Anti-Ro52 autoantibodies signal interstitial lung disease in juvenile dermatomyositis teaser

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Mon, 05/11/2020 - 11:16

 

Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.

And in a recent potential treatment advance, Janus kinase inhibition shows promise as a novel therapy for ILD in patients with juvenile dermatomyositis (JDM), added Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
 

Autoantibodies predict ILD in JDM

Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 3 (12%) of 25 patients with juvenile polymyositis and in 8 (18%) of 44 youths with juvenile connective tissue disease–myositis overlap. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: namely, 9% of the cohort were positive for anti–melanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl-tRNA synthetase (anti-Jo-1) autoantibodies were present in 4%.

Thirty-three of the 371 juvenile myositis patients had ILD based upon CT imaging, chest x-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo1. After controlling for the presence of these other myositis-specific autoantibodies, anti-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.

Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52 and anti-Jo1 positive (Ann Rheum Dis. 2019 Jul;78[7]:988-95).

Patients with anti-Ro autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
 

Potential treatment for ILD in JDM: JAK inhibitors

Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, IVIG, and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation–syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody–positive disease, according to Dr. Stevens.

For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody–positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.

Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals (Brain. 2019 Nov 1;142[11]:e59).

Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody–positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms (Rheumatology [Oxford]. 2019 Nov 22. doi: 10.1093/rheumatology/kez525. [Epub ahead of print]).

The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.

Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.

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Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.

And in a recent potential treatment advance, Janus kinase inhibition shows promise as a novel therapy for ILD in patients with juvenile dermatomyositis (JDM), added Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
 

Autoantibodies predict ILD in JDM

Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 3 (12%) of 25 patients with juvenile polymyositis and in 8 (18%) of 44 youths with juvenile connective tissue disease–myositis overlap. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: namely, 9% of the cohort were positive for anti–melanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl-tRNA synthetase (anti-Jo-1) autoantibodies were present in 4%.

Thirty-three of the 371 juvenile myositis patients had ILD based upon CT imaging, chest x-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo1. After controlling for the presence of these other myositis-specific autoantibodies, anti-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.

Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52 and anti-Jo1 positive (Ann Rheum Dis. 2019 Jul;78[7]:988-95).

Patients with anti-Ro autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
 

Potential treatment for ILD in JDM: JAK inhibitors

Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, IVIG, and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation–syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody–positive disease, according to Dr. Stevens.

For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody–positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.

Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals (Brain. 2019 Nov 1;142[11]:e59).

Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody–positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms (Rheumatology [Oxford]. 2019 Nov 22. doi: 10.1093/rheumatology/kez525. [Epub ahead of print]).

The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.

Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.

 

Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.

And in a recent potential treatment advance, Janus kinase inhibition shows promise as a novel therapy for ILD in patients with juvenile dermatomyositis (JDM), added Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
 

Autoantibodies predict ILD in JDM

Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 3 (12%) of 25 patients with juvenile polymyositis and in 8 (18%) of 44 youths with juvenile connective tissue disease–myositis overlap. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: namely, 9% of the cohort were positive for anti–melanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl-tRNA synthetase (anti-Jo-1) autoantibodies were present in 4%.

Thirty-three of the 371 juvenile myositis patients had ILD based upon CT imaging, chest x-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo1. After controlling for the presence of these other myositis-specific autoantibodies, anti-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.

Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52 and anti-Jo1 positive (Ann Rheum Dis. 2019 Jul;78[7]:988-95).

Patients with anti-Ro autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
 

Potential treatment for ILD in JDM: JAK inhibitors

Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, IVIG, and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation–syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody–positive disease, according to Dr. Stevens.

For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody–positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.

Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals (Brain. 2019 Nov 1;142[11]:e59).

Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody–positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms (Rheumatology [Oxford]. 2019 Nov 22. doi: 10.1093/rheumatology/kez525. [Epub ahead of print]).

The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.

Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.

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Plan now to address the COVID-19 mental health fallout

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Thu, 08/26/2021 - 16:08

COVID-19 affects the physical, psychological, and social health of people around the world. In the United States, newly reported cases are rising at alarming rates.

Dr. Lalasa Doppalapudi

As of early May, more than 1.3 million people were confirmed to be COVID-19 infected in the United States and more than 4 million cases were reported globally.1

According to new internal projections from the Centers for Disease Control and Prevention, by June 1, the number of daily deaths could reach about 3,000. By the end of June, a draft CDC report projects that the United States will see 200,000 new cases each day.2

COVID-19 undeniably harms mental health. It gravely instills uncertainty and anxiety, sometimes compounded by the grief of losing loved ones and not being able to mourn those losses in traditional ways. The pandemic also has led to occupational and/or financial losses. Physical distancing and shelter-in-place practices make it even harder to cope with those stresses, although those practices mitigate the dangers. The fears tied to those practices are thought to be keeping some patients with health problems from seeking needed care from hospital EDs.3 In light of the mental health crisis emerging because of the profound impact of this pandemic on all aspects of life, clinicians should start working with public health and political leaders to develop plans to address these issues now.
 

Known impact of previous outbreaks

Previous disease outbreaks evidence a similar pattern of heightened anxiety as the patterns seen with COVID-19. For example, during the 2009 swine flu outbreak, 36 surveys of more than 3,000 participants in the United Kingdom found that 9.6%-32.9% of the participants were “very” or “fairly” worried about the possibility of contracting swine flu.4 The 1995 Ebola outbreak in the Democratic Republic of the Congo produced stigmatization tied to the illness. That outbreak provided many lessons for physicians.5

The metaphors ascribed to different diseases affect communities’ responses to it. The SARS virus has been particularly insidious and has been thought of as a “plague.”6 Epidemics of all kinds cause fears, not only of contracting the disease and dying, but also of social exclusion.7 The emotional responses to COVID-19 can precipitate anxiety, depression, insomnia, and somatic symptoms. Acute stress disorder, PTSD, substance use, and suicide can emerge from maladaptive defenses intended to cope with pandemics.8,9

Repeated exposure to news media about the disease adds to theses stresss.10 Constant news consumption can result in panicky hoarding of resources, such as masks; gloves; first-aid kits; alcohol hand rubs; and daily necessities such as food, water, and toilet paper.
 

Who is most affected by outbreaks?

Those most affected after a disease outbreak are patients, their families, and medical personnel. In one study, researchers who conducted an online survey of 1,210 respondents in 194 cities in China during the early phase of the outbreak found that the psychological effects were worst among women, students, and vulnerable populations.11

Meanwhile, a 2003 cross-sectional survey of 1,115 ethnic Chinese adults in Hong Kong who responded to the SARS outbreak found that the respondents most likely to heed precautionary measures against the infection were “older, female, more educated people as well as those with a positive contact history and SARS-like symptoms.”12

Negative mental health consequences of a disease outbreak might persist long after the infection has dissipated. An increased association has been found between people with mental illness and posttraumatic stress following many disasters.13,14,15

Political and health care leaders should develop plans aimed at helping people copewith pandemics.16 Such strategies should include prioritizing treatment of the physical and mental health needs of patients infected with COVID-19 and of the general population. Screening for anxiety, depression, and suicidal thoughts ought to be implemented, and specialized psychiatric care teams should be assigned.17 We know that psychiatrists and other physicians turned to telemedicine to provide support, psychotherapy, and medical attention to patients soon after physical distancing measures were put into place. Those kinds of quick responses are important for our patients.

Fear of contagious diseases often creates social divisions. Governments should offer accurate information to reduce the detrimental effect of rumors and false propaganda.18 “Social distancing” is a misleading term; these practices should be referred to as “physical distancing.” We should encourage patients to maintain interpersonal contacts – albeit at a distance – to reach out to those in need, and to support one another during these troubled times.19



References

1. World Health Organization. Situation Report–107. 2020 May 6.

2. Centers for Disease Control and Prevention. Situation Update. 2020 Apr 30.

3. O’Brien M. “Are Americans in medical crisis avoiding the ER due to coronavirus?” PBS Newshour. 2020 May 6.

4. Rubin G et al. Health Technol Assess. 2010 Jul;14(340):183-266.

5. Hall R et al. Gen Hosp Psychiatry. 2008 Sep-Oct;30(5):466-52.

6. Verghese A. Clin Infect Dis. 2004;38:932-3.

7. Interagency Standing Committee. Briefing note on addressing health and psychosocial aspects of COVID-19 Outbreak – Version 11. 2020 Feb.

8. Sim K et al. J Psychosom Res. 2010;68:195-202.

9. Shigemura J et al. Psychiatry Clin Neurosci. 2020;74:281-2.

10. Garfin DR et al. Health Psychol. 2020 May;39(5):355-7.

11. Wang C et al. Int J Environ Res Public Health. 2020 Mar 6. doi: 10.3390/ijerph1751729.

12. Leung GM et al. J Epidemiol Community Health. 2003 Nov;57(1):857-63.

13. Xiang Y et al. Int J Biol Sci. 2020;16:1741-4.

14. Alvarez J, Hunt M. J Trauma Stress. 2005 Oct 18(5);18:497-505.

15. Cukor J et al. Depress Anxiety. 2011 Mar;28(3):210-7.

16. Horton R. Lancet. 2020 Feb;395(10222):400.

17. Xiang Y-T et al. Lancet Psychiatry. 2020 Feb 4;7:228-9.

18. World Health Organization. “Rational use of personal protective equipment (PPE) for coronavirus (COVID-19).” Interim Guidance. 2020 Mar.

19. Brooks S et al. Lancet 2020 Mar 14;395:912-20.

Dr. Doppalapudi is affiliated with Griffin Memorial Hospital in Norman, Okla. Dr. Lippmann is emeritus professor of psychiatry and also in family medicine at the University of Louisville (Ky.) Dr. Doppalapudi and Dr. Lippmann disclosed no conflicts of interest.

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COVID-19 affects the physical, psychological, and social health of people around the world. In the United States, newly reported cases are rising at alarming rates.

Dr. Lalasa Doppalapudi

As of early May, more than 1.3 million people were confirmed to be COVID-19 infected in the United States and more than 4 million cases were reported globally.1

According to new internal projections from the Centers for Disease Control and Prevention, by June 1, the number of daily deaths could reach about 3,000. By the end of June, a draft CDC report projects that the United States will see 200,000 new cases each day.2

COVID-19 undeniably harms mental health. It gravely instills uncertainty and anxiety, sometimes compounded by the grief of losing loved ones and not being able to mourn those losses in traditional ways. The pandemic also has led to occupational and/or financial losses. Physical distancing and shelter-in-place practices make it even harder to cope with those stresses, although those practices mitigate the dangers. The fears tied to those practices are thought to be keeping some patients with health problems from seeking needed care from hospital EDs.3 In light of the mental health crisis emerging because of the profound impact of this pandemic on all aspects of life, clinicians should start working with public health and political leaders to develop plans to address these issues now.
 

Known impact of previous outbreaks

Previous disease outbreaks evidence a similar pattern of heightened anxiety as the patterns seen with COVID-19. For example, during the 2009 swine flu outbreak, 36 surveys of more than 3,000 participants in the United Kingdom found that 9.6%-32.9% of the participants were “very” or “fairly” worried about the possibility of contracting swine flu.4 The 1995 Ebola outbreak in the Democratic Republic of the Congo produced stigmatization tied to the illness. That outbreak provided many lessons for physicians.5

The metaphors ascribed to different diseases affect communities’ responses to it. The SARS virus has been particularly insidious and has been thought of as a “plague.”6 Epidemics of all kinds cause fears, not only of contracting the disease and dying, but also of social exclusion.7 The emotional responses to COVID-19 can precipitate anxiety, depression, insomnia, and somatic symptoms. Acute stress disorder, PTSD, substance use, and suicide can emerge from maladaptive defenses intended to cope with pandemics.8,9

Repeated exposure to news media about the disease adds to theses stresss.10 Constant news consumption can result in panicky hoarding of resources, such as masks; gloves; first-aid kits; alcohol hand rubs; and daily necessities such as food, water, and toilet paper.
 

Who is most affected by outbreaks?

Those most affected after a disease outbreak are patients, their families, and medical personnel. In one study, researchers who conducted an online survey of 1,210 respondents in 194 cities in China during the early phase of the outbreak found that the psychological effects were worst among women, students, and vulnerable populations.11

Meanwhile, a 2003 cross-sectional survey of 1,115 ethnic Chinese adults in Hong Kong who responded to the SARS outbreak found that the respondents most likely to heed precautionary measures against the infection were “older, female, more educated people as well as those with a positive contact history and SARS-like symptoms.”12

Negative mental health consequences of a disease outbreak might persist long after the infection has dissipated. An increased association has been found between people with mental illness and posttraumatic stress following many disasters.13,14,15

Political and health care leaders should develop plans aimed at helping people copewith pandemics.16 Such strategies should include prioritizing treatment of the physical and mental health needs of patients infected with COVID-19 and of the general population. Screening for anxiety, depression, and suicidal thoughts ought to be implemented, and specialized psychiatric care teams should be assigned.17 We know that psychiatrists and other physicians turned to telemedicine to provide support, psychotherapy, and medical attention to patients soon after physical distancing measures were put into place. Those kinds of quick responses are important for our patients.

Fear of contagious diseases often creates social divisions. Governments should offer accurate information to reduce the detrimental effect of rumors and false propaganda.18 “Social distancing” is a misleading term; these practices should be referred to as “physical distancing.” We should encourage patients to maintain interpersonal contacts – albeit at a distance – to reach out to those in need, and to support one another during these troubled times.19



References

1. World Health Organization. Situation Report–107. 2020 May 6.

2. Centers for Disease Control and Prevention. Situation Update. 2020 Apr 30.

3. O’Brien M. “Are Americans in medical crisis avoiding the ER due to coronavirus?” PBS Newshour. 2020 May 6.

4. Rubin G et al. Health Technol Assess. 2010 Jul;14(340):183-266.

5. Hall R et al. Gen Hosp Psychiatry. 2008 Sep-Oct;30(5):466-52.

6. Verghese A. Clin Infect Dis. 2004;38:932-3.

7. Interagency Standing Committee. Briefing note on addressing health and psychosocial aspects of COVID-19 Outbreak – Version 11. 2020 Feb.

8. Sim K et al. J Psychosom Res. 2010;68:195-202.

9. Shigemura J et al. Psychiatry Clin Neurosci. 2020;74:281-2.

10. Garfin DR et al. Health Psychol. 2020 May;39(5):355-7.

11. Wang C et al. Int J Environ Res Public Health. 2020 Mar 6. doi: 10.3390/ijerph1751729.

12. Leung GM et al. J Epidemiol Community Health. 2003 Nov;57(1):857-63.

13. Xiang Y et al. Int J Biol Sci. 2020;16:1741-4.

14. Alvarez J, Hunt M. J Trauma Stress. 2005 Oct 18(5);18:497-505.

15. Cukor J et al. Depress Anxiety. 2011 Mar;28(3):210-7.

16. Horton R. Lancet. 2020 Feb;395(10222):400.

17. Xiang Y-T et al. Lancet Psychiatry. 2020 Feb 4;7:228-9.

18. World Health Organization. “Rational use of personal protective equipment (PPE) for coronavirus (COVID-19).” Interim Guidance. 2020 Mar.

19. Brooks S et al. Lancet 2020 Mar 14;395:912-20.

Dr. Doppalapudi is affiliated with Griffin Memorial Hospital in Norman, Okla. Dr. Lippmann is emeritus professor of psychiatry and also in family medicine at the University of Louisville (Ky.) Dr. Doppalapudi and Dr. Lippmann disclosed no conflicts of interest.

COVID-19 affects the physical, psychological, and social health of people around the world. In the United States, newly reported cases are rising at alarming rates.

Dr. Lalasa Doppalapudi

As of early May, more than 1.3 million people were confirmed to be COVID-19 infected in the United States and more than 4 million cases were reported globally.1

According to new internal projections from the Centers for Disease Control and Prevention, by June 1, the number of daily deaths could reach about 3,000. By the end of June, a draft CDC report projects that the United States will see 200,000 new cases each day.2

COVID-19 undeniably harms mental health. It gravely instills uncertainty and anxiety, sometimes compounded by the grief of losing loved ones and not being able to mourn those losses in traditional ways. The pandemic also has led to occupational and/or financial losses. Physical distancing and shelter-in-place practices make it even harder to cope with those stresses, although those practices mitigate the dangers. The fears tied to those practices are thought to be keeping some patients with health problems from seeking needed care from hospital EDs.3 In light of the mental health crisis emerging because of the profound impact of this pandemic on all aspects of life, clinicians should start working with public health and political leaders to develop plans to address these issues now.
 

Known impact of previous outbreaks

Previous disease outbreaks evidence a similar pattern of heightened anxiety as the patterns seen with COVID-19. For example, during the 2009 swine flu outbreak, 36 surveys of more than 3,000 participants in the United Kingdom found that 9.6%-32.9% of the participants were “very” or “fairly” worried about the possibility of contracting swine flu.4 The 1995 Ebola outbreak in the Democratic Republic of the Congo produced stigmatization tied to the illness. That outbreak provided many lessons for physicians.5

The metaphors ascribed to different diseases affect communities’ responses to it. The SARS virus has been particularly insidious and has been thought of as a “plague.”6 Epidemics of all kinds cause fears, not only of contracting the disease and dying, but also of social exclusion.7 The emotional responses to COVID-19 can precipitate anxiety, depression, insomnia, and somatic symptoms. Acute stress disorder, PTSD, substance use, and suicide can emerge from maladaptive defenses intended to cope with pandemics.8,9

Repeated exposure to news media about the disease adds to theses stresss.10 Constant news consumption can result in panicky hoarding of resources, such as masks; gloves; first-aid kits; alcohol hand rubs; and daily necessities such as food, water, and toilet paper.
 

Who is most affected by outbreaks?

Those most affected after a disease outbreak are patients, their families, and medical personnel. In one study, researchers who conducted an online survey of 1,210 respondents in 194 cities in China during the early phase of the outbreak found that the psychological effects were worst among women, students, and vulnerable populations.11

Meanwhile, a 2003 cross-sectional survey of 1,115 ethnic Chinese adults in Hong Kong who responded to the SARS outbreak found that the respondents most likely to heed precautionary measures against the infection were “older, female, more educated people as well as those with a positive contact history and SARS-like symptoms.”12

Negative mental health consequences of a disease outbreak might persist long after the infection has dissipated. An increased association has been found between people with mental illness and posttraumatic stress following many disasters.13,14,15

Political and health care leaders should develop plans aimed at helping people copewith pandemics.16 Such strategies should include prioritizing treatment of the physical and mental health needs of patients infected with COVID-19 and of the general population. Screening for anxiety, depression, and suicidal thoughts ought to be implemented, and specialized psychiatric care teams should be assigned.17 We know that psychiatrists and other physicians turned to telemedicine to provide support, psychotherapy, and medical attention to patients soon after physical distancing measures were put into place. Those kinds of quick responses are important for our patients.

Fear of contagious diseases often creates social divisions. Governments should offer accurate information to reduce the detrimental effect of rumors and false propaganda.18 “Social distancing” is a misleading term; these practices should be referred to as “physical distancing.” We should encourage patients to maintain interpersonal contacts – albeit at a distance – to reach out to those in need, and to support one another during these troubled times.19



References

1. World Health Organization. Situation Report–107. 2020 May 6.

2. Centers for Disease Control and Prevention. Situation Update. 2020 Apr 30.

3. O’Brien M. “Are Americans in medical crisis avoiding the ER due to coronavirus?” PBS Newshour. 2020 May 6.

4. Rubin G et al. Health Technol Assess. 2010 Jul;14(340):183-266.

5. Hall R et al. Gen Hosp Psychiatry. 2008 Sep-Oct;30(5):466-52.

6. Verghese A. Clin Infect Dis. 2004;38:932-3.

7. Interagency Standing Committee. Briefing note on addressing health and psychosocial aspects of COVID-19 Outbreak – Version 11. 2020 Feb.

8. Sim K et al. J Psychosom Res. 2010;68:195-202.

9. Shigemura J et al. Psychiatry Clin Neurosci. 2020;74:281-2.

10. Garfin DR et al. Health Psychol. 2020 May;39(5):355-7.

11. Wang C et al. Int J Environ Res Public Health. 2020 Mar 6. doi: 10.3390/ijerph1751729.

12. Leung GM et al. J Epidemiol Community Health. 2003 Nov;57(1):857-63.

13. Xiang Y et al. Int J Biol Sci. 2020;16:1741-4.

14. Alvarez J, Hunt M. J Trauma Stress. 2005 Oct 18(5);18:497-505.

15. Cukor J et al. Depress Anxiety. 2011 Mar;28(3):210-7.

16. Horton R. Lancet. 2020 Feb;395(10222):400.

17. Xiang Y-T et al. Lancet Psychiatry. 2020 Feb 4;7:228-9.

18. World Health Organization. “Rational use of personal protective equipment (PPE) for coronavirus (COVID-19).” Interim Guidance. 2020 Mar.

19. Brooks S et al. Lancet 2020 Mar 14;395:912-20.

Dr. Doppalapudi is affiliated with Griffin Memorial Hospital in Norman, Okla. Dr. Lippmann is emeritus professor of psychiatry and also in family medicine at the University of Louisville (Ky.) Dr. Doppalapudi and Dr. Lippmann disclosed no conflicts of interest.

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USPSTF round-up

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In 2019, the US Preventive Services Task Force published 19 recommendation statements on 11 topics. Two of the topics are new; 9 are topics the Task Force had previously reviewed and has updated (TABLE 1). Three of these topics have been covered in Practice Alert podcasts (mdedge.com/familymedicine) and will not be discussed here: risk assessment, genetic counseling, and genetic testing for breast cancer susceptibility gene mutations (October 2019); medications to reduce the risk of breast cancer (December 2019); and preexposure prophylaxis to prevent HIV infections (January 2020).

Topics addressed by the USPSTF in 2019

Of the 19 recommendation statements made in 2019 (TABLE 2), 5 were rated “A” and 5 were “B,” meaning the evidence shows that benefits outweigh harms and these interventions should be offered in primary care practice. There were 5 “D” recommendations for interventions that should not be offered because they are either ineffective or harms exceed benefits. There were 3 “I” statements on interventions having insufficient evidence on benefits or harms to warrant a recommendation. Only 1 recommendation was rated “C” (selectively offer based on individual factors); this assessment is the hardest one to interpret and implement. Keep in mind that all “A” and “B” recommendations must be covered by commercial health plans with no out-of-pocket cost to the patient (ie, no co-pay or deductible).

2019 USPSTF recommendation statements

New recommendation on preventing perinatal depression

One of 2 new topics reviewed in 2019 was the prevention of perinatal depression. (As noted, the other on preexposure prophylaxis to prevent HIV infection has already been covered in a Practice Alert podcast.) The Task Force found that the prevalence of depression is estimated at 8.9% among pregnant women and 37% at any point in the first year postpartum.1

Depression during pregnancy and the postpartum period is associated with adverse effects on the mother and infant, including higher rates of suicide and suicidal ideation and thoughts of harming the infant.1 Women with perinatal depression are also more likely to exhibit significantly lower levels of positive maternal behaviors, such as praising and playing with their child,2 and higher rates of negative maternal behaviors.2 Perinatal depression is also associated with increased rates of preterm birth and low birth weight.3

Mothers with postpartum depression have higher rates of early termination of breast feeding and lower adherence for recommended child preventive services including vaccination.1 Children of mothers with perinatal depression develop more behavior problems, have lower cognitive functioning, and have an increased risk of psychiatric disorders than do children of mothers without this condition.4,5

A number of risk factors are associated with perinatal depression, but no screening tool was found to have enough predictive value to be recommended. In deciding who should receive an offer or referral for counseling, the Task Force recommends as a practical approach providing “counseling interventions to women with 1 or more of the following: a history of depression, current depressive symptoms (that do not reach a diagnostic threshold), certain socioeconomic risk factors such as low income or adolescent or single parenthood, recent intimate partner violence, or mental health-related factors such as elevated anxiety symptoms or a history of significant negative life events.”1

There is no conclusive evidence to guide timing of counseling interventions, but most studies reviewed started them in the second trimester. These studies included cognitive behavioral therapy and interpersonal therapy and involved counseling sessions that ranged from 4 to 20 sessions and lasted for 4 to 70 weeks. They involved group and individual sessions, mostly in-person visits, and were provided by a variety of health professionals.6

Continue to: The studies reviewed showed...

 

 

The studies reviewed showed that counseling interventions reduced the likelihood of developing depression symptoms by 39%, with a number needed to treat of 13.5.6 Studies that looked at pregnancy and maternal and infant clinical outcomes were mixed but usually found little to no difference with counseling.6 Even so, the Task Force felt that a reduction in depression itself was enough to warrant a “B” recommendation.

Screening for abdominal aortic aneurisms

Ultrasound is underused in screening for abdominal aortic aneurisms (AAA) and preventing death from their rupture. (See “Whom should you screen for abdominal aortic aneurysm?”) The prevalence of AAA is the United States is unknown; in other western countries it varies from 1.2% to 3.3% in men and is declining due to decreased rates of smoking, the primary risk factor.

The risk of AAA rupture is related to the size of the aneurism, and surgical repair (either endovascular or open repair) is usually reserved for lesions > 5.5 cm in diameter or for smaller ones that are rapidly increasing in size. The standard of care for most aneurysms < 5.5 cm is to periodically monitor growth ­using ultrasound.

The 2019 recommendations on AAA screening are essentially the same as those made in 2004; evaluation of new evidence supported the previous recommendations. The Task Force recommends one-time screening for men ages 65 to 75 years who have ever smoked (B recommendation). Selective screening is recommended for men in this age group who have never smoked, based mainly on personal factors such as a family history of AAA, the presence of other arterial aneurisms, and the number of risk factors for cardiovascular disease (C recommendation).

The Task Force recommends against screening women ages 65 to 75 years with no history of smoking or family history of AAA, while the evidence was felt to be insufficient to make a recommendation for women in this age range who have either risk factor. This is problematic for family physicians since women with these risk factors are at increased risk of AAA compared with women without risk factors.8 And aneurisms in women appear to rupture more frequently at smaller sizes, although at a later age than in men.8 Operative mortality is also higher in women than in men8 and there is no direct evidence that screening improves outcomes for women.

Continue to: Screening for asymptomatic bacteriuria

 

 

Screening for asymptomatic bacteriuria

The Task Force re-examined and reconfirmed its previous recommendations on screening for asymptomatic bacteriuria in adults. It recommends in favor of it for pregnant women, using a urine culture to screen, and against it for all other adults. There is good evidence that treating screen-detected asymptomatic bacteriuria in pregnant women reduces the incidence of pyelonephritis in pregnancy.

The Task Force made this a “B” recommendation based on a lower prevalence of pyelonephritis found in more recent studies, making the overall magnitude of benefits moderate. There is also good evidence that treating asymptomatic bacteriuria in nonpregnant adults offers no benefits.9 The Task Force has re-examined this topic 5 times since 1996 with essentially the same results.

Screening for elevated lead levels in children and pregnant women

In 2019 the Task Force changed its 2006 recommendation on screening for elevated lead levels. The earlier recommendation advised against screening both children ages 1 to 5 years and pregnant women at average risk for elevated blood lead levels. In 2006 the Task Force also felt that evidence was insufficient to make a recommendation regarding children ages 1 to 5 years at elevated risk.

The Task Force now believes the evidence is insufficient to make a recommendation for all children ages 1 to 5 years and for pregnant women, thus moving from a “D” to an “I” recommendation for children and pregnant women with average risk. Even though there is little evidence to support screening for elevated lead levels in children ages 1 to 5 years and in pregnant women, the Task Force apparently did not feel comfortable recommending against testing, given that the cutoff for elevated blood lead levels has been lowered from 10 to 5 mcg/dL and that other sources of lead may now be more prevalent than in 2006.10

Perinatal counseling of women with known risks of depression reduces the likelihood of depressive symptoms by 39%.

Remember that the Medicaid Early and Periodic Screening, Diagnostic, and Treatment program requires that all children receive a blood lead test twice, at ages 12 and 24 months, and that previously unscreened children ages 36 to 72 months must be tested once.

Continue to: Additional updates with no recommendation changes

 

 

Additional updates with no recommendation changes

Four other topics were re-examined by the Task Force in 2019, resulting in no significant changes to recommendations (TABLE 2):

  • Screen for hepatitis B infection in pregnant women at the first prenatal visit (A recommendation; updated from 2009).
  • Screen for HIV infection in adolescents and adults ages 15 to 65 years, and in those younger and older who are at high risk, and during pregnancy (A recommendation; updated from 2013).
  • Provide topical medication for all newborns to prevent gonococcal ophthalmia neonatorum (A recommendation; first recommendation in 1996, updated in 2005 and 2011).
  • Avoid screening for pancreatic cancer in asymptomatic adults (D recommendation; updated from 2004).

Affirmation of USPSTF’s value

In only 1 out of 9 reassessments of past topics did the Task Force modify its previous recommendations in any significant way. This demonstrates that recommendations will usually stand the test of time if they are made using robust, evidence-based methods (that consider both benefits and harms) and they are not made when evidence is insufficient. That only 2 new topics could be addressed in 2019 may reflect a need for more resources for the Task Force.

References

1. USPSTF. Interventions to prevent perinatal depression: US Preventive Services Task Force recommendation statement. JAMA. 2019;321:580-587.

2. Lovejoy MC, Graczyk PA, O’Hare E, et al. Maternal depression and parenting behavior: a meta-analytic review. Clin Psychol Rev. 2000;20:561-592.

3. Szegda K, Markenson G, Bertone-Johnson ER, et al. Depression during pregnancy: a risk factor for adverse neonatal outcomes? A critical review of the literature. J Matern Fetal Neonatal Med. 2014;27:960-967.

4. Beck CT. The effects of postpartum depression on child development: a meta-analysis. Arch Psychiatr Nurs. 1998;12:12-20.

5. Santos IS, Matijasevich A, Barros AJ, et al. Antenatal and postnatal maternal mood symptoms and psychiatric disorders in pre-school children from the 2004 Pelotas Birth Cohort. J Affect Disord. 2014;164:112-117.

6. O’Connor E, Senger CA, Henniger ML, et al. Interventions to prevent perinatal depression. Evidence report and systematic review for the US preventive services task force. JAMA. 2019;321:588-601.

7. USPSTF. Screening for abdominal aortic aneurysm: US Preventive Services Task Force recommendation statement. JAMA. 2019;322:2211-2218.

8. Guirguis-Blake JM, Beil TL, Senger CA, et al. Primary care screening for abdominal aortic aneurysm: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2019;322:2219-2238.

9. USPSTF. Owens DK, Davidson KW, Krist AH, et al. Screening for asymptomatic bacteriuria in adults: US Preventive Services Task Force recommendation statement. JAMA. 2019;322:1188-1194.

10. USPSTF. Screening for elevated blood lead levels in children and pregnant women: US Preventive Services Task Force recommendation statement. JAMA. 2019;321:1502-1509.

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In 2019, the US Preventive Services Task Force published 19 recommendation statements on 11 topics. Two of the topics are new; 9 are topics the Task Force had previously reviewed and has updated (TABLE 1). Three of these topics have been covered in Practice Alert podcasts (mdedge.com/familymedicine) and will not be discussed here: risk assessment, genetic counseling, and genetic testing for breast cancer susceptibility gene mutations (October 2019); medications to reduce the risk of breast cancer (December 2019); and preexposure prophylaxis to prevent HIV infections (January 2020).

Topics addressed by the USPSTF in 2019

Of the 19 recommendation statements made in 2019 (TABLE 2), 5 were rated “A” and 5 were “B,” meaning the evidence shows that benefits outweigh harms and these interventions should be offered in primary care practice. There were 5 “D” recommendations for interventions that should not be offered because they are either ineffective or harms exceed benefits. There were 3 “I” statements on interventions having insufficient evidence on benefits or harms to warrant a recommendation. Only 1 recommendation was rated “C” (selectively offer based on individual factors); this assessment is the hardest one to interpret and implement. Keep in mind that all “A” and “B” recommendations must be covered by commercial health plans with no out-of-pocket cost to the patient (ie, no co-pay or deductible).

2019 USPSTF recommendation statements

New recommendation on preventing perinatal depression

One of 2 new topics reviewed in 2019 was the prevention of perinatal depression. (As noted, the other on preexposure prophylaxis to prevent HIV infection has already been covered in a Practice Alert podcast.) The Task Force found that the prevalence of depression is estimated at 8.9% among pregnant women and 37% at any point in the first year postpartum.1

Depression during pregnancy and the postpartum period is associated with adverse effects on the mother and infant, including higher rates of suicide and suicidal ideation and thoughts of harming the infant.1 Women with perinatal depression are also more likely to exhibit significantly lower levels of positive maternal behaviors, such as praising and playing with their child,2 and higher rates of negative maternal behaviors.2 Perinatal depression is also associated with increased rates of preterm birth and low birth weight.3

Mothers with postpartum depression have higher rates of early termination of breast feeding and lower adherence for recommended child preventive services including vaccination.1 Children of mothers with perinatal depression develop more behavior problems, have lower cognitive functioning, and have an increased risk of psychiatric disorders than do children of mothers without this condition.4,5

A number of risk factors are associated with perinatal depression, but no screening tool was found to have enough predictive value to be recommended. In deciding who should receive an offer or referral for counseling, the Task Force recommends as a practical approach providing “counseling interventions to women with 1 or more of the following: a history of depression, current depressive symptoms (that do not reach a diagnostic threshold), certain socioeconomic risk factors such as low income or adolescent or single parenthood, recent intimate partner violence, or mental health-related factors such as elevated anxiety symptoms or a history of significant negative life events.”1

There is no conclusive evidence to guide timing of counseling interventions, but most studies reviewed started them in the second trimester. These studies included cognitive behavioral therapy and interpersonal therapy and involved counseling sessions that ranged from 4 to 20 sessions and lasted for 4 to 70 weeks. They involved group and individual sessions, mostly in-person visits, and were provided by a variety of health professionals.6

Continue to: The studies reviewed showed...

 

 

The studies reviewed showed that counseling interventions reduced the likelihood of developing depression symptoms by 39%, with a number needed to treat of 13.5.6 Studies that looked at pregnancy and maternal and infant clinical outcomes were mixed but usually found little to no difference with counseling.6 Even so, the Task Force felt that a reduction in depression itself was enough to warrant a “B” recommendation.

Screening for abdominal aortic aneurisms

Ultrasound is underused in screening for abdominal aortic aneurisms (AAA) and preventing death from their rupture. (See “Whom should you screen for abdominal aortic aneurysm?”) The prevalence of AAA is the United States is unknown; in other western countries it varies from 1.2% to 3.3% in men and is declining due to decreased rates of smoking, the primary risk factor.

The risk of AAA rupture is related to the size of the aneurism, and surgical repair (either endovascular or open repair) is usually reserved for lesions > 5.5 cm in diameter or for smaller ones that are rapidly increasing in size. The standard of care for most aneurysms < 5.5 cm is to periodically monitor growth ­using ultrasound.

The 2019 recommendations on AAA screening are essentially the same as those made in 2004; evaluation of new evidence supported the previous recommendations. The Task Force recommends one-time screening for men ages 65 to 75 years who have ever smoked (B recommendation). Selective screening is recommended for men in this age group who have never smoked, based mainly on personal factors such as a family history of AAA, the presence of other arterial aneurisms, and the number of risk factors for cardiovascular disease (C recommendation).

The Task Force recommends against screening women ages 65 to 75 years with no history of smoking or family history of AAA, while the evidence was felt to be insufficient to make a recommendation for women in this age range who have either risk factor. This is problematic for family physicians since women with these risk factors are at increased risk of AAA compared with women without risk factors.8 And aneurisms in women appear to rupture more frequently at smaller sizes, although at a later age than in men.8 Operative mortality is also higher in women than in men8 and there is no direct evidence that screening improves outcomes for women.

Continue to: Screening for asymptomatic bacteriuria

 

 

Screening for asymptomatic bacteriuria

The Task Force re-examined and reconfirmed its previous recommendations on screening for asymptomatic bacteriuria in adults. It recommends in favor of it for pregnant women, using a urine culture to screen, and against it for all other adults. There is good evidence that treating screen-detected asymptomatic bacteriuria in pregnant women reduces the incidence of pyelonephritis in pregnancy.

The Task Force made this a “B” recommendation based on a lower prevalence of pyelonephritis found in more recent studies, making the overall magnitude of benefits moderate. There is also good evidence that treating asymptomatic bacteriuria in nonpregnant adults offers no benefits.9 The Task Force has re-examined this topic 5 times since 1996 with essentially the same results.

Screening for elevated lead levels in children and pregnant women

In 2019 the Task Force changed its 2006 recommendation on screening for elevated lead levels. The earlier recommendation advised against screening both children ages 1 to 5 years and pregnant women at average risk for elevated blood lead levels. In 2006 the Task Force also felt that evidence was insufficient to make a recommendation regarding children ages 1 to 5 years at elevated risk.

The Task Force now believes the evidence is insufficient to make a recommendation for all children ages 1 to 5 years and for pregnant women, thus moving from a “D” to an “I” recommendation for children and pregnant women with average risk. Even though there is little evidence to support screening for elevated lead levels in children ages 1 to 5 years and in pregnant women, the Task Force apparently did not feel comfortable recommending against testing, given that the cutoff for elevated blood lead levels has been lowered from 10 to 5 mcg/dL and that other sources of lead may now be more prevalent than in 2006.10

Perinatal counseling of women with known risks of depression reduces the likelihood of depressive symptoms by 39%.

Remember that the Medicaid Early and Periodic Screening, Diagnostic, and Treatment program requires that all children receive a blood lead test twice, at ages 12 and 24 months, and that previously unscreened children ages 36 to 72 months must be tested once.

Continue to: Additional updates with no recommendation changes

 

 

Additional updates with no recommendation changes

Four other topics were re-examined by the Task Force in 2019, resulting in no significant changes to recommendations (TABLE 2):

  • Screen for hepatitis B infection in pregnant women at the first prenatal visit (A recommendation; updated from 2009).
  • Screen for HIV infection in adolescents and adults ages 15 to 65 years, and in those younger and older who are at high risk, and during pregnancy (A recommendation; updated from 2013).
  • Provide topical medication for all newborns to prevent gonococcal ophthalmia neonatorum (A recommendation; first recommendation in 1996, updated in 2005 and 2011).
  • Avoid screening for pancreatic cancer in asymptomatic adults (D recommendation; updated from 2004).

Affirmation of USPSTF’s value

In only 1 out of 9 reassessments of past topics did the Task Force modify its previous recommendations in any significant way. This demonstrates that recommendations will usually stand the test of time if they are made using robust, evidence-based methods (that consider both benefits and harms) and they are not made when evidence is insufficient. That only 2 new topics could be addressed in 2019 may reflect a need for more resources for the Task Force.

In 2019, the US Preventive Services Task Force published 19 recommendation statements on 11 topics. Two of the topics are new; 9 are topics the Task Force had previously reviewed and has updated (TABLE 1). Three of these topics have been covered in Practice Alert podcasts (mdedge.com/familymedicine) and will not be discussed here: risk assessment, genetic counseling, and genetic testing for breast cancer susceptibility gene mutations (October 2019); medications to reduce the risk of breast cancer (December 2019); and preexposure prophylaxis to prevent HIV infections (January 2020).

Topics addressed by the USPSTF in 2019

Of the 19 recommendation statements made in 2019 (TABLE 2), 5 were rated “A” and 5 were “B,” meaning the evidence shows that benefits outweigh harms and these interventions should be offered in primary care practice. There were 5 “D” recommendations for interventions that should not be offered because they are either ineffective or harms exceed benefits. There were 3 “I” statements on interventions having insufficient evidence on benefits or harms to warrant a recommendation. Only 1 recommendation was rated “C” (selectively offer based on individual factors); this assessment is the hardest one to interpret and implement. Keep in mind that all “A” and “B” recommendations must be covered by commercial health plans with no out-of-pocket cost to the patient (ie, no co-pay or deductible).

2019 USPSTF recommendation statements

New recommendation on preventing perinatal depression

One of 2 new topics reviewed in 2019 was the prevention of perinatal depression. (As noted, the other on preexposure prophylaxis to prevent HIV infection has already been covered in a Practice Alert podcast.) The Task Force found that the prevalence of depression is estimated at 8.9% among pregnant women and 37% at any point in the first year postpartum.1

Depression during pregnancy and the postpartum period is associated with adverse effects on the mother and infant, including higher rates of suicide and suicidal ideation and thoughts of harming the infant.1 Women with perinatal depression are also more likely to exhibit significantly lower levels of positive maternal behaviors, such as praising and playing with their child,2 and higher rates of negative maternal behaviors.2 Perinatal depression is also associated with increased rates of preterm birth and low birth weight.3

Mothers with postpartum depression have higher rates of early termination of breast feeding and lower adherence for recommended child preventive services including vaccination.1 Children of mothers with perinatal depression develop more behavior problems, have lower cognitive functioning, and have an increased risk of psychiatric disorders than do children of mothers without this condition.4,5

A number of risk factors are associated with perinatal depression, but no screening tool was found to have enough predictive value to be recommended. In deciding who should receive an offer or referral for counseling, the Task Force recommends as a practical approach providing “counseling interventions to women with 1 or more of the following: a history of depression, current depressive symptoms (that do not reach a diagnostic threshold), certain socioeconomic risk factors such as low income or adolescent or single parenthood, recent intimate partner violence, or mental health-related factors such as elevated anxiety symptoms or a history of significant negative life events.”1

There is no conclusive evidence to guide timing of counseling interventions, but most studies reviewed started them in the second trimester. These studies included cognitive behavioral therapy and interpersonal therapy and involved counseling sessions that ranged from 4 to 20 sessions and lasted for 4 to 70 weeks. They involved group and individual sessions, mostly in-person visits, and were provided by a variety of health professionals.6

Continue to: The studies reviewed showed...

 

 

The studies reviewed showed that counseling interventions reduced the likelihood of developing depression symptoms by 39%, with a number needed to treat of 13.5.6 Studies that looked at pregnancy and maternal and infant clinical outcomes were mixed but usually found little to no difference with counseling.6 Even so, the Task Force felt that a reduction in depression itself was enough to warrant a “B” recommendation.

Screening for abdominal aortic aneurisms

Ultrasound is underused in screening for abdominal aortic aneurisms (AAA) and preventing death from their rupture. (See “Whom should you screen for abdominal aortic aneurysm?”) The prevalence of AAA is the United States is unknown; in other western countries it varies from 1.2% to 3.3% in men and is declining due to decreased rates of smoking, the primary risk factor.

The risk of AAA rupture is related to the size of the aneurism, and surgical repair (either endovascular or open repair) is usually reserved for lesions > 5.5 cm in diameter or for smaller ones that are rapidly increasing in size. The standard of care for most aneurysms < 5.5 cm is to periodically monitor growth ­using ultrasound.

The 2019 recommendations on AAA screening are essentially the same as those made in 2004; evaluation of new evidence supported the previous recommendations. The Task Force recommends one-time screening for men ages 65 to 75 years who have ever smoked (B recommendation). Selective screening is recommended for men in this age group who have never smoked, based mainly on personal factors such as a family history of AAA, the presence of other arterial aneurisms, and the number of risk factors for cardiovascular disease (C recommendation).

The Task Force recommends against screening women ages 65 to 75 years with no history of smoking or family history of AAA, while the evidence was felt to be insufficient to make a recommendation for women in this age range who have either risk factor. This is problematic for family physicians since women with these risk factors are at increased risk of AAA compared with women without risk factors.8 And aneurisms in women appear to rupture more frequently at smaller sizes, although at a later age than in men.8 Operative mortality is also higher in women than in men8 and there is no direct evidence that screening improves outcomes for women.

Continue to: Screening for asymptomatic bacteriuria

 

 

Screening for asymptomatic bacteriuria

The Task Force re-examined and reconfirmed its previous recommendations on screening for asymptomatic bacteriuria in adults. It recommends in favor of it for pregnant women, using a urine culture to screen, and against it for all other adults. There is good evidence that treating screen-detected asymptomatic bacteriuria in pregnant women reduces the incidence of pyelonephritis in pregnancy.

The Task Force made this a “B” recommendation based on a lower prevalence of pyelonephritis found in more recent studies, making the overall magnitude of benefits moderate. There is also good evidence that treating asymptomatic bacteriuria in nonpregnant adults offers no benefits.9 The Task Force has re-examined this topic 5 times since 1996 with essentially the same results.

Screening for elevated lead levels in children and pregnant women

In 2019 the Task Force changed its 2006 recommendation on screening for elevated lead levels. The earlier recommendation advised against screening both children ages 1 to 5 years and pregnant women at average risk for elevated blood lead levels. In 2006 the Task Force also felt that evidence was insufficient to make a recommendation regarding children ages 1 to 5 years at elevated risk.

The Task Force now believes the evidence is insufficient to make a recommendation for all children ages 1 to 5 years and for pregnant women, thus moving from a “D” to an “I” recommendation for children and pregnant women with average risk. Even though there is little evidence to support screening for elevated lead levels in children ages 1 to 5 years and in pregnant women, the Task Force apparently did not feel comfortable recommending against testing, given that the cutoff for elevated blood lead levels has been lowered from 10 to 5 mcg/dL and that other sources of lead may now be more prevalent than in 2006.10

Perinatal counseling of women with known risks of depression reduces the likelihood of depressive symptoms by 39%.

Remember that the Medicaid Early and Periodic Screening, Diagnostic, and Treatment program requires that all children receive a blood lead test twice, at ages 12 and 24 months, and that previously unscreened children ages 36 to 72 months must be tested once.

Continue to: Additional updates with no recommendation changes

 

 

Additional updates with no recommendation changes

Four other topics were re-examined by the Task Force in 2019, resulting in no significant changes to recommendations (TABLE 2):

  • Screen for hepatitis B infection in pregnant women at the first prenatal visit (A recommendation; updated from 2009).
  • Screen for HIV infection in adolescents and adults ages 15 to 65 years, and in those younger and older who are at high risk, and during pregnancy (A recommendation; updated from 2013).
  • Provide topical medication for all newborns to prevent gonococcal ophthalmia neonatorum (A recommendation; first recommendation in 1996, updated in 2005 and 2011).
  • Avoid screening for pancreatic cancer in asymptomatic adults (D recommendation; updated from 2004).

Affirmation of USPSTF’s value

In only 1 out of 9 reassessments of past topics did the Task Force modify its previous recommendations in any significant way. This demonstrates that recommendations will usually stand the test of time if they are made using robust, evidence-based methods (that consider both benefits and harms) and they are not made when evidence is insufficient. That only 2 new topics could be addressed in 2019 may reflect a need for more resources for the Task Force.

References

1. USPSTF. Interventions to prevent perinatal depression: US Preventive Services Task Force recommendation statement. JAMA. 2019;321:580-587.

2. Lovejoy MC, Graczyk PA, O’Hare E, et al. Maternal depression and parenting behavior: a meta-analytic review. Clin Psychol Rev. 2000;20:561-592.

3. Szegda K, Markenson G, Bertone-Johnson ER, et al. Depression during pregnancy: a risk factor for adverse neonatal outcomes? A critical review of the literature. J Matern Fetal Neonatal Med. 2014;27:960-967.

4. Beck CT. The effects of postpartum depression on child development: a meta-analysis. Arch Psychiatr Nurs. 1998;12:12-20.

5. Santos IS, Matijasevich A, Barros AJ, et al. Antenatal and postnatal maternal mood symptoms and psychiatric disorders in pre-school children from the 2004 Pelotas Birth Cohort. J Affect Disord. 2014;164:112-117.

6. O’Connor E, Senger CA, Henniger ML, et al. Interventions to prevent perinatal depression. Evidence report and systematic review for the US preventive services task force. JAMA. 2019;321:588-601.

7. USPSTF. Screening for abdominal aortic aneurysm: US Preventive Services Task Force recommendation statement. JAMA. 2019;322:2211-2218.

8. Guirguis-Blake JM, Beil TL, Senger CA, et al. Primary care screening for abdominal aortic aneurysm: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2019;322:2219-2238.

9. USPSTF. Owens DK, Davidson KW, Krist AH, et al. Screening for asymptomatic bacteriuria in adults: US Preventive Services Task Force recommendation statement. JAMA. 2019;322:1188-1194.

10. USPSTF. Screening for elevated blood lead levels in children and pregnant women: US Preventive Services Task Force recommendation statement. JAMA. 2019;321:1502-1509.

References

1. USPSTF. Interventions to prevent perinatal depression: US Preventive Services Task Force recommendation statement. JAMA. 2019;321:580-587.

2. Lovejoy MC, Graczyk PA, O’Hare E, et al. Maternal depression and parenting behavior: a meta-analytic review. Clin Psychol Rev. 2000;20:561-592.

3. Szegda K, Markenson G, Bertone-Johnson ER, et al. Depression during pregnancy: a risk factor for adverse neonatal outcomes? A critical review of the literature. J Matern Fetal Neonatal Med. 2014;27:960-967.

4. Beck CT. The effects of postpartum depression on child development: a meta-analysis. Arch Psychiatr Nurs. 1998;12:12-20.

5. Santos IS, Matijasevich A, Barros AJ, et al. Antenatal and postnatal maternal mood symptoms and psychiatric disorders in pre-school children from the 2004 Pelotas Birth Cohort. J Affect Disord. 2014;164:112-117.

6. O’Connor E, Senger CA, Henniger ML, et al. Interventions to prevent perinatal depression. Evidence report and systematic review for the US preventive services task force. JAMA. 2019;321:588-601.

7. USPSTF. Screening for abdominal aortic aneurysm: US Preventive Services Task Force recommendation statement. JAMA. 2019;322:2211-2218.

8. Guirguis-Blake JM, Beil TL, Senger CA, et al. Primary care screening for abdominal aortic aneurysm: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2019;322:2219-2238.

9. USPSTF. Owens DK, Davidson KW, Krist AH, et al. Screening for asymptomatic bacteriuria in adults: US Preventive Services Task Force recommendation statement. JAMA. 2019;322:1188-1194.

10. USPSTF. Screening for elevated blood lead levels in children and pregnant women: US Preventive Services Task Force recommendation statement. JAMA. 2019;321:1502-1509.

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How effective is that face mask?

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How effective is that face mask?

More and more, the streets of America are looking like those of Eastern countries (such as China) during previous public health crises. Americans are wearing face masks.

The best homemade masks are those with 2 layers of high-quality, heavyweight “quilter’s cotton” with a thread count of 180 or more.

In addition to social distancing and hand washing, face masks are a primary defense against COVID-19. N95 face masks protect against 95% of the particles that are likely to transmit respiratory infection microbes. Last month, the Centers for Disease Control and Prevention (CDC) recommended that we all use masks, in addition to social distancing, in public settings. Since there will not be a sufficient supply of N95 masks for the general public (and they are difficult to fit and wear properly), we are left with surgical masks and so-called DIY (do-it-yourself) masks. But do DIY face masks protect against COVID-19?

The National Academies of Sciences, Engineering, and Medicine published a scientific review of fabric face masks last month.1 They found 7 studies that evaluated either the ability of the mask to protect the wearer or to prevent the spread of infectious particles from a wearer. Performance ranged from very poor to 50% filtration depending on the material used. Jayaraman2 found a filtration rate of 50% for 4 layers of polyester knitted cut-pile fabric, the best material he tested. Davies3 compared a 2-layer cotton DIY mask with a surgical face mask and found that the cotton mask was 3 times less effective. And in the only randomized trial of cotton masks, the cotton 2-layer masks performed much worse than medical masks in protecting from respiratory infection (relative risk [RR] = 13).4 A study of COVID-19-infected patients found that neither surgical nor cotton masks were effective at blocking the virus from disseminating during coughing.5

The most recent lab testing of DIY masks was done at Wake Forest Institute for Regenerative Medicine, where they tested a variety of materials; the results were somewhat encouraging.6 The best homemade masks were those with “2 layers of high-quality, heavyweight ‘quilter’s cotton’ with a thread count of 180 or more, and those with especially tight weave and thicker thread such as batiks.”6 The best homemade masks achieved 79% filtration. But single-layer masks or double-layer designs of lower quality, lightweight cotton achieved as little as 1% filtration.

The bottom line: Mass production and use of N95-type masks would be most effective in preventing transmission in general public settings, but this seems unlikely. Surgical masks are next best. Well-constructed DIY masks are the last resort but can provide some protection against infection.

References

1. Besser R, Fischhoff B; National Academy of Sciences, Engineering, and Medicine. Rapid Expert Consultation on the Effectiveness of Fabric Masks for the COVID-19 Pandemic (April 8, 2020). www.nap.edu/read/25776/chapter/1. Published April 8, 2020. Accessed April 28, 2020.

2. Jayaraman S. Pandemic flu—textile solutions pilot: design and development of innovative medical masks [final technical report]. Atlanta, GA: Georgia Institute of Technology; 2012.

3. Davies A, Thompson K, Giri K, et al. Testing the efficacy of homemade masks: would they protect in an influenza pandemic? Disaster Med Public Health Prep. 2013;7:413-418.

4. MacIntyre CR, Seale H, Dung TC, et al. A cluster randomised trial of cloth masks compared with medical masks in healthcare workers. BMJ Open. 2015;5:e006577.

5. Bae S, Kim MC, Kim JY, et al. Effectiveness of surgical and cotton masks in blocking SARS-CoV-2: a controlled comparison in 4 patients [published online ahead of print April 6, 2020]. Ann Intern Med. 2020.

6. Wake Forest Baptist Medical Center. Testing shows type of cloth used in homemade masks makes a difference, doctors say. https://newsroom.wakehealth.edu/News-Releases/2020/04/Testing-Shows-Type-of-Cloth-Used-in-Homemade-Masks-Makes-a-­Difference. Published April 2, 2020. Accessed April 28, 2020.

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More and more, the streets of America are looking like those of Eastern countries (such as China) during previous public health crises. Americans are wearing face masks.

The best homemade masks are those with 2 layers of high-quality, heavyweight “quilter’s cotton” with a thread count of 180 or more.

In addition to social distancing and hand washing, face masks are a primary defense against COVID-19. N95 face masks protect against 95% of the particles that are likely to transmit respiratory infection microbes. Last month, the Centers for Disease Control and Prevention (CDC) recommended that we all use masks, in addition to social distancing, in public settings. Since there will not be a sufficient supply of N95 masks for the general public (and they are difficult to fit and wear properly), we are left with surgical masks and so-called DIY (do-it-yourself) masks. But do DIY face masks protect against COVID-19?

The National Academies of Sciences, Engineering, and Medicine published a scientific review of fabric face masks last month.1 They found 7 studies that evaluated either the ability of the mask to protect the wearer or to prevent the spread of infectious particles from a wearer. Performance ranged from very poor to 50% filtration depending on the material used. Jayaraman2 found a filtration rate of 50% for 4 layers of polyester knitted cut-pile fabric, the best material he tested. Davies3 compared a 2-layer cotton DIY mask with a surgical face mask and found that the cotton mask was 3 times less effective. And in the only randomized trial of cotton masks, the cotton 2-layer masks performed much worse than medical masks in protecting from respiratory infection (relative risk [RR] = 13).4 A study of COVID-19-infected patients found that neither surgical nor cotton masks were effective at blocking the virus from disseminating during coughing.5

The most recent lab testing of DIY masks was done at Wake Forest Institute for Regenerative Medicine, where they tested a variety of materials; the results were somewhat encouraging.6 The best homemade masks were those with “2 layers of high-quality, heavyweight ‘quilter’s cotton’ with a thread count of 180 or more, and those with especially tight weave and thicker thread such as batiks.”6 The best homemade masks achieved 79% filtration. But single-layer masks or double-layer designs of lower quality, lightweight cotton achieved as little as 1% filtration.

The bottom line: Mass production and use of N95-type masks would be most effective in preventing transmission in general public settings, but this seems unlikely. Surgical masks are next best. Well-constructed DIY masks are the last resort but can provide some protection against infection.

More and more, the streets of America are looking like those of Eastern countries (such as China) during previous public health crises. Americans are wearing face masks.

The best homemade masks are those with 2 layers of high-quality, heavyweight “quilter’s cotton” with a thread count of 180 or more.

In addition to social distancing and hand washing, face masks are a primary defense against COVID-19. N95 face masks protect against 95% of the particles that are likely to transmit respiratory infection microbes. Last month, the Centers for Disease Control and Prevention (CDC) recommended that we all use masks, in addition to social distancing, in public settings. Since there will not be a sufficient supply of N95 masks for the general public (and they are difficult to fit and wear properly), we are left with surgical masks and so-called DIY (do-it-yourself) masks. But do DIY face masks protect against COVID-19?

The National Academies of Sciences, Engineering, and Medicine published a scientific review of fabric face masks last month.1 They found 7 studies that evaluated either the ability of the mask to protect the wearer or to prevent the spread of infectious particles from a wearer. Performance ranged from very poor to 50% filtration depending on the material used. Jayaraman2 found a filtration rate of 50% for 4 layers of polyester knitted cut-pile fabric, the best material he tested. Davies3 compared a 2-layer cotton DIY mask with a surgical face mask and found that the cotton mask was 3 times less effective. And in the only randomized trial of cotton masks, the cotton 2-layer masks performed much worse than medical masks in protecting from respiratory infection (relative risk [RR] = 13).4 A study of COVID-19-infected patients found that neither surgical nor cotton masks were effective at blocking the virus from disseminating during coughing.5

The most recent lab testing of DIY masks was done at Wake Forest Institute for Regenerative Medicine, where they tested a variety of materials; the results were somewhat encouraging.6 The best homemade masks were those with “2 layers of high-quality, heavyweight ‘quilter’s cotton’ with a thread count of 180 or more, and those with especially tight weave and thicker thread such as batiks.”6 The best homemade masks achieved 79% filtration. But single-layer masks or double-layer designs of lower quality, lightweight cotton achieved as little as 1% filtration.

The bottom line: Mass production and use of N95-type masks would be most effective in preventing transmission in general public settings, but this seems unlikely. Surgical masks are next best. Well-constructed DIY masks are the last resort but can provide some protection against infection.

References

1. Besser R, Fischhoff B; National Academy of Sciences, Engineering, and Medicine. Rapid Expert Consultation on the Effectiveness of Fabric Masks for the COVID-19 Pandemic (April 8, 2020). www.nap.edu/read/25776/chapter/1. Published April 8, 2020. Accessed April 28, 2020.

2. Jayaraman S. Pandemic flu—textile solutions pilot: design and development of innovative medical masks [final technical report]. Atlanta, GA: Georgia Institute of Technology; 2012.

3. Davies A, Thompson K, Giri K, et al. Testing the efficacy of homemade masks: would they protect in an influenza pandemic? Disaster Med Public Health Prep. 2013;7:413-418.

4. MacIntyre CR, Seale H, Dung TC, et al. A cluster randomised trial of cloth masks compared with medical masks in healthcare workers. BMJ Open. 2015;5:e006577.

5. Bae S, Kim MC, Kim JY, et al. Effectiveness of surgical and cotton masks in blocking SARS-CoV-2: a controlled comparison in 4 patients [published online ahead of print April 6, 2020]. Ann Intern Med. 2020.

6. Wake Forest Baptist Medical Center. Testing shows type of cloth used in homemade masks makes a difference, doctors say. https://newsroom.wakehealth.edu/News-Releases/2020/04/Testing-Shows-Type-of-Cloth-Used-in-Homemade-Masks-Makes-a-­Difference. Published April 2, 2020. Accessed April 28, 2020.

References

1. Besser R, Fischhoff B; National Academy of Sciences, Engineering, and Medicine. Rapid Expert Consultation on the Effectiveness of Fabric Masks for the COVID-19 Pandemic (April 8, 2020). www.nap.edu/read/25776/chapter/1. Published April 8, 2020. Accessed April 28, 2020.

2. Jayaraman S. Pandemic flu—textile solutions pilot: design and development of innovative medical masks [final technical report]. Atlanta, GA: Georgia Institute of Technology; 2012.

3. Davies A, Thompson K, Giri K, et al. Testing the efficacy of homemade masks: would they protect in an influenza pandemic? Disaster Med Public Health Prep. 2013;7:413-418.

4. MacIntyre CR, Seale H, Dung TC, et al. A cluster randomised trial of cloth masks compared with medical masks in healthcare workers. BMJ Open. 2015;5:e006577.

5. Bae S, Kim MC, Kim JY, et al. Effectiveness of surgical and cotton masks in blocking SARS-CoV-2: a controlled comparison in 4 patients [published online ahead of print April 6, 2020]. Ann Intern Med. 2020.

6. Wake Forest Baptist Medical Center. Testing shows type of cloth used in homemade masks makes a difference, doctors say. https://newsroom.wakehealth.edu/News-Releases/2020/04/Testing-Shows-Type-of-Cloth-Used-in-Homemade-Masks-Makes-a-­Difference. Published April 2, 2020. Accessed April 28, 2020.

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Silent brain infarcts found in 3% of AFib patients, tied to cognitive decline

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Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.

Dr. David Conen

The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.

“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.

Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.

This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.

Dr. Fred Kusumoto

These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.

“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.



The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.

Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.

Dr. Christine M. Albert

Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.

SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.

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Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.

Dr. David Conen

The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.

“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.

Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.

This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.

Dr. Fred Kusumoto

These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.

“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.



The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.

Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.

Dr. Christine M. Albert

Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.

SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.

Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.

Dr. David Conen

The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.

“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.

Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.

This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.

Dr. Fred Kusumoto

These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.

“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.



The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.

Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.

Dr. Christine M. Albert

Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.

SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.

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Hypertriglyceridemia: A strategic approach

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Hypertriglyceridemia: A strategic approach

CASE 1

Tyler M, age 40, otherwise healthy, and with a body mass index (BMI) of 30, presents to your office for his annual physical examination. He does not have a history of alcohol or tobacco use.

Mr. M’s obesity raises concern about metabolic syndrome, which warrants evaluation for hypertriglyceridemia (HTG). You offer him lipid testing to estimate his risk of atherosclerotic cardiovascular disease (ASCVD).

The only abnormal value on the lipid panel is a triglyceride (TG) level of 264 mg/dL (normal, < 175 mg/dL). Mr. M’s 10-yr ASCVD risk is determined to be < 5%.

What, if any, intervention would be triggered by the finding of moderate HTG?

Heart
© ALICIA BUELOW

CASE 2

Alicia F, age 30, with a BMI of 28 and ASCVD risk < 7.5%, comes to the clinic for evaluation of anxiety and insomnia. She reports eating a high-carbohydrate diet and drinking 3 to 5 alcoholic beverages nightly to help her sleep.

Ms. F’s daily alcohol use prompts evaluation for HTG. Results show a TG level of 1300 mg/dL and a high-density lipoprotein (HDL) level of 25 mg/dL (healthy HDL levels: adult females, ≥ 50 mg/dL; adult males, ≥ 40 mg/dL). Other test results are normal, except for elevated transaminase levels (just under twice normal).

What, if any, action would be prompted by the patient’s severe HTG and below-normal HDL level?

Continue to: How HTG is defined

 

 

How HTG is defined: Causes, cutoffs, signs

HTG is most commonly caused by obesity and a sedentary lifestyle; certain associated comorbid medical conditions can also be a precipitant (Table 11,2). Because the condition is a result of polygenic phenotypic expression, even a genetically low-risk patient can present with HTG when exposed to certain medical conditions and environmental causes.

Causes of hypertriglyceridemia

Primary HTG (genetic or familial) is rare. Genetic testing may be considered for patients with TG > 1000 mg/dL (severely elevated TG = 500 to 1999 mg/dL, measured in fasting state*) or a family history of early ASCVD (TABLE 11,2).2,3

Even a genetically low-risk patient can present with hypertriglyceridemia when exposed to certain medical conditions and environmental causes.

Typically, HTG is asymptomatic. Xanthelasmas, xanthomas, and lipemia retinalis are found in hereditary disorders of elevated TGs. Occasionally, HTG manifests as chylomicronemia syndrome, characterized by recurrent abdominal pain, nausea, vomiting, and, in severe HTG, pancreatitis.3

 

Fine points of TG measurement

Triglycerides are a component of a complete lipid profile, which also includes total cholesterol, calculated low-density lipoprotein (LDL-C), and HDL.4 As in both case vignettes, detection of HTG is often incidental, when a lipid profile is ordered to evaluate the risk of ASCVD. (Of note, for people older than 20 years, the US Preventive Services Task Force no longer addresses the question, “Which population should be screened for dyslipidemia?” Instead, current recommendations answer the question, “For which population should statin therapy be prescribed?”5)

Effect on ASCVD risk assessment. TG levels are known to vary, depending on fasting or nonfasting status, with lower levels reported when fasting. An elevated TG level can lead to inaccurate calculation of LDL when using the Friedewald formula6:

LDL = total cholesterol – (triglycerides/5) – HDL

Continue to: The purpose of testing...

 

 

The purpose of testing lipids in a fasting state (> 9 hours) is to minimize the effects of an elevated TG level on the calculated LDL. In severe HTG, beta-quantitation by ultracentrifugation and electrophoresis can be performed to determine the LDL level directly.

Advantage of nonfasting measurement. When LDL-C is not a concern, there is, in fact, value in measuring TGs in the nonfasting state. Why? Because a nonfasting TG level is a better indicator of a patient’s average TG status: Studies have found a higher ASCVD risk in the setting of an elevated postprandial TG level accompanied by a low HDL level.7

Studies have found a higher ASCVD risk in the setting of an elevated postprandial triglyceride level accompanied by a low HDL level.

The Copenhagen City Heart Study identified postprandial HTG as an independent risk factor for atherogenicity, even in the setting of a normal fasting TG level.8 American Association of Clinical Endocrinologists and American College of Endocrinology guidelines endorse testing the nonfasting TG level when the fasting TG level is elevated in a lipid profile; if the nonfasting TG level is > 500 mg/dL, evaluation for secondary causes is warranted9,10 (Table 11,2).

 

In a practical sense, therefore, offering patients nonfasting lipid testing allows more people to obtain access to timely care.

Pancreatitis. Acute pancreatitis commonly prompts an evaluation for HTG. The risk of acute pancreatitis in the general population is 0.04%, but that risk increases to 8% to 31% for a person with HTG.11 Incidence when the TG level is > 500 mg/dL is thought to be increased because chylomicrons, acting as a TG carrier in the bloodstream, are responsible for pancreatitis.3 Treating HTG can reduce both the risk and recurrence of pancreatitis12,13; given that the postprandial TG level can change rapidly from severe to very severe (> 2000 mg/dL), multiple guidelines recommend pharmacotherapy to a TG goal of < 500-1000 mg/dL.1,9,13,14

Continue to: An ASCVD risk-HTG connection?

 

 

An ASCVD risk–HTG connection? In the population already at higher risk of ASCVD (> 7.5%), HTG is recognized as a risk-enhancing factor because of its atherogenic potential (Table 22); however, there is insufficient evidence that TGs have a role as an independent risk factor for ASCVD. In a population-based study of 58,000 people, 40 to 65 years of age, conducted at Copenhagen [Denmark] University Hospital, investigators found that those who did not meet criteria for statin treatment and who had a TG level > 264 mg/dL had a 10-year risk of a major adverse cardiovascular event similar to that of people who did meet criteria for statin therapy.15

Risk factors and risk-enhancing factors for atherosclerotic cardiovascular disease

The FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) and AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) studies, among others, have failed to show a significant reduction in coronary events by treating HTG.10

That said, it’s worth considering the findings of other trials:

  • In the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22) trial, an overall 28% reduction in endpoint events (myocardial infarction, acute coronary syndrome) was seen with high-intensity statin therapy, compared to moderate-intensity therapy.10 However, there was a sizeable residual risk identified that was theorized by investigators to be associated with high non-HDL lipoproteins, including TGs.
  • A 2016 study in Israel, in which 22 years of data on 15,355 patients with established ASCVD were studied, revealed that elevated TGs are associated with an increased long-term mortality risk that is independent of the HDL level.16
  • A cross-sectional study, nested in the prospective Copenhagen City Heart Study, demonstrated that HTG is associated with an increase in ischemic stroke events.17
 

Treatment

Therapeutic lifestyle changes

Changes in lifestyle are the foundation of management of, and recommended first-line treatment for, all patients with HTG. Patients with a moderately elevated TG level (175-499 mg/dL, measured in a fasting or nonfasting state) can be treated with therapeutic lifestyle changes alone1,2; a trial of 3 to 6 months (see specific interventions below) is recommended before considering adding medications.10

Weight loss. There is a strong association between BMI > 30 and HTG. Visceral adiposity is a much more significant risk than subcutaneous adipose tissue. Although weight loss to an ideal range is recommended, even a 10% to 15% reduction in an obese patient can reduce the TG level by 20%. A combination of moderate-intensity exercise and healthy eating habits appears to assist best with this intervention.18

Continue to: Exercise

 

 

Exercise. Thirty minutes a day of moderate-intensity exercise is associated with a significant drop in postprandial TG. This benefit can last as long as 3 days, suggesting a goal of at least 3 days a week of an active lifestyle. Such a program can include intermittent aerobics or mild resistance exercise.19

Healthy eating habits. The difference between a low-fat, high-carbohydrate diet and a high-fat, low-carbohydrate diet is less important than the overall benefit of weight loss from either of these diets. Complex carbohydrates are recommended over simple carbohydrates. A low-carbohydrate diet in a patient with diabetes has been demonstrated to improve the TG level, irrespective of weight change.20

The risk of acute pancreatitis in the general population is 0.04%, but that risk increases to 8% to 31% for a person with hypertriglyceridemia

A Mediterranean diet can reduce the TG level by 10% to 15%, and is recommended over a low-fat diet.14 (This diet generally includes a high intake of extra virgin olive oil; leafy green vegetables, fruits, cereals, nuts, and legumes; moderate intake of fish and other meat, dairy products, and red wine; and low intake of eggs and sugars.) The American Heart Association recommends 2 servings of fatty fish a week for its omega-3 oil benefit of reducing ASCVD risk. Working with a registered dietician to assist with lipid lowering can produce better results than physician-only instruction on healthy eating.9

 

Alcohol consumption. Complete cessation or moderation of alcohol consumption (1 drink a day/women and 2 drinks a day/men*) is recommended to improve HTG. Among secondary factors, alcohol is commonly the cause of an unusually high elevation of the TG level.14

Smoking cessation. Smoking increases the postprandial TG level.10 Complete cessation for just 1 year can reduce a person’s ASCVD risk by approximately 50%. However, in a clinical trial,22 smoking cessation did not significantly decrease the TG level—possibly because of the counterbalancing effect of weight gain following cessation.

Continue to: Medical therapy

 

 

Medical therapy

In addition to lifestyle modification, medications are recommended to reduce atherogenic potential in patients with moderate or severe HTG and an ASCVD risk > 7.5% (Table 34,13,18,23 and Table 42,9). Before initiating medical therapy, we recommend that you engage in shared decision-making with patients to (1) delineate treatment goals and (2) describe the risks and benefits of medications for HTG.2

Agents in your arsenal to treat hypertriglyceridemia

Statins. These agents are recommended first-line therapy for reducing ASCVD risk.2 If the TG level remains elevated (> 500 mg/dL) after statin therapy is maximized, an additional agent can be added—ie, a fibrate or fish oil (see below).

Strategies for when and how to treat HTG in adults

Fibrates. If a fibrate is used as an add-on to a statin, fenofibrate is preferred over gemfibrozil because it presents less risk of the severe myopathy that can develop when taken with a statin.13 Despite the effectiveness of fibrates in reducing the TG level, these drugs have not been shown to reduce overall mortality.24 The evidence on improved cardiovascular outcomes is subgroup-specific (ie, prevention of a second myocardial infarction in the setting of optimal statin use and elevated non-HDL lipoproteins).12 A study demonstrated that gemfibrozil reduced the incidence of transient ischemic attack and stroke in a subgroup of male US veterans who had coronary artery disease and a low HDL level.25

Fish oil. The omega-3 ethyl esters eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), available as EPA alone or in combination with DHA, do not interact with statins and are tolerated well. They reduce hypertriglyceridemia by 20% to 50%.13

Eicosapentaenoic acid, EPA plus DHA, and icosapent ethyl, an ethyl ester product containing EPA without DHA, are approved by the US Food and Drug Administration for HTG > 500 mg/dL, at a dosage of 2000 mg twice daily. In the REDUCE-IT trial, adding icosapent ethyl, 2 g twice daily, to a statin in patients with HTG was associated with fewer ischemic events, compared to placebo.23,26

Continue to: Fish oil formulations...

 

 

Fish oil formulations can inhibit platelet aggregation and increase bleeding time in otherwise healthy people; however, such episodes are minor and nonfatal. Patients on anticoagulation or an antiplatelet medication should be monitored periodically for bleeding events, although recommendations on how to monitor aren’t specified in a recent advisory by the American Heart Association.23

There is a strong association between a BMI > 30 and hypertriglyceridemia.

DHA was thought to increase the LDL-C levels and, by doing so, potentially counterbalance benefit,23,27 but most studies have failed to reproduce this effect.28 Instead, studies have shown minimal elevation of LDL-C when DHA is used to treat HTG.23,27

Niacin. At a dosage of 500-2000 mg/dL, niacin lowers the TG level by 10% to 30%. It also increases HDL by 10% to 40% and lowers LDL by 5% to 20%.13

Considerations in pancreatitis. For management of recurrent pancreatitis in patients with HTG, lifestyle modification remains the mainstay of treatment. When medication is considered for persistent severe HTG, fibrates have evidence of primary and secondary prevention of pancreatitis.11 When a patient is intolerant of fibrates, consider a different option to reduce the TG level—eg, fish oil supplementation.

CASE 1

Recommendation for Mr. M: Therapeutic lifestyle changes to address moderate HTG.

Continue to: Because Mr. M's...

 

 

Because Mr. M’s 10-yr ASCVD risk is < 5%, statin therapy is not indicated for risk reduction. With a fasting TG value < 500 mg/dL, he is not considered at increased risk of pancreatitis.

CASE 2

Recommendations for Ms. F:

  • Therapeutic lifestyle changes to address severe HTG. Ms. F agrees to wean off alcohol; add relaxation exercises before bedtime; do aerobic exercise 30 minutes a day, 3 times a week; decrease dietary carbohydrates daily by cutting portion size in half; and increase intake of fresh vegetables and lean protein.
  • Treatment with fenofibrate to reduce the risk of pancreatitis. Ms. F begins a trial. Six months into treatment, she has reduced her BMI to 24 and the TG level has fallen to < 500 mg/dL. Ms. F also reports that she is sleeping well, believes that she is able to manage her infrequent anxiety, and is now in a routine that feels sustainable.

You congratulate Ms. F on her success and support her decision to undertake a trial of discontinuing fenofibrate, after shared decision-making about the risks and potential benefits of doing so.

 

Summing up: Management of HTG

Keep these treatment strategy highlights in mind:

  • Lifestyle modification with a low-fat, low-carbohydrate diet, avoidance of alcohol, and moderate-intensity exercise is the mainstay of HTG management.
  • The latest evidence supports that (1) HTG is a risk-enhancing factor for ­ASCVD and (2) statin therapy is recommended for patients who have HTG and an ASCVD risk > 7.5%.
  • When the TG level remains elevated despite statin therapy and lifestyle changes, an omega-3 ethyl ester can be used as an adjunct for additional atherogenic risk reduction.
  • For severe HTG, a regimen of therapeutic lifestyle changes plus a fibrate is recommended to reduce the risk and recurrence of pancreatitis.1,24

* In comparison, a normal level of triglycerides is < 175 mg/dL; a moderately elevated level, measured in a fasting or nonfasting state, 175-499 mg/dL; and a very severely elevated level, ≥ 2000 mg/dL.2

CORRESPONDENCE
Ashwini Kamath Mulki, MD, Family Health Center, 1730 Chew Street, Allentown, PA 18104; [email protected].

References

1. Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:2969-2989.

2. Grundy SM, Stone NJ, Bailey AL, et al. AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73:e285-e350.

3. Brahm A, Hegele RA. Hypertriglyceridemia. Nutrients. 2013;5:981-1001.

4. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

5. US Preventive Services Task Force. Final recommendation statement. Statin use for the primary prevention of cardiovascular disease in adults: preventive medication. November 13, 2016. www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/statin-use-in-adults-preventive-medication. Accessed April 24, 2020.

6. Fukuyama N, Homma K, Wakana N, et al. Validation of the Friedewald equation for evaluation of plasma LDL-cholesterol. J Clin Biochem Nutr. 2007;43:1-5.

7. Scherer DJ, Nicholls SJ. Lowering triglycerides to modify cardiovascular risk: Will icosapent deliver? Vasc Health Risk Manag. 2015;11:203.

8. Nordestgaard BG, Benn M, Schnohr P, et al. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298:299-308.

9. Jellinger PS. American Association of Clinical Endocrinologists/American College of Endocrinology Management of Dyslipidemia and Prevention of Cardiovascular Disease Clinical Practice Guidelines. Diabetes Spectr. 2018;31:234-245.

10. Malhotra G, Sethi A, Arora R. Hypertriglyceridemia and cardiovascular outcomes. Am J Therapeut. 2016;23:e862-e870.

11. Carr RA, Rejowski BJ, Cote GA, et al. Systematic review of hypertriglyceridemia-induced acute pancreatitis: a more virulent etiology? Pancreatology. 2016;16:469-476.

12. Charlesworth A, Steger A, Crook MA. Acute pancreatitis associated with severe hypertriglyceridemia; a retrospective cohort study. Int J Surg. 2015;23(pt A):23-27.

13. Berglund L, Brunzell JD, Goldberg AC, et al. Treatment options for hypertriglyceridemia: from risk reduction to pancreatitis. Best Pract Res Clin Endocrinol Metab. 2014;28:423-437.

14. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2935-2959. [Erratum. J Am Coll Cardiol. 2014;63:3026.]

15. Madsen CM, Varbo A, Nordestgaard BG. Unmet need for primary prevention in individuals with hypertriglyceridaemia not eligible for statin therapy according to European Society of Cardiology/European Atherosclerosis Society guidelines: a contemporary population-based study. Euro Heart J. 2017;39:610-619.

16. Klempfner R, Erez A, Sagit B-Z, et al. Elevated triglyceride level is independently associated with increased all-cause mortality in patients with established coronary heart disease: twenty-two-year follow-up of the Bezafibrate Infarction Prevention Study and Registry. Circ Cardiovasc Qual Outcomes. 2016;9:100-108.

17. Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, et al. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA. 2008;300:2142-2152.

18. Miller M, Stone NJ, Ballantyne C, et al; American Heart Association Clinical Lipidology, Thrombosis, and Prevention Committee of the Council on Nutrition, Physical Activity, and MetabolismCouncil on Arteriosclerosis, Thrombosis and Vascular BiologyCouncil on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease. Triglycerides and cardiovascular disease. Circulation. 2011;123:2292-2333.

19. Graham TE. Exercise, postprandial triacylglyceridemia, and cardiovascular disease risk. Can J Appl Physiol. 2004;29:781-799.

20. Meng Y, Bai H, Wang S, et al. Efficacy of low carbohydrate diet for type 2 diabetes mellitus management: a systematic review and meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2017;131:124-131.

21. What is a standard drink? National Institute on Alcohol Abuse and Alcoholism Web site. www.niaaa.nih.gov/what-standard-drink. Accessed April 24, 2020.

22. Gepner AD, Piper ME, Johnson HM, et al. Effects of smoking and smoking cessation on lipids and lipoproteins: outcomes from a randomized clinical trial. Am Heart J. 2011;161:145-151.

23. Skulas-Ray AC, Wilson PWF, Harris WS, et al; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American Heart Association. Circulation. 2019;140:e673-e691.

24. Jakob T, Nordmann AJ, Schandelmaier S, et al. Fibrates for primary prevention of cardiovascular disease events. Cochrane Database Syst Rev. 2016;11:CD009753.

25. Lisak M, Demarin V, Trkanjec Z, et al. Hypertriglyceridemia as a possible independent risk factor for stroke. Acta Clin Croat. 2013;52:458-463.

26. Bhatt DL, Steg PG, Miller M, et al; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.

27. Barter P, Ginsberg HN. Effectiveness of combined statin plus omega-3 fatty acid therapy for mixed dyslipidemia. Am J Cardiol. 2008;102:1040-1045.

28. Bays H, Ballantyne C, Kastelein J, et al. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] Trial). Am J Cardiol. 2011;108:682-690.

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CASE 1

Tyler M, age 40, otherwise healthy, and with a body mass index (BMI) of 30, presents to your office for his annual physical examination. He does not have a history of alcohol or tobacco use.

Mr. M’s obesity raises concern about metabolic syndrome, which warrants evaluation for hypertriglyceridemia (HTG). You offer him lipid testing to estimate his risk of atherosclerotic cardiovascular disease (ASCVD).

The only abnormal value on the lipid panel is a triglyceride (TG) level of 264 mg/dL (normal, < 175 mg/dL). Mr. M’s 10-yr ASCVD risk is determined to be < 5%.

What, if any, intervention would be triggered by the finding of moderate HTG?

Heart
© ALICIA BUELOW

CASE 2

Alicia F, age 30, with a BMI of 28 and ASCVD risk < 7.5%, comes to the clinic for evaluation of anxiety and insomnia. She reports eating a high-carbohydrate diet and drinking 3 to 5 alcoholic beverages nightly to help her sleep.

Ms. F’s daily alcohol use prompts evaluation for HTG. Results show a TG level of 1300 mg/dL and a high-density lipoprotein (HDL) level of 25 mg/dL (healthy HDL levels: adult females, ≥ 50 mg/dL; adult males, ≥ 40 mg/dL). Other test results are normal, except for elevated transaminase levels (just under twice normal).

What, if any, action would be prompted by the patient’s severe HTG and below-normal HDL level?

Continue to: How HTG is defined

 

 

How HTG is defined: Causes, cutoffs, signs

HTG is most commonly caused by obesity and a sedentary lifestyle; certain associated comorbid medical conditions can also be a precipitant (Table 11,2). Because the condition is a result of polygenic phenotypic expression, even a genetically low-risk patient can present with HTG when exposed to certain medical conditions and environmental causes.

Causes of hypertriglyceridemia

Primary HTG (genetic or familial) is rare. Genetic testing may be considered for patients with TG > 1000 mg/dL (severely elevated TG = 500 to 1999 mg/dL, measured in fasting state*) or a family history of early ASCVD (TABLE 11,2).2,3

Even a genetically low-risk patient can present with hypertriglyceridemia when exposed to certain medical conditions and environmental causes.

Typically, HTG is asymptomatic. Xanthelasmas, xanthomas, and lipemia retinalis are found in hereditary disorders of elevated TGs. Occasionally, HTG manifests as chylomicronemia syndrome, characterized by recurrent abdominal pain, nausea, vomiting, and, in severe HTG, pancreatitis.3

 

Fine points of TG measurement

Triglycerides are a component of a complete lipid profile, which also includes total cholesterol, calculated low-density lipoprotein (LDL-C), and HDL.4 As in both case vignettes, detection of HTG is often incidental, when a lipid profile is ordered to evaluate the risk of ASCVD. (Of note, for people older than 20 years, the US Preventive Services Task Force no longer addresses the question, “Which population should be screened for dyslipidemia?” Instead, current recommendations answer the question, “For which population should statin therapy be prescribed?”5)

Effect on ASCVD risk assessment. TG levels are known to vary, depending on fasting or nonfasting status, with lower levels reported when fasting. An elevated TG level can lead to inaccurate calculation of LDL when using the Friedewald formula6:

LDL = total cholesterol – (triglycerides/5) – HDL

Continue to: The purpose of testing...

 

 

The purpose of testing lipids in a fasting state (> 9 hours) is to minimize the effects of an elevated TG level on the calculated LDL. In severe HTG, beta-quantitation by ultracentrifugation and electrophoresis can be performed to determine the LDL level directly.

Advantage of nonfasting measurement. When LDL-C is not a concern, there is, in fact, value in measuring TGs in the nonfasting state. Why? Because a nonfasting TG level is a better indicator of a patient’s average TG status: Studies have found a higher ASCVD risk in the setting of an elevated postprandial TG level accompanied by a low HDL level.7

Studies have found a higher ASCVD risk in the setting of an elevated postprandial triglyceride level accompanied by a low HDL level.

The Copenhagen City Heart Study identified postprandial HTG as an independent risk factor for atherogenicity, even in the setting of a normal fasting TG level.8 American Association of Clinical Endocrinologists and American College of Endocrinology guidelines endorse testing the nonfasting TG level when the fasting TG level is elevated in a lipid profile; if the nonfasting TG level is > 500 mg/dL, evaluation for secondary causes is warranted9,10 (Table 11,2).

 

In a practical sense, therefore, offering patients nonfasting lipid testing allows more people to obtain access to timely care.

Pancreatitis. Acute pancreatitis commonly prompts an evaluation for HTG. The risk of acute pancreatitis in the general population is 0.04%, but that risk increases to 8% to 31% for a person with HTG.11 Incidence when the TG level is > 500 mg/dL is thought to be increased because chylomicrons, acting as a TG carrier in the bloodstream, are responsible for pancreatitis.3 Treating HTG can reduce both the risk and recurrence of pancreatitis12,13; given that the postprandial TG level can change rapidly from severe to very severe (> 2000 mg/dL), multiple guidelines recommend pharmacotherapy to a TG goal of < 500-1000 mg/dL.1,9,13,14

Continue to: An ASCVD risk-HTG connection?

 

 

An ASCVD risk–HTG connection? In the population already at higher risk of ASCVD (> 7.5%), HTG is recognized as a risk-enhancing factor because of its atherogenic potential (Table 22); however, there is insufficient evidence that TGs have a role as an independent risk factor for ASCVD. In a population-based study of 58,000 people, 40 to 65 years of age, conducted at Copenhagen [Denmark] University Hospital, investigators found that those who did not meet criteria for statin treatment and who had a TG level > 264 mg/dL had a 10-year risk of a major adverse cardiovascular event similar to that of people who did meet criteria for statin therapy.15

Risk factors and risk-enhancing factors for atherosclerotic cardiovascular disease

The FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) and AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) studies, among others, have failed to show a significant reduction in coronary events by treating HTG.10

That said, it’s worth considering the findings of other trials:

  • In the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22) trial, an overall 28% reduction in endpoint events (myocardial infarction, acute coronary syndrome) was seen with high-intensity statin therapy, compared to moderate-intensity therapy.10 However, there was a sizeable residual risk identified that was theorized by investigators to be associated with high non-HDL lipoproteins, including TGs.
  • A 2016 study in Israel, in which 22 years of data on 15,355 patients with established ASCVD were studied, revealed that elevated TGs are associated with an increased long-term mortality risk that is independent of the HDL level.16
  • A cross-sectional study, nested in the prospective Copenhagen City Heart Study, demonstrated that HTG is associated with an increase in ischemic stroke events.17
 

Treatment

Therapeutic lifestyle changes

Changes in lifestyle are the foundation of management of, and recommended first-line treatment for, all patients with HTG. Patients with a moderately elevated TG level (175-499 mg/dL, measured in a fasting or nonfasting state) can be treated with therapeutic lifestyle changes alone1,2; a trial of 3 to 6 months (see specific interventions below) is recommended before considering adding medications.10

Weight loss. There is a strong association between BMI > 30 and HTG. Visceral adiposity is a much more significant risk than subcutaneous adipose tissue. Although weight loss to an ideal range is recommended, even a 10% to 15% reduction in an obese patient can reduce the TG level by 20%. A combination of moderate-intensity exercise and healthy eating habits appears to assist best with this intervention.18

Continue to: Exercise

 

 

Exercise. Thirty minutes a day of moderate-intensity exercise is associated with a significant drop in postprandial TG. This benefit can last as long as 3 days, suggesting a goal of at least 3 days a week of an active lifestyle. Such a program can include intermittent aerobics or mild resistance exercise.19

Healthy eating habits. The difference between a low-fat, high-carbohydrate diet and a high-fat, low-carbohydrate diet is less important than the overall benefit of weight loss from either of these diets. Complex carbohydrates are recommended over simple carbohydrates. A low-carbohydrate diet in a patient with diabetes has been demonstrated to improve the TG level, irrespective of weight change.20

The risk of acute pancreatitis in the general population is 0.04%, but that risk increases to 8% to 31% for a person with hypertriglyceridemia

A Mediterranean diet can reduce the TG level by 10% to 15%, and is recommended over a low-fat diet.14 (This diet generally includes a high intake of extra virgin olive oil; leafy green vegetables, fruits, cereals, nuts, and legumes; moderate intake of fish and other meat, dairy products, and red wine; and low intake of eggs and sugars.) The American Heart Association recommends 2 servings of fatty fish a week for its omega-3 oil benefit of reducing ASCVD risk. Working with a registered dietician to assist with lipid lowering can produce better results than physician-only instruction on healthy eating.9

 

Alcohol consumption. Complete cessation or moderation of alcohol consumption (1 drink a day/women and 2 drinks a day/men*) is recommended to improve HTG. Among secondary factors, alcohol is commonly the cause of an unusually high elevation of the TG level.14

Smoking cessation. Smoking increases the postprandial TG level.10 Complete cessation for just 1 year can reduce a person’s ASCVD risk by approximately 50%. However, in a clinical trial,22 smoking cessation did not significantly decrease the TG level—possibly because of the counterbalancing effect of weight gain following cessation.

Continue to: Medical therapy

 

 

Medical therapy

In addition to lifestyle modification, medications are recommended to reduce atherogenic potential in patients with moderate or severe HTG and an ASCVD risk > 7.5% (Table 34,13,18,23 and Table 42,9). Before initiating medical therapy, we recommend that you engage in shared decision-making with patients to (1) delineate treatment goals and (2) describe the risks and benefits of medications for HTG.2

Agents in your arsenal to treat hypertriglyceridemia

Statins. These agents are recommended first-line therapy for reducing ASCVD risk.2 If the TG level remains elevated (> 500 mg/dL) after statin therapy is maximized, an additional agent can be added—ie, a fibrate or fish oil (see below).

Strategies for when and how to treat HTG in adults

Fibrates. If a fibrate is used as an add-on to a statin, fenofibrate is preferred over gemfibrozil because it presents less risk of the severe myopathy that can develop when taken with a statin.13 Despite the effectiveness of fibrates in reducing the TG level, these drugs have not been shown to reduce overall mortality.24 The evidence on improved cardiovascular outcomes is subgroup-specific (ie, prevention of a second myocardial infarction in the setting of optimal statin use and elevated non-HDL lipoproteins).12 A study demonstrated that gemfibrozil reduced the incidence of transient ischemic attack and stroke in a subgroup of male US veterans who had coronary artery disease and a low HDL level.25

Fish oil. The omega-3 ethyl esters eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), available as EPA alone or in combination with DHA, do not interact with statins and are tolerated well. They reduce hypertriglyceridemia by 20% to 50%.13

Eicosapentaenoic acid, EPA plus DHA, and icosapent ethyl, an ethyl ester product containing EPA without DHA, are approved by the US Food and Drug Administration for HTG > 500 mg/dL, at a dosage of 2000 mg twice daily. In the REDUCE-IT trial, adding icosapent ethyl, 2 g twice daily, to a statin in patients with HTG was associated with fewer ischemic events, compared to placebo.23,26

Continue to: Fish oil formulations...

 

 

Fish oil formulations can inhibit platelet aggregation and increase bleeding time in otherwise healthy people; however, such episodes are minor and nonfatal. Patients on anticoagulation or an antiplatelet medication should be monitored periodically for bleeding events, although recommendations on how to monitor aren’t specified in a recent advisory by the American Heart Association.23

There is a strong association between a BMI > 30 and hypertriglyceridemia.

DHA was thought to increase the LDL-C levels and, by doing so, potentially counterbalance benefit,23,27 but most studies have failed to reproduce this effect.28 Instead, studies have shown minimal elevation of LDL-C when DHA is used to treat HTG.23,27

Niacin. At a dosage of 500-2000 mg/dL, niacin lowers the TG level by 10% to 30%. It also increases HDL by 10% to 40% and lowers LDL by 5% to 20%.13

Considerations in pancreatitis. For management of recurrent pancreatitis in patients with HTG, lifestyle modification remains the mainstay of treatment. When medication is considered for persistent severe HTG, fibrates have evidence of primary and secondary prevention of pancreatitis.11 When a patient is intolerant of fibrates, consider a different option to reduce the TG level—eg, fish oil supplementation.

CASE 1

Recommendation for Mr. M: Therapeutic lifestyle changes to address moderate HTG.

Continue to: Because Mr. M's...

 

 

Because Mr. M’s 10-yr ASCVD risk is < 5%, statin therapy is not indicated for risk reduction. With a fasting TG value < 500 mg/dL, he is not considered at increased risk of pancreatitis.

CASE 2

Recommendations for Ms. F:

  • Therapeutic lifestyle changes to address severe HTG. Ms. F agrees to wean off alcohol; add relaxation exercises before bedtime; do aerobic exercise 30 minutes a day, 3 times a week; decrease dietary carbohydrates daily by cutting portion size in half; and increase intake of fresh vegetables and lean protein.
  • Treatment with fenofibrate to reduce the risk of pancreatitis. Ms. F begins a trial. Six months into treatment, she has reduced her BMI to 24 and the TG level has fallen to < 500 mg/dL. Ms. F also reports that she is sleeping well, believes that she is able to manage her infrequent anxiety, and is now in a routine that feels sustainable.

You congratulate Ms. F on her success and support her decision to undertake a trial of discontinuing fenofibrate, after shared decision-making about the risks and potential benefits of doing so.

 

Summing up: Management of HTG

Keep these treatment strategy highlights in mind:

  • Lifestyle modification with a low-fat, low-carbohydrate diet, avoidance of alcohol, and moderate-intensity exercise is the mainstay of HTG management.
  • The latest evidence supports that (1) HTG is a risk-enhancing factor for ­ASCVD and (2) statin therapy is recommended for patients who have HTG and an ASCVD risk > 7.5%.
  • When the TG level remains elevated despite statin therapy and lifestyle changes, an omega-3 ethyl ester can be used as an adjunct for additional atherogenic risk reduction.
  • For severe HTG, a regimen of therapeutic lifestyle changes plus a fibrate is recommended to reduce the risk and recurrence of pancreatitis.1,24

* In comparison, a normal level of triglycerides is < 175 mg/dL; a moderately elevated level, measured in a fasting or nonfasting state, 175-499 mg/dL; and a very severely elevated level, ≥ 2000 mg/dL.2

CORRESPONDENCE
Ashwini Kamath Mulki, MD, Family Health Center, 1730 Chew Street, Allentown, PA 18104; [email protected].

CASE 1

Tyler M, age 40, otherwise healthy, and with a body mass index (BMI) of 30, presents to your office for his annual physical examination. He does not have a history of alcohol or tobacco use.

Mr. M’s obesity raises concern about metabolic syndrome, which warrants evaluation for hypertriglyceridemia (HTG). You offer him lipid testing to estimate his risk of atherosclerotic cardiovascular disease (ASCVD).

The only abnormal value on the lipid panel is a triglyceride (TG) level of 264 mg/dL (normal, < 175 mg/dL). Mr. M’s 10-yr ASCVD risk is determined to be < 5%.

What, if any, intervention would be triggered by the finding of moderate HTG?

Heart
© ALICIA BUELOW

CASE 2

Alicia F, age 30, with a BMI of 28 and ASCVD risk < 7.5%, comes to the clinic for evaluation of anxiety and insomnia. She reports eating a high-carbohydrate diet and drinking 3 to 5 alcoholic beverages nightly to help her sleep.

Ms. F’s daily alcohol use prompts evaluation for HTG. Results show a TG level of 1300 mg/dL and a high-density lipoprotein (HDL) level of 25 mg/dL (healthy HDL levels: adult females, ≥ 50 mg/dL; adult males, ≥ 40 mg/dL). Other test results are normal, except for elevated transaminase levels (just under twice normal).

What, if any, action would be prompted by the patient’s severe HTG and below-normal HDL level?

Continue to: How HTG is defined

 

 

How HTG is defined: Causes, cutoffs, signs

HTG is most commonly caused by obesity and a sedentary lifestyle; certain associated comorbid medical conditions can also be a precipitant (Table 11,2). Because the condition is a result of polygenic phenotypic expression, even a genetically low-risk patient can present with HTG when exposed to certain medical conditions and environmental causes.

Causes of hypertriglyceridemia

Primary HTG (genetic or familial) is rare. Genetic testing may be considered for patients with TG > 1000 mg/dL (severely elevated TG = 500 to 1999 mg/dL, measured in fasting state*) or a family history of early ASCVD (TABLE 11,2).2,3

Even a genetically low-risk patient can present with hypertriglyceridemia when exposed to certain medical conditions and environmental causes.

Typically, HTG is asymptomatic. Xanthelasmas, xanthomas, and lipemia retinalis are found in hereditary disorders of elevated TGs. Occasionally, HTG manifests as chylomicronemia syndrome, characterized by recurrent abdominal pain, nausea, vomiting, and, in severe HTG, pancreatitis.3

 

Fine points of TG measurement

Triglycerides are a component of a complete lipid profile, which also includes total cholesterol, calculated low-density lipoprotein (LDL-C), and HDL.4 As in both case vignettes, detection of HTG is often incidental, when a lipid profile is ordered to evaluate the risk of ASCVD. (Of note, for people older than 20 years, the US Preventive Services Task Force no longer addresses the question, “Which population should be screened for dyslipidemia?” Instead, current recommendations answer the question, “For which population should statin therapy be prescribed?”5)

Effect on ASCVD risk assessment. TG levels are known to vary, depending on fasting or nonfasting status, with lower levels reported when fasting. An elevated TG level can lead to inaccurate calculation of LDL when using the Friedewald formula6:

LDL = total cholesterol – (triglycerides/5) – HDL

Continue to: The purpose of testing...

 

 

The purpose of testing lipids in a fasting state (> 9 hours) is to minimize the effects of an elevated TG level on the calculated LDL. In severe HTG, beta-quantitation by ultracentrifugation and electrophoresis can be performed to determine the LDL level directly.

Advantage of nonfasting measurement. When LDL-C is not a concern, there is, in fact, value in measuring TGs in the nonfasting state. Why? Because a nonfasting TG level is a better indicator of a patient’s average TG status: Studies have found a higher ASCVD risk in the setting of an elevated postprandial TG level accompanied by a low HDL level.7

Studies have found a higher ASCVD risk in the setting of an elevated postprandial triglyceride level accompanied by a low HDL level.

The Copenhagen City Heart Study identified postprandial HTG as an independent risk factor for atherogenicity, even in the setting of a normal fasting TG level.8 American Association of Clinical Endocrinologists and American College of Endocrinology guidelines endorse testing the nonfasting TG level when the fasting TG level is elevated in a lipid profile; if the nonfasting TG level is > 500 mg/dL, evaluation for secondary causes is warranted9,10 (Table 11,2).

 

In a practical sense, therefore, offering patients nonfasting lipid testing allows more people to obtain access to timely care.

Pancreatitis. Acute pancreatitis commonly prompts an evaluation for HTG. The risk of acute pancreatitis in the general population is 0.04%, but that risk increases to 8% to 31% for a person with HTG.11 Incidence when the TG level is > 500 mg/dL is thought to be increased because chylomicrons, acting as a TG carrier in the bloodstream, are responsible for pancreatitis.3 Treating HTG can reduce both the risk and recurrence of pancreatitis12,13; given that the postprandial TG level can change rapidly from severe to very severe (> 2000 mg/dL), multiple guidelines recommend pharmacotherapy to a TG goal of < 500-1000 mg/dL.1,9,13,14

Continue to: An ASCVD risk-HTG connection?

 

 

An ASCVD risk–HTG connection? In the population already at higher risk of ASCVD (> 7.5%), HTG is recognized as a risk-enhancing factor because of its atherogenic potential (Table 22); however, there is insufficient evidence that TGs have a role as an independent risk factor for ASCVD. In a population-based study of 58,000 people, 40 to 65 years of age, conducted at Copenhagen [Denmark] University Hospital, investigators found that those who did not meet criteria for statin treatment and who had a TG level > 264 mg/dL had a 10-year risk of a major adverse cardiovascular event similar to that of people who did meet criteria for statin therapy.15

Risk factors and risk-enhancing factors for atherosclerotic cardiovascular disease

The FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) and AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) studies, among others, have failed to show a significant reduction in coronary events by treating HTG.10

That said, it’s worth considering the findings of other trials:

  • In the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22) trial, an overall 28% reduction in endpoint events (myocardial infarction, acute coronary syndrome) was seen with high-intensity statin therapy, compared to moderate-intensity therapy.10 However, there was a sizeable residual risk identified that was theorized by investigators to be associated with high non-HDL lipoproteins, including TGs.
  • A 2016 study in Israel, in which 22 years of data on 15,355 patients with established ASCVD were studied, revealed that elevated TGs are associated with an increased long-term mortality risk that is independent of the HDL level.16
  • A cross-sectional study, nested in the prospective Copenhagen City Heart Study, demonstrated that HTG is associated with an increase in ischemic stroke events.17
 

Treatment

Therapeutic lifestyle changes

Changes in lifestyle are the foundation of management of, and recommended first-line treatment for, all patients with HTG. Patients with a moderately elevated TG level (175-499 mg/dL, measured in a fasting or nonfasting state) can be treated with therapeutic lifestyle changes alone1,2; a trial of 3 to 6 months (see specific interventions below) is recommended before considering adding medications.10

Weight loss. There is a strong association between BMI > 30 and HTG. Visceral adiposity is a much more significant risk than subcutaneous adipose tissue. Although weight loss to an ideal range is recommended, even a 10% to 15% reduction in an obese patient can reduce the TG level by 20%. A combination of moderate-intensity exercise and healthy eating habits appears to assist best with this intervention.18

Continue to: Exercise

 

 

Exercise. Thirty minutes a day of moderate-intensity exercise is associated with a significant drop in postprandial TG. This benefit can last as long as 3 days, suggesting a goal of at least 3 days a week of an active lifestyle. Such a program can include intermittent aerobics or mild resistance exercise.19

Healthy eating habits. The difference between a low-fat, high-carbohydrate diet and a high-fat, low-carbohydrate diet is less important than the overall benefit of weight loss from either of these diets. Complex carbohydrates are recommended over simple carbohydrates. A low-carbohydrate diet in a patient with diabetes has been demonstrated to improve the TG level, irrespective of weight change.20

The risk of acute pancreatitis in the general population is 0.04%, but that risk increases to 8% to 31% for a person with hypertriglyceridemia

A Mediterranean diet can reduce the TG level by 10% to 15%, and is recommended over a low-fat diet.14 (This diet generally includes a high intake of extra virgin olive oil; leafy green vegetables, fruits, cereals, nuts, and legumes; moderate intake of fish and other meat, dairy products, and red wine; and low intake of eggs and sugars.) The American Heart Association recommends 2 servings of fatty fish a week for its omega-3 oil benefit of reducing ASCVD risk. Working with a registered dietician to assist with lipid lowering can produce better results than physician-only instruction on healthy eating.9

 

Alcohol consumption. Complete cessation or moderation of alcohol consumption (1 drink a day/women and 2 drinks a day/men*) is recommended to improve HTG. Among secondary factors, alcohol is commonly the cause of an unusually high elevation of the TG level.14

Smoking cessation. Smoking increases the postprandial TG level.10 Complete cessation for just 1 year can reduce a person’s ASCVD risk by approximately 50%. However, in a clinical trial,22 smoking cessation did not significantly decrease the TG level—possibly because of the counterbalancing effect of weight gain following cessation.

Continue to: Medical therapy

 

 

Medical therapy

In addition to lifestyle modification, medications are recommended to reduce atherogenic potential in patients with moderate or severe HTG and an ASCVD risk > 7.5% (Table 34,13,18,23 and Table 42,9). Before initiating medical therapy, we recommend that you engage in shared decision-making with patients to (1) delineate treatment goals and (2) describe the risks and benefits of medications for HTG.2

Agents in your arsenal to treat hypertriglyceridemia

Statins. These agents are recommended first-line therapy for reducing ASCVD risk.2 If the TG level remains elevated (> 500 mg/dL) after statin therapy is maximized, an additional agent can be added—ie, a fibrate or fish oil (see below).

Strategies for when and how to treat HTG in adults

Fibrates. If a fibrate is used as an add-on to a statin, fenofibrate is preferred over gemfibrozil because it presents less risk of the severe myopathy that can develop when taken with a statin.13 Despite the effectiveness of fibrates in reducing the TG level, these drugs have not been shown to reduce overall mortality.24 The evidence on improved cardiovascular outcomes is subgroup-specific (ie, prevention of a second myocardial infarction in the setting of optimal statin use and elevated non-HDL lipoproteins).12 A study demonstrated that gemfibrozil reduced the incidence of transient ischemic attack and stroke in a subgroup of male US veterans who had coronary artery disease and a low HDL level.25

Fish oil. The omega-3 ethyl esters eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), available as EPA alone or in combination with DHA, do not interact with statins and are tolerated well. They reduce hypertriglyceridemia by 20% to 50%.13

Eicosapentaenoic acid, EPA plus DHA, and icosapent ethyl, an ethyl ester product containing EPA without DHA, are approved by the US Food and Drug Administration for HTG > 500 mg/dL, at a dosage of 2000 mg twice daily. In the REDUCE-IT trial, adding icosapent ethyl, 2 g twice daily, to a statin in patients with HTG was associated with fewer ischemic events, compared to placebo.23,26

Continue to: Fish oil formulations...

 

 

Fish oil formulations can inhibit platelet aggregation and increase bleeding time in otherwise healthy people; however, such episodes are minor and nonfatal. Patients on anticoagulation or an antiplatelet medication should be monitored periodically for bleeding events, although recommendations on how to monitor aren’t specified in a recent advisory by the American Heart Association.23

There is a strong association between a BMI > 30 and hypertriglyceridemia.

DHA was thought to increase the LDL-C levels and, by doing so, potentially counterbalance benefit,23,27 but most studies have failed to reproduce this effect.28 Instead, studies have shown minimal elevation of LDL-C when DHA is used to treat HTG.23,27

Niacin. At a dosage of 500-2000 mg/dL, niacin lowers the TG level by 10% to 30%. It also increases HDL by 10% to 40% and lowers LDL by 5% to 20%.13

Considerations in pancreatitis. For management of recurrent pancreatitis in patients with HTG, lifestyle modification remains the mainstay of treatment. When medication is considered for persistent severe HTG, fibrates have evidence of primary and secondary prevention of pancreatitis.11 When a patient is intolerant of fibrates, consider a different option to reduce the TG level—eg, fish oil supplementation.

CASE 1

Recommendation for Mr. M: Therapeutic lifestyle changes to address moderate HTG.

Continue to: Because Mr. M's...

 

 

Because Mr. M’s 10-yr ASCVD risk is < 5%, statin therapy is not indicated for risk reduction. With a fasting TG value < 500 mg/dL, he is not considered at increased risk of pancreatitis.

CASE 2

Recommendations for Ms. F:

  • Therapeutic lifestyle changes to address severe HTG. Ms. F agrees to wean off alcohol; add relaxation exercises before bedtime; do aerobic exercise 30 minutes a day, 3 times a week; decrease dietary carbohydrates daily by cutting portion size in half; and increase intake of fresh vegetables and lean protein.
  • Treatment with fenofibrate to reduce the risk of pancreatitis. Ms. F begins a trial. Six months into treatment, she has reduced her BMI to 24 and the TG level has fallen to < 500 mg/dL. Ms. F also reports that she is sleeping well, believes that she is able to manage her infrequent anxiety, and is now in a routine that feels sustainable.

You congratulate Ms. F on her success and support her decision to undertake a trial of discontinuing fenofibrate, after shared decision-making about the risks and potential benefits of doing so.

 

Summing up: Management of HTG

Keep these treatment strategy highlights in mind:

  • Lifestyle modification with a low-fat, low-carbohydrate diet, avoidance of alcohol, and moderate-intensity exercise is the mainstay of HTG management.
  • The latest evidence supports that (1) HTG is a risk-enhancing factor for ­ASCVD and (2) statin therapy is recommended for patients who have HTG and an ASCVD risk > 7.5%.
  • When the TG level remains elevated despite statin therapy and lifestyle changes, an omega-3 ethyl ester can be used as an adjunct for additional atherogenic risk reduction.
  • For severe HTG, a regimen of therapeutic lifestyle changes plus a fibrate is recommended to reduce the risk and recurrence of pancreatitis.1,24

* In comparison, a normal level of triglycerides is < 175 mg/dL; a moderately elevated level, measured in a fasting or nonfasting state, 175-499 mg/dL; and a very severely elevated level, ≥ 2000 mg/dL.2

CORRESPONDENCE
Ashwini Kamath Mulki, MD, Family Health Center, 1730 Chew Street, Allentown, PA 18104; [email protected].

References

1. Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:2969-2989.

2. Grundy SM, Stone NJ, Bailey AL, et al. AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73:e285-e350.

3. Brahm A, Hegele RA. Hypertriglyceridemia. Nutrients. 2013;5:981-1001.

4. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

5. US Preventive Services Task Force. Final recommendation statement. Statin use for the primary prevention of cardiovascular disease in adults: preventive medication. November 13, 2016. www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/statin-use-in-adults-preventive-medication. Accessed April 24, 2020.

6. Fukuyama N, Homma K, Wakana N, et al. Validation of the Friedewald equation for evaluation of plasma LDL-cholesterol. J Clin Biochem Nutr. 2007;43:1-5.

7. Scherer DJ, Nicholls SJ. Lowering triglycerides to modify cardiovascular risk: Will icosapent deliver? Vasc Health Risk Manag. 2015;11:203.

8. Nordestgaard BG, Benn M, Schnohr P, et al. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298:299-308.

9. Jellinger PS. American Association of Clinical Endocrinologists/American College of Endocrinology Management of Dyslipidemia and Prevention of Cardiovascular Disease Clinical Practice Guidelines. Diabetes Spectr. 2018;31:234-245.

10. Malhotra G, Sethi A, Arora R. Hypertriglyceridemia and cardiovascular outcomes. Am J Therapeut. 2016;23:e862-e870.

11. Carr RA, Rejowski BJ, Cote GA, et al. Systematic review of hypertriglyceridemia-induced acute pancreatitis: a more virulent etiology? Pancreatology. 2016;16:469-476.

12. Charlesworth A, Steger A, Crook MA. Acute pancreatitis associated with severe hypertriglyceridemia; a retrospective cohort study. Int J Surg. 2015;23(pt A):23-27.

13. Berglund L, Brunzell JD, Goldberg AC, et al. Treatment options for hypertriglyceridemia: from risk reduction to pancreatitis. Best Pract Res Clin Endocrinol Metab. 2014;28:423-437.

14. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2935-2959. [Erratum. J Am Coll Cardiol. 2014;63:3026.]

15. Madsen CM, Varbo A, Nordestgaard BG. Unmet need for primary prevention in individuals with hypertriglyceridaemia not eligible for statin therapy according to European Society of Cardiology/European Atherosclerosis Society guidelines: a contemporary population-based study. Euro Heart J. 2017;39:610-619.

16. Klempfner R, Erez A, Sagit B-Z, et al. Elevated triglyceride level is independently associated with increased all-cause mortality in patients with established coronary heart disease: twenty-two-year follow-up of the Bezafibrate Infarction Prevention Study and Registry. Circ Cardiovasc Qual Outcomes. 2016;9:100-108.

17. Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, et al. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA. 2008;300:2142-2152.

18. Miller M, Stone NJ, Ballantyne C, et al; American Heart Association Clinical Lipidology, Thrombosis, and Prevention Committee of the Council on Nutrition, Physical Activity, and MetabolismCouncil on Arteriosclerosis, Thrombosis and Vascular BiologyCouncil on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease. Triglycerides and cardiovascular disease. Circulation. 2011;123:2292-2333.

19. Graham TE. Exercise, postprandial triacylglyceridemia, and cardiovascular disease risk. Can J Appl Physiol. 2004;29:781-799.

20. Meng Y, Bai H, Wang S, et al. Efficacy of low carbohydrate diet for type 2 diabetes mellitus management: a systematic review and meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2017;131:124-131.

21. What is a standard drink? National Institute on Alcohol Abuse and Alcoholism Web site. www.niaaa.nih.gov/what-standard-drink. Accessed April 24, 2020.

22. Gepner AD, Piper ME, Johnson HM, et al. Effects of smoking and smoking cessation on lipids and lipoproteins: outcomes from a randomized clinical trial. Am Heart J. 2011;161:145-151.

23. Skulas-Ray AC, Wilson PWF, Harris WS, et al; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American Heart Association. Circulation. 2019;140:e673-e691.

24. Jakob T, Nordmann AJ, Schandelmaier S, et al. Fibrates for primary prevention of cardiovascular disease events. Cochrane Database Syst Rev. 2016;11:CD009753.

25. Lisak M, Demarin V, Trkanjec Z, et al. Hypertriglyceridemia as a possible independent risk factor for stroke. Acta Clin Croat. 2013;52:458-463.

26. Bhatt DL, Steg PG, Miller M, et al; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.

27. Barter P, Ginsberg HN. Effectiveness of combined statin plus omega-3 fatty acid therapy for mixed dyslipidemia. Am J Cardiol. 2008;102:1040-1045.

28. Bays H, Ballantyne C, Kastelein J, et al. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] Trial). Am J Cardiol. 2011;108:682-690.

References

1. Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:2969-2989.

2. Grundy SM, Stone NJ, Bailey AL, et al. AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73:e285-e350.

3. Brahm A, Hegele RA. Hypertriglyceridemia. Nutrients. 2013;5:981-1001.

4. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

5. US Preventive Services Task Force. Final recommendation statement. Statin use for the primary prevention of cardiovascular disease in adults: preventive medication. November 13, 2016. www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/statin-use-in-adults-preventive-medication. Accessed April 24, 2020.

6. Fukuyama N, Homma K, Wakana N, et al. Validation of the Friedewald equation for evaluation of plasma LDL-cholesterol. J Clin Biochem Nutr. 2007;43:1-5.

7. Scherer DJ, Nicholls SJ. Lowering triglycerides to modify cardiovascular risk: Will icosapent deliver? Vasc Health Risk Manag. 2015;11:203.

8. Nordestgaard BG, Benn M, Schnohr P, et al. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298:299-308.

9. Jellinger PS. American Association of Clinical Endocrinologists/American College of Endocrinology Management of Dyslipidemia and Prevention of Cardiovascular Disease Clinical Practice Guidelines. Diabetes Spectr. 2018;31:234-245.

10. Malhotra G, Sethi A, Arora R. Hypertriglyceridemia and cardiovascular outcomes. Am J Therapeut. 2016;23:e862-e870.

11. Carr RA, Rejowski BJ, Cote GA, et al. Systematic review of hypertriglyceridemia-induced acute pancreatitis: a more virulent etiology? Pancreatology. 2016;16:469-476.

12. Charlesworth A, Steger A, Crook MA. Acute pancreatitis associated with severe hypertriglyceridemia; a retrospective cohort study. Int J Surg. 2015;23(pt A):23-27.

13. Berglund L, Brunzell JD, Goldberg AC, et al. Treatment options for hypertriglyceridemia: from risk reduction to pancreatitis. Best Pract Res Clin Endocrinol Metab. 2014;28:423-437.

14. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2935-2959. [Erratum. J Am Coll Cardiol. 2014;63:3026.]

15. Madsen CM, Varbo A, Nordestgaard BG. Unmet need for primary prevention in individuals with hypertriglyceridaemia not eligible for statin therapy according to European Society of Cardiology/European Atherosclerosis Society guidelines: a contemporary population-based study. Euro Heart J. 2017;39:610-619.

16. Klempfner R, Erez A, Sagit B-Z, et al. Elevated triglyceride level is independently associated with increased all-cause mortality in patients with established coronary heart disease: twenty-two-year follow-up of the Bezafibrate Infarction Prevention Study and Registry. Circ Cardiovasc Qual Outcomes. 2016;9:100-108.

17. Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, et al. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA. 2008;300:2142-2152.

18. Miller M, Stone NJ, Ballantyne C, et al; American Heart Association Clinical Lipidology, Thrombosis, and Prevention Committee of the Council on Nutrition, Physical Activity, and MetabolismCouncil on Arteriosclerosis, Thrombosis and Vascular BiologyCouncil on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease. Triglycerides and cardiovascular disease. Circulation. 2011;123:2292-2333.

19. Graham TE. Exercise, postprandial triacylglyceridemia, and cardiovascular disease risk. Can J Appl Physiol. 2004;29:781-799.

20. Meng Y, Bai H, Wang S, et al. Efficacy of low carbohydrate diet for type 2 diabetes mellitus management: a systematic review and meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2017;131:124-131.

21. What is a standard drink? National Institute on Alcohol Abuse and Alcoholism Web site. www.niaaa.nih.gov/what-standard-drink. Accessed April 24, 2020.

22. Gepner AD, Piper ME, Johnson HM, et al. Effects of smoking and smoking cessation on lipids and lipoproteins: outcomes from a randomized clinical trial. Am Heart J. 2011;161:145-151.

23. Skulas-Ray AC, Wilson PWF, Harris WS, et al; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American Heart Association. Circulation. 2019;140:e673-e691.

24. Jakob T, Nordmann AJ, Schandelmaier S, et al. Fibrates for primary prevention of cardiovascular disease events. Cochrane Database Syst Rev. 2016;11:CD009753.

25. Lisak M, Demarin V, Trkanjec Z, et al. Hypertriglyceridemia as a possible independent risk factor for stroke. Acta Clin Croat. 2013;52:458-463.

26. Bhatt DL, Steg PG, Miller M, et al; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.

27. Barter P, Ginsberg HN. Effectiveness of combined statin plus omega-3 fatty acid therapy for mixed dyslipidemia. Am J Cardiol. 2008;102:1040-1045.

28. Bays H, Ballantyne C, Kastelein J, et al. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] Trial). Am J Cardiol. 2011;108:682-690.

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PRACTICE RECOMMENDATIONS

› Evaluate patients for hypertriglyceridemia when they have a comorbid condition (eg, type 2 diabetes, obesity, hypothyroidism, metabolic syndrome, alcoholism). B

› Do not require fasting status when evaluating triglycerides in a lipid panel. B

› Make therapeutic lifestyle changes first-line treatment for hypertriglyceridemia. C

› Prescribe fibrates for severe hypertriglyceridemia to reduce the risk and recurrence of pancreatitis. A

› Prescribe a statin and an omega-3 fatty acid (fish oil) to lower the triglyceride level and thus reduce resulting atherogenicity when the risk of atherosclerotic cardiovascular disease is > 7.5%. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

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E-cigarette users topped 8 million in 2018

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Mon, 05/11/2020 - 07:39

About 8.1 million adults were using e-cigarettes in 2018, with use varying significantly by cigarette-smoking status and sociodemographics, according to a report from the National Center for Health Statistics.

Those 8.1 million individuals who were using e-cigarettes either every day or some days represented 3.2% of the total adult population, based on data from the 2018 National Health Interview Survey. An even larger proportion, 14.9%, said that they had at least tried an e-cigarette, Maria A. Villarroel, PhD, and associates at the NCHS said in a recent data brief.

Most cigarette smokers, both current and former, were even more likely to use e-cigarettes, they noted.

Former cigarette smokers who had quit within the last year were the most likely to use e-cigarettes – 57.3% had ever used one and 25.2% were current users – while current cigarette users (49.4% ever use and 9.7% current use) and former smokers who had quit 1-5 years before (48.6% ever use, 17.3% current) also were above-average e-cigarette consumers, they reported.

Use was significantly lower, however, among former cigarette smokers who had quit 5 or more years earlier (9.0% and 1.7%, respectively) and those who had never smoked (6.5% and 1.1%), the NCHS investigators said.

The survey data also showed much variation among the sociodemographic subgroups:

  • E-cigarette ever/current use was significantly higher in men (17.9% and 4.2%) than women (12.3% and 2.3%).
  • Whites were significantly more likely to use e-cigarettes (16.9% and 3.7%), compared with Hispanic (11.5% and 2.5%), black (10.0% and 1.6%), and Asian (10.2% and 2.2%) adults.
  • There was significant trend of decreasing use from age 18-24 years (25.8% and 7.6%) to 65 years and older (4.7% and 0.8%).

SOURCE: Villarroel MA et al. NCHS Data Brief No. 365, April 2020.

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About 8.1 million adults were using e-cigarettes in 2018, with use varying significantly by cigarette-smoking status and sociodemographics, according to a report from the National Center for Health Statistics.

Those 8.1 million individuals who were using e-cigarettes either every day or some days represented 3.2% of the total adult population, based on data from the 2018 National Health Interview Survey. An even larger proportion, 14.9%, said that they had at least tried an e-cigarette, Maria A. Villarroel, PhD, and associates at the NCHS said in a recent data brief.

Most cigarette smokers, both current and former, were even more likely to use e-cigarettes, they noted.

Former cigarette smokers who had quit within the last year were the most likely to use e-cigarettes – 57.3% had ever used one and 25.2% were current users – while current cigarette users (49.4% ever use and 9.7% current use) and former smokers who had quit 1-5 years before (48.6% ever use, 17.3% current) also were above-average e-cigarette consumers, they reported.

Use was significantly lower, however, among former cigarette smokers who had quit 5 or more years earlier (9.0% and 1.7%, respectively) and those who had never smoked (6.5% and 1.1%), the NCHS investigators said.

The survey data also showed much variation among the sociodemographic subgroups:

  • E-cigarette ever/current use was significantly higher in men (17.9% and 4.2%) than women (12.3% and 2.3%).
  • Whites were significantly more likely to use e-cigarettes (16.9% and 3.7%), compared with Hispanic (11.5% and 2.5%), black (10.0% and 1.6%), and Asian (10.2% and 2.2%) adults.
  • There was significant trend of decreasing use from age 18-24 years (25.8% and 7.6%) to 65 years and older (4.7% and 0.8%).

SOURCE: Villarroel MA et al. NCHS Data Brief No. 365, April 2020.

About 8.1 million adults were using e-cigarettes in 2018, with use varying significantly by cigarette-smoking status and sociodemographics, according to a report from the National Center for Health Statistics.

Those 8.1 million individuals who were using e-cigarettes either every day or some days represented 3.2% of the total adult population, based on data from the 2018 National Health Interview Survey. An even larger proportion, 14.9%, said that they had at least tried an e-cigarette, Maria A. Villarroel, PhD, and associates at the NCHS said in a recent data brief.

Most cigarette smokers, both current and former, were even more likely to use e-cigarettes, they noted.

Former cigarette smokers who had quit within the last year were the most likely to use e-cigarettes – 57.3% had ever used one and 25.2% were current users – while current cigarette users (49.4% ever use and 9.7% current use) and former smokers who had quit 1-5 years before (48.6% ever use, 17.3% current) also were above-average e-cigarette consumers, they reported.

Use was significantly lower, however, among former cigarette smokers who had quit 5 or more years earlier (9.0% and 1.7%, respectively) and those who had never smoked (6.5% and 1.1%), the NCHS investigators said.

The survey data also showed much variation among the sociodemographic subgroups:

  • E-cigarette ever/current use was significantly higher in men (17.9% and 4.2%) than women (12.3% and 2.3%).
  • Whites were significantly more likely to use e-cigarettes (16.9% and 3.7%), compared with Hispanic (11.5% and 2.5%), black (10.0% and 1.6%), and Asian (10.2% and 2.2%) adults.
  • There was significant trend of decreasing use from age 18-24 years (25.8% and 7.6%) to 65 years and older (4.7% and 0.8%).

SOURCE: Villarroel MA et al. NCHS Data Brief No. 365, April 2020.

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COVID-19 in pregnancy: Supplement oxygen if saturation dips below 94%

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Thu, 08/26/2021 - 16:08

Oxygen supplementation for pregnant women with COVID-19 should begin when saturations fall below 94%, according to physicians in the divisions of maternal-fetal medicine and surgical critical care at the University of Texas Medical Branch at Galveston.

Courtesy NIAID-RML

That’s a bit higher than the 92% cut point for nonpregnant women, but necessary due to the increased oxygen demand and oxygen partial pressure in pregnancy. The goal is a saturation of 94%-96%, said Luis Pacheco, MD, a maternal-fetal medicine and critical care specialist at the university, and associates.

Most pregnant women with coronavirus disease 2019 (COVID-19) will have mild disease, but some might require respiratory support, so Dr. Pacheco and associates addressed the issue in a commentary in Obstetrics & Gynecology.

Women on respiratory support should lie prone if under 20 weeks’ gestation to help with posterior lung recruitment and oxygenation.

If conventional oxygen therapy isn’t enough, high-flow nasal cannula (HFNC) at 60 L/min and 100% oxygen should be the next step, not positive-pressure ventilation. Positive pressure, another option, kicks off aerosols that increase the risk of viral transmission to medical staff. “This makes high-flow nasal cannula the first-line option for patients not responding to conventional oxygen therapy but who are not yet candidates for endotracheal intubation,” the team said. If women do well, the fraction of inspired oxygen should be weaned before the nasal cannula flow is decreased.

However, if they continue to struggle with dyspnea, tachypnea, and oxygen saturation after 30-60 minutes on HFNC, it’s time for mechanical ventilation, and fast. “Delays in recognizing early failure of high-flow nasal cannula ... may result in life-threatening hypoxemia at the time of induction and intubation (especially in pregnant patients with difficult airway anatomy),” the authors said.

For birth, Dr. Pacheco and associates recommended controlled delivery, likely cesarean, if respiration continues to deteriorate despite intubation, especially after 28 weeks’ gestation, instead of waiting for fetal distress and an ICU delivery. A single course of steroids is reasonable to help fetal lung development beforehand, if indicated.

As for fluid strategy during respiratory support, pregnant women are at higher risk for pulmonary edema with lung inflammation, so the authors cautioned against giving maintenance fluids, and said “if daily positive fluid balances are present, combined with worsening respiratory status, the use of furosemide (10-20 mg intravenously every 12 hours) may be indicated.”

For women stable on conventional oxygen therapy or HFNC, they suggested daily nonstress tests starting at 25 weeks’ gestation instead of continuous monitoring, to minimize the COVID-19 transmission risk for staff.

The team cautioned against nebulized treatments and sputum-inducing agents when possible as this may aerosolize the virus.

There was no external funding for the report, and the authors didn’t have any relevant financial disclosures.

SOURCE: Pacheco LD et al. Obstet Gynecol. 2020 Apr 29. doi: 10.1097/AOG.0000000000003929.

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Oxygen supplementation for pregnant women with COVID-19 should begin when saturations fall below 94%, according to physicians in the divisions of maternal-fetal medicine and surgical critical care at the University of Texas Medical Branch at Galveston.

Courtesy NIAID-RML

That’s a bit higher than the 92% cut point for nonpregnant women, but necessary due to the increased oxygen demand and oxygen partial pressure in pregnancy. The goal is a saturation of 94%-96%, said Luis Pacheco, MD, a maternal-fetal medicine and critical care specialist at the university, and associates.

Most pregnant women with coronavirus disease 2019 (COVID-19) will have mild disease, but some might require respiratory support, so Dr. Pacheco and associates addressed the issue in a commentary in Obstetrics & Gynecology.

Women on respiratory support should lie prone if under 20 weeks’ gestation to help with posterior lung recruitment and oxygenation.

If conventional oxygen therapy isn’t enough, high-flow nasal cannula (HFNC) at 60 L/min and 100% oxygen should be the next step, not positive-pressure ventilation. Positive pressure, another option, kicks off aerosols that increase the risk of viral transmission to medical staff. “This makes high-flow nasal cannula the first-line option for patients not responding to conventional oxygen therapy but who are not yet candidates for endotracheal intubation,” the team said. If women do well, the fraction of inspired oxygen should be weaned before the nasal cannula flow is decreased.

However, if they continue to struggle with dyspnea, tachypnea, and oxygen saturation after 30-60 minutes on HFNC, it’s time for mechanical ventilation, and fast. “Delays in recognizing early failure of high-flow nasal cannula ... may result in life-threatening hypoxemia at the time of induction and intubation (especially in pregnant patients with difficult airway anatomy),” the authors said.

For birth, Dr. Pacheco and associates recommended controlled delivery, likely cesarean, if respiration continues to deteriorate despite intubation, especially after 28 weeks’ gestation, instead of waiting for fetal distress and an ICU delivery. A single course of steroids is reasonable to help fetal lung development beforehand, if indicated.

As for fluid strategy during respiratory support, pregnant women are at higher risk for pulmonary edema with lung inflammation, so the authors cautioned against giving maintenance fluids, and said “if daily positive fluid balances are present, combined with worsening respiratory status, the use of furosemide (10-20 mg intravenously every 12 hours) may be indicated.”

For women stable on conventional oxygen therapy or HFNC, they suggested daily nonstress tests starting at 25 weeks’ gestation instead of continuous monitoring, to minimize the COVID-19 transmission risk for staff.

The team cautioned against nebulized treatments and sputum-inducing agents when possible as this may aerosolize the virus.

There was no external funding for the report, and the authors didn’t have any relevant financial disclosures.

SOURCE: Pacheco LD et al. Obstet Gynecol. 2020 Apr 29. doi: 10.1097/AOG.0000000000003929.

Oxygen supplementation for pregnant women with COVID-19 should begin when saturations fall below 94%, according to physicians in the divisions of maternal-fetal medicine and surgical critical care at the University of Texas Medical Branch at Galveston.

Courtesy NIAID-RML

That’s a bit higher than the 92% cut point for nonpregnant women, but necessary due to the increased oxygen demand and oxygen partial pressure in pregnancy. The goal is a saturation of 94%-96%, said Luis Pacheco, MD, a maternal-fetal medicine and critical care specialist at the university, and associates.

Most pregnant women with coronavirus disease 2019 (COVID-19) will have mild disease, but some might require respiratory support, so Dr. Pacheco and associates addressed the issue in a commentary in Obstetrics & Gynecology.

Women on respiratory support should lie prone if under 20 weeks’ gestation to help with posterior lung recruitment and oxygenation.

If conventional oxygen therapy isn’t enough, high-flow nasal cannula (HFNC) at 60 L/min and 100% oxygen should be the next step, not positive-pressure ventilation. Positive pressure, another option, kicks off aerosols that increase the risk of viral transmission to medical staff. “This makes high-flow nasal cannula the first-line option for patients not responding to conventional oxygen therapy but who are not yet candidates for endotracheal intubation,” the team said. If women do well, the fraction of inspired oxygen should be weaned before the nasal cannula flow is decreased.

However, if they continue to struggle with dyspnea, tachypnea, and oxygen saturation after 30-60 minutes on HFNC, it’s time for mechanical ventilation, and fast. “Delays in recognizing early failure of high-flow nasal cannula ... may result in life-threatening hypoxemia at the time of induction and intubation (especially in pregnant patients with difficult airway anatomy),” the authors said.

For birth, Dr. Pacheco and associates recommended controlled delivery, likely cesarean, if respiration continues to deteriorate despite intubation, especially after 28 weeks’ gestation, instead of waiting for fetal distress and an ICU delivery. A single course of steroids is reasonable to help fetal lung development beforehand, if indicated.

As for fluid strategy during respiratory support, pregnant women are at higher risk for pulmonary edema with lung inflammation, so the authors cautioned against giving maintenance fluids, and said “if daily positive fluid balances are present, combined with worsening respiratory status, the use of furosemide (10-20 mg intravenously every 12 hours) may be indicated.”

For women stable on conventional oxygen therapy or HFNC, they suggested daily nonstress tests starting at 25 weeks’ gestation instead of continuous monitoring, to minimize the COVID-19 transmission risk for staff.

The team cautioned against nebulized treatments and sputum-inducing agents when possible as this may aerosolize the virus.

There was no external funding for the report, and the authors didn’t have any relevant financial disclosures.

SOURCE: Pacheco LD et al. Obstet Gynecol. 2020 Apr 29. doi: 10.1097/AOG.0000000000003929.

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Too much or too little sleep spikes constipation

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Tue, 05/12/2020 - 11:50

Individuals who sleep more or less than average report significantly more constipation, compared with normal sleepers, based on data from 14,590 adults.

“Normal sleep duration is thought to be essential for healthy bowel function; however, the effect of either limited or excessive sleep duration on bowel patterns is poorly understood,” Adeyinka Adejumo, MD, of North Shore Medical Center, Salem, Mass., and colleagues wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.

To examine the association between sleep duration and bowel function, the researchers identified 14,590 adults aged 20 years and older who completed questionnaires on sleep and bowel health as part of the National Health and Nutrition Examination Survey (NHANES) during 2005-2010.

Sleep was divided into three categories based on standards from the National Sleep Foundation: short (less than 7 hours), normal (7-8 hours) and long (more than 8 hours).

Overall, constipation rates were significantly lower among normal sleepers (8.3%) compared with both short and long sleepers (11.0% and 12.5%, respectively; P < .0001 for both).

Bowel function was defined as normal, constipation, or diarrhea based on stool form and bowel movements per week. After controlling for demographic, lifestyle, and dietary factors, long sleepers and short sleepers were 61% and 38% more likely, respectively, to report constipation, compared with normal sleepers.

However, sleep duration was not related to diarrhea, the researchers noted. In addition, “A sensitivity analysis revealed that sleep duration did not mediate the relationship between comorbid factors (such as overall health, poverty index, obesity, and body mass index) and constipation,” they wrote.

The results suggest that decreased sleep is associated with constipation among adults in the United States, the researchers said. However, “further studies are needed to evaluate the physiologic mechanisms driving the impact of sleep duration on bowel function to determine whether sleep disorders or their underlying causes affect constipation,” they concluded.

“This study was necessary because up to 50% of Americans suffer from sleep disorders, out of which abnormal sleep duration is one of the most common and underdiagnosed, and associated with other diseases such as hypertension and diabetes,” Dr. Adejumo said in an interview. “However, disorders of bowel function (constipation and diarrhea), which affect almost 10%-15% of the population and result in significant health care burden, such as higher cost, hospital visits, abdominal discomfort, have not been studied among individuals with suboptimal sleep duration.”

Dr. Adejumo said he and his colleagues were surprised by their findings. “Although, based on our hypothesis, we thought that sleeping too long may be associated with constipation, we were shocked to note similar results among people who also sleep for short durations,” he noted.

“Previous studies had suggested that bowel contraction slows down considerably during sleep. It, therefore, will make sense that sleeping for too long may result in suppressed bowel motility and decreased bowel movement,” he said. “However, our results showed similar findings among short sleepers. We do not know the exact mechanism of these results. It may be that short sleep resulted in inadequate bowel rest, bowel muscle fatigue, and, subsequently, decreased bowel movement,” said Dr. Adejumo. “Or it may also be that brain-gut signaling pathways are disrupted among short sleepers, as is seen among IBS patients after a poor night sleep, resulting in higher constipation,” he added.

Clinicians should be aware of the impact of both short and long sleep on constipation, said Dr. Adejumo. “Individuals who are unable to have adequate periods of sleep due to other diseases, including insomnia, disrupted job schedules, or conditions with too long sleep, such as narcolepsy, may all additionally suffer from constipation. Such patients may need regular evaluation and treatment for constipation to improve their discomfort,” he said.

“To confirm our findings, other clinical studies with more granular data on sleep and constipation, are needed, as well as translational research to uncover the potential mechanisms of these findings,” he emphasized.

The researchers had no financial conflicts to disclose.
 

SOURCE: Adejumo A et al. DDW 2020. Abstract Sa1711.

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Individuals who sleep more or less than average report significantly more constipation, compared with normal sleepers, based on data from 14,590 adults.

“Normal sleep duration is thought to be essential for healthy bowel function; however, the effect of either limited or excessive sleep duration on bowel patterns is poorly understood,” Adeyinka Adejumo, MD, of North Shore Medical Center, Salem, Mass., and colleagues wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.

To examine the association between sleep duration and bowel function, the researchers identified 14,590 adults aged 20 years and older who completed questionnaires on sleep and bowel health as part of the National Health and Nutrition Examination Survey (NHANES) during 2005-2010.

Sleep was divided into three categories based on standards from the National Sleep Foundation: short (less than 7 hours), normal (7-8 hours) and long (more than 8 hours).

Overall, constipation rates were significantly lower among normal sleepers (8.3%) compared with both short and long sleepers (11.0% and 12.5%, respectively; P < .0001 for both).

Bowel function was defined as normal, constipation, or diarrhea based on stool form and bowel movements per week. After controlling for demographic, lifestyle, and dietary factors, long sleepers and short sleepers were 61% and 38% more likely, respectively, to report constipation, compared with normal sleepers.

However, sleep duration was not related to diarrhea, the researchers noted. In addition, “A sensitivity analysis revealed that sleep duration did not mediate the relationship between comorbid factors (such as overall health, poverty index, obesity, and body mass index) and constipation,” they wrote.

The results suggest that decreased sleep is associated with constipation among adults in the United States, the researchers said. However, “further studies are needed to evaluate the physiologic mechanisms driving the impact of sleep duration on bowel function to determine whether sleep disorders or their underlying causes affect constipation,” they concluded.

“This study was necessary because up to 50% of Americans suffer from sleep disorders, out of which abnormal sleep duration is one of the most common and underdiagnosed, and associated with other diseases such as hypertension and diabetes,” Dr. Adejumo said in an interview. “However, disorders of bowel function (constipation and diarrhea), which affect almost 10%-15% of the population and result in significant health care burden, such as higher cost, hospital visits, abdominal discomfort, have not been studied among individuals with suboptimal sleep duration.”

Dr. Adejumo said he and his colleagues were surprised by their findings. “Although, based on our hypothesis, we thought that sleeping too long may be associated with constipation, we were shocked to note similar results among people who also sleep for short durations,” he noted.

“Previous studies had suggested that bowel contraction slows down considerably during sleep. It, therefore, will make sense that sleeping for too long may result in suppressed bowel motility and decreased bowel movement,” he said. “However, our results showed similar findings among short sleepers. We do not know the exact mechanism of these results. It may be that short sleep resulted in inadequate bowel rest, bowel muscle fatigue, and, subsequently, decreased bowel movement,” said Dr. Adejumo. “Or it may also be that brain-gut signaling pathways are disrupted among short sleepers, as is seen among IBS patients after a poor night sleep, resulting in higher constipation,” he added.

Clinicians should be aware of the impact of both short and long sleep on constipation, said Dr. Adejumo. “Individuals who are unable to have adequate periods of sleep due to other diseases, including insomnia, disrupted job schedules, or conditions with too long sleep, such as narcolepsy, may all additionally suffer from constipation. Such patients may need regular evaluation and treatment for constipation to improve their discomfort,” he said.

“To confirm our findings, other clinical studies with more granular data on sleep and constipation, are needed, as well as translational research to uncover the potential mechanisms of these findings,” he emphasized.

The researchers had no financial conflicts to disclose.
 

SOURCE: Adejumo A et al. DDW 2020. Abstract Sa1711.

Individuals who sleep more or less than average report significantly more constipation, compared with normal sleepers, based on data from 14,590 adults.

“Normal sleep duration is thought to be essential for healthy bowel function; however, the effect of either limited or excessive sleep duration on bowel patterns is poorly understood,” Adeyinka Adejumo, MD, of North Shore Medical Center, Salem, Mass., and colleagues wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.

To examine the association between sleep duration and bowel function, the researchers identified 14,590 adults aged 20 years and older who completed questionnaires on sleep and bowel health as part of the National Health and Nutrition Examination Survey (NHANES) during 2005-2010.

Sleep was divided into three categories based on standards from the National Sleep Foundation: short (less than 7 hours), normal (7-8 hours) and long (more than 8 hours).

Overall, constipation rates were significantly lower among normal sleepers (8.3%) compared with both short and long sleepers (11.0% and 12.5%, respectively; P < .0001 for both).

Bowel function was defined as normal, constipation, or diarrhea based on stool form and bowel movements per week. After controlling for demographic, lifestyle, and dietary factors, long sleepers and short sleepers were 61% and 38% more likely, respectively, to report constipation, compared with normal sleepers.

However, sleep duration was not related to diarrhea, the researchers noted. In addition, “A sensitivity analysis revealed that sleep duration did not mediate the relationship between comorbid factors (such as overall health, poverty index, obesity, and body mass index) and constipation,” they wrote.

The results suggest that decreased sleep is associated with constipation among adults in the United States, the researchers said. However, “further studies are needed to evaluate the physiologic mechanisms driving the impact of sleep duration on bowel function to determine whether sleep disorders or their underlying causes affect constipation,” they concluded.

“This study was necessary because up to 50% of Americans suffer from sleep disorders, out of which abnormal sleep duration is one of the most common and underdiagnosed, and associated with other diseases such as hypertension and diabetes,” Dr. Adejumo said in an interview. “However, disorders of bowel function (constipation and diarrhea), which affect almost 10%-15% of the population and result in significant health care burden, such as higher cost, hospital visits, abdominal discomfort, have not been studied among individuals with suboptimal sleep duration.”

Dr. Adejumo said he and his colleagues were surprised by their findings. “Although, based on our hypothesis, we thought that sleeping too long may be associated with constipation, we were shocked to note similar results among people who also sleep for short durations,” he noted.

“Previous studies had suggested that bowel contraction slows down considerably during sleep. It, therefore, will make sense that sleeping for too long may result in suppressed bowel motility and decreased bowel movement,” he said. “However, our results showed similar findings among short sleepers. We do not know the exact mechanism of these results. It may be that short sleep resulted in inadequate bowel rest, bowel muscle fatigue, and, subsequently, decreased bowel movement,” said Dr. Adejumo. “Or it may also be that brain-gut signaling pathways are disrupted among short sleepers, as is seen among IBS patients after a poor night sleep, resulting in higher constipation,” he added.

Clinicians should be aware of the impact of both short and long sleep on constipation, said Dr. Adejumo. “Individuals who are unable to have adequate periods of sleep due to other diseases, including insomnia, disrupted job schedules, or conditions with too long sleep, such as narcolepsy, may all additionally suffer from constipation. Such patients may need regular evaluation and treatment for constipation to improve their discomfort,” he said.

“To confirm our findings, other clinical studies with more granular data on sleep and constipation, are needed, as well as translational research to uncover the potential mechanisms of these findings,” he emphasized.

The researchers had no financial conflicts to disclose.
 

SOURCE: Adejumo A et al. DDW 2020. Abstract Sa1711.

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Key clinical point: Both short sleepers and long sleepers reported significantly more constipation compared with normal sleepers.

Major finding: Overall constipation rates were 8.3% in normal sleepers, compared with 11.0% for short sleepers and 12.5% for long sleepers.

Study details: The data come from 14,590 adults who participated in NHANES between 2005 and 2010.

Disclosures: The researchers had no financial conflicts to disclose.

Source: Adejumo A et al. DDW 2020. Abstract Sa1711.

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With life in the balance, a pediatric palliative care program expands its work to adults

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Tue, 02/14/2023 - 13:02

In late March of 2020, when it became clear that hospitals in the greater New York City area would face a capacity crisis in caring for seriously ill patients with COVID-19, members of the leadership team at the Children’s Hospital at Montefiore (CHAM) in the Bronx, N.Y., convened to draft a response plan.

Courtesy Montefiore Health System
The Children's Hospital at Montefiore.

The recommendations put into action that day included moving the hospital’s emergency department from the lower level to the fourth floor, increasing the age limit for patients seen in the ED from 21 years of age to 30 and freeing up an entire hospital floor and a half to accommodate the anticipated surge of patients with COVID-19 admitted to Montefiore’s interconnected adult hospital, according to Sarah E. Norris, MD.

“We made multiple moves all at once,” said Dr. Norris, director of pediatric palliative care at CHAM. “It struck everyone as logical that palliative care had to be expanded, because all of the news we had received as the surge came to New York from around the world was full of death and uncertainty, and would require thoughtful conversations about end-of-life wishes at critical times and how to really respect the person and understand their values.”

Dr. Sarah E. Norris

When Dr. Norris left the leadership team meeting, she returned to her office, put her face in her hands, and sobbed as she began to process the gravity of what was ahead. “I cried because I knew that so many families were going to suffer a heartbreak, no matter how much we could do,” she said.
 

Stitching the QUILT

Over the next few days, Dr. Norris began recruiting colleagues from the large Montefiore Health System – most of whom she did not know – who met criteria for work deployment to expand CHAM’s palliative care program of clinician to 27 clinicians consisting of pediatricians, nurse practitioners, and psychologists, to meet the projected needs of COVID-19 patients and their families.

Some candidates for the effort, known as the Quality in Life Team (QUILT), were 65 years of age or older, considered at high risk for developing COVID-19-related complications themselves. Others were immunocompromised or had medical conditions that would not allow them to have direct contact with COVID-19 patients. “There were also clinicians in other parts of our health system whose practice hours were going to be severely reduced,” said Dr. Norris, who is board-certified in general pediatrics and in hospice and palliative care medicine.

Once she assembled QUILT, members participated in a 1-day rapid training webinar covering the basics of palliative care and grief, and readied themselves for one of three roles: physicians to provide face-to-face palliative care in CHAM; supportive callers to provide support to patients with COVID-19 and their families between 12:00-8:00 p.m. each day; and bereavement callers to reach out to families who lost loved ones to COVID-19 and provide grief counseling for 3 weeks.

“This allows families to have at least two contacts a day from the hospital: one from the medical team that’s giving them technical, medical information, and another from members of the QUILT team,” Dr. Norris said. “We provide support for the worry, anxiety, and fear that we know creeps in when you’re separated from your family member, especially during a pandemic when you watch TV and there’s a death count rising.”

During her early meetings with QUILT members via Zoom or on the phone, Dr. Norris encouraged them to stretch their skill sets and mindsets as they shifted from caring for children and adolescents to mostly adults. “Pediatricians are all about family; that’s why we get into this,” she said. “We’re used to treating your kids, but then, suddenly, the parent becomes our patient, like in COVID-19, or the grandparent becomes our patient. We treat you all the same; you’re part of our family. There has been no adult who has died ‘within our house’ that has died alone. There has either been a staff member at their bedside, or when possible, a family member. We are witnessing life until the last breath here.”
 

 

 

‘They have no loved ones with them’

One day, members of CHAM’s medical team contacted Dr. Norris about a patient with COVID-19 who’d been cared for by Montefiore clinicians all of his young life. The boy’s mother, who did not speak English, was at his bedside in the ICU, and the clinicians asked Dr. Norris to speak with her by cell phone while they prepared him for intubation.

“We were looking at each other through a glass window wall in our ICU,” Dr. Norris recalled. “I talked to her the entire time the team worked to put him on the breathing machine, through an interpreter. I asked her to tell me about her son and about her family, and she did. We developed a warm relationship. After that, every day I would see her son through the glass window wall. Every couple of days, I would have the privilege of talking to his mother by phone. At one point, she asked me, ‘Dr. Norris, do you think his lungs will heal?’ I had to tell her no. Almost selfishly, I was relieved we were on the phone, because she cried, and so did I. When he died, she was able to be by his side.”

Frederick J. Kaskel, MD, PhD, joined QUILT as a supportive caller after being asked to go home during his on-call shift on St. Patrick’s Day at CHAM, where he serves as chief emeritus of nephrology. “I was told that I was deemed to be at high risk because of my age,” the 75-year-old said. “The next day, a junior person took over for me, and 2 days later she got sick with COVID-19. She’s fine but she was home for 3 weeks sick as a dog. It was scary.”

Dr. Frederick J. Kaskel

In his role as a supportive caller, Dr. Kaskel found himself engaged in his share of detective work, trying to find phone numbers of next of kin for patients hospitalized with COVID-19. “When they come into the ER, they may not have been with a loved one or a family member; they may have been brought in by an EMT,” he said. “Some of them speak little English and others have little documentation with them. It takes a lot of work to get phone numbers.”

Once Dr. Kaskel reaches a loved one by phone, he introduces himself as a member of the QUILT team. “I tell them I’m not calling to update the medical status but just to talk to them about their loved one,” he said. “Then I usually ask, ‘So, how are you doing with this? The stress is enormous, the uncertainties.’ Then they open up and express their fears. I’ve had a lot of people say, ‘we have no money, and I don’t know how we’re going to pay rent for the apartment. We have to line up for food.’ I also ask what they do to alleviate stress. One guy said, ‘I drink a lot, but I’m careful.’ ”

Dr. Kaskel, who is also a past president of the American Society of Pediatric Nephrology, applies that same personable approach in daily conversations with adult patients hospitalized at CHAM with COVID-19, the majority of whom are African Americans in their 30s, 40s, and 50s. “Invariably, they ask, ‘Has my loved one been updated as to my status?’ ” he said. “The second thing they often say is, ‘I’m worried about infecting other people, but I also worry if I’m going to get through this. I’m really afraid I’m going to die.’ I say, ‘You have a wonderful team keeping track of you. They’re seeing you all the time and making changes to your medicines.’ ”

When patients express their fear of dying from the virus, Dr. Kaskel asks them how they’re coping with that fear. Most tell him that they pray.

“If they don’t answer, I ask if they have any hobbies, like ‘Are you watching TV? Are you reading? Do you have your cell phone?’ ” he said. “Then they open up and say things like, ‘I’m listening to music on the cell phone,’ or ‘I’m FaceTiming with my loved ones.’ The use of FaceTime is crucial, because they are in a hospital, critically ill, potentially dying alone with strangers. This really hit me on the first day [of this work]. They have no loved ones with them. They have strangers: the CHAM nurses, the medical residents, the social workers, and the doctors.”
 

 

 

No hospital cheeseburgers

QUILT began its work on April 6, and at one time provided palliative care services for a peak of 92 mostly adult patients with COVID-19. The supportive callers made 249 individual connections with patients and family members by phone from April 6-13, 162 connections from April 13-19, and 130 connections from April 20-26, according to Dr. Norris. As of April 28, the CHAM inpatient census of patients aged 18 years and over with COVID-19 was 42, “and we’re making 130 connections by phone to patients and family members each day,” she said.

QUILT bereavement callers are following 30 families, providing 3 weeks of acute grief counseling from the date of death. “A sad truth is that, here in New York, our entire funeral, burial, cremation system is overwhelmed in volume,” Dr. Norris said. “Only half of the patients we’re following 3 weeks out have been able to have their family member buried or cremated; many are still waiting. What strikes me here is that pediatricians are often partners in care. With time, we’re partners in care in heartbreak, and in the occasional victory. We mourn patients who have died. We’ve had colleagues who died from COVID-19 right here at our hospital. But we stand together like a family.”

Courtesy Dr. Sarah E. Norris
Dr. Sarah E. Norris

Dr. Norris recalled an older woman who came into CHAM’s ICU on a ventilator, critically ill from COVID-19. She called her husband at home every day with updates. “I got to know her husband, and I got to know her through him,” Dr. Norris said. “We talked every single day and she was able to graduate off of the breathing tube and out of the ICU, which was amazing.” The woman was moved to a floor in the adult hospital, but Dr. Norris continues to visit her and to provide her husband with updates, “because I’m devoted to them,” she said.

Recently, physicians in the adult hospital consulted with Dr. Norris about the woman. “They were trying to figure out what to do with her next,” she said. “Could she go home, or did she need rehab? They said, ‘We called you, Dr. Norris, because her husband thinks he can take her home.’ We know that COVID-19 really weakens people, so I went over to see her myself. I thought, ‘No single person could take care of an adult so weak at home.’ So, I called her husband and said, ‘I’m here with your wife, and I have to tell you; if she were my mother, I couldn’t take her home today. I need you to trust me.’ He said, ‘OK. We trust you and know that you have her best interest at heart.’ ”

Dr. Kaskel relayed the story of an older patient who was slowly recovering from COVID-19. During a phone call, he asked the man if there was anything he wanted at that moment.

“He said, ‘I’d love to see my wife and my children and my grandkids. I know I’m going to see them again, but right now, doc, if you could get me a cheeseburger with lettuce and tomato and ketchup and French fries from outside of the hospital, I’d be the happiest man in the world.’

I said, ‘What’s the matter with the cheeseburger made at the hospital?’

He said, ‘No! They can’t make the cheeseburger I want.’

I promised him I’d relay that message to the social worker responsible for the patient. I told her please, if you buy this for him, I’ll pay you back.”
 

Self-care and the next chapter

Twice each week, QUILT members gather in front of their computer monitors for mandatory Zoom meetings facilitated by two psychologists to share challenges, best practices, and to discuss the difficult work they’re doing. “We meet, because you cannot help someone if you cannot help yourself,” Dr. Norris said. “We have been encouraged each and every meeting to practice self-compassion, and to recognize that things happen during a pandemic – some will be the best you can do.”

She described organizing and serving on QUILT as a grounding experience with important lessons for the delivery of health care after the pandemic subsides and the team members return to their respective practices. “I think we’ve all gained a greater sense of humility, and we understand that the badge I wear every day does not protect me from becoming a patient, or from having my own family fall ill,” she said. “Here, we think about it very simply: ‘I’m going to treat you like you’re part of my own family.’ ”

Dr. Kaskel said that serving on QUILT as a supportive caller is an experience he won’t soon forget.

“The human bond is so accessible if you accept it,” he said. “If someone is an introvert that might not be able to draw out a stranger on the phone, then [he or she] shouldn’t do this [work]. But the fact that you can make a bond with someone that you’re not even seeing in person and know that both sides of this phone call are getting good vibes, that’s a remarkable feeling that I never really knew before, because I’ve never really had to do that before. It brings up feelings like I had after 9/11 – a unified approach to surviving this as people, as a community, the idea that ‘we will get through this,’ even though it’s totally different than anything before. The idea that there’s still hope. Those are things you can’t put a price on.”

An article about how CHAM transformed to provide care to adult COVID-19 patients was published online May 4, 2020, in the Journal of Pediatrics: doi: 10.1016/j.jpeds.2020.04.060.

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In late March of 2020, when it became clear that hospitals in the greater New York City area would face a capacity crisis in caring for seriously ill patients with COVID-19, members of the leadership team at the Children’s Hospital at Montefiore (CHAM) in the Bronx, N.Y., convened to draft a response plan.

Courtesy Montefiore Health System
The Children's Hospital at Montefiore.

The recommendations put into action that day included moving the hospital’s emergency department from the lower level to the fourth floor, increasing the age limit for patients seen in the ED from 21 years of age to 30 and freeing up an entire hospital floor and a half to accommodate the anticipated surge of patients with COVID-19 admitted to Montefiore’s interconnected adult hospital, according to Sarah E. Norris, MD.

“We made multiple moves all at once,” said Dr. Norris, director of pediatric palliative care at CHAM. “It struck everyone as logical that palliative care had to be expanded, because all of the news we had received as the surge came to New York from around the world was full of death and uncertainty, and would require thoughtful conversations about end-of-life wishes at critical times and how to really respect the person and understand their values.”

Dr. Sarah E. Norris

When Dr. Norris left the leadership team meeting, she returned to her office, put her face in her hands, and sobbed as she began to process the gravity of what was ahead. “I cried because I knew that so many families were going to suffer a heartbreak, no matter how much we could do,” she said.
 

Stitching the QUILT

Over the next few days, Dr. Norris began recruiting colleagues from the large Montefiore Health System – most of whom she did not know – who met criteria for work deployment to expand CHAM’s palliative care program of clinician to 27 clinicians consisting of pediatricians, nurse practitioners, and psychologists, to meet the projected needs of COVID-19 patients and their families.

Some candidates for the effort, known as the Quality in Life Team (QUILT), were 65 years of age or older, considered at high risk for developing COVID-19-related complications themselves. Others were immunocompromised or had medical conditions that would not allow them to have direct contact with COVID-19 patients. “There were also clinicians in other parts of our health system whose practice hours were going to be severely reduced,” said Dr. Norris, who is board-certified in general pediatrics and in hospice and palliative care medicine.

Once she assembled QUILT, members participated in a 1-day rapid training webinar covering the basics of palliative care and grief, and readied themselves for one of three roles: physicians to provide face-to-face palliative care in CHAM; supportive callers to provide support to patients with COVID-19 and their families between 12:00-8:00 p.m. each day; and bereavement callers to reach out to families who lost loved ones to COVID-19 and provide grief counseling for 3 weeks.

“This allows families to have at least two contacts a day from the hospital: one from the medical team that’s giving them technical, medical information, and another from members of the QUILT team,” Dr. Norris said. “We provide support for the worry, anxiety, and fear that we know creeps in when you’re separated from your family member, especially during a pandemic when you watch TV and there’s a death count rising.”

During her early meetings with QUILT members via Zoom or on the phone, Dr. Norris encouraged them to stretch their skill sets and mindsets as they shifted from caring for children and adolescents to mostly adults. “Pediatricians are all about family; that’s why we get into this,” she said. “We’re used to treating your kids, but then, suddenly, the parent becomes our patient, like in COVID-19, or the grandparent becomes our patient. We treat you all the same; you’re part of our family. There has been no adult who has died ‘within our house’ that has died alone. There has either been a staff member at their bedside, or when possible, a family member. We are witnessing life until the last breath here.”
 

 

 

‘They have no loved ones with them’

One day, members of CHAM’s medical team contacted Dr. Norris about a patient with COVID-19 who’d been cared for by Montefiore clinicians all of his young life. The boy’s mother, who did not speak English, was at his bedside in the ICU, and the clinicians asked Dr. Norris to speak with her by cell phone while they prepared him for intubation.

“We were looking at each other through a glass window wall in our ICU,” Dr. Norris recalled. “I talked to her the entire time the team worked to put him on the breathing machine, through an interpreter. I asked her to tell me about her son and about her family, and she did. We developed a warm relationship. After that, every day I would see her son through the glass window wall. Every couple of days, I would have the privilege of talking to his mother by phone. At one point, she asked me, ‘Dr. Norris, do you think his lungs will heal?’ I had to tell her no. Almost selfishly, I was relieved we were on the phone, because she cried, and so did I. When he died, she was able to be by his side.”

Frederick J. Kaskel, MD, PhD, joined QUILT as a supportive caller after being asked to go home during his on-call shift on St. Patrick’s Day at CHAM, where he serves as chief emeritus of nephrology. “I was told that I was deemed to be at high risk because of my age,” the 75-year-old said. “The next day, a junior person took over for me, and 2 days later she got sick with COVID-19. She’s fine but she was home for 3 weeks sick as a dog. It was scary.”

Dr. Frederick J. Kaskel

In his role as a supportive caller, Dr. Kaskel found himself engaged in his share of detective work, trying to find phone numbers of next of kin for patients hospitalized with COVID-19. “When they come into the ER, they may not have been with a loved one or a family member; they may have been brought in by an EMT,” he said. “Some of them speak little English and others have little documentation with them. It takes a lot of work to get phone numbers.”

Once Dr. Kaskel reaches a loved one by phone, he introduces himself as a member of the QUILT team. “I tell them I’m not calling to update the medical status but just to talk to them about their loved one,” he said. “Then I usually ask, ‘So, how are you doing with this? The stress is enormous, the uncertainties.’ Then they open up and express their fears. I’ve had a lot of people say, ‘we have no money, and I don’t know how we’re going to pay rent for the apartment. We have to line up for food.’ I also ask what they do to alleviate stress. One guy said, ‘I drink a lot, but I’m careful.’ ”

Dr. Kaskel, who is also a past president of the American Society of Pediatric Nephrology, applies that same personable approach in daily conversations with adult patients hospitalized at CHAM with COVID-19, the majority of whom are African Americans in their 30s, 40s, and 50s. “Invariably, they ask, ‘Has my loved one been updated as to my status?’ ” he said. “The second thing they often say is, ‘I’m worried about infecting other people, but I also worry if I’m going to get through this. I’m really afraid I’m going to die.’ I say, ‘You have a wonderful team keeping track of you. They’re seeing you all the time and making changes to your medicines.’ ”

When patients express their fear of dying from the virus, Dr. Kaskel asks them how they’re coping with that fear. Most tell him that they pray.

“If they don’t answer, I ask if they have any hobbies, like ‘Are you watching TV? Are you reading? Do you have your cell phone?’ ” he said. “Then they open up and say things like, ‘I’m listening to music on the cell phone,’ or ‘I’m FaceTiming with my loved ones.’ The use of FaceTime is crucial, because they are in a hospital, critically ill, potentially dying alone with strangers. This really hit me on the first day [of this work]. They have no loved ones with them. They have strangers: the CHAM nurses, the medical residents, the social workers, and the doctors.”
 

 

 

No hospital cheeseburgers

QUILT began its work on April 6, and at one time provided palliative care services for a peak of 92 mostly adult patients with COVID-19. The supportive callers made 249 individual connections with patients and family members by phone from April 6-13, 162 connections from April 13-19, and 130 connections from April 20-26, according to Dr. Norris. As of April 28, the CHAM inpatient census of patients aged 18 years and over with COVID-19 was 42, “and we’re making 130 connections by phone to patients and family members each day,” she said.

QUILT bereavement callers are following 30 families, providing 3 weeks of acute grief counseling from the date of death. “A sad truth is that, here in New York, our entire funeral, burial, cremation system is overwhelmed in volume,” Dr. Norris said. “Only half of the patients we’re following 3 weeks out have been able to have their family member buried or cremated; many are still waiting. What strikes me here is that pediatricians are often partners in care. With time, we’re partners in care in heartbreak, and in the occasional victory. We mourn patients who have died. We’ve had colleagues who died from COVID-19 right here at our hospital. But we stand together like a family.”

Courtesy Dr. Sarah E. Norris
Dr. Sarah E. Norris

Dr. Norris recalled an older woman who came into CHAM’s ICU on a ventilator, critically ill from COVID-19. She called her husband at home every day with updates. “I got to know her husband, and I got to know her through him,” Dr. Norris said. “We talked every single day and she was able to graduate off of the breathing tube and out of the ICU, which was amazing.” The woman was moved to a floor in the adult hospital, but Dr. Norris continues to visit her and to provide her husband with updates, “because I’m devoted to them,” she said.

Recently, physicians in the adult hospital consulted with Dr. Norris about the woman. “They were trying to figure out what to do with her next,” she said. “Could she go home, or did she need rehab? They said, ‘We called you, Dr. Norris, because her husband thinks he can take her home.’ We know that COVID-19 really weakens people, so I went over to see her myself. I thought, ‘No single person could take care of an adult so weak at home.’ So, I called her husband and said, ‘I’m here with your wife, and I have to tell you; if she were my mother, I couldn’t take her home today. I need you to trust me.’ He said, ‘OK. We trust you and know that you have her best interest at heart.’ ”

Dr. Kaskel relayed the story of an older patient who was slowly recovering from COVID-19. During a phone call, he asked the man if there was anything he wanted at that moment.

“He said, ‘I’d love to see my wife and my children and my grandkids. I know I’m going to see them again, but right now, doc, if you could get me a cheeseburger with lettuce and tomato and ketchup and French fries from outside of the hospital, I’d be the happiest man in the world.’

I said, ‘What’s the matter with the cheeseburger made at the hospital?’

He said, ‘No! They can’t make the cheeseburger I want.’

I promised him I’d relay that message to the social worker responsible for the patient. I told her please, if you buy this for him, I’ll pay you back.”
 

Self-care and the next chapter

Twice each week, QUILT members gather in front of their computer monitors for mandatory Zoom meetings facilitated by two psychologists to share challenges, best practices, and to discuss the difficult work they’re doing. “We meet, because you cannot help someone if you cannot help yourself,” Dr. Norris said. “We have been encouraged each and every meeting to practice self-compassion, and to recognize that things happen during a pandemic – some will be the best you can do.”

She described organizing and serving on QUILT as a grounding experience with important lessons for the delivery of health care after the pandemic subsides and the team members return to their respective practices. “I think we’ve all gained a greater sense of humility, and we understand that the badge I wear every day does not protect me from becoming a patient, or from having my own family fall ill,” she said. “Here, we think about it very simply: ‘I’m going to treat you like you’re part of my own family.’ ”

Dr. Kaskel said that serving on QUILT as a supportive caller is an experience he won’t soon forget.

“The human bond is so accessible if you accept it,” he said. “If someone is an introvert that might not be able to draw out a stranger on the phone, then [he or she] shouldn’t do this [work]. But the fact that you can make a bond with someone that you’re not even seeing in person and know that both sides of this phone call are getting good vibes, that’s a remarkable feeling that I never really knew before, because I’ve never really had to do that before. It brings up feelings like I had after 9/11 – a unified approach to surviving this as people, as a community, the idea that ‘we will get through this,’ even though it’s totally different than anything before. The idea that there’s still hope. Those are things you can’t put a price on.”

An article about how CHAM transformed to provide care to adult COVID-19 patients was published online May 4, 2020, in the Journal of Pediatrics: doi: 10.1016/j.jpeds.2020.04.060.

In late March of 2020, when it became clear that hospitals in the greater New York City area would face a capacity crisis in caring for seriously ill patients with COVID-19, members of the leadership team at the Children’s Hospital at Montefiore (CHAM) in the Bronx, N.Y., convened to draft a response plan.

Courtesy Montefiore Health System
The Children's Hospital at Montefiore.

The recommendations put into action that day included moving the hospital’s emergency department from the lower level to the fourth floor, increasing the age limit for patients seen in the ED from 21 years of age to 30 and freeing up an entire hospital floor and a half to accommodate the anticipated surge of patients with COVID-19 admitted to Montefiore’s interconnected adult hospital, according to Sarah E. Norris, MD.

“We made multiple moves all at once,” said Dr. Norris, director of pediatric palliative care at CHAM. “It struck everyone as logical that palliative care had to be expanded, because all of the news we had received as the surge came to New York from around the world was full of death and uncertainty, and would require thoughtful conversations about end-of-life wishes at critical times and how to really respect the person and understand their values.”

Dr. Sarah E. Norris

When Dr. Norris left the leadership team meeting, she returned to her office, put her face in her hands, and sobbed as she began to process the gravity of what was ahead. “I cried because I knew that so many families were going to suffer a heartbreak, no matter how much we could do,” she said.
 

Stitching the QUILT

Over the next few days, Dr. Norris began recruiting colleagues from the large Montefiore Health System – most of whom she did not know – who met criteria for work deployment to expand CHAM’s palliative care program of clinician to 27 clinicians consisting of pediatricians, nurse practitioners, and psychologists, to meet the projected needs of COVID-19 patients and their families.

Some candidates for the effort, known as the Quality in Life Team (QUILT), were 65 years of age or older, considered at high risk for developing COVID-19-related complications themselves. Others were immunocompromised or had medical conditions that would not allow them to have direct contact with COVID-19 patients. “There were also clinicians in other parts of our health system whose practice hours were going to be severely reduced,” said Dr. Norris, who is board-certified in general pediatrics and in hospice and palliative care medicine.

Once she assembled QUILT, members participated in a 1-day rapid training webinar covering the basics of palliative care and grief, and readied themselves for one of three roles: physicians to provide face-to-face palliative care in CHAM; supportive callers to provide support to patients with COVID-19 and their families between 12:00-8:00 p.m. each day; and bereavement callers to reach out to families who lost loved ones to COVID-19 and provide grief counseling for 3 weeks.

“This allows families to have at least two contacts a day from the hospital: one from the medical team that’s giving them technical, medical information, and another from members of the QUILT team,” Dr. Norris said. “We provide support for the worry, anxiety, and fear that we know creeps in when you’re separated from your family member, especially during a pandemic when you watch TV and there’s a death count rising.”

During her early meetings with QUILT members via Zoom or on the phone, Dr. Norris encouraged them to stretch their skill sets and mindsets as they shifted from caring for children and adolescents to mostly adults. “Pediatricians are all about family; that’s why we get into this,” she said. “We’re used to treating your kids, but then, suddenly, the parent becomes our patient, like in COVID-19, or the grandparent becomes our patient. We treat you all the same; you’re part of our family. There has been no adult who has died ‘within our house’ that has died alone. There has either been a staff member at their bedside, or when possible, a family member. We are witnessing life until the last breath here.”
 

 

 

‘They have no loved ones with them’

One day, members of CHAM’s medical team contacted Dr. Norris about a patient with COVID-19 who’d been cared for by Montefiore clinicians all of his young life. The boy’s mother, who did not speak English, was at his bedside in the ICU, and the clinicians asked Dr. Norris to speak with her by cell phone while they prepared him for intubation.

“We were looking at each other through a glass window wall in our ICU,” Dr. Norris recalled. “I talked to her the entire time the team worked to put him on the breathing machine, through an interpreter. I asked her to tell me about her son and about her family, and she did. We developed a warm relationship. After that, every day I would see her son through the glass window wall. Every couple of days, I would have the privilege of talking to his mother by phone. At one point, she asked me, ‘Dr. Norris, do you think his lungs will heal?’ I had to tell her no. Almost selfishly, I was relieved we were on the phone, because she cried, and so did I. When he died, she was able to be by his side.”

Frederick J. Kaskel, MD, PhD, joined QUILT as a supportive caller after being asked to go home during his on-call shift on St. Patrick’s Day at CHAM, where he serves as chief emeritus of nephrology. “I was told that I was deemed to be at high risk because of my age,” the 75-year-old said. “The next day, a junior person took over for me, and 2 days later she got sick with COVID-19. She’s fine but she was home for 3 weeks sick as a dog. It was scary.”

Dr. Frederick J. Kaskel

In his role as a supportive caller, Dr. Kaskel found himself engaged in his share of detective work, trying to find phone numbers of next of kin for patients hospitalized with COVID-19. “When they come into the ER, they may not have been with a loved one or a family member; they may have been brought in by an EMT,” he said. “Some of them speak little English and others have little documentation with them. It takes a lot of work to get phone numbers.”

Once Dr. Kaskel reaches a loved one by phone, he introduces himself as a member of the QUILT team. “I tell them I’m not calling to update the medical status but just to talk to them about their loved one,” he said. “Then I usually ask, ‘So, how are you doing with this? The stress is enormous, the uncertainties.’ Then they open up and express their fears. I’ve had a lot of people say, ‘we have no money, and I don’t know how we’re going to pay rent for the apartment. We have to line up for food.’ I also ask what they do to alleviate stress. One guy said, ‘I drink a lot, but I’m careful.’ ”

Dr. Kaskel, who is also a past president of the American Society of Pediatric Nephrology, applies that same personable approach in daily conversations with adult patients hospitalized at CHAM with COVID-19, the majority of whom are African Americans in their 30s, 40s, and 50s. “Invariably, they ask, ‘Has my loved one been updated as to my status?’ ” he said. “The second thing they often say is, ‘I’m worried about infecting other people, but I also worry if I’m going to get through this. I’m really afraid I’m going to die.’ I say, ‘You have a wonderful team keeping track of you. They’re seeing you all the time and making changes to your medicines.’ ”

When patients express their fear of dying from the virus, Dr. Kaskel asks them how they’re coping with that fear. Most tell him that they pray.

“If they don’t answer, I ask if they have any hobbies, like ‘Are you watching TV? Are you reading? Do you have your cell phone?’ ” he said. “Then they open up and say things like, ‘I’m listening to music on the cell phone,’ or ‘I’m FaceTiming with my loved ones.’ The use of FaceTime is crucial, because they are in a hospital, critically ill, potentially dying alone with strangers. This really hit me on the first day [of this work]. They have no loved ones with them. They have strangers: the CHAM nurses, the medical residents, the social workers, and the doctors.”
 

 

 

No hospital cheeseburgers

QUILT began its work on April 6, and at one time provided palliative care services for a peak of 92 mostly adult patients with COVID-19. The supportive callers made 249 individual connections with patients and family members by phone from April 6-13, 162 connections from April 13-19, and 130 connections from April 20-26, according to Dr. Norris. As of April 28, the CHAM inpatient census of patients aged 18 years and over with COVID-19 was 42, “and we’re making 130 connections by phone to patients and family members each day,” she said.

QUILT bereavement callers are following 30 families, providing 3 weeks of acute grief counseling from the date of death. “A sad truth is that, here in New York, our entire funeral, burial, cremation system is overwhelmed in volume,” Dr. Norris said. “Only half of the patients we’re following 3 weeks out have been able to have their family member buried or cremated; many are still waiting. What strikes me here is that pediatricians are often partners in care. With time, we’re partners in care in heartbreak, and in the occasional victory. We mourn patients who have died. We’ve had colleagues who died from COVID-19 right here at our hospital. But we stand together like a family.”

Courtesy Dr. Sarah E. Norris
Dr. Sarah E. Norris

Dr. Norris recalled an older woman who came into CHAM’s ICU on a ventilator, critically ill from COVID-19. She called her husband at home every day with updates. “I got to know her husband, and I got to know her through him,” Dr. Norris said. “We talked every single day and she was able to graduate off of the breathing tube and out of the ICU, which was amazing.” The woman was moved to a floor in the adult hospital, but Dr. Norris continues to visit her and to provide her husband with updates, “because I’m devoted to them,” she said.

Recently, physicians in the adult hospital consulted with Dr. Norris about the woman. “They were trying to figure out what to do with her next,” she said. “Could she go home, or did she need rehab? They said, ‘We called you, Dr. Norris, because her husband thinks he can take her home.’ We know that COVID-19 really weakens people, so I went over to see her myself. I thought, ‘No single person could take care of an adult so weak at home.’ So, I called her husband and said, ‘I’m here with your wife, and I have to tell you; if she were my mother, I couldn’t take her home today. I need you to trust me.’ He said, ‘OK. We trust you and know that you have her best interest at heart.’ ”

Dr. Kaskel relayed the story of an older patient who was slowly recovering from COVID-19. During a phone call, he asked the man if there was anything he wanted at that moment.

“He said, ‘I’d love to see my wife and my children and my grandkids. I know I’m going to see them again, but right now, doc, if you could get me a cheeseburger with lettuce and tomato and ketchup and French fries from outside of the hospital, I’d be the happiest man in the world.’

I said, ‘What’s the matter with the cheeseburger made at the hospital?’

He said, ‘No! They can’t make the cheeseburger I want.’

I promised him I’d relay that message to the social worker responsible for the patient. I told her please, if you buy this for him, I’ll pay you back.”
 

Self-care and the next chapter

Twice each week, QUILT members gather in front of their computer monitors for mandatory Zoom meetings facilitated by two psychologists to share challenges, best practices, and to discuss the difficult work they’re doing. “We meet, because you cannot help someone if you cannot help yourself,” Dr. Norris said. “We have been encouraged each and every meeting to practice self-compassion, and to recognize that things happen during a pandemic – some will be the best you can do.”

She described organizing and serving on QUILT as a grounding experience with important lessons for the delivery of health care after the pandemic subsides and the team members return to their respective practices. “I think we’ve all gained a greater sense of humility, and we understand that the badge I wear every day does not protect me from becoming a patient, or from having my own family fall ill,” she said. “Here, we think about it very simply: ‘I’m going to treat you like you’re part of my own family.’ ”

Dr. Kaskel said that serving on QUILT as a supportive caller is an experience he won’t soon forget.

“The human bond is so accessible if you accept it,” he said. “If someone is an introvert that might not be able to draw out a stranger on the phone, then [he or she] shouldn’t do this [work]. But the fact that you can make a bond with someone that you’re not even seeing in person and know that both sides of this phone call are getting good vibes, that’s a remarkable feeling that I never really knew before, because I’ve never really had to do that before. It brings up feelings like I had after 9/11 – a unified approach to surviving this as people, as a community, the idea that ‘we will get through this,’ even though it’s totally different than anything before. The idea that there’s still hope. Those are things you can’t put a price on.”

An article about how CHAM transformed to provide care to adult COVID-19 patients was published online May 4, 2020, in the Journal of Pediatrics: doi: 10.1016/j.jpeds.2020.04.060.

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