism or a manifestation of a primary process.⁴ Microvascular dysfunction may be more likely related to impairment of myocardial relaxation with extramural coronary compression.

Signs and symptoms of ABS mimic those of AMI, with angina-like chest pain as the main presenting symptom in about 50% of cases.¹⁰ Other symptoms include dyspnea and less commonly, syncope or sudden cardiac death. Decompensated left heart failure occurs in 50% of patients, with severe hemodynamic compromise and cardiogenic shock not being uncommon. Other complications that may occur are tachyarrhythmias (atrial or ventricular) and ventricular thromboembolism.⁴

Common ECG changes in ABS include precordial ST segment elevations, symmetric T wave inversions, and nonspecific T wave changes.^4,10 QT interval prolongation may be seen during the first days. Transient pathologic Q waves may be seen at presentation or afterward. These ECG changes tend to revert after weeks or months of presentation.

Elevation of cardiac biomarkers is usually present in laboratory data. Levels peak at 24 hours, and the degree of elevation is usually less than that seen in patients with an AMI.¹⁰ Most important, the degree of cardiac biomarker elevation is disproportionately low for the extent of involved coronary territory and left ventricular dysfunction. Other laboratory tests that are frequently altered are the BNP and pro-BNP levels, which are usually elevated due to transient left ventricular dysfunction. C-reactive protein elevates in most patients and indicates the presence of an acute inflammatory response.

Early coronary angiography should be performed in all patients with ABS to rule out the presence of a significant obstructive coronary lesion. Patients with ABS often have luminal irregularities or normal coronary vessels. However, concomitant obstructive coronary lesions may be found, especially in elderly patients.

The hallmark of ABS is a characteristic transient contractility abnormality of the left ventricle causing ballooning of the apex, which can be detected on left ventricular angiography or echocardiography. There are 3 distinct variants of ABS, according to the left ventricular myocardial wall segments involved.¹⁰ The classic form of takotsubo is characterized by hypokinesis, dyskinesis, or akinesis of the middle and apical segments of the left ventricle. The basal segment is usually spared and may be hyperdynamic. In the midventricular or apical sparing variant, the wall motion abnormalities are restricted to the midventricular segments, and apical contraction is preserved. This case resembles the atypical variant, because the midventricular segments were affected, whereas apical and basal regions were preserved. A rare variant of takotsubo exists with hypokinesis or akinesis of the base and preserved apical function.

Besides ABS and AMI, an important entity to consider in the differential diagnosis of transient wall motion abnormalities is regional myocarditis. Viral titers are helpful in excluding this condition. Furthermore, prolonged recovery is more commonly seen in myocarditis compared with ABS. Imaging studies are particularly helpful in this scenario.

Cardiac MRI demonstrates the wall motion abnormalities or apical ballooning typical for this condition and can differentiate ABS from myocarditis or MI. It is known that delayed myocardial enhancement is seen with myocardial fibrosis. Typically in ischemic cardiomyopathy, there is wall thinning with associated delayed enhancement that extends from the subendocardium to the epicardium (from 0%-90% of wall thickness) of a particular vascular territory. In myocarditis, the enhancement is usually seen in the involved intramyocardial (mesocardium) region, and the pattern is patchy. In ABS, the delayed enhancement is absent, because there is no fibrosis in the area of regional wall motion abnormalities, and wall thickness is usually normal.^9,10

No evidence-based guidelines for treating ABS are currently available. Most patients are initially treated with antiplatelets/anticoagulant therapy, nitrates, and diuretics if the patient presents with heart failure. Patients should be admitted to an intensive care unit for close cardiac monitoring. Once ABS is diagnosed and significant coronary stenosis is excluded, patients should receive standard supportive care and optimal neurohormonal therapy. This should include beta blocker or combined alpha/beta blocker agents, an ACE-I or angiotensin receptor blocker, and diuretics if appropriate. Once left ventricular function (LVF) is recovered, therapy with inhibitors of the renin-angiotensin system may be discontinued, but patients should remain on long-term alpha or beta blocker therapy, because the sympathetic blockade provided by these agents may prevent recurrences of this disease.¹⁰

Prognosis is generally favorable, and most patients recover to normal LVF over weeks to months. It is important to assess the LVF 4 to 6 weeks after the patient is discharged to confirm the diagnosis of ABS. Recurrence may occur in up to 9% of cases.¹⁰ Long-term mortality is similar compared with the age-matched general population.

Conclusion

Apical ballooning syndrome is a relatively novel cardiomyopathy that has gained important attention among the cardiovascular community, mostly because its clinical presentation mimics that of an acute coronary syndrome. Awareness of this entity will result in a more focused diagnosis and appropriate treatment. Managing both cardiac and emotional components of this disease will have a permanent impact in the reversibility and secondary prevention of this cardiomyopathy.

Acknowledgments
Special thanks to the Radiology Service at the VA Caribbean Healthcare System, in particular Dr. Frances Aulet for interpretation of the cardiac MRI results and assistance with MRI images.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Emotional stress can induce different responses in the body, particularly in the cardiovascular system. Apical ballooning syndrome (ABS), also known as takotsubo cardiomyopathy and broken heart syndrome, is a transient cardiomyopathy that mimics an acute myocardial infarction (AMI). Dote and colleagues first described this transient entity in Japan in the early 1990s.¹ A case review series reported that 57.2% of patients were Asian, 40% were white.² Mean patient age was 67 years, although cases of ABS have occurred in children and young adults.^3,4

The term tako-tsubo means “octopus trap,” which is the morphology that the left ventricle resembles during systole in patients with this syndrome.⁵ The pathophysiology of ABS is thought to be mediated by a catecholamine surge. The presentation of ABS is indistinguishable from an AMI. The majority of patients present with angina-like chest pain, ischemic changes on an electrocardiogram (ECG), pulmonary edema, and elevation of cardiac enzymes. Apical ballooning syndrome is accompanied by reversible left ventricular apical ballooning in the absence of angiographically significant coronary artery disease.

Typically, echocardiographic findings show a left ventricle with preserved function in the basal segments, moderate-to-severe dysfunction in the mid portion of the left ventricle, and hypokinesis, akinesis, or dyskinesis in the apex. A unique but not exclusive feature of this syndrome is the occurrence of a preceding emotional trigger, usually sudden or unexpected. Most patients are initially treated for an AMI until angiography can rule out coronary obstruction. After several weeks, the left ventricular systolic function usually returns to normal.

Case Presentation

A 49-year-old woman with a history of arterial hypertension, fibromyalgia, peptic ulcer disease, and major depressive disorder with multiple admissions to the psychiatric ward (last admission was 4 weeks prior to the current presentation) presented to the emergency department, reporting severe retrosternal, oppressive chest pain with 9/10 intensity and 3 hours’ duration. The pain was associated with nausea, vomiting, diaphoresis, and palpitations. She reported no previous episodes of exertional angina, fever, illicit drug use, recent illness, or travel. She also reported no prodromal symptoms.

Her initial vital signs were essentially unremarkable, except for mild hypertension (148/84 mm Hg). The physical examination showed an anxious patient in acute distress due to chest pain. A cardiovascular examination revealed a regular heart rate and rhythm, no audible murmurs or gallops, no jugular vein distention, clear breath sounds, and no peripheral edema. The rest of the examination was otherwise unremarkable. An initial 12-lead ECG showed a normal sinus rhythm without any ST-T changes (Figure 1).

The initial cardiac markers were elevated (troponin T 0.36 ng/mL, CK-MB 4.51 ng/mL), as were NT-proBNP levels (1,057 pg/mL). The rest of the laboratory results were essentially unremarkable. The patient was started on aspirin, clopidogrel, enoxaparin, eptifibatide, and IV nitrates. She was admitted to the coronary care unit with a diagnostic impression of non-ST elevation MI. Despite medical management, the patient’s chest pain persisted for several hours from her initial presentation. A repeated 12-lead ECG revealed new borderline (1-1.5 mm) ST segment elevation in V2-V3, suggestive of possible myocardial injury (Figure 2).

A bedside echocardiogram revealed severe wall motion abnor malities, ranging from hypokinesia to dyskinesia of all mid-to-distal left ventricular wall segments with sparing of the basal segment (Figure 3). The estimated left ventricular ejection fraction was 40% to 45%.

In view of these findings, the patient was taken to the catheterization laboratory for emergent coronary angiography, which ruled out significant obstructive coronary disease (Figure 4).

Left ventriculography in right and left anterior oblique projections revealed significant wall motion abnormalities of the mid-to-distal anterolateral and inferior wall segments, sparing the basal and apical segments, giving the appearance of ballooning in systole (Figure 5). The diagnosis of ABS involving the mid ventricular walls was explored.

Subsequent sets of cardiac enzymes at 4 and 8 hours after arrival remained elevated, with a maximum troponin T 0.55 and CK-MB of 11.19. Repeated 12-lead ECG 24 hours post coronary angiography revealed anterolateral T wave inversion (Figure 6).

Noncontrast enhanced cardiac magnetic resonance imaging (MRI) (Figure 7) performed 5 days later revealed wall motion abnormalities highly suggestive of ABS, supporting previous echocardiographic and ventriculography findings. Unfortunately, contrast-enhanced phase for evaluation of delayed enhancement could not be completed, because the patient did not continue the study.

Toxicology tests were negative for sympathomimetic drugs. Metanephrine levels were within the normal range. Viral titers for cytomegalovirus and coxsackie virus also were negative. Inflammatory markers were mildly elevated (erythrocyte sedimentation rate, 22 mm/h; C-reactive protein, 4.2 mg/L).

The patient was treated with supportive care, psychotropic therapy, angiotensin-converting enzyme inhibitor (ACE-I), and beta blocker therapy. Within 9 days, NT-proBNP levels normalized (from peak 8,834 pg/mL to 191.5 pg/mL).

Six weeks later, an echocardiogram confirmed resolution of wall motion abnormalities (Figure 8). Follow-up cardiac MRI showed complete resolution of segmental wall motion abnormalities and the apical ballooning, normal wall thickness, and absent delayed enhancement (Figure 9). These findings further supported the diagnosis of ABS and excluded MI and myocarditis.

Discussion

What is striking about takotsubo cardiomyopathy is that the clinical presentation resembles an AMI. Several studies have reported that 1.7% to 2.2% of patients who had suspected acute coronary syndrome were subsequently diagnosed with takotsubo cardiomyopathy.^6-8 Nearly 90% of reported cases involved postmenopausal women, and this may be related to loss of the cardioprotective effect of estrogen.^5,9

A preceding stressful emotional or physical event is usually identified in about two-thirds of the patients with ABS.⁹ Most common emotional triggers are death of a relative or friend, broken relationships, assaults, and rapes, among others. Physical triggers include severe sepsis, shock, acute respiratory failure, seizures, and intracranial bleeds. Sometimes a specific trigger cannot be identified from the history, but the absence of an emotional or physical trigger does not exclude the diagnosis.

Although the exact pathogenesis of ABS remains unclear, it is likely that multiple factors are involved. Some of the suggested mechanisms are high levels of catecholamines, multivessel epicardial spasm, or coronary microvascular dysfunction.⁴ The catecholamine hypothesis has been supported by the finding that several patients with pheochromocytoma and subarachnoid hemorrhage also present with high levels of catecholamine and a cardiomyopathy resembling ABS. Furthermore, ABS has been reported in patients on catecholamine infusions and those treated with agents that inhibit reuptake of catecholamines.⁵

The presence of multivessel coronary spasm was suggested by early small studies in Japan, but more recent case series have not validated this hypothesis.⁵ The microvascular dysfunction hypothesis is supported by the presence of myocardial ischemia, diagnosed by ECG changes and elevated troponins, in the absence of significant coronary disease. However, it remains unclear whether this is a primary mechanism or a manifestation of a primary process.⁴ Microvascular dysfunction may be more likely related to impairment of myocardial relaxation with extramural coronary compression.

Signs and symptoms of ABS mimic those of AMI, with angina-like chest pain as the main presenting symptom in about 50% of cases.¹⁰ Other symptoms include dyspnea and less commonly, syncope or sudden cardiac death. Decompensated left heart failure occurs in 50% of patients, with severe hemodynamic compromise and cardiogenic shock not being uncommon. Other complications that may occur are tachyarrhythmias (atrial or ventricular) and ventricular thromboembolism.⁴

Common ECG changes in ABS include precordial ST segment elevations, symmetric T wave inversions, and nonspecific T wave changes.^4,10 QT interval prolongation may be seen during the first days. Transient pathologic Q waves may be seen at presentation or afterward. These ECG changes tend to revert after weeks or months of presentation.

Elevation of cardiac biomarkers is usually present in laboratory data. Levels peak at 24 hours, and the degree of elevation is usually less than that seen in patients with an AMI.¹⁰ Most important, the degree of cardiac biomarker elevation is disproportionately low for the extent of involved coronary territory and left ventricular dysfunction. Other laboratory tests that are frequently altered are the BNP and pro-BNP levels, which are usually elevated due to transient left ventricular dysfunction. C-reactive protein elevates in most patients and indicates the presence of an acute inflammatory response.

Early coronary angiography should be performed in all patients with ABS to rule out the presence of a significant obstructive coronary lesion. Patients with ABS often have luminal irregularities or normal coronary vessels. However, concomitant obstructive coronary lesions may be found, especially in elderly patients.

The hallmark of ABS is a characteristic transient contractility abnormality of the left ventricle causing ballooning of the apex, which can be detected on left ventricular angiography or echocardiography. There are 3 distinct variants of ABS, according to the left ventricular myocardial wall segments involved.¹⁰ The classic form of takotsubo is characterized by hypokinesis, dyskinesis, or akinesis of the middle and apical segments of the left ventricle. The basal segment is usually spared and may be hyperdynamic. In the midventricular or apical sparing variant, the wall motion abnormalities are restricted to the midventricular segments, and apical contraction is preserved. This case resembles the atypical variant, because the midventricular segments were affected, whereas apical and basal regions were preserved. A rare variant of takotsubo exists with hypokinesis or akinesis of the base and preserved apical function.

Besides ABS and AMI, an important entity to consider in the differential diagnosis of transient wall motion abnormalities is regional myocarditis. Viral titers are helpful in excluding this condition. Furthermore, prolonged recovery is more commonly seen in myocarditis compared with ABS. Imaging studies are particularly helpful in this scenario.

Cardiac MRI demonstrates the wall motion abnormalities or apical ballooning typical for this condition and can differentiate ABS from myocarditis or MI. It is known that delayed myocardial enhancement is seen with myocardial fibrosis. Typically in ischemic cardiomyopathy, there is wall thinning with associated delayed enhancement that extends from the subendocardium to the epicardium (from 0%-90% of wall thickness) of a particular vascular territory. In myocarditis, the enhancement is usually seen in the involved intramyocardial (mesocardium) region, and the pattern is patchy. In ABS, the delayed enhancement is absent, because there is no fibrosis in the area of regional wall motion abnormalities, and wall thickness is usually normal.^9,10

No evidence-based guidelines for treating ABS are currently available. Most patients are initially treated with antiplatelets/anticoagulant therapy, nitrates, and diuretics if the patient presents with heart failure. Patients should be admitted to an intensive care unit for close cardiac monitoring. Once ABS is diagnosed and significant coronary stenosis is excluded, patients should receive standard supportive care and optimal neurohormonal therapy. This should include beta blocker or combined alpha/beta blocker agents, an ACE-I or angiotensin receptor blocker, and diuretics if appropriate. Once left ventricular function (LVF) is recovered, therapy with inhibitors of the renin-angiotensin system may be discontinued, but patients should remain on long-term alpha or beta blocker therapy, because the sympathetic blockade provided by these agents may prevent recurrences of this disease.¹⁰

Prognosis is generally favorable, and most patients recover to normal LVF over weeks to months. It is important to assess the LVF 4 to 6 weeks after the patient is discharged to confirm the diagnosis of ABS. Recurrence may occur in up to 9% of cases.¹⁰ Long-term mortality is similar compared with the age-matched general population.

Conclusion

Apical ballooning syndrome is a relatively novel cardiomyopathy that has gained important attention among the cardiovascular community, mostly because its clinical presentation mimics that of an acute coronary syndrome. Awareness of this entity will result in a more focused diagnosis and appropriate treatment. Managing both cardiac and emotional components of this disease will have a permanent impact in the reversibility and secondary prevention of this cardiomyopathy.

Acknowledgments
Special thanks to the Radiology Service at the VA Caribbean Healthcare System, in particular Dr. Frances Aulet for interpretation of the cardiac MRI results and assistance with MRI images.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

In 2010, the VA gave presumptive status to 9 infectious diseases that are endemic to southwest Asia and Afghanistan. This classification relieves the veteran of having to prove that an illness was connected to exposure during service in a specific region. The purpose of this secondary analysis is to determine the impact of the presumptive infectious disease (PID) ruling by the VHA by assessing the pre- and postruling health care use of veterans diagnosed with one of the infectious diseases.

Background

As of December 2012, 1.6 million veterans who served in Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) were eligible to receive VHA care. The number of combat related injuries is commonly released to the public, but figures related to noncombat illnesses, such as infectious diseases, are reported less frequently. Sixteen percent of the 899,752 OEF/OIF/OND veterans who received VHA care through December 2012 were diagnosed with an infectious disease.¹

Long-term disability stemming from any type of illness, disease, or injury is potentially compensable through VA disability compensation programs. The disability must be service-connected for a veteran to receive compensation; that is, it must be determined to be a likely by-product of “an illness, disease or injury incurred or aggravated while the soldier was on active military service.”² The benefit application process takes time, because service connection must be established prior to determining entitlement to disability benefits.²

Congress mandated that the VA determine the illnesses that justified a presumption of service-connection based on exposure to hazards of Iraq and Afghanistan service. In response, the VA requested that the Institute of Medicine (IOM) conduct a review of the scientific and medical literature to determine the diseases related to hazards of service in southwest Asia and Afghanistan.

In a 2006 report, the IOM identified several diseases that were relevant to and known to have been diagnosed among military personnel during and after deployment in these regions. On September 29, 2010, responding to the report, VA added brucellosis, Campylobacter jejuni, Coxiella burnetti (Q fever), malaria, Mycobacterium tuberculosis (TB), nontyphoid Salmonella, Shigella, visceral leishmaniasis, and West Nile virus to the list of presumptive illnesses.³ The final rule was published in the Federal Register and is codified in 38 C.F.R. § 3.317(c).⁴

Classifying an illness as presumptive relieves the veteran of having to prove that their illness was connected to exposure during service in a specific region, “…[shifting] the burden of proof concerning whether a disease or disability was caused or aggravated due to service from the Veteran to the VA.”⁵ Based on latency periods, 7 of the 9 diseases must manifest to a > 10% degree of disability within a year of separation from a qualifying period of service. No date boundary was set on the period of presumption for TB or visceral leishmaniasis.⁶

Methods

Veterans are eligible for VHA care when they separate from active-duty service, or they are deactivated at the completion of their reserve or guard tour. Veterans eligible for health care were identified using a roster file from the DoD Defense Manpower Data Center (DMDC). This file also contained demographic (eg, sex, race) and service (eg, branch, rank) information. Inpatient and outpatient health care data were extracted from the VHA Office of Public Health’s quarterly files.

Study Population

OEF/OIF/OND veterans whose roster file records indicated a deployment to Iraq, Kuwait, Saudi Arabia, the neutral zone (between Iraq and Saudi Arabia), Bahrain, Qatar, The United Arab Emirates, Oman, Gulf of Aden, Gulf of Oman, waters of the Persian Gulf, the Arabian Sea, the Red Sea, and Afghanistan were eligible for the study. These veterans had to have separated from service between June 28, 2009, and December 29, 2011, and sought VHA care within a year of separation. Veterans with a human immunodeficiency virus diagnosis, an illness that is highly correlated with TB, were excluded from the study, as were deceased and Coast Guard veterans.

The final study population of 107,030 OEF/OIF/OND veterans was further divided into 2 mutually exclusive study groups by assessing the ICD-9-CM code in the first diagnostic position. The first group, the PID group, was given priority. To be included in this group, a veteran must have been diagnosed with ≥ 1 of the following presumptive diseases within a year of separation (ICD-9-CM codes): Brucellosis (023), Campylobacter jejuni (008.43), Coxiella burnetti/Q fever (083.0), malaria (084), nontyphoid Salmonella (003), Shigella (004), or West Nile virus (066.4). For TB (010-018) and visceral leishmaniasis (085.0), a diagnosis could occur any time after separation.

Related: DoD Healthy Base Initiative

The second infectious disease group included veterans diagnosed with any infectious disease (ICD-9-CM codes 001-139) that was not a PID. To be considered for inclusion in the other infectious disease group, a veteran must have been diagnosed with the illness at any point after separation. This group was created as a control group for comparing differences in health care use of the veterans diagnosed with a PID both before and after the rule change. The illnesses within each study group were distinct, thus no direct comparisons were made between the groups. Instead, the magnitude of the difference in use before and after the presumptive disease ruling was compared.

Statistical Analysis

It is possible to have multiple services performed during a single outpatient visit, services that will generate separate bills, thus appearing to be different visits. For the purposes of this study, only 1 visit per day was counted when constructing the monthly health care counts for the 12 months before and after the date of diagnosis of a PID or another infectious disease. A general linear model was created to assess differences in the number of outpatient visits pre- and postruling, adjusting for the number of unique illnesses a veteran had. To adjust for normality in the model, the inverse log of the count of outpatient visits was used in the procedure. P values were compared with an á level of 0.05 to determine significance.

Results

Among the 107,030 veterans receiving VHA care between June 28, 2009, and December 29, 2011, < 0.1% (n = 98) were in the PID group, and 7% (n = 7,603) were in the other infectious disease group (Tables 1 and 2). A significantly smaller proportion of active-duty (“regular”) veterans was in the PID group (50.0%) compared with the other infectious disease group (63.9%). Conversely, a significantly larger proportion of reserve or guard veterans werein the PID group (51.0%) compared with the other infectious disease group (36.1%) (P = .0089). The PID group included a higher proportion of Hispanic veterans (16.3%) and a lower proportion of black veterans (7.1%) than did the other infectious disease group.

The opposite was observed in the other infectious disease group: There was a lower proportion of Hispanic veterans (12.6%) and a higher proportion of black veterans (17.0%). Veterans whose military occupation status indicated combat experience were highly represented in each of the disease groups, as were males. Army veterans were disproportionately represented in the PID group (76.5%) compared with the other infectious disease group (65.4%), whereas the opposite was true for Marine Corps veterans (13.3% and 18.9%, respectively)(Table 2).

To assess the impact of the ruling on the health care-seeking behaviors of veterans, each group was further divided by the timing of diagnosis, specifically, before or after the PID ruling on September 29, 2010. Forty-five percent of the study population received a diagnosis prior to the ruling. Thirty-six percent of the PID group and 30% of the other infectious disease study groups were diagnosed before the ruling (Table 3).

Veterans in the other infectious disease group who were diagnosed after the PID ruling had a significantly higher total number of outpatient visits than did those diagnosed before the ruling (P < .05). A small increase was observed in the median number of outpatient visits among veterans diagnosed with a PID preruling (median = 7) compared with those diagnosed postruling (median = 8), but the difference was not statistically significant. Veterans in the preruling PID group received a diagnosis < 117 days (median value) after separation from service, whereas those in the postruling group received a diagnosis < 291 days (median value) after separation from service (Table 3).

There was an increase in health care visits in the months directly before and after diagnosis, regardless of whether a veteran was diagnosed before or after the ruling. Figure 1 shows the total number of health care visits (visits for any condition) in the 12 months before and 12 months after a PID diagnosis, as well as the number of patients receiving care in those same months. In the months prior to receiving a diagnosis, the number of veterans receiving health care services followed the same trajectory as the total number of health care visits, regardless of the timing of the diagnosis. In the months after receiving a diagnosis, the trajectory for the total number of health care visits and the number of veterans generally followed the same path within the preruling group. In contrast, within the postruling group, the total number of visits was higher than the number of veterans, especially in the latter months, indicating that veterans were receiving services multiple times in a month.

The patterns of health care use in the other infectious disease group were similar to those of the PID group, though the trajectories were more symmetrical for the other infectious disease pre- and postruling groups. There is a distinct increase in the total number of health care visits until diagnosis and a steady decrease in the 12 months after diagnosis with a leveling off of health care use toward the end of the observation period (Figure 2).

Discussion

The rate of PIDs in the U.S. was different from the observed rate in the study population, albeit a limited comparison. In the U.S. in 2010, the reported incidence per 100,000 persons was 0.04 for brucellosis, 13.52 for Campylobacter jejuni, 17.73 for nontyphoid Salmonella, and 0.2 for West Nile virus, vs no cases reported in the study.^7,8 In contrast, the 2010-reported U.S. incidence rates per 100,000 persons with Q fever (0.04), malaria (0.58), and TB (3.64) were lower than those reported in the study population (3.32, 8.30, and 41.50 per 100,000 patients, respectively).⁷

Of the 107,030 OEF/OIF/OND veterans who received care during the study period, < 0.1% were diagnosed with a PIDs and 7% were diagnosed with a different infectious disease. Analysis indicated that 88 of the 98 PID were either TB or malaria cases. Thirty-six percent of the PID cases and 30% of the other infectious disease cases were diagnosed prior to the PID ruling. Veterans in the preruling PID and other infectious disease groups received a diagnosis within 4 or 5 months of becoming eligible for VHA services, whereas those in the postruling groups received a diagnosis within 10 months of eligibility, an observation that may have been caused by outliers and amplified by the small number of cases in the preruling PID group. However, this difference in time to diagnosis between the pre- and postruling groups does not seem to be a reflection of a delay in health care-seeking behavior in general: Veterans in both study groups sought VA services within 73 days of separating from active-duty service.

No significant difference in health care use was found between the pre- and postruling PID groups. When looking at the number of veterans receiving care each month and the total number of health care encounters, the ratio of encounters to veterans was less stable in the PID group than that of the other infectious disease group. Veterans with a PID received multiple outpatient services per month, especially in the postruling PID group. This may be a reflection of follow-up care needed for specific diseases.

Limitations

There are several limitations to note in the study. First, service members could have been diagnosed while still receiving health care services in the military health system, resulting in a low diagnosis rate within the VA. Second, the cases were identified solely based on ICD-9-CM codes; these are not confirmed diagnoses, and misclassification may occur. Future studies should consider incorporating laboratory results and other confirmatory methods of identification for case capture. A third limitation was the lack of availability of health care records outside of VHA. A large proportion of the study population was composed of the reserve/guard component. These veterans return to civilian jobs after separation and often have access to health care outside of VHA. Combined, these limitations affect the ability to identify the prevalence of infectious diseases among veterans.

Related: Women Using VA Health Care

Several findings could not be explored due to methodological limitations but warrant further exploration. First, the longer time period between eligibility and diagnosis post- vs preruling may be an indication that the ruling affected a veteran’s health care-seeking behavior. Second, it was possible that veterans presented with symptoms similar to one of the PIDs but were subsequently diagnosed with another infectious disease, which would affect the disease and use figures. Finally, studies should consider using confirmatory methods of diagnosis to assess the true prevalence of presumptive infectious diseases in the veteran population.

Conclusions

Very few PID cases were identified in the study population. This may be due to the limitation of the available data. However, some interesting findings such as a greater number of encounters for the infectious disease group post- vs preruling and differences in time between eligibility and diagnosis pre- and postruling were found and should be investigated further.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

In 2010, the VA gave presumptive status to 9 infectious diseases that are endemic to southwest Asia and Afghanistan. This classification relieves the veteran of having to prove that an illness was connected to exposure during service in a specific region. The purpose of this secondary analysis is to determine the impact of the presumptive infectious disease (PID) ruling by the VHA by assessing the pre- and postruling health care use of veterans diagnosed with one of the infectious diseases.

Background

As of December 2012, 1.6 million veterans who served in Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) were eligible to receive VHA care. The number of combat related injuries is commonly released to the public, but figures related to noncombat illnesses, such as infectious diseases, are reported less frequently. Sixteen percent of the 899,752 OEF/OIF/OND veterans who received VHA care through December 2012 were diagnosed with an infectious disease.¹

Long-term disability stemming from any type of illness, disease, or injury is potentially compensable through VA disability compensation programs. The disability must be service-connected for a veteran to receive compensation; that is, it must be determined to be a likely by-product of “an illness, disease or injury incurred or aggravated while the soldier was on active military service.”² The benefit application process takes time, because service connection must be established prior to determining entitlement to disability benefits.²

Congress mandated that the VA determine the illnesses that justified a presumption of service-connection based on exposure to hazards of Iraq and Afghanistan service. In response, the VA requested that the Institute of Medicine (IOM) conduct a review of the scientific and medical literature to determine the diseases related to hazards of service in southwest Asia and Afghanistan.

In a 2006 report, the IOM identified several diseases that were relevant to and known to have been diagnosed among military personnel during and after deployment in these regions. On September 29, 2010, responding to the report, VA added brucellosis, Campylobacter jejuni, Coxiella burnetti (Q fever), malaria, Mycobacterium tuberculosis (TB), nontyphoid Salmonella, Shigella, visceral leishmaniasis, and West Nile virus to the list of presumptive illnesses.³ The final rule was published in the Federal Register and is codified in 38 C.F.R. § 3.317(c).⁴

Classifying an illness as presumptive relieves the veteran of having to prove that their illness was connected to exposure during service in a specific region, “…[shifting] the burden of proof concerning whether a disease or disability was caused or aggravated due to service from the Veteran to the VA.”⁵ Based on latency periods, 7 of the 9 diseases must manifest to a > 10% degree of disability within a year of separation from a qualifying period of service. No date boundary was set on the period of presumption for TB or visceral leishmaniasis.⁶

Methods

Veterans are eligible for VHA care when they separate from active-duty service, or they are deactivated at the completion of their reserve or guard tour. Veterans eligible for health care were identified using a roster file from the DoD Defense Manpower Data Center (DMDC). This file also contained demographic (eg, sex, race) and service (eg, branch, rank) information. Inpatient and outpatient health care data were extracted from the VHA Office of Public Health’s quarterly files.

Study Population

OEF/OIF/OND veterans whose roster file records indicated a deployment to Iraq, Kuwait, Saudi Arabia, the neutral zone (between Iraq and Saudi Arabia), Bahrain, Qatar, The United Arab Emirates, Oman, Gulf of Aden, Gulf of Oman, waters of the Persian Gulf, the Arabian Sea, the Red Sea, and Afghanistan were eligible for the study. These veterans had to have separated from service between June 28, 2009, and December 29, 2011, and sought VHA care within a year of separation. Veterans with a human immunodeficiency virus diagnosis, an illness that is highly correlated with TB, were excluded from the study, as were deceased and Coast Guard veterans.

The final study population of 107,030 OEF/OIF/OND veterans was further divided into 2 mutually exclusive study groups by assessing the ICD-9-CM code in the first diagnostic position. The first group, the PID group, was given priority. To be included in this group, a veteran must have been diagnosed with ≥ 1 of the following presumptive diseases within a year of separation (ICD-9-CM codes): Brucellosis (023), Campylobacter jejuni (008.43), Coxiella burnetti/Q fever (083.0), malaria (084), nontyphoid Salmonella (003), Shigella (004), or West Nile virus (066.4). For TB (010-018) and visceral leishmaniasis (085.0), a diagnosis could occur any time after separation.

Related: DoD Healthy Base Initiative

The second infectious disease group included veterans diagnosed with any infectious disease (ICD-9-CM codes 001-139) that was not a PID. To be considered for inclusion in the other infectious disease group, a veteran must have been diagnosed with the illness at any point after separation. This group was created as a control group for comparing differences in health care use of the veterans diagnosed with a PID both before and after the rule change. The illnesses within each study group were distinct, thus no direct comparisons were made between the groups. Instead, the magnitude of the difference in use before and after the presumptive disease ruling was compared.

Statistical Analysis

It is possible to have multiple services performed during a single outpatient visit, services that will generate separate bills, thus appearing to be different visits. For the purposes of this study, only 1 visit per day was counted when constructing the monthly health care counts for the 12 months before and after the date of diagnosis of a PID or another infectious disease. A general linear model was created to assess differences in the number of outpatient visits pre- and postruling, adjusting for the number of unique illnesses a veteran had. To adjust for normality in the model, the inverse log of the count of outpatient visits was used in the procedure. P values were compared with an á level of 0.05 to determine significance.

Results

Among the 107,030 veterans receiving VHA care between June 28, 2009, and December 29, 2011, < 0.1% (n = 98) were in the PID group, and 7% (n = 7,603) were in the other infectious disease group (Tables 1 and 2). A significantly smaller proportion of active-duty (“regular”) veterans was in the PID group (50.0%) compared with the other infectious disease group (63.9%). Conversely, a significantly larger proportion of reserve or guard veterans werein the PID group (51.0%) compared with the other infectious disease group (36.1%) (P = .0089). The PID group included a higher proportion of Hispanic veterans (16.3%) and a lower proportion of black veterans (7.1%) than did the other infectious disease group.

The opposite was observed in the other infectious disease group: There was a lower proportion of Hispanic veterans (12.6%) and a higher proportion of black veterans (17.0%). Veterans whose military occupation status indicated combat experience were highly represented in each of the disease groups, as were males. Army veterans were disproportionately represented in the PID group (76.5%) compared with the other infectious disease group (65.4%), whereas the opposite was true for Marine Corps veterans (13.3% and 18.9%, respectively)(Table 2).

To assess the impact of the ruling on the health care-seeking behaviors of veterans, each group was further divided by the timing of diagnosis, specifically, before or after the PID ruling on September 29, 2010. Forty-five percent of the study population received a diagnosis prior to the ruling. Thirty-six percent of the PID group and 30% of the other infectious disease study groups were diagnosed before the ruling (Table 3).

Veterans in the other infectious disease group who were diagnosed after the PID ruling had a significantly higher total number of outpatient visits than did those diagnosed before the ruling (P < .05). A small increase was observed in the median number of outpatient visits among veterans diagnosed with a PID preruling (median = 7) compared with those diagnosed postruling (median = 8), but the difference was not statistically significant. Veterans in the preruling PID group received a diagnosis < 117 days (median value) after separation from service, whereas those in the postruling group received a diagnosis < 291 days (median value) after separation from service (Table 3).

There was an increase in health care visits in the months directly before and after diagnosis, regardless of whether a veteran was diagnosed before or after the ruling. Figure 1 shows the total number of health care visits (visits for any condition) in the 12 months before and 12 months after a PID diagnosis, as well as the number of patients receiving care in those same months. In the months prior to receiving a diagnosis, the number of veterans receiving health care services followed the same trajectory as the total number of health care visits, regardless of the timing of the diagnosis. In the months after receiving a diagnosis, the trajectory for the total number of health care visits and the number of veterans generally followed the same path within the preruling group. In contrast, within the postruling group, the total number of visits was higher than the number of veterans, especially in the latter months, indicating that veterans were receiving services multiple times in a month.

The patterns of health care use in the other infectious disease group were similar to those of the PID group, though the trajectories were more symmetrical for the other infectious disease pre- and postruling groups. There is a distinct increase in the total number of health care visits until diagnosis and a steady decrease in the 12 months after diagnosis with a leveling off of health care use toward the end of the observation period (Figure 2).

Discussion

The rate of PIDs in the U.S. was different from the observed rate in the study population, albeit a limited comparison. In the U.S. in 2010, the reported incidence per 100,000 persons was 0.04 for brucellosis, 13.52 for Campylobacter jejuni, 17.73 for nontyphoid Salmonella, and 0.2 for West Nile virus, vs no cases reported in the study.^7,8 In contrast, the 2010-reported U.S. incidence rates per 100,000 persons with Q fever (0.04), malaria (0.58), and TB (3.64) were lower than those reported in the study population (3.32, 8.30, and 41.50 per 100,000 patients, respectively).⁷

Of the 107,030 OEF/OIF/OND veterans who received care during the study period, < 0.1% were diagnosed with a PIDs and 7% were diagnosed with a different infectious disease. Analysis indicated that 88 of the 98 PID were either TB or malaria cases. Thirty-six percent of the PID cases and 30% of the other infectious disease cases were diagnosed prior to the PID ruling. Veterans in the preruling PID and other infectious disease groups received a diagnosis within 4 or 5 months of becoming eligible for VHA services, whereas those in the postruling groups received a diagnosis within 10 months of eligibility, an observation that may have been caused by outliers and amplified by the small number of cases in the preruling PID group. However, this difference in time to diagnosis between the pre- and postruling groups does not seem to be a reflection of a delay in health care-seeking behavior in general: Veterans in both study groups sought VA services within 73 days of separating from active-duty service.

No significant difference in health care use was found between the pre- and postruling PID groups. When looking at the number of veterans receiving care each month and the total number of health care encounters, the ratio of encounters to veterans was less stable in the PID group than that of the other infectious disease group. Veterans with a PID received multiple outpatient services per month, especially in the postruling PID group. This may be a reflection of follow-up care needed for specific diseases.

Limitations

There are several limitations to note in the study. First, service members could have been diagnosed while still receiving health care services in the military health system, resulting in a low diagnosis rate within the VA. Second, the cases were identified solely based on ICD-9-CM codes; these are not confirmed diagnoses, and misclassification may occur. Future studies should consider incorporating laboratory results and other confirmatory methods of identification for case capture. A third limitation was the lack of availability of health care records outside of VHA. A large proportion of the study population was composed of the reserve/guard component. These veterans return to civilian jobs after separation and often have access to health care outside of VHA. Combined, these limitations affect the ability to identify the prevalence of infectious diseases among veterans.

Related: Women Using VA Health Care

Several findings could not be explored due to methodological limitations but warrant further exploration. First, the longer time period between eligibility and diagnosis post- vs preruling may be an indication that the ruling affected a veteran’s health care-seeking behavior. Second, it was possible that veterans presented with symptoms similar to one of the PIDs but were subsequently diagnosed with another infectious disease, which would affect the disease and use figures. Finally, studies should consider using confirmatory methods of diagnosis to assess the true prevalence of presumptive infectious diseases in the veteran population.

Conclusions

Very few PID cases were identified in the study population. This may be due to the limitation of the available data. However, some interesting findings such as a greater number of encounters for the infectious disease group post- vs preruling and differences in time between eligibility and diagnosis pre- and postruling were found and should be investigated further.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

In 2010, the VA gave presumptive status to 9 infectious diseases that are endemic to southwest Asia and Afghanistan. This classification relieves the veteran of having to prove that an illness was connected to exposure during service in a specific region. The purpose of this secondary analysis is to determine the impact of the presumptive infectious disease (PID) ruling by the VHA by assessing the pre- and postruling health care use of veterans diagnosed with one of the infectious diseases.

Background

As of December 2012, 1.6 million veterans who served in Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) were eligible to receive VHA care. The number of combat related injuries is commonly released to the public, but figures related to noncombat illnesses, such as infectious diseases, are reported less frequently. Sixteen percent of the 899,752 OEF/OIF/OND veterans who received VHA care through December 2012 were diagnosed with an infectious disease.¹

Long-term disability stemming from any type of illness, disease, or injury is potentially compensable through VA disability compensation programs. The disability must be service-connected for a veteran to receive compensation; that is, it must be determined to be a likely by-product of “an illness, disease or injury incurred or aggravated while the soldier was on active military service.”² The benefit application process takes time, because service connection must be established prior to determining entitlement to disability benefits.²

Congress mandated that the VA determine the illnesses that justified a presumption of service-connection based on exposure to hazards of Iraq and Afghanistan service. In response, the VA requested that the Institute of Medicine (IOM) conduct a review of the scientific and medical literature to determine the diseases related to hazards of service in southwest Asia and Afghanistan.

In a 2006 report, the IOM identified several diseases that were relevant to and known to have been diagnosed among military personnel during and after deployment in these regions. On September 29, 2010, responding to the report, VA added brucellosis, Campylobacter jejuni, Coxiella burnetti (Q fever), malaria, Mycobacterium tuberculosis (TB), nontyphoid Salmonella, Shigella, visceral leishmaniasis, and West Nile virus to the list of presumptive illnesses.³ The final rule was published in the Federal Register and is codified in 38 C.F.R. § 3.317(c).⁴

Classifying an illness as presumptive relieves the veteran of having to prove that their illness was connected to exposure during service in a specific region, “…[shifting] the burden of proof concerning whether a disease or disability was caused or aggravated due to service from the Veteran to the VA.”⁵ Based on latency periods, 7 of the 9 diseases must manifest to a > 10% degree of disability within a year of separation from a qualifying period of service. No date boundary was set on the period of presumption for TB or visceral leishmaniasis.⁶

Methods

Veterans are eligible for VHA care when they separate from active-duty service, or they are deactivated at the completion of their reserve or guard tour. Veterans eligible for health care were identified using a roster file from the DoD Defense Manpower Data Center (DMDC). This file also contained demographic (eg, sex, race) and service (eg, branch, rank) information. Inpatient and outpatient health care data were extracted from the VHA Office of Public Health’s quarterly files.

Study Population

OEF/OIF/OND veterans whose roster file records indicated a deployment to Iraq, Kuwait, Saudi Arabia, the neutral zone (between Iraq and Saudi Arabia), Bahrain, Qatar, The United Arab Emirates, Oman, Gulf of Aden, Gulf of Oman, waters of the Persian Gulf, the Arabian Sea, the Red Sea, and Afghanistan were eligible for the study. These veterans had to have separated from service between June 28, 2009, and December 29, 2011, and sought VHA care within a year of separation. Veterans with a human immunodeficiency virus diagnosis, an illness that is highly correlated with TB, were excluded from the study, as were deceased and Coast Guard veterans.

The final study population of 107,030 OEF/OIF/OND veterans was further divided into 2 mutually exclusive study groups by assessing the ICD-9-CM code in the first diagnostic position. The first group, the PID group, was given priority. To be included in this group, a veteran must have been diagnosed with ≥ 1 of the following presumptive diseases within a year of separation (ICD-9-CM codes): Brucellosis (023), Campylobacter jejuni (008.43), Coxiella burnetti/Q fever (083.0), malaria (084), nontyphoid Salmonella (003), Shigella (004), or West Nile virus (066.4). For TB (010-018) and visceral leishmaniasis (085.0), a diagnosis could occur any time after separation.

Related: DoD Healthy Base Initiative

The second infectious disease group included veterans diagnosed with any infectious disease (ICD-9-CM codes 001-139) that was not a PID. To be considered for inclusion in the other infectious disease group, a veteran must have been diagnosed with the illness at any point after separation. This group was created as a control group for comparing differences in health care use of the veterans diagnosed with a PID both before and after the rule change. The illnesses within each study group were distinct, thus no direct comparisons were made between the groups. Instead, the magnitude of the difference in use before and after the presumptive disease ruling was compared.

Statistical Analysis

It is possible to have multiple services performed during a single outpatient visit, services that will generate separate bills, thus appearing to be different visits. For the purposes of this study, only 1 visit per day was counted when constructing the monthly health care counts for the 12 months before and after the date of diagnosis of a PID or another infectious disease. A general linear model was created to assess differences in the number of outpatient visits pre- and postruling, adjusting for the number of unique illnesses a veteran had. To adjust for normality in the model, the inverse log of the count of outpatient visits was used in the procedure. P values were compared with an á level of 0.05 to determine significance.

Results

Among the 107,030 veterans receiving VHA care between June 28, 2009, and December 29, 2011, < 0.1% (n = 98) were in the PID group, and 7% (n = 7,603) were in the other infectious disease group (Tables 1 and 2). A significantly smaller proportion of active-duty (“regular”) veterans was in the PID group (50.0%) compared with the other infectious disease group (63.9%). Conversely, a significantly larger proportion of reserve or guard veterans werein the PID group (51.0%) compared with the other infectious disease group (36.1%) (P = .0089). The PID group included a higher proportion of Hispanic veterans (16.3%) and a lower proportion of black veterans (7.1%) than did the other infectious disease group.

The opposite was observed in the other infectious disease group: There was a lower proportion of Hispanic veterans (12.6%) and a higher proportion of black veterans (17.0%). Veterans whose military occupation status indicated combat experience were highly represented in each of the disease groups, as were males. Army veterans were disproportionately represented in the PID group (76.5%) compared with the other infectious disease group (65.4%), whereas the opposite was true for Marine Corps veterans (13.3% and 18.9%, respectively)(Table 2).

To assess the impact of the ruling on the health care-seeking behaviors of veterans, each group was further divided by the timing of diagnosis, specifically, before or after the PID ruling on September 29, 2010. Forty-five percent of the study population received a diagnosis prior to the ruling. Thirty-six percent of the PID group and 30% of the other infectious disease study groups were diagnosed before the ruling (Table 3).

Veterans in the other infectious disease group who were diagnosed after the PID ruling had a significantly higher total number of outpatient visits than did those diagnosed before the ruling (P < .05). A small increase was observed in the median number of outpatient visits among veterans diagnosed with a PID preruling (median = 7) compared with those diagnosed postruling (median = 8), but the difference was not statistically significant. Veterans in the preruling PID group received a diagnosis < 117 days (median value) after separation from service, whereas those in the postruling group received a diagnosis < 291 days (median value) after separation from service (Table 3).

There was an increase in health care visits in the months directly before and after diagnosis, regardless of whether a veteran was diagnosed before or after the ruling. Figure 1 shows the total number of health care visits (visits for any condition) in the 12 months before and 12 months after a PID diagnosis, as well as the number of patients receiving care in those same months. In the months prior to receiving a diagnosis, the number of veterans receiving health care services followed the same trajectory as the total number of health care visits, regardless of the timing of the diagnosis. In the months after receiving a diagnosis, the trajectory for the total number of health care visits and the number of veterans generally followed the same path within the preruling group. In contrast, within the postruling group, the total number of visits was higher than the number of veterans, especially in the latter months, indicating that veterans were receiving services multiple times in a month.

The patterns of health care use in the other infectious disease group were similar to those of the PID group, though the trajectories were more symmetrical for the other infectious disease pre- and postruling groups. There is a distinct increase in the total number of health care visits until diagnosis and a steady decrease in the 12 months after diagnosis with a leveling off of health care use toward the end of the observation period (Figure 2).

Discussion

The rate of PIDs in the U.S. was different from the observed rate in the study population, albeit a limited comparison. In the U.S. in 2010, the reported incidence per 100,000 persons was 0.04 for brucellosis, 13.52 for Campylobacter jejuni, 17.73 for nontyphoid Salmonella, and 0.2 for West Nile virus, vs no cases reported in the study.^7,8 In contrast, the 2010-reported U.S. incidence rates per 100,000 persons with Q fever (0.04), malaria (0.58), and TB (3.64) were lower than those reported in the study population (3.32, 8.30, and 41.50 per 100,000 patients, respectively).⁷

Of the 107,030 OEF/OIF/OND veterans who received care during the study period, < 0.1% were diagnosed with a PIDs and 7% were diagnosed with a different infectious disease. Analysis indicated that 88 of the 98 PID were either TB or malaria cases. Thirty-six percent of the PID cases and 30% of the other infectious disease cases were diagnosed prior to the PID ruling. Veterans in the preruling PID and other infectious disease groups received a diagnosis within 4 or 5 months of becoming eligible for VHA services, whereas those in the postruling groups received a diagnosis within 10 months of eligibility, an observation that may have been caused by outliers and amplified by the small number of cases in the preruling PID group. However, this difference in time to diagnosis between the pre- and postruling groups does not seem to be a reflection of a delay in health care-seeking behavior in general: Veterans in both study groups sought VA services within 73 days of separating from active-duty service.

No significant difference in health care use was found between the pre- and postruling PID groups. When looking at the number of veterans receiving care each month and the total number of health care encounters, the ratio of encounters to veterans was less stable in the PID group than that of the other infectious disease group. Veterans with a PID received multiple outpatient services per month, especially in the postruling PID group. This may be a reflection of follow-up care needed for specific diseases.

Limitations

There are several limitations to note in the study. First, service members could have been diagnosed while still receiving health care services in the military health system, resulting in a low diagnosis rate within the VA. Second, the cases were identified solely based on ICD-9-CM codes; these are not confirmed diagnoses, and misclassification may occur. Future studies should consider incorporating laboratory results and other confirmatory methods of identification for case capture. A third limitation was the lack of availability of health care records outside of VHA. A large proportion of the study population was composed of the reserve/guard component. These veterans return to civilian jobs after separation and often have access to health care outside of VHA. Combined, these limitations affect the ability to identify the prevalence of infectious diseases among veterans.

Related: Women Using VA Health Care

Several findings could not be explored due to methodological limitations but warrant further exploration. First, the longer time period between eligibility and diagnosis post- vs preruling may be an indication that the ruling affected a veteran’s health care-seeking behavior. Second, it was possible that veterans presented with symptoms similar to one of the PIDs but were subsequently diagnosed with another infectious disease, which would affect the disease and use figures. Finally, studies should consider using confirmatory methods of diagnosis to assess the true prevalence of presumptive infectious diseases in the veteran population.

Conclusions

Very few PID cases were identified in the study population. This may be due to the limitation of the available data. However, some interesting findings such as a greater number of encounters for the infectious disease group post- vs preruling and differences in time between eligibility and diagnosis pre- and postruling were found and should be investigated further.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Onychomycosis is a chronic fungal infection of the nails. Dermatophytes are the most common etiologic agents, but yeasts and nondermatophyte molds also constitute a substantial number of cases.¹ An accumulation of debris under distorted, deformed, thickened, and discolored nails, particularly with ragged and furrowed edges, strongly suggests tinea unguium.² Candidal onychomycosis (CO) lacks gross distortion and accumulated detritus and mainly affects fingernails.³ Nondermatophytic molds cause 1.5% to 6% of cases of onychomycosis, mostly seen in toenails of elderly individuals with a history of trauma.⁴ Onychomycosis affects 5.5% of the world population⁵ and represents 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.⁶

The incidence of onychomycosis ranges from 0.5% to 5% in the general population in India.⁷ The incidence is particularly high in warm humid climates such as India.⁸ Researchers have found certain habits of the population in the Indian subcontinent (eg, walking with bare feet, wearing ill-fitting shoes, nail-biting [eg, onychophagia], working with chemicals) to be contributing factors for onychomycosis.⁹ Several studies have shown that the prevalence of onychomycosis increases with age, possibly due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, prolonged exposure to pathogenic fungi, suboptimal immune function, inactivity, or inability to trim the toenails and care for the feet.¹⁰ Nail infection is a cosmetic problem with serious physical and psychological morbidity and also serves as the fungal reservoir for skin infections. Besides destruction and disfigurement of the nail plate, onychomycosis can lead to self-consciousness and impairment of daily functioning.¹¹

Nail dystrophy occurs secondary to various systemic disorders or can be associated with other dermatologic conditions. Nail discoloration and other onychia should be differentiated from onychomycosis by classifying nail lesions as distal lateral subungual onychomycosis, proximal subungual onychomycosis (PSO), CO, white superficial onychomycosis (WSO), and total dystrophic onychomycosis.¹² Laboratory investigation is necessary to accurately differentiate between fungal infections and other skin diseases before starting treatment. Our hospital-based study sought to determine the incidence and epidemiology of onychomycosis with an analysis of 134 participants with clinically suspected onychomycosis. We evaluated prevalence based on age, sex, and occupation, as well as the most common pathogens.

Materials and Methods

Study Design and Participants

The study population consisted of 134 patients with clinically suspected onychomycosis who visited the dermatology department at the Veer Chandra Singh Garhwali Government Institute of Medical Sciences and Research Institute in Uttarakhand, India (October 2010 to October 2011). A thorough history was obtained and a detailed examination of the distorted nails was conducted in the microbiology laboratory. Patient history and demographic factors such as age, sex, occupation, and related history of risk factors for onychomycosis were recorded pro forma. Some of the details such as itching, family history of fungal infection, and prior cutaneous infections were recorded. Patients who were undergoing treatment with systemic or topical antifungal agents in the 4 weeks preceding the study period were excluded to rule out false-negative cases and to avoid the influence of antifungal agents on the disease course.

Assessments

Two samples were taken from each patient on different days. Participants were divided into 4 groups based on occupation: farmer, housewife, student, and other (eg, clerk, shopkeeper, painter). Clinical presentation of discoloration, onycholysis, subungual hyperkeratosis, and nail thickening affecting the distal and/or lateral nail plate was defined as distal lateral subungual onychomycosis; discoloration and onycholysis affecting the proximal part of the nail was defined as PSO; association with paronychia and distal and lateral onycholysis was defined as CO; white opaque patches on the nail surface were defined as WSO; and end-stage nail disease was defined as total dystrophic onychomycosis.

Prior to sampling, the nails were cleaned with a 70% alcohol solution. Nail clippings were obtained using presterilized nail clippers and a blunt no. 15 scalpel blade and were placed on sterilized black paper. Each nail sample was divided into 2 parts: one for direct microscopy and one for culture. Nail clippings were subjected to microscopic examination after clearing in 20% potassium hydroxide solution. The slides were examined for fungal hyphae, arthrospores, yeasts, and pseudohyphal forms. Culture was done with Emmons modification of Sabouraud dextrose agar (incubated at 27°C for molds and 37°C for yeasts) as well as with 0.4% chloramphenicol and 5% cycloheximide (incubated at 27°C). Culture tubes were examined daily for the first week and on alternate days thereafter for 4 weeks of incubation.

Dermatophytes were identified based on the colony morphology, growth rate, texture, border, and pigmentation in the obverse and reverse of culture media and microscopic examination using lactophenol cotton blue tease mount. Yeast colonies were identified microscopically with Gram stain, and species were identified by germ tube, carbohydrate assimilation, and fermentation tests.¹³ Nondermatophyte molds were identified by colony morphology, microscopic examination, and slide culture. Molds were considered as pathogens in the presence of the following criteria: (1) absence of other fungal growth in the same culture tube; (2) presence of mold growth in all 3 samples; and (3) presence of filaments identified on direct examination.

Results

Of 134 clinically suspected cases of onychomycosis, 78 (58.2%) were from fingernails and 56 (41.8%) from toenails. Clinical diagnosis was confirmed in 96 (71.6%) cases by both fungal culture and direct microscopy but was confirmed by direct microscopy alone in only 76 (56.7%) cases. False-negative results were found in 23.9% (32/134) of participants with direct microscopy and 9.0% (12/134) with fungal cultures. The results of direct microscopy and fungal culture are outlined in Table 1. The study included 78 (58.2%) males and 56 (41.8%) females with a mean age of 44 years. Highest prevalence (47.8%) was seen in participants older than 40 years and lowest prevalence (11.9%) in participants younger than 20 years. In total, 32.8% of participants were farmers, 31.3% were housewives, 14.9% were students, and 20.9% performed other occupations. Disease history at the time of first presentation varied from 1 month to more than 2 years; 33.6% of participants had a 1- to 6-month history of disease, while only 3.7% had a disease history of less than 1 month at presentation. The demographic data are further outlined in Table 2.

Distal lateral subungual onychomycosis was the most prevalent clinical pattern found in 66 (49.3%) participants; fungal isolates were found in 60 of these participants. The next most prevalent clinical pattern was PSO, which was found in 34 (25.4%) participants, 12 showing fungal growth. A clinical pattern of CO was noted in 28 (20.9%) participants, 22 showing fungal growth; WSO was noted in 10 (7.5%) participants, 2 showing fungal growth.

Of 96 culture-positive cases, dermatophytes were the most common pathogens isolated in 56 (58.3%) participants, followed by Candida species in 28 (29.2%) participants. Nondermatophyte molds were isolated in 12 (12.5%) participants. The various dermatophytes, Candida species, and nondermatophyte molds that were isolated on fungal culture are outlined in Table 3. Of the 96 participants with positive fungal cultures, 30 (31.2%) were farmers working with soil, 28 (29.2%) were housewives associated with wet work, 16 (16.7%) were students associated with increased physical exercise from extracurricular activity, and 22 (22.9%) were in other occupations (Table 4).

Comment

The term onychomycosis is derived from onyx, the Greek word for nail, and mykes, the Greek word for fungus. Onychomycosis is a chronic mycotic infection of the fingernails and toenails that can have a serious impact on patients’ quality of life. The fungi known to cause onychomycosis vary among geographic areas, primarily due to differences in climate.¹⁴ The isolation rate of onychomycosis in our hospital-based study was 71.6%, which is in accordance with various studies in India and abroad, including 60% in Karnataka, India⁵; 82.3% in Sikkim, India⁶; and 86.9% in Turkey.¹ However, other studies have shown lower isolation rates of 39.5% in Central Delhi, India,¹⁵ and 37.6% in Himachal Pradesh, India.¹⁶ Some patients with onychomycosis may not seek medical attention, which may explain the difference in the prevalence of onychomycosis observed worldwide.¹⁷ The prevalence of onychomycosis by age also varies. In our study, participants older than 40 years showed the highest prevalence (47.8%), which is in accordance with other studies from India¹⁸ and abroad.^19,20 In contrast, some Indian studies^15,21,22 have reported a higher prevalence in younger adults (ie, 21–30 years), which may be attributed to greater self-consciousness about nail discoloration and disfigurement as well as increased physical activity and different shoe-wearing habits. A higher prevalence in older adults, as observed in our study as well some other studies,^19,21 may be due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, longer exposure to pathogenic fungi, suboptimal immune function, inactivity, and poor hygiene.¹⁰

In our study, suspected onychomycosis was more common in males (58.2%) than in females (41.8%). These results are in accordance with many of the studies in the worldwide literature.^{1,10,11,15,16,23-25} A higher isolation rate in males worldwide may be due to common use of occlusive footwear, more exposure to outdoor conditions, and increased physical activity, leading to an increased likelihood of trauma. The importance of trauma to the nails as a predisposing factor for onychomycosis is well established.²⁴ In our study, the majority of males wore shoes regardless of occupation. Perspiration of the feet when wearing socks and/or shoes can generate a warm moist environment that promotes the growth of fungi and predisposes patients to onychomycosis. Similar observations have been reported by other investigators.^21,22,25,26

The incidence of onychomycosis was almost evenly distributed among farmers, housewives, and the miscellaneous group, whereas a high isolation rate was noted among students. Of 20 students included in our study, onychomycosis was confirmed in 16, which may be related to an increased use of synthetic sports shoes and socks that retain sweat as well as vigorous physical activity frequently resulting in nail injuries among this patient population.¹¹ Younger patients may be more conscious of their appearance and therefore may be more likely to seek treatment. Similar observations have been reported by other researchers.^15,21,22

In our study, dermatophytes were the most commonly found pathogens (58.3%), which is comparable to other studies.^15,18,22Trichophyton mentagrophytes was the most frequently isolated dermatophyte from cultures, which was in concordance with a study from Delhi.¹⁵ In some studies,^18,20,22Trichophyton rubrum has been reported as the most prevalent dermatophyte, but we identified Trichophyton rubrum in only 18 participants, which can be attributed to variations in epidemiology based on geographic region. Nondermatophyte molds were isolated in 12.5% of participants, with Aspergillus niger being the most common isolate found in 8 cases. Other isolated species were Alternaria alternata and Fusarium solani found in 2 cases each. Aspergillus niger has been reported in worldwide studies as an important cause of onychomycosis.^{15,18,19,21,22}

In 28 cases (29.2%) involving Candida species, Candida albicans, Candida parapsilosis, and Candida tropicalis were the most common pathogens, respectively, which is in accordance with many studies.^15,20-22,25 In 28 cases of CO, females (n=16) were affected more than males (n=12). All of the females were housewives and C albicans was predominantly isolated from the fingernails. Household responsibilities involving kitchen work (eg, cutting and peeling vegetables, washing utensils, cleaning the house/laundry) may chronically expose housewives to moist environments and make them more prone to injury, thus facilitating easy entry of fungal agents.

Distal lateral subungual onychomycosis was the most prevalent clinical type found (n=66), which is comparable to other reports.^20,22,25 Proximal subungual onychomycosis was the second most common type; however, a greater incidence has been reported by some researchers,^23,24 while others have reported a lower incidence.^20,21 Candidial onychomycosis and WSO were not common in our study, and PSO was not associated with any immunodeficiency disease, as reported by other researchers.^15,20

Of 134 suspected cases of onychomycosis, 71.6% were confirmed by both direct microscopy and fungal culture, but only 56.7% were confirmed by direct microscopy alone. If we had relied on microscopy with potassium hydroxide only, we would have missed 23.9% of cases. Therefore, nail scrapings should always be subjected to fungal culture as well as direct microscopy, as both are necessary for accurate diagnosis and treatment of onychomycosis. If onychomycosis is not successfully treated, it can act as a reservoir of fungal infection affecting other parts of the body with the potential to pass infection on to others.

Conclusion

Clinical examination alone is not sufficient for diagnosing onychomycosis^14,18,20; in many cases of suspected onychomycosis with nail changes, mycologic examination does not confirm fungal infection. In our study, only 71.6% of participants with nail changes proved to be of fungal etiology. Other researchers from different geographic locations have reported similar results with lower incidence (eg, 39.5%,¹⁵ 37.6%,¹⁶ 51.7%,¹⁸ 45.3%²¹) of fungal etiology in such cases. Therefore, both clinical and mycologic examinations are important for establishing the diagnosis and selecting the most suitable antifungal agent, which is possible only if the underlying pathogen is correctly identified.

Onychomycosis is a chronic fungal infection of the nails. Dermatophytes are the most common etiologic agents, but yeasts and nondermatophyte molds also constitute a substantial number of cases.¹ An accumulation of debris under distorted, deformed, thickened, and discolored nails, particularly with ragged and furrowed edges, strongly suggests tinea unguium.² Candidal onychomycosis (CO) lacks gross distortion and accumulated detritus and mainly affects fingernails.³ Nondermatophytic molds cause 1.5% to 6% of cases of onychomycosis, mostly seen in toenails of elderly individuals with a history of trauma.⁴ Onychomycosis affects 5.5% of the world population⁵ and represents 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.⁶

The incidence of onychomycosis ranges from 0.5% to 5% in the general population in India.⁷ The incidence is particularly high in warm humid climates such as India.⁸ Researchers have found certain habits of the population in the Indian subcontinent (eg, walking with bare feet, wearing ill-fitting shoes, nail-biting [eg, onychophagia], working with chemicals) to be contributing factors for onychomycosis.⁹ Several studies have shown that the prevalence of onychomycosis increases with age, possibly due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, prolonged exposure to pathogenic fungi, suboptimal immune function, inactivity, or inability to trim the toenails and care for the feet.¹⁰ Nail infection is a cosmetic problem with serious physical and psychological morbidity and also serves as the fungal reservoir for skin infections. Besides destruction and disfigurement of the nail plate, onychomycosis can lead to self-consciousness and impairment of daily functioning.¹¹

Nail dystrophy occurs secondary to various systemic disorders or can be associated with other dermatologic conditions. Nail discoloration and other onychia should be differentiated from onychomycosis by classifying nail lesions as distal lateral subungual onychomycosis, proximal subungual onychomycosis (PSO), CO, white superficial onychomycosis (WSO), and total dystrophic onychomycosis.¹² Laboratory investigation is necessary to accurately differentiate between fungal infections and other skin diseases before starting treatment. Our hospital-based study sought to determine the incidence and epidemiology of onychomycosis with an analysis of 134 participants with clinically suspected onychomycosis. We evaluated prevalence based on age, sex, and occupation, as well as the most common pathogens.

Materials and Methods

Study Design and Participants

The study population consisted of 134 patients with clinically suspected onychomycosis who visited the dermatology department at the Veer Chandra Singh Garhwali Government Institute of Medical Sciences and Research Institute in Uttarakhand, India (October 2010 to October 2011). A thorough history was obtained and a detailed examination of the distorted nails was conducted in the microbiology laboratory. Patient history and demographic factors such as age, sex, occupation, and related history of risk factors for onychomycosis were recorded pro forma. Some of the details such as itching, family history of fungal infection, and prior cutaneous infections were recorded. Patients who were undergoing treatment with systemic or topical antifungal agents in the 4 weeks preceding the study period were excluded to rule out false-negative cases and to avoid the influence of antifungal agents on the disease course.

Assessments

Two samples were taken from each patient on different days. Participants were divided into 4 groups based on occupation: farmer, housewife, student, and other (eg, clerk, shopkeeper, painter). Clinical presentation of discoloration, onycholysis, subungual hyperkeratosis, and nail thickening affecting the distal and/or lateral nail plate was defined as distal lateral subungual onychomycosis; discoloration and onycholysis affecting the proximal part of the nail was defined as PSO; association with paronychia and distal and lateral onycholysis was defined as CO; white opaque patches on the nail surface were defined as WSO; and end-stage nail disease was defined as total dystrophic onychomycosis.

Prior to sampling, the nails were cleaned with a 70% alcohol solution. Nail clippings were obtained using presterilized nail clippers and a blunt no. 15 scalpel blade and were placed on sterilized black paper. Each nail sample was divided into 2 parts: one for direct microscopy and one for culture. Nail clippings were subjected to microscopic examination after clearing in 20% potassium hydroxide solution. The slides were examined for fungal hyphae, arthrospores, yeasts, and pseudohyphal forms. Culture was done with Emmons modification of Sabouraud dextrose agar (incubated at 27°C for molds and 37°C for yeasts) as well as with 0.4% chloramphenicol and 5% cycloheximide (incubated at 27°C). Culture tubes were examined daily for the first week and on alternate days thereafter for 4 weeks of incubation.

Dermatophytes were identified based on the colony morphology, growth rate, texture, border, and pigmentation in the obverse and reverse of culture media and microscopic examination using lactophenol cotton blue tease mount. Yeast colonies were identified microscopically with Gram stain, and species were identified by germ tube, carbohydrate assimilation, and fermentation tests.¹³ Nondermatophyte molds were identified by colony morphology, microscopic examination, and slide culture. Molds were considered as pathogens in the presence of the following criteria: (1) absence of other fungal growth in the same culture tube; (2) presence of mold growth in all 3 samples; and (3) presence of filaments identified on direct examination.

Results

Of 134 clinically suspected cases of onychomycosis, 78 (58.2%) were from fingernails and 56 (41.8%) from toenails. Clinical diagnosis was confirmed in 96 (71.6%) cases by both fungal culture and direct microscopy but was confirmed by direct microscopy alone in only 76 (56.7%) cases. False-negative results were found in 23.9% (32/134) of participants with direct microscopy and 9.0% (12/134) with fungal cultures. The results of direct microscopy and fungal culture are outlined in Table 1. The study included 78 (58.2%) males and 56 (41.8%) females with a mean age of 44 years. Highest prevalence (47.8%) was seen in participants older than 40 years and lowest prevalence (11.9%) in participants younger than 20 years. In total, 32.8% of participants were farmers, 31.3% were housewives, 14.9% were students, and 20.9% performed other occupations. Disease history at the time of first presentation varied from 1 month to more than 2 years; 33.6% of participants had a 1- to 6-month history of disease, while only 3.7% had a disease history of less than 1 month at presentation. The demographic data are further outlined in Table 2.

Distal lateral subungual onychomycosis was the most prevalent clinical pattern found in 66 (49.3%) participants; fungal isolates were found in 60 of these participants. The next most prevalent clinical pattern was PSO, which was found in 34 (25.4%) participants, 12 showing fungal growth. A clinical pattern of CO was noted in 28 (20.9%) participants, 22 showing fungal growth; WSO was noted in 10 (7.5%) participants, 2 showing fungal growth.

Of 96 culture-positive cases, dermatophytes were the most common pathogens isolated in 56 (58.3%) participants, followed by Candida species in 28 (29.2%) participants. Nondermatophyte molds were isolated in 12 (12.5%) participants. The various dermatophytes, Candida species, and nondermatophyte molds that were isolated on fungal culture are outlined in Table 3. Of the 96 participants with positive fungal cultures, 30 (31.2%) were farmers working with soil, 28 (29.2%) were housewives associated with wet work, 16 (16.7%) were students associated with increased physical exercise from extracurricular activity, and 22 (22.9%) were in other occupations (Table 4).

Comment

The term onychomycosis is derived from onyx, the Greek word for nail, and mykes, the Greek word for fungus. Onychomycosis is a chronic mycotic infection of the fingernails and toenails that can have a serious impact on patients’ quality of life. The fungi known to cause onychomycosis vary among geographic areas, primarily due to differences in climate.¹⁴ The isolation rate of onychomycosis in our hospital-based study was 71.6%, which is in accordance with various studies in India and abroad, including 60% in Karnataka, India⁵; 82.3% in Sikkim, India⁶; and 86.9% in Turkey.¹ However, other studies have shown lower isolation rates of 39.5% in Central Delhi, India,¹⁵ and 37.6% in Himachal Pradesh, India.¹⁶ Some patients with onychomycosis may not seek medical attention, which may explain the difference in the prevalence of onychomycosis observed worldwide.¹⁷ The prevalence of onychomycosis by age also varies. In our study, participants older than 40 years showed the highest prevalence (47.8%), which is in accordance with other studies from India¹⁸ and abroad.^19,20 In contrast, some Indian studies^15,21,22 have reported a higher prevalence in younger adults (ie, 21–30 years), which may be attributed to greater self-consciousness about nail discoloration and disfigurement as well as increased physical activity and different shoe-wearing habits. A higher prevalence in older adults, as observed in our study as well some other studies,^19,21 may be due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, longer exposure to pathogenic fungi, suboptimal immune function, inactivity, and poor hygiene.¹⁰

In our study, suspected onychomycosis was more common in males (58.2%) than in females (41.8%). These results are in accordance with many of the studies in the worldwide literature.^{1,10,11,15,16,23-25} A higher isolation rate in males worldwide may be due to common use of occlusive footwear, more exposure to outdoor conditions, and increased physical activity, leading to an increased likelihood of trauma. The importance of trauma to the nails as a predisposing factor for onychomycosis is well established.²⁴ In our study, the majority of males wore shoes regardless of occupation. Perspiration of the feet when wearing socks and/or shoes can generate a warm moist environment that promotes the growth of fungi and predisposes patients to onychomycosis. Similar observations have been reported by other investigators.^21,22,25,26

The incidence of onychomycosis was almost evenly distributed among farmers, housewives, and the miscellaneous group, whereas a high isolation rate was noted among students. Of 20 students included in our study, onychomycosis was confirmed in 16, which may be related to an increased use of synthetic sports shoes and socks that retain sweat as well as vigorous physical activity frequently resulting in nail injuries among this patient population.¹¹ Younger patients may be more conscious of their appearance and therefore may be more likely to seek treatment. Similar observations have been reported by other researchers.^15,21,22

In our study, dermatophytes were the most commonly found pathogens (58.3%), which is comparable to other studies.^15,18,22Trichophyton mentagrophytes was the most frequently isolated dermatophyte from cultures, which was in concordance with a study from Delhi.¹⁵ In some studies,^18,20,22Trichophyton rubrum has been reported as the most prevalent dermatophyte, but we identified Trichophyton rubrum in only 18 participants, which can be attributed to variations in epidemiology based on geographic region. Nondermatophyte molds were isolated in 12.5% of participants, with Aspergillus niger being the most common isolate found in 8 cases. Other isolated species were Alternaria alternata and Fusarium solani found in 2 cases each. Aspergillus niger has been reported in worldwide studies as an important cause of onychomycosis.^{15,18,19,21,22}

In 28 cases (29.2%) involving Candida species, Candida albicans, Candida parapsilosis, and Candida tropicalis were the most common pathogens, respectively, which is in accordance with many studies.^15,20-22,25 In 28 cases of CO, females (n=16) were affected more than males (n=12). All of the females were housewives and C albicans was predominantly isolated from the fingernails. Household responsibilities involving kitchen work (eg, cutting and peeling vegetables, washing utensils, cleaning the house/laundry) may chronically expose housewives to moist environments and make them more prone to injury, thus facilitating easy entry of fungal agents.

Distal lateral subungual onychomycosis was the most prevalent clinical type found (n=66), which is comparable to other reports.^20,22,25 Proximal subungual onychomycosis was the second most common type; however, a greater incidence has been reported by some researchers,^23,24 while others have reported a lower incidence.^20,21 Candidial onychomycosis and WSO were not common in our study, and PSO was not associated with any immunodeficiency disease, as reported by other researchers.^15,20

Of 134 suspected cases of onychomycosis, 71.6% were confirmed by both direct microscopy and fungal culture, but only 56.7% were confirmed by direct microscopy alone. If we had relied on microscopy with potassium hydroxide only, we would have missed 23.9% of cases. Therefore, nail scrapings should always be subjected to fungal culture as well as direct microscopy, as both are necessary for accurate diagnosis and treatment of onychomycosis. If onychomycosis is not successfully treated, it can act as a reservoir of fungal infection affecting other parts of the body with the potential to pass infection on to others.

Conclusion

Clinical examination alone is not sufficient for diagnosing onychomycosis^14,18,20; in many cases of suspected onychomycosis with nail changes, mycologic examination does not confirm fungal infection. In our study, only 71.6% of participants with nail changes proved to be of fungal etiology. Other researchers from different geographic locations have reported similar results with lower incidence (eg, 39.5%,¹⁵ 37.6%,¹⁶ 51.7%,¹⁸ 45.3%²¹) of fungal etiology in such cases. Therefore, both clinical and mycologic examinations are important for establishing the diagnosis and selecting the most suitable antifungal agent, which is possible only if the underlying pathogen is correctly identified.

Onychomycosis is a chronic fungal infection of the nails. Dermatophytes are the most common etiologic agents, but yeasts and nondermatophyte molds also constitute a substantial number of cases.¹ An accumulation of debris under distorted, deformed, thickened, and discolored nails, particularly with ragged and furrowed edges, strongly suggests tinea unguium.² Candidal onychomycosis (CO) lacks gross distortion and accumulated detritus and mainly affects fingernails.³ Nondermatophytic molds cause 1.5% to 6% of cases of onychomycosis, mostly seen in toenails of elderly individuals with a history of trauma.⁴ Onychomycosis affects 5.5% of the world population⁵ and represents 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.⁶

The incidence of onychomycosis ranges from 0.5% to 5% in the general population in India.⁷ The incidence is particularly high in warm humid climates such as India.⁸ Researchers have found certain habits of the population in the Indian subcontinent (eg, walking with bare feet, wearing ill-fitting shoes, nail-biting [eg, onychophagia], working with chemicals) to be contributing factors for onychomycosis.⁹ Several studies have shown that the prevalence of onychomycosis increases with age, possibly due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, prolonged exposure to pathogenic fungi, suboptimal immune function, inactivity, or inability to trim the toenails and care for the feet.¹⁰ Nail infection is a cosmetic problem with serious physical and psychological morbidity and also serves as the fungal reservoir for skin infections. Besides destruction and disfigurement of the nail plate, onychomycosis can lead to self-consciousness and impairment of daily functioning.¹¹

Nail dystrophy occurs secondary to various systemic disorders or can be associated with other dermatologic conditions. Nail discoloration and other onychia should be differentiated from onychomycosis by classifying nail lesions as distal lateral subungual onychomycosis, proximal subungual onychomycosis (PSO), CO, white superficial onychomycosis (WSO), and total dystrophic onychomycosis.¹² Laboratory investigation is necessary to accurately differentiate between fungal infections and other skin diseases before starting treatment. Our hospital-based study sought to determine the incidence and epidemiology of onychomycosis with an analysis of 134 participants with clinically suspected onychomycosis. We evaluated prevalence based on age, sex, and occupation, as well as the most common pathogens.

Materials and Methods

Study Design and Participants

The study population consisted of 134 patients with clinically suspected onychomycosis who visited the dermatology department at the Veer Chandra Singh Garhwali Government Institute of Medical Sciences and Research Institute in Uttarakhand, India (October 2010 to October 2011). A thorough history was obtained and a detailed examination of the distorted nails was conducted in the microbiology laboratory. Patient history and demographic factors such as age, sex, occupation, and related history of risk factors for onychomycosis were recorded pro forma. Some of the details such as itching, family history of fungal infection, and prior cutaneous infections were recorded. Patients who were undergoing treatment with systemic or topical antifungal agents in the 4 weeks preceding the study period were excluded to rule out false-negative cases and to avoid the influence of antifungal agents on the disease course.

Assessments

Two samples were taken from each patient on different days. Participants were divided into 4 groups based on occupation: farmer, housewife, student, and other (eg, clerk, shopkeeper, painter). Clinical presentation of discoloration, onycholysis, subungual hyperkeratosis, and nail thickening affecting the distal and/or lateral nail plate was defined as distal lateral subungual onychomycosis; discoloration and onycholysis affecting the proximal part of the nail was defined as PSO; association with paronychia and distal and lateral onycholysis was defined as CO; white opaque patches on the nail surface were defined as WSO; and end-stage nail disease was defined as total dystrophic onychomycosis.

Prior to sampling, the nails were cleaned with a 70% alcohol solution. Nail clippings were obtained using presterilized nail clippers and a blunt no. 15 scalpel blade and were placed on sterilized black paper. Each nail sample was divided into 2 parts: one for direct microscopy and one for culture. Nail clippings were subjected to microscopic examination after clearing in 20% potassium hydroxide solution. The slides were examined for fungal hyphae, arthrospores, yeasts, and pseudohyphal forms. Culture was done with Emmons modification of Sabouraud dextrose agar (incubated at 27°C for molds and 37°C for yeasts) as well as with 0.4% chloramphenicol and 5% cycloheximide (incubated at 27°C). Culture tubes were examined daily for the first week and on alternate days thereafter for 4 weeks of incubation.

Dermatophytes were identified based on the colony morphology, growth rate, texture, border, and pigmentation in the obverse and reverse of culture media and microscopic examination using lactophenol cotton blue tease mount. Yeast colonies were identified microscopically with Gram stain, and species were identified by germ tube, carbohydrate assimilation, and fermentation tests.¹³ Nondermatophyte molds were identified by colony morphology, microscopic examination, and slide culture. Molds were considered as pathogens in the presence of the following criteria: (1) absence of other fungal growth in the same culture tube; (2) presence of mold growth in all 3 samples; and (3) presence of filaments identified on direct examination.

Results

Of 134 clinically suspected cases of onychomycosis, 78 (58.2%) were from fingernails and 56 (41.8%) from toenails. Clinical diagnosis was confirmed in 96 (71.6%) cases by both fungal culture and direct microscopy but was confirmed by direct microscopy alone in only 76 (56.7%) cases. False-negative results were found in 23.9% (32/134) of participants with direct microscopy and 9.0% (12/134) with fungal cultures. The results of direct microscopy and fungal culture are outlined in Table 1. The study included 78 (58.2%) males and 56 (41.8%) females with a mean age of 44 years. Highest prevalence (47.8%) was seen in participants older than 40 years and lowest prevalence (11.9%) in participants younger than 20 years. In total, 32.8% of participants were farmers, 31.3% were housewives, 14.9% were students, and 20.9% performed other occupations. Disease history at the time of first presentation varied from 1 month to more than 2 years; 33.6% of participants had a 1- to 6-month history of disease, while only 3.7% had a disease history of less than 1 month at presentation. The demographic data are further outlined in Table 2.

Distal lateral subungual onychomycosis was the most prevalent clinical pattern found in 66 (49.3%) participants; fungal isolates were found in 60 of these participants. The next most prevalent clinical pattern was PSO, which was found in 34 (25.4%) participants, 12 showing fungal growth. A clinical pattern of CO was noted in 28 (20.9%) participants, 22 showing fungal growth; WSO was noted in 10 (7.5%) participants, 2 showing fungal growth.

Of 96 culture-positive cases, dermatophytes were the most common pathogens isolated in 56 (58.3%) participants, followed by Candida species in 28 (29.2%) participants. Nondermatophyte molds were isolated in 12 (12.5%) participants. The various dermatophytes, Candida species, and nondermatophyte molds that were isolated on fungal culture are outlined in Table 3. Of the 96 participants with positive fungal cultures, 30 (31.2%) were farmers working with soil, 28 (29.2%) were housewives associated with wet work, 16 (16.7%) were students associated with increased physical exercise from extracurricular activity, and 22 (22.9%) were in other occupations (Table 4).

Comment

The term onychomycosis is derived from onyx, the Greek word for nail, and mykes, the Greek word for fungus. Onychomycosis is a chronic mycotic infection of the fingernails and toenails that can have a serious impact on patients’ quality of life. The fungi known to cause onychomycosis vary among geographic areas, primarily due to differences in climate.¹⁴ The isolation rate of onychomycosis in our hospital-based study was 71.6%, which is in accordance with various studies in India and abroad, including 60% in Karnataka, India⁵; 82.3% in Sikkim, India⁶; and 86.9% in Turkey.¹ However, other studies have shown lower isolation rates of 39.5% in Central Delhi, India,¹⁵ and 37.6% in Himachal Pradesh, India.¹⁶ Some patients with onychomycosis may not seek medical attention, which may explain the difference in the prevalence of onychomycosis observed worldwide.¹⁷ The prevalence of onychomycosis by age also varies. In our study, participants older than 40 years showed the highest prevalence (47.8%), which is in accordance with other studies from India¹⁸ and abroad.^19,20 In contrast, some Indian studies^15,21,22 have reported a higher prevalence in younger adults (ie, 21–30 years), which may be attributed to greater self-consciousness about nail discoloration and disfigurement as well as increased physical activity and different shoe-wearing habits. A higher prevalence in older adults, as observed in our study as well some other studies,^19,21 may be due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, longer exposure to pathogenic fungi, suboptimal immune function, inactivity, and poor hygiene.¹⁰

In our study, suspected onychomycosis was more common in males (58.2%) than in females (41.8%). These results are in accordance with many of the studies in the worldwide literature.^{1,10,11,15,16,23-25} A higher isolation rate in males worldwide may be due to common use of occlusive footwear, more exposure to outdoor conditions, and increased physical activity, leading to an increased likelihood of trauma. The importance of trauma to the nails as a predisposing factor for onychomycosis is well established.²⁴ In our study, the majority of males wore shoes regardless of occupation. Perspiration of the feet when wearing socks and/or shoes can generate a warm moist environment that promotes the growth of fungi and predisposes patients to onychomycosis. Similar observations have been reported by other investigators.^21,22,25,26

The incidence of onychomycosis was almost evenly distributed among farmers, housewives, and the miscellaneous group, whereas a high isolation rate was noted among students. Of 20 students included in our study, onychomycosis was confirmed in 16, which may be related to an increased use of synthetic sports shoes and socks that retain sweat as well as vigorous physical activity frequently resulting in nail injuries among this patient population.¹¹ Younger patients may be more conscious of their appearance and therefore may be more likely to seek treatment. Similar observations have been reported by other researchers.^15,21,22

In our study, dermatophytes were the most commonly found pathogens (58.3%), which is comparable to other studies.^15,18,22Trichophyton mentagrophytes was the most frequently isolated dermatophyte from cultures, which was in concordance with a study from Delhi.¹⁵ In some studies,^18,20,22Trichophyton rubrum has been reported as the most prevalent dermatophyte, but we identified Trichophyton rubrum in only 18 participants, which can be attributed to variations in epidemiology based on geographic region. Nondermatophyte molds were isolated in 12.5% of participants, with Aspergillus niger being the most common isolate found in 8 cases. Other isolated species were Alternaria alternata and Fusarium solani found in 2 cases each. Aspergillus niger has been reported in worldwide studies as an important cause of onychomycosis.^{15,18,19,21,22}

In 28 cases (29.2%) involving Candida species, Candida albicans, Candida parapsilosis, and Candida tropicalis were the most common pathogens, respectively, which is in accordance with many studies.^15,20-22,25 In 28 cases of CO, females (n=16) were affected more than males (n=12). All of the females were housewives and C albicans was predominantly isolated from the fingernails. Household responsibilities involving kitchen work (eg, cutting and peeling vegetables, washing utensils, cleaning the house/laundry) may chronically expose housewives to moist environments and make them more prone to injury, thus facilitating easy entry of fungal agents.

Distal lateral subungual onychomycosis was the most prevalent clinical type found (n=66), which is comparable to other reports.^20,22,25 Proximal subungual onychomycosis was the second most common type; however, a greater incidence has been reported by some researchers,^23,24 while others have reported a lower incidence.^20,21 Candidial onychomycosis and WSO were not common in our study, and PSO was not associated with any immunodeficiency disease, as reported by other researchers.^15,20

Of 134 suspected cases of onychomycosis, 71.6% were confirmed by both direct microscopy and fungal culture, but only 56.7% were confirmed by direct microscopy alone. If we had relied on microscopy with potassium hydroxide only, we would have missed 23.9% of cases. Therefore, nail scrapings should always be subjected to fungal culture as well as direct microscopy, as both are necessary for accurate diagnosis and treatment of onychomycosis. If onychomycosis is not successfully treated, it can act as a reservoir of fungal infection affecting other parts of the body with the potential to pass infection on to others.

Conclusion

Clinical examination alone is not sufficient for diagnosing onychomycosis^14,18,20; in many cases of suspected onychomycosis with nail changes, mycologic examination does not confirm fungal infection. In our study, only 71.6% of participants with nail changes proved to be of fungal etiology. Other researchers from different geographic locations have reported similar results with lower incidence (eg, 39.5%,¹⁵ 37.6%,¹⁶ 51.7%,¹⁸ 45.3%²¹) of fungal etiology in such cases. Therefore, both clinical and mycologic examinations are important for establishing the diagnosis and selecting the most suitable antifungal agent, which is possible only if the underlying pathogen is correctly identified.