Federal Practitioner

Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).

Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.

The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online  in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.

“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.

“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.

“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.

Time-honored treatments no more?

Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.

For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.

Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.

“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.

The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.

In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.

The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.

For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.

It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.

For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.

However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
 

Multidisciplinary care

For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.

Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.

Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.

“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.

The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
 

Opportunity for prevention?

The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.

While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.

“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.

“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.

“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.

The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.

This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.

A version of this article first appeared on Medscape.com.

Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).

Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.

The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online  in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.

“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.

“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.

“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.

Time-honored treatments no more?

Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.

For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.

Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.

“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.

The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.

In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.

The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.

For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.

It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.

For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.

However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
 

Multidisciplinary care

For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.

Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.

Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.

“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.

The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
 

Opportunity for prevention?

The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.

While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.

“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.

“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.

“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.

The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.

This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.

A version of this article first appeared on Medscape.com.

Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).

Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.

The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online  in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.

“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.

“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.

“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.

Time-honored treatments no more?

Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.

For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.

Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.

“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.

The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.

In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.

The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.

For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.

It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.

For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.

However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
 

Multidisciplinary care

For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.

Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.

Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.

“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.

The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
 

Opportunity for prevention?

The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.

While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.

“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.

“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.

“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.

The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.

This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.

A version of this article first appeared on Medscape.com.

The transition from perimenopause to menopause is accompanied by a proatherogenic shift in lipids and other circulating metabolites that potentially predispose women to cardiovascular disease (CVD). Now, for the first time, a new prospective cohort study quantifies the link between hormonal shifts and these lipid changes.

However, hormone therapy (HT) somewhat mitigates the shift and may help protect menopausal women from some elevated CVD risk, the same study suggests.

“Menopause is not avoidable, but perhaps the negative metabolite shift can be diminished by lifestyle choices such as eating healthily and being physically active,” senior author Eija Laakkonen, MD, University of Jyväskylä, Finland, told this news organization in an email.

“And women should especially pay attention to the quality of dietary fats and amount of exercise [they get] to maintain cardiorespiratory fitness,” she said, adding that women should discuss the option of HT with their health care providers.

Asked to comment, JoAnn Manson, MD, of Harvard Medical School, Boston, and past president of the North American Menopause Society, said there is strong evidence that women undergo negative cardiometabolic changes during the menopausal transition.

Changes include those in body composition (an increase in visceral fat and waist circumference), as well as unfavorable shifts in the lipid profile, as reflected by increases in low-density lipoprotein cholesterol (LDL-C) and triglycerides and a decrease in high-density lipoprotein cholesterol (HDL-C).

It’s also clear from a variety of cohort studies that HT blunts menopausal-related increases in body weight, percentage of body fat, as well as visceral fat, she said.

So the new findings do seem to “parallel” those of other perimenopausal to menopausal transition studies, which include HT having “favorable effects on lipids,” Dr. Manson said. HT “lowers LDL-C and increases HDL-C, and this is especially true when it is given orally,” but even transdermal delivery has shown some benefits, she observed.
 

Shift in hormones causes 10% of lipid changes after menopause

The new study, by Jari E. Karppinen, also of the University of Jyväskylä, and colleagues, was recently published in the European Journal of Preventive Cardiology. The data are from the Estrogenic Regulation of Muscle Apoptosis (ERMA) prospective cohort study.

In total, 218 women were tracked from perimenopause through to early postmenopause, 35 of whom started HT, mostly oral preparations. The women were followed for a median of 14 months. Their mean age was 51.7 years when their hormone and metabolite profiles were first measured.

Previous studies have shown that menopause is associated with levels of metabolites that promote CVD, but this study is the first to specifically link this shift with changes in female sex hormones, the researchers stress.

“Menopause was associated with a statistically significant change in 85 metabolite measures,” Mr. Karppinen and colleagues report.

Analyses showed that the menopausal hormonal shift directly explained the change in 64 of the 85 metabolites, with effect sizes ranging from 2.1% to 11.2%. 

These included increases in LDL-C, triglycerides, and fatty acids. Analyses were adjusted for age at baseline, duration of follow-up, education level, smoking status, alcohol use, physical activity, and diet quality.

More specifically, investigators found that all apoB-containing particle counts as well as particle diameters increased over follow-up, although no change occurred in HDL particles.

They also found cholesterol concentrations in all apoB-containing lipoprotein classes to increase and triglyceride concentrations to increase in very low-density lipoprotein and HDL particles.

“These findings, including HDL triglycerides, can be interpreted as signs of poor metabolic health since, despite higher HDL-C being good for health, high HDL triglyceride levels are associated with a higher risk of coronary heart disease,” Dr. Laakkonen emphasized.

Among the 35 women who initiated HT on study enrollment, investigators did note, on exploratory analysis, increases in HDL-C and reductions in LDL-C.

“The number of women starting HT was small, and the type of HT was not controlled,” Dr. Laakkonen cautioned, however.

“Nevertheless, our observations support clinical guidelines to initiate HT early into menopause, as this timing offers the greatest cardioprotective effect,” she added.

The study was supported by the Academy of Finland. The authors and Dr. Manson have reported no relevant financial relationships. Dr. Manson is a contributor to Medscape.

This article was updated on 5/20/2022.

A version of this article first appeared on Medscape.com.

The transition from perimenopause to menopause is accompanied by a proatherogenic shift in lipids and other circulating metabolites that potentially predispose women to cardiovascular disease (CVD). Now, for the first time, a new prospective cohort study quantifies the link between hormonal shifts and these lipid changes.

However, hormone therapy (HT) somewhat mitigates the shift and may help protect menopausal women from some elevated CVD risk, the same study suggests.

“Menopause is not avoidable, but perhaps the negative metabolite shift can be diminished by lifestyle choices such as eating healthily and being physically active,” senior author Eija Laakkonen, MD, University of Jyväskylä, Finland, told this news organization in an email.

“And women should especially pay attention to the quality of dietary fats and amount of exercise [they get] to maintain cardiorespiratory fitness,” she said, adding that women should discuss the option of HT with their health care providers.

Asked to comment, JoAnn Manson, MD, of Harvard Medical School, Boston, and past president of the North American Menopause Society, said there is strong evidence that women undergo negative cardiometabolic changes during the menopausal transition.

Changes include those in body composition (an increase in visceral fat and waist circumference), as well as unfavorable shifts in the lipid profile, as reflected by increases in low-density lipoprotein cholesterol (LDL-C) and triglycerides and a decrease in high-density lipoprotein cholesterol (HDL-C).

It’s also clear from a variety of cohort studies that HT blunts menopausal-related increases in body weight, percentage of body fat, as well as visceral fat, she said.

So the new findings do seem to “parallel” those of other perimenopausal to menopausal transition studies, which include HT having “favorable effects on lipids,” Dr. Manson said. HT “lowers LDL-C and increases HDL-C, and this is especially true when it is given orally,” but even transdermal delivery has shown some benefits, she observed.
 

Shift in hormones causes 10% of lipid changes after menopause

The new study, by Jari E. Karppinen, also of the University of Jyväskylä, and colleagues, was recently published in the European Journal of Preventive Cardiology. The data are from the Estrogenic Regulation of Muscle Apoptosis (ERMA) prospective cohort study.

In total, 218 women were tracked from perimenopause through to early postmenopause, 35 of whom started HT, mostly oral preparations. The women were followed for a median of 14 months. Their mean age was 51.7 years when their hormone and metabolite profiles were first measured.

Previous studies have shown that menopause is associated with levels of metabolites that promote CVD, but this study is the first to specifically link this shift with changes in female sex hormones, the researchers stress.

“Menopause was associated with a statistically significant change in 85 metabolite measures,” Mr. Karppinen and colleagues report.

Analyses showed that the menopausal hormonal shift directly explained the change in 64 of the 85 metabolites, with effect sizes ranging from 2.1% to 11.2%. 

These included increases in LDL-C, triglycerides, and fatty acids. Analyses were adjusted for age at baseline, duration of follow-up, education level, smoking status, alcohol use, physical activity, and diet quality.

More specifically, investigators found that all apoB-containing particle counts as well as particle diameters increased over follow-up, although no change occurred in HDL particles.

They also found cholesterol concentrations in all apoB-containing lipoprotein classes to increase and triglyceride concentrations to increase in very low-density lipoprotein and HDL particles.

“These findings, including HDL triglycerides, can be interpreted as signs of poor metabolic health since, despite higher HDL-C being good for health, high HDL triglyceride levels are associated with a higher risk of coronary heart disease,” Dr. Laakkonen emphasized.

Among the 35 women who initiated HT on study enrollment, investigators did note, on exploratory analysis, increases in HDL-C and reductions in LDL-C.

“The number of women starting HT was small, and the type of HT was not controlled,” Dr. Laakkonen cautioned, however.

“Nevertheless, our observations support clinical guidelines to initiate HT early into menopause, as this timing offers the greatest cardioprotective effect,” she added.

The study was supported by the Academy of Finland. The authors and Dr. Manson have reported no relevant financial relationships. Dr. Manson is a contributor to Medscape.

This article was updated on 5/20/2022.

A version of this article first appeared on Medscape.com.

The transition from perimenopause to menopause is accompanied by a proatherogenic shift in lipids and other circulating metabolites that potentially predispose women to cardiovascular disease (CVD). Now, for the first time, a new prospective cohort study quantifies the link between hormonal shifts and these lipid changes.

However, hormone therapy (HT) somewhat mitigates the shift and may help protect menopausal women from some elevated CVD risk, the same study suggests.

“Menopause is not avoidable, but perhaps the negative metabolite shift can be diminished by lifestyle choices such as eating healthily and being physically active,” senior author Eija Laakkonen, MD, University of Jyväskylä, Finland, told this news organization in an email.

“And women should especially pay attention to the quality of dietary fats and amount of exercise [they get] to maintain cardiorespiratory fitness,” she said, adding that women should discuss the option of HT with their health care providers.

Asked to comment, JoAnn Manson, MD, of Harvard Medical School, Boston, and past president of the North American Menopause Society, said there is strong evidence that women undergo negative cardiometabolic changes during the menopausal transition.

Changes include those in body composition (an increase in visceral fat and waist circumference), as well as unfavorable shifts in the lipid profile, as reflected by increases in low-density lipoprotein cholesterol (LDL-C) and triglycerides and a decrease in high-density lipoprotein cholesterol (HDL-C).

It’s also clear from a variety of cohort studies that HT blunts menopausal-related increases in body weight, percentage of body fat, as well as visceral fat, she said.

So the new findings do seem to “parallel” those of other perimenopausal to menopausal transition studies, which include HT having “favorable effects on lipids,” Dr. Manson said. HT “lowers LDL-C and increases HDL-C, and this is especially true when it is given orally,” but even transdermal delivery has shown some benefits, she observed.
 

Shift in hormones causes 10% of lipid changes after menopause

The new study, by Jari E. Karppinen, also of the University of Jyväskylä, and colleagues, was recently published in the European Journal of Preventive Cardiology. The data are from the Estrogenic Regulation of Muscle Apoptosis (ERMA) prospective cohort study.

In total, 218 women were tracked from perimenopause through to early postmenopause, 35 of whom started HT, mostly oral preparations. The women were followed for a median of 14 months. Their mean age was 51.7 years when their hormone and metabolite profiles were first measured.

Previous studies have shown that menopause is associated with levels of metabolites that promote CVD, but this study is the first to specifically link this shift with changes in female sex hormones, the researchers stress.

“Menopause was associated with a statistically significant change in 85 metabolite measures,” Mr. Karppinen and colleagues report.

Analyses showed that the menopausal hormonal shift directly explained the change in 64 of the 85 metabolites, with effect sizes ranging from 2.1% to 11.2%. 

These included increases in LDL-C, triglycerides, and fatty acids. Analyses were adjusted for age at baseline, duration of follow-up, education level, smoking status, alcohol use, physical activity, and diet quality.

More specifically, investigators found that all apoB-containing particle counts as well as particle diameters increased over follow-up, although no change occurred in HDL particles.

They also found cholesterol concentrations in all apoB-containing lipoprotein classes to increase and triglyceride concentrations to increase in very low-density lipoprotein and HDL particles.

“These findings, including HDL triglycerides, can be interpreted as signs of poor metabolic health since, despite higher HDL-C being good for health, high HDL triglyceride levels are associated with a higher risk of coronary heart disease,” Dr. Laakkonen emphasized.

Among the 35 women who initiated HT on study enrollment, investigators did note, on exploratory analysis, increases in HDL-C and reductions in LDL-C.

“The number of women starting HT was small, and the type of HT was not controlled,” Dr. Laakkonen cautioned, however.

“Nevertheless, our observations support clinical guidelines to initiate HT early into menopause, as this timing offers the greatest cardioprotective effect,” she added.

The study was supported by the Academy of Finland. The authors and Dr. Manson have reported no relevant financial relationships. Dr. Manson is a contributor to Medscape.

This article was updated on 5/20/2022.

A version of this article first appeared on Medscape.com.

In states that adopted Medicaid expansion following the implementation of the Affordable Care Act (ACA), patients with cancer have improved 2-year overall survival rates, compared with patients in states that did not adopt the expansion.

The finding comes from an American Cancer Society study of more than 2 million patients with newly diagnosed cancer, published online in the Journal of the National Cancer Institute.

The analysis also showed that the evidence was strongest for malignancies with poor prognosis such as lung, pancreatic, and liver cancer, and also for colorectal cancer.

Importantly, improvements in survival were larger in non-Hispanic Black patients and individuals residing in rural areas, suggesting there was a narrowing of disparities in cancer survival by race and rurality.

“Our findings provide further evidence of the importance of expanding Medicaid eligibility in all states, particularly considering the economic crisis and health care disruptions caused by the COVID-19 pandemic,” said lead author Xuesong Han, PhD, scientific director of health services research at the American Cancer Society, in a statement. “What’s encouraging is the American Rescue Plan Act of 2021 provides new incentives for Medicaid expansion in states that have yet to increase eligibility.”

The ACA provided states with incentives to expand Medicaid eligibility to all low-income adults under 138% federal poverty level, regardless of parental status.

As of last month, just 12 states have not yet opted for Medicaid expansion, even though the American Rescue Plan Act of 2021 provides new incentives for those remaining jurisdictions. But to date, none of the remaining states have taken advantage of these new incentives.

An interactive map showing the status of Medicare expansion by state is available here. The 12 states that have not adopted Medicare expansion (as of April) are Alabama, Florida, Georgia, Kansas, Mississippi, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Wisconsin, and Wyoming.  

The benefit of Medicaid expansion on cancer outcomes has already been observed in other studies. The first study to show a survival benefit was presented at the 2020 American Society of Clinical Oncology annual meeting. That analysis showed that cancer mortality declined by 29% in states that expanded Medicaid and by 25% in those that did not. The authors also noted that the greatest mortality benefit was observed in Hispanic patients.
 

Improved survival with expansion

In the current paper, Dr. Han and colleagues used population-based cancer registries from 42 states and compared data on patients aged 18-62 years who were diagnosed with cancer in a period of 2 years before (2010-2012) and after (2014-2016) ACA Medicaid expansion. They were followed through Sept. 30, 2013, and Dec. 31, 2017, respectively.

The analysis involved a total of 2.5 million patients, of whom 1.52 million lived in states that adopted Medicaid expansion and compared with 1 million patients were in states that did not.

Patients with grouped by sex, race and ethnicity, census tract-level poverty, and rurality. The authors note that non-Hispanic Black patients and those from high poverty areas and nonmetropolitan areas were disproportionately represented in nonexpansion states. 

During the 2-year follow-up period, a total of 453,487 deaths occurred (257,950 in expansion states and 195,537 in nonexpansion states).

Overall, patients in expansion states generally had better survival versus those in nonexpansion states, the authors comment. However, for most cancer types, overall survival improved after the ACA for both groups of states.

The 2-year overall survival increased from 80.6% before the ACA to 82.2% post ACA in expansion states and from 78.7% to 80% in nonexpansion states.

This extrapolated to net increase of 0.44 percentage points in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer, lung cancer, non-Hodgkin’s lymphoma, pancreatic cancer, and liver cancer.

For Hispanic patients, 2-year survival also increased but was similar in expansion and nonexpansion states, and little net change was associated with Medicaid expansion.

“Our study shows that the increase was largely driven by improvements in survival for cancer types with poor prognosis, suggesting improved access to timely and effective treatments,” said Dr. Han. “It adds to accumulating evidence of the multiple benefits of Medicaid expansion.”

A version of this article first appeared on Medscape.com.

In states that adopted Medicaid expansion following the implementation of the Affordable Care Act (ACA), patients with cancer have improved 2-year overall survival rates, compared with patients in states that did not adopt the expansion.

The finding comes from an American Cancer Society study of more than 2 million patients with newly diagnosed cancer, published online in the Journal of the National Cancer Institute.

The analysis also showed that the evidence was strongest for malignancies with poor prognosis such as lung, pancreatic, and liver cancer, and also for colorectal cancer.

Importantly, improvements in survival were larger in non-Hispanic Black patients and individuals residing in rural areas, suggesting there was a narrowing of disparities in cancer survival by race and rurality.

“Our findings provide further evidence of the importance of expanding Medicaid eligibility in all states, particularly considering the economic crisis and health care disruptions caused by the COVID-19 pandemic,” said lead author Xuesong Han, PhD, scientific director of health services research at the American Cancer Society, in a statement. “What’s encouraging is the American Rescue Plan Act of 2021 provides new incentives for Medicaid expansion in states that have yet to increase eligibility.”

The ACA provided states with incentives to expand Medicaid eligibility to all low-income adults under 138% federal poverty level, regardless of parental status.

As of last month, just 12 states have not yet opted for Medicaid expansion, even though the American Rescue Plan Act of 2021 provides new incentives for those remaining jurisdictions. But to date, none of the remaining states have taken advantage of these new incentives.

An interactive map showing the status of Medicare expansion by state is available here. The 12 states that have not adopted Medicare expansion (as of April) are Alabama, Florida, Georgia, Kansas, Mississippi, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Wisconsin, and Wyoming.  

The benefit of Medicaid expansion on cancer outcomes has already been observed in other studies. The first study to show a survival benefit was presented at the 2020 American Society of Clinical Oncology annual meeting. That analysis showed that cancer mortality declined by 29% in states that expanded Medicaid and by 25% in those that did not. The authors also noted that the greatest mortality benefit was observed in Hispanic patients.
 

Improved survival with expansion

In the current paper, Dr. Han and colleagues used population-based cancer registries from 42 states and compared data on patients aged 18-62 years who were diagnosed with cancer in a period of 2 years before (2010-2012) and after (2014-2016) ACA Medicaid expansion. They were followed through Sept. 30, 2013, and Dec. 31, 2017, respectively.

The analysis involved a total of 2.5 million patients, of whom 1.52 million lived in states that adopted Medicaid expansion and compared with 1 million patients were in states that did not.

Patients with grouped by sex, race and ethnicity, census tract-level poverty, and rurality. The authors note that non-Hispanic Black patients and those from high poverty areas and nonmetropolitan areas were disproportionately represented in nonexpansion states. 

During the 2-year follow-up period, a total of 453,487 deaths occurred (257,950 in expansion states and 195,537 in nonexpansion states).

Overall, patients in expansion states generally had better survival versus those in nonexpansion states, the authors comment. However, for most cancer types, overall survival improved after the ACA for both groups of states.

The 2-year overall survival increased from 80.6% before the ACA to 82.2% post ACA in expansion states and from 78.7% to 80% in nonexpansion states.

This extrapolated to net increase of 0.44 percentage points in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer, lung cancer, non-Hodgkin’s lymphoma, pancreatic cancer, and liver cancer.

For Hispanic patients, 2-year survival also increased but was similar in expansion and nonexpansion states, and little net change was associated with Medicaid expansion.

“Our study shows that the increase was largely driven by improvements in survival for cancer types with poor prognosis, suggesting improved access to timely and effective treatments,” said Dr. Han. “It adds to accumulating evidence of the multiple benefits of Medicaid expansion.”

A version of this article first appeared on Medscape.com.

In states that adopted Medicaid expansion following the implementation of the Affordable Care Act (ACA), patients with cancer have improved 2-year overall survival rates, compared with patients in states that did not adopt the expansion.

The finding comes from an American Cancer Society study of more than 2 million patients with newly diagnosed cancer, published online in the Journal of the National Cancer Institute.

The analysis also showed that the evidence was strongest for malignancies with poor prognosis such as lung, pancreatic, and liver cancer, and also for colorectal cancer.

Importantly, improvements in survival were larger in non-Hispanic Black patients and individuals residing in rural areas, suggesting there was a narrowing of disparities in cancer survival by race and rurality.

“Our findings provide further evidence of the importance of expanding Medicaid eligibility in all states, particularly considering the economic crisis and health care disruptions caused by the COVID-19 pandemic,” said lead author Xuesong Han, PhD, scientific director of health services research at the American Cancer Society, in a statement. “What’s encouraging is the American Rescue Plan Act of 2021 provides new incentives for Medicaid expansion in states that have yet to increase eligibility.”

The ACA provided states with incentives to expand Medicaid eligibility to all low-income adults under 138% federal poverty level, regardless of parental status.

As of last month, just 12 states have not yet opted for Medicaid expansion, even though the American Rescue Plan Act of 2021 provides new incentives for those remaining jurisdictions. But to date, none of the remaining states have taken advantage of these new incentives.

An interactive map showing the status of Medicare expansion by state is available here. The 12 states that have not adopted Medicare expansion (as of April) are Alabama, Florida, Georgia, Kansas, Mississippi, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Wisconsin, and Wyoming.  

The benefit of Medicaid expansion on cancer outcomes has already been observed in other studies. The first study to show a survival benefit was presented at the 2020 American Society of Clinical Oncology annual meeting. That analysis showed that cancer mortality declined by 29% in states that expanded Medicaid and by 25% in those that did not. The authors also noted that the greatest mortality benefit was observed in Hispanic patients.
 

Improved survival with expansion

In the current paper, Dr. Han and colleagues used population-based cancer registries from 42 states and compared data on patients aged 18-62 years who were diagnosed with cancer in a period of 2 years before (2010-2012) and after (2014-2016) ACA Medicaid expansion. They were followed through Sept. 30, 2013, and Dec. 31, 2017, respectively.

The analysis involved a total of 2.5 million patients, of whom 1.52 million lived in states that adopted Medicaid expansion and compared with 1 million patients were in states that did not.

Patients with grouped by sex, race and ethnicity, census tract-level poverty, and rurality. The authors note that non-Hispanic Black patients and those from high poverty areas and nonmetropolitan areas were disproportionately represented in nonexpansion states. 

During the 2-year follow-up period, a total of 453,487 deaths occurred (257,950 in expansion states and 195,537 in nonexpansion states).

Overall, patients in expansion states generally had better survival versus those in nonexpansion states, the authors comment. However, for most cancer types, overall survival improved after the ACA for both groups of states.

The 2-year overall survival increased from 80.6% before the ACA to 82.2% post ACA in expansion states and from 78.7% to 80% in nonexpansion states.

This extrapolated to net increase of 0.44 percentage points in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer, lung cancer, non-Hodgkin’s lymphoma, pancreatic cancer, and liver cancer.

For Hispanic patients, 2-year survival also increased but was similar in expansion and nonexpansion states, and little net change was associated with Medicaid expansion.

“Our study shows that the increase was largely driven by improvements in survival for cancer types with poor prognosis, suggesting improved access to timely and effective treatments,” said Dr. Han. “It adds to accumulating evidence of the multiple benefits of Medicaid expansion.”

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Nearly half of all patients with severe, uncontrolled asthma who received a full course of the biologic agent tezepelumab (Tezspire) in the NAVIGATOR trial had a complete response to treatment at 1 year, results of a prespecified exploratory analysis indicated.

Among 471 patients assigned to tezepelumab who completed the on-treatment period of the phase 3 randomized trial, 46% had a complete response at 52 weeks, compared with 24% of patients assigned to placebo.

Complete response was defined as reduction in exacerbations of at least 50% over the previous year, improvement from baseline in Asthma Control Questionnaire 6 (ACQ-6) total score of at least 0.5 points, improvement in prebronchodilator forced expiratory volume in 1 second (pre-BD FEV₁), and physician-assessed Clinical Global Impression measure of clinical change (CGI-C) score.

“These data further support the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma,” said Njira Lugogo, MD, of the division of pulmonary and critical care medicine at the University of Michigan, Ann Arbor.

Dr. Lugogo presented results of the exploratory analysis at the American Thoracic Society’s international conference.
 

Exacerbations reduced, lung function improved

Primary results from NAVIGATOR, published in The New England Journal of Medicine, showed that patients with severe, uncontrolled asthma randomly assigned to tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life compared with patients assigned to placebo.

The investigators noted that approximately 10% of patients with asthma have symptoms and exacerbations despite maximal standard-of-care controller therapy.

Tezepelumab is a human monoclonal antibody that inhibits action of thymic stromal lymphopoietin (TSLP), an epithelial cytokine that is released in response to airborne triggers of asthma. TSLP is a major contributor to initiation and persistence of airway inflammation, Dr. Lugogo said.

The on-treatment analysis looked at all patients in the trial who completed 52 weeks of treatment and had complete data for all criteria studied.

The odds ratios (OR) for patients on tezepelumab achieving each of the response criteria are shown in the table.

Exacerbations explored

In a separate presentation, Christopher S. Ambrose, MD, MBA, of AstraZeneca in Gaithersburg, Md., presented information from investigator-narrative descriptions of all hospitalization events related to asthma exacerbations (mild, moderate, or severe) that occurred while the investigator was blinded to each patient’s treatment assignment in NAVIGATOR.

In all, 39 of 531 patients (7.3%) assigned to placebo had a total of 78 exacerbations requiring hospitalization, compared with 13 of 528 patients (2.5%) assigned to tezepelumab. The latter group had a total of 14 exacerbations requiring hospitalization during the study.

Among hospitalized patients, 32 of the 39 assigned to placebo had severe, incapacitating exacerbations, compared with 5 of 13 assigned to tezepelumab.

Reported symptoms were generally similar between hospitalized patients in the two treatment groups, although there appeared to be trends toward lower incidence of dyspnea, fever, and tachycardia with tezepelumab.

Health care resource utilization, a surrogate marker for disease burden, was substantially lower for patients assigned to tezepelumab.

Infections were the most common triggers of exacerbations in both groups.

“These data provide further evidence that tezepelumab can reduce the burden of disease of severe uncontrolled asthma, both to patients and to health care systems,” Dr. Ambrose said.
 

Head-to-head studies needed

Although there have been no head-to-head comparisons of biologic agents for asthma to date, results of these studies suggest that tezepelumab has efficacy similar to that of other agents for reducing exacerbation, said Fernando Holguin, MD, MPH, from the University of Colorado at Denver, Aurora, who comoderated the oral session where the data were presented but was not involved in the study.

Biologic agents appear to be slightly more effective against type 2 inflammation in asthma, “but in general I think we give it to a broader severe population, so that’s exciting,” he told this news organization.

Comoderator Amisha Barochia, MBBS, MHS, of the National Institutes of Health, Bethesda, Md., told this news organization that head-to-head trials of biologic agents would provide important clinical information going forward.

“Should we switch to a different biologic or add a second biologic? Those are questions we need answers for,” she said.

The NAVIGATOR trial is funded by AstraZeneca and Amgen. Dr. Lugogo disclosed financial relationships with both companies. Dr. Holguin and Dr. Barochia have disclosed no financial relationships relevant to the studies presented.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Nearly half of all patients with severe, uncontrolled asthma who received a full course of the biologic agent tezepelumab (Tezspire) in the NAVIGATOR trial had a complete response to treatment at 1 year, results of a prespecified exploratory analysis indicated.

Among 471 patients assigned to tezepelumab who completed the on-treatment period of the phase 3 randomized trial, 46% had a complete response at 52 weeks, compared with 24% of patients assigned to placebo.

Complete response was defined as reduction in exacerbations of at least 50% over the previous year, improvement from baseline in Asthma Control Questionnaire 6 (ACQ-6) total score of at least 0.5 points, improvement in prebronchodilator forced expiratory volume in 1 second (pre-BD FEV₁), and physician-assessed Clinical Global Impression measure of clinical change (CGI-C) score.

“These data further support the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma,” said Njira Lugogo, MD, of the division of pulmonary and critical care medicine at the University of Michigan, Ann Arbor.

Dr. Lugogo presented results of the exploratory analysis at the American Thoracic Society’s international conference.
 

Exacerbations reduced, lung function improved

Primary results from NAVIGATOR, published in The New England Journal of Medicine, showed that patients with severe, uncontrolled asthma randomly assigned to tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life compared with patients assigned to placebo.

The investigators noted that approximately 10% of patients with asthma have symptoms and exacerbations despite maximal standard-of-care controller therapy.

Tezepelumab is a human monoclonal antibody that inhibits action of thymic stromal lymphopoietin (TSLP), an epithelial cytokine that is released in response to airborne triggers of asthma. TSLP is a major contributor to initiation and persistence of airway inflammation, Dr. Lugogo said.

The on-treatment analysis looked at all patients in the trial who completed 52 weeks of treatment and had complete data for all criteria studied.

The odds ratios (OR) for patients on tezepelumab achieving each of the response criteria are shown in the table.

Exacerbations explored

In a separate presentation, Christopher S. Ambrose, MD, MBA, of AstraZeneca in Gaithersburg, Md., presented information from investigator-narrative descriptions of all hospitalization events related to asthma exacerbations (mild, moderate, or severe) that occurred while the investigator was blinded to each patient’s treatment assignment in NAVIGATOR.

In all, 39 of 531 patients (7.3%) assigned to placebo had a total of 78 exacerbations requiring hospitalization, compared with 13 of 528 patients (2.5%) assigned to tezepelumab. The latter group had a total of 14 exacerbations requiring hospitalization during the study.

Among hospitalized patients, 32 of the 39 assigned to placebo had severe, incapacitating exacerbations, compared with 5 of 13 assigned to tezepelumab.

Reported symptoms were generally similar between hospitalized patients in the two treatment groups, although there appeared to be trends toward lower incidence of dyspnea, fever, and tachycardia with tezepelumab.

Health care resource utilization, a surrogate marker for disease burden, was substantially lower for patients assigned to tezepelumab.

Infections were the most common triggers of exacerbations in both groups.

“These data provide further evidence that tezepelumab can reduce the burden of disease of severe uncontrolled asthma, both to patients and to health care systems,” Dr. Ambrose said.
 

Head-to-head studies needed

Although there have been no head-to-head comparisons of biologic agents for asthma to date, results of these studies suggest that tezepelumab has efficacy similar to that of other agents for reducing exacerbation, said Fernando Holguin, MD, MPH, from the University of Colorado at Denver, Aurora, who comoderated the oral session where the data were presented but was not involved in the study.

Biologic agents appear to be slightly more effective against type 2 inflammation in asthma, “but in general I think we give it to a broader severe population, so that’s exciting,” he told this news organization.

Comoderator Amisha Barochia, MBBS, MHS, of the National Institutes of Health, Bethesda, Md., told this news organization that head-to-head trials of biologic agents would provide important clinical information going forward.

“Should we switch to a different biologic or add a second biologic? Those are questions we need answers for,” she said.

The NAVIGATOR trial is funded by AstraZeneca and Amgen. Dr. Lugogo disclosed financial relationships with both companies. Dr. Holguin and Dr. Barochia have disclosed no financial relationships relevant to the studies presented.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Nearly half of all patients with severe, uncontrolled asthma who received a full course of the biologic agent tezepelumab (Tezspire) in the NAVIGATOR trial had a complete response to treatment at 1 year, results of a prespecified exploratory analysis indicated.

Among 471 patients assigned to tezepelumab who completed the on-treatment period of the phase 3 randomized trial, 46% had a complete response at 52 weeks, compared with 24% of patients assigned to placebo.

Complete response was defined as reduction in exacerbations of at least 50% over the previous year, improvement from baseline in Asthma Control Questionnaire 6 (ACQ-6) total score of at least 0.5 points, improvement in prebronchodilator forced expiratory volume in 1 second (pre-BD FEV₁), and physician-assessed Clinical Global Impression measure of clinical change (CGI-C) score.

“These data further support the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma,” said Njira Lugogo, MD, of the division of pulmonary and critical care medicine at the University of Michigan, Ann Arbor.

Dr. Lugogo presented results of the exploratory analysis at the American Thoracic Society’s international conference.
 

Exacerbations reduced, lung function improved

Primary results from NAVIGATOR, published in The New England Journal of Medicine, showed that patients with severe, uncontrolled asthma randomly assigned to tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life compared with patients assigned to placebo.

The investigators noted that approximately 10% of patients with asthma have symptoms and exacerbations despite maximal standard-of-care controller therapy.

Tezepelumab is a human monoclonal antibody that inhibits action of thymic stromal lymphopoietin (TSLP), an epithelial cytokine that is released in response to airborne triggers of asthma. TSLP is a major contributor to initiation and persistence of airway inflammation, Dr. Lugogo said.

The on-treatment analysis looked at all patients in the trial who completed 52 weeks of treatment and had complete data for all criteria studied.

The odds ratios (OR) for patients on tezepelumab achieving each of the response criteria are shown in the table.

Exacerbations explored

In a separate presentation, Christopher S. Ambrose, MD, MBA, of AstraZeneca in Gaithersburg, Md., presented information from investigator-narrative descriptions of all hospitalization events related to asthma exacerbations (mild, moderate, or severe) that occurred while the investigator was blinded to each patient’s treatment assignment in NAVIGATOR.

In all, 39 of 531 patients (7.3%) assigned to placebo had a total of 78 exacerbations requiring hospitalization, compared with 13 of 528 patients (2.5%) assigned to tezepelumab. The latter group had a total of 14 exacerbations requiring hospitalization during the study.

Among hospitalized patients, 32 of the 39 assigned to placebo had severe, incapacitating exacerbations, compared with 5 of 13 assigned to tezepelumab.

Reported symptoms were generally similar between hospitalized patients in the two treatment groups, although there appeared to be trends toward lower incidence of dyspnea, fever, and tachycardia with tezepelumab.

Health care resource utilization, a surrogate marker for disease burden, was substantially lower for patients assigned to tezepelumab.

Infections were the most common triggers of exacerbations in both groups.

“These data provide further evidence that tezepelumab can reduce the burden of disease of severe uncontrolled asthma, both to patients and to health care systems,” Dr. Ambrose said.
 

Head-to-head studies needed

Although there have been no head-to-head comparisons of biologic agents for asthma to date, results of these studies suggest that tezepelumab has efficacy similar to that of other agents for reducing exacerbation, said Fernando Holguin, MD, MPH, from the University of Colorado at Denver, Aurora, who comoderated the oral session where the data were presented but was not involved in the study.

Biologic agents appear to be slightly more effective against type 2 inflammation in asthma, “but in general I think we give it to a broader severe population, so that’s exciting,” he told this news organization.

Comoderator Amisha Barochia, MBBS, MHS, of the National Institutes of Health, Bethesda, Md., told this news organization that head-to-head trials of biologic agents would provide important clinical information going forward.

“Should we switch to a different biologic or add a second biologic? Those are questions we need answers for,” she said.

The NAVIGATOR trial is funded by AstraZeneca and Amgen. Dr. Lugogo disclosed financial relationships with both companies. Dr. Holguin and Dr. Barochia have disclosed no financial relationships relevant to the studies presented.

A version of this article first appeared on Medscape.com.

Many of us are reluctant to throw things out.

We buy. We accumulate. We collect. Eventually our attics are packed with dusty heirlooms that we rarely, if ever, look at. Eventually we’re forced to pare down and head to the Goodwill.

But not all of us.

Hoarding – or the prolonged difficulty of discarding unneeded possessions – is pervasive in our culture, affecting nearly 3% of the population. This compulsive collecting, and unwillingness to part with “stuff,” is even the subject of multiple popular television series.

How do you conceptualize hoarding behavior?

The core feature of hoarding is the inability to throw things away. This can be due to many different reasons, whether there’s a strong sentimental attachment or the belief that you will need these items one day. Compulsive buying is often involved, and inevitable clutter.

How was hoarding first conceptualized among psychiatrists and psychologists? And when did the term first enter the lexicon?

It was originally conceptualized as a difficult-to-treat subtype of obsessive-compulsive disorder (OCD). A lot of that work identifying this subgroup was going on in the late 1980s and early 1990s. There was a small but growing group of researchers demonstrating that this is fundamentally different from OCD in several ways.

In terms of the clinical presentation, the comorbidity patterns are different from those for OCD. And the course is a little bit different; we see a progressive development across the lifespan, as opposed to a clear-cut diagnosis earlier in life, as is typically seen with OCD. By the time a lot of people seek treatment, they’re often being brought in by, say, family members when they’re a little bit older. With hoarding, there is also this consistent pattern of poor treatment response across the board, whether to selective serotonin reuptake inhibitors or behavioral therapy.

A lot of this work together led to advocacy for recognizing hoarding as an independent diagnosis in the DSM-5. I think official recognition by our “big book” prompted more attention to this population. Previously these patients probably would have been diagnosed with OCD, and it really isn’t appropriate to think of hoarding as purely an anxiety disorder.
 

Hoarding exposure and future mental health

You have a new study, published in Annals of Clinical Psychiatry, looking at mental health among adult children of parents with hoarding problems. Can you tell us what inspired you to run this study, and what you found?

There were a couple of factors.

We’d seen a lot of folks with hoarding in OCD specialty clinics, so my clinical experiences with this population certainly drew me to this general area. But then, at the same time, I have this broad training in child mental health. And childhood trauma or adverse childhood experiences, which can include being around hoarding, can be a very difficult thing to live through and deal with. And here I have to give a lot of credit to Suzanne Chabaud, PhD, of the OCD Institute of Greater New Orleans, who’s one of the coauthors on the paper. She’s been beating the drum of thinking about the family and kids of people with hoarding disorders for years. My interests came from some of those experiences, but she had the good idea of really looking at this problem in a detailed way.
 

Prior to your paper, had there been research on the prevalence of mental illnesses such as anxiety and depression in the children of people with hoarding behaviors?

That particular question was new to our paper. It was the first time anyone, to my knowledge, had looked at a validated assessment of anxiety and depression in this population.

How did you assess their symptoms and what did you find?

We asked study participants to think back on how they felt throughout their teenage years and gauged their responses with the Patient Health Questionnaire (PHQ), a measure of mental health disorders. I should say up front that we didn’t have a control group. But we found that among our 414 study participants, somewhere between 30% and 50% reported clinically significant anxiety or depressive symptoms, far higher than you’d expect in the normal population. So when looking back on how they were feeling as teenagers in that environment, they were struggling, and they often felt rejected by their parents.

We also found that almost 10% of participants were threatened with eviction at some point in their childhood; 15% had to live outside of their home at some point, because of the clutter; and 2% had involvement from child protective services and were removed from the home.
 

I know you recruited patients from online forums established by the children of hoarding parents. Presumably, these are the people most affected by this phenomenon. How does this play out in people who simply like to, say, collect something? Is this a continuum of behavior, with a breaking point at which it becomes a pathology?

I think it’s safe to conceptualize collecting and hoarding as a continuum, and you’ve got to draw a line somewhere in terms of clinical significance.

Did you assess whether the children of hoarders were more likely to hoard themselves as adults?

This is our follow-up paper; we haven’t looked at it yet.

But in looking at preliminary data, the prevalence seems pretty low, actually, at least in our sample. And as you mentioned, in our study there were folks who were seeking support specifically because they grew up in a really cluttered home.

Management

How do mental health providers typically address and treat hoarding?

To my knowledge, there are no current Food and Drug Administration–approved medications for hoarding, though psychiatrists will prescribe SSRIs and try to treat co-occurring problems such as depression and anxiety symptoms.

I can speak to cognitive-behavioral therapy (CBT) in a bit more detail. A number of randomized controlled trials support CBT for hoarding. I mentioned before that when we as a field treated hoarding akin to OCD and did exposure and response prevention therapy, we didn’t really target the specific features of hoarding. People didn’t do that well.

But now researchers are focusing on CBT interventions focused on discarding tasks that really address hoarding. You can create different categories for different items: Patients can either keep them, throw them out, or donate them. You can explore what thoughts or expectations are associated with these items and try to address them. Clinicians can help patients look at, say, different areas of their house and discuss what they might be willing to part with or at least think about parting with. You find their internal motivations for keeping things.

This sort of therapy generally takes longer than it does for, say, OCD. It can be a little bit slower, particularly if someone has a lot of stuff. And often it can involve doing home visits. In the age of Zoom this is a little bit easier because home visits aren’t always feasible.
 

What role does family play in managing hoarding? I imagine that including loved ones and friends in the process could be quite helpful.

Yes, absolutely. And social support, more broadly.

A colleague I worked with did a really interesting study where she looked at psychologist-delivered versus peer-delivered CBT for hoarding. They found that the biggest predictor of improved outcomes was having what they called a “clutter buddy,” which follows the Alcoholics Anonymous sponsor model. This would be somebody else struggling with the same problem who’s an accountability partner helping a patient follow through with their goals related to discarding. I think that finding underscores how important that social support is.
 

Any final thoughts for our audience of clinicians and researchers on how to approach hoarding?

I think there’s been a stigma – at least in psychology circles – that it’s not really treatable because of that earlier work with OCD. But on the CBT side, there’s now good reason to believe that people can live much happier lives and overcome this problem. CBT does seem to work for a lot of people with hoarding. That’s what I’d like to emphasize.

Dr. Stetka is executive editor for Medscape. A version of this article first appeared on Medscape.com.

Many of us are reluctant to throw things out.

We buy. We accumulate. We collect. Eventually our attics are packed with dusty heirlooms that we rarely, if ever, look at. Eventually we’re forced to pare down and head to the Goodwill.

But not all of us.

Hoarding – or the prolonged difficulty of discarding unneeded possessions – is pervasive in our culture, affecting nearly 3% of the population. This compulsive collecting, and unwillingness to part with “stuff,” is even the subject of multiple popular television series.

How do you conceptualize hoarding behavior?

The core feature of hoarding is the inability to throw things away. This can be due to many different reasons, whether there’s a strong sentimental attachment or the belief that you will need these items one day. Compulsive buying is often involved, and inevitable clutter.

How was hoarding first conceptualized among psychiatrists and psychologists? And when did the term first enter the lexicon?

It was originally conceptualized as a difficult-to-treat subtype of obsessive-compulsive disorder (OCD). A lot of that work identifying this subgroup was going on in the late 1980s and early 1990s. There was a small but growing group of researchers demonstrating that this is fundamentally different from OCD in several ways.

In terms of the clinical presentation, the comorbidity patterns are different from those for OCD. And the course is a little bit different; we see a progressive development across the lifespan, as opposed to a clear-cut diagnosis earlier in life, as is typically seen with OCD. By the time a lot of people seek treatment, they’re often being brought in by, say, family members when they’re a little bit older. With hoarding, there is also this consistent pattern of poor treatment response across the board, whether to selective serotonin reuptake inhibitors or behavioral therapy.

A lot of this work together led to advocacy for recognizing hoarding as an independent diagnosis in the DSM-5. I think official recognition by our “big book” prompted more attention to this population. Previously these patients probably would have been diagnosed with OCD, and it really isn’t appropriate to think of hoarding as purely an anxiety disorder.
 

Hoarding exposure and future mental health

You have a new study, published in Annals of Clinical Psychiatry, looking at mental health among adult children of parents with hoarding problems. Can you tell us what inspired you to run this study, and what you found?

There were a couple of factors.

We’d seen a lot of folks with hoarding in OCD specialty clinics, so my clinical experiences with this population certainly drew me to this general area. But then, at the same time, I have this broad training in child mental health. And childhood trauma or adverse childhood experiences, which can include being around hoarding, can be a very difficult thing to live through and deal with. And here I have to give a lot of credit to Suzanne Chabaud, PhD, of the OCD Institute of Greater New Orleans, who’s one of the coauthors on the paper. She’s been beating the drum of thinking about the family and kids of people with hoarding disorders for years. My interests came from some of those experiences, but she had the good idea of really looking at this problem in a detailed way.
 

Prior to your paper, had there been research on the prevalence of mental illnesses such as anxiety and depression in the children of people with hoarding behaviors?

That particular question was new to our paper. It was the first time anyone, to my knowledge, had looked at a validated assessment of anxiety and depression in this population.

How did you assess their symptoms and what did you find?

We asked study participants to think back on how they felt throughout their teenage years and gauged their responses with the Patient Health Questionnaire (PHQ), a measure of mental health disorders. I should say up front that we didn’t have a control group. But we found that among our 414 study participants, somewhere between 30% and 50% reported clinically significant anxiety or depressive symptoms, far higher than you’d expect in the normal population. So when looking back on how they were feeling as teenagers in that environment, they were struggling, and they often felt rejected by their parents.

We also found that almost 10% of participants were threatened with eviction at some point in their childhood; 15% had to live outside of their home at some point, because of the clutter; and 2% had involvement from child protective services and were removed from the home.
 

I know you recruited patients from online forums established by the children of hoarding parents. Presumably, these are the people most affected by this phenomenon. How does this play out in people who simply like to, say, collect something? Is this a continuum of behavior, with a breaking point at which it becomes a pathology?

I think it’s safe to conceptualize collecting and hoarding as a continuum, and you’ve got to draw a line somewhere in terms of clinical significance.

Did you assess whether the children of hoarders were more likely to hoard themselves as adults?

This is our follow-up paper; we haven’t looked at it yet.

But in looking at preliminary data, the prevalence seems pretty low, actually, at least in our sample. And as you mentioned, in our study there were folks who were seeking support specifically because they grew up in a really cluttered home.

Management

How do mental health providers typically address and treat hoarding?

To my knowledge, there are no current Food and Drug Administration–approved medications for hoarding, though psychiatrists will prescribe SSRIs and try to treat co-occurring problems such as depression and anxiety symptoms.

I can speak to cognitive-behavioral therapy (CBT) in a bit more detail. A number of randomized controlled trials support CBT for hoarding. I mentioned before that when we as a field treated hoarding akin to OCD and did exposure and response prevention therapy, we didn’t really target the specific features of hoarding. People didn’t do that well.

But now researchers are focusing on CBT interventions focused on discarding tasks that really address hoarding. You can create different categories for different items: Patients can either keep them, throw them out, or donate them. You can explore what thoughts or expectations are associated with these items and try to address them. Clinicians can help patients look at, say, different areas of their house and discuss what they might be willing to part with or at least think about parting with. You find their internal motivations for keeping things.

This sort of therapy generally takes longer than it does for, say, OCD. It can be a little bit slower, particularly if someone has a lot of stuff. And often it can involve doing home visits. In the age of Zoom this is a little bit easier because home visits aren’t always feasible.
 

What role does family play in managing hoarding? I imagine that including loved ones and friends in the process could be quite helpful.

Yes, absolutely. And social support, more broadly.

A colleague I worked with did a really interesting study where she looked at psychologist-delivered versus peer-delivered CBT for hoarding. They found that the biggest predictor of improved outcomes was having what they called a “clutter buddy,” which follows the Alcoholics Anonymous sponsor model. This would be somebody else struggling with the same problem who’s an accountability partner helping a patient follow through with their goals related to discarding. I think that finding underscores how important that social support is.
 

Any final thoughts for our audience of clinicians and researchers on how to approach hoarding?

I think there’s been a stigma – at least in psychology circles – that it’s not really treatable because of that earlier work with OCD. But on the CBT side, there’s now good reason to believe that people can live much happier lives and overcome this problem. CBT does seem to work for a lot of people with hoarding. That’s what I’d like to emphasize.

Dr. Stetka is executive editor for Medscape. A version of this article first appeared on Medscape.com.

Many of us are reluctant to throw things out.

We buy. We accumulate. We collect. Eventually our attics are packed with dusty heirlooms that we rarely, if ever, look at. Eventually we’re forced to pare down and head to the Goodwill.

But not all of us.

Hoarding – or the prolonged difficulty of discarding unneeded possessions – is pervasive in our culture, affecting nearly 3% of the population. This compulsive collecting, and unwillingness to part with “stuff,” is even the subject of multiple popular television series.

How do you conceptualize hoarding behavior?

The core feature of hoarding is the inability to throw things away. This can be due to many different reasons, whether there’s a strong sentimental attachment or the belief that you will need these items one day. Compulsive buying is often involved, and inevitable clutter.

How was hoarding first conceptualized among psychiatrists and psychologists? And when did the term first enter the lexicon?

It was originally conceptualized as a difficult-to-treat subtype of obsessive-compulsive disorder (OCD). A lot of that work identifying this subgroup was going on in the late 1980s and early 1990s. There was a small but growing group of researchers demonstrating that this is fundamentally different from OCD in several ways.

In terms of the clinical presentation, the comorbidity patterns are different from those for OCD. And the course is a little bit different; we see a progressive development across the lifespan, as opposed to a clear-cut diagnosis earlier in life, as is typically seen with OCD. By the time a lot of people seek treatment, they’re often being brought in by, say, family members when they’re a little bit older. With hoarding, there is also this consistent pattern of poor treatment response across the board, whether to selective serotonin reuptake inhibitors or behavioral therapy.

A lot of this work together led to advocacy for recognizing hoarding as an independent diagnosis in the DSM-5. I think official recognition by our “big book” prompted more attention to this population. Previously these patients probably would have been diagnosed with OCD, and it really isn’t appropriate to think of hoarding as purely an anxiety disorder.
 

Hoarding exposure and future mental health

You have a new study, published in Annals of Clinical Psychiatry, looking at mental health among adult children of parents with hoarding problems. Can you tell us what inspired you to run this study, and what you found?

There were a couple of factors.

We’d seen a lot of folks with hoarding in OCD specialty clinics, so my clinical experiences with this population certainly drew me to this general area. But then, at the same time, I have this broad training in child mental health. And childhood trauma or adverse childhood experiences, which can include being around hoarding, can be a very difficult thing to live through and deal with. And here I have to give a lot of credit to Suzanne Chabaud, PhD, of the OCD Institute of Greater New Orleans, who’s one of the coauthors on the paper. She’s been beating the drum of thinking about the family and kids of people with hoarding disorders for years. My interests came from some of those experiences, but she had the good idea of really looking at this problem in a detailed way.
 

Prior to your paper, had there been research on the prevalence of mental illnesses such as anxiety and depression in the children of people with hoarding behaviors?

That particular question was new to our paper. It was the first time anyone, to my knowledge, had looked at a validated assessment of anxiety and depression in this population.

How did you assess their symptoms and what did you find?

We asked study participants to think back on how they felt throughout their teenage years and gauged their responses with the Patient Health Questionnaire (PHQ), a measure of mental health disorders. I should say up front that we didn’t have a control group. But we found that among our 414 study participants, somewhere between 30% and 50% reported clinically significant anxiety or depressive symptoms, far higher than you’d expect in the normal population. So when looking back on how they were feeling as teenagers in that environment, they were struggling, and they often felt rejected by their parents.

We also found that almost 10% of participants were threatened with eviction at some point in their childhood; 15% had to live outside of their home at some point, because of the clutter; and 2% had involvement from child protective services and were removed from the home.
 

I know you recruited patients from online forums established by the children of hoarding parents. Presumably, these are the people most affected by this phenomenon. How does this play out in people who simply like to, say, collect something? Is this a continuum of behavior, with a breaking point at which it becomes a pathology?

I think it’s safe to conceptualize collecting and hoarding as a continuum, and you’ve got to draw a line somewhere in terms of clinical significance.

Did you assess whether the children of hoarders were more likely to hoard themselves as adults?

This is our follow-up paper; we haven’t looked at it yet.

But in looking at preliminary data, the prevalence seems pretty low, actually, at least in our sample. And as you mentioned, in our study there were folks who were seeking support specifically because they grew up in a really cluttered home.

Management

How do mental health providers typically address and treat hoarding?

To my knowledge, there are no current Food and Drug Administration–approved medications for hoarding, though psychiatrists will prescribe SSRIs and try to treat co-occurring problems such as depression and anxiety symptoms.

I can speak to cognitive-behavioral therapy (CBT) in a bit more detail. A number of randomized controlled trials support CBT for hoarding. I mentioned before that when we as a field treated hoarding akin to OCD and did exposure and response prevention therapy, we didn’t really target the specific features of hoarding. People didn’t do that well.

But now researchers are focusing on CBT interventions focused on discarding tasks that really address hoarding. You can create different categories for different items: Patients can either keep them, throw them out, or donate them. You can explore what thoughts or expectations are associated with these items and try to address them. Clinicians can help patients look at, say, different areas of their house and discuss what they might be willing to part with or at least think about parting with. You find their internal motivations for keeping things.

This sort of therapy generally takes longer than it does for, say, OCD. It can be a little bit slower, particularly if someone has a lot of stuff. And often it can involve doing home visits. In the age of Zoom this is a little bit easier because home visits aren’t always feasible.
 

What role does family play in managing hoarding? I imagine that including loved ones and friends in the process could be quite helpful.

Yes, absolutely. And social support, more broadly.

A colleague I worked with did a really interesting study where she looked at psychologist-delivered versus peer-delivered CBT for hoarding. They found that the biggest predictor of improved outcomes was having what they called a “clutter buddy,” which follows the Alcoholics Anonymous sponsor model. This would be somebody else struggling with the same problem who’s an accountability partner helping a patient follow through with their goals related to discarding. I think that finding underscores how important that social support is.
 

Any final thoughts for our audience of clinicians and researchers on how to approach hoarding?

I think there’s been a stigma – at least in psychology circles – that it’s not really treatable because of that earlier work with OCD. But on the CBT side, there’s now good reason to believe that people can live much happier lives and overcome this problem. CBT does seem to work for a lot of people with hoarding. That’s what I’d like to emphasize.

Dr. Stetka is executive editor for Medscape. A version of this article first appeared on Medscape.com.

Newly identified serum biomarkers have the potential to flag patients, via blood testing, with major depressive disorder (MDD) at high risk of suicide.

Investigators found patients with MDD who died by suicide had a gene expression signature in blood distinct from patients with MDD who died by other means.

The signature included genes involved in stress response changes, including polyamine metabolism, circadian rhythm, immune dysregulation, and telomere maintenance.

“These blood biomarkers are an important step toward developing blood tests to identify patients with imminent risk of ending their lives,” study investigator Adolfo Sequeira, PhD, associate researcher in the department of psychiatry and human behavior, University of California, Irvine, said in a news release.

“To our knowledge, this is the first study to analyze blood and brain samples in a well-defined population of MDDs demonstrating significant differences in gene expression associated with completed suicide,” Dr. Sequeira added.

The findings were published online in Translational Psychiatry.
 

A pressing challenge

Suicide rates in the United States have jumped by more than 35% over the past 2 decades, with more than 48,000 deaths by suicide occurring just last year. MDD is the most common diagnosis among completed suicides, and identifying individuals at the highest risk for suicide remains a “pressing challenge,” the researchers noted.

They looked for changes in gene expression associated with suicide in archived postmortem blood and brain samples from adults with MDD who died by suicide (MDD-S) or by other means (MDD-NS), as well as a group of controls with no psychiatric illness.

In total, there were blood and brain samples for 45 adults, including 53 blood samples and 69 dorsolateral prefrontal cortex (DLPFC) tissue samples.

In blood, investigators identified 14 genes that significantly differentiated MDD-S from MDD-NS. The top six genes differentially expressed in blood were PER3, MTPAP, SLC25A26, CD19, SOX9, and GAR1.

In addition, four genes showed significant changes in brain and blood between the MDD-S and MDD-NS groups. SOX9 was decreased and PER3 was increased in MDD-S in both blood and brain samples, while CD19 and TERF1 were increased in blood but decreased in DLPFC.

SOX9, an astrocytic marker in the brain and B-cell marker in blood, has been shown to be decreased in MDD-S compared with controls in the prefrontal cortex.

In the current study, researchers found that SOX9 expression was significantly reduced both in blood and brain in MDD-S compared with MDD-NS, “suggesting similar immune/astrocytic dysregulations in suicide that could be further investigated.”
 

Potential signatures, potential targets

PER3 is a circadian rhythm gene implicated in sleep disorders associated with shifts in circadian rhythms and is thought to increase susceptibility to MDD.

Mutations in PER3 have been shown previously to alter multiple systems, including response to antidepressants; and increased blood expression of PER1 has been linked to suicidality in women, the researchers noted. 

There also were significantly higher levels of two inflammatory markers (CD19 and CD6 genes) in blood of MDD-S patients compared to MDD-NS patients.

Another “significant” finding was the involvement of several mitochondrial genes in suicide, the researchers said. 

Two nuclear genes coding for mitochondria-located proteins MTPAP (a mitochondrial poly(A) polymerase) and the mitochondrial polyamine transporter SLC25A26 were increased in blood in MDD-S compared with MDD-NS and controls, suggesting that “mitochondrial alterations could be used as potential signatures to differentiate MDD-S from MDD-NS patients and also from controls.”

The researchers added that the genes found to be dysregulated in suicide represent potential targets for future drug therapies to prevent suicide and could also be used to develop a molecular test to identify individuals at high risk for suicide.

The study was funded by the National Institute of Mental Health, the American Society for Suicide Prevention, and the Pritzker Family Philanthropic Fund. The investigators have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Newly identified serum biomarkers have the potential to flag patients, via blood testing, with major depressive disorder (MDD) at high risk of suicide.

Investigators found patients with MDD who died by suicide had a gene expression signature in blood distinct from patients with MDD who died by other means.

The signature included genes involved in stress response changes, including polyamine metabolism, circadian rhythm, immune dysregulation, and telomere maintenance.

“These blood biomarkers are an important step toward developing blood tests to identify patients with imminent risk of ending their lives,” study investigator Adolfo Sequeira, PhD, associate researcher in the department of psychiatry and human behavior, University of California, Irvine, said in a news release.

“To our knowledge, this is the first study to analyze blood and brain samples in a well-defined population of MDDs demonstrating significant differences in gene expression associated with completed suicide,” Dr. Sequeira added.

The findings were published online in Translational Psychiatry.
 

A pressing challenge

Suicide rates in the United States have jumped by more than 35% over the past 2 decades, with more than 48,000 deaths by suicide occurring just last year. MDD is the most common diagnosis among completed suicides, and identifying individuals at the highest risk for suicide remains a “pressing challenge,” the researchers noted.

They looked for changes in gene expression associated with suicide in archived postmortem blood and brain samples from adults with MDD who died by suicide (MDD-S) or by other means (MDD-NS), as well as a group of controls with no psychiatric illness.

In total, there were blood and brain samples for 45 adults, including 53 blood samples and 69 dorsolateral prefrontal cortex (DLPFC) tissue samples.

In blood, investigators identified 14 genes that significantly differentiated MDD-S from MDD-NS. The top six genes differentially expressed in blood were PER3, MTPAP, SLC25A26, CD19, SOX9, and GAR1.

In addition, four genes showed significant changes in brain and blood between the MDD-S and MDD-NS groups. SOX9 was decreased and PER3 was increased in MDD-S in both blood and brain samples, while CD19 and TERF1 were increased in blood but decreased in DLPFC.

SOX9, an astrocytic marker in the brain and B-cell marker in blood, has been shown to be decreased in MDD-S compared with controls in the prefrontal cortex.

In the current study, researchers found that SOX9 expression was significantly reduced both in blood and brain in MDD-S compared with MDD-NS, “suggesting similar immune/astrocytic dysregulations in suicide that could be further investigated.”
 

Potential signatures, potential targets

PER3 is a circadian rhythm gene implicated in sleep disorders associated with shifts in circadian rhythms and is thought to increase susceptibility to MDD.

Mutations in PER3 have been shown previously to alter multiple systems, including response to antidepressants; and increased blood expression of PER1 has been linked to suicidality in women, the researchers noted. 

There also were significantly higher levels of two inflammatory markers (CD19 and CD6 genes) in blood of MDD-S patients compared to MDD-NS patients.

Another “significant” finding was the involvement of several mitochondrial genes in suicide, the researchers said. 

Two nuclear genes coding for mitochondria-located proteins MTPAP (a mitochondrial poly(A) polymerase) and the mitochondrial polyamine transporter SLC25A26 were increased in blood in MDD-S compared with MDD-NS and controls, suggesting that “mitochondrial alterations could be used as potential signatures to differentiate MDD-S from MDD-NS patients and also from controls.”

The researchers added that the genes found to be dysregulated in suicide represent potential targets for future drug therapies to prevent suicide and could also be used to develop a molecular test to identify individuals at high risk for suicide.

The study was funded by the National Institute of Mental Health, the American Society for Suicide Prevention, and the Pritzker Family Philanthropic Fund. The investigators have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Newly identified serum biomarkers have the potential to flag patients, via blood testing, with major depressive disorder (MDD) at high risk of suicide.

Investigators found patients with MDD who died by suicide had a gene expression signature in blood distinct from patients with MDD who died by other means.

The signature included genes involved in stress response changes, including polyamine metabolism, circadian rhythm, immune dysregulation, and telomere maintenance.

“These blood biomarkers are an important step toward developing blood tests to identify patients with imminent risk of ending their lives,” study investigator Adolfo Sequeira, PhD, associate researcher in the department of psychiatry and human behavior, University of California, Irvine, said in a news release.

“To our knowledge, this is the first study to analyze blood and brain samples in a well-defined population of MDDs demonstrating significant differences in gene expression associated with completed suicide,” Dr. Sequeira added.

The findings were published online in Translational Psychiatry.
 

A pressing challenge

Suicide rates in the United States have jumped by more than 35% over the past 2 decades, with more than 48,000 deaths by suicide occurring just last year. MDD is the most common diagnosis among completed suicides, and identifying individuals at the highest risk for suicide remains a “pressing challenge,” the researchers noted.

They looked for changes in gene expression associated with suicide in archived postmortem blood and brain samples from adults with MDD who died by suicide (MDD-S) or by other means (MDD-NS), as well as a group of controls with no psychiatric illness.

In total, there were blood and brain samples for 45 adults, including 53 blood samples and 69 dorsolateral prefrontal cortex (DLPFC) tissue samples.

In blood, investigators identified 14 genes that significantly differentiated MDD-S from MDD-NS. The top six genes differentially expressed in blood were PER3, MTPAP, SLC25A26, CD19, SOX9, and GAR1.

In addition, four genes showed significant changes in brain and blood between the MDD-S and MDD-NS groups. SOX9 was decreased and PER3 was increased in MDD-S in both blood and brain samples, while CD19 and TERF1 were increased in blood but decreased in DLPFC.

SOX9, an astrocytic marker in the brain and B-cell marker in blood, has been shown to be decreased in MDD-S compared with controls in the prefrontal cortex.

In the current study, researchers found that SOX9 expression was significantly reduced both in blood and brain in MDD-S compared with MDD-NS, “suggesting similar immune/astrocytic dysregulations in suicide that could be further investigated.”
 

Potential signatures, potential targets

PER3 is a circadian rhythm gene implicated in sleep disorders associated with shifts in circadian rhythms and is thought to increase susceptibility to MDD.

Mutations in PER3 have been shown previously to alter multiple systems, including response to antidepressants; and increased blood expression of PER1 has been linked to suicidality in women, the researchers noted. 

There also were significantly higher levels of two inflammatory markers (CD19 and CD6 genes) in blood of MDD-S patients compared to MDD-NS patients.

Another “significant” finding was the involvement of several mitochondrial genes in suicide, the researchers said. 

Two nuclear genes coding for mitochondria-located proteins MTPAP (a mitochondrial poly(A) polymerase) and the mitochondrial polyamine transporter SLC25A26 were increased in blood in MDD-S compared with MDD-NS and controls, suggesting that “mitochondrial alterations could be used as potential signatures to differentiate MDD-S from MDD-NS patients and also from controls.”

The researchers added that the genes found to be dysregulated in suicide represent potential targets for future drug therapies to prevent suicide and could also be used to develop a molecular test to identify individuals at high risk for suicide.

The study was funded by the National Institute of Mental Health, the American Society for Suicide Prevention, and the Pritzker Family Philanthropic Fund. The investigators have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An injection of bupivacaine following Mohs micrographic surgery procedures that have notable postsurgical pain significantly reduces pain scores and, importantly, use of postsurgical narcotics, a randomized trial shows.

“Single-dose, in-office bupivacaine administration immediately following reconstructions known to be high risk for pain reduces postoperative narcotic use and acute pain during the time period when our patients have the highest levels of pain,” said first author Vanessa B. Voss, MD, of the University of Missouri–Columbia, who presented the findings at the annual meeting of the American College of Mohs Surgery.

Dr. Vanessa Voss

“It was well tolerated, there were no adverse effects, and we recommend the consideration of using this in Mohs micrographic surgery reconstructions that are at the highest risk for pain,” she said.

Recent research has shown that Mohs micrographic surgeons have the highest rates of opioid prescribing of all dermatologists, with about 11% of patients undergoing a Mohs procedure prescribed the drugs for postoperative use, Dr. Voss explained.

Yet, with the ongoing opioid epidemic and even short courses of postoperative opioids placing patients at risk for addiction, the pressure is on to find alternative, nonaddictive strategies for the treatment of acute postoperative pain.

Bupivacaine is commonly used intraoperatively with other types of surgeries to reduce postoperative pain, with a favorable duration of action lasting up to 7 hours, compared with just 2-3 hours with lidocaine. And while its use in Mohs surgery is typically also intraoperative, along with lidocaine, the unique postoperative treatment approach in Mohs surgery has not been well studied, Dr. Voss noted.

To investigate, Dr. Voss and colleagues conducted the prospective, multicenter randomized trial, enrolling 174 patients undergoing Mohs micrographic surgery for skin cancer.

Patients were receiving complex flap reconstructions that have been specifically designated in an American Academy of Dermatology position statement to be high risk for pain following Mohs surgeries, and hence, more likely to involve prescriptions for opioids. These include reconstruction flaps of the scalp, ear, nose or lip, a wedge repair of the ear or lip, or a Mustarde cheek rotation flap.

The mean age of the patients was about 69 years, and about 65% were male. The two groups had no significant differences in demographics, tumor types, or repairs. They were randomized to receive either local injections of bupivacaine 0.5% (with no epinephrine) or placebo with sterile saline injection immediately following the procedure, with the total amount of injection standardized and dependent upon the flap surface area, ranging from 2.5 to 5 cm³.

For postoperative pain, all patients were prescribed acetaminophen 1,000 mg alternating with ibuprofen 400 mg, and tramadol, with instructions to only use tramadol as needed for breakthrough pain.

The reported use of narcotic analgesics by participants was significantly higher among those receiving placebo versus bupivacaine in the first 24 hours following surgery (odds ratio, 2.18; P = .03), as well as in the second 24 hours (OR, 2.18; P = .08) and at 48 hours combined (OR, 2.58; P < .01).

Those in the bupivacaine group also reported lower average pain scores, on a scale of 0-10, during the first 8-hour interval (mean difference, 1.6; P < .001). Importantly, overall, reports of pain medication use and the percentage of patients reporting pain under control were similar between groups, despite lower opioid use in the bupivacaine group.

“The percentage of patients reporting their pain to be under control was similar at all time intervals in both groups, so this means the bupivacaine group had their pain well-controlled despite fewer narcotics, with significant reductions in opioid use,” Dr. Voss noted.

Bupivacaine, though generally regarded as safe, has a reputation for being the most cardiotoxic of the local anesthetic agents; however, there were no such side effects reported in the study. Dr. Voss said the likely explanation is the use of low doses.

“In our study, we had no cardiotoxic effects when using up to 5 cc of 0.5%, which equates to 25 mg per patient,” she explained. This is considered a “very low dose,” since the maximum in the Food and Drug Administration pamphlet for local infiltration is 175 mg per patient every 3 hours, “yet is sufficient for reducing pain/narcotic use.”

She added that “surgeons must be careful to avoid accidental intravascular injection, which could increase risks of systemic toxicity, but this is very rare in the reconstruction settings described.”

Overall, the study suggests a potentially beneficial and unique nonopioid approach that is currently lacking for Mohs procedures associated with a high level of pain. “These findings offer a very effective intervention to reduce postoperative opioid use in this subset of patients,” Dr. Voss told this news organization. “There is not any other intervention that I am aware of to address this, although further study into other long-acting anesthetics may demonstrate similar effects.”

Dr. Justin J. Leitenberger

Commenting on the study, Justin J. Leitenberger, MD, session moderator, said that these “data could be impactful for reducing pain as well as the need for opioid medication after dermatologic surgery, both of which would be significant for our patients and public health outcomes.”

Among the challenges in treating pain following Mohs surgeries is that “every patient has a different pain threshold and expectation after surgery,” said Dr. Leitenberger, assistant professor of medicine and dermatology and codirector of dermatologic surgery, Mohs micrographic surgery, and laser and cosmetic surgery at Oregon Health & Science University, Portland.

“Patients undergoing larger repairs in tense areas of skin can experience increased pain and require prescription pain medication,” he said. “Bupivacaine, in this study, shows promise to provide longer lasting pain control from the surgical appointment and easier bridging to nonopioid pain control.”

Regarding the potential cardiotoxicities associated with the drug, Dr. Leitenberger agreed that the risks are low, and added that many surgeons have, in fact, switched to full use of bupivacaine, as opposed to combination with lidocaine, apparently without problems. “This is a small dose locally to the area after a procedure and I agree that the risks are minuscule,” he said.

“Of note, during national lidocaine shortages over the past few years, many practices transitioned to exclusive use of bupivacaine for the entire Mohs procedure, and [anecdotally], this transition did not result in toxicities that were reported,” Dr. Leitenberger said.

GW Medical Faculty Associates

Commenting further, Vishal Patel, MD, assistant professor of dermatology and hematology/oncology at George Washington University and director of cutaneous oncology at the GW Cancer Center, both in Washington, also agreed that the benefits appear important. “The benefit from using bupivacaine is encouraging on multiple levels,” he said in an interview.

“Given all that we know about opioids and their negative side effect profile as well as their limited help in cutaneous surgery pain control, the use of long-acting anesthetics is an innovative and reasonable approach to provide pain control in the immediate postoperative window when patients tend to have the most pain,” said Dr. Patel, who is also director of dermatologic surgery at George Washington University.

“After this window, acetaminophen and ibuprofen, which have been shown when used in tandem in an alternating schedule to be superior to opioids, provides an effective pain regimen,” he said. “For larger and more pain-sensitive patients, this appears to be a promising combination.”

Dr. Voss, Dr. Leitenberger, and Dr. Patel have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An injection of bupivacaine following Mohs micrographic surgery procedures that have notable postsurgical pain significantly reduces pain scores and, importantly, use of postsurgical narcotics, a randomized trial shows.

“Single-dose, in-office bupivacaine administration immediately following reconstructions known to be high risk for pain reduces postoperative narcotic use and acute pain during the time period when our patients have the highest levels of pain,” said first author Vanessa B. Voss, MD, of the University of Missouri–Columbia, who presented the findings at the annual meeting of the American College of Mohs Surgery.

Dr. Vanessa Voss

“It was well tolerated, there were no adverse effects, and we recommend the consideration of using this in Mohs micrographic surgery reconstructions that are at the highest risk for pain,” she said.

Recent research has shown that Mohs micrographic surgeons have the highest rates of opioid prescribing of all dermatologists, with about 11% of patients undergoing a Mohs procedure prescribed the drugs for postoperative use, Dr. Voss explained.

Yet, with the ongoing opioid epidemic and even short courses of postoperative opioids placing patients at risk for addiction, the pressure is on to find alternative, nonaddictive strategies for the treatment of acute postoperative pain.

Bupivacaine is commonly used intraoperatively with other types of surgeries to reduce postoperative pain, with a favorable duration of action lasting up to 7 hours, compared with just 2-3 hours with lidocaine. And while its use in Mohs surgery is typically also intraoperative, along with lidocaine, the unique postoperative treatment approach in Mohs surgery has not been well studied, Dr. Voss noted.

To investigate, Dr. Voss and colleagues conducted the prospective, multicenter randomized trial, enrolling 174 patients undergoing Mohs micrographic surgery for skin cancer.

Patients were receiving complex flap reconstructions that have been specifically designated in an American Academy of Dermatology position statement to be high risk for pain following Mohs surgeries, and hence, more likely to involve prescriptions for opioids. These include reconstruction flaps of the scalp, ear, nose or lip, a wedge repair of the ear or lip, or a Mustarde cheek rotation flap.

The mean age of the patients was about 69 years, and about 65% were male. The two groups had no significant differences in demographics, tumor types, or repairs. They were randomized to receive either local injections of bupivacaine 0.5% (with no epinephrine) or placebo with sterile saline injection immediately following the procedure, with the total amount of injection standardized and dependent upon the flap surface area, ranging from 2.5 to 5 cm³.

For postoperative pain, all patients were prescribed acetaminophen 1,000 mg alternating with ibuprofen 400 mg, and tramadol, with instructions to only use tramadol as needed for breakthrough pain.

The reported use of narcotic analgesics by participants was significantly higher among those receiving placebo versus bupivacaine in the first 24 hours following surgery (odds ratio, 2.18; P = .03), as well as in the second 24 hours (OR, 2.18; P = .08) and at 48 hours combined (OR, 2.58; P < .01).

Those in the bupivacaine group also reported lower average pain scores, on a scale of 0-10, during the first 8-hour interval (mean difference, 1.6; P < .001). Importantly, overall, reports of pain medication use and the percentage of patients reporting pain under control were similar between groups, despite lower opioid use in the bupivacaine group.

“The percentage of patients reporting their pain to be under control was similar at all time intervals in both groups, so this means the bupivacaine group had their pain well-controlled despite fewer narcotics, with significant reductions in opioid use,” Dr. Voss noted.

Bupivacaine, though generally regarded as safe, has a reputation for being the most cardiotoxic of the local anesthetic agents; however, there were no such side effects reported in the study. Dr. Voss said the likely explanation is the use of low doses.

“In our study, we had no cardiotoxic effects when using up to 5 cc of 0.5%, which equates to 25 mg per patient,” she explained. This is considered a “very low dose,” since the maximum in the Food and Drug Administration pamphlet for local infiltration is 175 mg per patient every 3 hours, “yet is sufficient for reducing pain/narcotic use.”

She added that “surgeons must be careful to avoid accidental intravascular injection, which could increase risks of systemic toxicity, but this is very rare in the reconstruction settings described.”

Overall, the study suggests a potentially beneficial and unique nonopioid approach that is currently lacking for Mohs procedures associated with a high level of pain. “These findings offer a very effective intervention to reduce postoperative opioid use in this subset of patients,” Dr. Voss told this news organization. “There is not any other intervention that I am aware of to address this, although further study into other long-acting anesthetics may demonstrate similar effects.”

Dr. Justin J. Leitenberger

Commenting on the study, Justin J. Leitenberger, MD, session moderator, said that these “data could be impactful for reducing pain as well as the need for opioid medication after dermatologic surgery, both of which would be significant for our patients and public health outcomes.”

Among the challenges in treating pain following Mohs surgeries is that “every patient has a different pain threshold and expectation after surgery,” said Dr. Leitenberger, assistant professor of medicine and dermatology and codirector of dermatologic surgery, Mohs micrographic surgery, and laser and cosmetic surgery at Oregon Health & Science University, Portland.

“Patients undergoing larger repairs in tense areas of skin can experience increased pain and require prescription pain medication,” he said. “Bupivacaine, in this study, shows promise to provide longer lasting pain control from the surgical appointment and easier bridging to nonopioid pain control.”

Regarding the potential cardiotoxicities associated with the drug, Dr. Leitenberger agreed that the risks are low, and added that many surgeons have, in fact, switched to full use of bupivacaine, as opposed to combination with lidocaine, apparently without problems. “This is a small dose locally to the area after a procedure and I agree that the risks are minuscule,” he said.

“Of note, during national lidocaine shortages over the past few years, many practices transitioned to exclusive use of bupivacaine for the entire Mohs procedure, and [anecdotally], this transition did not result in toxicities that were reported,” Dr. Leitenberger said.

GW Medical Faculty Associates

Commenting further, Vishal Patel, MD, assistant professor of dermatology and hematology/oncology at George Washington University and director of cutaneous oncology at the GW Cancer Center, both in Washington, also agreed that the benefits appear important. “The benefit from using bupivacaine is encouraging on multiple levels,” he said in an interview.

“Given all that we know about opioids and their negative side effect profile as well as their limited help in cutaneous surgery pain control, the use of long-acting anesthetics is an innovative and reasonable approach to provide pain control in the immediate postoperative window when patients tend to have the most pain,” said Dr. Patel, who is also director of dermatologic surgery at George Washington University.

“After this window, acetaminophen and ibuprofen, which have been shown when used in tandem in an alternating schedule to be superior to opioids, provides an effective pain regimen,” he said. “For larger and more pain-sensitive patients, this appears to be a promising combination.”

Dr. Voss, Dr. Leitenberger, and Dr. Patel have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An injection of bupivacaine following Mohs micrographic surgery procedures that have notable postsurgical pain significantly reduces pain scores and, importantly, use of postsurgical narcotics, a randomized trial shows.

“Single-dose, in-office bupivacaine administration immediately following reconstructions known to be high risk for pain reduces postoperative narcotic use and acute pain during the time period when our patients have the highest levels of pain,” said first author Vanessa B. Voss, MD, of the University of Missouri–Columbia, who presented the findings at the annual meeting of the American College of Mohs Surgery.

Dr. Vanessa Voss

“It was well tolerated, there were no adverse effects, and we recommend the consideration of using this in Mohs micrographic surgery reconstructions that are at the highest risk for pain,” she said.

Recent research has shown that Mohs micrographic surgeons have the highest rates of opioid prescribing of all dermatologists, with about 11% of patients undergoing a Mohs procedure prescribed the drugs for postoperative use, Dr. Voss explained.

Yet, with the ongoing opioid epidemic and even short courses of postoperative opioids placing patients at risk for addiction, the pressure is on to find alternative, nonaddictive strategies for the treatment of acute postoperative pain.

Bupivacaine is commonly used intraoperatively with other types of surgeries to reduce postoperative pain, with a favorable duration of action lasting up to 7 hours, compared with just 2-3 hours with lidocaine. And while its use in Mohs surgery is typically also intraoperative, along with lidocaine, the unique postoperative treatment approach in Mohs surgery has not been well studied, Dr. Voss noted.

To investigate, Dr. Voss and colleagues conducted the prospective, multicenter randomized trial, enrolling 174 patients undergoing Mohs micrographic surgery for skin cancer.

Patients were receiving complex flap reconstructions that have been specifically designated in an American Academy of Dermatology position statement to be high risk for pain following Mohs surgeries, and hence, more likely to involve prescriptions for opioids. These include reconstruction flaps of the scalp, ear, nose or lip, a wedge repair of the ear or lip, or a Mustarde cheek rotation flap.

The mean age of the patients was about 69 years, and about 65% were male. The two groups had no significant differences in demographics, tumor types, or repairs. They were randomized to receive either local injections of bupivacaine 0.5% (with no epinephrine) or placebo with sterile saline injection immediately following the procedure, with the total amount of injection standardized and dependent upon the flap surface area, ranging from 2.5 to 5 cm³.

For postoperative pain, all patients were prescribed acetaminophen 1,000 mg alternating with ibuprofen 400 mg, and tramadol, with instructions to only use tramadol as needed for breakthrough pain.

The reported use of narcotic analgesics by participants was significantly higher among those receiving placebo versus bupivacaine in the first 24 hours following surgery (odds ratio, 2.18; P = .03), as well as in the second 24 hours (OR, 2.18; P = .08) and at 48 hours combined (OR, 2.58; P < .01).

Those in the bupivacaine group also reported lower average pain scores, on a scale of 0-10, during the first 8-hour interval (mean difference, 1.6; P < .001). Importantly, overall, reports of pain medication use and the percentage of patients reporting pain under control were similar between groups, despite lower opioid use in the bupivacaine group.

“The percentage of patients reporting their pain to be under control was similar at all time intervals in both groups, so this means the bupivacaine group had their pain well-controlled despite fewer narcotics, with significant reductions in opioid use,” Dr. Voss noted.

Bupivacaine, though generally regarded as safe, has a reputation for being the most cardiotoxic of the local anesthetic agents; however, there were no such side effects reported in the study. Dr. Voss said the likely explanation is the use of low doses.

“In our study, we had no cardiotoxic effects when using up to 5 cc of 0.5%, which equates to 25 mg per patient,” she explained. This is considered a “very low dose,” since the maximum in the Food and Drug Administration pamphlet for local infiltration is 175 mg per patient every 3 hours, “yet is sufficient for reducing pain/narcotic use.”

She added that “surgeons must be careful to avoid accidental intravascular injection, which could increase risks of systemic toxicity, but this is very rare in the reconstruction settings described.”

Overall, the study suggests a potentially beneficial and unique nonopioid approach that is currently lacking for Mohs procedures associated with a high level of pain. “These findings offer a very effective intervention to reduce postoperative opioid use in this subset of patients,” Dr. Voss told this news organization. “There is not any other intervention that I am aware of to address this, although further study into other long-acting anesthetics may demonstrate similar effects.”

Dr. Justin J. Leitenberger

Commenting on the study, Justin J. Leitenberger, MD, session moderator, said that these “data could be impactful for reducing pain as well as the need for opioid medication after dermatologic surgery, both of which would be significant for our patients and public health outcomes.”

Among the challenges in treating pain following Mohs surgeries is that “every patient has a different pain threshold and expectation after surgery,” said Dr. Leitenberger, assistant professor of medicine and dermatology and codirector of dermatologic surgery, Mohs micrographic surgery, and laser and cosmetic surgery at Oregon Health & Science University, Portland.

“Patients undergoing larger repairs in tense areas of skin can experience increased pain and require prescription pain medication,” he said. “Bupivacaine, in this study, shows promise to provide longer lasting pain control from the surgical appointment and easier bridging to nonopioid pain control.”

Regarding the potential cardiotoxicities associated with the drug, Dr. Leitenberger agreed that the risks are low, and added that many surgeons have, in fact, switched to full use of bupivacaine, as opposed to combination with lidocaine, apparently without problems. “This is a small dose locally to the area after a procedure and I agree that the risks are minuscule,” he said.

“Of note, during national lidocaine shortages over the past few years, many practices transitioned to exclusive use of bupivacaine for the entire Mohs procedure, and [anecdotally], this transition did not result in toxicities that were reported,” Dr. Leitenberger said.

GW Medical Faculty Associates

Commenting further, Vishal Patel, MD, assistant professor of dermatology and hematology/oncology at George Washington University and director of cutaneous oncology at the GW Cancer Center, both in Washington, also agreed that the benefits appear important. “The benefit from using bupivacaine is encouraging on multiple levels,” he said in an interview.

“Given all that we know about opioids and their negative side effect profile as well as their limited help in cutaneous surgery pain control, the use of long-acting anesthetics is an innovative and reasonable approach to provide pain control in the immediate postoperative window when patients tend to have the most pain,” said Dr. Patel, who is also director of dermatologic surgery at George Washington University.

“After this window, acetaminophen and ibuprofen, which have been shown when used in tandem in an alternating schedule to be superior to opioids, provides an effective pain regimen,” he said. “For larger and more pain-sensitive patients, this appears to be a promising combination.”

Dr. Voss, Dr. Leitenberger, and Dr. Patel have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Several years have passed since I stood among a cohort of eager medical students wearing regalia that signaled a new beginning. Four years of grueling study culminated in a cacophony of unified voices, each reciting a pledge that I had longed to take since early adolescence. Together we celebrated, triumphant despite innumerable exams and various iterations of the Socratic method – all under the guise of assessing knowledge while in truth seeking to insidiously erode the crowd of prospective physicians. Yet our anxiety and uncertainty melted away as names were called, hands firmly clasped, and tassels transposed. For a moment in time, we stood on the precipice of victory, enthusiastic albeit oblivious of the tremendous obstacles that loomed ahead.

Wistfully I reminisce about the unequivocal joy that abounds within the protective shield of naiveté. Specifically, I think about that time when the edict of medicine and the art of being a physician felt congruent. Yet, reality is fickle and often supersedes expectation. Occasionally my thoughts drift to the early days of residency – a time during which the emotional weight of caring for vulnerable patients while learning to master my chosen specialty felt woefully insurmountable. I recall wading blindly through each rotation attempting to emulate the competent and compassionate care so effortlessly demonstrated by senior physicians as they moved through the health care system with apparent ease. They stepped fluidly, as I watched in awe through rose-tinted glasses.

As months passed into years, my perception cleared. What I initially viewed as graceful patient care belied a complex tapestry of health care workers often pressured into arduous decisions, not necessarily in service of a well-constructed treatment plan. Gradually, formidable barriers emerged, guidelines and restrictions embedded within a confining path that suffocated those who dared to cross it. As a result, a field built on the foundations of autonomy, benevolence, and nonmaleficence was slowly engulfed by a system fraught with contrivances. Amid such stressors, physical and psychological health grows tenuous. Classically, this overwhelming feeling of distress is recognized as burnout. Studies reformulated this malady to that which was first described in Vietnam war veterans, a condition known as “moral injury.”
 

The impact of burnout

To explain the development – and explore the complexities – of moral injury, we must return to 1975 when the term burnout was initially formulated by Herbert Freudenberger, PhD, a psychologist renowned for his work in substance use disorders, psychoanalysis, and clinical education.¹ Dr. Freudenberger’s studies noted incidences of heightened emotional and physical distress in his colleagues working in substance abuse and other clinics. He sought to define these experiences as well as understand his own battle with malaise, apathy, and frustration.¹ Ultimately, Dr. Freudenberger described burnout as “Becoming exhausted by making excessive demands on energy, strength, or resources in the workplace.”² Although it characteristically overlaps with depression and anxiety, burnout is conceptualized as a separate entity specifically forged within a context of perfectionism, integrity, and self-sacrifice.² Such qualities are integral in health care and, as a result, physicians are particularly vulnerable.

Since Dr. Freudenberger published “Burnout: The High Cost of Achievement” in 1980, immense research has assisted in not only identifying critical factors that contribute to its development but also the detrimental effects it has on physiological health.³ These include exhaustion from poor work conditions and extreme commitment to employee responsibilities that in turn precipitate mood destabilization and impaired work performance.³ Furthermore, research has also demonstrated that burnout triggers alterations in neural circuitry via the prefrontal cortex and the amygdala, structures critical for emotional regulation.⁴ To combat the ill effects of burnout while maintaining productivity and maximizing profit, several high-profile corporations instituted changes focusing on self-care, wellness, benefits, and incentives. Although these modifications are effective in decreasing the rate of employee turnover, such strategies are not easily transferable to health care. In fact, the rate of physician burnout has steadily increased over the past two decades as the business of medicine shifts towards longer hours, decreased reimbursement rates, and inexhaustible insurance stipulations.^2,5 Consequently, occupational dissatisfaction increases the risk of cynicism, frustration with patients, internalization of failure, and likelihood of early retirement.⁵ Moreover, burnout may also fracture interpersonal relationships as well as precipitate errors, negative patient outcomes, malpractice, and development of severe mental health conditions associated with high morbidity and mortality.^5,8

Although the concept of burnout is critical in understanding the side effects of stereotypical workplace culture, critics of the concept bemoan a suggestion of individual blame.^6,8 In essence, they argue that burnout is explained as a side effect of toxic workplace conditions, but covertly represents a lack of resilience, motivation, and ambition to thrive in a physically or emotionally taxing occupational setting.^6,8 Thus, the responsibility of acclimation lies upon the impacted individuals rather than the employer. For this reason, many strategies to ameliorate burnout are focused on the individual, including meditation, wellness retreats, creating or adjusting self-care regimens, or in some cases psychotherapy and psychopharmacology.⁶ Whereas burnout may respond (at least partially) to such interventions, without altering the causal factors, it is unlikely to remit. This is especially the case in health care, where systemic constraints lie beyond the control of an individual physician. Rather than promoting or specifically relying upon personal improvement and recovery, amendments are needed on multiple levels to affect meaningful change.
 

Moral injury

Similar to burnout, moral injury was not initially conceived within the scope of health care. In the 1990s Jonathan Shay, MD, PhD, identified veterans presenting with symptoms mimicking PTSD that failed to respond to standard, well established and efficacious treatments.^9-11 With further analysis he determined that veterans who demonstrated minimal improvement reported similar histories of guilt, shame, and disgust following perceived injustices enacted or abetted by immoral leaders.^10,11 Ultimately Shay identified three components of moral injury: 1. A betrayal of what is morally right; 2. By someone who holds legitimate priority; 3. In a high stakes situation.¹⁰

This definition was further modified in 2007 by Brett Linz, PhD, and colleagues as: “Perpetuating, failing to prevent, or bearing witness to acts that transgress deeply held moral beliefs and expectations.”^10,11 By expanding this description to include distress experienced by physicians and health care workers, Wendy Dean and Simon Talbot (in 2018 and 2019 respectively) explored how the health care system leads practitioners to deliver what they identify as substandard treatment.^6-8 This results in disillusionment and lays the foundation for ethical and moral dilemmas in clinicians.

Themes of moral injury are repeatedly cited in various surveys and studies as a cause for occupational dissatisfaction. As physicians and other health care professionals reel from the aftermath of COVID-19, the effects of reconfiguring medicine into a business-oriented framework are glaringly conspicuous. Vast hospital nursing shortages, high patient census exacerbated by the political misuse and polarization of science, and insufficient availability of psychiatric beds, have culminated in a deluge of psychological strain in emergency medical physicians. Furthermore, pressure from administrators, mandated patient satisfaction measures, tedious electronic medical record systems, and copious licensing and certification requirements, contribute to physician distress as they attempt to navigate a system that challenges the vows which they swore to uphold.⁸ Because the cost of pursuing a medical degree frequently necessitates acquisition of loans that, without a physician income, may be difficult to repay,⁹ many doctors feel trapped within a seemingly endless cycle of misgiving that contributes to emotional exhaustion, pessimism, and low morale.

In my next series of The Myth of the Superdoctor columns, we will explore various factors that potentiate risk of moral injury. From medical school and residency training to corporate infrastructure and insurance obstacles, I will seek to discern and deliberate strategies for repair and rehabilitation. It is my hope that together we will illuminate the myriad complexities within the business of medicine, and become advocates and harbingers of change not only for physicians and health care workers but also for the sake of our patients and their families.

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

References

1. King N. When a Psychologist Succumbed to Stress, He Coined The Term Burnout. 2016 Dec 8. NPR: All Things Considered.

2. Maslach C and Leiter MP. World Psychiatry. 2016 Jun;15(2):103-11. doi: 10.1002/wps.20311.

3. InformedHealth.org and Institute for Quality and Efficiency in Health Care. Depression: What is burnout?. https://www.ncbi.nlm.nih.gov/books/NBK279286/.

4. Michel A. Burnout and the Brain. Observer. 2016 Jan 29. https://www.psychologicalscience.org/observer/burnout-and-the-brain.

5. Patel RS et al. Behav Sci. 2018;8(11):98. doi:10.3390/bs8110098.

6. Dean W and Talbot S. Physicians aren’t ‘burning out.’ They’re suffering from moral injury. Stat. 2018 Jul 26. https://www.statnews.com/2018/07/26/physicians-not-burning-out-they-are-suffering-moral-injury/.

7. Dean W and Talbot S. Moral injury and burnout in medicine: A year of lessons learned. Stat. 2019 Jul 26. https://www.statnews.com/2019/07/26/moral-injury-burnout-medicine-lessons-learned/.

8. Dean W et al. Reframing Clinician Distress: Moral Injury Not Burnout. Fed Pract. 2019 Sep; 36(9):400-2. https://www.mdedge.com/fedprac/article/207458/mental-health/reframing-clinician-distress-moral-injury-not-burnout.

9. Bailey M. Beyond Burnout: Docs Decry ‘Moral Injury’ From Financial Pressures of Health Care. KHN. 2020 Feb 4. https://khn.org/news/beyond-burnout-docs-decry-moral-injury-from-financial-pressures-of-health-care/.

10. Litz B et al. Clin Psychol Rev. 2009 Dec;29(8):695-706. doi: 10.1016/j.cpr.2009.07.003.

11. Norman S and Maguen S. Moral Injury. PTSD: National Center for PTSD. https://www.ptsd.va.gov/professional/treat/cooccurring/moral_injury.asp.

Several years have passed since I stood among a cohort of eager medical students wearing regalia that signaled a new beginning. Four years of grueling study culminated in a cacophony of unified voices, each reciting a pledge that I had longed to take since early adolescence. Together we celebrated, triumphant despite innumerable exams and various iterations of the Socratic method – all under the guise of assessing knowledge while in truth seeking to insidiously erode the crowd of prospective physicians. Yet our anxiety and uncertainty melted away as names were called, hands firmly clasped, and tassels transposed. For a moment in time, we stood on the precipice of victory, enthusiastic albeit oblivious of the tremendous obstacles that loomed ahead.

Wistfully I reminisce about the unequivocal joy that abounds within the protective shield of naiveté. Specifically, I think about that time when the edict of medicine and the art of being a physician felt congruent. Yet, reality is fickle and often supersedes expectation. Occasionally my thoughts drift to the early days of residency – a time during which the emotional weight of caring for vulnerable patients while learning to master my chosen specialty felt woefully insurmountable. I recall wading blindly through each rotation attempting to emulate the competent and compassionate care so effortlessly demonstrated by senior physicians as they moved through the health care system with apparent ease. They stepped fluidly, as I watched in awe through rose-tinted glasses.

As months passed into years, my perception cleared. What I initially viewed as graceful patient care belied a complex tapestry of health care workers often pressured into arduous decisions, not necessarily in service of a well-constructed treatment plan. Gradually, formidable barriers emerged, guidelines and restrictions embedded within a confining path that suffocated those who dared to cross it. As a result, a field built on the foundations of autonomy, benevolence, and nonmaleficence was slowly engulfed by a system fraught with contrivances. Amid such stressors, physical and psychological health grows tenuous. Classically, this overwhelming feeling of distress is recognized as burnout. Studies reformulated this malady to that which was first described in Vietnam war veterans, a condition known as “moral injury.”
 

The impact of burnout

To explain the development – and explore the complexities – of moral injury, we must return to 1975 when the term burnout was initially formulated by Herbert Freudenberger, PhD, a psychologist renowned for his work in substance use disorders, psychoanalysis, and clinical education.¹ Dr. Freudenberger’s studies noted incidences of heightened emotional and physical distress in his colleagues working in substance abuse and other clinics. He sought to define these experiences as well as understand his own battle with malaise, apathy, and frustration.¹ Ultimately, Dr. Freudenberger described burnout as “Becoming exhausted by making excessive demands on energy, strength, or resources in the workplace.”² Although it characteristically overlaps with depression and anxiety, burnout is conceptualized as a separate entity specifically forged within a context of perfectionism, integrity, and self-sacrifice.² Such qualities are integral in health care and, as a result, physicians are particularly vulnerable.

Since Dr. Freudenberger published “Burnout: The High Cost of Achievement” in 1980, immense research has assisted in not only identifying critical factors that contribute to its development but also the detrimental effects it has on physiological health.³ These include exhaustion from poor work conditions and extreme commitment to employee responsibilities that in turn precipitate mood destabilization and impaired work performance.³ Furthermore, research has also demonstrated that burnout triggers alterations in neural circuitry via the prefrontal cortex and the amygdala, structures critical for emotional regulation.⁴ To combat the ill effects of burnout while maintaining productivity and maximizing profit, several high-profile corporations instituted changes focusing on self-care, wellness, benefits, and incentives. Although these modifications are effective in decreasing the rate of employee turnover, such strategies are not easily transferable to health care. In fact, the rate of physician burnout has steadily increased over the past two decades as the business of medicine shifts towards longer hours, decreased reimbursement rates, and inexhaustible insurance stipulations.^2,5 Consequently, occupational dissatisfaction increases the risk of cynicism, frustration with patients, internalization of failure, and likelihood of early retirement.⁵ Moreover, burnout may also fracture interpersonal relationships as well as precipitate errors, negative patient outcomes, malpractice, and development of severe mental health conditions associated with high morbidity and mortality.^5,8

Although the concept of burnout is critical in understanding the side effects of stereotypical workplace culture, critics of the concept bemoan a suggestion of individual blame.^6,8 In essence, they argue that burnout is explained as a side effect of toxic workplace conditions, but covertly represents a lack of resilience, motivation, and ambition to thrive in a physically or emotionally taxing occupational setting.^6,8 Thus, the responsibility of acclimation lies upon the impacted individuals rather than the employer. For this reason, many strategies to ameliorate burnout are focused on the individual, including meditation, wellness retreats, creating or adjusting self-care regimens, or in some cases psychotherapy and psychopharmacology.⁶ Whereas burnout may respond (at least partially) to such interventions, without altering the causal factors, it is unlikely to remit. This is especially the case in health care, where systemic constraints lie beyond the control of an individual physician. Rather than promoting or specifically relying upon personal improvement and recovery, amendments are needed on multiple levels to affect meaningful change.
 

Moral injury

Similar to burnout, moral injury was not initially conceived within the scope of health care. In the 1990s Jonathan Shay, MD, PhD, identified veterans presenting with symptoms mimicking PTSD that failed to respond to standard, well established and efficacious treatments.^9-11 With further analysis he determined that veterans who demonstrated minimal improvement reported similar histories of guilt, shame, and disgust following perceived injustices enacted or abetted by immoral leaders.^10,11 Ultimately Shay identified three components of moral injury: 1. A betrayal of what is morally right; 2. By someone who holds legitimate priority; 3. In a high stakes situation.¹⁰

This definition was further modified in 2007 by Brett Linz, PhD, and colleagues as: “Perpetuating, failing to prevent, or bearing witness to acts that transgress deeply held moral beliefs and expectations.”^10,11 By expanding this description to include distress experienced by physicians and health care workers, Wendy Dean and Simon Talbot (in 2018 and 2019 respectively) explored how the health care system leads practitioners to deliver what they identify as substandard treatment.^6-8 This results in disillusionment and lays the foundation for ethical and moral dilemmas in clinicians.

Themes of moral injury are repeatedly cited in various surveys and studies as a cause for occupational dissatisfaction. As physicians and other health care professionals reel from the aftermath of COVID-19, the effects of reconfiguring medicine into a business-oriented framework are glaringly conspicuous. Vast hospital nursing shortages, high patient census exacerbated by the political misuse and polarization of science, and insufficient availability of psychiatric beds, have culminated in a deluge of psychological strain in emergency medical physicians. Furthermore, pressure from administrators, mandated patient satisfaction measures, tedious electronic medical record systems, and copious licensing and certification requirements, contribute to physician distress as they attempt to navigate a system that challenges the vows which they swore to uphold.⁸ Because the cost of pursuing a medical degree frequently necessitates acquisition of loans that, without a physician income, may be difficult to repay,⁹ many doctors feel trapped within a seemingly endless cycle of misgiving that contributes to emotional exhaustion, pessimism, and low morale.

In my next series of The Myth of the Superdoctor columns, we will explore various factors that potentiate risk of moral injury. From medical school and residency training to corporate infrastructure and insurance obstacles, I will seek to discern and deliberate strategies for repair and rehabilitation. It is my hope that together we will illuminate the myriad complexities within the business of medicine, and become advocates and harbingers of change not only for physicians and health care workers but also for the sake of our patients and their families.

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

References

1. King N. When a Psychologist Succumbed to Stress, He Coined The Term Burnout. 2016 Dec 8. NPR: All Things Considered.

2. Maslach C and Leiter MP. World Psychiatry. 2016 Jun;15(2):103-11. doi: 10.1002/wps.20311.

3. InformedHealth.org and Institute for Quality and Efficiency in Health Care. Depression: What is burnout?. https://www.ncbi.nlm.nih.gov/books/NBK279286/.

4. Michel A. Burnout and the Brain. Observer. 2016 Jan 29. https://www.psychologicalscience.org/observer/burnout-and-the-brain.

5. Patel RS et al. Behav Sci. 2018;8(11):98. doi:10.3390/bs8110098.

6. Dean W and Talbot S. Physicians aren’t ‘burning out.’ They’re suffering from moral injury. Stat. 2018 Jul 26. https://www.statnews.com/2018/07/26/physicians-not-burning-out-they-are-suffering-moral-injury/.

7. Dean W and Talbot S. Moral injury and burnout in medicine: A year of lessons learned. Stat. 2019 Jul 26. https://www.statnews.com/2019/07/26/moral-injury-burnout-medicine-lessons-learned/.

8. Dean W et al. Reframing Clinician Distress: Moral Injury Not Burnout. Fed Pract. 2019 Sep; 36(9):400-2. https://www.mdedge.com/fedprac/article/207458/mental-health/reframing-clinician-distress-moral-injury-not-burnout.

9. Bailey M. Beyond Burnout: Docs Decry ‘Moral Injury’ From Financial Pressures of Health Care. KHN. 2020 Feb 4. https://khn.org/news/beyond-burnout-docs-decry-moral-injury-from-financial-pressures-of-health-care/.

10. Litz B et al. Clin Psychol Rev. 2009 Dec;29(8):695-706. doi: 10.1016/j.cpr.2009.07.003.

11. Norman S and Maguen S. Moral Injury. PTSD: National Center for PTSD. https://www.ptsd.va.gov/professional/treat/cooccurring/moral_injury.asp.

Several years have passed since I stood among a cohort of eager medical students wearing regalia that signaled a new beginning. Four years of grueling study culminated in a cacophony of unified voices, each reciting a pledge that I had longed to take since early adolescence. Together we celebrated, triumphant despite innumerable exams and various iterations of the Socratic method – all under the guise of assessing knowledge while in truth seeking to insidiously erode the crowd of prospective physicians. Yet our anxiety and uncertainty melted away as names were called, hands firmly clasped, and tassels transposed. For a moment in time, we stood on the precipice of victory, enthusiastic albeit oblivious of the tremendous obstacles that loomed ahead.

Wistfully I reminisce about the unequivocal joy that abounds within the protective shield of naiveté. Specifically, I think about that time when the edict of medicine and the art of being a physician felt congruent. Yet, reality is fickle and often supersedes expectation. Occasionally my thoughts drift to the early days of residency – a time during which the emotional weight of caring for vulnerable patients while learning to master my chosen specialty felt woefully insurmountable. I recall wading blindly through each rotation attempting to emulate the competent and compassionate care so effortlessly demonstrated by senior physicians as they moved through the health care system with apparent ease. They stepped fluidly, as I watched in awe through rose-tinted glasses.

As months passed into years, my perception cleared. What I initially viewed as graceful patient care belied a complex tapestry of health care workers often pressured into arduous decisions, not necessarily in service of a well-constructed treatment plan. Gradually, formidable barriers emerged, guidelines and restrictions embedded within a confining path that suffocated those who dared to cross it. As a result, a field built on the foundations of autonomy, benevolence, and nonmaleficence was slowly engulfed by a system fraught with contrivances. Amid such stressors, physical and psychological health grows tenuous. Classically, this overwhelming feeling of distress is recognized as burnout. Studies reformulated this malady to that which was first described in Vietnam war veterans, a condition known as “moral injury.”
 

The impact of burnout

To explain the development – and explore the complexities – of moral injury, we must return to 1975 when the term burnout was initially formulated by Herbert Freudenberger, PhD, a psychologist renowned for his work in substance use disorders, psychoanalysis, and clinical education.¹ Dr. Freudenberger’s studies noted incidences of heightened emotional and physical distress in his colleagues working in substance abuse and other clinics. He sought to define these experiences as well as understand his own battle with malaise, apathy, and frustration.¹ Ultimately, Dr. Freudenberger described burnout as “Becoming exhausted by making excessive demands on energy, strength, or resources in the workplace.”² Although it characteristically overlaps with depression and anxiety, burnout is conceptualized as a separate entity specifically forged within a context of perfectionism, integrity, and self-sacrifice.² Such qualities are integral in health care and, as a result, physicians are particularly vulnerable.

Since Dr. Freudenberger published “Burnout: The High Cost of Achievement” in 1980, immense research has assisted in not only identifying critical factors that contribute to its development but also the detrimental effects it has on physiological health.³ These include exhaustion from poor work conditions and extreme commitment to employee responsibilities that in turn precipitate mood destabilization and impaired work performance.³ Furthermore, research has also demonstrated that burnout triggers alterations in neural circuitry via the prefrontal cortex and the amygdala, structures critical for emotional regulation.⁴ To combat the ill effects of burnout while maintaining productivity and maximizing profit, several high-profile corporations instituted changes focusing on self-care, wellness, benefits, and incentives. Although these modifications are effective in decreasing the rate of employee turnover, such strategies are not easily transferable to health care. In fact, the rate of physician burnout has steadily increased over the past two decades as the business of medicine shifts towards longer hours, decreased reimbursement rates, and inexhaustible insurance stipulations.^2,5 Consequently, occupational dissatisfaction increases the risk of cynicism, frustration with patients, internalization of failure, and likelihood of early retirement.⁵ Moreover, burnout may also fracture interpersonal relationships as well as precipitate errors, negative patient outcomes, malpractice, and development of severe mental health conditions associated with high morbidity and mortality.^5,8

Although the concept of burnout is critical in understanding the side effects of stereotypical workplace culture, critics of the concept bemoan a suggestion of individual blame.^6,8 In essence, they argue that burnout is explained as a side effect of toxic workplace conditions, but covertly represents a lack of resilience, motivation, and ambition to thrive in a physically or emotionally taxing occupational setting.^6,8 Thus, the responsibility of acclimation lies upon the impacted individuals rather than the employer. For this reason, many strategies to ameliorate burnout are focused on the individual, including meditation, wellness retreats, creating or adjusting self-care regimens, or in some cases psychotherapy and psychopharmacology.⁶ Whereas burnout may respond (at least partially) to such interventions, without altering the causal factors, it is unlikely to remit. This is especially the case in health care, where systemic constraints lie beyond the control of an individual physician. Rather than promoting or specifically relying upon personal improvement and recovery, amendments are needed on multiple levels to affect meaningful change.
 

Moral injury

Similar to burnout, moral injury was not initially conceived within the scope of health care. In the 1990s Jonathan Shay, MD, PhD, identified veterans presenting with symptoms mimicking PTSD that failed to respond to standard, well established and efficacious treatments.^9-11 With further analysis he determined that veterans who demonstrated minimal improvement reported similar histories of guilt, shame, and disgust following perceived injustices enacted or abetted by immoral leaders.^10,11 Ultimately Shay identified three components of moral injury: 1. A betrayal of what is morally right; 2. By someone who holds legitimate priority; 3. In a high stakes situation.¹⁰

This definition was further modified in 2007 by Brett Linz, PhD, and colleagues as: “Perpetuating, failing to prevent, or bearing witness to acts that transgress deeply held moral beliefs and expectations.”^10,11 By expanding this description to include distress experienced by physicians and health care workers, Wendy Dean and Simon Talbot (in 2018 and 2019 respectively) explored how the health care system leads practitioners to deliver what they identify as substandard treatment.^6-8 This results in disillusionment and lays the foundation for ethical and moral dilemmas in clinicians.

Themes of moral injury are repeatedly cited in various surveys and studies as a cause for occupational dissatisfaction. As physicians and other health care professionals reel from the aftermath of COVID-19, the effects of reconfiguring medicine into a business-oriented framework are glaringly conspicuous. Vast hospital nursing shortages, high patient census exacerbated by the political misuse and polarization of science, and insufficient availability of psychiatric beds, have culminated in a deluge of psychological strain in emergency medical physicians. Furthermore, pressure from administrators, mandated patient satisfaction measures, tedious electronic medical record systems, and copious licensing and certification requirements, contribute to physician distress as they attempt to navigate a system that challenges the vows which they swore to uphold.⁸ Because the cost of pursuing a medical degree frequently necessitates acquisition of loans that, without a physician income, may be difficult to repay,⁹ many doctors feel trapped within a seemingly endless cycle of misgiving that contributes to emotional exhaustion, pessimism, and low morale.

In my next series of The Myth of the Superdoctor columns, we will explore various factors that potentiate risk of moral injury. From medical school and residency training to corporate infrastructure and insurance obstacles, I will seek to discern and deliberate strategies for repair and rehabilitation. It is my hope that together we will illuminate the myriad complexities within the business of medicine, and become advocates and harbingers of change not only for physicians and health care workers but also for the sake of our patients and their families.

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

References

1. King N. When a Psychologist Succumbed to Stress, He Coined The Term Burnout. 2016 Dec 8. NPR: All Things Considered.

2. Maslach C and Leiter MP. World Psychiatry. 2016 Jun;15(2):103-11. doi: 10.1002/wps.20311.

3. InformedHealth.org and Institute for Quality and Efficiency in Health Care. Depression: What is burnout?. https://www.ncbi.nlm.nih.gov/books/NBK279286/.

4. Michel A. Burnout and the Brain. Observer. 2016 Jan 29. https://www.psychologicalscience.org/observer/burnout-and-the-brain.

5. Patel RS et al. Behav Sci. 2018;8(11):98. doi:10.3390/bs8110098.

6. Dean W and Talbot S. Physicians aren’t ‘burning out.’ They’re suffering from moral injury. Stat. 2018 Jul 26. https://www.statnews.com/2018/07/26/physicians-not-burning-out-they-are-suffering-moral-injury/.

7. Dean W and Talbot S. Moral injury and burnout in medicine: A year of lessons learned. Stat. 2019 Jul 26. https://www.statnews.com/2019/07/26/moral-injury-burnout-medicine-lessons-learned/.

8. Dean W et al. Reframing Clinician Distress: Moral Injury Not Burnout. Fed Pract. 2019 Sep; 36(9):400-2. https://www.mdedge.com/fedprac/article/207458/mental-health/reframing-clinician-distress-moral-injury-not-burnout.

9. Bailey M. Beyond Burnout: Docs Decry ‘Moral Injury’ From Financial Pressures of Health Care. KHN. 2020 Feb 4. https://khn.org/news/beyond-burnout-docs-decry-moral-injury-from-financial-pressures-of-health-care/.

10. Litz B et al. Clin Psychol Rev. 2009 Dec;29(8):695-706. doi: 10.1016/j.cpr.2009.07.003.

11. Norman S and Maguen S. Moral Injury. PTSD: National Center for PTSD. https://www.ptsd.va.gov/professional/treat/cooccurring/moral_injury.asp.