NATIONAL HARBOR, MD–The US Department of Veterans Affairs (VA) is in the midst of a significant change in the way it will deliver care to veterans. Agency officials remain optimistic that the change will be for the better, and early indications are positive.

The change is being driven by the VA Maintaining Internal Systems and Strengthening Integrated Outside Networks (Mission) Act of 2018, a bill that opens health services options for veterans and integrates VA-administered care and care from community-based providers.

“This is change that is enhancing their experience in the system, and this is enhancing their options and the quality of the options in the system,” Jennifer MacDonald, MD, chief consultant to the principal deputy undersecretary for health at the VA, said during a December 3 session at the AMSUS 2019 annual meeting. “We need also for our workforce to understand how important they are to us across this degree of change.”

Dr. MacDonald highlighted integration with community-based care, including a community urgent care provision that allows veterans to access urgent care facilities and receive care without the need for prior authorization.

“The important piece about that is that we are also looking at the way this care has been accessed,” she said. “By and large, what we have seen from the data is that veterans are indeed seeking community urgent care at a site close to home. This may be CVS or Walgreens. It may be a stand-alone urgent care with a bit more functionality than those Minute Clinics tend to have. We are seeing veterans typically access care through those sites for those minor concerns and illnesses.”

However, she noted that this type of access does not alter the role the VA plays in administration of health care services.

“We are seeing them come back to VA for the majority of their care and for their core care–when there are serious issues, when insulin needs to be adjusted for diabetes, when there are heart disease medications that need to be refilled–we are seeing veterans not seek out urgent care, but come to us, and that is exactly what we want,” she said. “We want the continuity of care to continue and we want to help guide people to the right care, right place, right time.”

Dr. MacDonald also highlighted the expansion of a program that provides a stipend to caregivers that allows veterans to avoid institutionalization and remain within the community under that caregiver’s (a family or friend) supervision. This will expand by year’s end to Vietnam War-era veterans and within 2 years, to veterans that fall between the Vietnam War-era and the September 11, 2001, terrorist attacks.

“We wanted to do this equitably across all eras of veterans,” she said. “This now gives us that opportunity.”

Telehealth also plays a key role.

“For the first time ever, VA now has what we term ‘anywhere-to-anywhere’ telehealth under the Mission Act, an enormous opportunity for us,” she said. “Since we stretch … from New York City to Guam, we need the opportunity to provide care where it may be difficult to recruit and retain providers wherever veterans choose to live,” she said. “We believe that we should be able to meet people where they are regardless of where they choose to live. That’s an aspirational vision, but it is one we believe is exceptionally important and indeed we are moving toward that.”

These are just the beginning; the full implementation of the act goes out to 2034.

According to Dr. MacDonald, the agency is working hard to engage both veterans and the workforce to keep tabs on how the implementation is going.

“It’s a fundamental change in the day-to-day business that they’ve been doing, sometimes for years, and so extremely important across this change is that we have set up processes and now a joint operations center and a number of forums to hear directly from our front line and make sure that their issues are our issues in central office, in DC here, and that they feel heard and that they know that when they have needs, those needs are actioned,” she said.

The VA, under the Mission Act, is also working hard to engage health care providers in the community, including making VA training to community partners, including training on opioid use, suicide prevent and military culture.

However, all these change are for naught if the veterans are not on board. But so far, Dr. MacDonald said the early feedback is very positive.

She cited a VFW survey that asked a question about the Mission Act changes so far and whether they would recommend the VA to other veterans. Ninety percent of the respondents answered they would.

“That’s our marker that we are getting somewhere with these changes and the way we do business,” she said. “That is what we want to see continue to increase.”

NATIONAL HARBOR, MD–The US Department of Veterans Affairs (VA) is in the midst of a significant change in the way it will deliver care to veterans. Agency officials remain optimistic that the change will be for the better, and early indications are positive.

The change is being driven by the VA Maintaining Internal Systems and Strengthening Integrated Outside Networks (Mission) Act of 2018, a bill that opens health services options for veterans and integrates VA-administered care and care from community-based providers.

“This is change that is enhancing their experience in the system, and this is enhancing their options and the quality of the options in the system,” Jennifer MacDonald, MD, chief consultant to the principal deputy undersecretary for health at the VA, said during a December 3 session at the AMSUS 2019 annual meeting. “We need also for our workforce to understand how important they are to us across this degree of change.”

Dr. MacDonald highlighted integration with community-based care, including a community urgent care provision that allows veterans to access urgent care facilities and receive care without the need for prior authorization.

“The important piece about that is that we are also looking at the way this care has been accessed,” she said. “By and large, what we have seen from the data is that veterans are indeed seeking community urgent care at a site close to home. This may be CVS or Walgreens. It may be a stand-alone urgent care with a bit more functionality than those Minute Clinics tend to have. We are seeing veterans typically access care through those sites for those minor concerns and illnesses.”

However, she noted that this type of access does not alter the role the VA plays in administration of health care services.

“We are seeing them come back to VA for the majority of their care and for their core care–when there are serious issues, when insulin needs to be adjusted for diabetes, when there are heart disease medications that need to be refilled–we are seeing veterans not seek out urgent care, but come to us, and that is exactly what we want,” she said. “We want the continuity of care to continue and we want to help guide people to the right care, right place, right time.”

Dr. MacDonald also highlighted the expansion of a program that provides a stipend to caregivers that allows veterans to avoid institutionalization and remain within the community under that caregiver’s (a family or friend) supervision. This will expand by year’s end to Vietnam War-era veterans and within 2 years, to veterans that fall between the Vietnam War-era and the September 11, 2001, terrorist attacks.

“We wanted to do this equitably across all eras of veterans,” she said. “This now gives us that opportunity.”

Telehealth also plays a key role.

“For the first time ever, VA now has what we term ‘anywhere-to-anywhere’ telehealth under the Mission Act, an enormous opportunity for us,” she said. “Since we stretch … from New York City to Guam, we need the opportunity to provide care where it may be difficult to recruit and retain providers wherever veterans choose to live,” she said. “We believe that we should be able to meet people where they are regardless of where they choose to live. That’s an aspirational vision, but it is one we believe is exceptionally important and indeed we are moving toward that.”

These are just the beginning; the full implementation of the act goes out to 2034.

According to Dr. MacDonald, the agency is working hard to engage both veterans and the workforce to keep tabs on how the implementation is going.

“It’s a fundamental change in the day-to-day business that they’ve been doing, sometimes for years, and so extremely important across this change is that we have set up processes and now a joint operations center and a number of forums to hear directly from our front line and make sure that their issues are our issues in central office, in DC here, and that they feel heard and that they know that when they have needs, those needs are actioned,” she said.

The VA, under the Mission Act, is also working hard to engage health care providers in the community, including making VA training to community partners, including training on opioid use, suicide prevent and military culture.

However, all these change are for naught if the veterans are not on board. But so far, Dr. MacDonald said the early feedback is very positive.

She cited a VFW survey that asked a question about the Mission Act changes so far and whether they would recommend the VA to other veterans. Ninety percent of the respondents answered they would.

“That’s our marker that we are getting somewhere with these changes and the way we do business,” she said. “That is what we want to see continue to increase.”

NATIONAL HARBOR, MD–The US Department of Veterans Affairs (VA) is in the midst of a significant change in the way it will deliver care to veterans. Agency officials remain optimistic that the change will be for the better, and early indications are positive.

The change is being driven by the VA Maintaining Internal Systems and Strengthening Integrated Outside Networks (Mission) Act of 2018, a bill that opens health services options for veterans and integrates VA-administered care and care from community-based providers.

“This is change that is enhancing their experience in the system, and this is enhancing their options and the quality of the options in the system,” Jennifer MacDonald, MD, chief consultant to the principal deputy undersecretary for health at the VA, said during a December 3 session at the AMSUS 2019 annual meeting. “We need also for our workforce to understand how important they are to us across this degree of change.”

Dr. MacDonald highlighted integration with community-based care, including a community urgent care provision that allows veterans to access urgent care facilities and receive care without the need for prior authorization.

“The important piece about that is that we are also looking at the way this care has been accessed,” she said. “By and large, what we have seen from the data is that veterans are indeed seeking community urgent care at a site close to home. This may be CVS or Walgreens. It may be a stand-alone urgent care with a bit more functionality than those Minute Clinics tend to have. We are seeing veterans typically access care through those sites for those minor concerns and illnesses.”

However, she noted that this type of access does not alter the role the VA plays in administration of health care services.

“We are seeing them come back to VA for the majority of their care and for their core care–when there are serious issues, when insulin needs to be adjusted for diabetes, when there are heart disease medications that need to be refilled–we are seeing veterans not seek out urgent care, but come to us, and that is exactly what we want,” she said. “We want the continuity of care to continue and we want to help guide people to the right care, right place, right time.”

Dr. MacDonald also highlighted the expansion of a program that provides a stipend to caregivers that allows veterans to avoid institutionalization and remain within the community under that caregiver’s (a family or friend) supervision. This will expand by year’s end to Vietnam War-era veterans and within 2 years, to veterans that fall between the Vietnam War-era and the September 11, 2001, terrorist attacks.

“We wanted to do this equitably across all eras of veterans,” she said. “This now gives us that opportunity.”

Telehealth also plays a key role.

“For the first time ever, VA now has what we term ‘anywhere-to-anywhere’ telehealth under the Mission Act, an enormous opportunity for us,” she said. “Since we stretch … from New York City to Guam, we need the opportunity to provide care where it may be difficult to recruit and retain providers wherever veterans choose to live,” she said. “We believe that we should be able to meet people where they are regardless of where they choose to live. That’s an aspirational vision, but it is one we believe is exceptionally important and indeed we are moving toward that.”

These are just the beginning; the full implementation of the act goes out to 2034.

According to Dr. MacDonald, the agency is working hard to engage both veterans and the workforce to keep tabs on how the implementation is going.

“It’s a fundamental change in the day-to-day business that they’ve been doing, sometimes for years, and so extremely important across this change is that we have set up processes and now a joint operations center and a number of forums to hear directly from our front line and make sure that their issues are our issues in central office, in DC here, and that they feel heard and that they know that when they have needs, those needs are actioned,” she said.

The VA, under the Mission Act, is also working hard to engage health care providers in the community, including making VA training to community partners, including training on opioid use, suicide prevent and military culture.

However, all these change are for naught if the veterans are not on board. But so far, Dr. MacDonald said the early feedback is very positive.

She cited a VFW survey that asked a question about the Mission Act changes so far and whether they would recommend the VA to other veterans. Ninety percent of the respondents answered they would.

“That’s our marker that we are getting somewhere with these changes and the way we do business,” she said. “That is what we want to see continue to increase.”

The introduction over the last decade of new systemic therapies for the treatment of hormone receptor positive, HER2-negative metastatic breast cancer has not translated into improved survival in a real-world setting, results of a retrospective study suggest.

Among 2,197 patients who received at least one line of systemic therapy for hormone receptor positive, HER2-negative metastatic breast cancer (HR+/HER2– MBC) from 2003 to 2013, there were no significant differences in median duration of hormonal therapy or median overall survival (OS) for patients treated in any of three time spans during that 10-year period, reported Dan Le, MD, MHA, of BC Cancer, Surrey, B.C., and colleagues.

“Despite the introduction of 9 new adjuvant therapies and 2 new metastatic treatments, survival in the metastatic setting for HR-positive, HER2-negative breast cancer did not improve between 2003 and 2013,” they wrote in a report published in Cancer.

Improvements in adjuvant therapy such as the introduction of cyclin-dependent kinase inhibitors (CDKI) may result in fewer relapses but may also affect the response of relapsed cancers to additional lines of therapy, the authors contended.

“Improved adjuvant therapy means that the cancers that do relapse may have more adverse biology, either intrinsically or because of selective pressure and clonal evolution from exposure to more and better drugs in the adjuvant setting. These factors could, in part, explain the lack of improved survival over time observed in this study,” they wrote.

To see whether significant increases in progression-free survival (PFS) in a clinical trial translated into improved outcomes – including OS – in population-based settings, the investigators identified 2,432 patients with HR+/HER2– MBC from data in the prospective Breast Cancer Outcomes Unit Database of BC Cancer. Of this group, 2,197 received at least one line of systemic therapy after an MBC diagnosis, and 1,752 received first and/or second-line hormonal therapy as well.

The patients were treated in one of three time cohorts: from 2003 through 2005, 2007 through 2009, or 2011 through 2013.

Nine new adjuvant systemic therapies with or without neoadjuvant therapy were approved by BC Cancer during the study period. For the entire decade of the study, the mean survival time was 3.1 years, and the median OS was 2.0 years.

The longest survival for patients diagnosed from 2003 through 2005 was 14.6 years, with 18.1% of these patients living at least 5 years after diagnosis. For patients diagnosed from 2007 through 2009, the longest survival was 10.6 years, with 17.7% of these patients living 5 years or longer post diagnosis. For patients in the most recent cohort (with patients diagnosed after August 2012 excluded), the longest survival was 6.6 years, with 17.3% living at least 5 years after diagnosis.

Overall, patients had a median of 9 months of first-line hormonal treatment, and 6.1 months of second-line hormonal therapy, with nearly identical duration across all three time cohorts.

“Ultimately, it seems likely that the greater the proportion of patients we cure with modern adjuvant therapy, the more challenging it will be to improve outcomes for patients with relapsed disease. This underscores the importance of 1) making continued progress in the adjuvant management of potentially curable breast cancer by first studying new therapeutic agents in the metastatic setting and 2) developing a better understanding of how selective pressure and clonal evolution may lead to more resistant biologic phenotypes in MBC,” the investigators wrote.

No specific study funding was disclosed. No authors disclosed potential conflicts of interest.

SOURCE: Le D et al. Cancer 2019 Nov 21. doi: 10.1002/cncr.32631.

The introduction over the last decade of new systemic therapies for the treatment of hormone receptor positive, HER2-negative metastatic breast cancer has not translated into improved survival in a real-world setting, results of a retrospective study suggest.

Among 2,197 patients who received at least one line of systemic therapy for hormone receptor positive, HER2-negative metastatic breast cancer (HR+/HER2– MBC) from 2003 to 2013, there were no significant differences in median duration of hormonal therapy or median overall survival (OS) for patients treated in any of three time spans during that 10-year period, reported Dan Le, MD, MHA, of BC Cancer, Surrey, B.C., and colleagues.

“Despite the introduction of 9 new adjuvant therapies and 2 new metastatic treatments, survival in the metastatic setting for HR-positive, HER2-negative breast cancer did not improve between 2003 and 2013,” they wrote in a report published in Cancer.

Improvements in adjuvant therapy such as the introduction of cyclin-dependent kinase inhibitors (CDKI) may result in fewer relapses but may also affect the response of relapsed cancers to additional lines of therapy, the authors contended.

“Improved adjuvant therapy means that the cancers that do relapse may have more adverse biology, either intrinsically or because of selective pressure and clonal evolution from exposure to more and better drugs in the adjuvant setting. These factors could, in part, explain the lack of improved survival over time observed in this study,” they wrote.

To see whether significant increases in progression-free survival (PFS) in a clinical trial translated into improved outcomes – including OS – in population-based settings, the investigators identified 2,432 patients with HR+/HER2– MBC from data in the prospective Breast Cancer Outcomes Unit Database of BC Cancer. Of this group, 2,197 received at least one line of systemic therapy after an MBC diagnosis, and 1,752 received first and/or second-line hormonal therapy as well.

The patients were treated in one of three time cohorts: from 2003 through 2005, 2007 through 2009, or 2011 through 2013.

Nine new adjuvant systemic therapies with or without neoadjuvant therapy were approved by BC Cancer during the study period. For the entire decade of the study, the mean survival time was 3.1 years, and the median OS was 2.0 years.

The longest survival for patients diagnosed from 2003 through 2005 was 14.6 years, with 18.1% of these patients living at least 5 years after diagnosis. For patients diagnosed from 2007 through 2009, the longest survival was 10.6 years, with 17.7% of these patients living 5 years or longer post diagnosis. For patients in the most recent cohort (with patients diagnosed after August 2012 excluded), the longest survival was 6.6 years, with 17.3% living at least 5 years after diagnosis.

Overall, patients had a median of 9 months of first-line hormonal treatment, and 6.1 months of second-line hormonal therapy, with nearly identical duration across all three time cohorts.

“Ultimately, it seems likely that the greater the proportion of patients we cure with modern adjuvant therapy, the more challenging it will be to improve outcomes for patients with relapsed disease. This underscores the importance of 1) making continued progress in the adjuvant management of potentially curable breast cancer by first studying new therapeutic agents in the metastatic setting and 2) developing a better understanding of how selective pressure and clonal evolution may lead to more resistant biologic phenotypes in MBC,” the investigators wrote.

No specific study funding was disclosed. No authors disclosed potential conflicts of interest.

SOURCE: Le D et al. Cancer 2019 Nov 21. doi: 10.1002/cncr.32631.

The introduction over the last decade of new systemic therapies for the treatment of hormone receptor positive, HER2-negative metastatic breast cancer has not translated into improved survival in a real-world setting, results of a retrospective study suggest.

Among 2,197 patients who received at least one line of systemic therapy for hormone receptor positive, HER2-negative metastatic breast cancer (HR+/HER2– MBC) from 2003 to 2013, there were no significant differences in median duration of hormonal therapy or median overall survival (OS) for patients treated in any of three time spans during that 10-year period, reported Dan Le, MD, MHA, of BC Cancer, Surrey, B.C., and colleagues.

“Despite the introduction of 9 new adjuvant therapies and 2 new metastatic treatments, survival in the metastatic setting for HR-positive, HER2-negative breast cancer did not improve between 2003 and 2013,” they wrote in a report published in Cancer.

Improvements in adjuvant therapy such as the introduction of cyclin-dependent kinase inhibitors (CDKI) may result in fewer relapses but may also affect the response of relapsed cancers to additional lines of therapy, the authors contended.

“Improved adjuvant therapy means that the cancers that do relapse may have more adverse biology, either intrinsically or because of selective pressure and clonal evolution from exposure to more and better drugs in the adjuvant setting. These factors could, in part, explain the lack of improved survival over time observed in this study,” they wrote.

To see whether significant increases in progression-free survival (PFS) in a clinical trial translated into improved outcomes – including OS – in population-based settings, the investigators identified 2,432 patients with HR+/HER2– MBC from data in the prospective Breast Cancer Outcomes Unit Database of BC Cancer. Of this group, 2,197 received at least one line of systemic therapy after an MBC diagnosis, and 1,752 received first and/or second-line hormonal therapy as well.

The patients were treated in one of three time cohorts: from 2003 through 2005, 2007 through 2009, or 2011 through 2013.

Nine new adjuvant systemic therapies with or without neoadjuvant therapy were approved by BC Cancer during the study period. For the entire decade of the study, the mean survival time was 3.1 years, and the median OS was 2.0 years.

The longest survival for patients diagnosed from 2003 through 2005 was 14.6 years, with 18.1% of these patients living at least 5 years after diagnosis. For patients diagnosed from 2007 through 2009, the longest survival was 10.6 years, with 17.7% of these patients living 5 years or longer post diagnosis. For patients in the most recent cohort (with patients diagnosed after August 2012 excluded), the longest survival was 6.6 years, with 17.3% living at least 5 years after diagnosis.

Overall, patients had a median of 9 months of first-line hormonal treatment, and 6.1 months of second-line hormonal therapy, with nearly identical duration across all three time cohorts.

“Ultimately, it seems likely that the greater the proportion of patients we cure with modern adjuvant therapy, the more challenging it will be to improve outcomes for patients with relapsed disease. This underscores the importance of 1) making continued progress in the adjuvant management of potentially curable breast cancer by first studying new therapeutic agents in the metastatic setting and 2) developing a better understanding of how selective pressure and clonal evolution may lead to more resistant biologic phenotypes in MBC,” the investigators wrote.

No specific study funding was disclosed. No authors disclosed potential conflicts of interest.

SOURCE: Le D et al. Cancer 2019 Nov 21. doi: 10.1002/cncr.32631.

Three years ago, lesions began appearing on this now 68-year-old woman’s legs. They have grown in size and number, and their roughness disturbs the patient. She has been told the lesions are related to aging, but she has never seen anything like them on her friends or family—and she is worried about what they might mean for her health.

Her primary care provider diagnosed warts and performed cryotherapy on several of the lesions. However, the pain was intolerable and the treatment ineffective. To add insult to injury, each treated spot blistered and took more than a month to heal, leaving behind a pinkish brown blemish.

In all other respects, the patient’s health is excellent.

EXAMINATION
Both legs, from the upper thighs to the tops of the feet, are covered with thousands of uniformly distributed, tiny, keratotic, rough, dry papules. All the lesions are essentially identical: white, with no associated signs of inflammation. The patient’s skin is quite dry in general. Neither her palms nor soles are affected.

What’s the diagnosis?

DISCUSSION
The most common problem seen in dermatology offices worldwide is seborrheic keratosis (SK), a totally benign epidermal excrescence that appears to be related to aging and heredity. Most patients are in their 50s when they first notice an SK, and with a bit of luck, they will only see a few in their lifetime. But some patients develop hundreds of SKs, many of which become quite large (3-5 cm) and unsightly. In certain circumstances, SKs can herald the arrival of an occult carcinoma (the Leser-Trelat sign).

This patient has what some consider a variant of SK, called stucco keratosis. These lesions manifest almost exclusively on the lower legs and feet—perhaps due to the relative lack of sebaceous glands in those areas—and most often on men older than 60. Distressing as they are, stucco keratoses have no pathologic implications.

Grossly and histologically, stucco keratoses are different from ordinary SKs. Each stucco keratosis lesion is essentially identical to the others, with a spiculated surface, white color, and average diameter of 2 to 3 mm. Histologically, they demonstrate a thickened epidermis with focal exophytic upward projections that resemble church spires. The lesions do not extend into the dermis.

Treatment of stucco keratoses is, at best, tedious, painful, and futile. The modalities used are cryotherapy or electrodessication with curettage. For a degree of comfort, use of a loofah after bathing will remove or smooth down a few lesions, but this process must be followed by application of a heavy emollient. Alas, regrowth is a certainty.

TAKE-HOME LEARNING POINTS

• Stucco keratosis is considered a variant of seborrheic keratosis, although they differ in several significant ways.
• The lesions of stucco keratosis are fairly uniform in appearance: white, rough, spiculated, epidermal papules measuring 2 to 3 mm.
• Stucco keratoses affect about 10% of the population (men more often than women) and have no racial predilection or pathologic implications.
• The lesions are found almost exclusively on the legs, from the knees down to and including the dorsa of the feet.
• Treatment is far from satisfactory, for multiple reasons, including resultant pain and scarring.

Three years ago, lesions began appearing on this now 68-year-old woman’s legs. They have grown in size and number, and their roughness disturbs the patient. She has been told the lesions are related to aging, but she has never seen anything like them on her friends or family—and she is worried about what they might mean for her health.

Her primary care provider diagnosed warts and performed cryotherapy on several of the lesions. However, the pain was intolerable and the treatment ineffective. To add insult to injury, each treated spot blistered and took more than a month to heal, leaving behind a pinkish brown blemish.

In all other respects, the patient’s health is excellent.

EXAMINATION
Both legs, from the upper thighs to the tops of the feet, are covered with thousands of uniformly distributed, tiny, keratotic, rough, dry papules. All the lesions are essentially identical: white, with no associated signs of inflammation. The patient’s skin is quite dry in general. Neither her palms nor soles are affected.

What’s the diagnosis?

DISCUSSION
The most common problem seen in dermatology offices worldwide is seborrheic keratosis (SK), a totally benign epidermal excrescence that appears to be related to aging and heredity. Most patients are in their 50s when they first notice an SK, and with a bit of luck, they will only see a few in their lifetime. But some patients develop hundreds of SKs, many of which become quite large (3-5 cm) and unsightly. In certain circumstances, SKs can herald the arrival of an occult carcinoma (the Leser-Trelat sign).

This patient has what some consider a variant of SK, called stucco keratosis. These lesions manifest almost exclusively on the lower legs and feet—perhaps due to the relative lack of sebaceous glands in those areas—and most often on men older than 60. Distressing as they are, stucco keratoses have no pathologic implications.

Grossly and histologically, stucco keratoses are different from ordinary SKs. Each stucco keratosis lesion is essentially identical to the others, with a spiculated surface, white color, and average diameter of 2 to 3 mm. Histologically, they demonstrate a thickened epidermis with focal exophytic upward projections that resemble church spires. The lesions do not extend into the dermis.

Treatment of stucco keratoses is, at best, tedious, painful, and futile. The modalities used are cryotherapy or electrodessication with curettage. For a degree of comfort, use of a loofah after bathing will remove or smooth down a few lesions, but this process must be followed by application of a heavy emollient. Alas, regrowth is a certainty.

TAKE-HOME LEARNING POINTS

• Stucco keratosis is considered a variant of seborrheic keratosis, although they differ in several significant ways.
• The lesions of stucco keratosis are fairly uniform in appearance: white, rough, spiculated, epidermal papules measuring 2 to 3 mm.
• Stucco keratoses affect about 10% of the population (men more often than women) and have no racial predilection or pathologic implications.
• The lesions are found almost exclusively on the legs, from the knees down to and including the dorsa of the feet.
• Treatment is far from satisfactory, for multiple reasons, including resultant pain and scarring.

Three years ago, lesions began appearing on this now 68-year-old woman’s legs. They have grown in size and number, and their roughness disturbs the patient. She has been told the lesions are related to aging, but she has never seen anything like them on her friends or family—and she is worried about what they might mean for her health.

Her primary care provider diagnosed warts and performed cryotherapy on several of the lesions. However, the pain was intolerable and the treatment ineffective. To add insult to injury, each treated spot blistered and took more than a month to heal, leaving behind a pinkish brown blemish.

In all other respects, the patient’s health is excellent.

EXAMINATION
Both legs, from the upper thighs to the tops of the feet, are covered with thousands of uniformly distributed, tiny, keratotic, rough, dry papules. All the lesions are essentially identical: white, with no associated signs of inflammation. The patient’s skin is quite dry in general. Neither her palms nor soles are affected.

What’s the diagnosis?

DISCUSSION
The most common problem seen in dermatology offices worldwide is seborrheic keratosis (SK), a totally benign epidermal excrescence that appears to be related to aging and heredity. Most patients are in their 50s when they first notice an SK, and with a bit of luck, they will only see a few in their lifetime. But some patients develop hundreds of SKs, many of which become quite large (3-5 cm) and unsightly. In certain circumstances, SKs can herald the arrival of an occult carcinoma (the Leser-Trelat sign).

This patient has what some consider a variant of SK, called stucco keratosis. These lesions manifest almost exclusively on the lower legs and feet—perhaps due to the relative lack of sebaceous glands in those areas—and most often on men older than 60. Distressing as they are, stucco keratoses have no pathologic implications.

Grossly and histologically, stucco keratoses are different from ordinary SKs. Each stucco keratosis lesion is essentially identical to the others, with a spiculated surface, white color, and average diameter of 2 to 3 mm. Histologically, they demonstrate a thickened epidermis with focal exophytic upward projections that resemble church spires. The lesions do not extend into the dermis.

Treatment of stucco keratoses is, at best, tedious, painful, and futile. The modalities used are cryotherapy or electrodessication with curettage. For a degree of comfort, use of a loofah after bathing will remove or smooth down a few lesions, but this process must be followed by application of a heavy emollient. Alas, regrowth is a certainty.

TAKE-HOME LEARNING POINTS

• Stucco keratosis is considered a variant of seborrheic keratosis, although they differ in several significant ways.
• The lesions of stucco keratosis are fairly uniform in appearance: white, rough, spiculated, epidermal papules measuring 2 to 3 mm.
• Stucco keratoses affect about 10% of the population (men more often than women) and have no racial predilection or pathologic implications.
• The lesions are found almost exclusively on the legs, from the knees down to and including the dorsa of the feet.
• Treatment is far from satisfactory, for multiple reasons, including resultant pain and scarring.

In the Nov. 1, 2019, issue of JAMA Neurology, an editorial argues that it’s time for neurologists to start managing high blood pressure.

GlobalStock/Getty Images

It makes some very valid points: that targeting a systolic blood pressure of less than 120 mm Hg results in lower rates of cardiovascular events and all causes of mortality, that poorly controlled hypertension leads to debilitating neurologic conditions, and that high blood pressure is the most common modifiable risk factor for stroke.

All are strong points. I agree with them and definitely believe that more can and should be done to control hypertension.

The editorial then goes on to say that “first and foremost we are charging neurologists with actively diagnosing hypertension and prescribing medications when appropriate.”

Uh, no. I’m not going to be the one managing hypertension, nor should any outpatient neurologist.

Outpatient hypertension treatment has historically been, and should remain, the province of general practitioners, cardiologists, and nephrologists. Too many cooks, as they say, spoils the broth. I don’t want to be in a situation where two (or more) doctors are simultaneously trying to treat the same condition. On that path lies danger.

This doesn’t mean I ignore blood pressure. On the contrary, I take it (myself) at every patient visit, and put it in my note. In most cases I do nothing further, as nothing further needs to be done. On occasion, though, if it’s concerningly high, I’ll write it down for the patient and direct them to call the physician handling it. I also fax a note about it to that office, and if it’s dangerously high will call the doctor myself.

But try to manage it? No. Elevated readings definitely overlap with my world, but treating them shouldn’t.

The article says that, for some chronic patients, neurologists are their de facto internist. Perhaps for a few, but when a patient calls with concerns about a respiratory ailment, gastrointestinal problem, or other nonneurologic issue, I tell them to call their general practitioner. If they don’t have one I’m happy to give them the names and phone numbers of colleagues who practice that field, or even urgent care and emergency department information if needed. Just because I see them for their neurologic problems doesn’t qualify me to practice another branch of medicine.

Beyond the dangers of having more than one doctor involved, as a specialist it’s not practical for me to know the antihypertensive medications – possibly the largest group of agents on the market, – in detail, with their mechanisms of action, side effects, and contraindications. Yes, I do keep a handful in mind, since they’re needed off label for migraines and tremors, but not in the kind of detail a cardiologist would. I have to keep track of enough medications in my specialty as it is.

I wouldn’t try to handle blood pressure any more than I’d expect a nephrologist to treat epilepsy. It’s just looking for trouble.

Even when covering the hospital, I’ll stay out of that arena. This doesn’t mean I ignore blood pressure in such serious conditions as stroke or posterior reversible encephalopathy syndrome. I’m more than happy to provide guidelines and parameters. But as far as choosing the medications and doses? No.

Like driving, we all have to share the road. We may even be focused on the same journey (or patient). But part of practicing medicine and handling traffic is knowing when to stay in your lane.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In the Nov. 1, 2019, issue of JAMA Neurology, an editorial argues that it’s time for neurologists to start managing high blood pressure.

GlobalStock/Getty Images

It makes some very valid points: that targeting a systolic blood pressure of less than 120 mm Hg results in lower rates of cardiovascular events and all causes of mortality, that poorly controlled hypertension leads to debilitating neurologic conditions, and that high blood pressure is the most common modifiable risk factor for stroke.

All are strong points. I agree with them and definitely believe that more can and should be done to control hypertension.

The editorial then goes on to say that “first and foremost we are charging neurologists with actively diagnosing hypertension and prescribing medications when appropriate.”

Uh, no. I’m not going to be the one managing hypertension, nor should any outpatient neurologist.

Outpatient hypertension treatment has historically been, and should remain, the province of general practitioners, cardiologists, and nephrologists. Too many cooks, as they say, spoils the broth. I don’t want to be in a situation where two (or more) doctors are simultaneously trying to treat the same condition. On that path lies danger.

This doesn’t mean I ignore blood pressure. On the contrary, I take it (myself) at every patient visit, and put it in my note. In most cases I do nothing further, as nothing further needs to be done. On occasion, though, if it’s concerningly high, I’ll write it down for the patient and direct them to call the physician handling it. I also fax a note about it to that office, and if it’s dangerously high will call the doctor myself.

But try to manage it? No. Elevated readings definitely overlap with my world, but treating them shouldn’t.

The article says that, for some chronic patients, neurologists are their de facto internist. Perhaps for a few, but when a patient calls with concerns about a respiratory ailment, gastrointestinal problem, or other nonneurologic issue, I tell them to call their general practitioner. If they don’t have one I’m happy to give them the names and phone numbers of colleagues who practice that field, or even urgent care and emergency department information if needed. Just because I see them for their neurologic problems doesn’t qualify me to practice another branch of medicine.

Beyond the dangers of having more than one doctor involved, as a specialist it’s not practical for me to know the antihypertensive medications – possibly the largest group of agents on the market, – in detail, with their mechanisms of action, side effects, and contraindications. Yes, I do keep a handful in mind, since they’re needed off label for migraines and tremors, but not in the kind of detail a cardiologist would. I have to keep track of enough medications in my specialty as it is.

I wouldn’t try to handle blood pressure any more than I’d expect a nephrologist to treat epilepsy. It’s just looking for trouble.

Even when covering the hospital, I’ll stay out of that arena. This doesn’t mean I ignore blood pressure in such serious conditions as stroke or posterior reversible encephalopathy syndrome. I’m more than happy to provide guidelines and parameters. But as far as choosing the medications and doses? No.

Like driving, we all have to share the road. We may even be focused on the same journey (or patient). But part of practicing medicine and handling traffic is knowing when to stay in your lane.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In the Nov. 1, 2019, issue of JAMA Neurology, an editorial argues that it’s time for neurologists to start managing high blood pressure.

GlobalStock/Getty Images

It makes some very valid points: that targeting a systolic blood pressure of less than 120 mm Hg results in lower rates of cardiovascular events and all causes of mortality, that poorly controlled hypertension leads to debilitating neurologic conditions, and that high blood pressure is the most common modifiable risk factor for stroke.

All are strong points. I agree with them and definitely believe that more can and should be done to control hypertension.

The editorial then goes on to say that “first and foremost we are charging neurologists with actively diagnosing hypertension and prescribing medications when appropriate.”

Uh, no. I’m not going to be the one managing hypertension, nor should any outpatient neurologist.

Outpatient hypertension treatment has historically been, and should remain, the province of general practitioners, cardiologists, and nephrologists. Too many cooks, as they say, spoils the broth. I don’t want to be in a situation where two (or more) doctors are simultaneously trying to treat the same condition. On that path lies danger.

This doesn’t mean I ignore blood pressure. On the contrary, I take it (myself) at every patient visit, and put it in my note. In most cases I do nothing further, as nothing further needs to be done. On occasion, though, if it’s concerningly high, I’ll write it down for the patient and direct them to call the physician handling it. I also fax a note about it to that office, and if it’s dangerously high will call the doctor myself.

But try to manage it? No. Elevated readings definitely overlap with my world, but treating them shouldn’t.

The article says that, for some chronic patients, neurologists are their de facto internist. Perhaps for a few, but when a patient calls with concerns about a respiratory ailment, gastrointestinal problem, or other nonneurologic issue, I tell them to call their general practitioner. If they don’t have one I’m happy to give them the names and phone numbers of colleagues who practice that field, or even urgent care and emergency department information if needed. Just because I see them for their neurologic problems doesn’t qualify me to practice another branch of medicine.

Beyond the dangers of having more than one doctor involved, as a specialist it’s not practical for me to know the antihypertensive medications – possibly the largest group of agents on the market, – in detail, with their mechanisms of action, side effects, and contraindications. Yes, I do keep a handful in mind, since they’re needed off label for migraines and tremors, but not in the kind of detail a cardiologist would. I have to keep track of enough medications in my specialty as it is.

I wouldn’t try to handle blood pressure any more than I’d expect a nephrologist to treat epilepsy. It’s just looking for trouble.

Even when covering the hospital, I’ll stay out of that arena. This doesn’t mean I ignore blood pressure in such serious conditions as stroke or posterior reversible encephalopathy syndrome. I’m more than happy to provide guidelines and parameters. But as far as choosing the medications and doses? No.

Like driving, we all have to share the road. We may even be focused on the same journey (or patient). But part of practicing medicine and handling traffic is knowing when to stay in your lane.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Single-fraction radiation could not be shown to be noninferior to multi-fraction radiation at improving walking function in patients with spinal compression from metastatic cancer, but the small differences seen in a noninferiority trial may not matter to patients, investigators suggest.

Among 686 patients with spinal compression from metastatic cancer randomly assigned in a clinical trial to receive either 8 Gy of radiation in a single fraction or 20 Gy delivered in 5 fractions over 5 consecutive days, 69.3% of patients in the single-fraction arm had good ambulatory status at 8 weeks, compared with 72.7% of patients in the multi-fraction arm (P for noninferiority = .06), reported Peter J Hoskin, BSc, MBBS, MD, of Mount Vernon Cancer Centre in Northwood, England, and colleagues.

The trial did not meet the endpoint of noninferiority of single-fraction radiation for improving ambulation at 8 weeks because the lower limit of the 95% confidence interval (CI) was –11.5%, overlapping the noninferiority margin of –11%.

“However, for all other time points, the CI limits were within the noninferiority margin, and the observed risk differences between single-fraction and multi-fraction radiotherapy groups in ambulatory status were small and unlikely to be of clinical importance,” the investigators wrote in JAMA.

The authors note that although radiotherapy is widely used as a palliative measure for patients with spinal canal compression caused my metastatic disease, there is no agreement on the optimum schedule, with some guidelines recommending higher doses in multiple fractions, and others recommending a single 8 Gy does for patients with painful spinal sites.

To see whether single-fraction radiation could be noninferior to multi-fraction, the investigators enrolled patients in 42 sites in the United Kingdom and 5 in Australia into the SCORAD trial, and randomly assigned them to either single-fraction (345 patients) or multi-fraction (341 patients) radiation. The median age of those enrolled was 70 years, and 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer.

As noted, the primary endpoint of noninferiority of single-fraction radiation at improving ambulatory status at week 8 was not met. Ambulatory status was based on a 4-point scale and was classified as either grade 1: ambulatory without the use of aids and grade 5 of 5 of muscle power, or grade 2: ambulatory with aids or grade 4 of 5 of muscle power.

An analysis of secondary endpoints showed that the difference in ambulatory status grade 1 or 2 in the single- vs. multi-fraction group at week 1 was −0.4% (P value for noninferiority = .004), at week 4 it was −0.7% (P value for noninferiority = .01), and at week 12 it was 4.1% (P value for noninferiority = .002).

Overall survival rates at 12 weeks were 50% in the single-fraction group vs. 55% in the multi-fraction group; this difference was not statistically significant.

Of 11 other secondary endpoints analyzed, including ambulatory and safety endpoints, the between-group differences were not statistically significant or did not meet noninferiority criteria, the authors noted.

They concluded that although the trial did not meet the primary endpoint, ”the extent to which the lower bound of the CI overlapped with the noninferiority margin should be taken into account when interpreting the clinical importance of these findings.”

Cancer Research UK and Cancer Council Queensland funded the trial. Dr. Hoskin reported being supported by the National Institute for Health Research Manchester Biomedical Research Centre.

SOURCE: Hoskin PJ et al. JAMA 2019 Dec 3. doi: 10.1001/jama.2019.17913.

Single-fraction radiation could not be shown to be noninferior to multi-fraction radiation at improving walking function in patients with spinal compression from metastatic cancer, but the small differences seen in a noninferiority trial may not matter to patients, investigators suggest.

Among 686 patients with spinal compression from metastatic cancer randomly assigned in a clinical trial to receive either 8 Gy of radiation in a single fraction or 20 Gy delivered in 5 fractions over 5 consecutive days, 69.3% of patients in the single-fraction arm had good ambulatory status at 8 weeks, compared with 72.7% of patients in the multi-fraction arm (P for noninferiority = .06), reported Peter J Hoskin, BSc, MBBS, MD, of Mount Vernon Cancer Centre in Northwood, England, and colleagues.

The trial did not meet the endpoint of noninferiority of single-fraction radiation for improving ambulation at 8 weeks because the lower limit of the 95% confidence interval (CI) was –11.5%, overlapping the noninferiority margin of –11%.

“However, for all other time points, the CI limits were within the noninferiority margin, and the observed risk differences between single-fraction and multi-fraction radiotherapy groups in ambulatory status were small and unlikely to be of clinical importance,” the investigators wrote in JAMA.

The authors note that although radiotherapy is widely used as a palliative measure for patients with spinal canal compression caused my metastatic disease, there is no agreement on the optimum schedule, with some guidelines recommending higher doses in multiple fractions, and others recommending a single 8 Gy does for patients with painful spinal sites.

To see whether single-fraction radiation could be noninferior to multi-fraction, the investigators enrolled patients in 42 sites in the United Kingdom and 5 in Australia into the SCORAD trial, and randomly assigned them to either single-fraction (345 patients) or multi-fraction (341 patients) radiation. The median age of those enrolled was 70 years, and 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer.

As noted, the primary endpoint of noninferiority of single-fraction radiation at improving ambulatory status at week 8 was not met. Ambulatory status was based on a 4-point scale and was classified as either grade 1: ambulatory without the use of aids and grade 5 of 5 of muscle power, or grade 2: ambulatory with aids or grade 4 of 5 of muscle power.

An analysis of secondary endpoints showed that the difference in ambulatory status grade 1 or 2 in the single- vs. multi-fraction group at week 1 was −0.4% (P value for noninferiority = .004), at week 4 it was −0.7% (P value for noninferiority = .01), and at week 12 it was 4.1% (P value for noninferiority = .002).

Overall survival rates at 12 weeks were 50% in the single-fraction group vs. 55% in the multi-fraction group; this difference was not statistically significant.

Of 11 other secondary endpoints analyzed, including ambulatory and safety endpoints, the between-group differences were not statistically significant or did not meet noninferiority criteria, the authors noted.

They concluded that although the trial did not meet the primary endpoint, ”the extent to which the lower bound of the CI overlapped with the noninferiority margin should be taken into account when interpreting the clinical importance of these findings.”

Cancer Research UK and Cancer Council Queensland funded the trial. Dr. Hoskin reported being supported by the National Institute for Health Research Manchester Biomedical Research Centre.

SOURCE: Hoskin PJ et al. JAMA 2019 Dec 3. doi: 10.1001/jama.2019.17913.

Single-fraction radiation could not be shown to be noninferior to multi-fraction radiation at improving walking function in patients with spinal compression from metastatic cancer, but the small differences seen in a noninferiority trial may not matter to patients, investigators suggest.

Among 686 patients with spinal compression from metastatic cancer randomly assigned in a clinical trial to receive either 8 Gy of radiation in a single fraction or 20 Gy delivered in 5 fractions over 5 consecutive days, 69.3% of patients in the single-fraction arm had good ambulatory status at 8 weeks, compared with 72.7% of patients in the multi-fraction arm (P for noninferiority = .06), reported Peter J Hoskin, BSc, MBBS, MD, of Mount Vernon Cancer Centre in Northwood, England, and colleagues.

The trial did not meet the endpoint of noninferiority of single-fraction radiation for improving ambulation at 8 weeks because the lower limit of the 95% confidence interval (CI) was –11.5%, overlapping the noninferiority margin of –11%.

“However, for all other time points, the CI limits were within the noninferiority margin, and the observed risk differences between single-fraction and multi-fraction radiotherapy groups in ambulatory status were small and unlikely to be of clinical importance,” the investigators wrote in JAMA.

The authors note that although radiotherapy is widely used as a palliative measure for patients with spinal canal compression caused my metastatic disease, there is no agreement on the optimum schedule, with some guidelines recommending higher doses in multiple fractions, and others recommending a single 8 Gy does for patients with painful spinal sites.

To see whether single-fraction radiation could be noninferior to multi-fraction, the investigators enrolled patients in 42 sites in the United Kingdom and 5 in Australia into the SCORAD trial, and randomly assigned them to either single-fraction (345 patients) or multi-fraction (341 patients) radiation. The median age of those enrolled was 70 years, and 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer.

As noted, the primary endpoint of noninferiority of single-fraction radiation at improving ambulatory status at week 8 was not met. Ambulatory status was based on a 4-point scale and was classified as either grade 1: ambulatory without the use of aids and grade 5 of 5 of muscle power, or grade 2: ambulatory with aids or grade 4 of 5 of muscle power.

An analysis of secondary endpoints showed that the difference in ambulatory status grade 1 or 2 in the single- vs. multi-fraction group at week 1 was −0.4% (P value for noninferiority = .004), at week 4 it was −0.7% (P value for noninferiority = .01), and at week 12 it was 4.1% (P value for noninferiority = .002).

Overall survival rates at 12 weeks were 50% in the single-fraction group vs. 55% in the multi-fraction group; this difference was not statistically significant.

Of 11 other secondary endpoints analyzed, including ambulatory and safety endpoints, the between-group differences were not statistically significant or did not meet noninferiority criteria, the authors noted.

They concluded that although the trial did not meet the primary endpoint, ”the extent to which the lower bound of the CI overlapped with the noninferiority margin should be taken into account when interpreting the clinical importance of these findings.”

Cancer Research UK and Cancer Council Queensland funded the trial. Dr. Hoskin reported being supported by the National Institute for Health Research Manchester Biomedical Research Centre.

SOURCE: Hoskin PJ et al. JAMA 2019 Dec 3. doi: 10.1001/jama.2019.17913.

NATIONAL HARBOR, MD – More work and planning is needed for veterans after they serve in the Armed Forces, Rep. Brad Wenstrup, MD (R-Ohio), told attendees of the 2019 AMSUS annual meeting.

Rep. Wenstrup, in his December 3 keynote address, suggested that in addition to recruiters asking about what enlistees want to do in the military, they also should be asking what they want to do after military service.

“Let’s plan for that right now because it’s so much better, it’s so much healthier when you have a plan,” he said, noting that many military members struggle when integrating back into civilian life: They don’t have a plan, and they don’t feel “essential” and part of a team the way they did while serving. He pointed to graduating college students who have made plans for their next steps.

“We need to do the same thing for our troops who serve us [and] prepare them for what is next,” he said.

In addition to ensuring the health and well-being of service members when they come home, Rep. Wenstrup also discussed the need to ensure that medical staff are prepared for emergencies, identifying it as one of the challenges of military medicine right now.

“It’s a challenge for a lot in the active component when we are not at war … to sustain those skills, and it is very frustrating to the providers all the way around,” Rep. Wenstrup said. He noted that a lot of military medical staff help keep and refine those skills by working in the trauma department of major city hospitals.

“We are working together to try and bring our military assets, our civilian assets, DEA, whatever we can, together so that we make sure that we can provide and be ready,” he said. “And the importance of building these bridges is key to the future of medicine,” especially in a time of domestic crisis, so that all medical personnel, civilian and military, can work together for the common good of providing that service. “These are bridges we have to build.”

Rep. Wenstrup also talked about the need to do more to ensure a healthier population.

“The key is how do we live healthier, longer, because that is the real savings. A healthy nation is a stronger nation,” he said.

When comparing the amounts paid to providers for surgery with those paid for health and wellness, he contended that high payments for surgeons are due to the high skill set required for difficult procedures. However, health and wellness providers are paid poorly, as is payment for the management of chronic illness. “We don’t pay very well to the doctor who works with the patient and prevents the need to do open heart surgery,” he said. “Let’s start looking at that. Let’s start keeping people healthier longer.”

gtwachtman@mdedge.com

NATIONAL HARBOR, MD – More work and planning is needed for veterans after they serve in the Armed Forces, Rep. Brad Wenstrup, MD (R-Ohio), told attendees of the 2019 AMSUS annual meeting.

Rep. Wenstrup, in his December 3 keynote address, suggested that in addition to recruiters asking about what enlistees want to do in the military, they also should be asking what they want to do after military service.

“Let’s plan for that right now because it’s so much better, it’s so much healthier when you have a plan,” he said, noting that many military members struggle when integrating back into civilian life: They don’t have a plan, and they don’t feel “essential” and part of a team the way they did while serving. He pointed to graduating college students who have made plans for their next steps.

“We need to do the same thing for our troops who serve us [and] prepare them for what is next,” he said.

In addition to ensuring the health and well-being of service members when they come home, Rep. Wenstrup also discussed the need to ensure that medical staff are prepared for emergencies, identifying it as one of the challenges of military medicine right now.

“It’s a challenge for a lot in the active component when we are not at war … to sustain those skills, and it is very frustrating to the providers all the way around,” Rep. Wenstrup said. He noted that a lot of military medical staff help keep and refine those skills by working in the trauma department of major city hospitals.

“We are working together to try and bring our military assets, our civilian assets, DEA, whatever we can, together so that we make sure that we can provide and be ready,” he said. “And the importance of building these bridges is key to the future of medicine,” especially in a time of domestic crisis, so that all medical personnel, civilian and military, can work together for the common good of providing that service. “These are bridges we have to build.”

Rep. Wenstrup also talked about the need to do more to ensure a healthier population.

“The key is how do we live healthier, longer, because that is the real savings. A healthy nation is a stronger nation,” he said.

When comparing the amounts paid to providers for surgery with those paid for health and wellness, he contended that high payments for surgeons are due to the high skill set required for difficult procedures. However, health and wellness providers are paid poorly, as is payment for the management of chronic illness. “We don’t pay very well to the doctor who works with the patient and prevents the need to do open heart surgery,” he said. “Let’s start looking at that. Let’s start keeping people healthier longer.”

gtwachtman@mdedge.com

NATIONAL HARBOR, MD – More work and planning is needed for veterans after they serve in the Armed Forces, Rep. Brad Wenstrup, MD (R-Ohio), told attendees of the 2019 AMSUS annual meeting.

Rep. Wenstrup, in his December 3 keynote address, suggested that in addition to recruiters asking about what enlistees want to do in the military, they also should be asking what they want to do after military service.

“Let’s plan for that right now because it’s so much better, it’s so much healthier when you have a plan,” he said, noting that many military members struggle when integrating back into civilian life: They don’t have a plan, and they don’t feel “essential” and part of a team the way they did while serving. He pointed to graduating college students who have made plans for their next steps.

“We need to do the same thing for our troops who serve us [and] prepare them for what is next,” he said.

In addition to ensuring the health and well-being of service members when they come home, Rep. Wenstrup also discussed the need to ensure that medical staff are prepared for emergencies, identifying it as one of the challenges of military medicine right now.

“It’s a challenge for a lot in the active component when we are not at war … to sustain those skills, and it is very frustrating to the providers all the way around,” Rep. Wenstrup said. He noted that a lot of military medical staff help keep and refine those skills by working in the trauma department of major city hospitals.

“We are working together to try and bring our military assets, our civilian assets, DEA, whatever we can, together so that we make sure that we can provide and be ready,” he said. “And the importance of building these bridges is key to the future of medicine,” especially in a time of domestic crisis, so that all medical personnel, civilian and military, can work together for the common good of providing that service. “These are bridges we have to build.”

Rep. Wenstrup also talked about the need to do more to ensure a healthier population.

“The key is how do we live healthier, longer, because that is the real savings. A healthy nation is a stronger nation,” he said.

When comparing the amounts paid to providers for surgery with those paid for health and wellness, he contended that high payments for surgeons are due to the high skill set required for difficult procedures. However, health and wellness providers are paid poorly, as is payment for the management of chronic illness. “We don’t pay very well to the doctor who works with the patient and prevents the need to do open heart surgery,” he said. “Let’s start looking at that. Let’s start keeping people healthier longer.”

gtwachtman@mdedge.com

Study Overview

Objective. To compare the benefit of apixaban with a vitamin K antagonist and compare aspirin with placebo in patients with atrial fibrillation who had acute coronary syndrome or underwent percutaneous coronary intervention (PCI) and were planning to take a P2Y12 inhibitor.

Design. Multicenter, international, open-label, prospective randomized controlled trial with a 2-by-2 factorial design.

Setting and participants. 4614 patients who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor.

Intervention. Patients were assigned by means of an interactive voice-response system to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months.

Main outcome measures. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events.

Main results. At 6 months, major or clinically relevant nonmajor bleeding had occurred in 10.5% of the patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.58-0.81, P < 0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (HR 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR 0.83; 95% CI, 0.74-0.93; P = 0.002) and similar incidence of ischemic events.

Conclusion. Among patients with atrial fibrillation and recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban without aspirin resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than the regimens that included a vitamin K antagonist, aspirin, or both.

 

 

Commentary

PCI is performed in about 20% of patients with atrial fibrillation. These patients require dual antiplatelet therapy to prevent ischemic events, combined with long-term anticoagulation to prevent stroke due to atrial fibrillation. Because the combination of anticoagulation and antiplatelet therapy is associated with a higher risk of bleeding, balancing the risk and benefit of dual antiplatelet therapy and anticoagulation in this population is crucial.

Previous studies have assessed the risk and benefit associated with anticoagulation and antiplatelet therapy. When warfarin plus clopidogrel (double therapy) was compared with warfarin, aspirin, and clopidogrel (triple therapy) in patients with acute coronary syndromes and stable ischemic coronary disease undergoing PCI, use of clopidogrel without aspirin (double therapy) was associated with a significant reduction in bleeding complications (19.4% versus 44.4%, HR, 0.36; 95% CI, 0.26-0.20; P < 0.0001) without increasing thrombotic events.¹ Recent studies have compared triple therapy with warfarin to double therapy using direct oral anticoagulants (DOAC). The PIONEER AF-PCI study, which compared low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor to vitamin K antagonist plus dual antiplatelet therapy, found that the rates of clinically significant bleeding were lower in the low-dose rivaroxaban group compared to the triple-therapy group with a vitamin K antagonist (16.8% versus 26.7%; HR, 0.59; 95% CI, 0.47-0.76; P < 0.001).² Similarly, the RE-DUAL PCI studied dabigatran and showed that the dual therapy group with dabigatran had a lower incidence of major or clinically relevant nonmajor bleeding events during follow-up compared to triple therapy including a vitamin K antagonist (15.4% versus 26.9%; HR, 0.52; 95% CI, 0.42-0.63; P < 0.001).³

In this context, Lopes at al investigated the clinical question of dual therapy versus triple therapy by performing a well-designed randomized clinical trial. In this trial with a 2-by-2 factorial design, the authors studied the effect of apixaban compared to vitamin K antagonist and the effect of aspirin compared to placebo. Major or clinically relevant nonmajor bleeding occurred in 10.5% of patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (HR 0.69; 95% CI, 0.58-0.81; P < 0.001). The incidence of major or clinically relevant nonmajor bleeding was higher in patients receiving aspirin than in those receiving placebo (16.1% versus 9.0%; HR, 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR, 0.83; 95% CI, 0.74-0.93; P = 0.002). The incidence of ischemic events was similar between the apixaban group and vitamin K antagonist group and between the aspirin group and placebo group.

The strengths of this current study include the large number of patients it enrolled. Taking the results from the PIONEER-AF, RE-DUAL PCI, and AUGUSTUS trials, it is clear that DOAC reduces the risk of bleeding compared to vitamin K antagonist. In addition, the AUGUSTUS trial was the first that evaluated the effect of aspirin in patients treated with DOAC and antiplatelet therapy. Aspirin was associated with increased risk of bleeding, with a similar rate of ischemic events compared to placebo.

The AUGUSTUS trial has several limitations. Although the incidence of ischemic events was similar between the apixaban group and the vitamin K antagonist group, the study was not powered to evaluate for individual ischemic outcomes. However, there was no clear evidence of an increase in harm. Since more than 90% of P2Y12 inhibitors used were clopidogrel, the safety and efficacy of combining apixaban with ticagrelor or prasugrel will require further study.

Applications for Clinical Practice

In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, dual therapy with a P2Y12 inhibitor and DOAC should be favored over a regimen that includes a vitamin K antagonist and/or aspirin.

—Taishi Hirai, MD, University of Missouri Medical Center, and John Blair, MD, University of Chicago Medical Center

Study Overview

Objective. To compare the benefit of apixaban with a vitamin K antagonist and compare aspirin with placebo in patients with atrial fibrillation who had acute coronary syndrome or underwent percutaneous coronary intervention (PCI) and were planning to take a P2Y12 inhibitor.

Design. Multicenter, international, open-label, prospective randomized controlled trial with a 2-by-2 factorial design.

Setting and participants. 4614 patients who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor.

Intervention. Patients were assigned by means of an interactive voice-response system to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months.

Main outcome measures. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events.

Main results. At 6 months, major or clinically relevant nonmajor bleeding had occurred in 10.5% of the patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.58-0.81, P < 0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (HR 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR 0.83; 95% CI, 0.74-0.93; P = 0.002) and similar incidence of ischemic events.

Conclusion. Among patients with atrial fibrillation and recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban without aspirin resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than the regimens that included a vitamin K antagonist, aspirin, or both.

 

 

Commentary

PCI is performed in about 20% of patients with atrial fibrillation. These patients require dual antiplatelet therapy to prevent ischemic events, combined with long-term anticoagulation to prevent stroke due to atrial fibrillation. Because the combination of anticoagulation and antiplatelet therapy is associated with a higher risk of bleeding, balancing the risk and benefit of dual antiplatelet therapy and anticoagulation in this population is crucial.

Previous studies have assessed the risk and benefit associated with anticoagulation and antiplatelet therapy. When warfarin plus clopidogrel (double therapy) was compared with warfarin, aspirin, and clopidogrel (triple therapy) in patients with acute coronary syndromes and stable ischemic coronary disease undergoing PCI, use of clopidogrel without aspirin (double therapy) was associated with a significant reduction in bleeding complications (19.4% versus 44.4%, HR, 0.36; 95% CI, 0.26-0.20; P < 0.0001) without increasing thrombotic events.¹ Recent studies have compared triple therapy with warfarin to double therapy using direct oral anticoagulants (DOAC). The PIONEER AF-PCI study, which compared low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor to vitamin K antagonist plus dual antiplatelet therapy, found that the rates of clinically significant bleeding were lower in the low-dose rivaroxaban group compared to the triple-therapy group with a vitamin K antagonist (16.8% versus 26.7%; HR, 0.59; 95% CI, 0.47-0.76; P < 0.001).² Similarly, the RE-DUAL PCI studied dabigatran and showed that the dual therapy group with dabigatran had a lower incidence of major or clinically relevant nonmajor bleeding events during follow-up compared to triple therapy including a vitamin K antagonist (15.4% versus 26.9%; HR, 0.52; 95% CI, 0.42-0.63; P < 0.001).³

In this context, Lopes at al investigated the clinical question of dual therapy versus triple therapy by performing a well-designed randomized clinical trial. In this trial with a 2-by-2 factorial design, the authors studied the effect of apixaban compared to vitamin K antagonist and the effect of aspirin compared to placebo. Major or clinically relevant nonmajor bleeding occurred in 10.5% of patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (HR 0.69; 95% CI, 0.58-0.81; P < 0.001). The incidence of major or clinically relevant nonmajor bleeding was higher in patients receiving aspirin than in those receiving placebo (16.1% versus 9.0%; HR, 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR, 0.83; 95% CI, 0.74-0.93; P = 0.002). The incidence of ischemic events was similar between the apixaban group and vitamin K antagonist group and between the aspirin group and placebo group.

The strengths of this current study include the large number of patients it enrolled. Taking the results from the PIONEER-AF, RE-DUAL PCI, and AUGUSTUS trials, it is clear that DOAC reduces the risk of bleeding compared to vitamin K antagonist. In addition, the AUGUSTUS trial was the first that evaluated the effect of aspirin in patients treated with DOAC and antiplatelet therapy. Aspirin was associated with increased risk of bleeding, with a similar rate of ischemic events compared to placebo.

The AUGUSTUS trial has several limitations. Although the incidence of ischemic events was similar between the apixaban group and the vitamin K antagonist group, the study was not powered to evaluate for individual ischemic outcomes. However, there was no clear evidence of an increase in harm. Since more than 90% of P2Y12 inhibitors used were clopidogrel, the safety and efficacy of combining apixaban with ticagrelor or prasugrel will require further study.

Applications for Clinical Practice

In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, dual therapy with a P2Y12 inhibitor and DOAC should be favored over a regimen that includes a vitamin K antagonist and/or aspirin.

—Taishi Hirai, MD, University of Missouri Medical Center, and John Blair, MD, University of Chicago Medical Center

Study Overview

Objective. To compare the benefit of apixaban with a vitamin K antagonist and compare aspirin with placebo in patients with atrial fibrillation who had acute coronary syndrome or underwent percutaneous coronary intervention (PCI) and were planning to take a P2Y12 inhibitor.

Design. Multicenter, international, open-label, prospective randomized controlled trial with a 2-by-2 factorial design.

Setting and participants. 4614 patients who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor.

Intervention. Patients were assigned by means of an interactive voice-response system to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months.

Main outcome measures. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events.

Main results. At 6 months, major or clinically relevant nonmajor bleeding had occurred in 10.5% of the patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.58-0.81, P < 0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (HR 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR 0.83; 95% CI, 0.74-0.93; P = 0.002) and similar incidence of ischemic events.

Conclusion. Among patients with atrial fibrillation and recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban without aspirin resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than the regimens that included a vitamin K antagonist, aspirin, or both.

 

 

Commentary

PCI is performed in about 20% of patients with atrial fibrillation. These patients require dual antiplatelet therapy to prevent ischemic events, combined with long-term anticoagulation to prevent stroke due to atrial fibrillation. Because the combination of anticoagulation and antiplatelet therapy is associated with a higher risk of bleeding, balancing the risk and benefit of dual antiplatelet therapy and anticoagulation in this population is crucial.

Previous studies have assessed the risk and benefit associated with anticoagulation and antiplatelet therapy. When warfarin plus clopidogrel (double therapy) was compared with warfarin, aspirin, and clopidogrel (triple therapy) in patients with acute coronary syndromes and stable ischemic coronary disease undergoing PCI, use of clopidogrel without aspirin (double therapy) was associated with a significant reduction in bleeding complications (19.4% versus 44.4%, HR, 0.36; 95% CI, 0.26-0.20; P < 0.0001) without increasing thrombotic events.¹ Recent studies have compared triple therapy with warfarin to double therapy using direct oral anticoagulants (DOAC). The PIONEER AF-PCI study, which compared low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor to vitamin K antagonist plus dual antiplatelet therapy, found that the rates of clinically significant bleeding were lower in the low-dose rivaroxaban group compared to the triple-therapy group with a vitamin K antagonist (16.8% versus 26.7%; HR, 0.59; 95% CI, 0.47-0.76; P < 0.001).² Similarly, the RE-DUAL PCI studied dabigatran and showed that the dual therapy group with dabigatran had a lower incidence of major or clinically relevant nonmajor bleeding events during follow-up compared to triple therapy including a vitamin K antagonist (15.4% versus 26.9%; HR, 0.52; 95% CI, 0.42-0.63; P < 0.001).³

In this context, Lopes at al investigated the clinical question of dual therapy versus triple therapy by performing a well-designed randomized clinical trial. In this trial with a 2-by-2 factorial design, the authors studied the effect of apixaban compared to vitamin K antagonist and the effect of aspirin compared to placebo. Major or clinically relevant nonmajor bleeding occurred in 10.5% of patients receiving apixaban, as compared to 14.7% of those receiving a vitamin K antagonist (HR 0.69; 95% CI, 0.58-0.81; P < 0.001). The incidence of major or clinically relevant nonmajor bleeding was higher in patients receiving aspirin than in those receiving placebo (16.1% versus 9.0%; HR, 1.89; 95% CI, 1.59-2.24; P < 0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% versus 27.4%; HR, 0.83; 95% CI, 0.74-0.93; P = 0.002). The incidence of ischemic events was similar between the apixaban group and vitamin K antagonist group and between the aspirin group and placebo group.

The strengths of this current study include the large number of patients it enrolled. Taking the results from the PIONEER-AF, RE-DUAL PCI, and AUGUSTUS trials, it is clear that DOAC reduces the risk of bleeding compared to vitamin K antagonist. In addition, the AUGUSTUS trial was the first that evaluated the effect of aspirin in patients treated with DOAC and antiplatelet therapy. Aspirin was associated with increased risk of bleeding, with a similar rate of ischemic events compared to placebo.

The AUGUSTUS trial has several limitations. Although the incidence of ischemic events was similar between the apixaban group and the vitamin K antagonist group, the study was not powered to evaluate for individual ischemic outcomes. However, there was no clear evidence of an increase in harm. Since more than 90% of P2Y12 inhibitors used were clopidogrel, the safety and efficacy of combining apixaban with ticagrelor or prasugrel will require further study.

Applications for Clinical Practice

In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, dual therapy with a P2Y12 inhibitor and DOAC should be favored over a regimen that includes a vitamin K antagonist and/or aspirin.

—Taishi Hirai, MD, University of Missouri Medical Center, and John Blair, MD, University of Chicago Medical Center

From the Dartmouth Institute for Health Policy & Clinical Practice, Geisel School of Medicine, Hanover, NH (Ms. Manohar and Dr. Oliver), the Department of Community & Family Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH (Ms. Perkins, Ms. Laurion, and Dr. Oliver), and the Multiple Sclerosis Specialty Care Program, Concord Hospital, Concord, NH (Dr. Oliver).

Abstract

• Background: Patient-reported outcomes (PROs), including patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs), can be used to assess perceived health status, functioning, quality of life, and experience of care. Complex chronic illnesses such as multiple sclerosis (MS) affect multiple aspects of health, and PROs can be applied in assessment and decision-making in MS care as well as in research pertaining to MS.
• Objective: To provide a general review of PROs, with a specific focus on implications for MS care.
• Methods: Evidence synthesis of available literature on PROs in MS care.
• Results: PROs (including PROMs and PREMs) have historically been utilized in research and are now being applied in clinical, improvement, and population health settings using learning health system approaches in many disease populations, including MS. Many challenges complicate the use of PROs in MS care, including reliability, validity, and interpretability of PROMs, as well as feasibility barriers due to time and financial constraints in clinical settings.
• Conclusion: PROs have the potential to better inform clinical care, empower patient-centered care, inform health care improvement efforts, and create the conditions for coproduction of health care services.

Keywords: PRO; PROM; patient-reported outcome measure; patient-reported experience measure; quality of life; patient-centered care.

Multiple sclerosis (MS) is a disabling, complex, chronic, immune-mediated disorder of the central nervous system (CNS). MS causes inflammatory and degenerative damage in the CNS, which disrupts signaling pathways.¹ It is most commonly diagnosed in young adults and affects 2.3 million people worldwide.² People with MS experience very different disease courses and a wide range of neurological symptoms, including visual, somatic, mental health, sensory, motor, and cognitive problems.^1-3 Relapsing-remitting MS, the most common form, affects 85% of those with MS and is characterized by periods of relapse (exacerbation) and remission.¹ Other forms of MS (primary progressive and secondary progressive MS) are characterized by progressive deterioration and worsening symptom severity without exacerbations. Disease-modifying therapies (DMTs) can reduce the frequency of exacerbations and disability progression, but unfortunately there is no cure for MS. Treatment is focused on increasing quality of life, minimizing disability, and maximizing wellness.

Patient-reported outcomes (PROs) describe the perceived health status, function, and/or experience of a person as obtained by direct self-report. Patient-reported outcome measures (PROMs) are validated PROs that can be used to inform clinical care,⁴ and have demonstrated effectiveness in improving patient-provider communication and decision-making.^5-7 PROMs are currently used in some MS clinical trials to determine the impact of experimental interventions,^8-10 and are also being used to inform and improve clinical care in some settings. Especially for persons with MS, they can provide individualized perspectives about health experience and outcomes.¹¹ In more advanced applications, PROMs can be used to improve face-to-face collaborations between clinicians and patients and to inform patient-centered systems of care.^12-14 PROMs can also be used to inform systems-level improvement for entire patient populations.^15,16

In this article, we review current applications of PROs and PROMs in the care of persons with MS, as well as current limitations and barriers to their use.

CASE STUDY

Marion is a 26-year-old woman who first developed MS symptoms at age 16, including increased sensitivity to heat, blurry vision, and numbness in her legs (note: this case was developed based on interviews with persons with MS, obtained with appropriate consents, and does not represent a specific patient). At that time, her clinician attributed her symptoms to a car accident she had been in a few months before. Later, at age 20, she developed abdominal paresthesia, which her clinician attributed to an episode of shingles. At age 23, she developed double vision. She was evaluated by a neurologist and was diagnosed with MS. Marion started care with an MS specialists, who worked with her towards her goals of having a family, working, and exercising. In addition to appropriate medical care, she started martial arts training and biking for exercise and transitioned to a consulting position with flexible hours and the ability to work from home. Her daughter was born a year later.

At a recent visit to her neurologist, Marion reviews her health diary, in which she has been tracking her fatigue levels throughout the day and when she has to visit the bathroom. The PRO diary also helps her remember details that she might not otherwise be able to recall at the time of her clinic visit. They review the diary entrees together to develop a shared understanding of what Marion has been experiencing and identify trends in the PRO data. They discuss symptom management and use the PRO information from the diary to help guide adjustments to her physical therapy routine and medication regimen.

Part of Marion’s “PRO package” includes the Center for Epidemiologic Studies Depression Scale (CES-D), a validated depression screening and symptom severity questionnaire that she completes every 3 months. Although she denies being depressed, she has noticed that her CES-D scores in recent months have been consistently increasing. This prompts a discussion about mental health in MS and a referral to work on depression with the MS mental health specialist. Marion and the mental health specialist use CES-D measures at baseline and during treatment to set a remission target and to track progress during treatment. Marion finds this helpful because she says it is hard for her to “wrap my hands around depression… it’s not something that there is a blood test or a MRI for.” Marion is encouraged by being able to see her CES-D scores change as her depression severity decreases, and this helps motivate her to keep engaged in treatment.

PROs and PROMs: General Applications

PROs are measures obtained directly from an individual without a priori interpretation by a clinician.^9,17 PROs capture individual perspectives on symptoms, capability, disability, and health-related quality of life.⁹ With increasing emphasis on patient-centered care,¹⁸ individual perspectives and preferences elicited using PROMs may be able to inform better quality of care and patient-centered disease treatment and management.^19-21

PROMs are standardized, validated questionnaires used to assess PROs and can be generic or condition-specific. Generic PROMs can be used in any patient population. The SF-36²² is a set of quality of life measures that assess perceived ability to complete physical tasks and routine activities, general health status, fatigue, social functioning, pain, and emotional and mental health.²³ Condition-specific PROMs can be used for particular patient populations and are helpful in identifying changes in health status for a specific disease, disability, or surgery. For example, the PDQ-39 assesses 8 dimensions of daily living, functioning, and well-being for people with Parkinson’s disease.²⁴

PROMs have been used in some MS clinical trials and research studies to determine the effectiveness of experimental treatments from the viewpoint of study participants.^9,25,26 PROs can also be utilized in clinical care to facilitate communication of needs and track health outcomes,²⁷ and can inform improvement in outcomes for health systems and populations. They can also be used to assess experience of care,²⁸ encouraging a focus on high-quality outcomes through PRO-connected reimbursement mechanisms,²⁹ and provide aggregate data to evaluate clinical practice, population health outcomes, and the effectiveness of public policies.²⁷

Patient-reported experience measures (PREMs) assess patient satisfaction and experience of health care.^30,31 CollaboRATE³² is a PREM that assesses the degree of shared decision-making occurring between patients and clinicians during clinical care. PREMs are currently used for assessing self-efficacy and in shared decision-making and health care improvement applications. PREMs have yet to be developed specifically for persons with MS.

PROMs in MS Care

Generic PROMs have shown that persons with MS are disproportionately burdened by poor quality of life.^33-35 Other generic PROMs, like the SF-36,³⁶ the Sickness Impact Profile,³⁷ and versions of the Health Utilities Index,³⁸ can be used to gather information on dysfunction and to determine quality and duration of life modified by MS-related dysfunction and disability. MS-specific PROMs are used to assess MS impairments, including pain, fatigue, cognition, sexual dysfunction, and depression.^12,39-42 PROMs have also been used in MS clinical trials, including the Multiple Sclerosis Impact Scale-29 (MSIS-29),^43,44 the Leeds MS QoL (LMSQoL),^45,46 the Functional Assessment of MS (FAMS),⁴⁷ the Hamburg Quality of Life Questionnaire in MS (HAQUAMS),⁴⁸ the MS Quality of Life-54 (MSQoL-54),⁴⁹ the MS International QoL (MUSIQoL),⁵⁰ and the Patient-Reported Indices for MS Activity Limitations Scale (PRIMUS).⁵¹

Condition-specific PROMs are more sensitive to changes in health status and functioning for persons with MS compared to generic PROMs. They are also more reliable during MS remission and relapse periods.^44,52 For example, the SF-36 has floor and ceiling effects in MS populations—a high proportion of persons with MS are scored at the maximum or minimum levels of the scale, limiting discriminant capability.²² As a result, a “combined approach” using both generic and MS-specific measures is often recommended.⁵³ Some MS PROMs (eg, MSQoL-54) include generic questions found in the SF-36 as well as additional MS-specific questions or scales.

The variety of PROMs available (see Table for a selected listing) introduces a significant challenge to using them—limited generalizability and difficulty comparing PROs across MS studies. Efforts to establish common PROMs have been undertaken to address this problem.⁵⁴ The National Institute of Neurologicical Disorders and Stroke (NINDS) sponsored the development of a neurological quality of life battery, the Neuro-QOL.⁵⁵ Neuro-QOL measures the physical, mental, and social effects of neurological conditions in adults and children with neurological disorders and has the capability to facilitate comparisons across different neurological conditions. Additionally, the Patient-Reported Outcomes Measure Information System (PROMIS) has been developed to assess physical, mental, and social effects of chronic disease. PROMIS has a hybrid design that includes generic and MS-specific measures (such as PROMIS FatigueMS).⁵⁶ PROMIS can be used to assess persons with MS as well as to compare the MS population with other populations with chronic illness.

PROMs have varying levels of reliability and validity. The Evaluating the Measure of Patient-Reported Outcomes⁵⁷ study evaluated the development process of MS PROMs,⁴³ and found that the MSIS-29 and LMSQoL had the highest overall reliability among the most common MS PROMs. However, both scored poorly on validity due to lack of patient involvement during development. This questions the overall capability of existing MS PROMs to accurately and consistently assess PROs in persons with MS.

 

 

“Feed-Forward” PROMs

Oliver and colleagues¹⁶ have described “feed-forward” PROM applications in MS care in a community hospital setting using a learning health system approach. This MS clinic uses feed-forward PROs to inform clinical care—PRO data are gathered before the clinic visit and analyzed ahead of or during the clinic visit by the clinician. Patients are asked to arrive early and complete a questionnaire comprised of PROMs measuring disability, functioning, quality of life, cognitive ability, pain, fatigue, sleep quality, anxiety, and depression. Clinicians score the PROMs and input scores into the electronic health record before the clinical encounter. During the clinic visit, PROM data is visually displayed so that the clinician and patient can discuss results and use the data to better inform decision-making. The visual data display contains longitudinal information, displaying trends in health status across multiple domains, and includes specified thresholds for clinically active symptom levels (Figure).¹⁶ Longitudinal monitoring of PROM data allows for real-time assessment of goal-related progress throughout treatment. As illustrated previously by Marion’s case study, the use of real-time feed-forward PROM data can strengthen the partnership between patient and clinician as well as improve empowerment, engagement, self-monitoring, and adherence.

PRO Dashboards

Performance dashboards are increasingly used in health care to visually display clinical and PRO data for individual patients, systems, and populations over time. Dashboards display a parsimonious group of critically important measures to give clinicians and patients a longitudinal view of PRO status. They can inform decision-making in clinical care, operations, health care improvement efforts, and population health initiatives.⁵⁸ Effective dashboards allow for user customization with meaningful measures, knowledge discovery for analysis of health problems, accessibility of health information, clear visualization, alerts for unexpected data values, and system connectivity.^59,60 Appropriate development of PRO dashboards requires meaningful patient and clinician involvement via focus groups and key informant interviews, Delphi process approaches to prioritize and finalize selection of priority measures, iterative building of the interface with design input from key informants and stakeholders (co-design), and pilot testing to assess feasibility and acceptability of use.^61-63

Other Applications of PROs/PROMs in MS

Learning Health Systems

The National Quality Forum (NQF) and the Centers for Medicaid and Medicare Services have adopted PROs for use in quality measurement.^64-66 This includes a movement towards the use of LHS, defined as a health system in which information from patients and clinicians is systematically collected and synthesized with external evidence to inform clinical care, improvement, and research.^67-70 Often a LHS is undertaken as a collaborative effort between multiple health care centers to improve quality and outcomes of care.⁷⁰ The MS Continuous Quality Improvement Collaborative (MS-CQI), the first multi-center systems-level health care improvement research collaborative for MS,⁷¹ as well as IBD Qorus and the Cystic Fibrosis Care Center Network utilize LHS approaches.^72-77

IBD Qorus is a LHS developed by the Crohn’s and Colitis Foundation that uses performance dashboards to better inform clinical care for people with inflammatory bowel disease. It also employs system-level dashboards for performance benchmarking in quality improvement initiatives and aggregate-level dashboards to assess population health status.^78,79 MS-CQI uses a LHS approach to inform the improvement of MS care across multiple centers using a comprehensive dashboard, including PROMs, for benchmarking and to monitor system and population health status. MS-CQI collects PROMs using a secure online platform that can be accessed by persons with MS and their clinicians and also includes a journaling feature for collecting qualitative information and for reference and self-monitoring.⁷¹

MS Research

PROMs are used in clinical and epidemiological research to evaluate many aspects of MS, including the FAMS, the PDSS, the Fatigue Impact Scale (FIS), and others.^80-82 For example, the PROMIS FatigueMS and the Fatigue Performance Scale have been used to assess the impact of MS-related fatigue on social participation.⁸³ Generic and MS-specific PROMs have been used to assess pain levels for people with MS,^84-87 and multiple MS-specific PROMs, like PRIMUS and MSQoL-54,⁴³ as well as the SF-36³⁹ include pain assessment scales. PROMs have also been used to assess MS-related bladder, bowel, and sexual dysfunction. Urgency, frequency, and incontinence affect up to 75% of patients with MS,⁸⁸ and many PROMs, such as the LMSQoL, MUSIQoL, and the MSQoL-54, are able to evaluate bladder control and sexual functioning.^43,89

PROMs are employed in MS clinical trials to help assess the tolerability and effectiveness of DMTs.^90,91 PROs have been used as secondary endpoints to understand the global experience of a DMT from the patient perspective.^92-94 There are 15 FDA-approved DMTs for MS, and clinical trials for 6 of these have used PROMs as an effectiveness end point.^54,91,95,96 However, most DMT clinical trials are powered for MRI, relapse rate, or disease progression primary outcomes rather than PROMs, often resulting in underpowered PROM analyses.⁹⁷ In addition, many PROMs are not appropriate for use in DMT clinical trials.^98,99

In order to bridge the gap between clinical research and practice, some industry entities are championing “patient-focused drug development” approaches. The Accelerated Cure Project for MS has launched iConquerMS, which collects PROMs from persons with MS to further PRO research in MS and follows 4700 individuals with MS worldwide.¹⁰⁰ In 2018, the American College of Physicians announced a collaboration with an industry partner to share data to inform DMT clinical trials and develop and validate PROMs specifically designed for DMT clinical trials.¹⁰¹

Population Health

Registries following large cohorts of people with MS have the potential to develop knowledge about disease progression, treatment patterns, and outcomes.¹⁰² The Swedish EIMS study has identified associations between pre-disease body mass index and MS prognosis,¹⁰² alcohol and tobacco consumption affecting MS risk,^103,104 and exposure to shift work at a young age and increased MS risk.¹⁰⁵ The North American Research Committee on MS^83,106,107 and iConquerMS registries are “PROM-driven” and have been useful in identifying reductions in disease progression in people using DMTs.^107,108 The New York State MS Consortium has identified important demographic characteristics that influence MS progression.^109,110 PROs can also be used to determine risk of MS-related mortality¹¹¹ and decline in quality of life.^112,113 Limitations of these approaches include use of different PROMs, inconsistencies in data collection processes, and different follow-up intervals used across registries.¹⁰²

Patient-Centered Care

The Institute of Medicine defines patient-centeredness as “care that is respectful and responsive to individual patient preferences, needs, and values and ensures that patient values guide all clinical decisions.”¹¹⁴ PROs are useful for identifying a patient’s individual health concerns and preferences, something that is needed when treating a highly variable chronic health condition like MS. The use of PROs can help clinicicans visualize the lived experience of persons with MS and identify personal preferences,¹¹⁵ as well as improve self-monitoring, self-management, self-efficacy, adherence, wellness, and coping ability.¹¹⁶ At the system level, PROs can inform improvement initiatives and patient-centered care design efforts.^117-120

Selecting PROMs

Initiatives from groups like the COnsensus-based Standards for the Selection of health Measurement INstruments (COSMIN)¹²¹ and the International Society for Quality of Life Research (ISOQOL)¹⁰⁸ offer guidance on selecting PROs. The NINDS has promoted common data collection between clinical studies of the brain and nervous system.¹²² General guidance from these sources recommends first considering the outcome and target population, selecting PROMs to measure the outcome through a synthesis of the available evidence, assessing validity and reliability of selected PROMs, and using standard measures that can be compared across studies or populations.^108,121 Other factors include feasibility, acceptability, and burden of use for patients, clinicians, and systems, as well as literacy, cultural, and linguistic factors.¹²³

The NQF recommends that consideration be given to individual patient needs, insurance factors, clinical setting constraints, and available resources when selecting PROMs.¹²⁴ To maximize response rate, PROMs that are sensitive, reliable, valid, and developed in a comparative demographic of patients are advised.¹²⁵ ISOQOL has released a User’s Guide and several companion guides on implementing and utilizing PROMs.^108,126,127 Finally, PRO-Performance Measures (PRO-PMs) are sometimes used to assess whether PROMs are appropriately contributing to performance improvement and accountability.¹²⁴

The Cons of PROs

Time and Software Constraints

PROs can disrupt busy clinical care environments and overextend clinical staff.¹²⁵ Online collection of PROs outside of clinical encounters can relieve PRO-related burden, but this requires finding and funding appropriate secure online networks to effectively collect PROs.¹²⁸ In 2015, only 60% of people seen for primary care visits could access or view their records online, and of those, only 57% used messaging for medical questions or concerns.¹²⁹ Ideally, online patient portal or mobile health apps could synchronize directly to electronic health records or virtual scribes to transfer patient communications into clinical documentation.¹³⁰ There has been limited success with this approach in European countries¹³¹ and with some chronic illness conditions in the United States.⁷⁴

Electronic health technologies, including mobile health (mHealth) solutions, have improved the self-monitoring and self-management capability of patients with MS via information sharing in patient networks, assistive technologies, smartphone applications, and wearable devices.^132,133 A recent study found that communication modes included secure online patient portal use (29%) and email use (21%), and among those who owned tablets or smartphones, 46% used mHealth apps.¹³⁴ Social media use has been associated with increased peer/social/emotional support and increased access to health information, as well as clinical monitoring and behavior change.^134,135 Individuals using mHealth apps are younger, have comorbidities, and have higher socioeconomic and education levels,^135,136 suggesting that inequities in mHealth access exist.

Burden on People with MS

Questionnaires can be time-consuming and cause mental distress if not appropriately facilitated.¹³⁷ Decreasing questionnaire length and providing the option for PROMs to be delivered and completed online or outside of the clinic context can reduce burden.¹³⁸ Additionally, while some people are consistent in sharing their PROs, others struggle with using computers, especially while experiencing severe symptoms, forget to complete PROMs, or simply do not have internet access due to financial or geographic constraints.¹³⁹ A group of disabled and elderly persons with MS reported barriers to internet use due to visual deficits, small website font sizes, and distracting color schemes.¹⁴⁰

Interpretability

Interpreting PROMs and displays of longitudinal PROM data can be a challenge for persons with MS and their clinicians. There is little standardization in how PROMs are scored and presented, and there is often confusion about thresholds for clinical significance and how PROM scores can be compared to other PROMs.^141,142 While guidelines exist for implementing PRO scores in clinical settings,^126,143 there are few that aid PROM interpretation. As a result, clinicians often seek research evidence for PROMs used in other similar patient populations as a benchmark,^142-144 or compare them to other patients seen in their clinical practice.

Longitudinal PRO data are usually displayed in simple line graphs.^145,146 Overall, line graphs have been found to have the highest ease of understanding by both patients and clinicians, but sometimes can be confusing.¹⁴⁷ For example, upward trending lines are usually viewed as improvement and downward trending lines as decline; however, upward trending scores on a PROM can indicate decline, such as increasing fatigue severity. Annotation of visual displays can help. Patients and clinicians find that employing thresholds and color coding is useful, and better than “stoplight” red-yellow-green shading schemes or red-circle formats to indicate data that warrant attention.¹⁴²

Error Risks

PROs are not free of risk for error, especially if they are used independently of other information sources, such as clinical interview, examination, and diagnostic testing, or if they are utilized too frequently, too infrequently, or are duplicated in practice. If a PRO instrument is employed too frequently, score changes may reflect learning effects rather than actual clinical status. Conversely, if used too infrequently, PRO information will not be timely enough to inform real-time clinical practice. Duplication of PRO assessments (eg, multiple measures of the same PRO for the same patient on the same day) or use of multiple PRO measures to assess the same aspect (eg, 2 measures used to assess fatigue) could introduce unnecessary complexity and confusion to interpretation of PRO results.

PRO measures also can be biased or modified by clinical status and/or perceptions of people with MS at the time of assessment. For example, cognitive impairment, whether at baseline state or due to a cognitive MS relapse event, could impact patients’ ability to understand and respond to PRO assessments, producing erroneous results. However, when used appropriately, PROs targeting cognitive dysfunction may be able to detect onset of cognitive events or help to measure recovery from them. Finally, PROs measure perceived (self-reported) status, which may not be an accurate depiction of actual status.

All of these potential pitfalls support the argument that PROs should be utilized to augment the clinical interview, examination, and diagnostic (objective) testing aspects of comprehensive MS care. In this way, PROs can be correlated with other information sources to deepen the shared understanding of health status between a person with MS and her clinician, increasing the potential to make better treatment decisions and care plans together in partnership.

Value and Cost

National groups such as the Patient-Centered Outcomes Research Institute (PCORI) are working with regulatory bodies, funding agencies, insurance providers, patient advocacy groups, researchers, providers, and specialty groups to investigate how PROMs can be implemented into value-based health care reforms, including value-based reimbursement.¹⁴⁸ However, practical PRO implementation requires considerable time and resources, and many methodological and operational questions must be addressed before widespread adoption and reimbursement for PROMs will be feasible.^148,149

 

 

Summary

PROs can generate valuable information about perceived health status, function, quality of life, and experience of care using self-reported sources. Validated PRO assessment tools include PROMs and PREMs. PROs are currently utilized in research settings (especially PROMs) but are also being used in clinical practice, quality improvement initiatives, and population health applications using LHS approaches. PROs have the advantages of empowering and informing persons with MS and clinicians to optimize patient-centered care, improve systems of care, and study population health outcomes. Barriers include PROM validity, reliability, comparability, specificity, interpretability, equity, time, and cost. Generic PROMs and PREMs, and some MS-specific PROMs, can be used for persons with MS. Unfortunately, no PREMs have been developed specifically for persons with MS, and this is an area for future research. With appropriate development and utilization in LHS applications, PROs can inform patient-centered clinical care, system-level improvement initiatives, and population health research, and have the potential to help facilitate coproduction of health care services.

Acknowledgments: The authors thank Ann Cabot, DO, of the MS Specialty Care Program at Concord Hospital and (especially) peer mentors from a peer outreach wellness program for people with MS (who have asked to remain anonymous) for interviews conducted with their permission to inform the case study described in this article. The case study used in this manuscript has been de-identified, with some aspects modified from actual, and the person in the case study is fictitiously named.

Corresponding author: Brant Oliver, PhD, MS, MPH, APRN-BC, Department of Community & Family Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756; brant.j.oliver@dartmouth.edu.

Financial disclosures: None.

From the Dartmouth Institute for Health Policy & Clinical Practice, Geisel School of Medicine, Hanover, NH (Ms. Manohar and Dr. Oliver), the Department of Community & Family Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH (Ms. Perkins, Ms. Laurion, and Dr. Oliver), and the Multiple Sclerosis Specialty Care Program, Concord Hospital, Concord, NH (Dr. Oliver).

Abstract

• Background: Patient-reported outcomes (PROs), including patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs), can be used to assess perceived health status, functioning, quality of life, and experience of care. Complex chronic illnesses such as multiple sclerosis (MS) affect multiple aspects of health, and PROs can be applied in assessment and decision-making in MS care as well as in research pertaining to MS.
• Objective: To provide a general review of PROs, with a specific focus on implications for MS care.
• Methods: Evidence synthesis of available literature on PROs in MS care.
• Results: PROs (including PROMs and PREMs) have historically been utilized in research and are now being applied in clinical, improvement, and population health settings using learning health system approaches in many disease populations, including MS. Many challenges complicate the use of PROs in MS care, including reliability, validity, and interpretability of PROMs, as well as feasibility barriers due to time and financial constraints in clinical settings.
• Conclusion: PROs have the potential to better inform clinical care, empower patient-centered care, inform health care improvement efforts, and create the conditions for coproduction of health care services.

Keywords: PRO; PROM; patient-reported outcome measure; patient-reported experience measure; quality of life; patient-centered care.

Multiple sclerosis (MS) is a disabling, complex, chronic, immune-mediated disorder of the central nervous system (CNS). MS causes inflammatory and degenerative damage in the CNS, which disrupts signaling pathways.¹ It is most commonly diagnosed in young adults and affects 2.3 million people worldwide.² People with MS experience very different disease courses and a wide range of neurological symptoms, including visual, somatic, mental health, sensory, motor, and cognitive problems.^1-3 Relapsing-remitting MS, the most common form, affects 85% of those with MS and is characterized by periods of relapse (exacerbation) and remission.¹ Other forms of MS (primary progressive and secondary progressive MS) are characterized by progressive deterioration and worsening symptom severity without exacerbations. Disease-modifying therapies (DMTs) can reduce the frequency of exacerbations and disability progression, but unfortunately there is no cure for MS. Treatment is focused on increasing quality of life, minimizing disability, and maximizing wellness.

Patient-reported outcomes (PROs) describe the perceived health status, function, and/or experience of a person as obtained by direct self-report. Patient-reported outcome measures (PROMs) are validated PROs that can be used to inform clinical care,⁴ and have demonstrated effectiveness in improving patient-provider communication and decision-making.^5-7 PROMs are currently used in some MS clinical trials to determine the impact of experimental interventions,^8-10 and are also being used to inform and improve clinical care in some settings. Especially for persons with MS, they can provide individualized perspectives about health experience and outcomes.¹¹ In more advanced applications, PROMs can be used to improve face-to-face collaborations between clinicians and patients and to inform patient-centered systems of care.^12-14 PROMs can also be used to inform systems-level improvement for entire patient populations.^15,16

In this article, we review current applications of PROs and PROMs in the care of persons with MS, as well as current limitations and barriers to their use.

CASE STUDY

Marion is a 26-year-old woman who first developed MS symptoms at age 16, including increased sensitivity to heat, blurry vision, and numbness in her legs (note: this case was developed based on interviews with persons with MS, obtained with appropriate consents, and does not represent a specific patient). At that time, her clinician attributed her symptoms to a car accident she had been in a few months before. Later, at age 20, she developed abdominal paresthesia, which her clinician attributed to an episode of shingles. At age 23, she developed double vision. She was evaluated by a neurologist and was diagnosed with MS. Marion started care with an MS specialists, who worked with her towards her goals of having a family, working, and exercising. In addition to appropriate medical care, she started martial arts training and biking for exercise and transitioned to a consulting position with flexible hours and the ability to work from home. Her daughter was born a year later.

At a recent visit to her neurologist, Marion reviews her health diary, in which she has been tracking her fatigue levels throughout the day and when she has to visit the bathroom. The PRO diary also helps her remember details that she might not otherwise be able to recall at the time of her clinic visit. They review the diary entrees together to develop a shared understanding of what Marion has been experiencing and identify trends in the PRO data. They discuss symptom management and use the PRO information from the diary to help guide adjustments to her physical therapy routine and medication regimen.

Part of Marion’s “PRO package” includes the Center for Epidemiologic Studies Depression Scale (CES-D), a validated depression screening and symptom severity questionnaire that she completes every 3 months. Although she denies being depressed, she has noticed that her CES-D scores in recent months have been consistently increasing. This prompts a discussion about mental health in MS and a referral to work on depression with the MS mental health specialist. Marion and the mental health specialist use CES-D measures at baseline and during treatment to set a remission target and to track progress during treatment. Marion finds this helpful because she says it is hard for her to “wrap my hands around depression… it’s not something that there is a blood test or a MRI for.” Marion is encouraged by being able to see her CES-D scores change as her depression severity decreases, and this helps motivate her to keep engaged in treatment.

PROs and PROMs: General Applications

PROs are measures obtained directly from an individual without a priori interpretation by a clinician.^9,17 PROs capture individual perspectives on symptoms, capability, disability, and health-related quality of life.⁹ With increasing emphasis on patient-centered care,¹⁸ individual perspectives and preferences elicited using PROMs may be able to inform better quality of care and patient-centered disease treatment and management.^19-21

PROMs are standardized, validated questionnaires used to assess PROs and can be generic or condition-specific. Generic PROMs can be used in any patient population. The SF-36²² is a set of quality of life measures that assess perceived ability to complete physical tasks and routine activities, general health status, fatigue, social functioning, pain, and emotional and mental health.²³ Condition-specific PROMs can be used for particular patient populations and are helpful in identifying changes in health status for a specific disease, disability, or surgery. For example, the PDQ-39 assesses 8 dimensions of daily living, functioning, and well-being for people with Parkinson’s disease.²⁴

PROMs have been used in some MS clinical trials and research studies to determine the effectiveness of experimental treatments from the viewpoint of study participants.^9,25,26 PROs can also be utilized in clinical care to facilitate communication of needs and track health outcomes,²⁷ and can inform improvement in outcomes for health systems and populations. They can also be used to assess experience of care,²⁸ encouraging a focus on high-quality outcomes through PRO-connected reimbursement mechanisms,²⁹ and provide aggregate data to evaluate clinical practice, population health outcomes, and the effectiveness of public policies.²⁷

Patient-reported experience measures (PREMs) assess patient satisfaction and experience of health care.^30,31 CollaboRATE³² is a PREM that assesses the degree of shared decision-making occurring between patients and clinicians during clinical care. PREMs are currently used for assessing self-efficacy and in shared decision-making and health care improvement applications. PREMs have yet to be developed specifically for persons with MS.

PROMs in MS Care

Generic PROMs have shown that persons with MS are disproportionately burdened by poor quality of life.^33-35 Other generic PROMs, like the SF-36,³⁶ the Sickness Impact Profile,³⁷ and versions of the Health Utilities Index,³⁸ can be used to gather information on dysfunction and to determine quality and duration of life modified by MS-related dysfunction and disability. MS-specific PROMs are used to assess MS impairments, including pain, fatigue, cognition, sexual dysfunction, and depression.^12,39-42 PROMs have also been used in MS clinical trials, including the Multiple Sclerosis Impact Scale-29 (MSIS-29),^43,44 the Leeds MS QoL (LMSQoL),^45,46 the Functional Assessment of MS (FAMS),⁴⁷ the Hamburg Quality of Life Questionnaire in MS (HAQUAMS),⁴⁸ the MS Quality of Life-54 (MSQoL-54),⁴⁹ the MS International QoL (MUSIQoL),⁵⁰ and the Patient-Reported Indices for MS Activity Limitations Scale (PRIMUS).⁵¹

Condition-specific PROMs are more sensitive to changes in health status and functioning for persons with MS compared to generic PROMs. They are also more reliable during MS remission and relapse periods.^44,52 For example, the SF-36 has floor and ceiling effects in MS populations—a high proportion of persons with MS are scored at the maximum or minimum levels of the scale, limiting discriminant capability.²² As a result, a “combined approach” using both generic and MS-specific measures is often recommended.⁵³ Some MS PROMs (eg, MSQoL-54) include generic questions found in the SF-36 as well as additional MS-specific questions or scales.

The variety of PROMs available (see Table for a selected listing) introduces a significant challenge to using them—limited generalizability and difficulty comparing PROs across MS studies. Efforts to establish common PROMs have been undertaken to address this problem.⁵⁴ The National Institute of Neurologicical Disorders and Stroke (NINDS) sponsored the development of a neurological quality of life battery, the Neuro-QOL.⁵⁵ Neuro-QOL measures the physical, mental, and social effects of neurological conditions in adults and children with neurological disorders and has the capability to facilitate comparisons across different neurological conditions. Additionally, the Patient-Reported Outcomes Measure Information System (PROMIS) has been developed to assess physical, mental, and social effects of chronic disease. PROMIS has a hybrid design that includes generic and MS-specific measures (such as PROMIS FatigueMS).⁵⁶ PROMIS can be used to assess persons with MS as well as to compare the MS population with other populations with chronic illness.

PROMs have varying levels of reliability and validity. The Evaluating the Measure of Patient-Reported Outcomes⁵⁷ study evaluated the development process of MS PROMs,⁴³ and found that the MSIS-29 and LMSQoL had the highest overall reliability among the most common MS PROMs. However, both scored poorly on validity due to lack of patient involvement during development. This questions the overall capability of existing MS PROMs to accurately and consistently assess PROs in persons with MS.

 

 

“Feed-Forward” PROMs

Oliver and colleagues¹⁶ have described “feed-forward” PROM applications in MS care in a community hospital setting using a learning health system approach. This MS clinic uses feed-forward PROs to inform clinical care—PRO data are gathered before the clinic visit and analyzed ahead of or during the clinic visit by the clinician. Patients are asked to arrive early and complete a questionnaire comprised of PROMs measuring disability, functioning, quality of life, cognitive ability, pain, fatigue, sleep quality, anxiety, and depression. Clinicians score the PROMs and input scores into the electronic health record before the clinical encounter. During the clinic visit, PROM data is visually displayed so that the clinician and patient can discuss results and use the data to better inform decision-making. The visual data display contains longitudinal information, displaying trends in health status across multiple domains, and includes specified thresholds for clinically active symptom levels (Figure).¹⁶ Longitudinal monitoring of PROM data allows for real-time assessment of goal-related progress throughout treatment. As illustrated previously by Marion’s case study, the use of real-time feed-forward PROM data can strengthen the partnership between patient and clinician as well as improve empowerment, engagement, self-monitoring, and adherence.

PRO Dashboards

Performance dashboards are increasingly used in health care to visually display clinical and PRO data for individual patients, systems, and populations over time. Dashboards display a parsimonious group of critically important measures to give clinicians and patients a longitudinal view of PRO status. They can inform decision-making in clinical care, operations, health care improvement efforts, and population health initiatives.⁵⁸ Effective dashboards allow for user customization with meaningful measures, knowledge discovery for analysis of health problems, accessibility of health information, clear visualization, alerts for unexpected data values, and system connectivity.^59,60 Appropriate development of PRO dashboards requires meaningful patient and clinician involvement via focus groups and key informant interviews, Delphi process approaches to prioritize and finalize selection of priority measures, iterative building of the interface with design input from key informants and stakeholders (co-design), and pilot testing to assess feasibility and acceptability of use.^61-63

Other Applications of PROs/PROMs in MS

Learning Health Systems

The National Quality Forum (NQF) and the Centers for Medicaid and Medicare Services have adopted PROs for use in quality measurement.^64-66 This includes a movement towards the use of LHS, defined as a health system in which information from patients and clinicians is systematically collected and synthesized with external evidence to inform clinical care, improvement, and research.^67-70 Often a LHS is undertaken as a collaborative effort between multiple health care centers to improve quality and outcomes of care.⁷⁰ The MS Continuous Quality Improvement Collaborative (MS-CQI), the first multi-center systems-level health care improvement research collaborative for MS,⁷¹ as well as IBD Qorus and the Cystic Fibrosis Care Center Network utilize LHS approaches.^72-77

IBD Qorus is a LHS developed by the Crohn’s and Colitis Foundation that uses performance dashboards to better inform clinical care for people with inflammatory bowel disease. It also employs system-level dashboards for performance benchmarking in quality improvement initiatives and aggregate-level dashboards to assess population health status.^78,79 MS-CQI uses a LHS approach to inform the improvement of MS care across multiple centers using a comprehensive dashboard, including PROMs, for benchmarking and to monitor system and population health status. MS-CQI collects PROMs using a secure online platform that can be accessed by persons with MS and their clinicians and also includes a journaling feature for collecting qualitative information and for reference and self-monitoring.⁷¹

MS Research

PROMs are used in clinical and epidemiological research to evaluate many aspects of MS, including the FAMS, the PDSS, the Fatigue Impact Scale (FIS), and others.^80-82 For example, the PROMIS FatigueMS and the Fatigue Performance Scale have been used to assess the impact of MS-related fatigue on social participation.⁸³ Generic and MS-specific PROMs have been used to assess pain levels for people with MS,^84-87 and multiple MS-specific PROMs, like PRIMUS and MSQoL-54,⁴³ as well as the SF-36³⁹ include pain assessment scales. PROMs have also been used to assess MS-related bladder, bowel, and sexual dysfunction. Urgency, frequency, and incontinence affect up to 75% of patients with MS,⁸⁸ and many PROMs, such as the LMSQoL, MUSIQoL, and the MSQoL-54, are able to evaluate bladder control and sexual functioning.^43,89

PROMs are employed in MS clinical trials to help assess the tolerability and effectiveness of DMTs.^90,91 PROs have been used as secondary endpoints to understand the global experience of a DMT from the patient perspective.^92-94 There are 15 FDA-approved DMTs for MS, and clinical trials for 6 of these have used PROMs as an effectiveness end point.^54,91,95,96 However, most DMT clinical trials are powered for MRI, relapse rate, or disease progression primary outcomes rather than PROMs, often resulting in underpowered PROM analyses.⁹⁷ In addition, many PROMs are not appropriate for use in DMT clinical trials.^98,99

In order to bridge the gap between clinical research and practice, some industry entities are championing “patient-focused drug development” approaches. The Accelerated Cure Project for MS has launched iConquerMS, which collects PROMs from persons with MS to further PRO research in MS and follows 4700 individuals with MS worldwide.¹⁰⁰ In 2018, the American College of Physicians announced a collaboration with an industry partner to share data to inform DMT clinical trials and develop and validate PROMs specifically designed for DMT clinical trials.¹⁰¹

Population Health

Registries following large cohorts of people with MS have the potential to develop knowledge about disease progression, treatment patterns, and outcomes.¹⁰² The Swedish EIMS study has identified associations between pre-disease body mass index and MS prognosis,¹⁰² alcohol and tobacco consumption affecting MS risk,^103,104 and exposure to shift work at a young age and increased MS risk.¹⁰⁵ The North American Research Committee on MS^83,106,107 and iConquerMS registries are “PROM-driven” and have been useful in identifying reductions in disease progression in people using DMTs.^107,108 The New York State MS Consortium has identified important demographic characteristics that influence MS progression.^109,110 PROs can also be used to determine risk of MS-related mortality¹¹¹ and decline in quality of life.^112,113 Limitations of these approaches include use of different PROMs, inconsistencies in data collection processes, and different follow-up intervals used across registries.¹⁰²

Patient-Centered Care

The Institute of Medicine defines patient-centeredness as “care that is respectful and responsive to individual patient preferences, needs, and values and ensures that patient values guide all clinical decisions.”¹¹⁴ PROs are useful for identifying a patient’s individual health concerns and preferences, something that is needed when treating a highly variable chronic health condition like MS. The use of PROs can help clinicicans visualize the lived experience of persons with MS and identify personal preferences,¹¹⁵ as well as improve self-monitoring, self-management, self-efficacy, adherence, wellness, and coping ability.¹¹⁶ At the system level, PROs can inform improvement initiatives and patient-centered care design efforts.^117-120

Selecting PROMs

Initiatives from groups like the COnsensus-based Standards for the Selection of health Measurement INstruments (COSMIN)¹²¹ and the International Society for Quality of Life Research (ISOQOL)¹⁰⁸ offer guidance on selecting PROs. The NINDS has promoted common data collection between clinical studies of the brain and nervous system.¹²² General guidance from these sources recommends first considering the outcome and target population, selecting PROMs to measure the outcome through a synthesis of the available evidence, assessing validity and reliability of selected PROMs, and using standard measures that can be compared across studies or populations.^108,121 Other factors include feasibility, acceptability, and burden of use for patients, clinicians, and systems, as well as literacy, cultural, and linguistic factors.¹²³

The NQF recommends that consideration be given to individual patient needs, insurance factors, clinical setting constraints, and available resources when selecting PROMs.¹²⁴ To maximize response rate, PROMs that are sensitive, reliable, valid, and developed in a comparative demographic of patients are advised.¹²⁵ ISOQOL has released a User’s Guide and several companion guides on implementing and utilizing PROMs.^108,126,127 Finally, PRO-Performance Measures (PRO-PMs) are sometimes used to assess whether PROMs are appropriately contributing to performance improvement and accountability.¹²⁴

The Cons of PROs

Time and Software Constraints

PROs can disrupt busy clinical care environments and overextend clinical staff.¹²⁵ Online collection of PROs outside of clinical encounters can relieve PRO-related burden, but this requires finding and funding appropriate secure online networks to effectively collect PROs.¹²⁸ In 2015, only 60% of people seen for primary care visits could access or view their records online, and of those, only 57% used messaging for medical questions or concerns.¹²⁹ Ideally, online patient portal or mobile health apps could synchronize directly to electronic health records or virtual scribes to transfer patient communications into clinical documentation.¹³⁰ There has been limited success with this approach in European countries¹³¹ and with some chronic illness conditions in the United States.⁷⁴

Electronic health technologies, including mobile health (mHealth) solutions, have improved the self-monitoring and self-management capability of patients with MS via information sharing in patient networks, assistive technologies, smartphone applications, and wearable devices.^132,133 A recent study found that communication modes included secure online patient portal use (29%) and email use (21%), and among those who owned tablets or smartphones, 46% used mHealth apps.¹³⁴ Social media use has been associated with increased peer/social/emotional support and increased access to health information, as well as clinical monitoring and behavior change.^134,135 Individuals using mHealth apps are younger, have comorbidities, and have higher socioeconomic and education levels,^135,136 suggesting that inequities in mHealth access exist.

Burden on People with MS

Questionnaires can be time-consuming and cause mental distress if not appropriately facilitated.¹³⁷ Decreasing questionnaire length and providing the option for PROMs to be delivered and completed online or outside of the clinic context can reduce burden.¹³⁸ Additionally, while some people are consistent in sharing their PROs, others struggle with using computers, especially while experiencing severe symptoms, forget to complete PROMs, or simply do not have internet access due to financial or geographic constraints.¹³⁹ A group of disabled and elderly persons with MS reported barriers to internet use due to visual deficits, small website font sizes, and distracting color schemes.¹⁴⁰

Interpretability

Interpreting PROMs and displays of longitudinal PROM data can be a challenge for persons with MS and their clinicians. There is little standardization in how PROMs are scored and presented, and there is often confusion about thresholds for clinical significance and how PROM scores can be compared to other PROMs.^141,142 While guidelines exist for implementing PRO scores in clinical settings,^126,143 there are few that aid PROM interpretation. As a result, clinicians often seek research evidence for PROMs used in other similar patient populations as a benchmark,^142-144 or compare them to other patients seen in their clinical practice.

Longitudinal PRO data are usually displayed in simple line graphs.^145,146 Overall, line graphs have been found to have the highest ease of understanding by both patients and clinicians, but sometimes can be confusing.¹⁴⁷ For example, upward trending lines are usually viewed as improvement and downward trending lines as decline; however, upward trending scores on a PROM can indicate decline, such as increasing fatigue severity. Annotation of visual displays can help. Patients and clinicians find that employing thresholds and color coding is useful, and better than “stoplight” red-yellow-green shading schemes or red-circle formats to indicate data that warrant attention.¹⁴²

Error Risks

PROs are not free of risk for error, especially if they are used independently of other information sources, such as clinical interview, examination, and diagnostic testing, or if they are utilized too frequently, too infrequently, or are duplicated in practice. If a PRO instrument is employed too frequently, score changes may reflect learning effects rather than actual clinical status. Conversely, if used too infrequently, PRO information will not be timely enough to inform real-time clinical practice. Duplication of PRO assessments (eg, multiple measures of the same PRO for the same patient on the same day) or use of multiple PRO measures to assess the same aspect (eg, 2 measures used to assess fatigue) could introduce unnecessary complexity and confusion to interpretation of PRO results.

PRO measures also can be biased or modified by clinical status and/or perceptions of people with MS at the time of assessment. For example, cognitive impairment, whether at baseline state or due to a cognitive MS relapse event, could impact patients’ ability to understand and respond to PRO assessments, producing erroneous results. However, when used appropriately, PROs targeting cognitive dysfunction may be able to detect onset of cognitive events or help to measure recovery from them. Finally, PROs measure perceived (self-reported) status, which may not be an accurate depiction of actual status.

All of these potential pitfalls support the argument that PROs should be utilized to augment the clinical interview, examination, and diagnostic (objective) testing aspects of comprehensive MS care. In this way, PROs can be correlated with other information sources to deepen the shared understanding of health status between a person with MS and her clinician, increasing the potential to make better treatment decisions and care plans together in partnership.

Value and Cost

National groups such as the Patient-Centered Outcomes Research Institute (PCORI) are working with regulatory bodies, funding agencies, insurance providers, patient advocacy groups, researchers, providers, and specialty groups to investigate how PROMs can be implemented into value-based health care reforms, including value-based reimbursement.¹⁴⁸ However, practical PRO implementation requires considerable time and resources, and many methodological and operational questions must be addressed before widespread adoption and reimbursement for PROMs will be feasible.^148,149

 

 

Summary

PROs can generate valuable information about perceived health status, function, quality of life, and experience of care using self-reported sources. Validated PRO assessment tools include PROMs and PREMs. PROs are currently utilized in research settings (especially PROMs) but are also being used in clinical practice, quality improvement initiatives, and population health applications using LHS approaches. PROs have the advantages of empowering and informing persons with MS and clinicians to optimize patient-centered care, improve systems of care, and study population health outcomes. Barriers include PROM validity, reliability, comparability, specificity, interpretability, equity, time, and cost. Generic PROMs and PREMs, and some MS-specific PROMs, can be used for persons with MS. Unfortunately, no PREMs have been developed specifically for persons with MS, and this is an area for future research. With appropriate development and utilization in LHS applications, PROs can inform patient-centered clinical care, system-level improvement initiatives, and population health research, and have the potential to help facilitate coproduction of health care services.

Acknowledgments: The authors thank Ann Cabot, DO, of the MS Specialty Care Program at Concord Hospital and (especially) peer mentors from a peer outreach wellness program for people with MS (who have asked to remain anonymous) for interviews conducted with their permission to inform the case study described in this article. The case study used in this manuscript has been de-identified, with some aspects modified from actual, and the person in the case study is fictitiously named.

Corresponding author: Brant Oliver, PhD, MS, MPH, APRN-BC, Department of Community & Family Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756; brant.j.oliver@dartmouth.edu.

Financial disclosures: None.

From the Dartmouth Institute for Health Policy & Clinical Practice, Geisel School of Medicine, Hanover, NH (Ms. Manohar and Dr. Oliver), the Department of Community & Family Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH (Ms. Perkins, Ms. Laurion, and Dr. Oliver), and the Multiple Sclerosis Specialty Care Program, Concord Hospital, Concord, NH (Dr. Oliver).

Abstract

• Background: Patient-reported outcomes (PROs), including patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs), can be used to assess perceived health status, functioning, quality of life, and experience of care. Complex chronic illnesses such as multiple sclerosis (MS) affect multiple aspects of health, and PROs can be applied in assessment and decision-making in MS care as well as in research pertaining to MS.
• Objective: To provide a general review of PROs, with a specific focus on implications for MS care.
• Methods: Evidence synthesis of available literature on PROs in MS care.
• Results: PROs (including PROMs and PREMs) have historically been utilized in research and are now being applied in clinical, improvement, and population health settings using learning health system approaches in many disease populations, including MS. Many challenges complicate the use of PROs in MS care, including reliability, validity, and interpretability of PROMs, as well as feasibility barriers due to time and financial constraints in clinical settings.
• Conclusion: PROs have the potential to better inform clinical care, empower patient-centered care, inform health care improvement efforts, and create the conditions for coproduction of health care services.

Keywords: PRO; PROM; patient-reported outcome measure; patient-reported experience measure; quality of life; patient-centered care.

Multiple sclerosis (MS) is a disabling, complex, chronic, immune-mediated disorder of the central nervous system (CNS). MS causes inflammatory and degenerative damage in the CNS, which disrupts signaling pathways.¹ It is most commonly diagnosed in young adults and affects 2.3 million people worldwide.² People with MS experience very different disease courses and a wide range of neurological symptoms, including visual, somatic, mental health, sensory, motor, and cognitive problems.^1-3 Relapsing-remitting MS, the most common form, affects 85% of those with MS and is characterized by periods of relapse (exacerbation) and remission.¹ Other forms of MS (primary progressive and secondary progressive MS) are characterized by progressive deterioration and worsening symptom severity without exacerbations. Disease-modifying therapies (DMTs) can reduce the frequency of exacerbations and disability progression, but unfortunately there is no cure for MS. Treatment is focused on increasing quality of life, minimizing disability, and maximizing wellness.

Patient-reported outcomes (PROs) describe the perceived health status, function, and/or experience of a person as obtained by direct self-report. Patient-reported outcome measures (PROMs) are validated PROs that can be used to inform clinical care,⁴ and have demonstrated effectiveness in improving patient-provider communication and decision-making.^5-7 PROMs are currently used in some MS clinical trials to determine the impact of experimental interventions,^8-10 and are also being used to inform and improve clinical care in some settings. Especially for persons with MS, they can provide individualized perspectives about health experience and outcomes.¹¹ In more advanced applications, PROMs can be used to improve face-to-face collaborations between clinicians and patients and to inform patient-centered systems of care.^12-14 PROMs can also be used to inform systems-level improvement for entire patient populations.^15,16

In this article, we review current applications of PROs and PROMs in the care of persons with MS, as well as current limitations and barriers to their use.

CASE STUDY

Marion is a 26-year-old woman who first developed MS symptoms at age 16, including increased sensitivity to heat, blurry vision, and numbness in her legs (note: this case was developed based on interviews with persons with MS, obtained with appropriate consents, and does not represent a specific patient). At that time, her clinician attributed her symptoms to a car accident she had been in a few months before. Later, at age 20, she developed abdominal paresthesia, which her clinician attributed to an episode of shingles. At age 23, she developed double vision. She was evaluated by a neurologist and was diagnosed with MS. Marion started care with an MS specialists, who worked with her towards her goals of having a family, working, and exercising. In addition to appropriate medical care, she started martial arts training and biking for exercise and transitioned to a consulting position with flexible hours and the ability to work from home. Her daughter was born a year later.

At a recent visit to her neurologist, Marion reviews her health diary, in which she has been tracking her fatigue levels throughout the day and when she has to visit the bathroom. The PRO diary also helps her remember details that she might not otherwise be able to recall at the time of her clinic visit. They review the diary entrees together to develop a shared understanding of what Marion has been experiencing and identify trends in the PRO data. They discuss symptom management and use the PRO information from the diary to help guide adjustments to her physical therapy routine and medication regimen.

Part of Marion’s “PRO package” includes the Center for Epidemiologic Studies Depression Scale (CES-D), a validated depression screening and symptom severity questionnaire that she completes every 3 months. Although she denies being depressed, she has noticed that her CES-D scores in recent months have been consistently increasing. This prompts a discussion about mental health in MS and a referral to work on depression with the MS mental health specialist. Marion and the mental health specialist use CES-D measures at baseline and during treatment to set a remission target and to track progress during treatment. Marion finds this helpful because she says it is hard for her to “wrap my hands around depression… it’s not something that there is a blood test or a MRI for.” Marion is encouraged by being able to see her CES-D scores change as her depression severity decreases, and this helps motivate her to keep engaged in treatment.

PROs and PROMs: General Applications

PROs are measures obtained directly from an individual without a priori interpretation by a clinician.^9,17 PROs capture individual perspectives on symptoms, capability, disability, and health-related quality of life.⁹ With increasing emphasis on patient-centered care,¹⁸ individual perspectives and preferences elicited using PROMs may be able to inform better quality of care and patient-centered disease treatment and management.^19-21

PROMs are standardized, validated questionnaires used to assess PROs and can be generic or condition-specific. Generic PROMs can be used in any patient population. The SF-36²² is a set of quality of life measures that assess perceived ability to complete physical tasks and routine activities, general health status, fatigue, social functioning, pain, and emotional and mental health.²³ Condition-specific PROMs can be used for particular patient populations and are helpful in identifying changes in health status for a specific disease, disability, or surgery. For example, the PDQ-39 assesses 8 dimensions of daily living, functioning, and well-being for people with Parkinson’s disease.²⁴

PROMs have been used in some MS clinical trials and research studies to determine the effectiveness of experimental treatments from the viewpoint of study participants.^9,25,26 PROs can also be utilized in clinical care to facilitate communication of needs and track health outcomes,²⁷ and can inform improvement in outcomes for health systems and populations. They can also be used to assess experience of care,²⁸ encouraging a focus on high-quality outcomes through PRO-connected reimbursement mechanisms,²⁹ and provide aggregate data to evaluate clinical practice, population health outcomes, and the effectiveness of public policies.²⁷

Patient-reported experience measures (PREMs) assess patient satisfaction and experience of health care.^30,31 CollaboRATE³² is a PREM that assesses the degree of shared decision-making occurring between patients and clinicians during clinical care. PREMs are currently used for assessing self-efficacy and in shared decision-making and health care improvement applications. PREMs have yet to be developed specifically for persons with MS.

PROMs in MS Care

Generic PROMs have shown that persons with MS are disproportionately burdened by poor quality of life.^33-35 Other generic PROMs, like the SF-36,³⁶ the Sickness Impact Profile,³⁷ and versions of the Health Utilities Index,³⁸ can be used to gather information on dysfunction and to determine quality and duration of life modified by MS-related dysfunction and disability. MS-specific PROMs are used to assess MS impairments, including pain, fatigue, cognition, sexual dysfunction, and depression.^12,39-42 PROMs have also been used in MS clinical trials, including the Multiple Sclerosis Impact Scale-29 (MSIS-29),^43,44 the Leeds MS QoL (LMSQoL),^45,46 the Functional Assessment of MS (FAMS),⁴⁷ the Hamburg Quality of Life Questionnaire in MS (HAQUAMS),⁴⁸ the MS Quality of Life-54 (MSQoL-54),⁴⁹ the MS International QoL (MUSIQoL),⁵⁰ and the Patient-Reported Indices for MS Activity Limitations Scale (PRIMUS).⁵¹

Condition-specific PROMs are more sensitive to changes in health status and functioning for persons with MS compared to generic PROMs. They are also more reliable during MS remission and relapse periods.^44,52 For example, the SF-36 has floor and ceiling effects in MS populations—a high proportion of persons with MS are scored at the maximum or minimum levels of the scale, limiting discriminant capability.²² As a result, a “combined approach” using both generic and MS-specific measures is often recommended.⁵³ Some MS PROMs (eg, MSQoL-54) include generic questions found in the SF-36 as well as additional MS-specific questions or scales.

The variety of PROMs available (see Table for a selected listing) introduces a significant challenge to using them—limited generalizability and difficulty comparing PROs across MS studies. Efforts to establish common PROMs have been undertaken to address this problem.⁵⁴ The National Institute of Neurologicical Disorders and Stroke (NINDS) sponsored the development of a neurological quality of life battery, the Neuro-QOL.⁵⁵ Neuro-QOL measures the physical, mental, and social effects of neurological conditions in adults and children with neurological disorders and has the capability to facilitate comparisons across different neurological conditions. Additionally, the Patient-Reported Outcomes Measure Information System (PROMIS) has been developed to assess physical, mental, and social effects of chronic disease. PROMIS has a hybrid design that includes generic and MS-specific measures (such as PROMIS FatigueMS).⁵⁶ PROMIS can be used to assess persons with MS as well as to compare the MS population with other populations with chronic illness.

PROMs have varying levels of reliability and validity. The Evaluating the Measure of Patient-Reported Outcomes⁵⁷ study evaluated the development process of MS PROMs,⁴³ and found that the MSIS-29 and LMSQoL had the highest overall reliability among the most common MS PROMs. However, both scored poorly on validity due to lack of patient involvement during development. This questions the overall capability of existing MS PROMs to accurately and consistently assess PROs in persons with MS.

 

 

“Feed-Forward” PROMs

Oliver and colleagues¹⁶ have described “feed-forward” PROM applications in MS care in a community hospital setting using a learning health system approach. This MS clinic uses feed-forward PROs to inform clinical care—PRO data are gathered before the clinic visit and analyzed ahead of or during the clinic visit by the clinician. Patients are asked to arrive early and complete a questionnaire comprised of PROMs measuring disability, functioning, quality of life, cognitive ability, pain, fatigue, sleep quality, anxiety, and depression. Clinicians score the PROMs and input scores into the electronic health record before the clinical encounter. During the clinic visit, PROM data is visually displayed so that the clinician and patient can discuss results and use the data to better inform decision-making. The visual data display contains longitudinal information, displaying trends in health status across multiple domains, and includes specified thresholds for clinically active symptom levels (Figure).¹⁶ Longitudinal monitoring of PROM data allows for real-time assessment of goal-related progress throughout treatment. As illustrated previously by Marion’s case study, the use of real-time feed-forward PROM data can strengthen the partnership between patient and clinician as well as improve empowerment, engagement, self-monitoring, and adherence.

PRO Dashboards

Performance dashboards are increasingly used in health care to visually display clinical and PRO data for individual patients, systems, and populations over time. Dashboards display a parsimonious group of critically important measures to give clinicians and patients a longitudinal view of PRO status. They can inform decision-making in clinical care, operations, health care improvement efforts, and population health initiatives.⁵⁸ Effective dashboards allow for user customization with meaningful measures, knowledge discovery for analysis of health problems, accessibility of health information, clear visualization, alerts for unexpected data values, and system connectivity.^59,60 Appropriate development of PRO dashboards requires meaningful patient and clinician involvement via focus groups and key informant interviews, Delphi process approaches to prioritize and finalize selection of priority measures, iterative building of the interface with design input from key informants and stakeholders (co-design), and pilot testing to assess feasibility and acceptability of use.^61-63

Other Applications of PROs/PROMs in MS

Learning Health Systems

The National Quality Forum (NQF) and the Centers for Medicaid and Medicare Services have adopted PROs for use in quality measurement.^64-66 This includes a movement towards the use of LHS, defined as a health system in which information from patients and clinicians is systematically collected and synthesized with external evidence to inform clinical care, improvement, and research.^67-70 Often a LHS is undertaken as a collaborative effort between multiple health care centers to improve quality and outcomes of care.⁷⁰ The MS Continuous Quality Improvement Collaborative (MS-CQI), the first multi-center systems-level health care improvement research collaborative for MS,⁷¹ as well as IBD Qorus and the Cystic Fibrosis Care Center Network utilize LHS approaches.^72-77

IBD Qorus is a LHS developed by the Crohn’s and Colitis Foundation that uses performance dashboards to better inform clinical care for people with inflammatory bowel disease. It also employs system-level dashboards for performance benchmarking in quality improvement initiatives and aggregate-level dashboards to assess population health status.^78,79 MS-CQI uses a LHS approach to inform the improvement of MS care across multiple centers using a comprehensive dashboard, including PROMs, for benchmarking and to monitor system and population health status. MS-CQI collects PROMs using a secure online platform that can be accessed by persons with MS and their clinicians and also includes a journaling feature for collecting qualitative information and for reference and self-monitoring.⁷¹

MS Research

PROMs are used in clinical and epidemiological research to evaluate many aspects of MS, including the FAMS, the PDSS, the Fatigue Impact Scale (FIS), and others.^80-82 For example, the PROMIS FatigueMS and the Fatigue Performance Scale have been used to assess the impact of MS-related fatigue on social participation.⁸³ Generic and MS-specific PROMs have been used to assess pain levels for people with MS,^84-87 and multiple MS-specific PROMs, like PRIMUS and MSQoL-54,⁴³ as well as the SF-36³⁹ include pain assessment scales. PROMs have also been used to assess MS-related bladder, bowel, and sexual dysfunction. Urgency, frequency, and incontinence affect up to 75% of patients with MS,⁸⁸ and many PROMs, such as the LMSQoL, MUSIQoL, and the MSQoL-54, are able to evaluate bladder control and sexual functioning.^43,89

PROMs are employed in MS clinical trials to help assess the tolerability and effectiveness of DMTs.^90,91 PROs have been used as secondary endpoints to understand the global experience of a DMT from the patient perspective.^92-94 There are 15 FDA-approved DMTs for MS, and clinical trials for 6 of these have used PROMs as an effectiveness end point.^54,91,95,96 However, most DMT clinical trials are powered for MRI, relapse rate, or disease progression primary outcomes rather than PROMs, often resulting in underpowered PROM analyses.⁹⁷ In addition, many PROMs are not appropriate for use in DMT clinical trials.^98,99

In order to bridge the gap between clinical research and practice, some industry entities are championing “patient-focused drug development” approaches. The Accelerated Cure Project for MS has launched iConquerMS, which collects PROMs from persons with MS to further PRO research in MS and follows 4700 individuals with MS worldwide.¹⁰⁰ In 2018, the American College of Physicians announced a collaboration with an industry partner to share data to inform DMT clinical trials and develop and validate PROMs specifically designed for DMT clinical trials.¹⁰¹

Population Health

Registries following large cohorts of people with MS have the potential to develop knowledge about disease progression, treatment patterns, and outcomes.¹⁰² The Swedish EIMS study has identified associations between pre-disease body mass index and MS prognosis,¹⁰² alcohol and tobacco consumption affecting MS risk,^103,104 and exposure to shift work at a young age and increased MS risk.¹⁰⁵ The North American Research Committee on MS^83,106,107 and iConquerMS registries are “PROM-driven” and have been useful in identifying reductions in disease progression in people using DMTs.^107,108 The New York State MS Consortium has identified important demographic characteristics that influence MS progression.^109,110 PROs can also be used to determine risk of MS-related mortality¹¹¹ and decline in quality of life.^112,113 Limitations of these approaches include use of different PROMs, inconsistencies in data collection processes, and different follow-up intervals used across registries.¹⁰²

Patient-Centered Care

The Institute of Medicine defines patient-centeredness as “care that is respectful and responsive to individual patient preferences, needs, and values and ensures that patient values guide all clinical decisions.”¹¹⁴ PROs are useful for identifying a patient’s individual health concerns and preferences, something that is needed when treating a highly variable chronic health condition like MS. The use of PROs can help clinicicans visualize the lived experience of persons with MS and identify personal preferences,¹¹⁵ as well as improve self-monitoring, self-management, self-efficacy, adherence, wellness, and coping ability.¹¹⁶ At the system level, PROs can inform improvement initiatives and patient-centered care design efforts.^117-120

Selecting PROMs

Initiatives from groups like the COnsensus-based Standards for the Selection of health Measurement INstruments (COSMIN)¹²¹ and the International Society for Quality of Life Research (ISOQOL)¹⁰⁸ offer guidance on selecting PROs. The NINDS has promoted common data collection between clinical studies of the brain and nervous system.¹²² General guidance from these sources recommends first considering the outcome and target population, selecting PROMs to measure the outcome through a synthesis of the available evidence, assessing validity and reliability of selected PROMs, and using standard measures that can be compared across studies or populations.^108,121 Other factors include feasibility, acceptability, and burden of use for patients, clinicians, and systems, as well as literacy, cultural, and linguistic factors.¹²³

The NQF recommends that consideration be given to individual patient needs, insurance factors, clinical setting constraints, and available resources when selecting PROMs.¹²⁴ To maximize response rate, PROMs that are sensitive, reliable, valid, and developed in a comparative demographic of patients are advised.¹²⁵ ISOQOL has released a User’s Guide and several companion guides on implementing and utilizing PROMs.^108,126,127 Finally, PRO-Performance Measures (PRO-PMs) are sometimes used to assess whether PROMs are appropriately contributing to performance improvement and accountability.¹²⁴

The Cons of PROs

Time and Software Constraints

PROs can disrupt busy clinical care environments and overextend clinical staff.¹²⁵ Online collection of PROs outside of clinical encounters can relieve PRO-related burden, but this requires finding and funding appropriate secure online networks to effectively collect PROs.¹²⁸ In 2015, only 60% of people seen for primary care visits could access or view their records online, and of those, only 57% used messaging for medical questions or concerns.¹²⁹ Ideally, online patient portal or mobile health apps could synchronize directly to electronic health records or virtual scribes to transfer patient communications into clinical documentation.¹³⁰ There has been limited success with this approach in European countries¹³¹ and with some chronic illness conditions in the United States.⁷⁴

Electronic health technologies, including mobile health (mHealth) solutions, have improved the self-monitoring and self-management capability of patients with MS via information sharing in patient networks, assistive technologies, smartphone applications, and wearable devices.^132,133 A recent study found that communication modes included secure online patient portal use (29%) and email use (21%), and among those who owned tablets or smartphones, 46% used mHealth apps.¹³⁴ Social media use has been associated with increased peer/social/emotional support and increased access to health information, as well as clinical monitoring and behavior change.^134,135 Individuals using mHealth apps are younger, have comorbidities, and have higher socioeconomic and education levels,^135,136 suggesting that inequities in mHealth access exist.

Burden on People with MS

Questionnaires can be time-consuming and cause mental distress if not appropriately facilitated.¹³⁷ Decreasing questionnaire length and providing the option for PROMs to be delivered and completed online or outside of the clinic context can reduce burden.¹³⁸ Additionally, while some people are consistent in sharing their PROs, others struggle with using computers, especially while experiencing severe symptoms, forget to complete PROMs, or simply do not have internet access due to financial or geographic constraints.¹³⁹ A group of disabled and elderly persons with MS reported barriers to internet use due to visual deficits, small website font sizes, and distracting color schemes.¹⁴⁰

Interpretability

Interpreting PROMs and displays of longitudinal PROM data can be a challenge for persons with MS and their clinicians. There is little standardization in how PROMs are scored and presented, and there is often confusion about thresholds for clinical significance and how PROM scores can be compared to other PROMs.^141,142 While guidelines exist for implementing PRO scores in clinical settings,^126,143 there are few that aid PROM interpretation. As a result, clinicians often seek research evidence for PROMs used in other similar patient populations as a benchmark,^142-144 or compare them to other patients seen in their clinical practice.

Longitudinal PRO data are usually displayed in simple line graphs.^145,146 Overall, line graphs have been found to have the highest ease of understanding by both patients and clinicians, but sometimes can be confusing.¹⁴⁷ For example, upward trending lines are usually viewed as improvement and downward trending lines as decline; however, upward trending scores on a PROM can indicate decline, such as increasing fatigue severity. Annotation of visual displays can help. Patients and clinicians find that employing thresholds and color coding is useful, and better than “stoplight” red-yellow-green shading schemes or red-circle formats to indicate data that warrant attention.¹⁴²

Error Risks

PROs are not free of risk for error, especially if they are used independently of other information sources, such as clinical interview, examination, and diagnostic testing, or if they are utilized too frequently, too infrequently, or are duplicated in practice. If a PRO instrument is employed too frequently, score changes may reflect learning effects rather than actual clinical status. Conversely, if used too infrequently, PRO information will not be timely enough to inform real-time clinical practice. Duplication of PRO assessments (eg, multiple measures of the same PRO for the same patient on the same day) or use of multiple PRO measures to assess the same aspect (eg, 2 measures used to assess fatigue) could introduce unnecessary complexity and confusion to interpretation of PRO results.

PRO measures also can be biased or modified by clinical status and/or perceptions of people with MS at the time of assessment. For example, cognitive impairment, whether at baseline state or due to a cognitive MS relapse event, could impact patients’ ability to understand and respond to PRO assessments, producing erroneous results. However, when used appropriately, PROs targeting cognitive dysfunction may be able to detect onset of cognitive events or help to measure recovery from them. Finally, PROs measure perceived (self-reported) status, which may not be an accurate depiction of actual status.

All of these potential pitfalls support the argument that PROs should be utilized to augment the clinical interview, examination, and diagnostic (objective) testing aspects of comprehensive MS care. In this way, PROs can be correlated with other information sources to deepen the shared understanding of health status between a person with MS and her clinician, increasing the potential to make better treatment decisions and care plans together in partnership.

Value and Cost

National groups such as the Patient-Centered Outcomes Research Institute (PCORI) are working with regulatory bodies, funding agencies, insurance providers, patient advocacy groups, researchers, providers, and specialty groups to investigate how PROMs can be implemented into value-based health care reforms, including value-based reimbursement.¹⁴⁸ However, practical PRO implementation requires considerable time and resources, and many methodological and operational questions must be addressed before widespread adoption and reimbursement for PROMs will be feasible.^148,149

 

 

Summary

PROs can generate valuable information about perceived health status, function, quality of life, and experience of care using self-reported sources. Validated PRO assessment tools include PROMs and PREMs. PROs are currently utilized in research settings (especially PROMs) but are also being used in clinical practice, quality improvement initiatives, and population health applications using LHS approaches. PROs have the advantages of empowering and informing persons with MS and clinicians to optimize patient-centered care, improve systems of care, and study population health outcomes. Barriers include PROM validity, reliability, comparability, specificity, interpretability, equity, time, and cost. Generic PROMs and PREMs, and some MS-specific PROMs, can be used for persons with MS. Unfortunately, no PREMs have been developed specifically for persons with MS, and this is an area for future research. With appropriate development and utilization in LHS applications, PROs can inform patient-centered clinical care, system-level improvement initiatives, and population health research, and have the potential to help facilitate coproduction of health care services.

Acknowledgments: The authors thank Ann Cabot, DO, of the MS Specialty Care Program at Concord Hospital and (especially) peer mentors from a peer outreach wellness program for people with MS (who have asked to remain anonymous) for interviews conducted with their permission to inform the case study described in this article. The case study used in this manuscript has been de-identified, with some aspects modified from actual, and the person in the case study is fictitiously named.

Corresponding author: Brant Oliver, PhD, MS, MPH, APRN-BC, Department of Community & Family Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756; brant.j.oliver@dartmouth.edu.

Financial disclosures: None.

From the University of Miami, Department of Pediatrics and Department of Medicine, Miami, FL.

Abstract

• Objective: Pediatric fungemia is associated with a low risk of fungal endocarditis and renal infections. The majority of current guidelines do not recommend routine abdominal imaging/echocardiograms in the evaluation of fungemia, but such imaging has been routinely ordered for patients on the pediatric gastroenterology service at our institution. Our goals were to assess the financial impact of this deviation from current clinical guidelines and redefine the standard work to reduce overutilization of abdominal ultrasounds and echocardiograms. Specifically, our goal was to reduce imaging by 50% by 18 months.
• Methods: Root cause analysis showed a lack of familiarity with current evidence. Using this data, countermeasures were implemented, including practitioner education of guidelines and creation of a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Balancing measures were missed episodes of fungal endocarditis and renal infection.
• Results: During the period January 1, 2016 to November 19, 2017, 18 of 21 episodes of fungemia in our pediatric institution occurred in patients admitted to the pediatric gastroenterology service. Abdominal imaging and echocardiograms were done 100% of the time, with no positive findings and an estimated cost of approximately $58,000. Post-intervention from November 20, 2017 to April 3, 2019, 7 of 13 episodes of fungemia occurred on this service. Frequency of abdominal imaging and echocardiograms decreased to 43% and 57%, respectively. No episodes of fungal endocarditis or renal infection were identified.
• Conclusion: Overutilization of abdominal imaging and echocardiograms in pediatric fungemia evaluation can be safely decreased.

Keywords: guidelines; cost; candidemia; endocarditis.

Practitioners may remain under the impression that routine abdominal ultrasounds (US) and echocardiograms (echo) are indicated in fungemia to evaluate for fungal endocarditis and renal infection, although these conditions are rare and limited to a subset of the population.^1-10 Risk factors include prematurity, immunosuppression, prior bacterial endocarditis, abnormal cardiac valves, and previous urogenital surgeries.¹¹

The 2016 Infectious Diseases Society of America (IDSA) guidelines do not recommend routine US or echo but rather provide scenarios in which Candida endocarditis should be suspected, and these include: persistently positive blood cultures, persistent fevers despite appropriate therapy, and clinical signs that may suggest endocarditis, such as a new heart murmur, heart failure, or embolic phenomena.¹¹ IDSA recommends abdominal imaging in neonates with persistently positive blood cultures to evaluate the urogenital system, in addition to the liver and spleen. They also recommend abdominal imaging in symptomatic ascending Candida pyelonephritis beyond the neonatal period and in chronic disseminated candidiasis; the latter is uncommon and seen almost exclusively in patients recovering from neutropenia with a hematologic malignancy.¹¹

We also reviewed guidelines on fungemia originating outside the United States. The 2010 Canadian clinical guidelines on invasive candidiasis do not explicitly recommend routine imaging, but rather state that various imaging studies, including US and echo among others, may be helpful.¹² The German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy published a joint recommendation against routine US and echo in uncomplicated candidemia in 2011.¹³

The European Society for Clinical Microbiology and Infectious Diseases is the only society that recommends routine echo. Their 2012 guidelines on candidiasis recommend transesophageal echo in adults¹⁴ and echocardiography in children,¹⁵ as well as abdominal imaging in the diagnosis of chronic disseminated candidiasis in adults with hematological malignancies/hematopoietic stem cell transplantation.¹⁶

The 2013 Brazilian guidelines explicitly recommend against routine abdominal imaging and echo because of the low frequency of visceral lesions in adults with candidemia and recommend reserving imaging for those with persistently positive blood cultures or with clinical signs/symptoms suggestive of endocarditis/abdominal infection or clinical deterioration.¹⁷ The 2014 Japanese guidelines recommend ruling out chronic disseminated candidiasis in these patients with symptoms during the neutrophil recovery phase, but do not mention routinely imaging other patients. They do not address the role of echocardiography.¹⁸

Although physicians in the United Sates typically follow IDSA guidelines, abdominal US and echo were ordered routinely for patients with fungemia on the pediatric gastroenterology service at our institution, leading to higher medical costs and waste of medical resources. Our goals were to assess the current standard work for fungemia evaluation on this service, assess the impact of its deviation from current clinical guidelines, and redefine the standard work by (1) presenting current evidence to practitioners taking care of patients on this service, (2) providing a clinical pathway that allowed for variations where appropriate, and (3) providing a plan for pediatric fungemia management. Our SMART (Specific, Measurable, Attainable, Relevant and Timely) goal was to reduce overutilization of abdominal US and echo in pediatric patients with fungemia on the pediatric gastroenterology service by 50%.

Methods

Study, Setting, and Participants

We executed this quality improvement project at a quaternary care pediatric hospital affiliated with a school of medicine. The project scope consisted of inpatient pediatric patients with fungemia on the pediatric gastroenterology service admitted to the wards or pediatric critical care unit at this institution, along with the practitioners caring for these patients. The project was part of an institutional quality improvement initiative program. The quality improvement team included quality improvement experts from the departments of medicine and pediatrics, a pediatric resident and student, and physicians from the divisions of pediatric infectious disease, pediatric critical care, and pediatric gastroenterology. This study qualified for Institutional Review Board (IRB) exemption based on the University’s IRB stipulations.

Current Condition

Root cause analysis was performed by creating a process map of the current standard work and a fishbone diagram (Figure 1). We incorporated feedback from voice of the customer in the root cause analysis. In this analysis, the voice of the customer came from the bedside floor nurses, ultrasound clerk and sonographer, echo technician, cardiology fellow, and microbiology medical technician. We got their feedback on our process map, its accuracy and ways to expand, their thoughts on the problem and why we have this problem, and any solutions they could offer to help improve the problem. Some of the key points obtained were: echos were not routinely done on the floors and were not considered urgent as they often did not change management; the sonographer and those from the cardiology department felt imaging was often overutilized because of misconceptions and lack of available hospital guidelines. Suggested solutions included provider education with reference to Duke’s criteria and establishing a clinical pathway approved by all concerned departments.

Prior to education, we surveyed current practices of practitioners on teams caring for these patients, which included physicians of all levels (attendings, fellows, residents) as well as nurse practitioners and medical students from the department of pediatrics and divisions of pediatric gastroenterology, pediatric infectious disease, and pediatric critical care medicine.

 

 

Countermeasures

Practitioner Education. In October 2017 practitioners were given a 20-minute presentation on the latest international guidelines on fungemia. Fifty-nine practitioners completed pre- and post-test surveys. Eight respondents were excluded due to incomplete surveys. We compared self-reported frequencies of ordering abdominal imaging and echo before the presentation with intention to order post education. Intention to change clinical practice after the presentation was also surveyed.

Clinical Pathway. Education alone may not result in sustainability, and thus we provided a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Inter-department buy-in was also necessary for success. It was important to get the input from the various teams (infectious disease, cardiology, gastroenterology, and critical care), which was done by incorporating members from those divisions in the project or getting their feedback through voice of the customer analysis.

We redefined standard work based on current evidence and created a clinical pathway during March 2018 that included variations when appropriate (Figure 2). We presented the clinical pathway to practitioners and distributed it via email. We also made it available to pediatric residents and fellows on their mobile institutional work resource application.

Electronic Order Set. We created an electronic order set for pediatric fungemia management and made it available in the electronic health record May 2018.

Measurement

Cases of fungemia were identified through the electronic health record pre-intervention (January 1, 2016 through November 19, 2017) and post-intervention (November 20, 2019 through April 3, 2019). An episode of fungemia was defined as an encounter with 1 or more positive blood culture(s) for Candida species or Cryptococcus species. We manually identified patients belonging to the pediatric gastroenterology service and reviewed these charts to determine the presenting complaint, organism isolated, transplant status, central lines status, risk factors, if abdominal imaging or echocardiography were done for the episode of fungemia, and their corresponding results. We calculated overall and per patient medical charges by using the average charges at our institution of US and echocardiography with a cardiology consult. These average charges were provided by patient financial services and the pediatric cardiology department, respectively. To address non-technical expenditures, we calculated the average time taken for transport to and from radiology and the echo suite for each identified patient. We identified missed fungal endocarditis and fungal balls as balancing measures.

 

 

Results

Survey

Among the 51 practitioners surveyed, 36% were performing routine echo and 22% self-reported performing routine abdominal imaging. After education, no respondents planned to routinely do echo or abdominal imaging. All but 1 respondent planned to change their practice for evaluation of fungemia patients based on the presentation (eFigure 1).

Baseline Data

Over the 23-month period from January 1, 2016 to November 19, 2017, there were 21 episodes of fungemia, 18 of which occurred in patients on the pediatric gastroenterology service (2 of the 18 were transplant recipients). For the 18 episodes on this service, abdominal imaging and echo were done 100% of the time, with 0 positive findings (eFigure 2).

Of those 18 episodes, the average age was 4.6 years, with two-thirds of the population being male. There were 3 patients with multiple episodes that accounted for 8 of the episodes (3, 3, and 2 episodes each). Fever was the most common presenting complaint. The most common organism was Candida parapsilosis (6 of the 18 episodes). All episodes but one involved a central line, and all central lines were removed when present except for one case. Of the risk factors, 3 episodes occurred in neutropenic patients, and for 1 episode the patient had a questionable history of fungal endocarditis (and was on fungal prophylaxis). There were no patients with recent cardiac/urogenital surgery or prior fungal balls. No episodes had clinical symptoms suggestive of fungal endocarditis or fungal balls.

Post-Intervention Data

Over the subsequent 17-month period (November 11, 2017 to April 3, 2019), there were 13 episodes of candidemia. There were no episodes of Cryptococcus fungemia. Seven episodes occurred in patients on the pediatric gastroenterology service (2 of the 7 occurred in transplant recipients). Abdominal imaging was done in 3 of these episodes (43%), and in 2 of these 3 episodes, imaging was done at an outside institution prior to arrival, with no positive results (eFigure 2).

Echocardiography was done 57% of the time (n = 4), with echo being done at an outside institution prior to arrival half of the time (n = 2), with no endocarditis identified. The cases of abdominal imaging and echo done at outside institutions prior to arrival were not impacted by the countermeasures. Excluding those 2 patients who had both abdominal imaging and echocardiography done prior to arrival, the overall rate of imaging (both abdominal imaging and echo) done after countermeasures were instituted was 30% (Figure 3).

Of those 7 episodes, the average age was 6.8 years (57% female). There were no patients with multiple episodes. The most common presenting complaint was fever. The most common organism was Candida albicans (3 of the 7 episodes). All episodes involved a central line, which was removed in all cases except for one. Of the risk factors, 2 episodes were in neutropenic patients, and 1 episode had a history of bacterial endocarditis (not related to fungemia). No episodes occurred in patients with prior fungal renal infection, urogenital malformations, or recent cardiac/urogenital surgery. No episodes had clinical symptoms suggestive of fungal endocarditis or renal infection. No episodes of fungal endocarditis or renal infection were identified.

On average, a patient at our institution undergoing abdominal US and echo with a cardiology consult results in medical waste of approximately $3200 per patient. This cost does not take into account other miscellaneous charges possibly incurred, such as the radiologist interpreting the findings and transportation. Baseline data calculations show that patients waste on average 55 minutes in physical transport, and this does not take into account wait times.

Discussion

Candidemia contributes to 10% of central-line associated blood stream infections (CLABSI).¹⁹ Increased usage of indwelling central catheters for administration of parenteral nutrition will inevitably result in practitioners encountering cases of candidemia when caring for this population. As seen from our results, the majority of episodes of candidemia at our institution occurred on the pediatric gastroenterology service, and thus redefining standard work on this service will be impactful.

Candida parapsilosis and Candida albicans were the most common causative agents before and after intervention, respectively, but overall the most common organism was Candida albicans, which is in keeping with that of CLABSI in the literature.¹⁹ Growth of Candida parapsilosis has been particularly linked to CLABSI.¹⁹ The third most common organism in our study was Candida glabrata, which is the second most common cause of candidemia in CLABSI.¹⁹

The cases of positive abdominal imaging in fungemia in the literature are limited to the neonatal population^1-4 and chronic disseminated candidiasis in patients with hematologic malignancies/neutropenia/immunosuppression.^5,6 In fungal endocarditis, the reported cases were generally in neonates,^1,3,7 critically ill patients,⁸ patients with hematologic malignancies/neutropenia/immunosuppression,^6,9 or those with a cardiac history.^9,10 This population differs from the patient population on the pediatric gastroenterology service. Patients on this service may not need US or echo. Performing abdominal US and echo in fungemia patients in whom such imaging is not indicated may result in medical waste of approximately $3200 per patient. There is also a waste of medical resources and time.

We found almost all practitioners are willing to change clinical practice once provided with current guidelines. Face-to-face oral presentations allowed for questions and interaction, making this form of information dissemination better than e-mails or handouts.

Though the numbers were small over the short study period, we were able to decrease overutilization of abdominal imaging and echo after implementing countermeasures. Frequency decreased from 100% to 43% and 57% for abdominal imaging and echo, respectively. Imaging that was done after the countermeasures were implemented was mainly attributed to imaging patients underwent prior to presenting to our institution. This reinforces the need for education at other institutions as well. Of the balancing measures assessed, there were no missed cases of fungal balls or fungal endocarditis. Additionally, of the total 34 episodes of fungemia assessed (21 before and 13 after), even among those with risk factors, there were no cases of fungal endocarditis or renal infection.

The findings from this quality improvement project underscore current recommendations that, despite common misconceptions, routine abdominal US and echo are not indicated in all cases of fungemia. Case-by-case assessment based on the clinical scenario remains key to management of fungemia to avoid unnecessary medical interventions.

Corresponding author: Donna Cheung, MBBS, 200 Hawkins Drive, BT 1120-G, Iowa City, IA 52242; donna.ann.cheung@gmail.com.

Financial support: None.

From the University of Miami, Department of Pediatrics and Department of Medicine, Miami, FL.

Abstract

• Objective: Pediatric fungemia is associated with a low risk of fungal endocarditis and renal infections. The majority of current guidelines do not recommend routine abdominal imaging/echocardiograms in the evaluation of fungemia, but such imaging has been routinely ordered for patients on the pediatric gastroenterology service at our institution. Our goals were to assess the financial impact of this deviation from current clinical guidelines and redefine the standard work to reduce overutilization of abdominal ultrasounds and echocardiograms. Specifically, our goal was to reduce imaging by 50% by 18 months.
• Methods: Root cause analysis showed a lack of familiarity with current evidence. Using this data, countermeasures were implemented, including practitioner education of guidelines and creation of a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Balancing measures were missed episodes of fungal endocarditis and renal infection.
• Results: During the period January 1, 2016 to November 19, 2017, 18 of 21 episodes of fungemia in our pediatric institution occurred in patients admitted to the pediatric gastroenterology service. Abdominal imaging and echocardiograms were done 100% of the time, with no positive findings and an estimated cost of approximately $58,000. Post-intervention from November 20, 2017 to April 3, 2019, 7 of 13 episodes of fungemia occurred on this service. Frequency of abdominal imaging and echocardiograms decreased to 43% and 57%, respectively. No episodes of fungal endocarditis or renal infection were identified.
• Conclusion: Overutilization of abdominal imaging and echocardiograms in pediatric fungemia evaluation can be safely decreased.

Keywords: guidelines; cost; candidemia; endocarditis.

Practitioners may remain under the impression that routine abdominal ultrasounds (US) and echocardiograms (echo) are indicated in fungemia to evaluate for fungal endocarditis and renal infection, although these conditions are rare and limited to a subset of the population.^1-10 Risk factors include prematurity, immunosuppression, prior bacterial endocarditis, abnormal cardiac valves, and previous urogenital surgeries.¹¹

The 2016 Infectious Diseases Society of America (IDSA) guidelines do not recommend routine US or echo but rather provide scenarios in which Candida endocarditis should be suspected, and these include: persistently positive blood cultures, persistent fevers despite appropriate therapy, and clinical signs that may suggest endocarditis, such as a new heart murmur, heart failure, or embolic phenomena.¹¹ IDSA recommends abdominal imaging in neonates with persistently positive blood cultures to evaluate the urogenital system, in addition to the liver and spleen. They also recommend abdominal imaging in symptomatic ascending Candida pyelonephritis beyond the neonatal period and in chronic disseminated candidiasis; the latter is uncommon and seen almost exclusively in patients recovering from neutropenia with a hematologic malignancy.¹¹

We also reviewed guidelines on fungemia originating outside the United States. The 2010 Canadian clinical guidelines on invasive candidiasis do not explicitly recommend routine imaging, but rather state that various imaging studies, including US and echo among others, may be helpful.¹² The German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy published a joint recommendation against routine US and echo in uncomplicated candidemia in 2011.¹³

The European Society for Clinical Microbiology and Infectious Diseases is the only society that recommends routine echo. Their 2012 guidelines on candidiasis recommend transesophageal echo in adults¹⁴ and echocardiography in children,¹⁵ as well as abdominal imaging in the diagnosis of chronic disseminated candidiasis in adults with hematological malignancies/hematopoietic stem cell transplantation.¹⁶

The 2013 Brazilian guidelines explicitly recommend against routine abdominal imaging and echo because of the low frequency of visceral lesions in adults with candidemia and recommend reserving imaging for those with persistently positive blood cultures or with clinical signs/symptoms suggestive of endocarditis/abdominal infection or clinical deterioration.¹⁷ The 2014 Japanese guidelines recommend ruling out chronic disseminated candidiasis in these patients with symptoms during the neutrophil recovery phase, but do not mention routinely imaging other patients. They do not address the role of echocardiography.¹⁸

Although physicians in the United Sates typically follow IDSA guidelines, abdominal US and echo were ordered routinely for patients with fungemia on the pediatric gastroenterology service at our institution, leading to higher medical costs and waste of medical resources. Our goals were to assess the current standard work for fungemia evaluation on this service, assess the impact of its deviation from current clinical guidelines, and redefine the standard work by (1) presenting current evidence to practitioners taking care of patients on this service, (2) providing a clinical pathway that allowed for variations where appropriate, and (3) providing a plan for pediatric fungemia management. Our SMART (Specific, Measurable, Attainable, Relevant and Timely) goal was to reduce overutilization of abdominal US and echo in pediatric patients with fungemia on the pediatric gastroenterology service by 50%.

Methods

Study, Setting, and Participants

We executed this quality improvement project at a quaternary care pediatric hospital affiliated with a school of medicine. The project scope consisted of inpatient pediatric patients with fungemia on the pediatric gastroenterology service admitted to the wards or pediatric critical care unit at this institution, along with the practitioners caring for these patients. The project was part of an institutional quality improvement initiative program. The quality improvement team included quality improvement experts from the departments of medicine and pediatrics, a pediatric resident and student, and physicians from the divisions of pediatric infectious disease, pediatric critical care, and pediatric gastroenterology. This study qualified for Institutional Review Board (IRB) exemption based on the University’s IRB stipulations.

Current Condition

Root cause analysis was performed by creating a process map of the current standard work and a fishbone diagram (Figure 1). We incorporated feedback from voice of the customer in the root cause analysis. In this analysis, the voice of the customer came from the bedside floor nurses, ultrasound clerk and sonographer, echo technician, cardiology fellow, and microbiology medical technician. We got their feedback on our process map, its accuracy and ways to expand, their thoughts on the problem and why we have this problem, and any solutions they could offer to help improve the problem. Some of the key points obtained were: echos were not routinely done on the floors and were not considered urgent as they often did not change management; the sonographer and those from the cardiology department felt imaging was often overutilized because of misconceptions and lack of available hospital guidelines. Suggested solutions included provider education with reference to Duke’s criteria and establishing a clinical pathway approved by all concerned departments.

Prior to education, we surveyed current practices of practitioners on teams caring for these patients, which included physicians of all levels (attendings, fellows, residents) as well as nurse practitioners and medical students from the department of pediatrics and divisions of pediatric gastroenterology, pediatric infectious disease, and pediatric critical care medicine.

 

 

Countermeasures

Practitioner Education. In October 2017 practitioners were given a 20-minute presentation on the latest international guidelines on fungemia. Fifty-nine practitioners completed pre- and post-test surveys. Eight respondents were excluded due to incomplete surveys. We compared self-reported frequencies of ordering abdominal imaging and echo before the presentation with intention to order post education. Intention to change clinical practice after the presentation was also surveyed.

Clinical Pathway. Education alone may not result in sustainability, and thus we provided a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Inter-department buy-in was also necessary for success. It was important to get the input from the various teams (infectious disease, cardiology, gastroenterology, and critical care), which was done by incorporating members from those divisions in the project or getting their feedback through voice of the customer analysis.

We redefined standard work based on current evidence and created a clinical pathway during March 2018 that included variations when appropriate (Figure 2). We presented the clinical pathway to practitioners and distributed it via email. We also made it available to pediatric residents and fellows on their mobile institutional work resource application.

Electronic Order Set. We created an electronic order set for pediatric fungemia management and made it available in the electronic health record May 2018.

Measurement

Cases of fungemia were identified through the electronic health record pre-intervention (January 1, 2016 through November 19, 2017) and post-intervention (November 20, 2019 through April 3, 2019). An episode of fungemia was defined as an encounter with 1 or more positive blood culture(s) for Candida species or Cryptococcus species. We manually identified patients belonging to the pediatric gastroenterology service and reviewed these charts to determine the presenting complaint, organism isolated, transplant status, central lines status, risk factors, if abdominal imaging or echocardiography were done for the episode of fungemia, and their corresponding results. We calculated overall and per patient medical charges by using the average charges at our institution of US and echocardiography with a cardiology consult. These average charges were provided by patient financial services and the pediatric cardiology department, respectively. To address non-technical expenditures, we calculated the average time taken for transport to and from radiology and the echo suite for each identified patient. We identified missed fungal endocarditis and fungal balls as balancing measures.

 

 

Results

Survey

Among the 51 practitioners surveyed, 36% were performing routine echo and 22% self-reported performing routine abdominal imaging. After education, no respondents planned to routinely do echo or abdominal imaging. All but 1 respondent planned to change their practice for evaluation of fungemia patients based on the presentation (eFigure 1).

Baseline Data

Over the 23-month period from January 1, 2016 to November 19, 2017, there were 21 episodes of fungemia, 18 of which occurred in patients on the pediatric gastroenterology service (2 of the 18 were transplant recipients). For the 18 episodes on this service, abdominal imaging and echo were done 100% of the time, with 0 positive findings (eFigure 2).

Of those 18 episodes, the average age was 4.6 years, with two-thirds of the population being male. There were 3 patients with multiple episodes that accounted for 8 of the episodes (3, 3, and 2 episodes each). Fever was the most common presenting complaint. The most common organism was Candida parapsilosis (6 of the 18 episodes). All episodes but one involved a central line, and all central lines were removed when present except for one case. Of the risk factors, 3 episodes occurred in neutropenic patients, and for 1 episode the patient had a questionable history of fungal endocarditis (and was on fungal prophylaxis). There were no patients with recent cardiac/urogenital surgery or prior fungal balls. No episodes had clinical symptoms suggestive of fungal endocarditis or fungal balls.

Post-Intervention Data

Over the subsequent 17-month period (November 11, 2017 to April 3, 2019), there were 13 episodes of candidemia. There were no episodes of Cryptococcus fungemia. Seven episodes occurred in patients on the pediatric gastroenterology service (2 of the 7 occurred in transplant recipients). Abdominal imaging was done in 3 of these episodes (43%), and in 2 of these 3 episodes, imaging was done at an outside institution prior to arrival, with no positive results (eFigure 2).

Echocardiography was done 57% of the time (n = 4), with echo being done at an outside institution prior to arrival half of the time (n = 2), with no endocarditis identified. The cases of abdominal imaging and echo done at outside institutions prior to arrival were not impacted by the countermeasures. Excluding those 2 patients who had both abdominal imaging and echocardiography done prior to arrival, the overall rate of imaging (both abdominal imaging and echo) done after countermeasures were instituted was 30% (Figure 3).

Of those 7 episodes, the average age was 6.8 years (57% female). There were no patients with multiple episodes. The most common presenting complaint was fever. The most common organism was Candida albicans (3 of the 7 episodes). All episodes involved a central line, which was removed in all cases except for one. Of the risk factors, 2 episodes were in neutropenic patients, and 1 episode had a history of bacterial endocarditis (not related to fungemia). No episodes occurred in patients with prior fungal renal infection, urogenital malformations, or recent cardiac/urogenital surgery. No episodes had clinical symptoms suggestive of fungal endocarditis or renal infection. No episodes of fungal endocarditis or renal infection were identified.

On average, a patient at our institution undergoing abdominal US and echo with a cardiology consult results in medical waste of approximately $3200 per patient. This cost does not take into account other miscellaneous charges possibly incurred, such as the radiologist interpreting the findings and transportation. Baseline data calculations show that patients waste on average 55 minutes in physical transport, and this does not take into account wait times.

Discussion

Candidemia contributes to 10% of central-line associated blood stream infections (CLABSI).¹⁹ Increased usage of indwelling central catheters for administration of parenteral nutrition will inevitably result in practitioners encountering cases of candidemia when caring for this population. As seen from our results, the majority of episodes of candidemia at our institution occurred on the pediatric gastroenterology service, and thus redefining standard work on this service will be impactful.

Candida parapsilosis and Candida albicans were the most common causative agents before and after intervention, respectively, but overall the most common organism was Candida albicans, which is in keeping with that of CLABSI in the literature.¹⁹ Growth of Candida parapsilosis has been particularly linked to CLABSI.¹⁹ The third most common organism in our study was Candida glabrata, which is the second most common cause of candidemia in CLABSI.¹⁹

The cases of positive abdominal imaging in fungemia in the literature are limited to the neonatal population^1-4 and chronic disseminated candidiasis in patients with hematologic malignancies/neutropenia/immunosuppression.^5,6 In fungal endocarditis, the reported cases were generally in neonates,^1,3,7 critically ill patients,⁸ patients with hematologic malignancies/neutropenia/immunosuppression,^6,9 or those with a cardiac history.^9,10 This population differs from the patient population on the pediatric gastroenterology service. Patients on this service may not need US or echo. Performing abdominal US and echo in fungemia patients in whom such imaging is not indicated may result in medical waste of approximately $3200 per patient. There is also a waste of medical resources and time.

We found almost all practitioners are willing to change clinical practice once provided with current guidelines. Face-to-face oral presentations allowed for questions and interaction, making this form of information dissemination better than e-mails or handouts.

Though the numbers were small over the short study period, we were able to decrease overutilization of abdominal imaging and echo after implementing countermeasures. Frequency decreased from 100% to 43% and 57% for abdominal imaging and echo, respectively. Imaging that was done after the countermeasures were implemented was mainly attributed to imaging patients underwent prior to presenting to our institution. This reinforces the need for education at other institutions as well. Of the balancing measures assessed, there were no missed cases of fungal balls or fungal endocarditis. Additionally, of the total 34 episodes of fungemia assessed (21 before and 13 after), even among those with risk factors, there were no cases of fungal endocarditis or renal infection.

The findings from this quality improvement project underscore current recommendations that, despite common misconceptions, routine abdominal US and echo are not indicated in all cases of fungemia. Case-by-case assessment based on the clinical scenario remains key to management of fungemia to avoid unnecessary medical interventions.

Corresponding author: Donna Cheung, MBBS, 200 Hawkins Drive, BT 1120-G, Iowa City, IA 52242; donna.ann.cheung@gmail.com.

Financial support: None.

From the University of Miami, Department of Pediatrics and Department of Medicine, Miami, FL.

Abstract

• Objective: Pediatric fungemia is associated with a low risk of fungal endocarditis and renal infections. The majority of current guidelines do not recommend routine abdominal imaging/echocardiograms in the evaluation of fungemia, but such imaging has been routinely ordered for patients on the pediatric gastroenterology service at our institution. Our goals were to assess the financial impact of this deviation from current clinical guidelines and redefine the standard work to reduce overutilization of abdominal ultrasounds and echocardiograms. Specifically, our goal was to reduce imaging by 50% by 18 months.
• Methods: Root cause analysis showed a lack of familiarity with current evidence. Using this data, countermeasures were implemented, including practitioner education of guidelines and creation of a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Balancing measures were missed episodes of fungal endocarditis and renal infection.
• Results: During the period January 1, 2016 to November 19, 2017, 18 of 21 episodes of fungemia in our pediatric institution occurred in patients admitted to the pediatric gastroenterology service. Abdominal imaging and echocardiograms were done 100% of the time, with no positive findings and an estimated cost of approximately $58,000. Post-intervention from November 20, 2017 to April 3, 2019, 7 of 13 episodes of fungemia occurred on this service. Frequency of abdominal imaging and echocardiograms decreased to 43% and 57%, respectively. No episodes of fungal endocarditis or renal infection were identified.
• Conclusion: Overutilization of abdominal imaging and echocardiograms in pediatric fungemia evaluation can be safely decreased.

Keywords: guidelines; cost; candidemia; endocarditis.

Practitioners may remain under the impression that routine abdominal ultrasounds (US) and echocardiograms (echo) are indicated in fungemia to evaluate for fungal endocarditis and renal infection, although these conditions are rare and limited to a subset of the population.^1-10 Risk factors include prematurity, immunosuppression, prior bacterial endocarditis, abnormal cardiac valves, and previous urogenital surgeries.¹¹

The 2016 Infectious Diseases Society of America (IDSA) guidelines do not recommend routine US or echo but rather provide scenarios in which Candida endocarditis should be suspected, and these include: persistently positive blood cultures, persistent fevers despite appropriate therapy, and clinical signs that may suggest endocarditis, such as a new heart murmur, heart failure, or embolic phenomena.¹¹ IDSA recommends abdominal imaging in neonates with persistently positive blood cultures to evaluate the urogenital system, in addition to the liver and spleen. They also recommend abdominal imaging in symptomatic ascending Candida pyelonephritis beyond the neonatal period and in chronic disseminated candidiasis; the latter is uncommon and seen almost exclusively in patients recovering from neutropenia with a hematologic malignancy.¹¹

We also reviewed guidelines on fungemia originating outside the United States. The 2010 Canadian clinical guidelines on invasive candidiasis do not explicitly recommend routine imaging, but rather state that various imaging studies, including US and echo among others, may be helpful.¹² The German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy published a joint recommendation against routine US and echo in uncomplicated candidemia in 2011.¹³

The European Society for Clinical Microbiology and Infectious Diseases is the only society that recommends routine echo. Their 2012 guidelines on candidiasis recommend transesophageal echo in adults¹⁴ and echocardiography in children,¹⁵ as well as abdominal imaging in the diagnosis of chronic disseminated candidiasis in adults with hematological malignancies/hematopoietic stem cell transplantation.¹⁶

The 2013 Brazilian guidelines explicitly recommend against routine abdominal imaging and echo because of the low frequency of visceral lesions in adults with candidemia and recommend reserving imaging for those with persistently positive blood cultures or with clinical signs/symptoms suggestive of endocarditis/abdominal infection or clinical deterioration.¹⁷ The 2014 Japanese guidelines recommend ruling out chronic disseminated candidiasis in these patients with symptoms during the neutrophil recovery phase, but do not mention routinely imaging other patients. They do not address the role of echocardiography.¹⁸

Although physicians in the United Sates typically follow IDSA guidelines, abdominal US and echo were ordered routinely for patients with fungemia on the pediatric gastroenterology service at our institution, leading to higher medical costs and waste of medical resources. Our goals were to assess the current standard work for fungemia evaluation on this service, assess the impact of its deviation from current clinical guidelines, and redefine the standard work by (1) presenting current evidence to practitioners taking care of patients on this service, (2) providing a clinical pathway that allowed for variations where appropriate, and (3) providing a plan for pediatric fungemia management. Our SMART (Specific, Measurable, Attainable, Relevant and Timely) goal was to reduce overutilization of abdominal US and echo in pediatric patients with fungemia on the pediatric gastroenterology service by 50%.

Methods

Study, Setting, and Participants

We executed this quality improvement project at a quaternary care pediatric hospital affiliated with a school of medicine. The project scope consisted of inpatient pediatric patients with fungemia on the pediatric gastroenterology service admitted to the wards or pediatric critical care unit at this institution, along with the practitioners caring for these patients. The project was part of an institutional quality improvement initiative program. The quality improvement team included quality improvement experts from the departments of medicine and pediatrics, a pediatric resident and student, and physicians from the divisions of pediatric infectious disease, pediatric critical care, and pediatric gastroenterology. This study qualified for Institutional Review Board (IRB) exemption based on the University’s IRB stipulations.

Current Condition

Root cause analysis was performed by creating a process map of the current standard work and a fishbone diagram (Figure 1). We incorporated feedback from voice of the customer in the root cause analysis. In this analysis, the voice of the customer came from the bedside floor nurses, ultrasound clerk and sonographer, echo technician, cardiology fellow, and microbiology medical technician. We got their feedback on our process map, its accuracy and ways to expand, their thoughts on the problem and why we have this problem, and any solutions they could offer to help improve the problem. Some of the key points obtained were: echos were not routinely done on the floors and were not considered urgent as they often did not change management; the sonographer and those from the cardiology department felt imaging was often overutilized because of misconceptions and lack of available hospital guidelines. Suggested solutions included provider education with reference to Duke’s criteria and establishing a clinical pathway approved by all concerned departments.

Prior to education, we surveyed current practices of practitioners on teams caring for these patients, which included physicians of all levels (attendings, fellows, residents) as well as nurse practitioners and medical students from the department of pediatrics and divisions of pediatric gastroenterology, pediatric infectious disease, and pediatric critical care medicine.

 

 

Countermeasures

Practitioner Education. In October 2017 practitioners were given a 20-minute presentation on the latest international guidelines on fungemia. Fifty-nine practitioners completed pre- and post-test surveys. Eight respondents were excluded due to incomplete surveys. We compared self-reported frequencies of ordering abdominal imaging and echo before the presentation with intention to order post education. Intention to change clinical practice after the presentation was also surveyed.

Clinical Pathway. Education alone may not result in sustainability, and thus we provided a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Inter-department buy-in was also necessary for success. It was important to get the input from the various teams (infectious disease, cardiology, gastroenterology, and critical care), which was done by incorporating members from those divisions in the project or getting their feedback through voice of the customer analysis.

We redefined standard work based on current evidence and created a clinical pathway during March 2018 that included variations when appropriate (Figure 2). We presented the clinical pathway to practitioners and distributed it via email. We also made it available to pediatric residents and fellows on their mobile institutional work resource application.

Electronic Order Set. We created an electronic order set for pediatric fungemia management and made it available in the electronic health record May 2018.

Measurement

Cases of fungemia were identified through the electronic health record pre-intervention (January 1, 2016 through November 19, 2017) and post-intervention (November 20, 2019 through April 3, 2019). An episode of fungemia was defined as an encounter with 1 or more positive blood culture(s) for Candida species or Cryptococcus species. We manually identified patients belonging to the pediatric gastroenterology service and reviewed these charts to determine the presenting complaint, organism isolated, transplant status, central lines status, risk factors, if abdominal imaging or echocardiography were done for the episode of fungemia, and their corresponding results. We calculated overall and per patient medical charges by using the average charges at our institution of US and echocardiography with a cardiology consult. These average charges were provided by patient financial services and the pediatric cardiology department, respectively. To address non-technical expenditures, we calculated the average time taken for transport to and from radiology and the echo suite for each identified patient. We identified missed fungal endocarditis and fungal balls as balancing measures.

 

 

Results

Survey

Among the 51 practitioners surveyed, 36% were performing routine echo and 22% self-reported performing routine abdominal imaging. After education, no respondents planned to routinely do echo or abdominal imaging. All but 1 respondent planned to change their practice for evaluation of fungemia patients based on the presentation (eFigure 1).

Baseline Data

Over the 23-month period from January 1, 2016 to November 19, 2017, there were 21 episodes of fungemia, 18 of which occurred in patients on the pediatric gastroenterology service (2 of the 18 were transplant recipients). For the 18 episodes on this service, abdominal imaging and echo were done 100% of the time, with 0 positive findings (eFigure 2).

Of those 18 episodes, the average age was 4.6 years, with two-thirds of the population being male. There were 3 patients with multiple episodes that accounted for 8 of the episodes (3, 3, and 2 episodes each). Fever was the most common presenting complaint. The most common organism was Candida parapsilosis (6 of the 18 episodes). All episodes but one involved a central line, and all central lines were removed when present except for one case. Of the risk factors, 3 episodes occurred in neutropenic patients, and for 1 episode the patient had a questionable history of fungal endocarditis (and was on fungal prophylaxis). There were no patients with recent cardiac/urogenital surgery or prior fungal balls. No episodes had clinical symptoms suggestive of fungal endocarditis or fungal balls.

Post-Intervention Data

Over the subsequent 17-month period (November 11, 2017 to April 3, 2019), there were 13 episodes of candidemia. There were no episodes of Cryptococcus fungemia. Seven episodes occurred in patients on the pediatric gastroenterology service (2 of the 7 occurred in transplant recipients). Abdominal imaging was done in 3 of these episodes (43%), and in 2 of these 3 episodes, imaging was done at an outside institution prior to arrival, with no positive results (eFigure 2).

Echocardiography was done 57% of the time (n = 4), with echo being done at an outside institution prior to arrival half of the time (n = 2), with no endocarditis identified. The cases of abdominal imaging and echo done at outside institutions prior to arrival were not impacted by the countermeasures. Excluding those 2 patients who had both abdominal imaging and echocardiography done prior to arrival, the overall rate of imaging (both abdominal imaging and echo) done after countermeasures were instituted was 30% (Figure 3).

Of those 7 episodes, the average age was 6.8 years (57% female). There were no patients with multiple episodes. The most common presenting complaint was fever. The most common organism was Candida albicans (3 of the 7 episodes). All episodes involved a central line, which was removed in all cases except for one. Of the risk factors, 2 episodes were in neutropenic patients, and 1 episode had a history of bacterial endocarditis (not related to fungemia). No episodes occurred in patients with prior fungal renal infection, urogenital malformations, or recent cardiac/urogenital surgery. No episodes had clinical symptoms suggestive of fungal endocarditis or renal infection. No episodes of fungal endocarditis or renal infection were identified.

On average, a patient at our institution undergoing abdominal US and echo with a cardiology consult results in medical waste of approximately $3200 per patient. This cost does not take into account other miscellaneous charges possibly incurred, such as the radiologist interpreting the findings and transportation. Baseline data calculations show that patients waste on average 55 minutes in physical transport, and this does not take into account wait times.

Discussion

Candidemia contributes to 10% of central-line associated blood stream infections (CLABSI).¹⁹ Increased usage of indwelling central catheters for administration of parenteral nutrition will inevitably result in practitioners encountering cases of candidemia when caring for this population. As seen from our results, the majority of episodes of candidemia at our institution occurred on the pediatric gastroenterology service, and thus redefining standard work on this service will be impactful.

Candida parapsilosis and Candida albicans were the most common causative agents before and after intervention, respectively, but overall the most common organism was Candida albicans, which is in keeping with that of CLABSI in the literature.¹⁹ Growth of Candida parapsilosis has been particularly linked to CLABSI.¹⁹ The third most common organism in our study was Candida glabrata, which is the second most common cause of candidemia in CLABSI.¹⁹

The cases of positive abdominal imaging in fungemia in the literature are limited to the neonatal population^1-4 and chronic disseminated candidiasis in patients with hematologic malignancies/neutropenia/immunosuppression.^5,6 In fungal endocarditis, the reported cases were generally in neonates,^1,3,7 critically ill patients,⁸ patients with hematologic malignancies/neutropenia/immunosuppression,^6,9 or those with a cardiac history.^9,10 This population differs from the patient population on the pediatric gastroenterology service. Patients on this service may not need US or echo. Performing abdominal US and echo in fungemia patients in whom such imaging is not indicated may result in medical waste of approximately $3200 per patient. There is also a waste of medical resources and time.

We found almost all practitioners are willing to change clinical practice once provided with current guidelines. Face-to-face oral presentations allowed for questions and interaction, making this form of information dissemination better than e-mails or handouts.

Though the numbers were small over the short study period, we were able to decrease overutilization of abdominal imaging and echo after implementing countermeasures. Frequency decreased from 100% to 43% and 57% for abdominal imaging and echo, respectively. Imaging that was done after the countermeasures were implemented was mainly attributed to imaging patients underwent prior to presenting to our institution. This reinforces the need for education at other institutions as well. Of the balancing measures assessed, there were no missed cases of fungal balls or fungal endocarditis. Additionally, of the total 34 episodes of fungemia assessed (21 before and 13 after), even among those with risk factors, there were no cases of fungal endocarditis or renal infection.

The findings from this quality improvement project underscore current recommendations that, despite common misconceptions, routine abdominal US and echo are not indicated in all cases of fungemia. Case-by-case assessment based on the clinical scenario remains key to management of fungemia to avoid unnecessary medical interventions.

Corresponding author: Donna Cheung, MBBS, 200 Hawkins Drive, BT 1120-G, Iowa City, IA 52242; donna.ann.cheung@gmail.com.

Financial support: None.