The introduction of eculizumab, a monoclonal antibody targeting C5 of the complement cascade, revolutionized the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a rare hematologic disorder characterized by complement-mediated intravascular hemolysis, bone marrow failure, and thrombophilia. Treatment options for PNH were limited before eculizumab was approved by the Food and Drug Administration in 2007.

Its use resulted in the inhibition of intravascular hemolysis, hemoglobin stabilization, and substantial reductions in transfusion requirements. Moreover, eculizumab had the unexpected effect of reducing the risk of thromboembolic complications, the most severe complication of PNH. Patients treated with eculizumab experienced fewer thrombotic events (4%), compared with historical cohorts (27%). Importantly, 5-year overall survival rates for patients with PNH taking eculizumab improved more than 90%, compared wity the 80% reported historically.

More than 10 years later, we are tasked with assessing the impact of this drug. Unquestionably, eculizumab has done more for PNH than we could have hoped for. However, 10 years of additional data reveal the limitations of this groundbreaking therapy. Despite the overall sustained response and survival benefit, hematologic response remains variable. Complete normalization of hemoglobin occurs in less than one-third of patients. Transfusion requirements persist in many patients. Residual anemia during eculizumab therapy is at least partly attributed to bone marrow failure, a feature the complement inhibition does not address. Still, pharmacokinetic limitations of the drug also contribute to the lack of complete responses. There is residual intravascular hemolysis because of insufficient inhibition of C5 and the emergence of C3-mediated extravascular hemolysis constitutes an unanticipated mechanistic complication of all C5-mediated therapies.

The last few years have seen a surge in novel anticomplement agents, which improve upon the already well-established inhibition of C5 but also explore the efficacy of targeting earlier aspects of the complement pathway. During the American Society of Hematology (ASH) annual meeting, we had exciting updates on some of the promising new kids on the block.

Ravulizumab, the newest C5 monoclonal antibody approved by the FDA for PNH, displays more robust C5 inhibition, thereby reducing the breakthrough hemolysis still seen with eculizumab use. Crovalimab, also an anti-C5 humanized antibody, is engineered with Sequential Monoclonal Antibody Recycling Technology that improves the half-life of the drug and facilitates subcutaneous dosing while still achieving complete C5 inhibition. Some of the most exciting data is on danicopan, a small-molecule factor D inhibitor that targets the alternative pathway thereby inhibiting C3 convertase and blocking extravascular hemolysis. It has shown promise as a stand-alone agent, as well as with combined C5 inhibition, while promising safety, a reasonable concern as we explore the long-term risks of targeting the proximal complement pathway.

I was recently asked to comment on how the new complement inhibitors are addressing unmet needs in PNH. While the recent presentations at ASH demonstrate an improvement on the efficacy of C5 inhibition, pharmacokinetics, and drug delivery – all which translate to improved hemoglobin and reduced breakthrough hemolysis for PNH patients – I am most excited at the promise this new generation of drugs holds for other diseases. Since its approval for PNH, eculizumab has also been approved for use in atypical hemolytic uremic syndrome (aHUS), myasthenia gravis, and neuromyelitis optica spectrum disorder.

Perhaps the greatest potential I envision for the new generation of drugs is in aHUS, a chronic disease characterized by hemolytic anemia, thrombocytopenia, and end-stage renal disease that cannot be cured with renal transplantation. The pathophysiology involves dysregulation of complement activation because of genetic mutations or autoantibodies to key proteins in the complement cascade. Though we have experienced some success with eculizumab, responses can be incomplete, particularly in patients with C5 mutations. The newer drugs offer the opportunity to inhibit complement activation at both proximal and distal aspects of the cascade, which may prove ideal in a disease in which the affected protein is not consistent. Moreover, preclinical and clinical trials have shown promise for these novel complement inhibitors in other autoimmune diseases: antibody-mediated vasculitis, C3 glomerulopathy, catastrophic antibody syndrome, membranous nephropathy, and lupus nephritis.

The surge of new complement inhibitors could revolutionize our strategy for treatment of autoimmune-mediated diseases, in which downstream complement activation can manifest with life-threatening tissue injury. Inhibition of complement offers a promising strategy for blocking downstream immune-mediated effector mechanisms of injury common in several autoimmune diseases.

As the results from various clinical trials come to fruition, it will be exciting to determine how to best use this new generation of drugs to target new diseases and whether the next decade is poised to eclipse the progress in complement therapy already established by eculizumab.
 

Dr. Sosa is a benign hematologist at Fox Chase Cancer Center in Philadelphia. Her research interests are in thromboembolic disease, with a focus in racial and gender disparities.

The introduction of eculizumab, a monoclonal antibody targeting C5 of the complement cascade, revolutionized the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a rare hematologic disorder characterized by complement-mediated intravascular hemolysis, bone marrow failure, and thrombophilia. Treatment options for PNH were limited before eculizumab was approved by the Food and Drug Administration in 2007.

Its use resulted in the inhibition of intravascular hemolysis, hemoglobin stabilization, and substantial reductions in transfusion requirements. Moreover, eculizumab had the unexpected effect of reducing the risk of thromboembolic complications, the most severe complication of PNH. Patients treated with eculizumab experienced fewer thrombotic events (4%), compared with historical cohorts (27%). Importantly, 5-year overall survival rates for patients with PNH taking eculizumab improved more than 90%, compared wity the 80% reported historically.

More than 10 years later, we are tasked with assessing the impact of this drug. Unquestionably, eculizumab has done more for PNH than we could have hoped for. However, 10 years of additional data reveal the limitations of this groundbreaking therapy. Despite the overall sustained response and survival benefit, hematologic response remains variable. Complete normalization of hemoglobin occurs in less than one-third of patients. Transfusion requirements persist in many patients. Residual anemia during eculizumab therapy is at least partly attributed to bone marrow failure, a feature the complement inhibition does not address. Still, pharmacokinetic limitations of the drug also contribute to the lack of complete responses. There is residual intravascular hemolysis because of insufficient inhibition of C5 and the emergence of C3-mediated extravascular hemolysis constitutes an unanticipated mechanistic complication of all C5-mediated therapies.

The last few years have seen a surge in novel anticomplement agents, which improve upon the already well-established inhibition of C5 but also explore the efficacy of targeting earlier aspects of the complement pathway. During the American Society of Hematology (ASH) annual meeting, we had exciting updates on some of the promising new kids on the block.

Ravulizumab, the newest C5 monoclonal antibody approved by the FDA for PNH, displays more robust C5 inhibition, thereby reducing the breakthrough hemolysis still seen with eculizumab use. Crovalimab, also an anti-C5 humanized antibody, is engineered with Sequential Monoclonal Antibody Recycling Technology that improves the half-life of the drug and facilitates subcutaneous dosing while still achieving complete C5 inhibition. Some of the most exciting data is on danicopan, a small-molecule factor D inhibitor that targets the alternative pathway thereby inhibiting C3 convertase and blocking extravascular hemolysis. It has shown promise as a stand-alone agent, as well as with combined C5 inhibition, while promising safety, a reasonable concern as we explore the long-term risks of targeting the proximal complement pathway.

I was recently asked to comment on how the new complement inhibitors are addressing unmet needs in PNH. While the recent presentations at ASH demonstrate an improvement on the efficacy of C5 inhibition, pharmacokinetics, and drug delivery – all which translate to improved hemoglobin and reduced breakthrough hemolysis for PNH patients – I am most excited at the promise this new generation of drugs holds for other diseases. Since its approval for PNH, eculizumab has also been approved for use in atypical hemolytic uremic syndrome (aHUS), myasthenia gravis, and neuromyelitis optica spectrum disorder.

Perhaps the greatest potential I envision for the new generation of drugs is in aHUS, a chronic disease characterized by hemolytic anemia, thrombocytopenia, and end-stage renal disease that cannot be cured with renal transplantation. The pathophysiology involves dysregulation of complement activation because of genetic mutations or autoantibodies to key proteins in the complement cascade. Though we have experienced some success with eculizumab, responses can be incomplete, particularly in patients with C5 mutations. The newer drugs offer the opportunity to inhibit complement activation at both proximal and distal aspects of the cascade, which may prove ideal in a disease in which the affected protein is not consistent. Moreover, preclinical and clinical trials have shown promise for these novel complement inhibitors in other autoimmune diseases: antibody-mediated vasculitis, C3 glomerulopathy, catastrophic antibody syndrome, membranous nephropathy, and lupus nephritis.

The surge of new complement inhibitors could revolutionize our strategy for treatment of autoimmune-mediated diseases, in which downstream complement activation can manifest with life-threatening tissue injury. Inhibition of complement offers a promising strategy for blocking downstream immune-mediated effector mechanisms of injury common in several autoimmune diseases.

As the results from various clinical trials come to fruition, it will be exciting to determine how to best use this new generation of drugs to target new diseases and whether the next decade is poised to eclipse the progress in complement therapy already established by eculizumab.
 

Dr. Sosa is a benign hematologist at Fox Chase Cancer Center in Philadelphia. Her research interests are in thromboembolic disease, with a focus in racial and gender disparities.

The introduction of eculizumab, a monoclonal antibody targeting C5 of the complement cascade, revolutionized the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a rare hematologic disorder characterized by complement-mediated intravascular hemolysis, bone marrow failure, and thrombophilia. Treatment options for PNH were limited before eculizumab was approved by the Food and Drug Administration in 2007.

Its use resulted in the inhibition of intravascular hemolysis, hemoglobin stabilization, and substantial reductions in transfusion requirements. Moreover, eculizumab had the unexpected effect of reducing the risk of thromboembolic complications, the most severe complication of PNH. Patients treated with eculizumab experienced fewer thrombotic events (4%), compared with historical cohorts (27%). Importantly, 5-year overall survival rates for patients with PNH taking eculizumab improved more than 90%, compared wity the 80% reported historically.

More than 10 years later, we are tasked with assessing the impact of this drug. Unquestionably, eculizumab has done more for PNH than we could have hoped for. However, 10 years of additional data reveal the limitations of this groundbreaking therapy. Despite the overall sustained response and survival benefit, hematologic response remains variable. Complete normalization of hemoglobin occurs in less than one-third of patients. Transfusion requirements persist in many patients. Residual anemia during eculizumab therapy is at least partly attributed to bone marrow failure, a feature the complement inhibition does not address. Still, pharmacokinetic limitations of the drug also contribute to the lack of complete responses. There is residual intravascular hemolysis because of insufficient inhibition of C5 and the emergence of C3-mediated extravascular hemolysis constitutes an unanticipated mechanistic complication of all C5-mediated therapies.

The last few years have seen a surge in novel anticomplement agents, which improve upon the already well-established inhibition of C5 but also explore the efficacy of targeting earlier aspects of the complement pathway. During the American Society of Hematology (ASH) annual meeting, we had exciting updates on some of the promising new kids on the block.

Ravulizumab, the newest C5 monoclonal antibody approved by the FDA for PNH, displays more robust C5 inhibition, thereby reducing the breakthrough hemolysis still seen with eculizumab use. Crovalimab, also an anti-C5 humanized antibody, is engineered with Sequential Monoclonal Antibody Recycling Technology that improves the half-life of the drug and facilitates subcutaneous dosing while still achieving complete C5 inhibition. Some of the most exciting data is on danicopan, a small-molecule factor D inhibitor that targets the alternative pathway thereby inhibiting C3 convertase and blocking extravascular hemolysis. It has shown promise as a stand-alone agent, as well as with combined C5 inhibition, while promising safety, a reasonable concern as we explore the long-term risks of targeting the proximal complement pathway.

I was recently asked to comment on how the new complement inhibitors are addressing unmet needs in PNH. While the recent presentations at ASH demonstrate an improvement on the efficacy of C5 inhibition, pharmacokinetics, and drug delivery – all which translate to improved hemoglobin and reduced breakthrough hemolysis for PNH patients – I am most excited at the promise this new generation of drugs holds for other diseases. Since its approval for PNH, eculizumab has also been approved for use in atypical hemolytic uremic syndrome (aHUS), myasthenia gravis, and neuromyelitis optica spectrum disorder.

Perhaps the greatest potential I envision for the new generation of drugs is in aHUS, a chronic disease characterized by hemolytic anemia, thrombocytopenia, and end-stage renal disease that cannot be cured with renal transplantation. The pathophysiology involves dysregulation of complement activation because of genetic mutations or autoantibodies to key proteins in the complement cascade. Though we have experienced some success with eculizumab, responses can be incomplete, particularly in patients with C5 mutations. The newer drugs offer the opportunity to inhibit complement activation at both proximal and distal aspects of the cascade, which may prove ideal in a disease in which the affected protein is not consistent. Moreover, preclinical and clinical trials have shown promise for these novel complement inhibitors in other autoimmune diseases: antibody-mediated vasculitis, C3 glomerulopathy, catastrophic antibody syndrome, membranous nephropathy, and lupus nephritis.

The surge of new complement inhibitors could revolutionize our strategy for treatment of autoimmune-mediated diseases, in which downstream complement activation can manifest with life-threatening tissue injury. Inhibition of complement offers a promising strategy for blocking downstream immune-mediated effector mechanisms of injury common in several autoimmune diseases.

As the results from various clinical trials come to fruition, it will be exciting to determine how to best use this new generation of drugs to target new diseases and whether the next decade is poised to eclipse the progress in complement therapy already established by eculizumab.
 

Dr. Sosa is a benign hematologist at Fox Chase Cancer Center in Philadelphia. Her research interests are in thromboembolic disease, with a focus in racial and gender disparities.

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

Burnout among physicians appears to have decreased slightly in the past few years, but remains a significant problem for the medical profession, according to the Medscape National Physician Burnout & Suicide Report 2020: The Generational Divide.

olm26250/Thinkstock

A survey of more than 15,000 physicians revealed that 42% reported being burned out, down from 46% who responded to the survey 5 years ago. However, there are variations in the rates based on certain demographic factors such as specialty, age, and gender.

Urology sits at the top of the list as the specialty that is experiencing the highest rate of burnout, with 54% of urologists responding to the survey reporting burnout. Neurology and nephrology followed with rates of burnout at 50% and 49%, respectively. The next five specialties on the list all reported burnout rates of 46%: diabetes and endocrinology, family medicine, radiology, ob.gyn., and rheumatology. Pulmonology specialists reported a burnout rate of 41%. Gastroenterologists reported burnout rates of 37%.

The survey divided participants into three age categories – Millennial (ages 25-39 years), Generation X (ages 40-54 years), and Baby Boomer (ages 55-73 years). Both Millennials and Baby Boomers reported similar rates of burnout (38% and 39%, respectively) and those in Generation X reported a higher rate of burnout (48%).

This higher rate is not unexpected. The survey results cite Carol Bernstein, MD, of the Albert Einstein College of Medicine, New York, as noting that midcareer “is typically the time of highest burnout, which is where Gen Xers are in their career trajectory, suggesting a number of factors outside of work such as caring for children and elderly parents, planning for retirement, can play a role in contributing to burnout.”

Women also reported a higher rate of burnout, although the rate has dropped from the survey conducted 5 years ago. The rate of burnout among women reported for the 2020 survey was 48%, down from 51% reported 5 years ago. By comparison, the rate of burnout for men was 37% in 2020, down from 43% in 2015.

In terms of what is causing burnout, the biggest contributor is the bureaucratic tasks (charting and paperwork, for example) that physicians must complete, which 55% of respondents to the survey said was the leading cause of burnout. Next was spending too many hours at work (33%); lack of respect from administrators, employers, colleagues, and staff (32%); and the increased computerization of the practice, including the use of electronic health records (30%).

When broken down by age category, the bureaucratic tasks was tops in all three groups (57% for Millennials, 56% for Generation X, and 54% for Baby Boomers), but what ranks next differs slightly by age group. For Millennials, the next two factors were too many hours at work (38%) and lack of respect (35%). Generation X respondents cited the same two factors, both at 33%. Baby Boomers cited computerization as their second-highest factor (41%) and spending too many hours at work as the third-highest factor (31%).

The generations had different approaches to coping with burnout. Millennials (56%) reported sleep as their top-ranked coping strategy, while Gen Xers and Baby Boomers ranked exercise and personal isolation as their top choice. For these two older groups, sleep was ranked last, after other activities such as talking with family and friends.

The survey also asked about depression, and respondents reported a similar rate across all age groups (15%, 18%, and 16%, respectively). Among those who said they were depressed, the three age groups had similar rates of suicidal thoughts (21%, 24%, and 22%).

Perhaps the most striking finding of the survey is the number of physicians who would take a pay cut to achieve a better work-life balance. Among Millennials, 52% would accept a pay cut, compared with 48% of Generation X and 49% of Baby Boomers. A surprising number (36%, 34%, and 31%, respectively, reported that they would accept a $10,000-$20,000 pay cut to have a 20% reduction in work hours. [email protected]

*This story was updated on 1/22/2020.

SOURCE: Kane L et al. Medscape National Physician Burnout & Suicide Report 2020: The Generational Divide. Medscape. 2020 Jan 15.

Burnout among physicians appears to have decreased slightly in the past few years, but remains a significant problem for the medical profession, according to the Medscape National Physician Burnout & Suicide Report 2020: The Generational Divide.

olm26250/Thinkstock

A survey of more than 15,000 physicians revealed that 42% reported being burned out, down from 46% who responded to the survey 5 years ago. However, there are variations in the rates based on certain demographic factors such as specialty, age, and gender.

Urology sits at the top of the list as the specialty that is experiencing the highest rate of burnout, with 54% of urologists responding to the survey reporting burnout. Neurology and nephrology followed with rates of burnout at 50% and 49%, respectively. The next five specialties on the list all reported burnout rates of 46%: diabetes and endocrinology, family medicine, radiology, ob.gyn., and rheumatology. Pulmonology specialists reported a burnout rate of 41%. Gastroenterologists reported burnout rates of 37%.

The survey divided participants into three age categories – Millennial (ages 25-39 years), Generation X (ages 40-54 years), and Baby Boomer (ages 55-73 years). Both Millennials and Baby Boomers reported similar rates of burnout (38% and 39%, respectively) and those in Generation X reported a higher rate of burnout (48%).

This higher rate is not unexpected. The survey results cite Carol Bernstein, MD, of the Albert Einstein College of Medicine, New York, as noting that midcareer “is typically the time of highest burnout, which is where Gen Xers are in their career trajectory, suggesting a number of factors outside of work such as caring for children and elderly parents, planning for retirement, can play a role in contributing to burnout.”

Women also reported a higher rate of burnout, although the rate has dropped from the survey conducted 5 years ago. The rate of burnout among women reported for the 2020 survey was 48%, down from 51% reported 5 years ago. By comparison, the rate of burnout for men was 37% in 2020, down from 43% in 2015.

In terms of what is causing burnout, the biggest contributor is the bureaucratic tasks (charting and paperwork, for example) that physicians must complete, which 55% of respondents to the survey said was the leading cause of burnout. Next was spending too many hours at work (33%); lack of respect from administrators, employers, colleagues, and staff (32%); and the increased computerization of the practice, including the use of electronic health records (30%).

When broken down by age category, the bureaucratic tasks was tops in all three groups (57% for Millennials, 56% for Generation X, and 54% for Baby Boomers), but what ranks next differs slightly by age group. For Millennials, the next two factors were too many hours at work (38%) and lack of respect (35%). Generation X respondents cited the same two factors, both at 33%. Baby Boomers cited computerization as their second-highest factor (41%) and spending too many hours at work as the third-highest factor (31%).

The generations had different approaches to coping with burnout. Millennials (56%) reported sleep as their top-ranked coping strategy, while Gen Xers and Baby Boomers ranked exercise and personal isolation as their top choice. For these two older groups, sleep was ranked last, after other activities such as talking with family and friends.

The survey also asked about depression, and respondents reported a similar rate across all age groups (15%, 18%, and 16%, respectively). Among those who said they were depressed, the three age groups had similar rates of suicidal thoughts (21%, 24%, and 22%).

Perhaps the most striking finding of the survey is the number of physicians who would take a pay cut to achieve a better work-life balance. Among Millennials, 52% would accept a pay cut, compared with 48% of Generation X and 49% of Baby Boomers. A surprising number (36%, 34%, and 31%, respectively, reported that they would accept a $10,000-$20,000 pay cut to have a 20% reduction in work hours. [email protected]

*This story was updated on 1/22/2020.

SOURCE: Kane L et al. Medscape National Physician Burnout & Suicide Report 2020: The Generational Divide. Medscape. 2020 Jan 15.

Burnout among physicians appears to have decreased slightly in the past few years, but remains a significant problem for the medical profession, according to the Medscape National Physician Burnout & Suicide Report 2020: The Generational Divide.

olm26250/Thinkstock

A survey of more than 15,000 physicians revealed that 42% reported being burned out, down from 46% who responded to the survey 5 years ago. However, there are variations in the rates based on certain demographic factors such as specialty, age, and gender.

Urology sits at the top of the list as the specialty that is experiencing the highest rate of burnout, with 54% of urologists responding to the survey reporting burnout. Neurology and nephrology followed with rates of burnout at 50% and 49%, respectively. The next five specialties on the list all reported burnout rates of 46%: diabetes and endocrinology, family medicine, radiology, ob.gyn., and rheumatology. Pulmonology specialists reported a burnout rate of 41%. Gastroenterologists reported burnout rates of 37%.

The survey divided participants into three age categories – Millennial (ages 25-39 years), Generation X (ages 40-54 years), and Baby Boomer (ages 55-73 years). Both Millennials and Baby Boomers reported similar rates of burnout (38% and 39%, respectively) and those in Generation X reported a higher rate of burnout (48%).

This higher rate is not unexpected. The survey results cite Carol Bernstein, MD, of the Albert Einstein College of Medicine, New York, as noting that midcareer “is typically the time of highest burnout, which is where Gen Xers are in their career trajectory, suggesting a number of factors outside of work such as caring for children and elderly parents, planning for retirement, can play a role in contributing to burnout.”

Women also reported a higher rate of burnout, although the rate has dropped from the survey conducted 5 years ago. The rate of burnout among women reported for the 2020 survey was 48%, down from 51% reported 5 years ago. By comparison, the rate of burnout for men was 37% in 2020, down from 43% in 2015.

In terms of what is causing burnout, the biggest contributor is the bureaucratic tasks (charting and paperwork, for example) that physicians must complete, which 55% of respondents to the survey said was the leading cause of burnout. Next was spending too many hours at work (33%); lack of respect from administrators, employers, colleagues, and staff (32%); and the increased computerization of the practice, including the use of electronic health records (30%).

When broken down by age category, the bureaucratic tasks was tops in all three groups (57% for Millennials, 56% for Generation X, and 54% for Baby Boomers), but what ranks next differs slightly by age group. For Millennials, the next two factors were too many hours at work (38%) and lack of respect (35%). Generation X respondents cited the same two factors, both at 33%. Baby Boomers cited computerization as their second-highest factor (41%) and spending too many hours at work as the third-highest factor (31%).

The generations had different approaches to coping with burnout. Millennials (56%) reported sleep as their top-ranked coping strategy, while Gen Xers and Baby Boomers ranked exercise and personal isolation as their top choice. For these two older groups, sleep was ranked last, after other activities such as talking with family and friends.

The survey also asked about depression, and respondents reported a similar rate across all age groups (15%, 18%, and 16%, respectively). Among those who said they were depressed, the three age groups had similar rates of suicidal thoughts (21%, 24%, and 22%).

Perhaps the most striking finding of the survey is the number of physicians who would take a pay cut to achieve a better work-life balance. Among Millennials, 52% would accept a pay cut, compared with 48% of Generation X and 49% of Baby Boomers. A surprising number (36%, 34%, and 31%, respectively, reported that they would accept a $10,000-$20,000 pay cut to have a 20% reduction in work hours. [email protected]

*This story was updated on 1/22/2020.

SOURCE: Kane L et al. Medscape National Physician Burnout & Suicide Report 2020: The Generational Divide. Medscape. 2020 Jan 15.

Adult survivors of pediatric cancers appear to be experiencing fewer major cardiac events in adulthood partly because of reduced radiotherapy exposure, especially among survivors of Hodgkin lymphoma, recent research published in BMJ has shown.

“Contemporary cancer treatment has focused on advancing cure rates while attempting to minimize long term adverse effects,” Daniel A. Mulrooney, MD, of the Division of Cancer Survivorship, Department of Oncology, at St. Jude Children’s Research Hospital, Arlington, Va., and colleagues wrote. “Patterns of exposure to cardiotoxic treatment have changed over time, with fewer children receiving chest directed radiation, with lower doses and smaller volumes for those who do, and an increased use of anthracyclines, albeit with reduced cumulative doses as the risk for late-onset heart failure became apparent.”

Although research has been published on improved survival rates of children who underwent cancer treatment in the 1990s, compared with those who received treatment in the 1980s and 1970s, Dr. Mulrooney and colleagues set out to determine whether cardiac outcomes were reduced as well. They conducted a retrospective study of 23,462 5-year survivors of pediatric cancer, which consisted of leukemia, brain cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal tumors, neuroblastoma, soft-tissue sarcomas, and bone sarcomas diagnosed between January 1970 and December 1999. Researchers compared the cardiac outcomes of the survivors, including heart failure, coronary artery disease, valvular heart disease, pericardial disease, and arrhythmias, with a comparison group of their siblings (n = 5,057) separated by decade. The adult survivors tended to be women (46% vs. 40%) with a median age of 6.1 years at diagnosis and 27.7 years at final follow-up.

Of the 6,193 participants treated for cancer in the 1970s, the 20-year cumulative incidence of heart failure was 0.69%, while the 9,363 participants treated in the 1980s had an incidence of 0.74%, and 7,906 participants in the 1990s had a cumulative incidence of 0.54% over 20 years. The 20-year cumulative incidence for coronary artery disease (CAD) was 0.38% for participants in the 1970s, 0.24% for participants in the 1980s, and 0.19% for participants in the 1990s (P less than .01). Researchers noted the 20-year cumulative incidence of valvular disease, pericardial disease, and arrhythmias did not decrease between the 1970s and the 1990s.

When comparing the rate of major cardiac events of participants in the 1980s and 1990s with those of the 1970s, CAD diagnoses significantly decreased in the 1980s (hazard ratio, 0.65; 95% confidence interval, 0.45-0.92) and 1990s (HR, 0.53; 95% CI, 0.36-0.77), while there was no significant decrease in heart failure or valvular heart disease risk over time. After adjusting for cardiac radiation, overall risk for CAD was attenuated (HR, 0.90; 0.78-1.05), and Hodgkin lymphoma survivors saw the greatest change between unadjusted (HR, 0.77; 95% CI, 0.66-0.89) and adjusted risk (HR, 0.87; 95% CI, 0.69-1.10) when accounting for cardiac radiation.

“While additional longitudinal follow-up is needed to establish whether similar reductions in the cumulative incidence of heart failure can be confirmed in multivariable analysis, these results suggest that efforts to modify cancer therapies in children and promote health surveillance for survivors are beginning to show benefits not only in overall survival but also in late adverse cardiac effects,” the researchers concluded.

In a related editorial, Mike Hawkins, DPhil, of the Centre for Childhood Cancer Survivor Studies, Institute of Applied Health Research at the University of Birmingham (England), and colleagues said that, while measuring cardiotoxicity is important for this patient population, traditional risk factors with independent associations to cardiac outcomes should also be studied. Guidelines on follow-up for these patients are also needed to inform clinical practice, such as those produced by the International Late Effects of Childhood Cancer Guideline Harmonization Group, they added.

“Survivorship issues are extremely important to patients, their families, and their doctors,” they said. “In two research priority setting initiatives in the United Kingdom, detailed consultation with patients with cancer, survivors, families, friends, and healthcare professionals identified further research into the consequences of cancer as a top priority.”

This study was funded by grants from the National Cancer Institute, Cancer Center Support (CORE) to St. Jude Children’s Research Hospital and American Lebanese Syrian Associated Charities. The authors of the study and the editorial reported no relevant conflicts of interest.

SOURCE: Mulrooney A et al. BMJ. 2020. doi: 10.1136/bmj.l6794.

Adult survivors of pediatric cancers appear to be experiencing fewer major cardiac events in adulthood partly because of reduced radiotherapy exposure, especially among survivors of Hodgkin lymphoma, recent research published in BMJ has shown.

“Contemporary cancer treatment has focused on advancing cure rates while attempting to minimize long term adverse effects,” Daniel A. Mulrooney, MD, of the Division of Cancer Survivorship, Department of Oncology, at St. Jude Children’s Research Hospital, Arlington, Va., and colleagues wrote. “Patterns of exposure to cardiotoxic treatment have changed over time, with fewer children receiving chest directed radiation, with lower doses and smaller volumes for those who do, and an increased use of anthracyclines, albeit with reduced cumulative doses as the risk for late-onset heart failure became apparent.”

Although research has been published on improved survival rates of children who underwent cancer treatment in the 1990s, compared with those who received treatment in the 1980s and 1970s, Dr. Mulrooney and colleagues set out to determine whether cardiac outcomes were reduced as well. They conducted a retrospective study of 23,462 5-year survivors of pediatric cancer, which consisted of leukemia, brain cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal tumors, neuroblastoma, soft-tissue sarcomas, and bone sarcomas diagnosed between January 1970 and December 1999. Researchers compared the cardiac outcomes of the survivors, including heart failure, coronary artery disease, valvular heart disease, pericardial disease, and arrhythmias, with a comparison group of their siblings (n = 5,057) separated by decade. The adult survivors tended to be women (46% vs. 40%) with a median age of 6.1 years at diagnosis and 27.7 years at final follow-up.

Of the 6,193 participants treated for cancer in the 1970s, the 20-year cumulative incidence of heart failure was 0.69%, while the 9,363 participants treated in the 1980s had an incidence of 0.74%, and 7,906 participants in the 1990s had a cumulative incidence of 0.54% over 20 years. The 20-year cumulative incidence for coronary artery disease (CAD) was 0.38% for participants in the 1970s, 0.24% for participants in the 1980s, and 0.19% for participants in the 1990s (P less than .01). Researchers noted the 20-year cumulative incidence of valvular disease, pericardial disease, and arrhythmias did not decrease between the 1970s and the 1990s.

When comparing the rate of major cardiac events of participants in the 1980s and 1990s with those of the 1970s, CAD diagnoses significantly decreased in the 1980s (hazard ratio, 0.65; 95% confidence interval, 0.45-0.92) and 1990s (HR, 0.53; 95% CI, 0.36-0.77), while there was no significant decrease in heart failure or valvular heart disease risk over time. After adjusting for cardiac radiation, overall risk for CAD was attenuated (HR, 0.90; 0.78-1.05), and Hodgkin lymphoma survivors saw the greatest change between unadjusted (HR, 0.77; 95% CI, 0.66-0.89) and adjusted risk (HR, 0.87; 95% CI, 0.69-1.10) when accounting for cardiac radiation.

“While additional longitudinal follow-up is needed to establish whether similar reductions in the cumulative incidence of heart failure can be confirmed in multivariable analysis, these results suggest that efforts to modify cancer therapies in children and promote health surveillance for survivors are beginning to show benefits not only in overall survival but also in late adverse cardiac effects,” the researchers concluded.

In a related editorial, Mike Hawkins, DPhil, of the Centre for Childhood Cancer Survivor Studies, Institute of Applied Health Research at the University of Birmingham (England), and colleagues said that, while measuring cardiotoxicity is important for this patient population, traditional risk factors with independent associations to cardiac outcomes should also be studied. Guidelines on follow-up for these patients are also needed to inform clinical practice, such as those produced by the International Late Effects of Childhood Cancer Guideline Harmonization Group, they added.

“Survivorship issues are extremely important to patients, their families, and their doctors,” they said. “In two research priority setting initiatives in the United Kingdom, detailed consultation with patients with cancer, survivors, families, friends, and healthcare professionals identified further research into the consequences of cancer as a top priority.”

This study was funded by grants from the National Cancer Institute, Cancer Center Support (CORE) to St. Jude Children’s Research Hospital and American Lebanese Syrian Associated Charities. The authors of the study and the editorial reported no relevant conflicts of interest.

SOURCE: Mulrooney A et al. BMJ. 2020. doi: 10.1136/bmj.l6794.

Adult survivors of pediatric cancers appear to be experiencing fewer major cardiac events in adulthood partly because of reduced radiotherapy exposure, especially among survivors of Hodgkin lymphoma, recent research published in BMJ has shown.

“Contemporary cancer treatment has focused on advancing cure rates while attempting to minimize long term adverse effects,” Daniel A. Mulrooney, MD, of the Division of Cancer Survivorship, Department of Oncology, at St. Jude Children’s Research Hospital, Arlington, Va., and colleagues wrote. “Patterns of exposure to cardiotoxic treatment have changed over time, with fewer children receiving chest directed radiation, with lower doses and smaller volumes for those who do, and an increased use of anthracyclines, albeit with reduced cumulative doses as the risk for late-onset heart failure became apparent.”

Although research has been published on improved survival rates of children who underwent cancer treatment in the 1990s, compared with those who received treatment in the 1980s and 1970s, Dr. Mulrooney and colleagues set out to determine whether cardiac outcomes were reduced as well. They conducted a retrospective study of 23,462 5-year survivors of pediatric cancer, which consisted of leukemia, brain cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal tumors, neuroblastoma, soft-tissue sarcomas, and bone sarcomas diagnosed between January 1970 and December 1999. Researchers compared the cardiac outcomes of the survivors, including heart failure, coronary artery disease, valvular heart disease, pericardial disease, and arrhythmias, with a comparison group of their siblings (n = 5,057) separated by decade. The adult survivors tended to be women (46% vs. 40%) with a median age of 6.1 years at diagnosis and 27.7 years at final follow-up.

Of the 6,193 participants treated for cancer in the 1970s, the 20-year cumulative incidence of heart failure was 0.69%, while the 9,363 participants treated in the 1980s had an incidence of 0.74%, and 7,906 participants in the 1990s had a cumulative incidence of 0.54% over 20 years. The 20-year cumulative incidence for coronary artery disease (CAD) was 0.38% for participants in the 1970s, 0.24% for participants in the 1980s, and 0.19% for participants in the 1990s (P less than .01). Researchers noted the 20-year cumulative incidence of valvular disease, pericardial disease, and arrhythmias did not decrease between the 1970s and the 1990s.

When comparing the rate of major cardiac events of participants in the 1980s and 1990s with those of the 1970s, CAD diagnoses significantly decreased in the 1980s (hazard ratio, 0.65; 95% confidence interval, 0.45-0.92) and 1990s (HR, 0.53; 95% CI, 0.36-0.77), while there was no significant decrease in heart failure or valvular heart disease risk over time. After adjusting for cardiac radiation, overall risk for CAD was attenuated (HR, 0.90; 0.78-1.05), and Hodgkin lymphoma survivors saw the greatest change between unadjusted (HR, 0.77; 95% CI, 0.66-0.89) and adjusted risk (HR, 0.87; 95% CI, 0.69-1.10) when accounting for cardiac radiation.

“While additional longitudinal follow-up is needed to establish whether similar reductions in the cumulative incidence of heart failure can be confirmed in multivariable analysis, these results suggest that efforts to modify cancer therapies in children and promote health surveillance for survivors are beginning to show benefits not only in overall survival but also in late adverse cardiac effects,” the researchers concluded.

In a related editorial, Mike Hawkins, DPhil, of the Centre for Childhood Cancer Survivor Studies, Institute of Applied Health Research at the University of Birmingham (England), and colleagues said that, while measuring cardiotoxicity is important for this patient population, traditional risk factors with independent associations to cardiac outcomes should also be studied. Guidelines on follow-up for these patients are also needed to inform clinical practice, such as those produced by the International Late Effects of Childhood Cancer Guideline Harmonization Group, they added.

“Survivorship issues are extremely important to patients, their families, and their doctors,” they said. “In two research priority setting initiatives in the United Kingdom, detailed consultation with patients with cancer, survivors, families, friends, and healthcare professionals identified further research into the consequences of cancer as a top priority.”

This study was funded by grants from the National Cancer Institute, Cancer Center Support (CORE) to St. Jude Children’s Research Hospital and American Lebanese Syrian Associated Charities. The authors of the study and the editorial reported no relevant conflicts of interest.

SOURCE: Mulrooney A et al. BMJ. 2020. doi: 10.1136/bmj.l6794.

When Elizabeth Wurtzel wrote “Prozac Nation,” an autobiographical account published in 1994 of her experience with depression and psychiatric medications, she helped shift the public dialogue about mental illness, and in doing so chipped away at the stigma that continues to haunt many of our patients.

Ms. Wurtzel, who died recently at age 52, wrote about depression passionately and matter-of-factly.

As she stated in “Prozac Nation”: “Depression was the loneliest &*%$ thing on earth. There were no halfway houses for depressives, no Depression Anonymous meetings that I knew of. Yes, of course, there were mental hospitals like McLean and Bellevue and Payne Whitney and the Menninger Clinic, but I couldn’t hope to end up in one of those places unless I made a suicide attempt serious enough to warrant oxygen or stitches or a stomach pump.

“I used to wish – to pray to God for the courage and strength – that I’d have the guts not to get better, but to slit my wrists and get a whole lot worse so I could land in some mental ward, where real help might have been possible.”

Think of where the public consciousness was in 1994. Peter D. Kramer, MD, had started the conversation on Prozac a year earlier with his book, “Listening to Prozac,” Kurt Cobain died by suicide in 1994, and 2 years later President Bill Clinton signed the Personal Responsibility and Work Opportunity Reconciliation Act, a law that “reformed” welfare and some say made it more difficult for low-income Americans to secure psychiatric and addiction services (Milbank Q. 2005 Mar;83[1]:65-99).

Prozac, as we know, was the first SSRI on the market in the late 1980s and was hailed as a major medication breakthrough in the treatment of depression. It lacked the side effects of the tricyclic antidepressants of previous years and did not have the potentially dangerous food restrictions associated with monoamine oxidase inhibitors.

Interestingly, the major reviews of Ms. Wurtzel’s book, mainly written by men, were negative. Those reviews focused more on the lifestyle of Ms. Wurtzel, her introspection, and how difficult life was for her, rather than the importance of the book. To me, her writing skills were exceptional, as was her willingness to put her lifestyle and suffering on the line.

The literary critics failed to recognize the book’s importance in unmasking the massive denial of mental illnesses and what Ms. Wurtzel was trying to get across. There have been many successful male writers over the years whose lives were difficult and replete with emotional pain and suffering, and their work was lauded. Regardless of the reviews’ negativity, readers found her book open and enlightening, making it a bestseller – thus paving the way for better and more-open discussion of mental disorders. It also became a touchstone in discussions of antidepressants in the psychiatric literature (Lancet. 1998 Sep 26. doi: 10.1016/S0140-6736(98)08418-9; Lancet. 2015 Oct 1. doi: 10.1016/S2215-0366[15]00430-7; and Biol Psychiatry. 2018 Dec 1;84[11]:e73-5).

However, unfortunately, the stigma still exists on many levels, often starting with the medical profession itself. In my experience over the years in teaching and supervising medical students, many of those not interested in becoming a psychiatrist all too often could not wait for their psych rotation to be over. Generally, they did not take the rotation seriously. I’ve even heard students making light of the delusions and paranoia seen in the suffering of acutely ill patients.

We can take this even further within the profession. I have had many referrals from far too many extremely competent physicians, across many medical specialties, who would refer to their patient as “sort of crazy.” Those physicians want the best for their patients, clearly, in making the referral, but they need to change their thinking and, therefore, their vocabulary about mental disorders. I’d like to see these physicians be more respectful of our patients – just as I would be if I were referring a patient complaining of fatigue and joint pain to a general internist or rheumatologist.

I once knew a brilliant orthopedic surgeon who, when he made a referral, would sit down with the patient and clearly explain why they were not crazy but had an anxiety or a mood problem that he didn’t treat but had a person to refer to who could help. Likewise, I know an ophthalmologist who tells his patients with some emotional symptoms that they are experiencing a difficult situation and would benefit from help that he is not able to provide but could be resolved with another type of specialist who works with their “difficulties.” We clearly need more docs like this who go out of their specialty to explain what patients might need – despite the administrative burden exacted by EMRs on doctors’ time and energy.

As we grow more tolerant in our culture and eliminate distasteful words about people and groups, maybe we should try and avoid the word crazy – even in our general vocabulary. Furthermore, in social situations, while out to dinner with friends, at the gym, or even while in the workplace, just as we may refer to our primary care doc as the best or report we have the best cardiologist or dermatologist, we rarely hear someone being open about the best psychiatrist, psychologist, or therapist in the same manner.

“If ‘Prozac Nation’ has any particular purpose,” she wrote in the afterword, “it would be to come out and say that clinical depression is a real problem, that it ruins lives, that it ends lives, that it very nearly ended my life, that it afflicts many, many people, many very bright and worthy and thoughtful and caring people, people who could probably save the world or at the very least do it some real good.” Those people are our patients, and medicine should take the lead in working further to destigmatize mental illness.

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

When Elizabeth Wurtzel wrote “Prozac Nation,” an autobiographical account published in 1994 of her experience with depression and psychiatric medications, she helped shift the public dialogue about mental illness, and in doing so chipped away at the stigma that continues to haunt many of our patients.

Ms. Wurtzel, who died recently at age 52, wrote about depression passionately and matter-of-factly.

As she stated in “Prozac Nation”: “Depression was the loneliest &*%$ thing on earth. There were no halfway houses for depressives, no Depression Anonymous meetings that I knew of. Yes, of course, there were mental hospitals like McLean and Bellevue and Payne Whitney and the Menninger Clinic, but I couldn’t hope to end up in one of those places unless I made a suicide attempt serious enough to warrant oxygen or stitches or a stomach pump.

“I used to wish – to pray to God for the courage and strength – that I’d have the guts not to get better, but to slit my wrists and get a whole lot worse so I could land in some mental ward, where real help might have been possible.”

Think of where the public consciousness was in 1994. Peter D. Kramer, MD, had started the conversation on Prozac a year earlier with his book, “Listening to Prozac,” Kurt Cobain died by suicide in 1994, and 2 years later President Bill Clinton signed the Personal Responsibility and Work Opportunity Reconciliation Act, a law that “reformed” welfare and some say made it more difficult for low-income Americans to secure psychiatric and addiction services (Milbank Q. 2005 Mar;83[1]:65-99).

Prozac, as we know, was the first SSRI on the market in the late 1980s and was hailed as a major medication breakthrough in the treatment of depression. It lacked the side effects of the tricyclic antidepressants of previous years and did not have the potentially dangerous food restrictions associated with monoamine oxidase inhibitors.

Interestingly, the major reviews of Ms. Wurtzel’s book, mainly written by men, were negative. Those reviews focused more on the lifestyle of Ms. Wurtzel, her introspection, and how difficult life was for her, rather than the importance of the book. To me, her writing skills were exceptional, as was her willingness to put her lifestyle and suffering on the line.

The literary critics failed to recognize the book’s importance in unmasking the massive denial of mental illnesses and what Ms. Wurtzel was trying to get across. There have been many successful male writers over the years whose lives were difficult and replete with emotional pain and suffering, and their work was lauded. Regardless of the reviews’ negativity, readers found her book open and enlightening, making it a bestseller – thus paving the way for better and more-open discussion of mental disorders. It also became a touchstone in discussions of antidepressants in the psychiatric literature (Lancet. 1998 Sep 26. doi: 10.1016/S0140-6736(98)08418-9; Lancet. 2015 Oct 1. doi: 10.1016/S2215-0366[15]00430-7; and Biol Psychiatry. 2018 Dec 1;84[11]:e73-5).

However, unfortunately, the stigma still exists on many levels, often starting with the medical profession itself. In my experience over the years in teaching and supervising medical students, many of those not interested in becoming a psychiatrist all too often could not wait for their psych rotation to be over. Generally, they did not take the rotation seriously. I’ve even heard students making light of the delusions and paranoia seen in the suffering of acutely ill patients.

We can take this even further within the profession. I have had many referrals from far too many extremely competent physicians, across many medical specialties, who would refer to their patient as “sort of crazy.” Those physicians want the best for their patients, clearly, in making the referral, but they need to change their thinking and, therefore, their vocabulary about mental disorders. I’d like to see these physicians be more respectful of our patients – just as I would be if I were referring a patient complaining of fatigue and joint pain to a general internist or rheumatologist.

I once knew a brilliant orthopedic surgeon who, when he made a referral, would sit down with the patient and clearly explain why they were not crazy but had an anxiety or a mood problem that he didn’t treat but had a person to refer to who could help. Likewise, I know an ophthalmologist who tells his patients with some emotional symptoms that they are experiencing a difficult situation and would benefit from help that he is not able to provide but could be resolved with another type of specialist who works with their “difficulties.” We clearly need more docs like this who go out of their specialty to explain what patients might need – despite the administrative burden exacted by EMRs on doctors’ time and energy.

As we grow more tolerant in our culture and eliminate distasteful words about people and groups, maybe we should try and avoid the word crazy – even in our general vocabulary. Furthermore, in social situations, while out to dinner with friends, at the gym, or even while in the workplace, just as we may refer to our primary care doc as the best or report we have the best cardiologist or dermatologist, we rarely hear someone being open about the best psychiatrist, psychologist, or therapist in the same manner.

“If ‘Prozac Nation’ has any particular purpose,” she wrote in the afterword, “it would be to come out and say that clinical depression is a real problem, that it ruins lives, that it ends lives, that it very nearly ended my life, that it afflicts many, many people, many very bright and worthy and thoughtful and caring people, people who could probably save the world or at the very least do it some real good.” Those people are our patients, and medicine should take the lead in working further to destigmatize mental illness.

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

When Elizabeth Wurtzel wrote “Prozac Nation,” an autobiographical account published in 1994 of her experience with depression and psychiatric medications, she helped shift the public dialogue about mental illness, and in doing so chipped away at the stigma that continues to haunt many of our patients.

Ms. Wurtzel, who died recently at age 52, wrote about depression passionately and matter-of-factly.

As she stated in “Prozac Nation”: “Depression was the loneliest &*%$ thing on earth. There were no halfway houses for depressives, no Depression Anonymous meetings that I knew of. Yes, of course, there were mental hospitals like McLean and Bellevue and Payne Whitney and the Menninger Clinic, but I couldn’t hope to end up in one of those places unless I made a suicide attempt serious enough to warrant oxygen or stitches or a stomach pump.

“I used to wish – to pray to God for the courage and strength – that I’d have the guts not to get better, but to slit my wrists and get a whole lot worse so I could land in some mental ward, where real help might have been possible.”

Think of where the public consciousness was in 1994. Peter D. Kramer, MD, had started the conversation on Prozac a year earlier with his book, “Listening to Prozac,” Kurt Cobain died by suicide in 1994, and 2 years later President Bill Clinton signed the Personal Responsibility and Work Opportunity Reconciliation Act, a law that “reformed” welfare and some say made it more difficult for low-income Americans to secure psychiatric and addiction services (Milbank Q. 2005 Mar;83[1]:65-99).

Prozac, as we know, was the first SSRI on the market in the late 1980s and was hailed as a major medication breakthrough in the treatment of depression. It lacked the side effects of the tricyclic antidepressants of previous years and did not have the potentially dangerous food restrictions associated with monoamine oxidase inhibitors.

Interestingly, the major reviews of Ms. Wurtzel’s book, mainly written by men, were negative. Those reviews focused more on the lifestyle of Ms. Wurtzel, her introspection, and how difficult life was for her, rather than the importance of the book. To me, her writing skills were exceptional, as was her willingness to put her lifestyle and suffering on the line.

The literary critics failed to recognize the book’s importance in unmasking the massive denial of mental illnesses and what Ms. Wurtzel was trying to get across. There have been many successful male writers over the years whose lives were difficult and replete with emotional pain and suffering, and their work was lauded. Regardless of the reviews’ negativity, readers found her book open and enlightening, making it a bestseller – thus paving the way for better and more-open discussion of mental disorders. It also became a touchstone in discussions of antidepressants in the psychiatric literature (Lancet. 1998 Sep 26. doi: 10.1016/S0140-6736(98)08418-9; Lancet. 2015 Oct 1. doi: 10.1016/S2215-0366[15]00430-7; and Biol Psychiatry. 2018 Dec 1;84[11]:e73-5).

However, unfortunately, the stigma still exists on many levels, often starting with the medical profession itself. In my experience over the years in teaching and supervising medical students, many of those not interested in becoming a psychiatrist all too often could not wait for their psych rotation to be over. Generally, they did not take the rotation seriously. I’ve even heard students making light of the delusions and paranoia seen in the suffering of acutely ill patients.

We can take this even further within the profession. I have had many referrals from far too many extremely competent physicians, across many medical specialties, who would refer to their patient as “sort of crazy.” Those physicians want the best for their patients, clearly, in making the referral, but they need to change their thinking and, therefore, their vocabulary about mental disorders. I’d like to see these physicians be more respectful of our patients – just as I would be if I were referring a patient complaining of fatigue and joint pain to a general internist or rheumatologist.

I once knew a brilliant orthopedic surgeon who, when he made a referral, would sit down with the patient and clearly explain why they were not crazy but had an anxiety or a mood problem that he didn’t treat but had a person to refer to who could help. Likewise, I know an ophthalmologist who tells his patients with some emotional symptoms that they are experiencing a difficult situation and would benefit from help that he is not able to provide but could be resolved with another type of specialist who works with their “difficulties.” We clearly need more docs like this who go out of their specialty to explain what patients might need – despite the administrative burden exacted by EMRs on doctors’ time and energy.

As we grow more tolerant in our culture and eliminate distasteful words about people and groups, maybe we should try and avoid the word crazy – even in our general vocabulary. Furthermore, in social situations, while out to dinner with friends, at the gym, or even while in the workplace, just as we may refer to our primary care doc as the best or report we have the best cardiologist or dermatologist, we rarely hear someone being open about the best psychiatrist, psychologist, or therapist in the same manner.

“If ‘Prozac Nation’ has any particular purpose,” she wrote in the afterword, “it would be to come out and say that clinical depression is a real problem, that it ruins lives, that it ends lives, that it very nearly ended my life, that it afflicts many, many people, many very bright and worthy and thoughtful and caring people, people who could probably save the world or at the very least do it some real good.” Those people are our patients, and medicine should take the lead in working further to destigmatize mental illness.

Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.

“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.

The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.

Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.

There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.

“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.

The study was sponsored by the European Research Council. The authors had no relevant disclosures.

[email protected]

SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.

About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.

“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.

The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.

Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.

There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.

“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.

The study was sponsored by the European Research Council. The authors had no relevant disclosures.

[email protected]

SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.

About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.

“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.

The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.

Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.

There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.

“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.

The study was sponsored by the European Research Council. The authors had no relevant disclosures.

[email protected]

SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.

Insomnia is a common problem for veterans with PTSD, and the frequency of sleep problems is associated with increasing severity of PTSD, according to a study published in of the Journal of Traumatic Stress.

Raymond C. Rosen, PhD, of the New England Research Institutes, Watertown, Mass., and coauthors wrote that exploration of the relationship between PTSD and insomnia is complicated by the fact that it can be difficult to separate out disturbed sleep from other elements of PTSD, and because of the presence of other comorbidities in veterans, such as depression and traumatic brain injury.

The cohort study involved 1,643 veterans – roughly equal numbers of women and men – of Iraq and Afghanistan. Around two-thirds of the cohort had a diagnosis of PTSD. The participants completed a self-administered survey online or by mail, and were also assessed in a telephone interview, then followed up within 2-4 years.

While the prevalence of sleep problems was high across the cohort, the study found that 74% of participants with PTSD at baseline said they had experienced sleep difficulties for at least half of the previous 30 days, and one-third had been prescribed for a sedative-hypnotic drug in the past year.

In comparison, veterans without PTSD had fewer sleep problems and were prescribed significantly fewer sedative-hypnotic drugs.

The prevalence of sleep problems was similar in men and women with PTSD, although women had significantly higher rates of sedative-hypnotic prescriptions than men (40.4% vs. 35%, P = .006). A similar gender difference in prescription rates was seen in individuals without PTSD.

The study found that, although there was only a weak association between the severity of PTSD symptoms at baseline and the frequency of sleep problems at follow-up, there was a stronger association in reverse. Veterans with a higher frequency of sleep problems at baseline showed a significant increase in PTSD symptoms at follow-up.

The authors commented that this was in line with previous studies finding a similar effect of sleep disturbance on PTSD severity, both in military personnel and civilians.

“From a neurobiological perspective, it has been proposed that chronic sleep loss can lead to emotional dysregulation or heightened autonomic arousal, which in turn may be a risk factor for PTSD in trauma-exposed individuals,” they wrote. “It has also been proposed that prior sleep disturbance may attenuate the effects of extinction learning, leading to more enduring or severe symptoms in trauma-exposed individuals with concomitant sleep disorders.”

Given this association, the authors called for more attention to be given to identifying, diagnosing, and treating sleep disorders in veterans with and without PTSD.

The authors noted that they did not have access to polysomnographic data for participants, and were also unable to assess the prevalence, frequency, or intensity of nightmares in the cohort.

The study was supported by the Department of Defense. Conflict of interest disclosures were unavailable.

SOURCE: Rosen RC et al. J Trauma Stress. 2020;32:936-45.

Insomnia is a common problem for veterans with PTSD, and the frequency of sleep problems is associated with increasing severity of PTSD, according to a study published in of the Journal of Traumatic Stress.

Raymond C. Rosen, PhD, of the New England Research Institutes, Watertown, Mass., and coauthors wrote that exploration of the relationship between PTSD and insomnia is complicated by the fact that it can be difficult to separate out disturbed sleep from other elements of PTSD, and because of the presence of other comorbidities in veterans, such as depression and traumatic brain injury.

The cohort study involved 1,643 veterans – roughly equal numbers of women and men – of Iraq and Afghanistan. Around two-thirds of the cohort had a diagnosis of PTSD. The participants completed a self-administered survey online or by mail, and were also assessed in a telephone interview, then followed up within 2-4 years.

While the prevalence of sleep problems was high across the cohort, the study found that 74% of participants with PTSD at baseline said they had experienced sleep difficulties for at least half of the previous 30 days, and one-third had been prescribed for a sedative-hypnotic drug in the past year.

In comparison, veterans without PTSD had fewer sleep problems and were prescribed significantly fewer sedative-hypnotic drugs.

The prevalence of sleep problems was similar in men and women with PTSD, although women had significantly higher rates of sedative-hypnotic prescriptions than men (40.4% vs. 35%, P = .006). A similar gender difference in prescription rates was seen in individuals without PTSD.

The study found that, although there was only a weak association between the severity of PTSD symptoms at baseline and the frequency of sleep problems at follow-up, there was a stronger association in reverse. Veterans with a higher frequency of sleep problems at baseline showed a significant increase in PTSD symptoms at follow-up.

The authors commented that this was in line with previous studies finding a similar effect of sleep disturbance on PTSD severity, both in military personnel and civilians.

“From a neurobiological perspective, it has been proposed that chronic sleep loss can lead to emotional dysregulation or heightened autonomic arousal, which in turn may be a risk factor for PTSD in trauma-exposed individuals,” they wrote. “It has also been proposed that prior sleep disturbance may attenuate the effects of extinction learning, leading to more enduring or severe symptoms in trauma-exposed individuals with concomitant sleep disorders.”

Given this association, the authors called for more attention to be given to identifying, diagnosing, and treating sleep disorders in veterans with and without PTSD.

The authors noted that they did not have access to polysomnographic data for participants, and were also unable to assess the prevalence, frequency, or intensity of nightmares in the cohort.

The study was supported by the Department of Defense. Conflict of interest disclosures were unavailable.

SOURCE: Rosen RC et al. J Trauma Stress. 2020;32:936-45.

Insomnia is a common problem for veterans with PTSD, and the frequency of sleep problems is associated with increasing severity of PTSD, according to a study published in of the Journal of Traumatic Stress.

Raymond C. Rosen, PhD, of the New England Research Institutes, Watertown, Mass., and coauthors wrote that exploration of the relationship between PTSD and insomnia is complicated by the fact that it can be difficult to separate out disturbed sleep from other elements of PTSD, and because of the presence of other comorbidities in veterans, such as depression and traumatic brain injury.

The cohort study involved 1,643 veterans – roughly equal numbers of women and men – of Iraq and Afghanistan. Around two-thirds of the cohort had a diagnosis of PTSD. The participants completed a self-administered survey online or by mail, and were also assessed in a telephone interview, then followed up within 2-4 years.

While the prevalence of sleep problems was high across the cohort, the study found that 74% of participants with PTSD at baseline said they had experienced sleep difficulties for at least half of the previous 30 days, and one-third had been prescribed for a sedative-hypnotic drug in the past year.

In comparison, veterans without PTSD had fewer sleep problems and were prescribed significantly fewer sedative-hypnotic drugs.

The prevalence of sleep problems was similar in men and women with PTSD, although women had significantly higher rates of sedative-hypnotic prescriptions than men (40.4% vs. 35%, P = .006). A similar gender difference in prescription rates was seen in individuals without PTSD.

The study found that, although there was only a weak association between the severity of PTSD symptoms at baseline and the frequency of sleep problems at follow-up, there was a stronger association in reverse. Veterans with a higher frequency of sleep problems at baseline showed a significant increase in PTSD symptoms at follow-up.

The authors commented that this was in line with previous studies finding a similar effect of sleep disturbance on PTSD severity, both in military personnel and civilians.

“From a neurobiological perspective, it has been proposed that chronic sleep loss can lead to emotional dysregulation or heightened autonomic arousal, which in turn may be a risk factor for PTSD in trauma-exposed individuals,” they wrote. “It has also been proposed that prior sleep disturbance may attenuate the effects of extinction learning, leading to more enduring or severe symptoms in trauma-exposed individuals with concomitant sleep disorders.”

Given this association, the authors called for more attention to be given to identifying, diagnosing, and treating sleep disorders in veterans with and without PTSD.

The authors noted that they did not have access to polysomnographic data for participants, and were also unable to assess the prevalence, frequency, or intensity of nightmares in the cohort.

The study was supported by the Department of Defense. Conflict of interest disclosures were unavailable.

SOURCE: Rosen RC et al. J Trauma Stress. 2020;32:936-45.

A new study of claims-based data has found that the incidence and prevalence of nontuberculous mycobacterial (NTM) lung disease is increasing in most states.

Dr. George Kubica/CDC

To assess the NTM lung disease burden on a national level, Kevin L. Winthrop, MD, of Oregon Health & Science University, Portland, and associates analyzed patient data from a U.S. managed care claims database between 2008 and 2015. Their findings were published in the Annals of the American Thoracic Society.

A case of NTM lung disease was defined as a patient with at least two medical claims with the disease’s diagnostic codes – 031.0 and A31.0 – that were at least 30 days apart. Of the 74,984,596 beneficiaries in the database, 9,476 met the case definition for NTM lung disease; 69% (n = 6,530) were women.

From 2008 to 2015, the annual incidence of NTM lung disease increased from 3.13 (95% confidence interval, 2.88-3.40) to 4.73 (95% CI, 4.43-5.05) per 100,000 person-years, with the average rate of yearly change being +5.2% (95% CI, 4.0%-6.4%; P less than .01).The annual prevalence increased from 6.78 (95% CI, 6.45-7.14) to 11.70 (95% CI, 11.26-12.16) per 100,000 persons, with the average rate of yearly change being +7.5% (95% CI, 6.7-8.2%; P less than .01).

The majority of NTM lung disease in the United States is caused by Mycobacterium avium complex (17), although other species such as M. abscessus, M. kansasii, M. xenopi, and others contribute to this disease burden.

“It’s a classic chicken-or-egg scenario,” said Sachin Gupta, MD, a pulmonologist in San Francisco, in regard to the rising numbers. “Increased awareness of NTM lung disease is, in part, why we’re seeing prevalence and incidence go up. And yet the disease itself may also be growing in clusters and pockets, as the data show, in various places across the nation.

“The worrisome aspect here,” he added, “is that future studies will likely show that, as incidence is increasing, mortality is increasing as well. That speaks to the challenges with these bugs: Very hard to diagnose, very hard to treat.”

The authors acknowledged their study’s limitations, including the lack of microbiologic or radiographic confirmation of the NTM infection and the inherent shortcomings of claims data–based studies overall. They did note a previous report, however, that “claims-based case identification has a high positive predictive value of approximately 82% for NTM lung disease.”

The study was funded by Insmed; the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases; and the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.

SOURCE: Winthrop KL et al. Ann Am Thorac Soc. 2019 Dec 13. doi: 10.1513/AnnalsATS.201804-236OC.

A new study of claims-based data has found that the incidence and prevalence of nontuberculous mycobacterial (NTM) lung disease is increasing in most states.

Dr. George Kubica/CDC

To assess the NTM lung disease burden on a national level, Kevin L. Winthrop, MD, of Oregon Health & Science University, Portland, and associates analyzed patient data from a U.S. managed care claims database between 2008 and 2015. Their findings were published in the Annals of the American Thoracic Society.

A case of NTM lung disease was defined as a patient with at least two medical claims with the disease’s diagnostic codes – 031.0 and A31.0 – that were at least 30 days apart. Of the 74,984,596 beneficiaries in the database, 9,476 met the case definition for NTM lung disease; 69% (n = 6,530) were women.

From 2008 to 2015, the annual incidence of NTM lung disease increased from 3.13 (95% confidence interval, 2.88-3.40) to 4.73 (95% CI, 4.43-5.05) per 100,000 person-years, with the average rate of yearly change being +5.2% (95% CI, 4.0%-6.4%; P less than .01).The annual prevalence increased from 6.78 (95% CI, 6.45-7.14) to 11.70 (95% CI, 11.26-12.16) per 100,000 persons, with the average rate of yearly change being +7.5% (95% CI, 6.7-8.2%; P less than .01).

The majority of NTM lung disease in the United States is caused by Mycobacterium avium complex (17), although other species such as M. abscessus, M. kansasii, M. xenopi, and others contribute to this disease burden.

“It’s a classic chicken-or-egg scenario,” said Sachin Gupta, MD, a pulmonologist in San Francisco, in regard to the rising numbers. “Increased awareness of NTM lung disease is, in part, why we’re seeing prevalence and incidence go up. And yet the disease itself may also be growing in clusters and pockets, as the data show, in various places across the nation.

“The worrisome aspect here,” he added, “is that future studies will likely show that, as incidence is increasing, mortality is increasing as well. That speaks to the challenges with these bugs: Very hard to diagnose, very hard to treat.”

The authors acknowledged their study’s limitations, including the lack of microbiologic or radiographic confirmation of the NTM infection and the inherent shortcomings of claims data–based studies overall. They did note a previous report, however, that “claims-based case identification has a high positive predictive value of approximately 82% for NTM lung disease.”

The study was funded by Insmed; the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases; and the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.

SOURCE: Winthrop KL et al. Ann Am Thorac Soc. 2019 Dec 13. doi: 10.1513/AnnalsATS.201804-236OC.

A new study of claims-based data has found that the incidence and prevalence of nontuberculous mycobacterial (NTM) lung disease is increasing in most states.

Dr. George Kubica/CDC

To assess the NTM lung disease burden on a national level, Kevin L. Winthrop, MD, of Oregon Health & Science University, Portland, and associates analyzed patient data from a U.S. managed care claims database between 2008 and 2015. Their findings were published in the Annals of the American Thoracic Society.

A case of NTM lung disease was defined as a patient with at least two medical claims with the disease’s diagnostic codes – 031.0 and A31.0 – that were at least 30 days apart. Of the 74,984,596 beneficiaries in the database, 9,476 met the case definition for NTM lung disease; 69% (n = 6,530) were women.

From 2008 to 2015, the annual incidence of NTM lung disease increased from 3.13 (95% confidence interval, 2.88-3.40) to 4.73 (95% CI, 4.43-5.05) per 100,000 person-years, with the average rate of yearly change being +5.2% (95% CI, 4.0%-6.4%; P less than .01).The annual prevalence increased from 6.78 (95% CI, 6.45-7.14) to 11.70 (95% CI, 11.26-12.16) per 100,000 persons, with the average rate of yearly change being +7.5% (95% CI, 6.7-8.2%; P less than .01).

The majority of NTM lung disease in the United States is caused by Mycobacterium avium complex (17), although other species such as M. abscessus, M. kansasii, M. xenopi, and others contribute to this disease burden.

“It’s a classic chicken-or-egg scenario,” said Sachin Gupta, MD, a pulmonologist in San Francisco, in regard to the rising numbers. “Increased awareness of NTM lung disease is, in part, why we’re seeing prevalence and incidence go up. And yet the disease itself may also be growing in clusters and pockets, as the data show, in various places across the nation.

“The worrisome aspect here,” he added, “is that future studies will likely show that, as incidence is increasing, mortality is increasing as well. That speaks to the challenges with these bugs: Very hard to diagnose, very hard to treat.”

The authors acknowledged their study’s limitations, including the lack of microbiologic or radiographic confirmation of the NTM infection and the inherent shortcomings of claims data–based studies overall. They did note a previous report, however, that “claims-based case identification has a high positive predictive value of approximately 82% for NTM lung disease.”

The study was funded by Insmed; the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases; and the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.

SOURCE: Winthrop KL et al. Ann Am Thorac Soc. 2019 Dec 13. doi: 10.1513/AnnalsATS.201804-236OC.

LA JOLLA, CALIF. – The first time that legendary actor Alan Alda conducted an interview for “Scientific American Frontiers” on PBS, an award-winning series that ran for more than a decade, he remembers learning a lesson in humility.

Doug Brunk/MDedge News

“I wasn’t as smart as I thought I was,” he told a crowd of largely scientists and medical professionals who gathered in a small auditorium on the campus of Scripps Research on Jan. 16, 2020. “I didn’t realize the value of ignorance. I have a natural supply of it. I began to use it and say [to interviewees]: ‘I don’t understand what that means.’ Sometimes it would be basic physics and they’d look at me like I was a school child. I am a very curious person. What I discovered was, I was bringing out their humanity by my own curiosity, by the way I related to them, which I developed through studying improvisation as an actor, and relating as an actor to other actors.”

Mr. Alda, 83, appeared on the research campus to announce that Scripps Research is the new West Coast home of Alda Communication Training, which will work in tandem with the Alan Alda Center for Communicating Science at the State University of New York at Stony Brook, a nonprofit organization that Mr. Alda helped found in 2009.
 

Immersive training experience

“This will be a center where people can come to get training in effective communication,” said Mr. Alda, who is the winner of six Emmy Awards and six Golden Globe awards. “It’s an experiential kind of training. We don’t give tips. We don’t give lectures. We put you through exercises that are fun and actually make you laugh, but turn you into a better communicator, so you’re better able to connect to the people you’re talking to.”

To date, the Alan Alda Center for Communicating Science has trained more than 15,000 scientific leaders in the United States and other countries. The location at Scripps Research makes it more convenient for West Coast–based researchers and industry leaders to participate. “One of the things we wished, for years, we had was a place where we could train scientists and researchers and medical professionals all up and down the West Coast,” he said.

Recently, more than 30 of Scripps Research scientists participated in Mr. Alda’s training program, an immersive and engaging experience that helps participants learn to empathize with an audience and present their work in a way that connects with different stakeholders. The skills and strategies can help participants relate to prospective investors and philanthropists, government officials, members of the media, peers across scientific disciplines, and the general public.

Earlier in the day that he spoke on the Scripps campus, Mr. Alda encountered some of the Scripps researchers who had participated in that training. “One group of scientists came in and we shook hands,” he said. “They introduced themselves and said: ‘We’re working on infectious diseases.’ I said: ‘Oh my God; I just shook hands with you!’ No matter what I asked them, they had a clear way to express what they did. Then I realized they had studied with Alda Communications.”
 

Why communication matters

During the early stages of forming what became the Alan Alda Center for Communicating Science, one Nobel Prize winner at a major university dismissed the importance of improving the communication skills of young scientists. “He said to me: ‘We don’t have time for that; we have too much science to teach,’ ” said Mr. Alda, who played Army surgeon “Hawkeye” Pierce on the TV series “M*A*S*H”. “But communication is the essence of science. How can you do science unless you communicate with other scientists? There’s a stereotype that scientists are not as good at communicating as other people are. It’s true that they often speak a language that a lot of us don’t understand, but we all speak a language that is hard for other people to understand if we know something in great depth. We want to tell all the details; we want to speak in our special language because it makes us feel good.”

He underscored the importance of scientists being able to effectively communicate with the general public, “because the public needs to understand how important science is to their lives. It matters because at a place like [Scripps Research], understanding how nature works is put to work to keep our health secure.” Members of the public, he continued, “are busy living their lives; they’re busy working and bringing up their children. They haven’t spent 20, 30, 40 years devoted to a single aspect of nature the way scientists have. We can’t expect them to know as much as professional scientists, so we have to help them understand it. I hope we find ways to increase curiosity. I don’t know how to do that. I wish somebody would do a study on it, how you can take someone with a modicum of curiosity and help them enlarge it so it gives them the pleasure of discovering things about nature or understanding things about nature that other people don’t discover. Curiosity is the key to staying alive. That would bring us to a point of more people understanding science.”

Cultivating a sense of responsibility is another key to effective communication. “It’s the job of the person leading the discussion to make clear to the person listening,” Mr. Alda said. “You get the impression that ‘this person is my responsibility. I have to take care of them, so they understand what’s going on.’ ”
 

Parkinson’s disease diagnosis

During a question-and-answer session, Mr. Alda opened up about his Parkinson’s disease, which he said was diagnosed about 5 years ago. In 2018, he decided to speak publicly about his diagnosis for the first time.

“The reason was that I wanted to communicate to people who had recently been diagnosed not to believe or give into the stereotype that when you get a diagnosis, your life is over,” said Mr. Alda, who received the Public Welfare Medal from the National Academy of Sciences in 2016. “Under the burden of that belief, some people won’t tell their family or workplace colleagues. There are exercises you can do and medications you can take to prolong the time it takes before Parkinson’s gets much more serious. It’s not to diminish the fact that it can get really bad; but to think that your life is over as soon as you get a diagnosis is wrong.”

He added: “I’ve gone 5 years and I’m almost busier than I’ve ever been. I’m getting a lot accomplished and I look forward to I don’t know how many years. As long as I have them, I’m going to be grateful. It’s amazing how great it feels not to keep the diagnosis a secret.”

The first 2-day training session at Scripps Research will be held in June 2020. Additional sessions are scheduled to take place in October and December. Registration is available at aldacommunicationtraining.com/workshops.

[email protected]

LA JOLLA, CALIF. – The first time that legendary actor Alan Alda conducted an interview for “Scientific American Frontiers” on PBS, an award-winning series that ran for more than a decade, he remembers learning a lesson in humility.

Doug Brunk/MDedge News

“I wasn’t as smart as I thought I was,” he told a crowd of largely scientists and medical professionals who gathered in a small auditorium on the campus of Scripps Research on Jan. 16, 2020. “I didn’t realize the value of ignorance. I have a natural supply of it. I began to use it and say [to interviewees]: ‘I don’t understand what that means.’ Sometimes it would be basic physics and they’d look at me like I was a school child. I am a very curious person. What I discovered was, I was bringing out their humanity by my own curiosity, by the way I related to them, which I developed through studying improvisation as an actor, and relating as an actor to other actors.”

Mr. Alda, 83, appeared on the research campus to announce that Scripps Research is the new West Coast home of Alda Communication Training, which will work in tandem with the Alan Alda Center for Communicating Science at the State University of New York at Stony Brook, a nonprofit organization that Mr. Alda helped found in 2009.
 

Immersive training experience

“This will be a center where people can come to get training in effective communication,” said Mr. Alda, who is the winner of six Emmy Awards and six Golden Globe awards. “It’s an experiential kind of training. We don’t give tips. We don’t give lectures. We put you through exercises that are fun and actually make you laugh, but turn you into a better communicator, so you’re better able to connect to the people you’re talking to.”

To date, the Alan Alda Center for Communicating Science has trained more than 15,000 scientific leaders in the United States and other countries. The location at Scripps Research makes it more convenient for West Coast–based researchers and industry leaders to participate. “One of the things we wished, for years, we had was a place where we could train scientists and researchers and medical professionals all up and down the West Coast,” he said.

Recently, more than 30 of Scripps Research scientists participated in Mr. Alda’s training program, an immersive and engaging experience that helps participants learn to empathize with an audience and present their work in a way that connects with different stakeholders. The skills and strategies can help participants relate to prospective investors and philanthropists, government officials, members of the media, peers across scientific disciplines, and the general public.

Earlier in the day that he spoke on the Scripps campus, Mr. Alda encountered some of the Scripps researchers who had participated in that training. “One group of scientists came in and we shook hands,” he said. “They introduced themselves and said: ‘We’re working on infectious diseases.’ I said: ‘Oh my God; I just shook hands with you!’ No matter what I asked them, they had a clear way to express what they did. Then I realized they had studied with Alda Communications.”
 

Why communication matters

During the early stages of forming what became the Alan Alda Center for Communicating Science, one Nobel Prize winner at a major university dismissed the importance of improving the communication skills of young scientists. “He said to me: ‘We don’t have time for that; we have too much science to teach,’ ” said Mr. Alda, who played Army surgeon “Hawkeye” Pierce on the TV series “M*A*S*H”. “But communication is the essence of science. How can you do science unless you communicate with other scientists? There’s a stereotype that scientists are not as good at communicating as other people are. It’s true that they often speak a language that a lot of us don’t understand, but we all speak a language that is hard for other people to understand if we know something in great depth. We want to tell all the details; we want to speak in our special language because it makes us feel good.”

He underscored the importance of scientists being able to effectively communicate with the general public, “because the public needs to understand how important science is to their lives. It matters because at a place like [Scripps Research], understanding how nature works is put to work to keep our health secure.” Members of the public, he continued, “are busy living their lives; they’re busy working and bringing up their children. They haven’t spent 20, 30, 40 years devoted to a single aspect of nature the way scientists have. We can’t expect them to know as much as professional scientists, so we have to help them understand it. I hope we find ways to increase curiosity. I don’t know how to do that. I wish somebody would do a study on it, how you can take someone with a modicum of curiosity and help them enlarge it so it gives them the pleasure of discovering things about nature or understanding things about nature that other people don’t discover. Curiosity is the key to staying alive. That would bring us to a point of more people understanding science.”

Cultivating a sense of responsibility is another key to effective communication. “It’s the job of the person leading the discussion to make clear to the person listening,” Mr. Alda said. “You get the impression that ‘this person is my responsibility. I have to take care of them, so they understand what’s going on.’ ”
 

Parkinson’s disease diagnosis

During a question-and-answer session, Mr. Alda opened up about his Parkinson’s disease, which he said was diagnosed about 5 years ago. In 2018, he decided to speak publicly about his diagnosis for the first time.

“The reason was that I wanted to communicate to people who had recently been diagnosed not to believe or give into the stereotype that when you get a diagnosis, your life is over,” said Mr. Alda, who received the Public Welfare Medal from the National Academy of Sciences in 2016. “Under the burden of that belief, some people won’t tell their family or workplace colleagues. There are exercises you can do and medications you can take to prolong the time it takes before Parkinson’s gets much more serious. It’s not to diminish the fact that it can get really bad; but to think that your life is over as soon as you get a diagnosis is wrong.”

He added: “I’ve gone 5 years and I’m almost busier than I’ve ever been. I’m getting a lot accomplished and I look forward to I don’t know how many years. As long as I have them, I’m going to be grateful. It’s amazing how great it feels not to keep the diagnosis a secret.”

The first 2-day training session at Scripps Research will be held in June 2020. Additional sessions are scheduled to take place in October and December. Registration is available at aldacommunicationtraining.com/workshops.

[email protected]

LA JOLLA, CALIF. – The first time that legendary actor Alan Alda conducted an interview for “Scientific American Frontiers” on PBS, an award-winning series that ran for more than a decade, he remembers learning a lesson in humility.

Doug Brunk/MDedge News

“I wasn’t as smart as I thought I was,” he told a crowd of largely scientists and medical professionals who gathered in a small auditorium on the campus of Scripps Research on Jan. 16, 2020. “I didn’t realize the value of ignorance. I have a natural supply of it. I began to use it and say [to interviewees]: ‘I don’t understand what that means.’ Sometimes it would be basic physics and they’d look at me like I was a school child. I am a very curious person. What I discovered was, I was bringing out their humanity by my own curiosity, by the way I related to them, which I developed through studying improvisation as an actor, and relating as an actor to other actors.”

Mr. Alda, 83, appeared on the research campus to announce that Scripps Research is the new West Coast home of Alda Communication Training, which will work in tandem with the Alan Alda Center for Communicating Science at the State University of New York at Stony Brook, a nonprofit organization that Mr. Alda helped found in 2009.
 

Immersive training experience

“This will be a center where people can come to get training in effective communication,” said Mr. Alda, who is the winner of six Emmy Awards and six Golden Globe awards. “It’s an experiential kind of training. We don’t give tips. We don’t give lectures. We put you through exercises that are fun and actually make you laugh, but turn you into a better communicator, so you’re better able to connect to the people you’re talking to.”

To date, the Alan Alda Center for Communicating Science has trained more than 15,000 scientific leaders in the United States and other countries. The location at Scripps Research makes it more convenient for West Coast–based researchers and industry leaders to participate. “One of the things we wished, for years, we had was a place where we could train scientists and researchers and medical professionals all up and down the West Coast,” he said.

Recently, more than 30 of Scripps Research scientists participated in Mr. Alda’s training program, an immersive and engaging experience that helps participants learn to empathize with an audience and present their work in a way that connects with different stakeholders. The skills and strategies can help participants relate to prospective investors and philanthropists, government officials, members of the media, peers across scientific disciplines, and the general public.

Earlier in the day that he spoke on the Scripps campus, Mr. Alda encountered some of the Scripps researchers who had participated in that training. “One group of scientists came in and we shook hands,” he said. “They introduced themselves and said: ‘We’re working on infectious diseases.’ I said: ‘Oh my God; I just shook hands with you!’ No matter what I asked them, they had a clear way to express what they did. Then I realized they had studied with Alda Communications.”
 

Why communication matters

During the early stages of forming what became the Alan Alda Center for Communicating Science, one Nobel Prize winner at a major university dismissed the importance of improving the communication skills of young scientists. “He said to me: ‘We don’t have time for that; we have too much science to teach,’ ” said Mr. Alda, who played Army surgeon “Hawkeye” Pierce on the TV series “M*A*S*H”. “But communication is the essence of science. How can you do science unless you communicate with other scientists? There’s a stereotype that scientists are not as good at communicating as other people are. It’s true that they often speak a language that a lot of us don’t understand, but we all speak a language that is hard for other people to understand if we know something in great depth. We want to tell all the details; we want to speak in our special language because it makes us feel good.”

He underscored the importance of scientists being able to effectively communicate with the general public, “because the public needs to understand how important science is to their lives. It matters because at a place like [Scripps Research], understanding how nature works is put to work to keep our health secure.” Members of the public, he continued, “are busy living their lives; they’re busy working and bringing up their children. They haven’t spent 20, 30, 40 years devoted to a single aspect of nature the way scientists have. We can’t expect them to know as much as professional scientists, so we have to help them understand it. I hope we find ways to increase curiosity. I don’t know how to do that. I wish somebody would do a study on it, how you can take someone with a modicum of curiosity and help them enlarge it so it gives them the pleasure of discovering things about nature or understanding things about nature that other people don’t discover. Curiosity is the key to staying alive. That would bring us to a point of more people understanding science.”

Cultivating a sense of responsibility is another key to effective communication. “It’s the job of the person leading the discussion to make clear to the person listening,” Mr. Alda said. “You get the impression that ‘this person is my responsibility. I have to take care of them, so they understand what’s going on.’ ”
 

Parkinson’s disease diagnosis

During a question-and-answer session, Mr. Alda opened up about his Parkinson’s disease, which he said was diagnosed about 5 years ago. In 2018, he decided to speak publicly about his diagnosis for the first time.

“The reason was that I wanted to communicate to people who had recently been diagnosed not to believe or give into the stereotype that when you get a diagnosis, your life is over,” said Mr. Alda, who received the Public Welfare Medal from the National Academy of Sciences in 2016. “Under the burden of that belief, some people won’t tell their family or workplace colleagues. There are exercises you can do and medications you can take to prolong the time it takes before Parkinson’s gets much more serious. It’s not to diminish the fact that it can get really bad; but to think that your life is over as soon as you get a diagnosis is wrong.”

He added: “I’ve gone 5 years and I’m almost busier than I’ve ever been. I’m getting a lot accomplished and I look forward to I don’t know how many years. As long as I have them, I’m going to be grateful. It’s amazing how great it feels not to keep the diagnosis a secret.”

The first 2-day training session at Scripps Research will be held in June 2020. Additional sessions are scheduled to take place in October and December. Registration is available at aldacommunicationtraining.com/workshops.

[email protected]

In this edition of “How I Will Treat My Next Patient,” I highlight the potential role of circulating tumor DNA (ctDNA) monitoring in patients with a history of nonmetastatic colorectal cancer (CRC) and the approval of a new targeted agent for a subset of patients with gastrointestinal stromal tumors (GISTs). Taken together, this information may guide the management of selected patients with gastrointestinal malignancies, now and in the future.

ctDNA in colorectal cancer

Unfortunately, among patients with CRC with standard blood monitoring, multiple, incurable metastases are the predominant finding when relapse occurs. To improve upon the detection of potentially curable recurrent disease, researchers performed a cross-sectional, observational study of routine monitoring of ctDNA in patients with stage I-III CRC. The patients were also monitored with carcinoembryonic antigen (CEA) levels and imaging in accordance with guidelines from the National Comprehensive Cancer Network (Cancer. 2020 Jan 7. doi: 10.1002/cncr.32695). The investigators used the COLVERA assay of methylated CBAT1/IKZF1 for ctDNA monitoring and the LIAISON CEA plasma test.

Among the 50 patients with recurrence and 177 without recurrence of CRC who met all blood and imaging collection criteria, ctDNA testing offered a sensitivity of 68.1%, compared with 31.9% for CEA (P = .0002), with comparable specificity (97.9% vs. 96.4%; P = 1.000). Over about a 4-year time period, ctDNA detected an additional 18 patients (38%) with recurrence who did not have an elevated plasma CEA, whereas there was only 1 case (2.1%) with an elevated plasma CEA and negative ctDNA test.

Among recurrences considered amenable to surgery with curative intent, (n = 20), ctDNA was positive in 60% of patients, compared with only 20% for CEA (P = .010). Multivariate analysis indicated that ctDNA was an independent predictor of recurrence, whereas CEA was not.

The authors concluded that the methylated BCAT1/IKZF1 ctDNA test was superior to CEA monitoring after initial treatment for potentially curable CRC.

How these results influence practice

The current study adds to the body of work showing superior sensitivity of ctDNA monitoring in the detection of recurrence in patients with solid tumors. In May 2019, this column highlighted the work of Yuxuan Wang, MD, PhD, and colleagues in 58 patients with stages I-III CRC; over a similar duration of follow-up as in the current study (JAMA Oncol. 2019;5[8]:1118-23), Dr. Wang found that 10 of 13 recurrences (77%) were detected by monitoring ctDNA levels. CEA levels were detected 63% of recurrences.

The central, critical hypothesis of these efforts is that the earlier detection of metastatic disease will lead to improved survival for patients with CRC. As the authors state in their discussion, that hypothesis remains tantalizing but unproven.

Prospective, randomized trials like the recently opened COBRA trial (NRG-GI005), which tests ctDNA assay–directed therapy in patients with stage IIA CRC, deserve our enthusiastic support. Research with similar designs will establish the value of ctDNA monitoring as a biomarker for early intervention in patients with stage IV disease and for selecting patients after primary therapy who are unlikely to have been cured and who could potentially benefit from adjuvant therapy.

Monitoring ctDNA is a research tool that could be practice changing in the near future. It has shown enough promise to justify prospective, randomized trials to determine whether its superior sensitivity translates into improved survival.
 

Avapritinib for mutated GIST

The platelet-derived growth factor receptor–alpha (PDGFRA) gene encodes PDGFRA, a member of the type III tyrosine kinase receptor family, which includes the stem cell factor receptor, KIT (present in 95% of GISTs). PDGFRA and KIT have domains with specific roles in tyrosine kinase activation. Several PDGF isoforms bind and activate PDGFRA.

Among patients with GISTs, clinical responses to imatinib and other tyrosine kinase inhibitors (TKIs) correlate with tumor genotype. For example, many GISTs that progress within 6 months of TKI initiation lack mutations in KIT or PDGFRA or have a PDGFRA D842 mutation.

The Food and Drug Administration recently approved avapritinib (Ayvakit) for adults with unresectable or metastatic GISTs with a PDGFRA exon 18 mutation. The approval was based on the results of the NAVIGATOR trial, a single-arm, multicenter, open-label study of 43 patients with PDGFRA exon 18 mutations, including 38 patients with a PDGFRA D842V mutation.

The patients received 300 mg avapritinib once daily and 84% responded to avapritinib, though most were partial responses. Among patients with a D842V mutation, the response rate was also high – at 89% – but most responses were partial. At a median follow-up of 10.6 months, median response duration was not reached, but 61% of responses exceeded 6 months. Toxicity included asthenia, gastrointestinal and central nervous system side effects (including intracranial hemorrhage), hair color changes, lacrimation, and dizziness.

Avapritinib is the first drug approved specifically for patients with advanced or unresectable GISTs with a PDGFRA exon 18 mutation.

How these results influence practice

PDGFRA exon 18 mutations occur in 5%-7% of GISTs and are believed to stabilize the kinase activation loop, perhaps accounting for slow, steady growth of these tumors over a long time period and resistance to TKIs. The most frequent mutation results in an exon 18 D842V substitution (75% of all PDGFRA-mutated tumors). Although dramatic progress has been made in the treatment of patients with GIST since 2000, in patients with GISTs harboring PDGFRA exon 18 mutations, responses to treatment are rare and, when they occur, are more abbreviated.

With a high response rate and impressive response duration, avapritinib will be a valuable resource for oncologists treating this uncommon subset of patients with GISTs. The opportunity to convert unresectable tumors to potentially curable ones seems within reach.

The difficult dilemma will be to decide when treatment is needed and drug-related toxicity is justified in patients with slowly progressive tumors and few symptoms. As with so many decisions in oncology, until newer agents with fewer toxicities and higher complete response rates are developed, the proper time for any individual patient to embark on treatment with avapritinib will be found at the intersection of “precision medicine” and “clinical judgment.”

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I Will Treat My Next Patient,” I highlight the potential role of circulating tumor DNA (ctDNA) monitoring in patients with a history of nonmetastatic colorectal cancer (CRC) and the approval of a new targeted agent for a subset of patients with gastrointestinal stromal tumors (GISTs). Taken together, this information may guide the management of selected patients with gastrointestinal malignancies, now and in the future.

ctDNA in colorectal cancer

Unfortunately, among patients with CRC with standard blood monitoring, multiple, incurable metastases are the predominant finding when relapse occurs. To improve upon the detection of potentially curable recurrent disease, researchers performed a cross-sectional, observational study of routine monitoring of ctDNA in patients with stage I-III CRC. The patients were also monitored with carcinoembryonic antigen (CEA) levels and imaging in accordance with guidelines from the National Comprehensive Cancer Network (Cancer. 2020 Jan 7. doi: 10.1002/cncr.32695). The investigators used the COLVERA assay of methylated CBAT1/IKZF1 for ctDNA monitoring and the LIAISON CEA plasma test.

Among the 50 patients with recurrence and 177 without recurrence of CRC who met all blood and imaging collection criteria, ctDNA testing offered a sensitivity of 68.1%, compared with 31.9% for CEA (P = .0002), with comparable specificity (97.9% vs. 96.4%; P = 1.000). Over about a 4-year time period, ctDNA detected an additional 18 patients (38%) with recurrence who did not have an elevated plasma CEA, whereas there was only 1 case (2.1%) with an elevated plasma CEA and negative ctDNA test.

Among recurrences considered amenable to surgery with curative intent, (n = 20), ctDNA was positive in 60% of patients, compared with only 20% for CEA (P = .010). Multivariate analysis indicated that ctDNA was an independent predictor of recurrence, whereas CEA was not.

The authors concluded that the methylated BCAT1/IKZF1 ctDNA test was superior to CEA monitoring after initial treatment for potentially curable CRC.

How these results influence practice

The current study adds to the body of work showing superior sensitivity of ctDNA monitoring in the detection of recurrence in patients with solid tumors. In May 2019, this column highlighted the work of Yuxuan Wang, MD, PhD, and colleagues in 58 patients with stages I-III CRC; over a similar duration of follow-up as in the current study (JAMA Oncol. 2019;5[8]:1118-23), Dr. Wang found that 10 of 13 recurrences (77%) were detected by monitoring ctDNA levels. CEA levels were detected 63% of recurrences.

The central, critical hypothesis of these efforts is that the earlier detection of metastatic disease will lead to improved survival for patients with CRC. As the authors state in their discussion, that hypothesis remains tantalizing but unproven.

Prospective, randomized trials like the recently opened COBRA trial (NRG-GI005), which tests ctDNA assay–directed therapy in patients with stage IIA CRC, deserve our enthusiastic support. Research with similar designs will establish the value of ctDNA monitoring as a biomarker for early intervention in patients with stage IV disease and for selecting patients after primary therapy who are unlikely to have been cured and who could potentially benefit from adjuvant therapy.

Monitoring ctDNA is a research tool that could be practice changing in the near future. It has shown enough promise to justify prospective, randomized trials to determine whether its superior sensitivity translates into improved survival.
 

Avapritinib for mutated GIST

The platelet-derived growth factor receptor–alpha (PDGFRA) gene encodes PDGFRA, a member of the type III tyrosine kinase receptor family, which includes the stem cell factor receptor, KIT (present in 95% of GISTs). PDGFRA and KIT have domains with specific roles in tyrosine kinase activation. Several PDGF isoforms bind and activate PDGFRA.

Among patients with GISTs, clinical responses to imatinib and other tyrosine kinase inhibitors (TKIs) correlate with tumor genotype. For example, many GISTs that progress within 6 months of TKI initiation lack mutations in KIT or PDGFRA or have a PDGFRA D842 mutation.

The Food and Drug Administration recently approved avapritinib (Ayvakit) for adults with unresectable or metastatic GISTs with a PDGFRA exon 18 mutation. The approval was based on the results of the NAVIGATOR trial, a single-arm, multicenter, open-label study of 43 patients with PDGFRA exon 18 mutations, including 38 patients with a PDGFRA D842V mutation.

The patients received 300 mg avapritinib once daily and 84% responded to avapritinib, though most were partial responses. Among patients with a D842V mutation, the response rate was also high – at 89% – but most responses were partial. At a median follow-up of 10.6 months, median response duration was not reached, but 61% of responses exceeded 6 months. Toxicity included asthenia, gastrointestinal and central nervous system side effects (including intracranial hemorrhage), hair color changes, lacrimation, and dizziness.

Avapritinib is the first drug approved specifically for patients with advanced or unresectable GISTs with a PDGFRA exon 18 mutation.

How these results influence practice

PDGFRA exon 18 mutations occur in 5%-7% of GISTs and are believed to stabilize the kinase activation loop, perhaps accounting for slow, steady growth of these tumors over a long time period and resistance to TKIs. The most frequent mutation results in an exon 18 D842V substitution (75% of all PDGFRA-mutated tumors). Although dramatic progress has been made in the treatment of patients with GIST since 2000, in patients with GISTs harboring PDGFRA exon 18 mutations, responses to treatment are rare and, when they occur, are more abbreviated.

With a high response rate and impressive response duration, avapritinib will be a valuable resource for oncologists treating this uncommon subset of patients with GISTs. The opportunity to convert unresectable tumors to potentially curable ones seems within reach.

The difficult dilemma will be to decide when treatment is needed and drug-related toxicity is justified in patients with slowly progressive tumors and few symptoms. As with so many decisions in oncology, until newer agents with fewer toxicities and higher complete response rates are developed, the proper time for any individual patient to embark on treatment with avapritinib will be found at the intersection of “precision medicine” and “clinical judgment.”

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I Will Treat My Next Patient,” I highlight the potential role of circulating tumor DNA (ctDNA) monitoring in patients with a history of nonmetastatic colorectal cancer (CRC) and the approval of a new targeted agent for a subset of patients with gastrointestinal stromal tumors (GISTs). Taken together, this information may guide the management of selected patients with gastrointestinal malignancies, now and in the future.

ctDNA in colorectal cancer

Unfortunately, among patients with CRC with standard blood monitoring, multiple, incurable metastases are the predominant finding when relapse occurs. To improve upon the detection of potentially curable recurrent disease, researchers performed a cross-sectional, observational study of routine monitoring of ctDNA in patients with stage I-III CRC. The patients were also monitored with carcinoembryonic antigen (CEA) levels and imaging in accordance with guidelines from the National Comprehensive Cancer Network (Cancer. 2020 Jan 7. doi: 10.1002/cncr.32695). The investigators used the COLVERA assay of methylated CBAT1/IKZF1 for ctDNA monitoring and the LIAISON CEA plasma test.

Among the 50 patients with recurrence and 177 without recurrence of CRC who met all blood and imaging collection criteria, ctDNA testing offered a sensitivity of 68.1%, compared with 31.9% for CEA (P = .0002), with comparable specificity (97.9% vs. 96.4%; P = 1.000). Over about a 4-year time period, ctDNA detected an additional 18 patients (38%) with recurrence who did not have an elevated plasma CEA, whereas there was only 1 case (2.1%) with an elevated plasma CEA and negative ctDNA test.

Among recurrences considered amenable to surgery with curative intent, (n = 20), ctDNA was positive in 60% of patients, compared with only 20% for CEA (P = .010). Multivariate analysis indicated that ctDNA was an independent predictor of recurrence, whereas CEA was not.

The authors concluded that the methylated BCAT1/IKZF1 ctDNA test was superior to CEA monitoring after initial treatment for potentially curable CRC.

How these results influence practice

The current study adds to the body of work showing superior sensitivity of ctDNA monitoring in the detection of recurrence in patients with solid tumors. In May 2019, this column highlighted the work of Yuxuan Wang, MD, PhD, and colleagues in 58 patients with stages I-III CRC; over a similar duration of follow-up as in the current study (JAMA Oncol. 2019;5[8]:1118-23), Dr. Wang found that 10 of 13 recurrences (77%) were detected by monitoring ctDNA levels. CEA levels were detected 63% of recurrences.

The central, critical hypothesis of these efforts is that the earlier detection of metastatic disease will lead to improved survival for patients with CRC. As the authors state in their discussion, that hypothesis remains tantalizing but unproven.

Prospective, randomized trials like the recently opened COBRA trial (NRG-GI005), which tests ctDNA assay–directed therapy in patients with stage IIA CRC, deserve our enthusiastic support. Research with similar designs will establish the value of ctDNA monitoring as a biomarker for early intervention in patients with stage IV disease and for selecting patients after primary therapy who are unlikely to have been cured and who could potentially benefit from adjuvant therapy.

Monitoring ctDNA is a research tool that could be practice changing in the near future. It has shown enough promise to justify prospective, randomized trials to determine whether its superior sensitivity translates into improved survival.
 

Avapritinib for mutated GIST

The platelet-derived growth factor receptor–alpha (PDGFRA) gene encodes PDGFRA, a member of the type III tyrosine kinase receptor family, which includes the stem cell factor receptor, KIT (present in 95% of GISTs). PDGFRA and KIT have domains with specific roles in tyrosine kinase activation. Several PDGF isoforms bind and activate PDGFRA.

Among patients with GISTs, clinical responses to imatinib and other tyrosine kinase inhibitors (TKIs) correlate with tumor genotype. For example, many GISTs that progress within 6 months of TKI initiation lack mutations in KIT or PDGFRA or have a PDGFRA D842 mutation.

The Food and Drug Administration recently approved avapritinib (Ayvakit) for adults with unresectable or metastatic GISTs with a PDGFRA exon 18 mutation. The approval was based on the results of the NAVIGATOR trial, a single-arm, multicenter, open-label study of 43 patients with PDGFRA exon 18 mutations, including 38 patients with a PDGFRA D842V mutation.

The patients received 300 mg avapritinib once daily and 84% responded to avapritinib, though most were partial responses. Among patients with a D842V mutation, the response rate was also high – at 89% – but most responses were partial. At a median follow-up of 10.6 months, median response duration was not reached, but 61% of responses exceeded 6 months. Toxicity included asthenia, gastrointestinal and central nervous system side effects (including intracranial hemorrhage), hair color changes, lacrimation, and dizziness.

Avapritinib is the first drug approved specifically for patients with advanced or unresectable GISTs with a PDGFRA exon 18 mutation.

How these results influence practice

PDGFRA exon 18 mutations occur in 5%-7% of GISTs and are believed to stabilize the kinase activation loop, perhaps accounting for slow, steady growth of these tumors over a long time period and resistance to TKIs. The most frequent mutation results in an exon 18 D842V substitution (75% of all PDGFRA-mutated tumors). Although dramatic progress has been made in the treatment of patients with GIST since 2000, in patients with GISTs harboring PDGFRA exon 18 mutations, responses to treatment are rare and, when they occur, are more abbreviated.

With a high response rate and impressive response duration, avapritinib will be a valuable resource for oncologists treating this uncommon subset of patients with GISTs. The opportunity to convert unresectable tumors to potentially curable ones seems within reach.

The difficult dilemma will be to decide when treatment is needed and drug-related toxicity is justified in patients with slowly progressive tumors and few symptoms. As with so many decisions in oncology, until newer agents with fewer toxicities and higher complete response rates are developed, the proper time for any individual patient to embark on treatment with avapritinib will be found at the intersection of “precision medicine” and “clinical judgment.”

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.