LOS ANGELES – A peanut allergy prevention strategy based upon regular consumption of peanut-containing foods from infancy to age 5 continued to provide protection even after peanut intake was halted for a full year from age 5 to 6, according to new results from an extension of the landmark LEAP trial, known as LEAP-On, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The impetus for LEAP-On was the investigators’ concern that a period of peanut avoidance might cause loss of the protective state. But that didn’t occur.

“I think there is no doubt that we have prevented peanut allergy so far in these high-risk children. Next, the LEAP-Ad Lib study will tell us whether we’ve prevented it by age 10,” said Dr. Gideon Lack of King’s College London, who headed LEAP-On.

Bruce Jancin/Frontline Medical News

A second major randomized trial known as EAT (Enquiring About Tolerance) presented at the meeting provided further support for early dietary introduction of allergenic foods. EAT differed from LEAP (Learning Early About Peanut Allergy) and LEAP-On in that it ambitiously randomized infants to early introduction or avoidance of not one but six allergenic foods: peanut, cooked egg, cow’s milk, fish, sesame, and wheat. Also, while LEAP and LEAP-On involved roughly 600 infants known to be at very high risk for allergy, EAT was conducted in a general population of 1,303 infants who weren’t at increased risk, all of whom were exclusively breast-fed until the intervention beginning at age 3 months.

The presentation of the LEAP-On and EAT results at the AAAAI annual meeting was a major event marked by the National Institute of Allergy and Infectious Diseases by same-day release of new NIAID-sponsored draft recommendations for the diagnosis and management of food allergies.

In a press conference held at the AAAAI annual meeting to announce the start of a 45-day public comment period for the draft update of the 2010 guidelines, Dr. Daniel Rotrosen, director of NIAID’s division of allergy, immunology and transplantation, said the new guidelines were developed largely in response to the compelling LEAP findings. That trial demonstrated that sustained consumption of peanut starting in infancy resulted in an 81% lower rate of peanut allergy at age 5 years compared to a strategy of peanut avoidance (N Engl J Med. 2015;372:803-13).

Bruce Jancin/Frontline Medical News

The draft guidelines, now available on the NIAID website, represent a sharp departure from the former recommendation that physicians encourage exclusive breastfeeding for the first 6 months of life followed by cautious introduction of other foods. Whereas the former orthodoxy was that delayed introduction of allergenic foods protects against development of food allergy, the new evidence-based concept supported by the LEAP and EAT findings is that just the opposite is true: that is, introduction of such foods during the period of immunologic plasticity in infancy induces tolerance.

Thus, the draft guidelines recommend that infants at high risk for peanut allergy because they have severe eczema and/or egg allergy should have introduction of peanut-containing food at 4-6 months of age to reduce their risk of peanut allergy, preceded by evaluation using peanut-specific IgE or skin prick testing to make sure it’s safe. That age window coincides with well-child visits and vaccination schedules, Dr. Rotrosen noted.

These guidelines represent the consensus of 26 organizations that participated in their development. Among them are the American Academy of Pediatrics, the American Academy of Family Physicians, the American Academy of Dermatology, the American College of Gastroenterology, and AAAAI.

“I expect the new guidelines, when finalized, to be endorsed by the leadership of all the participating organizations,” Dr. Rotrosen said.

The new paradigm will require cultural change, said Dr. James R. Baker Jr., CEO and chief medical officer of Food Allergy Research and Education, a nonprofit organization that provided partial funding for LEAP and LEAP-On.

Bruce Jancin/Frontline Medical News

“I think for a long time we’ve vilified these foods. There’s nothing inherently wrong with their intake, and that’s a message we need to get across to parents and physicians so they can start thinking differently,” he said.

“The good news about these studies is that they show there’s no reason not to do this,” Dr. Baker added. “There’s no harm that comes from the early introduction.”

Dr. Lack, who led the EAT trial, noted that the study didn’t meet it’s primary endpoint of a significantly lower prevalence of food allergy to any of the six intervention foods at age 3 years in the intention-to-treat analysis. But adherence to the demanding EAT early-introduction protocol was a problem. Indeed, only 43% of participants adhered to the study protocol. In a per-protocol analysis restricted to the adherent group, however, early introduction was associated with a highly significant 67% reduction in the relative risk of food allergy at 3 years of age compared to controls. And for the two most prevalent food allergies – to peanut and egg – the relative risk reductions in the early-introduction group were 100% and 75%, respectively.

 

The EAT results suggest that an effective preventive dose of peanut in infants at least 3 months of age is roughly 2 g of peanut protein per week, equivalent to just under 2 tsp of peanut butter, according to Dr. Lack.

Simultaneously with presentation of the LEAP-On and EAT trials in Los Angeles, the studies were published online at NEJM.org (doi: 10.1056/NEJMoa1514210 for LEAP-ON and 10.1056/NEJMoa1514209 for EAT).

LEAP-On was supported primarily by NIAID. EAT was funded mainly by the UK Foods Standards Agency and the Medical Research Council. Dr. Lack reported receiving grants from those agencies as well as Food Allergy Research and Education.

LOS ANGELES – A peanut allergy prevention strategy based upon regular consumption of peanut-containing foods from infancy to age 5 continued to provide protection even after peanut intake was halted for a full year from age 5 to 6, according to new results from an extension of the landmark LEAP trial, known as LEAP-On, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The impetus for LEAP-On was the investigators’ concern that a period of peanut avoidance might cause loss of the protective state. But that didn’t occur.

“I think there is no doubt that we have prevented peanut allergy so far in these high-risk children. Next, the LEAP-Ad Lib study will tell us whether we’ve prevented it by age 10,” said Dr. Gideon Lack of King’s College London, who headed LEAP-On.

Bruce Jancin/Frontline Medical News

A second major randomized trial known as EAT (Enquiring About Tolerance) presented at the meeting provided further support for early dietary introduction of allergenic foods. EAT differed from LEAP (Learning Early About Peanut Allergy) and LEAP-On in that it ambitiously randomized infants to early introduction or avoidance of not one but six allergenic foods: peanut, cooked egg, cow’s milk, fish, sesame, and wheat. Also, while LEAP and LEAP-On involved roughly 600 infants known to be at very high risk for allergy, EAT was conducted in a general population of 1,303 infants who weren’t at increased risk, all of whom were exclusively breast-fed until the intervention beginning at age 3 months.

The presentation of the LEAP-On and EAT results at the AAAAI annual meeting was a major event marked by the National Institute of Allergy and Infectious Diseases by same-day release of new NIAID-sponsored draft recommendations for the diagnosis and management of food allergies.

In a press conference held at the AAAAI annual meeting to announce the start of a 45-day public comment period for the draft update of the 2010 guidelines, Dr. Daniel Rotrosen, director of NIAID’s division of allergy, immunology and transplantation, said the new guidelines were developed largely in response to the compelling LEAP findings. That trial demonstrated that sustained consumption of peanut starting in infancy resulted in an 81% lower rate of peanut allergy at age 5 years compared to a strategy of peanut avoidance (N Engl J Med. 2015;372:803-13).

Bruce Jancin/Frontline Medical News

The draft guidelines, now available on the NIAID website, represent a sharp departure from the former recommendation that physicians encourage exclusive breastfeeding for the first 6 months of life followed by cautious introduction of other foods. Whereas the former orthodoxy was that delayed introduction of allergenic foods protects against development of food allergy, the new evidence-based concept supported by the LEAP and EAT findings is that just the opposite is true: that is, introduction of such foods during the period of immunologic plasticity in infancy induces tolerance.

Thus, the draft guidelines recommend that infants at high risk for peanut allergy because they have severe eczema and/or egg allergy should have introduction of peanut-containing food at 4-6 months of age to reduce their risk of peanut allergy, preceded by evaluation using peanut-specific IgE or skin prick testing to make sure it’s safe. That age window coincides with well-child visits and vaccination schedules, Dr. Rotrosen noted.

These guidelines represent the consensus of 26 organizations that participated in their development. Among them are the American Academy of Pediatrics, the American Academy of Family Physicians, the American Academy of Dermatology, the American College of Gastroenterology, and AAAAI.

“I expect the new guidelines, when finalized, to be endorsed by the leadership of all the participating organizations,” Dr. Rotrosen said.

The new paradigm will require cultural change, said Dr. James R. Baker Jr., CEO and chief medical officer of Food Allergy Research and Education, a nonprofit organization that provided partial funding for LEAP and LEAP-On.

Bruce Jancin/Frontline Medical News

“I think for a long time we’ve vilified these foods. There’s nothing inherently wrong with their intake, and that’s a message we need to get across to parents and physicians so they can start thinking differently,” he said.

“The good news about these studies is that they show there’s no reason not to do this,” Dr. Baker added. “There’s no harm that comes from the early introduction.”

Dr. Lack, who led the EAT trial, noted that the study didn’t meet it’s primary endpoint of a significantly lower prevalence of food allergy to any of the six intervention foods at age 3 years in the intention-to-treat analysis. But adherence to the demanding EAT early-introduction protocol was a problem. Indeed, only 43% of participants adhered to the study protocol. In a per-protocol analysis restricted to the adherent group, however, early introduction was associated with a highly significant 67% reduction in the relative risk of food allergy at 3 years of age compared to controls. And for the two most prevalent food allergies – to peanut and egg – the relative risk reductions in the early-introduction group were 100% and 75%, respectively.

 

The EAT results suggest that an effective preventive dose of peanut in infants at least 3 months of age is roughly 2 g of peanut protein per week, equivalent to just under 2 tsp of peanut butter, according to Dr. Lack.

Simultaneously with presentation of the LEAP-On and EAT trials in Los Angeles, the studies were published online at NEJM.org (doi: 10.1056/NEJMoa1514210 for LEAP-ON and 10.1056/NEJMoa1514209 for EAT).

LEAP-On was supported primarily by NIAID. EAT was funded mainly by the UK Foods Standards Agency and the Medical Research Council. Dr. Lack reported receiving grants from those agencies as well as Food Allergy Research and Education.

LOS ANGELES – A peanut allergy prevention strategy based upon regular consumption of peanut-containing foods from infancy to age 5 continued to provide protection even after peanut intake was halted for a full year from age 5 to 6, according to new results from an extension of the landmark LEAP trial, known as LEAP-On, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The impetus for LEAP-On was the investigators’ concern that a period of peanut avoidance might cause loss of the protective state. But that didn’t occur.

“I think there is no doubt that we have prevented peanut allergy so far in these high-risk children. Next, the LEAP-Ad Lib study will tell us whether we’ve prevented it by age 10,” said Dr. Gideon Lack of King’s College London, who headed LEAP-On.

Bruce Jancin/Frontline Medical News

A second major randomized trial known as EAT (Enquiring About Tolerance) presented at the meeting provided further support for early dietary introduction of allergenic foods. EAT differed from LEAP (Learning Early About Peanut Allergy) and LEAP-On in that it ambitiously randomized infants to early introduction or avoidance of not one but six allergenic foods: peanut, cooked egg, cow’s milk, fish, sesame, and wheat. Also, while LEAP and LEAP-On involved roughly 600 infants known to be at very high risk for allergy, EAT was conducted in a general population of 1,303 infants who weren’t at increased risk, all of whom were exclusively breast-fed until the intervention beginning at age 3 months.

The presentation of the LEAP-On and EAT results at the AAAAI annual meeting was a major event marked by the National Institute of Allergy and Infectious Diseases by same-day release of new NIAID-sponsored draft recommendations for the diagnosis and management of food allergies.

In a press conference held at the AAAAI annual meeting to announce the start of a 45-day public comment period for the draft update of the 2010 guidelines, Dr. Daniel Rotrosen, director of NIAID’s division of allergy, immunology and transplantation, said the new guidelines were developed largely in response to the compelling LEAP findings. That trial demonstrated that sustained consumption of peanut starting in infancy resulted in an 81% lower rate of peanut allergy at age 5 years compared to a strategy of peanut avoidance (N Engl J Med. 2015;372:803-13).

Bruce Jancin/Frontline Medical News

The draft guidelines, now available on the NIAID website, represent a sharp departure from the former recommendation that physicians encourage exclusive breastfeeding for the first 6 months of life followed by cautious introduction of other foods. Whereas the former orthodoxy was that delayed introduction of allergenic foods protects against development of food allergy, the new evidence-based concept supported by the LEAP and EAT findings is that just the opposite is true: that is, introduction of such foods during the period of immunologic plasticity in infancy induces tolerance.

Thus, the draft guidelines recommend that infants at high risk for peanut allergy because they have severe eczema and/or egg allergy should have introduction of peanut-containing food at 4-6 months of age to reduce their risk of peanut allergy, preceded by evaluation using peanut-specific IgE or skin prick testing to make sure it’s safe. That age window coincides with well-child visits and vaccination schedules, Dr. Rotrosen noted.

These guidelines represent the consensus of 26 organizations that participated in their development. Among them are the American Academy of Pediatrics, the American Academy of Family Physicians, the American Academy of Dermatology, the American College of Gastroenterology, and AAAAI.

“I expect the new guidelines, when finalized, to be endorsed by the leadership of all the participating organizations,” Dr. Rotrosen said.

The new paradigm will require cultural change, said Dr. James R. Baker Jr., CEO and chief medical officer of Food Allergy Research and Education, a nonprofit organization that provided partial funding for LEAP and LEAP-On.

Bruce Jancin/Frontline Medical News

“I think for a long time we’ve vilified these foods. There’s nothing inherently wrong with their intake, and that’s a message we need to get across to parents and physicians so they can start thinking differently,” he said.

“The good news about these studies is that they show there’s no reason not to do this,” Dr. Baker added. “There’s no harm that comes from the early introduction.”

Dr. Lack, who led the EAT trial, noted that the study didn’t meet it’s primary endpoint of a significantly lower prevalence of food allergy to any of the six intervention foods at age 3 years in the intention-to-treat analysis. But adherence to the demanding EAT early-introduction protocol was a problem. Indeed, only 43% of participants adhered to the study protocol. In a per-protocol analysis restricted to the adherent group, however, early introduction was associated with a highly significant 67% reduction in the relative risk of food allergy at 3 years of age compared to controls. And for the two most prevalent food allergies – to peanut and egg – the relative risk reductions in the early-introduction group were 100% and 75%, respectively.

 

The EAT results suggest that an effective preventive dose of peanut in infants at least 3 months of age is roughly 2 g of peanut protein per week, equivalent to just under 2 tsp of peanut butter, according to Dr. Lack.

Simultaneously with presentation of the LEAP-On and EAT trials in Los Angeles, the studies were published online at NEJM.org (doi: 10.1056/NEJMoa1514210 for LEAP-ON and 10.1056/NEJMoa1514209 for EAT).

LEAP-On was supported primarily by NIAID. EAT was funded mainly by the UK Foods Standards Agency and the Medical Research Council. Dr. Lack reported receiving grants from those agencies as well as Food Allergy Research and Education.

At #HospMed16 Plenary, the U.S. Surgeon General, Vice Admiral Vivek H. Murthy, MD, MBA, spoke to a standing-room-only crowd about how hospitalists can lead in “Bringing Health to America.”

Dr. Murthy, who previously worked as a hospitalist in Boston, spoke about how the urgency to build a foundation for health in America, where chronic illness and healthcare costs have skyrocketed, could not be any greater. Health is the key to opportunity, he said. He explored the following strategies to make America healthier:

1. Make the pursuit of healthy appealing;
2. Improve the safety of our communities;
3. Focus on the mind and spirit; and,
4. Cultivate our ability to give and receive kindness.

Specifically, hospitalists should contemplate the following questions:

• How can hospitalists leverage their leadership in the hospital to improve systems and create a culture that supports healing and health?
• How can hospitalists be a powerful of force of change both inside and outside the hospital?
• How can hospitalists inspire the next generation of physicians to safeguard the health of their community by treating and preventing illness?

Dr. Murthy challenged hospitalists to commit to strengthening the foundation of health in our country and shift our culture towards the well-being of our communities through prevention.

He left the group by saying, “In the end, the world gets better when people choose to come together to make it better.” TH

At #HospMed16 Plenary, the U.S. Surgeon General, Vice Admiral Vivek H. Murthy, MD, MBA, spoke to a standing-room-only crowd about how hospitalists can lead in “Bringing Health to America.”

Dr. Murthy, who previously worked as a hospitalist in Boston, spoke about how the urgency to build a foundation for health in America, where chronic illness and healthcare costs have skyrocketed, could not be any greater. Health is the key to opportunity, he said. He explored the following strategies to make America healthier:

1. Make the pursuit of healthy appealing;
2. Improve the safety of our communities;
3. Focus on the mind and spirit; and,
4. Cultivate our ability to give and receive kindness.

Specifically, hospitalists should contemplate the following questions:

• How can hospitalists leverage their leadership in the hospital to improve systems and create a culture that supports healing and health?
• How can hospitalists be a powerful of force of change both inside and outside the hospital?
• How can hospitalists inspire the next generation of physicians to safeguard the health of their community by treating and preventing illness?

Dr. Murthy challenged hospitalists to commit to strengthening the foundation of health in our country and shift our culture towards the well-being of our communities through prevention.

He left the group by saying, “In the end, the world gets better when people choose to come together to make it better.” TH

At #HospMed16 Plenary, the U.S. Surgeon General, Vice Admiral Vivek H. Murthy, MD, MBA, spoke to a standing-room-only crowd about how hospitalists can lead in “Bringing Health to America.”

Dr. Murthy, who previously worked as a hospitalist in Boston, spoke about how the urgency to build a foundation for health in America, where chronic illness and healthcare costs have skyrocketed, could not be any greater. Health is the key to opportunity, he said. He explored the following strategies to make America healthier:

1. Make the pursuit of healthy appealing;
2. Improve the safety of our communities;
3. Focus on the mind and spirit; and,
4. Cultivate our ability to give and receive kindness.

Specifically, hospitalists should contemplate the following questions:

• How can hospitalists leverage their leadership in the hospital to improve systems and create a culture that supports healing and health?
• How can hospitalists be a powerful of force of change both inside and outside the hospital?
• How can hospitalists inspire the next generation of physicians to safeguard the health of their community by treating and preventing illness?

Dr. Murthy challenged hospitalists to commit to strengthening the foundation of health in our country and shift our culture towards the well-being of our communities through prevention.

He left the group by saying, “In the end, the world gets better when people choose to come together to make it better.” TH

LOS ANGELES – Adults over age 55 with asthma and depression have nearly twice as many emergency department visits for asthma as do asthma patients without depression, based on findings in 402 asthma patients, Dr. Pooja O. Patel reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Comorbid depression also is associated with more asthma-related sleep disturbances and worse health-related quality of life, even though spirometry findings are similar in asthma patients with and without depression, added Dr. Patel of the University of Michigan, Ann Arbor.

jancin

She analyzed data on 7,256 adults over age 55 who participated in the National Health and Nutrition Examination Survey during 2007-2012. The prevalence of physician-diagnosed asthma in this nationally representative group of older adults was 5.5%. And 196 of those 402 asthma patients, or fully 49%, had comorbid depression as defined by their scores on the Patient Health Questionnaire-9 (PHQ-9), a validated brief and reliable self-administered measure of depression severity.

One or more emergency department visits for asthma within the last 12 months occurred in 18.8% of the group with asthma alone, compared with 28.1% in those with comorbid depression. In a multivariate regression analysis adjusted for the demographic differences, this translated to a twofold increased likelihood of ED visits specifically for asthma in the group with asthma and depression.

These data make a compelling case for routine screening for depression in older adults with asthma. The PHQ-9 is a good, simple tool for this purpose. Future studies will need to be done in order to learn whether early identification and treatment of comorbid depression in older asthmatic adults will result in improved asthma outcomes, but that is a reasonable hope, Dr. Patel added.

Why is asthma control worse in older adults with depression? In an interview, Dr. Patel said she thinks demographic differences may play a role. The older asthma patients with depression had less education and lower socioeconomic status than those without depression. Also, depression could adversely affect adherence to asthma controller medications, as depression is linked to worse medication adherence.

Dr. Patel reported having no financial conflicts regarding her study.

[email protected]

LOS ANGELES – Adults over age 55 with asthma and depression have nearly twice as many emergency department visits for asthma as do asthma patients without depression, based on findings in 402 asthma patients, Dr. Pooja O. Patel reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Comorbid depression also is associated with more asthma-related sleep disturbances and worse health-related quality of life, even though spirometry findings are similar in asthma patients with and without depression, added Dr. Patel of the University of Michigan, Ann Arbor.

jancin

She analyzed data on 7,256 adults over age 55 who participated in the National Health and Nutrition Examination Survey during 2007-2012. The prevalence of physician-diagnosed asthma in this nationally representative group of older adults was 5.5%. And 196 of those 402 asthma patients, or fully 49%, had comorbid depression as defined by their scores on the Patient Health Questionnaire-9 (PHQ-9), a validated brief and reliable self-administered measure of depression severity.

One or more emergency department visits for asthma within the last 12 months occurred in 18.8% of the group with asthma alone, compared with 28.1% in those with comorbid depression. In a multivariate regression analysis adjusted for the demographic differences, this translated to a twofold increased likelihood of ED visits specifically for asthma in the group with asthma and depression.

These data make a compelling case for routine screening for depression in older adults with asthma. The PHQ-9 is a good, simple tool for this purpose. Future studies will need to be done in order to learn whether early identification and treatment of comorbid depression in older asthmatic adults will result in improved asthma outcomes, but that is a reasonable hope, Dr. Patel added.

Why is asthma control worse in older adults with depression? In an interview, Dr. Patel said she thinks demographic differences may play a role. The older asthma patients with depression had less education and lower socioeconomic status than those without depression. Also, depression could adversely affect adherence to asthma controller medications, as depression is linked to worse medication adherence.

Dr. Patel reported having no financial conflicts regarding her study.

[email protected]

LOS ANGELES – Adults over age 55 with asthma and depression have nearly twice as many emergency department visits for asthma as do asthma patients without depression, based on findings in 402 asthma patients, Dr. Pooja O. Patel reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Comorbid depression also is associated with more asthma-related sleep disturbances and worse health-related quality of life, even though spirometry findings are similar in asthma patients with and without depression, added Dr. Patel of the University of Michigan, Ann Arbor.

jancin

She analyzed data on 7,256 adults over age 55 who participated in the National Health and Nutrition Examination Survey during 2007-2012. The prevalence of physician-diagnosed asthma in this nationally representative group of older adults was 5.5%. And 196 of those 402 asthma patients, or fully 49%, had comorbid depression as defined by their scores on the Patient Health Questionnaire-9 (PHQ-9), a validated brief and reliable self-administered measure of depression severity.

One or more emergency department visits for asthma within the last 12 months occurred in 18.8% of the group with asthma alone, compared with 28.1% in those with comorbid depression. In a multivariate regression analysis adjusted for the demographic differences, this translated to a twofold increased likelihood of ED visits specifically for asthma in the group with asthma and depression.

These data make a compelling case for routine screening for depression in older adults with asthma. The PHQ-9 is a good, simple tool for this purpose. Future studies will need to be done in order to learn whether early identification and treatment of comorbid depression in older asthmatic adults will result in improved asthma outcomes, but that is a reasonable hope, Dr. Patel added.

Why is asthma control worse in older adults with depression? In an interview, Dr. Patel said she thinks demographic differences may play a role. The older asthma patients with depression had less education and lower socioeconomic status than those without depression. Also, depression could adversely affect adherence to asthma controller medications, as depression is linked to worse medication adherence.

Dr. Patel reported having no financial conflicts regarding her study.

[email protected]

It is always noteworthy when the headlines in the medical and mainstream media appear to be the same.

Typically, this means one of two things: 1) Sensationalism has propelled a minor issue into the common lexicon; or 2) a truly serious issue has grown to the point where the whole world is finally taking notice.

With the recent resurgence of Zika virus, something that initially seemed to be the former has unmistakably developed into the latter, and health care providers are again facing an age-old question: How do we adequately fight an evolving and serious illness in the midst of an ever-changing battlefield?

As has been the case countless times before, the answer to this question really lies in early identification. One might think that the advent of modern technology would make this a much easier proposition, but that has not exactly been the case.

In fact, recent Ebola and Zika outbreaks have actually served to demonstrate a big problem in many modern electronic health records: poor clinical decision support.

In this column, we felt it would be helpful to highlight this shortcoming, and make the suggestion that in the world of EHRs …

Change needs to be faster than Zika

Zika virus is not new (it was first identified in the Zika Forest of Uganda in 1947), and neither is the concept of serious mosquito-born illness. While the current Zika hot zones are South America, Central America, Mexico, and the Caribbean, case reports indicate the virus is quickly migrating. At the time of this writing, more than 150 travel-associated cases of Zika have been identified in the continental United States, and it is clear that the consequences of undiagnosed Zika in pregnancy can be devastating.

Furthermore, Zika is just the latest of many viruses to threaten the health and welfare of modern civilization (for example, Ebola, swine flu, SARS, and so on), so screening and prevention is far from a novel idea.

Unfortunately, electronic record vendors don’t seem to have gotten the message that the ability to adapt quickly to public health threats should be a core element of any modern EHR.

On the contrary, EHRs seem to be designed for fixed “best practice” workflows, and updates are often slow in coming (typically requiring a major upgrade or “patch”). This renders them fairly unable to react nimbly to change.

This fact became evident to us as we attempted to implement a reminder for staff members to perform a Zika-focused travel history on all patients. We felt it was critical for this reminder to be prominent, be easy to interact with, and appear at the most appropriate time for screening.

Despite multiple attempts, we discovered that our top-ranked, industry-leading EHR was unable to do this seemingly straightforward task, and eventually we reverted to the age-old practice of hanging signs in all of the exam rooms. These encouraged patients to inform their doctor “of worrisome symptoms or recent travel history to affected areas.”

We refuse to accept the inability of any modern electronic health record to create simple and flexible clinical support rules and improve on the efficacy of the paper sign. This, especially in light of the fact that one of the core requirements of the Meaningful Use (MU) program – for which all EHRs are certified – is clinical decision support!

Unfortunately, the MU guidelines are not specific, so most vendors choose to include a standard set of rules and don’t allow the ability for customization. That just isn’t good enough. If Ebola and Zika have taught the health information technology community one thing, it’s that …

It is time for smarter EHRs!

For many people, the notion of artificial intelligence seems to be science fiction, but they don’t realize they are carrying incredible “AI” devices with them everywhere they go. We are, of course, referring to our cell phones, which seem to be getting more intelligent all the time.

If you own an iPhone, you may have noticed it often seems to know where you are about to drive and how long it will take you to get there. This can be a bit creepy at first, until you realize how helpful – and smart – it actually is.

Essentially, our devices are constantly collecting data, reading the patterns of our lives, and learning ways to enhance them. Smartphones have revolutionized how we communicate, work, and play. Why, then, can’t our electronic health record software do the same?

It will surprise exactly none of our readers that the Meaningful Use program has fallen short of its goal of promoting the true benefits of electronic records. Many critics have suggested that the incentive program has faltered because EHRs have made physicians work harder, without helping them work smarter.

 

Zika virus proves the critics correct. Beyond creating just simple reminders as mentioned above, EHRs should be able to make intelligent suggestions based on patient data and current practice guidelines.

Some EHRs get it half correct. For example, they are “smart” enough to remind clinicians that women of a certain age should have mammograms, but they fall short in the ability to efficiently update those reminders when the U.S. Preventive Services Task Force updates the screening recommendation (as they did recently).

Other EHRs do allow you to customize preventative health reminders, but do not place them in a position of prominence – so they are easily overlooked by providers as they care for patients.

Few products seem to get it just right, and it’s time for this to change.

Simply put, as questions in the media loom about how to stop this rising threat, we as frontline health care providers should have the tools – and the decision support – required to provide meaningful answers.

Dr. Notte is a family physician and clinical informaticist for Abington (Pa.) Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records. Dr. Skolnik is associate director of the family medicine residency program at Abington Memorial Hospital and professor of family and community medicine at Temple University in Philadelphia.

It is always noteworthy when the headlines in the medical and mainstream media appear to be the same.

Typically, this means one of two things: 1) Sensationalism has propelled a minor issue into the common lexicon; or 2) a truly serious issue has grown to the point where the whole world is finally taking notice.

With the recent resurgence of Zika virus, something that initially seemed to be the former has unmistakably developed into the latter, and health care providers are again facing an age-old question: How do we adequately fight an evolving and serious illness in the midst of an ever-changing battlefield?

As has been the case countless times before, the answer to this question really lies in early identification. One might think that the advent of modern technology would make this a much easier proposition, but that has not exactly been the case.

In fact, recent Ebola and Zika outbreaks have actually served to demonstrate a big problem in many modern electronic health records: poor clinical decision support.

In this column, we felt it would be helpful to highlight this shortcoming, and make the suggestion that in the world of EHRs …

Change needs to be faster than Zika

Zika virus is not new (it was first identified in the Zika Forest of Uganda in 1947), and neither is the concept of serious mosquito-born illness. While the current Zika hot zones are South America, Central America, Mexico, and the Caribbean, case reports indicate the virus is quickly migrating. At the time of this writing, more than 150 travel-associated cases of Zika have been identified in the continental United States, and it is clear that the consequences of undiagnosed Zika in pregnancy can be devastating.

Furthermore, Zika is just the latest of many viruses to threaten the health and welfare of modern civilization (for example, Ebola, swine flu, SARS, and so on), so screening and prevention is far from a novel idea.

Unfortunately, electronic record vendors don’t seem to have gotten the message that the ability to adapt quickly to public health threats should be a core element of any modern EHR.

On the contrary, EHRs seem to be designed for fixed “best practice” workflows, and updates are often slow in coming (typically requiring a major upgrade or “patch”). This renders them fairly unable to react nimbly to change.

This fact became evident to us as we attempted to implement a reminder for staff members to perform a Zika-focused travel history on all patients. We felt it was critical for this reminder to be prominent, be easy to interact with, and appear at the most appropriate time for screening.

Despite multiple attempts, we discovered that our top-ranked, industry-leading EHR was unable to do this seemingly straightforward task, and eventually we reverted to the age-old practice of hanging signs in all of the exam rooms. These encouraged patients to inform their doctor “of worrisome symptoms or recent travel history to affected areas.”

We refuse to accept the inability of any modern electronic health record to create simple and flexible clinical support rules and improve on the efficacy of the paper sign. This, especially in light of the fact that one of the core requirements of the Meaningful Use (MU) program – for which all EHRs are certified – is clinical decision support!

Unfortunately, the MU guidelines are not specific, so most vendors choose to include a standard set of rules and don’t allow the ability for customization. That just isn’t good enough. If Ebola and Zika have taught the health information technology community one thing, it’s that …

It is time for smarter EHRs!

For many people, the notion of artificial intelligence seems to be science fiction, but they don’t realize they are carrying incredible “AI” devices with them everywhere they go. We are, of course, referring to our cell phones, which seem to be getting more intelligent all the time.

If you own an iPhone, you may have noticed it often seems to know where you are about to drive and how long it will take you to get there. This can be a bit creepy at first, until you realize how helpful – and smart – it actually is.

Essentially, our devices are constantly collecting data, reading the patterns of our lives, and learning ways to enhance them. Smartphones have revolutionized how we communicate, work, and play. Why, then, can’t our electronic health record software do the same?

It will surprise exactly none of our readers that the Meaningful Use program has fallen short of its goal of promoting the true benefits of electronic records. Many critics have suggested that the incentive program has faltered because EHRs have made physicians work harder, without helping them work smarter.

 

Zika virus proves the critics correct. Beyond creating just simple reminders as mentioned above, EHRs should be able to make intelligent suggestions based on patient data and current practice guidelines.

Some EHRs get it half correct. For example, they are “smart” enough to remind clinicians that women of a certain age should have mammograms, but they fall short in the ability to efficiently update those reminders when the U.S. Preventive Services Task Force updates the screening recommendation (as they did recently).

Other EHRs do allow you to customize preventative health reminders, but do not place them in a position of prominence – so they are easily overlooked by providers as they care for patients.

Few products seem to get it just right, and it’s time for this to change.

Simply put, as questions in the media loom about how to stop this rising threat, we as frontline health care providers should have the tools – and the decision support – required to provide meaningful answers.

Dr. Notte is a family physician and clinical informaticist for Abington (Pa.) Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records. Dr. Skolnik is associate director of the family medicine residency program at Abington Memorial Hospital and professor of family and community medicine at Temple University in Philadelphia.

It is always noteworthy when the headlines in the medical and mainstream media appear to be the same.

Typically, this means one of two things: 1) Sensationalism has propelled a minor issue into the common lexicon; or 2) a truly serious issue has grown to the point where the whole world is finally taking notice.

With the recent resurgence of Zika virus, something that initially seemed to be the former has unmistakably developed into the latter, and health care providers are again facing an age-old question: How do we adequately fight an evolving and serious illness in the midst of an ever-changing battlefield?

As has been the case countless times before, the answer to this question really lies in early identification. One might think that the advent of modern technology would make this a much easier proposition, but that has not exactly been the case.

In fact, recent Ebola and Zika outbreaks have actually served to demonstrate a big problem in many modern electronic health records: poor clinical decision support.

In this column, we felt it would be helpful to highlight this shortcoming, and make the suggestion that in the world of EHRs …

Change needs to be faster than Zika

Zika virus is not new (it was first identified in the Zika Forest of Uganda in 1947), and neither is the concept of serious mosquito-born illness. While the current Zika hot zones are South America, Central America, Mexico, and the Caribbean, case reports indicate the virus is quickly migrating. At the time of this writing, more than 150 travel-associated cases of Zika have been identified in the continental United States, and it is clear that the consequences of undiagnosed Zika in pregnancy can be devastating.

Furthermore, Zika is just the latest of many viruses to threaten the health and welfare of modern civilization (for example, Ebola, swine flu, SARS, and so on), so screening and prevention is far from a novel idea.

Unfortunately, electronic record vendors don’t seem to have gotten the message that the ability to adapt quickly to public health threats should be a core element of any modern EHR.

On the contrary, EHRs seem to be designed for fixed “best practice” workflows, and updates are often slow in coming (typically requiring a major upgrade or “patch”). This renders them fairly unable to react nimbly to change.

This fact became evident to us as we attempted to implement a reminder for staff members to perform a Zika-focused travel history on all patients. We felt it was critical for this reminder to be prominent, be easy to interact with, and appear at the most appropriate time for screening.

Despite multiple attempts, we discovered that our top-ranked, industry-leading EHR was unable to do this seemingly straightforward task, and eventually we reverted to the age-old practice of hanging signs in all of the exam rooms. These encouraged patients to inform their doctor “of worrisome symptoms or recent travel history to affected areas.”

We refuse to accept the inability of any modern electronic health record to create simple and flexible clinical support rules and improve on the efficacy of the paper sign. This, especially in light of the fact that one of the core requirements of the Meaningful Use (MU) program – for which all EHRs are certified – is clinical decision support!

Unfortunately, the MU guidelines are not specific, so most vendors choose to include a standard set of rules and don’t allow the ability for customization. That just isn’t good enough. If Ebola and Zika have taught the health information technology community one thing, it’s that …

It is time for smarter EHRs!

For many people, the notion of artificial intelligence seems to be science fiction, but they don’t realize they are carrying incredible “AI” devices with them everywhere they go. We are, of course, referring to our cell phones, which seem to be getting more intelligent all the time.

If you own an iPhone, you may have noticed it often seems to know where you are about to drive and how long it will take you to get there. This can be a bit creepy at first, until you realize how helpful – and smart – it actually is.

Essentially, our devices are constantly collecting data, reading the patterns of our lives, and learning ways to enhance them. Smartphones have revolutionized how we communicate, work, and play. Why, then, can’t our electronic health record software do the same?

It will surprise exactly none of our readers that the Meaningful Use program has fallen short of its goal of promoting the true benefits of electronic records. Many critics have suggested that the incentive program has faltered because EHRs have made physicians work harder, without helping them work smarter.

 

Zika virus proves the critics correct. Beyond creating just simple reminders as mentioned above, EHRs should be able to make intelligent suggestions based on patient data and current practice guidelines.

Some EHRs get it half correct. For example, they are “smart” enough to remind clinicians that women of a certain age should have mammograms, but they fall short in the ability to efficiently update those reminders when the U.S. Preventive Services Task Force updates the screening recommendation (as they did recently).

Other EHRs do allow you to customize preventative health reminders, but do not place them in a position of prominence – so they are easily overlooked by providers as they care for patients.

Few products seem to get it just right, and it’s time for this to change.

Simply put, as questions in the media loom about how to stop this rising threat, we as frontline health care providers should have the tools – and the decision support – required to provide meaningful answers.

Dr. Notte is a family physician and clinical informaticist for Abington (Pa.) Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records. Dr. Skolnik is associate director of the family medicine residency program at Abington Memorial Hospital and professor of family and community medicine at Temple University in Philadelphia.

Ibrutinib (Imbruvica) has been approved as a first-line treatment for patients with chronic lymphocytic leukemia (CLL), irrespective of their treatment history, according to a statement issued by the manufacturer, AbbVie.

The approval is based on data from the randomized, multicenter, open-label phase III RESONATE-2 trial, which evaluated the use of ibrutinib versus chlorambucil in 269 treatment-naive patients with CLL or small lymphocytic lymphoma (SLL) aged 65 years or older. The RESONATE-2 data were presented at the 2015 annual meeting of the American Society of Hematology.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

“The progression-free survival data seen in these previously untreated CLL patients are strong and encouraging,” Dr. Jan Burger of the University of Texas MD Anderson Cancer Center, Houston, and the lead investigator of RESONATE-2, said in the AbbVie statement. “This is especially important for first-line CLL patients, when considering the safety profile. This treatment represents another option for these patients.”

The National Comprehensive Cancer Network also recently published an update to its clinical practice guidelines for non-Hodgkin’s lymphomas, granting Imbruvica a category 1 recommendation for certain CLL patients, including as a first-line treatment option for frail CLL patients with significant comorbidities, as well as for CLL patients with or without del 17p or the genetic mutation TP53 who are 70 years or older, or younger patients with significant comorbidities, the AbbVie statement noted.

Imbruvica has been jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and by Janssen Biotech.

[email protected]

Ibrutinib (Imbruvica) has been approved as a first-line treatment for patients with chronic lymphocytic leukemia (CLL), irrespective of their treatment history, according to a statement issued by the manufacturer, AbbVie.

The approval is based on data from the randomized, multicenter, open-label phase III RESONATE-2 trial, which evaluated the use of ibrutinib versus chlorambucil in 269 treatment-naive patients with CLL or small lymphocytic lymphoma (SLL) aged 65 years or older. The RESONATE-2 data were presented at the 2015 annual meeting of the American Society of Hematology.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

“The progression-free survival data seen in these previously untreated CLL patients are strong and encouraging,” Dr. Jan Burger of the University of Texas MD Anderson Cancer Center, Houston, and the lead investigator of RESONATE-2, said in the AbbVie statement. “This is especially important for first-line CLL patients, when considering the safety profile. This treatment represents another option for these patients.”

The National Comprehensive Cancer Network also recently published an update to its clinical practice guidelines for non-Hodgkin’s lymphomas, granting Imbruvica a category 1 recommendation for certain CLL patients, including as a first-line treatment option for frail CLL patients with significant comorbidities, as well as for CLL patients with or without del 17p or the genetic mutation TP53 who are 70 years or older, or younger patients with significant comorbidities, the AbbVie statement noted.

Imbruvica has been jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and by Janssen Biotech.

[email protected]

Ibrutinib (Imbruvica) has been approved as a first-line treatment for patients with chronic lymphocytic leukemia (CLL), irrespective of their treatment history, according to a statement issued by the manufacturer, AbbVie.

The approval is based on data from the randomized, multicenter, open-label phase III RESONATE-2 trial, which evaluated the use of ibrutinib versus chlorambucil in 269 treatment-naive patients with CLL or small lymphocytic lymphoma (SLL) aged 65 years or older. The RESONATE-2 data were presented at the 2015 annual meeting of the American Society of Hematology.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

“The progression-free survival data seen in these previously untreated CLL patients are strong and encouraging,” Dr. Jan Burger of the University of Texas MD Anderson Cancer Center, Houston, and the lead investigator of RESONATE-2, said in the AbbVie statement. “This is especially important for first-line CLL patients, when considering the safety profile. This treatment represents another option for these patients.”

The National Comprehensive Cancer Network also recently published an update to its clinical practice guidelines for non-Hodgkin’s lymphomas, granting Imbruvica a category 1 recommendation for certain CLL patients, including as a first-line treatment option for frail CLL patients with significant comorbidities, as well as for CLL patients with or without del 17p or the genetic mutation TP53 who are 70 years or older, or younger patients with significant comorbidities, the AbbVie statement noted.

Imbruvica has been jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and by Janssen Biotech.

[email protected]

If primary care physicians initiated therapy in patients with mild to moderate acne, they could significantly decrease referrals to dermatologists, reduce patient waiting times, and cut health care costs, based on a study published online March 6 in JAMA Dermatology.

The researchers used retrospective data to model two treatment algorithms for initiating acne therapy based on evaluations of 253 dermatology referrals by primary care physicians at a single center. Half of the acne patients had not received any topical or systemic treatment prior to their referral to a dermatologist.

Two treatment algorithms were modeled for initiating acne therapy: In the first, the primary care physicians initiated topical acne treatments; in the second, they initiated topical treatments and systemic antibiotics.

If primary care physicians initiated topical acne therapy, the first algorithm predicted a 48% reduction in initial referrals to dermatologists, a 40% overall reduction in referrals, a mean 28.6-day reduction in delay to treatment, and an associated cost savings of $20.28 per patient.

Following the second algorithm entirely eliminated referrals for 72% of patients, reduced initial referrals by 86.7%, and reduced the mean delay to treatment by 27.9 days; the cost savings was $35.68 per patient, wrote Dr. Kristina J. Liu of the Harvard Combined Dermatology Residency Program and coauthors (JAMA Dermatol. 2016 March 6. doi: 10.1001/jamadermatol.2016.0183).

“Our findings are extracted from and applicable to patients who already have access to primary care clinicians. While patients can be efficiently treated by presenting directly to a dermatologist, in many health plans, a referral from primary care is a requisite step that precludes this possibility. Furthermore, 235 patients (93%) in our cohort were being managed by their primary care clinicians for other health conditions in addition to acne. Given these other health concerns, the patients in our study would likely access their primary care clinicians regardless of the problem of acne. Thus, the judicious use of primary care resources to manage acne as part of the holistic care of the patient can prove to be a time- and cost-saving strategy,” the authors wrote.

In addition, 32% of the referrals in the study were for acne plus another dermatologic issue, and such patients likely require dermatologic evaluation regardless of primary care clinician-driven acne management, the authors added.

One author declared employment with Walgreens Boots Alliance. No other conflicts of interest were declared.

If primary care physicians initiated therapy in patients with mild to moderate acne, they could significantly decrease referrals to dermatologists, reduce patient waiting times, and cut health care costs, based on a study published online March 6 in JAMA Dermatology.

The researchers used retrospective data to model two treatment algorithms for initiating acne therapy based on evaluations of 253 dermatology referrals by primary care physicians at a single center. Half of the acne patients had not received any topical or systemic treatment prior to their referral to a dermatologist.

Two treatment algorithms were modeled for initiating acne therapy: In the first, the primary care physicians initiated topical acne treatments; in the second, they initiated topical treatments and systemic antibiotics.

If primary care physicians initiated topical acne therapy, the first algorithm predicted a 48% reduction in initial referrals to dermatologists, a 40% overall reduction in referrals, a mean 28.6-day reduction in delay to treatment, and an associated cost savings of $20.28 per patient.

Following the second algorithm entirely eliminated referrals for 72% of patients, reduced initial referrals by 86.7%, and reduced the mean delay to treatment by 27.9 days; the cost savings was $35.68 per patient, wrote Dr. Kristina J. Liu of the Harvard Combined Dermatology Residency Program and coauthors (JAMA Dermatol. 2016 March 6. doi: 10.1001/jamadermatol.2016.0183).

“Our findings are extracted from and applicable to patients who already have access to primary care clinicians. While patients can be efficiently treated by presenting directly to a dermatologist, in many health plans, a referral from primary care is a requisite step that precludes this possibility. Furthermore, 235 patients (93%) in our cohort were being managed by their primary care clinicians for other health conditions in addition to acne. Given these other health concerns, the patients in our study would likely access their primary care clinicians regardless of the problem of acne. Thus, the judicious use of primary care resources to manage acne as part of the holistic care of the patient can prove to be a time- and cost-saving strategy,” the authors wrote.

In addition, 32% of the referrals in the study were for acne plus another dermatologic issue, and such patients likely require dermatologic evaluation regardless of primary care clinician-driven acne management, the authors added.

One author declared employment with Walgreens Boots Alliance. No other conflicts of interest were declared.

If primary care physicians initiated therapy in patients with mild to moderate acne, they could significantly decrease referrals to dermatologists, reduce patient waiting times, and cut health care costs, based on a study published online March 6 in JAMA Dermatology.

The researchers used retrospective data to model two treatment algorithms for initiating acne therapy based on evaluations of 253 dermatology referrals by primary care physicians at a single center. Half of the acne patients had not received any topical or systemic treatment prior to their referral to a dermatologist.

Two treatment algorithms were modeled for initiating acne therapy: In the first, the primary care physicians initiated topical acne treatments; in the second, they initiated topical treatments and systemic antibiotics.

If primary care physicians initiated topical acne therapy, the first algorithm predicted a 48% reduction in initial referrals to dermatologists, a 40% overall reduction in referrals, a mean 28.6-day reduction in delay to treatment, and an associated cost savings of $20.28 per patient.

Following the second algorithm entirely eliminated referrals for 72% of patients, reduced initial referrals by 86.7%, and reduced the mean delay to treatment by 27.9 days; the cost savings was $35.68 per patient, wrote Dr. Kristina J. Liu of the Harvard Combined Dermatology Residency Program and coauthors (JAMA Dermatol. 2016 March 6. doi: 10.1001/jamadermatol.2016.0183).

“Our findings are extracted from and applicable to patients who already have access to primary care clinicians. While patients can be efficiently treated by presenting directly to a dermatologist, in many health plans, a referral from primary care is a requisite step that precludes this possibility. Furthermore, 235 patients (93%) in our cohort were being managed by their primary care clinicians for other health conditions in addition to acne. Given these other health concerns, the patients in our study would likely access their primary care clinicians regardless of the problem of acne. Thus, the judicious use of primary care resources to manage acne as part of the holistic care of the patient can prove to be a time- and cost-saving strategy,” the authors wrote.

In addition, 32% of the referrals in the study were for acne plus another dermatologic issue, and such patients likely require dermatologic evaluation regardless of primary care clinician-driven acne management, the authors added.

One author declared employment with Walgreens Boots Alliance. No other conflicts of interest were declared.

WASHINGTON – Almost 41% of black women surveyed described hair loss that was consistent with central centrifugal cicatricial alopecia (CCCA), but only about 9% said they had been diagnosed with the condition, Dr. Yolanda Lenzy reported at the annual meeting of the American Academy of Dermatology.

In a video interview at the meeting, Dr. Lenzy of the University of Connecticut, Farmington, discussed the results of a hair survey she conducted with the Black Women’s Health Study at Boston University’s Slone Epidemiology Center. Nearly 6,000 women have completed the survey to date.

“For many years, it was thought to be due to hair styling practices,” but there are new data showing that genetics can be an important cause, she said, referring to research from South Africa indicating that CCCA can be inherited in an autosomal dominant fashion.

Dr. Lenzy, who practices dermatology in Chicopee, Mass., used a central hair loss photographic scale in the study, which also can be helpful in the office to monitor hair loss and “to quantify how much hair loss a person has … in terms of: Are they getting worse? Do they go from stage 3 to stage 5 or stage 1 to stage 3?”

[email protected]

WASHINGTON – Almost 41% of black women surveyed described hair loss that was consistent with central centrifugal cicatricial alopecia (CCCA), but only about 9% said they had been diagnosed with the condition, Dr. Yolanda Lenzy reported at the annual meeting of the American Academy of Dermatology.

In a video interview at the meeting, Dr. Lenzy of the University of Connecticut, Farmington, discussed the results of a hair survey she conducted with the Black Women’s Health Study at Boston University’s Slone Epidemiology Center. Nearly 6,000 women have completed the survey to date.

“For many years, it was thought to be due to hair styling practices,” but there are new data showing that genetics can be an important cause, she said, referring to research from South Africa indicating that CCCA can be inherited in an autosomal dominant fashion.

Dr. Lenzy, who practices dermatology in Chicopee, Mass., used a central hair loss photographic scale in the study, which also can be helpful in the office to monitor hair loss and “to quantify how much hair loss a person has … in terms of: Are they getting worse? Do they go from stage 3 to stage 5 or stage 1 to stage 3?”

[email protected]

WASHINGTON – Almost 41% of black women surveyed described hair loss that was consistent with central centrifugal cicatricial alopecia (CCCA), but only about 9% said they had been diagnosed with the condition, Dr. Yolanda Lenzy reported at the annual meeting of the American Academy of Dermatology.

In a video interview at the meeting, Dr. Lenzy of the University of Connecticut, Farmington, discussed the results of a hair survey she conducted with the Black Women’s Health Study at Boston University’s Slone Epidemiology Center. Nearly 6,000 women have completed the survey to date.

“For many years, it was thought to be due to hair styling practices,” but there are new data showing that genetics can be an important cause, she said, referring to research from South Africa indicating that CCCA can be inherited in an autosomal dominant fashion.

Dr. Lenzy, who practices dermatology in Chicopee, Mass., used a central hair loss photographic scale in the study, which also can be helpful in the office to monitor hair loss and “to quantify how much hair loss a person has … in terms of: Are they getting worse? Do they go from stage 3 to stage 5 or stage 1 to stage 3?”

[email protected]

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From the Albert Einstein College of Medicine, Division of Pediatric Gastroenterology and Nutrition, Children’s Hospital at Montefiore, Bronx, NY.

 

Abstract

• Objective: To review diagnostic challenges and management strategies in children with nonalcoholic fatty liver disease (NAFLD).
• Methods: Review of the literaure.
• Results: NAFLD is common in the United States and should be suspected in overweight or obese children with an elevated serum alanine aminotransferase level. The differential diagnosis for these patients is broad, however, and liver biopsy—the gold standard test—should be undertaken selectively after an appropriate workup. Patients should be counseled on lifestyle modifications, whereas vitamin E therapy can be initiated for those with biopsy-proven disease.
• Conclusion: Providers should have a high degree of suspicion for NAFLD, approaching the workup and diagnosis in an incremental, step-wise fashion. Further research is needed to standardize the diagnostic approach, identify reliable, noninvasive diagnostic measures, and develop novel treatment modalities.

 

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, affecting approximately 10% of children and a third of all adults in the United States [1–3]. It is a significant public health challenge and is estimated to soon be the number one indication for liver transplantation in adults.

NAFLD is a generic term encompassing 2 distinct conditions defined by their histopathology: simple steatosis and nonalcoholic steatohepatitis (NASH). Simple steatosis is characterized by predominantly macrovesicular—meaning large droplet—cytoplasmic lipid inclusions found in ≥ 5% of hepatocytes. NASH is defined as hepatic steatosis plus the additional features of inflammation, hepatocyte ballooning, and/or fibrosis. There are some adult data [4-6] and 1 retrospective pediatric study [7] demonstrating that over time, NAFLD may progress. That is, steatosis may progress to NASH and some patients with fibrosis will ultimately develop cirrhosis. If intervention is provided early in the histologic spectrum, NAFLD can be reversed [4,8] and late complications—such as cirrhosis, hepatocellular carcinoma, or liver transplantation—may be prevented.

It is important to highlight that the above definitions are based on histology and that a liver biopsy cannot be reasonably obtained in such a large percentage of the U.S. population. This case-based review will therefore focus primarily on the current diagnostic challenges facing health care providers as well as management strategies in children with presumed NAFLD.

 

Case Study

Initial Presentation

As you finish your charts at the end of a busy clinic day, you identify 3 patients who may have NAFLD:

 

 

History

All 3 patients presented to your office for a routine annual physical before the start of the school year and are asymptomatic. None of the patients has a family history of liver disease and their previously diagnosed comorbidities are listed in the table above. No patient is taking medications other than patient C, who is on metformin.

All 3 children have a smooth, velvety rash on their necks consistent with acanthosis nigricans with an otherwise normal physical exam. The liver and spleen are difficult to palpate but are seemingly normal.

• What is the typical presentation for a child with NAFLD?

Most children with NAFLD are asymptomatic, though some may present with vague right upper quadrant abdominal pain. It is unclear, however, if the pain is caused by NAFLD or is rather an unrelated symptom that brings the child to the attention of a physician. In addition, hepatomegaly can be found in over 30% to 40% of patients [9]. For children without abdominal pain or hepatomegaly, most are recognized by an elevated serum alanine aminotransferase (ALT) or findings of increased liver echogenicity on ultrasonography.

Serum Alanine Aminotransferase

Serum aminotransferases are one of the more common screening tests for NAFLD. However, ALT is highly insensitive at commonly used thresholds and is also nonspecific. As documented in the SAFETY study, the upper limit of normal for ALT in healthy children should be set around 25 U/L in boys and 22 U/L in girls [10]. Yet even at these thresholds, the sensitivity of ALT to diagnose NAFLD is 80% in boys and 92% in girls, whereas specificity is 79% and 85%, respectively [10]. These findings are largely consistent with adult studies [11–14]. Furthermore, ALT does not correlate well with disease severity and children may still have NASH or significant fibrosis with normal values. In a well-characterized cohort of 91 children with biopsy-proven NAFLD, for example, early fibrosis was identified in 12% of children with a normal ALT (≤ 22 U/L for girls and ≤ 25 U/L in boys) [15]. Advanced fibrosis or cirrhosis was seen in 9% of children with an ALT up to 2 times this upper limit [15]. Thus, reliance on the serum ALT may significantly underestimate the prevalence and severity of liver injury.

Ultrasonography

Children with NAFLD typically have findings of increased hepatic echogenicity on abdominal ultrasonography. However, there are multiple limitations to sonography. First, ultrasound is insensitive for identifying mild steatosis if less than 30% of hepatocytes are affected [16,17]. Second, increased hepatic echogenicity is nonspecific and may be caused by inflammation, fibrosis, or intrahepatic accumulation of iron, copper, or glycogen. Third, there can be considerable inter- and intra-operator variability. And lastly, there is some evidence that ultrasounds do not add benefit to diagnosing children with NAFLD [18].

• Which patients are at risk for developing hepatic steatosis and NASH?

Weight, Age, and Gender

There is a strong, direct correlation between body mass index (BMI) and NAFLD. The Study of Child and Adolescent Liver Epidemiology (SCALE)—a sentinel pediatric autopsy study of 742 children—found that 5% of normal weight children, 16% of overweight children, and 38% of obese children had NAFLD. The SCALE study also demonstrated an increasing prevalence with age, such that NAFLD was present in 17.3% of 15- to 19-year-olds but only in 0.2% of 2- to 4-year-olds [1]. With regards to gender, NAFLD is roughly twice as prevalent in males [18–20]. While the exact etiology of this difference is unclear, hormonal differences are a leading hypothesis.

 

Ethnicity

NAFLD is most common in Hispanics, followed by Asians, Caucasians, and African Americans. Research suggests that genetics may be largely responsible for these ethnic disparities. For example, the I148M allele of PNPLA3 (a single nucleotide polymorphism) is strongly associated with steatosis, NASH, and fibrosis [21] and is most common in Hispanics, with a 50% carrier frequency in some cohorts [22]. Conversely, African Americans are more likely to carry the S453I allele of PNPLA3, which is associated with decreased hepatic steatosis [22]. There is also considerable variability within ethnic groups. For example, Mexican-American children appear to be at the highest risk for steatosis or NASH among Hispanics, whereas Filipino-American children are believed to have higher disease prevalence than Cambodian or Vietnamese Americans [1].

Comorbidities

NAFLD is associated with obesity, insulin resistance and diabetes, cardiovascular disease, the metabolic syndrome [23], decreased quality of life [24,25], and obstructive sleep apnea (OSA). These associations generally hold even after controlling for the other confounders listed. It is important to note that these data come largely from cross-sectional studies and direct causation has yet to be determined.

Insulin resistance in particular is strongly associated with NAFLD—so much so, in fact, that some consider it to be the hepatic manifestation of the metabolic syndrome. Additionally, children with features of the metabolic syndrome are more likely to have advanced histologic features of NAFLD [23]. There are also intriguing data from small pediatric studies to suggest that OSA may contribute to the development of hepatic fibrosis. In one study of 25 children with biopsy-proven NAFLD, for example, the presence of OSA and hypoxemia correlated with the degree of hepatic fibrosis [26]. In a slightly larger study of 65 children, OSA was also strongly associated with significant hepatic fibrosis (odds ratio, 5.91; 95% confidence interval, 3.23–7.42; P < 0.001). The duration of hypoxemia also correlated with histologic findings of inflammation and circulating biomarkers of apoptosis and fibrogenesis [27].

Other Laboratory Tests

Several studies have documented an association between elevated gamma-glutamyl transferase (GGT) and hepatic fibrosis [28,29], though others have been conflicting [30,31]. Pediatric studies have also demonstrated an inverse correlation between NASH and total bilirubin [32], serum potassium [33], and serum ceruloplasmin [34]. In addition, there are a number of serum biomarkers or biomarker panels commercially available for use in adults. Because similar efficacy data are unavailable in children, however, serum biomarkers should be primarily used for research purposes only.

• Who should be screened for NAFLD? And how?

Published professional society recommendations differ significantly with regards to screening. In 2007, the American Academy of Pediatrics suggested screening obese children over 10 years of age or overweight children with additional risk factors with biannual liver tests [35]. There were no management recommendations made for elevated aminotransferase levels other than for subspecialty referral. In 2012, the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) recommended obtaining an ultrasound and liver tests in every obese child [36]. One month later, however, the American Gastroenterological Association, American Association for the Study of Liver Disease, and the American College of Gastroenterology published joint guidelines without screening recommendations “due to a paucity of evidence” [37].

Because these statements conflict and are based heavily on expert opinion, one should consider the risks, benefits, and costs to screening large numbers of patients. Until additional research clarifies this controversy, we suggest that providers individualize their screening practices to their population and the risks of each individual patient. For example, we would consider screening children who are obese; Hispanic or Asian; have multiple features of the metabolic syndrome; and/or those who have a family history of NAFLD. Further, we recommend screening children for NAFLD with serum liver enzymes only and not with ultrasonography.

Case Continued: Laboratory Results

ALT and GGT tests are ordered and the results are as follows:

• What is the differential for children with suspected NAFLD?

 

The differential for NAFLD is remarkably broad and includes any condition that could lead to an elevated ALT or hepatic steatosis. Several of the more common etiologies in the differential are listed in the proceeding section. A list of “red flags” is shown in the Table and, if any are present, should alert the practitioner to the possible presence of alternative disease.

Autoimmune Hepatitis (AIH)

AIH is a progressive necro-inflammatory disorder of the liver characterized by elevated aminotransferases, positive autoantibodies, and distinctive histologic features. AIH is believed to occur in genetically predisposed patients in response to an environmental trigger. There is a female predominance and it can present in any age or ethnic group.

AIH is divided in 2 subtypes. Type 1 disease is characterized by a positive antinuclear (ANA) antibody and anti-smooth muscle antibody. More commonly, it presents in adolescence with an indolent course—many patients are asymptomatic until they develop features of cirrhosis and portal hypertension. Conversely, type 2 AIH is characterized by a positive liver kidney microsomal (LKM) antibody and tends to present acutely in young children. It is important to note that antibody titers can be falsely positive in a significant percentage of patients and, in such cases, are often mildly elevated [38]. We strongly suggest children with positive autoantibody titers be evaluated by a specialist.

Treatment should be started promptly to avoid progression to cirrhosis and should also done so in consultation with a pediatric gastroenterologist or hepatologist. The prognosis of AIH with immunosuppression is favorable, with long-term remission rates of approximately 80%. Transplantation is typically required in the remaining 10% to 20% [39].

Celiac Disease

Celiac disease is an autoimmune, inflammatory enteropathy caused by exposure to gluten in genetically susceptible individuals. Up to a third of all children presenting with celiac will have an elevated serum ALT [40]. Additional symptoms/features are both variable and nonspecific: abdominal pain, poor growth, diarrhea, or constipation, among others. Celiac is diagnosed by duodenal biopsy or a sufficiently elevated tissue transglutaminase antibody level [41]. Treatment with a strict gluten-free diet will resolve the enteropathy and normalize the serum aminotransferases.

Wilson’s Disease

Wilson’s disease is a metabolic disorder leading to copper deposition in the liver, brain, cornea, and kidneys. It is caused by an ATP7B gene mutation and inherited in an autosomal recessive fashion. Patients may present with asymptomatic liver disease, chronic hepatitis, acute liver failure, or with symptoms of portal hypertension. Neuropsychiatric symptoms may also be prominent. Screening tests include a serum ceruloplasmin and 24-hour urinary copper quantification. Because diagnosing Wilson’s disease can be challenging, however, further testing should occur in consultation with a pediatric gastroenterologist or hepatologist.

Viral Hepatitis

Chronic viral infections such as hepatitis B and C are still common etiologies of liver disease in the United States. However, universal vaccination and blood donor screening have reduced the risk of transmission; new antiviral agents will likely further decrease the prevalence and transmission risk over time. Acute viral hepatitis—cytomegalovirus, Epstein-Barr virus, hepatitis A, or hepatitis E—should also be considered in children who present with appropriate symptoms and an elevated ALT.

Drug-Induced

Drug-induced liver injury (DILI) can present with elevated serum aminotransferases (hepatocellular pattern), an elevated bilirubin (cholestatic pattern), or a mixed picture. Idiosyncratic DILI in children is commonly caused by antimicrobial or central nervous system agents and usually presents with a hepatocellular injury pattern. Substance abuse, including alcohol, is common and should also be investigated as the source of underlying liver disease.

Muscle Disease

Aspartate aminotransferase (AST) and ALT are present in hepatocytes, myocytes, and red blood cells, among other tissues. Thus, children with congenital myopathies or myositis can have elevated aminotransferases, typically with the AST higher than the ALT. In these patients, checking a creatine phosphokinase (CPK) level may lead to the correct diagnosis and limit unnecessary testing.

Other Metabolic Disorders

Myriad metabolic disorders present with liver disease and/or elevated serum aminotransferase levels. Individually, these conditions are rare but, collectively, are relatively common. Two of the more occult conditions—lysosomal acid lipase deficiency (LAL-D) and alpha-1 antitrypsin (A1A) deficiency—are discussed in further detail below.

LAL-D is an autosomal recessive disease resulting in the accumulation of cholesterol esters and triglycerides in lysosomes. Patients typically present with hepatomegaly and mildly elevated aminotransferases, an elevated LDL, low HDL cholesterol, and increased hepatic echogenicity on ultrasound. If a biopsy is obtained, microvesicular steatosis is predominant as opposed to macrovesicular steatosis found in NAFLD. The diagnosis of LAL-D can be made on a commercially available dry blood spot enzymatic assay or genetic testing and treatment has recently been FDA approved.

A1A deficiency is an autosomal recessive disease diagnosable by an alpha-1-antitrypsin phenotype. The clinical presentation is characterized by neonatal cholestasis in the infantile form and by hepatitis, cirrhosis and portal hypertension in older children. Classic symptoms of emphysema and chronic lung disease present in adulthood.

• What further testing should be performed in children with suspected NAFLD?

For obese children with an elevated ALT or evidence of increased hepatic echogenicity, ESPGHAN recommends targeting the workup according to the child’s age [36]. According to their consensus statement, they recommend an upfront, thorough laboratory evaluation in children less than 10 years of age and consideration of a liver biopsy upon completion. For children over 10 years of age at low risk for NASH or fibrosis, additional laboratory evaluation is suggested 3 to 6 months after failed lifestyle interventions. In general, the recommended workup includes testing for conditions discussed in the section above such as viral hepatitis, AIH, Wilson’s disease, and others. If negative, ESPGHAN states that a liver biopsy should be “considered.”

The question of whether or not to obtain a liver biopsy is controversial, though there are several clear advantages to doing so. First, biopsy is the gold standard test for diagnosing NAFLD and there are no highly accurate, noninvasive tests currently approved for use in children. Second, biopsy is a more definitive means of ruling out competing diagnoses such as AIH. Third, biopsy may provide prognostic data. In a retrospective adult study of 136 patients, for example, those who presented with simple steatosis had a roughly 3% chance of progressing to cirrhosis within 10 years. If a patient within this cohort presented with NASH, however, the progression risk was approximately 30% within 5 years [42,43]. Fourth, due to potential side effects of medications, position papers recommend obtaining a liver biopsy prior to the initiation of pharmacotherapy [37]. Lastly, the risk for serious morbidity from a liver biopsy is low [44,45]. Alternatively, one must acknowledge the risks of liver biopsy: morbidity, sampling bias, invasiveness, cost, and sedation risks in children.

Our suggested approach to these patients is shown in the Figure. Specifically, for older, asymptomatic, overweight or obese children with a mildly elevated ALT and normal direct bilirubin level, we believe that a trial of lifesyle modification can be safely initated prior to initiation of extensive laboratory testing or referral for biopsy. With that said, for children with any of the other “red flags” listed in the Table, early referral to an expert should be strongly considered.

 

Case Continued: Biopsy Results

You refer your patients to a gastroenterologist. Tests for viral hepatitis, A1A deficiency, celiac disease, muscle disorders, Wilson’s disease, and AIH are negative. Ultimately, a liver biopsy is performed on all 3 children without complications. The results are presented below.

• What is the treatment of NAFLD?

Lifestyle Modification

Lifestyle modifications are the mainstay of treatment for NAFLD. In adult studies, weight loss of more than 5% reduces hepatic steatosis whereas weight loss of more than 9% improves or eliminates NASH [47]. We recommend that children engage in age-appropriate, enjoyable, moderate- or vigorous-intensity aerobic activity for 60 minutes a day [48]. In addition, there should be a focus on reducing sedentary behavior by limiting screen time and a concerted effort to engage the family in lifestyle modifications.

Dietary interventions to treat NAFLD are less concrete but there is a growing body of literature to suggest that dietary fructose is particularly harmful. In adults, for example, fructose consumption is associated with the development of NAFLD [49] and hepatic fibrosis [50]. Recent data in adolescents has similarly documented an association between NAFLD incidence and energy-adjusted fructose intake [51]. It is worth highlighting that these clinical findings are also biologically plausible, as fructose is primarily metabolized within hepatocytes and has recently been shown to increase de novo lipogenesis [52,53]. In general, we suggest a well-balanced diet of unprocessed foods—that is, with limited added sugars—sufficient to induce gradual weight loss in older children or body weight maintenance in younger children.

Medications

Vitamin E is the only medication with proven efficacy in children, as demonstrated in the TONIC trial [20]. TONIC was a double-blind, multicenter, placebo-controlled study with 3 treatment arms: 800 IU of vitamin E daily, 1000 mg of metformin daily, or placebo. Metformin did not reduce the serum ALT or significantly improve liver histology and should therefore not be used for these indications. However, patients treated with vitamin E had a statistically significant improvement in the NAFLD activity score (a histologic grading system comprising steatosis, inflammation, and hepatocyte ballooning) and resolution of NASH when compared to placebo. For these reasons—as well as a paucity of other viable treatment options—vitamin E is routinely prescribed for children with biopsy-proven NASH. However, the long- term risks of high-dose vitamin E therapy in children are largely unknown.

Polyunsaturated fats such as docosahexaenoic acid (DHA) [54] and probiotics such as VSL #3 [55] have showed efficacy reducing hepatic steatosis in small, randomized clinical trials. Both medications need to be further validated before they can be recommended for use in children. Conversely, ursodeoxycholic acid has not been found to be efficacious in children with NAFLD [56], whereas phase IIb data on cysteamine is expected soon. There are currently insufficient data to recommend bariatric surgery as treatment for NAFLD in adolescence.

Case Continued: Follow-up

After their biopsies, both patients with NASH (patients A and B) are started on vitamin E therapy. All 3 patients continue to report for follow-up visits without short-term complications, though they have still been unable to significantly reduce their body mass index and have a persistently elevated serum ALT.

Summary

NAFLD is a common condition in the United States with serious personal and public health ramifications. This case-based review highlights the diagnostic and management challenges in children with NAFLD and the unique role primary care providers play in caring for these patients.

 

Corresponding author: Bryan Rudolph, MD, Albert Einstein College of Medicine, Division of Pediatric Gastroenterology and Nutrition, Children’s Hospital at Montefiore, 3415 Bainbridge Ave., Bronx, NY 10467, [email protected].

Financial disclosures: None.

From the Albert Einstein College of Medicine, Division of Pediatric Gastroenterology and Nutrition, Children’s Hospital at Montefiore, Bronx, NY.

 

Abstract

• Objective: To review diagnostic challenges and management strategies in children with nonalcoholic fatty liver disease (NAFLD).
• Methods: Review of the literaure.
• Results: NAFLD is common in the United States and should be suspected in overweight or obese children with an elevated serum alanine aminotransferase level. The differential diagnosis for these patients is broad, however, and liver biopsy—the gold standard test—should be undertaken selectively after an appropriate workup. Patients should be counseled on lifestyle modifications, whereas vitamin E therapy can be initiated for those with biopsy-proven disease.
• Conclusion: Providers should have a high degree of suspicion for NAFLD, approaching the workup and diagnosis in an incremental, step-wise fashion. Further research is needed to standardize the diagnostic approach, identify reliable, noninvasive diagnostic measures, and develop novel treatment modalities.

 

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, affecting approximately 10% of children and a third of all adults in the United States [1–3]. It is a significant public health challenge and is estimated to soon be the number one indication for liver transplantation in adults.

NAFLD is a generic term encompassing 2 distinct conditions defined by their histopathology: simple steatosis and nonalcoholic steatohepatitis (NASH). Simple steatosis is characterized by predominantly macrovesicular—meaning large droplet—cytoplasmic lipid inclusions found in ≥ 5% of hepatocytes. NASH is defined as hepatic steatosis plus the additional features of inflammation, hepatocyte ballooning, and/or fibrosis. There are some adult data [4-6] and 1 retrospective pediatric study [7] demonstrating that over time, NAFLD may progress. That is, steatosis may progress to NASH and some patients with fibrosis will ultimately develop cirrhosis. If intervention is provided early in the histologic spectrum, NAFLD can be reversed [4,8] and late complications—such as cirrhosis, hepatocellular carcinoma, or liver transplantation—may be prevented.

It is important to highlight that the above definitions are based on histology and that a liver biopsy cannot be reasonably obtained in such a large percentage of the U.S. population. This case-based review will therefore focus primarily on the current diagnostic challenges facing health care providers as well as management strategies in children with presumed NAFLD.

 

Case Study

Initial Presentation

As you finish your charts at the end of a busy clinic day, you identify 3 patients who may have NAFLD:

 

 

History

All 3 patients presented to your office for a routine annual physical before the start of the school year and are asymptomatic. None of the patients has a family history of liver disease and their previously diagnosed comorbidities are listed in the table above. No patient is taking medications other than patient C, who is on metformin.

All 3 children have a smooth, velvety rash on their necks consistent with acanthosis nigricans with an otherwise normal physical exam. The liver and spleen are difficult to palpate but are seemingly normal.

• What is the typical presentation for a child with NAFLD?

Most children with NAFLD are asymptomatic, though some may present with vague right upper quadrant abdominal pain. It is unclear, however, if the pain is caused by NAFLD or is rather an unrelated symptom that brings the child to the attention of a physician. In addition, hepatomegaly can be found in over 30% to 40% of patients [9]. For children without abdominal pain or hepatomegaly, most are recognized by an elevated serum alanine aminotransferase (ALT) or findings of increased liver echogenicity on ultrasonography.

Serum Alanine Aminotransferase

Serum aminotransferases are one of the more common screening tests for NAFLD. However, ALT is highly insensitive at commonly used thresholds and is also nonspecific. As documented in the SAFETY study, the upper limit of normal for ALT in healthy children should be set around 25 U/L in boys and 22 U/L in girls [10]. Yet even at these thresholds, the sensitivity of ALT to diagnose NAFLD is 80% in boys and 92% in girls, whereas specificity is 79% and 85%, respectively [10]. These findings are largely consistent with adult studies [11–14]. Furthermore, ALT does not correlate well with disease severity and children may still have NASH or significant fibrosis with normal values. In a well-characterized cohort of 91 children with biopsy-proven NAFLD, for example, early fibrosis was identified in 12% of children with a normal ALT (≤ 22 U/L for girls and ≤ 25 U/L in boys) [15]. Advanced fibrosis or cirrhosis was seen in 9% of children with an ALT up to 2 times this upper limit [15]. Thus, reliance on the serum ALT may significantly underestimate the prevalence and severity of liver injury.

Ultrasonography

Children with NAFLD typically have findings of increased hepatic echogenicity on abdominal ultrasonography. However, there are multiple limitations to sonography. First, ultrasound is insensitive for identifying mild steatosis if less than 30% of hepatocytes are affected [16,17]. Second, increased hepatic echogenicity is nonspecific and may be caused by inflammation, fibrosis, or intrahepatic accumulation of iron, copper, or glycogen. Third, there can be considerable inter- and intra-operator variability. And lastly, there is some evidence that ultrasounds do not add benefit to diagnosing children with NAFLD [18].

• Which patients are at risk for developing hepatic steatosis and NASH?

Weight, Age, and Gender

There is a strong, direct correlation between body mass index (BMI) and NAFLD. The Study of Child and Adolescent Liver Epidemiology (SCALE)—a sentinel pediatric autopsy study of 742 children—found that 5% of normal weight children, 16% of overweight children, and 38% of obese children had NAFLD. The SCALE study also demonstrated an increasing prevalence with age, such that NAFLD was present in 17.3% of 15- to 19-year-olds but only in 0.2% of 2- to 4-year-olds [1]. With regards to gender, NAFLD is roughly twice as prevalent in males [18–20]. While the exact etiology of this difference is unclear, hormonal differences are a leading hypothesis.

 

Ethnicity

NAFLD is most common in Hispanics, followed by Asians, Caucasians, and African Americans. Research suggests that genetics may be largely responsible for these ethnic disparities. For example, the I148M allele of PNPLA3 (a single nucleotide polymorphism) is strongly associated with steatosis, NASH, and fibrosis [21] and is most common in Hispanics, with a 50% carrier frequency in some cohorts [22]. Conversely, African Americans are more likely to carry the S453I allele of PNPLA3, which is associated with decreased hepatic steatosis [22]. There is also considerable variability within ethnic groups. For example, Mexican-American children appear to be at the highest risk for steatosis or NASH among Hispanics, whereas Filipino-American children are believed to have higher disease prevalence than Cambodian or Vietnamese Americans [1].

Comorbidities

NAFLD is associated with obesity, insulin resistance and diabetes, cardiovascular disease, the metabolic syndrome [23], decreased quality of life [24,25], and obstructive sleep apnea (OSA). These associations generally hold even after controlling for the other confounders listed. It is important to note that these data come largely from cross-sectional studies and direct causation has yet to be determined.

Insulin resistance in particular is strongly associated with NAFLD—so much so, in fact, that some consider it to be the hepatic manifestation of the metabolic syndrome. Additionally, children with features of the metabolic syndrome are more likely to have advanced histologic features of NAFLD [23]. There are also intriguing data from small pediatric studies to suggest that OSA may contribute to the development of hepatic fibrosis. In one study of 25 children with biopsy-proven NAFLD, for example, the presence of OSA and hypoxemia correlated with the degree of hepatic fibrosis [26]. In a slightly larger study of 65 children, OSA was also strongly associated with significant hepatic fibrosis (odds ratio, 5.91; 95% confidence interval, 3.23–7.42; P < 0.001). The duration of hypoxemia also correlated with histologic findings of inflammation and circulating biomarkers of apoptosis and fibrogenesis [27].

Other Laboratory Tests

Several studies have documented an association between elevated gamma-glutamyl transferase (GGT) and hepatic fibrosis [28,29], though others have been conflicting [30,31]. Pediatric studies have also demonstrated an inverse correlation between NASH and total bilirubin [32], serum potassium [33], and serum ceruloplasmin [34]. In addition, there are a number of serum biomarkers or biomarker panels commercially available for use in adults. Because similar efficacy data are unavailable in children, however, serum biomarkers should be primarily used for research purposes only.

• Who should be screened for NAFLD? And how?

Published professional society recommendations differ significantly with regards to screening. In 2007, the American Academy of Pediatrics suggested screening obese children over 10 years of age or overweight children with additional risk factors with biannual liver tests [35]. There were no management recommendations made for elevated aminotransferase levels other than for subspecialty referral. In 2012, the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) recommended obtaining an ultrasound and liver tests in every obese child [36]. One month later, however, the American Gastroenterological Association, American Association for the Study of Liver Disease, and the American College of Gastroenterology published joint guidelines without screening recommendations “due to a paucity of evidence” [37].

Because these statements conflict and are based heavily on expert opinion, one should consider the risks, benefits, and costs to screening large numbers of patients. Until additional research clarifies this controversy, we suggest that providers individualize their screening practices to their population and the risks of each individual patient. For example, we would consider screening children who are obese; Hispanic or Asian; have multiple features of the metabolic syndrome; and/or those who have a family history of NAFLD. Further, we recommend screening children for NAFLD with serum liver enzymes only and not with ultrasonography.

Case Continued: Laboratory Results

ALT and GGT tests are ordered and the results are as follows:

• What is the differential for children with suspected NAFLD?

 

The differential for NAFLD is remarkably broad and includes any condition that could lead to an elevated ALT or hepatic steatosis. Several of the more common etiologies in the differential are listed in the proceeding section. A list of “red flags” is shown in the Table and, if any are present, should alert the practitioner to the possible presence of alternative disease.

Autoimmune Hepatitis (AIH)

AIH is a progressive necro-inflammatory disorder of the liver characterized by elevated aminotransferases, positive autoantibodies, and distinctive histologic features. AIH is believed to occur in genetically predisposed patients in response to an environmental trigger. There is a female predominance and it can present in any age or ethnic group.

AIH is divided in 2 subtypes. Type 1 disease is characterized by a positive antinuclear (ANA) antibody and anti-smooth muscle antibody. More commonly, it presents in adolescence with an indolent course—many patients are asymptomatic until they develop features of cirrhosis and portal hypertension. Conversely, type 2 AIH is characterized by a positive liver kidney microsomal (LKM) antibody and tends to present acutely in young children. It is important to note that antibody titers can be falsely positive in a significant percentage of patients and, in such cases, are often mildly elevated [38]. We strongly suggest children with positive autoantibody titers be evaluated by a specialist.

Treatment should be started promptly to avoid progression to cirrhosis and should also done so in consultation with a pediatric gastroenterologist or hepatologist. The prognosis of AIH with immunosuppression is favorable, with long-term remission rates of approximately 80%. Transplantation is typically required in the remaining 10% to 20% [39].

Celiac Disease

Celiac disease is an autoimmune, inflammatory enteropathy caused by exposure to gluten in genetically susceptible individuals. Up to a third of all children presenting with celiac will have an elevated serum ALT [40]. Additional symptoms/features are both variable and nonspecific: abdominal pain, poor growth, diarrhea, or constipation, among others. Celiac is diagnosed by duodenal biopsy or a sufficiently elevated tissue transglutaminase antibody level [41]. Treatment with a strict gluten-free diet will resolve the enteropathy and normalize the serum aminotransferases.

Wilson’s Disease

Wilson’s disease is a metabolic disorder leading to copper deposition in the liver, brain, cornea, and kidneys. It is caused by an ATP7B gene mutation and inherited in an autosomal recessive fashion. Patients may present with asymptomatic liver disease, chronic hepatitis, acute liver failure, or with symptoms of portal hypertension. Neuropsychiatric symptoms may also be prominent. Screening tests include a serum ceruloplasmin and 24-hour urinary copper quantification. Because diagnosing Wilson’s disease can be challenging, however, further testing should occur in consultation with a pediatric gastroenterologist or hepatologist.

Viral Hepatitis

Chronic viral infections such as hepatitis B and C are still common etiologies of liver disease in the United States. However, universal vaccination and blood donor screening have reduced the risk of transmission; new antiviral agents will likely further decrease the prevalence and transmission risk over time. Acute viral hepatitis—cytomegalovirus, Epstein-Barr virus, hepatitis A, or hepatitis E—should also be considered in children who present with appropriate symptoms and an elevated ALT.

Drug-Induced

Drug-induced liver injury (DILI) can present with elevated serum aminotransferases (hepatocellular pattern), an elevated bilirubin (cholestatic pattern), or a mixed picture. Idiosyncratic DILI in children is commonly caused by antimicrobial or central nervous system agents and usually presents with a hepatocellular injury pattern. Substance abuse, including alcohol, is common and should also be investigated as the source of underlying liver disease.

Muscle Disease

Aspartate aminotransferase (AST) and ALT are present in hepatocytes, myocytes, and red blood cells, among other tissues. Thus, children with congenital myopathies or myositis can have elevated aminotransferases, typically with the AST higher than the ALT. In these patients, checking a creatine phosphokinase (CPK) level may lead to the correct diagnosis and limit unnecessary testing.

Other Metabolic Disorders

Myriad metabolic disorders present with liver disease and/or elevated serum aminotransferase levels. Individually, these conditions are rare but, collectively, are relatively common. Two of the more occult conditions—lysosomal acid lipase deficiency (LAL-D) and alpha-1 antitrypsin (A1A) deficiency—are discussed in further detail below.

LAL-D is an autosomal recessive disease resulting in the accumulation of cholesterol esters and triglycerides in lysosomes. Patients typically present with hepatomegaly and mildly elevated aminotransferases, an elevated LDL, low HDL cholesterol, and increased hepatic echogenicity on ultrasound. If a biopsy is obtained, microvesicular steatosis is predominant as opposed to macrovesicular steatosis found in NAFLD. The diagnosis of LAL-D can be made on a commercially available dry blood spot enzymatic assay or genetic testing and treatment has recently been FDA approved.

A1A deficiency is an autosomal recessive disease diagnosable by an alpha-1-antitrypsin phenotype. The clinical presentation is characterized by neonatal cholestasis in the infantile form and by hepatitis, cirrhosis and portal hypertension in older children. Classic symptoms of emphysema and chronic lung disease present in adulthood.

• What further testing should be performed in children with suspected NAFLD?

For obese children with an elevated ALT or evidence of increased hepatic echogenicity, ESPGHAN recommends targeting the workup according to the child’s age [36]. According to their consensus statement, they recommend an upfront, thorough laboratory evaluation in children less than 10 years of age and consideration of a liver biopsy upon completion. For children over 10 years of age at low risk for NASH or fibrosis, additional laboratory evaluation is suggested 3 to 6 months after failed lifestyle interventions. In general, the recommended workup includes testing for conditions discussed in the section above such as viral hepatitis, AIH, Wilson’s disease, and others. If negative, ESPGHAN states that a liver biopsy should be “considered.”

The question of whether or not to obtain a liver biopsy is controversial, though there are several clear advantages to doing so. First, biopsy is the gold standard test for diagnosing NAFLD and there are no highly accurate, noninvasive tests currently approved for use in children. Second, biopsy is a more definitive means of ruling out competing diagnoses such as AIH. Third, biopsy may provide prognostic data. In a retrospective adult study of 136 patients, for example, those who presented with simple steatosis had a roughly 3% chance of progressing to cirrhosis within 10 years. If a patient within this cohort presented with NASH, however, the progression risk was approximately 30% within 5 years [42,43]. Fourth, due to potential side effects of medications, position papers recommend obtaining a liver biopsy prior to the initiation of pharmacotherapy [37]. Lastly, the risk for serious morbidity from a liver biopsy is low [44,45]. Alternatively, one must acknowledge the risks of liver biopsy: morbidity, sampling bias, invasiveness, cost, and sedation risks in children.

Our suggested approach to these patients is shown in the Figure. Specifically, for older, asymptomatic, overweight or obese children with a mildly elevated ALT and normal direct bilirubin level, we believe that a trial of lifesyle modification can be safely initated prior to initiation of extensive laboratory testing or referral for biopsy. With that said, for children with any of the other “red flags” listed in the Table, early referral to an expert should be strongly considered.

 

Case Continued: Biopsy Results

You refer your patients to a gastroenterologist. Tests for viral hepatitis, A1A deficiency, celiac disease, muscle disorders, Wilson’s disease, and AIH are negative. Ultimately, a liver biopsy is performed on all 3 children without complications. The results are presented below.

• What is the treatment of NAFLD?

Lifestyle Modification

Lifestyle modifications are the mainstay of treatment for NAFLD. In adult studies, weight loss of more than 5% reduces hepatic steatosis whereas weight loss of more than 9% improves or eliminates NASH [47]. We recommend that children engage in age-appropriate, enjoyable, moderate- or vigorous-intensity aerobic activity for 60 minutes a day [48]. In addition, there should be a focus on reducing sedentary behavior by limiting screen time and a concerted effort to engage the family in lifestyle modifications.

Dietary interventions to treat NAFLD are less concrete but there is a growing body of literature to suggest that dietary fructose is particularly harmful. In adults, for example, fructose consumption is associated with the development of NAFLD [49] and hepatic fibrosis [50]. Recent data in adolescents has similarly documented an association between NAFLD incidence and energy-adjusted fructose intake [51]. It is worth highlighting that these clinical findings are also biologically plausible, as fructose is primarily metabolized within hepatocytes and has recently been shown to increase de novo lipogenesis [52,53]. In general, we suggest a well-balanced diet of unprocessed foods—that is, with limited added sugars—sufficient to induce gradual weight loss in older children or body weight maintenance in younger children.

Medications

Vitamin E is the only medication with proven efficacy in children, as demonstrated in the TONIC trial [20]. TONIC was a double-blind, multicenter, placebo-controlled study with 3 treatment arms: 800 IU of vitamin E daily, 1000 mg of metformin daily, or placebo. Metformin did not reduce the serum ALT or significantly improve liver histology and should therefore not be used for these indications. However, patients treated with vitamin E had a statistically significant improvement in the NAFLD activity score (a histologic grading system comprising steatosis, inflammation, and hepatocyte ballooning) and resolution of NASH when compared to placebo. For these reasons—as well as a paucity of other viable treatment options—vitamin E is routinely prescribed for children with biopsy-proven NASH. However, the long- term risks of high-dose vitamin E therapy in children are largely unknown.

Polyunsaturated fats such as docosahexaenoic acid (DHA) [54] and probiotics such as VSL #3 [55] have showed efficacy reducing hepatic steatosis in small, randomized clinical trials. Both medications need to be further validated before they can be recommended for use in children. Conversely, ursodeoxycholic acid has not been found to be efficacious in children with NAFLD [56], whereas phase IIb data on cysteamine is expected soon. There are currently insufficient data to recommend bariatric surgery as treatment for NAFLD in adolescence.

Case Continued: Follow-up

After their biopsies, both patients with NASH (patients A and B) are started on vitamin E therapy. All 3 patients continue to report for follow-up visits without short-term complications, though they have still been unable to significantly reduce their body mass index and have a persistently elevated serum ALT.

Summary

NAFLD is a common condition in the United States with serious personal and public health ramifications. This case-based review highlights the diagnostic and management challenges in children with NAFLD and the unique role primary care providers play in caring for these patients.

 

Corresponding author: Bryan Rudolph, MD, Albert Einstein College of Medicine, Division of Pediatric Gastroenterology and Nutrition, Children’s Hospital at Montefiore, 3415 Bainbridge Ave., Bronx, NY 10467, [email protected].

Financial disclosures: None.

From the Albert Einstein College of Medicine, Division of Pediatric Gastroenterology and Nutrition, Children’s Hospital at Montefiore, Bronx, NY.

 

Abstract

• Objective: To review diagnostic challenges and management strategies in children with nonalcoholic fatty liver disease (NAFLD).
• Methods: Review of the literaure.
• Results: NAFLD is common in the United States and should be suspected in overweight or obese children with an elevated serum alanine aminotransferase level. The differential diagnosis for these patients is broad, however, and liver biopsy—the gold standard test—should be undertaken selectively after an appropriate workup. Patients should be counseled on lifestyle modifications, whereas vitamin E therapy can be initiated for those with biopsy-proven disease.
• Conclusion: Providers should have a high degree of suspicion for NAFLD, approaching the workup and diagnosis in an incremental, step-wise fashion. Further research is needed to standardize the diagnostic approach, identify reliable, noninvasive diagnostic measures, and develop novel treatment modalities.

 

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, affecting approximately 10% of children and a third of all adults in the United States [1–3]. It is a significant public health challenge and is estimated to soon be the number one indication for liver transplantation in adults.

NAFLD is a generic term encompassing 2 distinct conditions defined by their histopathology: simple steatosis and nonalcoholic steatohepatitis (NASH). Simple steatosis is characterized by predominantly macrovesicular—meaning large droplet—cytoplasmic lipid inclusions found in ≥ 5% of hepatocytes. NASH is defined as hepatic steatosis plus the additional features of inflammation, hepatocyte ballooning, and/or fibrosis. There are some adult data [4-6] and 1 retrospective pediatric study [7] demonstrating that over time, NAFLD may progress. That is, steatosis may progress to NASH and some patients with fibrosis will ultimately develop cirrhosis. If intervention is provided early in the histologic spectrum, NAFLD can be reversed [4,8] and late complications—such as cirrhosis, hepatocellular carcinoma, or liver transplantation—may be prevented.

It is important to highlight that the above definitions are based on histology and that a liver biopsy cannot be reasonably obtained in such a large percentage of the U.S. population. This case-based review will therefore focus primarily on the current diagnostic challenges facing health care providers as well as management strategies in children with presumed NAFLD.

 

Case Study

Initial Presentation

As you finish your charts at the end of a busy clinic day, you identify 3 patients who may have NAFLD:

 

 

History

All 3 patients presented to your office for a routine annual physical before the start of the school year and are asymptomatic. None of the patients has a family history of liver disease and their previously diagnosed comorbidities are listed in the table above. No patient is taking medications other than patient C, who is on metformin.

All 3 children have a smooth, velvety rash on their necks consistent with acanthosis nigricans with an otherwise normal physical exam. The liver and spleen are difficult to palpate but are seemingly normal.

• What is the typical presentation for a child with NAFLD?

Most children with NAFLD are asymptomatic, though some may present with vague right upper quadrant abdominal pain. It is unclear, however, if the pain is caused by NAFLD or is rather an unrelated symptom that brings the child to the attention of a physician. In addition, hepatomegaly can be found in over 30% to 40% of patients [9]. For children without abdominal pain or hepatomegaly, most are recognized by an elevated serum alanine aminotransferase (ALT) or findings of increased liver echogenicity on ultrasonography.

Serum Alanine Aminotransferase

Serum aminotransferases are one of the more common screening tests for NAFLD. However, ALT is highly insensitive at commonly used thresholds and is also nonspecific. As documented in the SAFETY study, the upper limit of normal for ALT in healthy children should be set around 25 U/L in boys and 22 U/L in girls [10]. Yet even at these thresholds, the sensitivity of ALT to diagnose NAFLD is 80% in boys and 92% in girls, whereas specificity is 79% and 85%, respectively [10]. These findings are largely consistent with adult studies [11–14]. Furthermore, ALT does not correlate well with disease severity and children may still have NASH or significant fibrosis with normal values. In a well-characterized cohort of 91 children with biopsy-proven NAFLD, for example, early fibrosis was identified in 12% of children with a normal ALT (≤ 22 U/L for girls and ≤ 25 U/L in boys) [15]. Advanced fibrosis or cirrhosis was seen in 9% of children with an ALT up to 2 times this upper limit [15]. Thus, reliance on the serum ALT may significantly underestimate the prevalence and severity of liver injury.

Ultrasonography

Children with NAFLD typically have findings of increased hepatic echogenicity on abdominal ultrasonography. However, there are multiple limitations to sonography. First, ultrasound is insensitive for identifying mild steatosis if less than 30% of hepatocytes are affected [16,17]. Second, increased hepatic echogenicity is nonspecific and may be caused by inflammation, fibrosis, or intrahepatic accumulation of iron, copper, or glycogen. Third, there can be considerable inter- and intra-operator variability. And lastly, there is some evidence that ultrasounds do not add benefit to diagnosing children with NAFLD [18].

• Which patients are at risk for developing hepatic steatosis and NASH?

Weight, Age, and Gender

There is a strong, direct correlation between body mass index (BMI) and NAFLD. The Study of Child and Adolescent Liver Epidemiology (SCALE)—a sentinel pediatric autopsy study of 742 children—found that 5% of normal weight children, 16% of overweight children, and 38% of obese children had NAFLD. The SCALE study also demonstrated an increasing prevalence with age, such that NAFLD was present in 17.3% of 15- to 19-year-olds but only in 0.2% of 2- to 4-year-olds [1]. With regards to gender, NAFLD is roughly twice as prevalent in males [18–20]. While the exact etiology of this difference is unclear, hormonal differences are a leading hypothesis.

 

Ethnicity

NAFLD is most common in Hispanics, followed by Asians, Caucasians, and African Americans. Research suggests that genetics may be largely responsible for these ethnic disparities. For example, the I148M allele of PNPLA3 (a single nucleotide polymorphism) is strongly associated with steatosis, NASH, and fibrosis [21] and is most common in Hispanics, with a 50% carrier frequency in some cohorts [22]. Conversely, African Americans are more likely to carry the S453I allele of PNPLA3, which is associated with decreased hepatic steatosis [22]. There is also considerable variability within ethnic groups. For example, Mexican-American children appear to be at the highest risk for steatosis or NASH among Hispanics, whereas Filipino-American children are believed to have higher disease prevalence than Cambodian or Vietnamese Americans [1].

Comorbidities

NAFLD is associated with obesity, insulin resistance and diabetes, cardiovascular disease, the metabolic syndrome [23], decreased quality of life [24,25], and obstructive sleep apnea (OSA). These associations generally hold even after controlling for the other confounders listed. It is important to note that these data come largely from cross-sectional studies and direct causation has yet to be determined.

Insulin resistance in particular is strongly associated with NAFLD—so much so, in fact, that some consider it to be the hepatic manifestation of the metabolic syndrome. Additionally, children with features of the metabolic syndrome are more likely to have advanced histologic features of NAFLD [23]. There are also intriguing data from small pediatric studies to suggest that OSA may contribute to the development of hepatic fibrosis. In one study of 25 children with biopsy-proven NAFLD, for example, the presence of OSA and hypoxemia correlated with the degree of hepatic fibrosis [26]. In a slightly larger study of 65 children, OSA was also strongly associated with significant hepatic fibrosis (odds ratio, 5.91; 95% confidence interval, 3.23–7.42; P < 0.001). The duration of hypoxemia also correlated with histologic findings of inflammation and circulating biomarkers of apoptosis and fibrogenesis [27].

Other Laboratory Tests

Several studies have documented an association between elevated gamma-glutamyl transferase (GGT) and hepatic fibrosis [28,29], though others have been conflicting [30,31]. Pediatric studies have also demonstrated an inverse correlation between NASH and total bilirubin [32], serum potassium [33], and serum ceruloplasmin [34]. In addition, there are a number of serum biomarkers or biomarker panels commercially available for use in adults. Because similar efficacy data are unavailable in children, however, serum biomarkers should be primarily used for research purposes only.

• Who should be screened for NAFLD? And how?

Published professional society recommendations differ significantly with regards to screening. In 2007, the American Academy of Pediatrics suggested screening obese children over 10 years of age or overweight children with additional risk factors with biannual liver tests [35]. There were no management recommendations made for elevated aminotransferase levels other than for subspecialty referral. In 2012, the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) recommended obtaining an ultrasound and liver tests in every obese child [36]. One month later, however, the American Gastroenterological Association, American Association for the Study of Liver Disease, and the American College of Gastroenterology published joint guidelines without screening recommendations “due to a paucity of evidence” [37].

Because these statements conflict and are based heavily on expert opinion, one should consider the risks, benefits, and costs to screening large numbers of patients. Until additional research clarifies this controversy, we suggest that providers individualize their screening practices to their population and the risks of each individual patient. For example, we would consider screening children who are obese; Hispanic or Asian; have multiple features of the metabolic syndrome; and/or those who have a family history of NAFLD. Further, we recommend screening children for NAFLD with serum liver enzymes only and not with ultrasonography.

Case Continued: Laboratory Results

ALT and GGT tests are ordered and the results are as follows:

• What is the differential for children with suspected NAFLD?

 

The differential for NAFLD is remarkably broad and includes any condition that could lead to an elevated ALT or hepatic steatosis. Several of the more common etiologies in the differential are listed in the proceeding section. A list of “red flags” is shown in the Table and, if any are present, should alert the practitioner to the possible presence of alternative disease.

Autoimmune Hepatitis (AIH)

AIH is a progressive necro-inflammatory disorder of the liver characterized by elevated aminotransferases, positive autoantibodies, and distinctive histologic features. AIH is believed to occur in genetically predisposed patients in response to an environmental trigger. There is a female predominance and it can present in any age or ethnic group.

AIH is divided in 2 subtypes. Type 1 disease is characterized by a positive antinuclear (ANA) antibody and anti-smooth muscle antibody. More commonly, it presents in adolescence with an indolent course—many patients are asymptomatic until they develop features of cirrhosis and portal hypertension. Conversely, type 2 AIH is characterized by a positive liver kidney microsomal (LKM) antibody and tends to present acutely in young children. It is important to note that antibody titers can be falsely positive in a significant percentage of patients and, in such cases, are often mildly elevated [38]. We strongly suggest children with positive autoantibody titers be evaluated by a specialist.

Treatment should be started promptly to avoid progression to cirrhosis and should also done so in consultation with a pediatric gastroenterologist or hepatologist. The prognosis of AIH with immunosuppression is favorable, with long-term remission rates of approximately 80%. Transplantation is typically required in the remaining 10% to 20% [39].

Celiac Disease

Celiac disease is an autoimmune, inflammatory enteropathy caused by exposure to gluten in genetically susceptible individuals. Up to a third of all children presenting with celiac will have an elevated serum ALT [40]. Additional symptoms/features are both variable and nonspecific: abdominal pain, poor growth, diarrhea, or constipation, among others. Celiac is diagnosed by duodenal biopsy or a sufficiently elevated tissue transglutaminase antibody level [41]. Treatment with a strict gluten-free diet will resolve the enteropathy and normalize the serum aminotransferases.

Wilson’s Disease

Wilson’s disease is a metabolic disorder leading to copper deposition in the liver, brain, cornea, and kidneys. It is caused by an ATP7B gene mutation and inherited in an autosomal recessive fashion. Patients may present with asymptomatic liver disease, chronic hepatitis, acute liver failure, or with symptoms of portal hypertension. Neuropsychiatric symptoms may also be prominent. Screening tests include a serum ceruloplasmin and 24-hour urinary copper quantification. Because diagnosing Wilson’s disease can be challenging, however, further testing should occur in consultation with a pediatric gastroenterologist or hepatologist.

Viral Hepatitis

Chronic viral infections such as hepatitis B and C are still common etiologies of liver disease in the United States. However, universal vaccination and blood donor screening have reduced the risk of transmission; new antiviral agents will likely further decrease the prevalence and transmission risk over time. Acute viral hepatitis—cytomegalovirus, Epstein-Barr virus, hepatitis A, or hepatitis E—should also be considered in children who present with appropriate symptoms and an elevated ALT.

Drug-Induced

Drug-induced liver injury (DILI) can present with elevated serum aminotransferases (hepatocellular pattern), an elevated bilirubin (cholestatic pattern), or a mixed picture. Idiosyncratic DILI in children is commonly caused by antimicrobial or central nervous system agents and usually presents with a hepatocellular injury pattern. Substance abuse, including alcohol, is common and should also be investigated as the source of underlying liver disease.

Muscle Disease

Aspartate aminotransferase (AST) and ALT are present in hepatocytes, myocytes, and red blood cells, among other tissues. Thus, children with congenital myopathies or myositis can have elevated aminotransferases, typically with the AST higher than the ALT. In these patients, checking a creatine phosphokinase (CPK) level may lead to the correct diagnosis and limit unnecessary testing.

Other Metabolic Disorders

Myriad metabolic disorders present with liver disease and/or elevated serum aminotransferase levels. Individually, these conditions are rare but, collectively, are relatively common. Two of the more occult conditions—lysosomal acid lipase deficiency (LAL-D) and alpha-1 antitrypsin (A1A) deficiency—are discussed in further detail below.

LAL-D is an autosomal recessive disease resulting in the accumulation of cholesterol esters and triglycerides in lysosomes. Patients typically present with hepatomegaly and mildly elevated aminotransferases, an elevated LDL, low HDL cholesterol, and increased hepatic echogenicity on ultrasound. If a biopsy is obtained, microvesicular steatosis is predominant as opposed to macrovesicular steatosis found in NAFLD. The diagnosis of LAL-D can be made on a commercially available dry blood spot enzymatic assay or genetic testing and treatment has recently been FDA approved.

A1A deficiency is an autosomal recessive disease diagnosable by an alpha-1-antitrypsin phenotype. The clinical presentation is characterized by neonatal cholestasis in the infantile form and by hepatitis, cirrhosis and portal hypertension in older children. Classic symptoms of emphysema and chronic lung disease present in adulthood.

• What further testing should be performed in children with suspected NAFLD?

For obese children with an elevated ALT or evidence of increased hepatic echogenicity, ESPGHAN recommends targeting the workup according to the child’s age [36]. According to their consensus statement, they recommend an upfront, thorough laboratory evaluation in children less than 10 years of age and consideration of a liver biopsy upon completion. For children over 10 years of age at low risk for NASH or fibrosis, additional laboratory evaluation is suggested 3 to 6 months after failed lifestyle interventions. In general, the recommended workup includes testing for conditions discussed in the section above such as viral hepatitis, AIH, Wilson’s disease, and others. If negative, ESPGHAN states that a liver biopsy should be “considered.”

The question of whether or not to obtain a liver biopsy is controversial, though there are several clear advantages to doing so. First, biopsy is the gold standard test for diagnosing NAFLD and there are no highly accurate, noninvasive tests currently approved for use in children. Second, biopsy is a more definitive means of ruling out competing diagnoses such as AIH. Third, biopsy may provide prognostic data. In a retrospective adult study of 136 patients, for example, those who presented with simple steatosis had a roughly 3% chance of progressing to cirrhosis within 10 years. If a patient within this cohort presented with NASH, however, the progression risk was approximately 30% within 5 years [42,43]. Fourth, due to potential side effects of medications, position papers recommend obtaining a liver biopsy prior to the initiation of pharmacotherapy [37]. Lastly, the risk for serious morbidity from a liver biopsy is low [44,45]. Alternatively, one must acknowledge the risks of liver biopsy: morbidity, sampling bias, invasiveness, cost, and sedation risks in children.

Our suggested approach to these patients is shown in the Figure. Specifically, for older, asymptomatic, overweight or obese children with a mildly elevated ALT and normal direct bilirubin level, we believe that a trial of lifesyle modification can be safely initated prior to initiation of extensive laboratory testing or referral for biopsy. With that said, for children with any of the other “red flags” listed in the Table, early referral to an expert should be strongly considered.

 

Case Continued: Biopsy Results

You refer your patients to a gastroenterologist. Tests for viral hepatitis, A1A deficiency, celiac disease, muscle disorders, Wilson’s disease, and AIH are negative. Ultimately, a liver biopsy is performed on all 3 children without complications. The results are presented below.

• What is the treatment of NAFLD?

Lifestyle Modification

Lifestyle modifications are the mainstay of treatment for NAFLD. In adult studies, weight loss of more than 5% reduces hepatic steatosis whereas weight loss of more than 9% improves or eliminates NASH [47]. We recommend that children engage in age-appropriate, enjoyable, moderate- or vigorous-intensity aerobic activity for 60 minutes a day [48]. In addition, there should be a focus on reducing sedentary behavior by limiting screen time and a concerted effort to engage the family in lifestyle modifications.

Dietary interventions to treat NAFLD are less concrete but there is a growing body of literature to suggest that dietary fructose is particularly harmful. In adults, for example, fructose consumption is associated with the development of NAFLD [49] and hepatic fibrosis [50]. Recent data in adolescents has similarly documented an association between NAFLD incidence and energy-adjusted fructose intake [51]. It is worth highlighting that these clinical findings are also biologically plausible, as fructose is primarily metabolized within hepatocytes and has recently been shown to increase de novo lipogenesis [52,53]. In general, we suggest a well-balanced diet of unprocessed foods—that is, with limited added sugars—sufficient to induce gradual weight loss in older children or body weight maintenance in younger children.

Medications

Vitamin E is the only medication with proven efficacy in children, as demonstrated in the TONIC trial [20]. TONIC was a double-blind, multicenter, placebo-controlled study with 3 treatment arms: 800 IU of vitamin E daily, 1000 mg of metformin daily, or placebo. Metformin did not reduce the serum ALT or significantly improve liver histology and should therefore not be used for these indications. However, patients treated with vitamin E had a statistically significant improvement in the NAFLD activity score (a histologic grading system comprising steatosis, inflammation, and hepatocyte ballooning) and resolution of NASH when compared to placebo. For these reasons—as well as a paucity of other viable treatment options—vitamin E is routinely prescribed for children with biopsy-proven NASH. However, the long- term risks of high-dose vitamin E therapy in children are largely unknown.

Polyunsaturated fats such as docosahexaenoic acid (DHA) [54] and probiotics such as VSL #3 [55] have showed efficacy reducing hepatic steatosis in small, randomized clinical trials. Both medications need to be further validated before they can be recommended for use in children. Conversely, ursodeoxycholic acid has not been found to be efficacious in children with NAFLD [56], whereas phase IIb data on cysteamine is expected soon. There are currently insufficient data to recommend bariatric surgery as treatment for NAFLD in adolescence.

Case Continued: Follow-up

After their biopsies, both patients with NASH (patients A and B) are started on vitamin E therapy. All 3 patients continue to report for follow-up visits without short-term complications, though they have still been unable to significantly reduce their body mass index and have a persistently elevated serum ALT.

Summary

NAFLD is a common condition in the United States with serious personal and public health ramifications. This case-based review highlights the diagnostic and management challenges in children with NAFLD and the unique role primary care providers play in caring for these patients.

 

Corresponding author: Bryan Rudolph, MD, Albert Einstein College of Medicine, Division of Pediatric Gastroenterology and Nutrition, Children’s Hospital at Montefiore, 3415 Bainbridge Ave., Bronx, NY 10467, [email protected].

Financial disclosures: None.

From the Johns Hopkins Bayview Medical Center, Baltimore, MD (Drs. Johnson, Knight, Maygers, and Zakaria), and Duke University Hospital, Durham, NC (Dr. Mock).

 

Abstract

• Objective: To determine patterns of telemetry use at a tertiary academic institution and identify factors contributing to noncompliance with guidelines regarding telemetry use.
• Methods: Web-based survey of 180 providers, including internal medicine residents and cardiovascular disease fellows, hospitalists, non-hospitalist teaching attending physicians, nurse practitioners, and physician assistants.
• Results: Of the 180 providers surveyed, 67 (37%) replied. Most providers (76%) were unaware of guidelines regarding appropriate telemetry use and 85% selected inappropriate diagnoses as warranting telemetry. Only 21% routinely discontinued the telemetry order within 48 hours.
• Conclusions: Many providers at a tertiary academic institution utilize continuous telemetry inappropriately and are unaware of telemetry guidelines. These findings should guide interventions to improve telemetry utilization.

 

For many decades, telemetry has been widely used in the management and monitoring of patients with possible acute coronary syndromes (ACS), arrhythmias, cardiac events, and strokes [1]. In addition, telemetry has often been used in other clinical scenarios with less rigorous data supporting its use [2–4]. As a result, in 2004 the American Heart Association (AHA) issued guidelines providing recommendations for best practices in hospital ECG monitoring. Indications for telemetry were classified into 3 diagnosis-driven groups: class I (indicated in all patients), class II (indicated in most patients, may be of benefit) and class III (not indicated, no therapeutic benefit) [2]. However, these recommendations have not been widely followed and telemetry is inappropriately used for many inpatients [5,6].

There are several reasons why clinicians fail to adhere to guidelines, including knowledge deficits, attitudes regarding the current guidelines, and institution-specific factors influencing practitioner behaviors [7]. In response to reports of widespread telemetry overuse, the Choosing Wisely Campaign of the American Board of Internal Medicine Foundation has championed judicious telemetry use, advocating evidence-based, protocol-driven telemetry management for patients not in intensive care units who do not meet guideline-based criteria for continuous telemetry [8].

In order to understand patterns of telemetry use at our academic institution and identify factors associated with this practice, we systematically analyzed telemetry use perceptions through provider surveys. We hypothesized that providers have misperceptions about appropriate use of telemetry and that this knowledge gap results in overuse of telemetry at our institution.

Methods

Setting

Johns Hopkins Bayview Medical Center is a 400-bed academic medical center serving southeastern Baltimore. Providers included internal medicine residents and cardiovascular disease fellows who rotate to the medical center and Johns Hopkins Hospital, hospitalists, non-hospitalist teaching attending physicians, nurse practitioners (NPs), and physician assistants (PAs).

Current Telemetry Practice

Remote telemetric monitoring is available in all adult, non-intensive care units of the hospital except for the psychiatry unit. However, the number of monitors are limited and it is not possible to monitor every patient if the wards are at capacity. Obstetrics uses its own unique cardiac monitoring system and thus was not included in the survey. Each monitor (IntelliVue, Philips Healthcare, Amsterdam, Netherlands) is attached to the patient using 5 lead wires, with electrocardiographic data transmitted to a monitoring station based in the progressive care unit, a cardio-pulmonary step-down unit. Monitors can be ordered in one of 3 manners, as mandated by hospital policy:

1. Continuous telemetry – Telemetry monitoring is uninterrupted until discontinued by a provider.
2. Telemetry protocol – Within 12 hours of telemetry placement, a monitor technician generates a report, which is reviewed by the nurse caring for the patient. The nurse performs an electrocardiogram (ECG) if the patient meets pre-specified criteria for telemetry discontinuation, which includes the absence of arrhythmias, troponin elevations, chest pain, or hemodynamic instability. The repeat ECG is then read and signed by the provider. After these criteria are met, telemetry can be discontinued.
3. Stroke telemetry protocol – Telemetry is applied for 48 hours, mainly for detection of paroxysmal atrial fibrillation. Monitoring can be temporarily discontinued if the patient requires magnetic resonance imaging, which interferes with the telemetric monitors.

When entering any of the 3 possible telemetry orders in our computerized provider order entry system (Meditech, Westwood, MA), the ordering provider is required to indicate baseline rhythm, pacemaker presence, and desired heart rate warning parameters. Once the order is electronically signed, a monitor technician notes the order in a logbook and assigns the patient a telemeter, which is applied by the patient’s nurse.

If a monitored patient develops any predefined abnormal rhythm, audible alerts notify monitor technicians and an alert is sent to a portable telephone carried by the patient’s assigned nurse. Either the monitoring technician or the nurse then has the discretion to silence the alarm, note it in the chart, and/or contact the patient’s provider. If alerts are recorded, then a sample telemetry monitoring strip is saved into the patient’s paper medical chart.

 

Survey Instrument

After approval from the Johns Hopkins institutional review board, we queried providers who worked on the medicine and cardiology wards to assess the context and culture in which telemetry monitoring is used (see Appendix). The study was exempt from requiring informed consent. All staff had the option to decline study participation. We administered the survey using an online survey software program (SurveyMonkey, Palo Alto, CA), sending survey links via email to all internal medicine residents, cardiovascular disease fellows, internal medicine and cardiology teaching attending physicians, hospitalists, NPs, and PAs. Respondents completed the survey anonymously. To increase response rates, providers were sent a monthly reminder email. The survey was open from March 2014 to May 2014 for a total of 3 months.

Analysis

The survey data were compiled and analyzed using Microsoft Excel (Mac version 14.4; Microsoft, Redmond, WA). Variables are displayed as numbers and percentages, as appropriate.

Results

Of the 180 invited providers, 67 replied, for a response rate of 37%. Residents were the largest group of respondents (42%), followed by non-hospitalist teaching attending physicians (31%), hospitalists (21%), fellows (4%), and one PA (1%) (Table).

All providers reported having ordered telemetry, but almost all were either unaware of (76%) or only somewhat familiar with (21%) the AHA guidelines for appropriate telemetry use. Notably, the vast majority of fellows and residents reported that they were not at all familiar with the guidelines (100% and 96%, respectively). When asked why providers do not adhere to telemetry guidelines, lack of awareness of and lack of familiarity with the guidelines were the top 2 choices among respondents (Figure 1). 

Despite acknowledging unfamiliarity with the guidelines, 60% (40/67) felt their own ordering practices were consistent with the guidelines the majority of the time. The majority of respondents (64%, 43/67) felt that telemetry was not being appropriately utilized at their institution.

Additionally, most providers acknowledged experiencing adverse effects of telemetry: 86% (57/66) had experienced delayed patient transfers from the emergency department to inpatient floors due to telemetry unavailability and 97% (65/67) had experienced some delay in obtaining tests or studies for their telemetry-monitored patients. Despite acknowledging the potential consequences of telemetry use, only 21% (14/66) of providers routinely (ie, > 75% of the time) discontinued telemetry within 48 hours. Fifteen percent (10/65) routinely allowed telemetry to continue until the time of patient discharge. When discontinued, it was mainly due to the provider’s decision (57%); however, respondents noted that nurses prompted telemetry discontinuation 28% of the time.

Finally, providers viewed a list of 14 diagnoses, only 3 of which met criteria for telemetry use per AHA guidelines—myocardial infarction/ACS, myocarditis, and ingestion of a cardiotoxic drug (Figure 2). Participants were asked to select the diagnoses for which they would order telemetry. Eighty-five percent (57/67) selected at least 1 inappropriate diagnosis. The most commonly selected inappropriate diagnoses in descending order were substance withdrawal (57%), gastrointestinal bleed (43%), pulmonary embolus with normal heart rate and blood pressure (37%), altered mental status (33%), acute renal failure with normal electrolytes (18%), and exacerbation of obstructive lung disease (12%). Seven respondents (10%) selected only the guideline-supported diagnoses.

The majority of providers (40/67) agreed that “better provider education” would be the most effective method for improving communication between providers and nurses regarding telemetry use. Rather than choosing one of the available answer choices (Figure 3), some providers offered write-in suggestions for improving communication about telemetry, especially with regard to limited telemeter availability. Examples included: “The biggest barrier to compliance with tele guidelines is that providers don’t know which of their patients are on tele; especially when taking over care from another colleague.” Similarly, another provider wrote, “I wish… there was a prompt or sign that the patient is on tele… When we encounter tele shortages, I have to ask [the charge nurse] if there is any patient who no longer needs tele… We need to pay more attention.”

 

Discussion

Consistent with previous studies [3–5,9–15], the majority of providers at our institution do not think continuous telemetry is appropriately utilized. Most survey respondents acknowledged a lack of awareness surrounding current guideline recommendations, which could explain why providers often do not follow them. Despite conceding their knowledge deficits, providers assumed their practice patterns for ordering telemetry were “appropriate”(ie, guideline-supported). This assertion may be incorrect as the majority of providers in our survey chose at least 1 non–guideline-supported indication for telemetry. Other studies have suggested additional reasons for inappropriate telemetry utilization. Providers may disagree with guideline recommendations, may assign lesser importance to guidelines when caring for an individual patient, or may fall victim to inertia (ie, not ordering telemetry appropriately simply because changing one’s practice pattern is difficult) [7].

In addition, the majority of our providers perceived telemetry overuse, which has been well-recognized nationwide [4]. While we did not assess this directly, other studies suggest that providers may overuse telemetry to provide a sense of reassurance when caring for a sick patient, since continuous telemetry is perceived to provide a higher level of care [6,15–17]. Unfortunately, no study has shown a benefit for continuous telemetry when placed for non-guideline-based diagnoses—whether for cardiac or non-cardiac diagnoses [3,9–11,13,14]. Likewise, the guidelines suggest that telemetry use should be time-limited, since the majority of benefit is accrued in the first 48 hours. Beyond that time, no study has shown a clear benefit to continuous telemetry [2]. Therefore, telemetry overuse may lead to unnecessarily increased costs without added benefits [3,9–11,13–15,18].

Our conclusions are tempered by the nature of our survey data. We recognize that our survey has not been previously validated. In addition, our response rates were low. This low sample size may lead to under-representation of diverse ideas. Also, our survey results may not be generalizable, since our study was conducted at a single academic hospital. Our institution’s telemetry ordering culture may differ from others, therefore making our results less applicable to other centers.

Despite these limitations, our results aid in understanding attitudes that surround the use of continuous telemetry, which can shape formal educational interventions to encourage appropriate guideline-based telemetry use. Since our providers agree on the need for more education about the guidelines, components such as online modules or in-person lecture educational sessions, newsletters, email communications, and incorporation of AHA guidelines into the institution’s automated computer order entry system could be utilized [17]. Didactic interventions could be designed especially for trainees given their overall lack of familiarity with the guidelines. Another potential intervention could include supplying providers with publically shared personalized measures of their own practices, since providers benefit from reinforcement and individualized feedback on appropriate utilization practices [19]. Previous studies have suggested that a multidisciplinary approach to patient care leads to positive outcomes [20,21], and in our experience, nursing input is absolutely critical in outlining potential problems and in developing solutions. Our findings suggest that nurses could play an active role in alerting providers when patients have telemetry in use and identifying patients who may no longer need it.

In summary, we have shown that many providers at a tertiary academic institution utilized continuous telemetry inappropriately, and were unaware of guidelines surrounding telemetry use. Future interventions aimed at educating providers, encouraging dialogue between staff, and enabling guideline-supported utilization may increase appropriate telemetry use leading to lower cost and improved quality of patient care.

 

Acknowledgment: The authors wish to thank Dr. Colleen Christmas, Dr. Panagis Galiatsatos, Mrs. Barbara Brigade, Ms. Joetta Love, Ms. Terri Rigsby, and Mrs. Lisa Shirk for their invaluable technical and administrative support.

Corresponding author: Amber Johnson, MD, MBA, 200 Lothrop St., S-553 Scaife Hall, Pittsburgh, PA 15213, [email protected].

Financial disclosures: None.

From the Johns Hopkins Bayview Medical Center, Baltimore, MD (Drs. Johnson, Knight, Maygers, and Zakaria), and Duke University Hospital, Durham, NC (Dr. Mock).

 

Abstract

• Objective: To determine patterns of telemetry use at a tertiary academic institution and identify factors contributing to noncompliance with guidelines regarding telemetry use.
• Methods: Web-based survey of 180 providers, including internal medicine residents and cardiovascular disease fellows, hospitalists, non-hospitalist teaching attending physicians, nurse practitioners, and physician assistants.
• Results: Of the 180 providers surveyed, 67 (37%) replied. Most providers (76%) were unaware of guidelines regarding appropriate telemetry use and 85% selected inappropriate diagnoses as warranting telemetry. Only 21% routinely discontinued the telemetry order within 48 hours.
• Conclusions: Many providers at a tertiary academic institution utilize continuous telemetry inappropriately and are unaware of telemetry guidelines. These findings should guide interventions to improve telemetry utilization.

 

For many decades, telemetry has been widely used in the management and monitoring of patients with possible acute coronary syndromes (ACS), arrhythmias, cardiac events, and strokes [1]. In addition, telemetry has often been used in other clinical scenarios with less rigorous data supporting its use [2–4]. As a result, in 2004 the American Heart Association (AHA) issued guidelines providing recommendations for best practices in hospital ECG monitoring. Indications for telemetry were classified into 3 diagnosis-driven groups: class I (indicated in all patients), class II (indicated in most patients, may be of benefit) and class III (not indicated, no therapeutic benefit) [2]. However, these recommendations have not been widely followed and telemetry is inappropriately used for many inpatients [5,6].

There are several reasons why clinicians fail to adhere to guidelines, including knowledge deficits, attitudes regarding the current guidelines, and institution-specific factors influencing practitioner behaviors [7]. In response to reports of widespread telemetry overuse, the Choosing Wisely Campaign of the American Board of Internal Medicine Foundation has championed judicious telemetry use, advocating evidence-based, protocol-driven telemetry management for patients not in intensive care units who do not meet guideline-based criteria for continuous telemetry [8].

In order to understand patterns of telemetry use at our academic institution and identify factors associated with this practice, we systematically analyzed telemetry use perceptions through provider surveys. We hypothesized that providers have misperceptions about appropriate use of telemetry and that this knowledge gap results in overuse of telemetry at our institution.

Methods

Setting

Johns Hopkins Bayview Medical Center is a 400-bed academic medical center serving southeastern Baltimore. Providers included internal medicine residents and cardiovascular disease fellows who rotate to the medical center and Johns Hopkins Hospital, hospitalists, non-hospitalist teaching attending physicians, nurse practitioners (NPs), and physician assistants (PAs).

Current Telemetry Practice

Remote telemetric monitoring is available in all adult, non-intensive care units of the hospital except for the psychiatry unit. However, the number of monitors are limited and it is not possible to monitor every patient if the wards are at capacity. Obstetrics uses its own unique cardiac monitoring system and thus was not included in the survey. Each monitor (IntelliVue, Philips Healthcare, Amsterdam, Netherlands) is attached to the patient using 5 lead wires, with electrocardiographic data transmitted to a monitoring station based in the progressive care unit, a cardio-pulmonary step-down unit. Monitors can be ordered in one of 3 manners, as mandated by hospital policy:

1. Continuous telemetry – Telemetry monitoring is uninterrupted until discontinued by a provider.
2. Telemetry protocol – Within 12 hours of telemetry placement, a monitor technician generates a report, which is reviewed by the nurse caring for the patient. The nurse performs an electrocardiogram (ECG) if the patient meets pre-specified criteria for telemetry discontinuation, which includes the absence of arrhythmias, troponin elevations, chest pain, or hemodynamic instability. The repeat ECG is then read and signed by the provider. After these criteria are met, telemetry can be discontinued.
3. Stroke telemetry protocol – Telemetry is applied for 48 hours, mainly for detection of paroxysmal atrial fibrillation. Monitoring can be temporarily discontinued if the patient requires magnetic resonance imaging, which interferes with the telemetric monitors.

When entering any of the 3 possible telemetry orders in our computerized provider order entry system (Meditech, Westwood, MA), the ordering provider is required to indicate baseline rhythm, pacemaker presence, and desired heart rate warning parameters. Once the order is electronically signed, a monitor technician notes the order in a logbook and assigns the patient a telemeter, which is applied by the patient’s nurse.

If a monitored patient develops any predefined abnormal rhythm, audible alerts notify monitor technicians and an alert is sent to a portable telephone carried by the patient’s assigned nurse. Either the monitoring technician or the nurse then has the discretion to silence the alarm, note it in the chart, and/or contact the patient’s provider. If alerts are recorded, then a sample telemetry monitoring strip is saved into the patient’s paper medical chart.

 

Survey Instrument

After approval from the Johns Hopkins institutional review board, we queried providers who worked on the medicine and cardiology wards to assess the context and culture in which telemetry monitoring is used (see Appendix). The study was exempt from requiring informed consent. All staff had the option to decline study participation. We administered the survey using an online survey software program (SurveyMonkey, Palo Alto, CA), sending survey links via email to all internal medicine residents, cardiovascular disease fellows, internal medicine and cardiology teaching attending physicians, hospitalists, NPs, and PAs. Respondents completed the survey anonymously. To increase response rates, providers were sent a monthly reminder email. The survey was open from March 2014 to May 2014 for a total of 3 months.

Analysis

The survey data were compiled and analyzed using Microsoft Excel (Mac version 14.4; Microsoft, Redmond, WA). Variables are displayed as numbers and percentages, as appropriate.

Results

Of the 180 invited providers, 67 replied, for a response rate of 37%. Residents were the largest group of respondents (42%), followed by non-hospitalist teaching attending physicians (31%), hospitalists (21%), fellows (4%), and one PA (1%) (Table).

All providers reported having ordered telemetry, but almost all were either unaware of (76%) or only somewhat familiar with (21%) the AHA guidelines for appropriate telemetry use. Notably, the vast majority of fellows and residents reported that they were not at all familiar with the guidelines (100% and 96%, respectively). When asked why providers do not adhere to telemetry guidelines, lack of awareness of and lack of familiarity with the guidelines were the top 2 choices among respondents (Figure 1). 

Despite acknowledging unfamiliarity with the guidelines, 60% (40/67) felt their own ordering practices were consistent with the guidelines the majority of the time. The majority of respondents (64%, 43/67) felt that telemetry was not being appropriately utilized at their institution.

Additionally, most providers acknowledged experiencing adverse effects of telemetry: 86% (57/66) had experienced delayed patient transfers from the emergency department to inpatient floors due to telemetry unavailability and 97% (65/67) had experienced some delay in obtaining tests or studies for their telemetry-monitored patients. Despite acknowledging the potential consequences of telemetry use, only 21% (14/66) of providers routinely (ie, > 75% of the time) discontinued telemetry within 48 hours. Fifteen percent (10/65) routinely allowed telemetry to continue until the time of patient discharge. When discontinued, it was mainly due to the provider’s decision (57%); however, respondents noted that nurses prompted telemetry discontinuation 28% of the time.

Finally, providers viewed a list of 14 diagnoses, only 3 of which met criteria for telemetry use per AHA guidelines—myocardial infarction/ACS, myocarditis, and ingestion of a cardiotoxic drug (Figure 2). Participants were asked to select the diagnoses for which they would order telemetry. Eighty-five percent (57/67) selected at least 1 inappropriate diagnosis. The most commonly selected inappropriate diagnoses in descending order were substance withdrawal (57%), gastrointestinal bleed (43%), pulmonary embolus with normal heart rate and blood pressure (37%), altered mental status (33%), acute renal failure with normal electrolytes (18%), and exacerbation of obstructive lung disease (12%). Seven respondents (10%) selected only the guideline-supported diagnoses.

The majority of providers (40/67) agreed that “better provider education” would be the most effective method for improving communication between providers and nurses regarding telemetry use. Rather than choosing one of the available answer choices (Figure 3), some providers offered write-in suggestions for improving communication about telemetry, especially with regard to limited telemeter availability. Examples included: “The biggest barrier to compliance with tele guidelines is that providers don’t know which of their patients are on tele; especially when taking over care from another colleague.” Similarly, another provider wrote, “I wish… there was a prompt or sign that the patient is on tele… When we encounter tele shortages, I have to ask [the charge nurse] if there is any patient who no longer needs tele… We need to pay more attention.”

 

Discussion

Consistent with previous studies [3–5,9–15], the majority of providers at our institution do not think continuous telemetry is appropriately utilized. Most survey respondents acknowledged a lack of awareness surrounding current guideline recommendations, which could explain why providers often do not follow them. Despite conceding their knowledge deficits, providers assumed their practice patterns for ordering telemetry were “appropriate”(ie, guideline-supported). This assertion may be incorrect as the majority of providers in our survey chose at least 1 non–guideline-supported indication for telemetry. Other studies have suggested additional reasons for inappropriate telemetry utilization. Providers may disagree with guideline recommendations, may assign lesser importance to guidelines when caring for an individual patient, or may fall victim to inertia (ie, not ordering telemetry appropriately simply because changing one’s practice pattern is difficult) [7].

In addition, the majority of our providers perceived telemetry overuse, which has been well-recognized nationwide [4]. While we did not assess this directly, other studies suggest that providers may overuse telemetry to provide a sense of reassurance when caring for a sick patient, since continuous telemetry is perceived to provide a higher level of care [6,15–17]. Unfortunately, no study has shown a benefit for continuous telemetry when placed for non-guideline-based diagnoses—whether for cardiac or non-cardiac diagnoses [3,9–11,13,14]. Likewise, the guidelines suggest that telemetry use should be time-limited, since the majority of benefit is accrued in the first 48 hours. Beyond that time, no study has shown a clear benefit to continuous telemetry [2]. Therefore, telemetry overuse may lead to unnecessarily increased costs without added benefits [3,9–11,13–15,18].

Our conclusions are tempered by the nature of our survey data. We recognize that our survey has not been previously validated. In addition, our response rates were low. This low sample size may lead to under-representation of diverse ideas. Also, our survey results may not be generalizable, since our study was conducted at a single academic hospital. Our institution’s telemetry ordering culture may differ from others, therefore making our results less applicable to other centers.

Despite these limitations, our results aid in understanding attitudes that surround the use of continuous telemetry, which can shape formal educational interventions to encourage appropriate guideline-based telemetry use. Since our providers agree on the need for more education about the guidelines, components such as online modules or in-person lecture educational sessions, newsletters, email communications, and incorporation of AHA guidelines into the institution’s automated computer order entry system could be utilized [17]. Didactic interventions could be designed especially for trainees given their overall lack of familiarity with the guidelines. Another potential intervention could include supplying providers with publically shared personalized measures of their own practices, since providers benefit from reinforcement and individualized feedback on appropriate utilization practices [19]. Previous studies have suggested that a multidisciplinary approach to patient care leads to positive outcomes [20,21], and in our experience, nursing input is absolutely critical in outlining potential problems and in developing solutions. Our findings suggest that nurses could play an active role in alerting providers when patients have telemetry in use and identifying patients who may no longer need it.

In summary, we have shown that many providers at a tertiary academic institution utilized continuous telemetry inappropriately, and were unaware of guidelines surrounding telemetry use. Future interventions aimed at educating providers, encouraging dialogue between staff, and enabling guideline-supported utilization may increase appropriate telemetry use leading to lower cost and improved quality of patient care.

 

Acknowledgment: The authors wish to thank Dr. Colleen Christmas, Dr. Panagis Galiatsatos, Mrs. Barbara Brigade, Ms. Joetta Love, Ms. Terri Rigsby, and Mrs. Lisa Shirk for their invaluable technical and administrative support.

Corresponding author: Amber Johnson, MD, MBA, 200 Lothrop St., S-553 Scaife Hall, Pittsburgh, PA 15213, [email protected].

Financial disclosures: None.

From the Johns Hopkins Bayview Medical Center, Baltimore, MD (Drs. Johnson, Knight, Maygers, and Zakaria), and Duke University Hospital, Durham, NC (Dr. Mock).

 

Abstract

• Objective: To determine patterns of telemetry use at a tertiary academic institution and identify factors contributing to noncompliance with guidelines regarding telemetry use.
• Methods: Web-based survey of 180 providers, including internal medicine residents and cardiovascular disease fellows, hospitalists, non-hospitalist teaching attending physicians, nurse practitioners, and physician assistants.
• Results: Of the 180 providers surveyed, 67 (37%) replied. Most providers (76%) were unaware of guidelines regarding appropriate telemetry use and 85% selected inappropriate diagnoses as warranting telemetry. Only 21% routinely discontinued the telemetry order within 48 hours.
• Conclusions: Many providers at a tertiary academic institution utilize continuous telemetry inappropriately and are unaware of telemetry guidelines. These findings should guide interventions to improve telemetry utilization.

 

For many decades, telemetry has been widely used in the management and monitoring of patients with possible acute coronary syndromes (ACS), arrhythmias, cardiac events, and strokes [1]. In addition, telemetry has often been used in other clinical scenarios with less rigorous data supporting its use [2–4]. As a result, in 2004 the American Heart Association (AHA) issued guidelines providing recommendations for best practices in hospital ECG monitoring. Indications for telemetry were classified into 3 diagnosis-driven groups: class I (indicated in all patients), class II (indicated in most patients, may be of benefit) and class III (not indicated, no therapeutic benefit) [2]. However, these recommendations have not been widely followed and telemetry is inappropriately used for many inpatients [5,6].

There are several reasons why clinicians fail to adhere to guidelines, including knowledge deficits, attitudes regarding the current guidelines, and institution-specific factors influencing practitioner behaviors [7]. In response to reports of widespread telemetry overuse, the Choosing Wisely Campaign of the American Board of Internal Medicine Foundation has championed judicious telemetry use, advocating evidence-based, protocol-driven telemetry management for patients not in intensive care units who do not meet guideline-based criteria for continuous telemetry [8].

In order to understand patterns of telemetry use at our academic institution and identify factors associated with this practice, we systematically analyzed telemetry use perceptions through provider surveys. We hypothesized that providers have misperceptions about appropriate use of telemetry and that this knowledge gap results in overuse of telemetry at our institution.

Methods

Setting

Johns Hopkins Bayview Medical Center is a 400-bed academic medical center serving southeastern Baltimore. Providers included internal medicine residents and cardiovascular disease fellows who rotate to the medical center and Johns Hopkins Hospital, hospitalists, non-hospitalist teaching attending physicians, nurse practitioners (NPs), and physician assistants (PAs).

Current Telemetry Practice

Remote telemetric monitoring is available in all adult, non-intensive care units of the hospital except for the psychiatry unit. However, the number of monitors are limited and it is not possible to monitor every patient if the wards are at capacity. Obstetrics uses its own unique cardiac monitoring system and thus was not included in the survey. Each monitor (IntelliVue, Philips Healthcare, Amsterdam, Netherlands) is attached to the patient using 5 lead wires, with electrocardiographic data transmitted to a monitoring station based in the progressive care unit, a cardio-pulmonary step-down unit. Monitors can be ordered in one of 3 manners, as mandated by hospital policy:

1. Continuous telemetry – Telemetry monitoring is uninterrupted until discontinued by a provider.
2. Telemetry protocol – Within 12 hours of telemetry placement, a monitor technician generates a report, which is reviewed by the nurse caring for the patient. The nurse performs an electrocardiogram (ECG) if the patient meets pre-specified criteria for telemetry discontinuation, which includes the absence of arrhythmias, troponin elevations, chest pain, or hemodynamic instability. The repeat ECG is then read and signed by the provider. After these criteria are met, telemetry can be discontinued.
3. Stroke telemetry protocol – Telemetry is applied for 48 hours, mainly for detection of paroxysmal atrial fibrillation. Monitoring can be temporarily discontinued if the patient requires magnetic resonance imaging, which interferes with the telemetric monitors.

When entering any of the 3 possible telemetry orders in our computerized provider order entry system (Meditech, Westwood, MA), the ordering provider is required to indicate baseline rhythm, pacemaker presence, and desired heart rate warning parameters. Once the order is electronically signed, a monitor technician notes the order in a logbook and assigns the patient a telemeter, which is applied by the patient’s nurse.

If a monitored patient develops any predefined abnormal rhythm, audible alerts notify monitor technicians and an alert is sent to a portable telephone carried by the patient’s assigned nurse. Either the monitoring technician or the nurse then has the discretion to silence the alarm, note it in the chart, and/or contact the patient’s provider. If alerts are recorded, then a sample telemetry monitoring strip is saved into the patient’s paper medical chart.

 

Survey Instrument

After approval from the Johns Hopkins institutional review board, we queried providers who worked on the medicine and cardiology wards to assess the context and culture in which telemetry monitoring is used (see Appendix). The study was exempt from requiring informed consent. All staff had the option to decline study participation. We administered the survey using an online survey software program (SurveyMonkey, Palo Alto, CA), sending survey links via email to all internal medicine residents, cardiovascular disease fellows, internal medicine and cardiology teaching attending physicians, hospitalists, NPs, and PAs. Respondents completed the survey anonymously. To increase response rates, providers were sent a monthly reminder email. The survey was open from March 2014 to May 2014 for a total of 3 months.

Analysis

The survey data were compiled and analyzed using Microsoft Excel (Mac version 14.4; Microsoft, Redmond, WA). Variables are displayed as numbers and percentages, as appropriate.

Results

Of the 180 invited providers, 67 replied, for a response rate of 37%. Residents were the largest group of respondents (42%), followed by non-hospitalist teaching attending physicians (31%), hospitalists (21%), fellows (4%), and one PA (1%) (Table).

All providers reported having ordered telemetry, but almost all were either unaware of (76%) or only somewhat familiar with (21%) the AHA guidelines for appropriate telemetry use. Notably, the vast majority of fellows and residents reported that they were not at all familiar with the guidelines (100% and 96%, respectively). When asked why providers do not adhere to telemetry guidelines, lack of awareness of and lack of familiarity with the guidelines were the top 2 choices among respondents (Figure 1). 

Despite acknowledging unfamiliarity with the guidelines, 60% (40/67) felt their own ordering practices were consistent with the guidelines the majority of the time. The majority of respondents (64%, 43/67) felt that telemetry was not being appropriately utilized at their institution.

Additionally, most providers acknowledged experiencing adverse effects of telemetry: 86% (57/66) had experienced delayed patient transfers from the emergency department to inpatient floors due to telemetry unavailability and 97% (65/67) had experienced some delay in obtaining tests or studies for their telemetry-monitored patients. Despite acknowledging the potential consequences of telemetry use, only 21% (14/66) of providers routinely (ie, > 75% of the time) discontinued telemetry within 48 hours. Fifteen percent (10/65) routinely allowed telemetry to continue until the time of patient discharge. When discontinued, it was mainly due to the provider’s decision (57%); however, respondents noted that nurses prompted telemetry discontinuation 28% of the time.

Finally, providers viewed a list of 14 diagnoses, only 3 of which met criteria for telemetry use per AHA guidelines—myocardial infarction/ACS, myocarditis, and ingestion of a cardiotoxic drug (Figure 2). Participants were asked to select the diagnoses for which they would order telemetry. Eighty-five percent (57/67) selected at least 1 inappropriate diagnosis. The most commonly selected inappropriate diagnoses in descending order were substance withdrawal (57%), gastrointestinal bleed (43%), pulmonary embolus with normal heart rate and blood pressure (37%), altered mental status (33%), acute renal failure with normal electrolytes (18%), and exacerbation of obstructive lung disease (12%). Seven respondents (10%) selected only the guideline-supported diagnoses.

The majority of providers (40/67) agreed that “better provider education” would be the most effective method for improving communication between providers and nurses regarding telemetry use. Rather than choosing one of the available answer choices (Figure 3), some providers offered write-in suggestions for improving communication about telemetry, especially with regard to limited telemeter availability. Examples included: “The biggest barrier to compliance with tele guidelines is that providers don’t know which of their patients are on tele; especially when taking over care from another colleague.” Similarly, another provider wrote, “I wish… there was a prompt or sign that the patient is on tele… When we encounter tele shortages, I have to ask [the charge nurse] if there is any patient who no longer needs tele… We need to pay more attention.”

 

Discussion

Consistent with previous studies [3–5,9–15], the majority of providers at our institution do not think continuous telemetry is appropriately utilized. Most survey respondents acknowledged a lack of awareness surrounding current guideline recommendations, which could explain why providers often do not follow them. Despite conceding their knowledge deficits, providers assumed their practice patterns for ordering telemetry were “appropriate”(ie, guideline-supported). This assertion may be incorrect as the majority of providers in our survey chose at least 1 non–guideline-supported indication for telemetry. Other studies have suggested additional reasons for inappropriate telemetry utilization. Providers may disagree with guideline recommendations, may assign lesser importance to guidelines when caring for an individual patient, or may fall victim to inertia (ie, not ordering telemetry appropriately simply because changing one’s practice pattern is difficult) [7].

In addition, the majority of our providers perceived telemetry overuse, which has been well-recognized nationwide [4]. While we did not assess this directly, other studies suggest that providers may overuse telemetry to provide a sense of reassurance when caring for a sick patient, since continuous telemetry is perceived to provide a higher level of care [6,15–17]. Unfortunately, no study has shown a benefit for continuous telemetry when placed for non-guideline-based diagnoses—whether for cardiac or non-cardiac diagnoses [3,9–11,13,14]. Likewise, the guidelines suggest that telemetry use should be time-limited, since the majority of benefit is accrued in the first 48 hours. Beyond that time, no study has shown a clear benefit to continuous telemetry [2]. Therefore, telemetry overuse may lead to unnecessarily increased costs without added benefits [3,9–11,13–15,18].

Our conclusions are tempered by the nature of our survey data. We recognize that our survey has not been previously validated. In addition, our response rates were low. This low sample size may lead to under-representation of diverse ideas. Also, our survey results may not be generalizable, since our study was conducted at a single academic hospital. Our institution’s telemetry ordering culture may differ from others, therefore making our results less applicable to other centers.

Despite these limitations, our results aid in understanding attitudes that surround the use of continuous telemetry, which can shape formal educational interventions to encourage appropriate guideline-based telemetry use. Since our providers agree on the need for more education about the guidelines, components such as online modules or in-person lecture educational sessions, newsletters, email communications, and incorporation of AHA guidelines into the institution’s automated computer order entry system could be utilized [17]. Didactic interventions could be designed especially for trainees given their overall lack of familiarity with the guidelines. Another potential intervention could include supplying providers with publically shared personalized measures of their own practices, since providers benefit from reinforcement and individualized feedback on appropriate utilization practices [19]. Previous studies have suggested that a multidisciplinary approach to patient care leads to positive outcomes [20,21], and in our experience, nursing input is absolutely critical in outlining potential problems and in developing solutions. Our findings suggest that nurses could play an active role in alerting providers when patients have telemetry in use and identifying patients who may no longer need it.

In summary, we have shown that many providers at a tertiary academic institution utilized continuous telemetry inappropriately, and were unaware of guidelines surrounding telemetry use. Future interventions aimed at educating providers, encouraging dialogue between staff, and enabling guideline-supported utilization may increase appropriate telemetry use leading to lower cost and improved quality of patient care.

 

Acknowledgment: The authors wish to thank Dr. Colleen Christmas, Dr. Panagis Galiatsatos, Mrs. Barbara Brigade, Ms. Joetta Love, Ms. Terri Rigsby, and Mrs. Lisa Shirk for their invaluable technical and administrative support.

Corresponding author: Amber Johnson, MD, MBA, 200 Lothrop St., S-553 Scaife Hall, Pittsburgh, PA 15213, [email protected].

Financial disclosures: None.