Federal Practitioner

Acute kidney injury (AKI) is a frequent complication among patients hospitalized for COVID-19, with incidence rates of 39% and 52% in two independent, European case series presented recently at the International Society of Nephrology: 2021 World Congress. Many of the cases progressed to more severe, stage 3 AKI. Factors linked with incident AKI in the two reports included use of mechanical ventilation, vasopressors, or diuretics, and elevations in inflammatory markers.

Mohammed Haneefa Nizamudeen/Getty Images

The new findings confirm several U.S. reports published during the past year. In those reports, roughly a third of patients hospitalized for COVID-19 developed AKI during their hospital stay, said Jay L. Koyner, MD, during another renal conference, the National Kidney Foundation 2021 Spring Clinical Meetings.

Experience has shown it’s bad news when hospitalized COVID-19 patients develop AKI, which can prove fatal or can lead to the development or worsening of chronic kidney disease (CKD), which in some cases rapidly progresses to end-stage disease.
 

COVID-19 giving nephrologists an opportunity to improve AKI care

“COVID is giving us an opportunity to do a better job of taking care of patients who develop AKI, which is something that nephrologists have not often excelled at doing,” said Dr. Koyner, professor and director of the nephrology ICU at the University of Chicago.

“Many studies will look at how we can manage COVID-19 patients better after they develop AKI, because I suspect a large number of these patients will wind up with CKD,” Dr. Koyner said during his talk.

He cited several lessons from reports of AKI that occurs in patients hospitalized for COVID-19:

• Preexisting CKD, , and severe COVID-19 appear to be risk factors for developing COVID-related AKI.
• Patients who develop AKI during acutely severe COVID-19 may have slightly worse outcomes than patients without COVID-19 who develop AKI.
• Certain genetic susceptibilities may play a role in developing COVID-19–related AKI.
• Routine follow-up of AKI is generally inadequate and is not standardized, whether AKI develops while ill with COVID-19 or in other settings.

The most encouraging AKI takeaway from COVID-19’s first year is that its incidence among patients hospitalized with COVID-19 appears to have dropped from very high rates early on, possibly because of more routine use of steroids for critically ill patients with COVID-19 and a reduction in the use of ventilators, Dr. Koyner suggested.
 

In-hospital diuretic treatment links with AKI

One of the World Congress of Nephrology reports involved 1,248 patients admitted with confirmed COVID-19 at two tertiary care hospitals in London during March–May 2020. The average age of the patients was 69 years, 59% were men, and 17% had CKD at admission, as determined on the basis of estimated glomerular filtration rate <60 mL/min per 1.73 m².

During hospitalization, 487 patients (39%) developed AKI, including 175 (14%) with stage 3 AKI and 109 (9%) who required renal replacement therapy (dialysis or kidney transplant). The incidence of AKI peaked 5 weeks after COVID-19 admission, Paul Jewell and associates from King’s College Hospital, London, reported in a poster.

Multivariate analysis identified several demographic and clinical variables that were significantly linked with an increased risk of developing AKI: male sex (which boosted risk by 55%), Black race (79% higher risk), CKD at admission (triple the risk), being hypertensive on admission (73% higher risk), and being administered diuretics during hospitalization (69% higher risk).

The findings of a risk linked with diuretic use “supports the cautious use of diuretics in patients hospitalized with COVID-19, especially in the presence of background renal impairment,” the authors said.

For patients with incident AKI, the 30-day mortality rate was significantly increased; mortality was 59% higher among patients who developed stage 1 AKI and was roughly triple among patients who developed stage 2 or 3 AKI.
 

Second report links ventilation, vasopressors with worse AKI

A separate report from clinicians at Charité Hospital, Berlin, retrospectively analyzed 223 patients admitted with symptomatic COVID-19 to three Charité sites during March–June 2020. During hospitalization, 117 patients (52%) developed AKI, including 70 (31%) with stage 3 disease; 67 (30%) required renal replacement therapy. Half the patients with stage 3 AKI required ICU admission.

Compared with patients with less severe AKI, patients who developed stage 3 AKI were more often male, older, and had a higher body mass index.

In a multivariate model, compared with patients who developed less severe AKI, those who developed stage 3 disease also were significantly more likely to have received mechanical ventilation or vasopressor drugs and were more likely to have increased levels of leukocytes or procalcitonin, two inflammatory markers, Jan-Hendrink B. Hardenburg, MD, a Charité nephrologist, and associates reported in a poster at the meeting.

Mechanical ventilation was linked with a sixfold higher rate of stage 3 AKI, and treatment with vasopressor drugs was linked with a threefold higher rate. Elevations in procalcitonin or leukocyte levels were linked with about 60% increases in rates of stage 3 AKI. For both of these risk factors, temporal relationships were tighter; increases in both values appeared just before onset of stage 3 disease.

Dr. Joyner has been a speaker on behalf of NXStage Medical; a consultant to Astute Medical, Baxter, Mallinckrodt, Pfizer, and Sphingotec; and he has received research funding from Astute, Bioporto, NxStage, and Satellite Healthcare. Mr. Jewell and Dr. Hardenburg disclosed no relevant financial relationships.

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

Acute kidney injury (AKI) is a frequent complication among patients hospitalized for COVID-19, with incidence rates of 39% and 52% in two independent, European case series presented recently at the International Society of Nephrology: 2021 World Congress. Many of the cases progressed to more severe, stage 3 AKI. Factors linked with incident AKI in the two reports included use of mechanical ventilation, vasopressors, or diuretics, and elevations in inflammatory markers.

Mohammed Haneefa Nizamudeen/Getty Images

The new findings confirm several U.S. reports published during the past year. In those reports, roughly a third of patients hospitalized for COVID-19 developed AKI during their hospital stay, said Jay L. Koyner, MD, during another renal conference, the National Kidney Foundation 2021 Spring Clinical Meetings.

Experience has shown it’s bad news when hospitalized COVID-19 patients develop AKI, which can prove fatal or can lead to the development or worsening of chronic kidney disease (CKD), which in some cases rapidly progresses to end-stage disease.
 

COVID-19 giving nephrologists an opportunity to improve AKI care

“COVID is giving us an opportunity to do a better job of taking care of patients who develop AKI, which is something that nephrologists have not often excelled at doing,” said Dr. Koyner, professor and director of the nephrology ICU at the University of Chicago.

“Many studies will look at how we can manage COVID-19 patients better after they develop AKI, because I suspect a large number of these patients will wind up with CKD,” Dr. Koyner said during his talk.

He cited several lessons from reports of AKI that occurs in patients hospitalized for COVID-19:

• Preexisting CKD, , and severe COVID-19 appear to be risk factors for developing COVID-related AKI.
• Patients who develop AKI during acutely severe COVID-19 may have slightly worse outcomes than patients without COVID-19 who develop AKI.
• Certain genetic susceptibilities may play a role in developing COVID-19–related AKI.
• Routine follow-up of AKI is generally inadequate and is not standardized, whether AKI develops while ill with COVID-19 or in other settings.

The most encouraging AKI takeaway from COVID-19’s first year is that its incidence among patients hospitalized with COVID-19 appears to have dropped from very high rates early on, possibly because of more routine use of steroids for critically ill patients with COVID-19 and a reduction in the use of ventilators, Dr. Koyner suggested.
 

In-hospital diuretic treatment links with AKI

One of the World Congress of Nephrology reports involved 1,248 patients admitted with confirmed COVID-19 at two tertiary care hospitals in London during March–May 2020. The average age of the patients was 69 years, 59% were men, and 17% had CKD at admission, as determined on the basis of estimated glomerular filtration rate <60 mL/min per 1.73 m².

During hospitalization, 487 patients (39%) developed AKI, including 175 (14%) with stage 3 AKI and 109 (9%) who required renal replacement therapy (dialysis or kidney transplant). The incidence of AKI peaked 5 weeks after COVID-19 admission, Paul Jewell and associates from King’s College Hospital, London, reported in a poster.

Multivariate analysis identified several demographic and clinical variables that were significantly linked with an increased risk of developing AKI: male sex (which boosted risk by 55%), Black race (79% higher risk), CKD at admission (triple the risk), being hypertensive on admission (73% higher risk), and being administered diuretics during hospitalization (69% higher risk).

The findings of a risk linked with diuretic use “supports the cautious use of diuretics in patients hospitalized with COVID-19, especially in the presence of background renal impairment,” the authors said.

For patients with incident AKI, the 30-day mortality rate was significantly increased; mortality was 59% higher among patients who developed stage 1 AKI and was roughly triple among patients who developed stage 2 or 3 AKI.
 

Second report links ventilation, vasopressors with worse AKI

A separate report from clinicians at Charité Hospital, Berlin, retrospectively analyzed 223 patients admitted with symptomatic COVID-19 to three Charité sites during March–June 2020. During hospitalization, 117 patients (52%) developed AKI, including 70 (31%) with stage 3 disease; 67 (30%) required renal replacement therapy. Half the patients with stage 3 AKI required ICU admission.

Compared with patients with less severe AKI, patients who developed stage 3 AKI were more often male, older, and had a higher body mass index.

In a multivariate model, compared with patients who developed less severe AKI, those who developed stage 3 disease also were significantly more likely to have received mechanical ventilation or vasopressor drugs and were more likely to have increased levels of leukocytes or procalcitonin, two inflammatory markers, Jan-Hendrink B. Hardenburg, MD, a Charité nephrologist, and associates reported in a poster at the meeting.

Mechanical ventilation was linked with a sixfold higher rate of stage 3 AKI, and treatment with vasopressor drugs was linked with a threefold higher rate. Elevations in procalcitonin or leukocyte levels were linked with about 60% increases in rates of stage 3 AKI. For both of these risk factors, temporal relationships were tighter; increases in both values appeared just before onset of stage 3 disease.

Dr. Joyner has been a speaker on behalf of NXStage Medical; a consultant to Astute Medical, Baxter, Mallinckrodt, Pfizer, and Sphingotec; and he has received research funding from Astute, Bioporto, NxStage, and Satellite Healthcare. Mr. Jewell and Dr. Hardenburg disclosed no relevant financial relationships.

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

Acute kidney injury (AKI) is a frequent complication among patients hospitalized for COVID-19, with incidence rates of 39% and 52% in two independent, European case series presented recently at the International Society of Nephrology: 2021 World Congress. Many of the cases progressed to more severe, stage 3 AKI. Factors linked with incident AKI in the two reports included use of mechanical ventilation, vasopressors, or diuretics, and elevations in inflammatory markers.

Mohammed Haneefa Nizamudeen/Getty Images

The new findings confirm several U.S. reports published during the past year. In those reports, roughly a third of patients hospitalized for COVID-19 developed AKI during their hospital stay, said Jay L. Koyner, MD, during another renal conference, the National Kidney Foundation 2021 Spring Clinical Meetings.

Experience has shown it’s bad news when hospitalized COVID-19 patients develop AKI, which can prove fatal or can lead to the development or worsening of chronic kidney disease (CKD), which in some cases rapidly progresses to end-stage disease.
 

COVID-19 giving nephrologists an opportunity to improve AKI care

“COVID is giving us an opportunity to do a better job of taking care of patients who develop AKI, which is something that nephrologists have not often excelled at doing,” said Dr. Koyner, professor and director of the nephrology ICU at the University of Chicago.

“Many studies will look at how we can manage COVID-19 patients better after they develop AKI, because I suspect a large number of these patients will wind up with CKD,” Dr. Koyner said during his talk.

He cited several lessons from reports of AKI that occurs in patients hospitalized for COVID-19:

• Preexisting CKD, , and severe COVID-19 appear to be risk factors for developing COVID-related AKI.
• Patients who develop AKI during acutely severe COVID-19 may have slightly worse outcomes than patients without COVID-19 who develop AKI.
• Certain genetic susceptibilities may play a role in developing COVID-19–related AKI.
• Routine follow-up of AKI is generally inadequate and is not standardized, whether AKI develops while ill with COVID-19 or in other settings.

The most encouraging AKI takeaway from COVID-19’s first year is that its incidence among patients hospitalized with COVID-19 appears to have dropped from very high rates early on, possibly because of more routine use of steroids for critically ill patients with COVID-19 and a reduction in the use of ventilators, Dr. Koyner suggested.
 

In-hospital diuretic treatment links with AKI

One of the World Congress of Nephrology reports involved 1,248 patients admitted with confirmed COVID-19 at two tertiary care hospitals in London during March–May 2020. The average age of the patients was 69 years, 59% were men, and 17% had CKD at admission, as determined on the basis of estimated glomerular filtration rate <60 mL/min per 1.73 m².

During hospitalization, 487 patients (39%) developed AKI, including 175 (14%) with stage 3 AKI and 109 (9%) who required renal replacement therapy (dialysis or kidney transplant). The incidence of AKI peaked 5 weeks after COVID-19 admission, Paul Jewell and associates from King’s College Hospital, London, reported in a poster.

Multivariate analysis identified several demographic and clinical variables that were significantly linked with an increased risk of developing AKI: male sex (which boosted risk by 55%), Black race (79% higher risk), CKD at admission (triple the risk), being hypertensive on admission (73% higher risk), and being administered diuretics during hospitalization (69% higher risk).

The findings of a risk linked with diuretic use “supports the cautious use of diuretics in patients hospitalized with COVID-19, especially in the presence of background renal impairment,” the authors said.

For patients with incident AKI, the 30-day mortality rate was significantly increased; mortality was 59% higher among patients who developed stage 1 AKI and was roughly triple among patients who developed stage 2 or 3 AKI.
 

Second report links ventilation, vasopressors with worse AKI

A separate report from clinicians at Charité Hospital, Berlin, retrospectively analyzed 223 patients admitted with symptomatic COVID-19 to three Charité sites during March–June 2020. During hospitalization, 117 patients (52%) developed AKI, including 70 (31%) with stage 3 disease; 67 (30%) required renal replacement therapy. Half the patients with stage 3 AKI required ICU admission.

Compared with patients with less severe AKI, patients who developed stage 3 AKI were more often male, older, and had a higher body mass index.

In a multivariate model, compared with patients who developed less severe AKI, those who developed stage 3 disease also were significantly more likely to have received mechanical ventilation or vasopressor drugs and were more likely to have increased levels of leukocytes or procalcitonin, two inflammatory markers, Jan-Hendrink B. Hardenburg, MD, a Charité nephrologist, and associates reported in a poster at the meeting.

Mechanical ventilation was linked with a sixfold higher rate of stage 3 AKI, and treatment with vasopressor drugs was linked with a threefold higher rate. Elevations in procalcitonin or leukocyte levels were linked with about 60% increases in rates of stage 3 AKI. For both of these risk factors, temporal relationships were tighter; increases in both values appeared just before onset of stage 3 disease.

Dr. Joyner has been a speaker on behalf of NXStage Medical; a consultant to Astute Medical, Baxter, Mallinckrodt, Pfizer, and Sphingotec; and he has received research funding from Astute, Bioporto, NxStage, and Satellite Healthcare. Mr. Jewell and Dr. Hardenburg disclosed no relevant financial relationships.

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

People with clinically diagnosed depression and anxiety may be prone to developing Alzheimer’s disease at a younger age than other people, and those with a history of posttraumatic stress disorder may be prone to Alzheimer’s disease onset even earlier in life, according to findings from a review of 1,500 patients with Alzheimer’s disease from a single-center population.

“Could psychosis symptoms be the proverbial canary in a coal mine?” Emily Eijansantos, a medical student at the University of California, San Francisco, said in reporting results of the chart review at the 2021 annual meeting of the American Academy of Neurology. “Previously in this cohort it was found that neurodevelopmental factors as well as chronic insults such as autoimmunity and seizure were also associated with an early age of onset in Alzheimer’s disease.”

The link between depression and autoimmunity, and anxiety and seizure “beg more questions about underlying pathophysiology,” she said. The study included 750 patients with early-onset Alzheimer’s disease and a similar number of late-onset patients from the UCSF Memory and Aging Center.
 

An inverse correlation between psychiatric disorders and age of Alzheimer’s onset

In the total study population, 43.5% (n = 652) had a previous diagnosis of depression and 32.3% (n = 485) had been diagnosed with anxiety. That, Ms. Eijansantos said, falls into similar ranges that other studies have reported.

“When we look at individual psychiatric disorders, we find that those with depression, anxiety, or PTSD are younger on average,” she said. “Patients with depression and anxiety are more [likely] female and have less vascular risk factors, and we observed an association between depression and autoimmunity, anxiety, and seizures.”

Specifically, patients with a history of depression were 2.2 years younger, on average, at the age of onset than patients without such history (P = .01); those with anxiety were 3 years younger on average (P = .01); and those with PTSD were 6.8 years younger on average, although only 1% (n = 15) of study subjects had PTSD, making for a small sample to study. These age-of-onset disparities didn’t appear among patients with previously diagnosed bipolar disorder (BPD) or schizophrenia.

Ms. Eijansantos noted that there were no differences in education attained or apolipoprotein-E gene status between the patients with and without a history of psychosis, and, within the subgroups of individual psychiatric disorders, there were no differences between patients with past and current or formal and informal diagnoses.

“When we split the cohort into quintiles based on age of Alzheimer’s disease onset, we find an inverse correlation between the amount of depression, anxiety, and PTSD endorsed and their ages of onset,” Ms. Eijansantos said. For example, the youngest quintile had a greater than 50% rate of depression while the oldest quintile had a depression rate around 36%. A similar spread was found with anxiety: a rate around 46% in the youngest quantile versus around 25% in the oldest, whereas rates of PTSD, BPD, and schizophrenia were similar across the five age-of-onset groups.

Patients with a history of multiple psychiatric disorders had an even younger age of onset. “We see that those with two psychiatric disorder are younger than those with one, and those with three psychiatric disorders are younger still,” Ms. Eijansantos said. “And we find that the Alzheimer’s disease age-at-onset reduction doubles with each additional psychiatric disorder.” Multiple disorders also adversely impacted survival, she said.

Because they found no difference between patients with past versus active symptoms and informal versus formal diagnosis, Ms. Eijansantos explained that they further studied the National Alzheimer’s Coordinating Center cohort of 8,267 patients with Alzheimer’s disease and found a similar relationship between psychiatric history and age of onset among patients with depression or anxiety or both. This cohort also documented symptom severity, she noted. “So when we look at depression and anxiety we find similar reductions in the Alzheimer’s disease age of onset with each increasing degree of symptom severity,” she said.

“Does this mean that psychiatric disease is a risk factor for Alzheimr’s disease?” Ms. Eijansantos said. “We can’t answer that with this study because it was only designed to see if the psychiatric factors modulate the age of onset in those that have Alzheimer’s disease, but taken together we believe that these results fit the framework that there are pathophysiological and profound differences between earlier and later presentations of Alzheimer’s disease.”

She pointed to reports that early-onset Alzheimer’s disease is associated with more aggressive tau pathology and that depression is associated with tau. However, the evidence supporting a link between amyloid and psychiatric disease is less certain, she said.
 

Preliminary and speculative findings

Senior study author Zachary Miller, MD, an assistant professor in the UCSF Memory and Aging Center, explained the significance of the study findings of potential links between depression and autoimmunity, and anxiety and seizure. “There may be distinct underlying pathophysiological mechanisms in patients with Alzheimer’s disease who have symptoms of depression versus anxiety,” he said, acknowledging the findings “are quite preliminary and our interpretations quite speculative.”

The findings raise the question that the symptomatic presentation of greater amounts of depression in early-onset Alzheimer’s disease may be moderated by an underlying neuroinflammatory insult, he said. “If so, depression symptomatology could then be seen as a possible clinical marker of this inflammatory response and possibly be used in testing clinical endpoints for future intervention trials,” Dr. Miller said. “Similarly, if neuronal hyperexcitability in Alzheimer’s disease manifests itself as either seizure and/or anxiety, this would have significant impact for therapeutic monitoring and treatment.”

He said a multicenter study of Alzheimer’s disease cohorts would validate the findings. “At the same time, we are also interested in looking deeper into these findings, investigating the potential cognitive and neuroanatomical correlates associated with these conditions,” Dr. Miller said.

Clinical phenotyping may provide more insight into the relationship between psychosis and age of Alzheimer’s disease onset, said Vijay K. Ramanan, MD, PhD, an assistant professor of neurology at Mayo Clinic in Rochester, Minn.

People with clinically diagnosed depression and anxiety may be prone to developing Alzheimer’s disease at a younger age than other people, and those with a history of posttraumatic stress disorder may be prone to Alzheimer’s disease onset even earlier in life, according to findings from a review of 1,500 patients with Alzheimer’s disease from a single-center population.

“Could psychosis symptoms be the proverbial canary in a coal mine?” Emily Eijansantos, a medical student at the University of California, San Francisco, said in reporting results of the chart review at the 2021 annual meeting of the American Academy of Neurology. “Previously in this cohort it was found that neurodevelopmental factors as well as chronic insults such as autoimmunity and seizure were also associated with an early age of onset in Alzheimer’s disease.”

The link between depression and autoimmunity, and anxiety and seizure “beg more questions about underlying pathophysiology,” she said. The study included 750 patients with early-onset Alzheimer’s disease and a similar number of late-onset patients from the UCSF Memory and Aging Center.
 

An inverse correlation between psychiatric disorders and age of Alzheimer’s onset

In the total study population, 43.5% (n = 652) had a previous diagnosis of depression and 32.3% (n = 485) had been diagnosed with anxiety. That, Ms. Eijansantos said, falls into similar ranges that other studies have reported.

“When we look at individual psychiatric disorders, we find that those with depression, anxiety, or PTSD are younger on average,” she said. “Patients with depression and anxiety are more [likely] female and have less vascular risk factors, and we observed an association between depression and autoimmunity, anxiety, and seizures.”

Specifically, patients with a history of depression were 2.2 years younger, on average, at the age of onset than patients without such history (P = .01); those with anxiety were 3 years younger on average (P = .01); and those with PTSD were 6.8 years younger on average, although only 1% (n = 15) of study subjects had PTSD, making for a small sample to study. These age-of-onset disparities didn’t appear among patients with previously diagnosed bipolar disorder (BPD) or schizophrenia.

Ms. Eijansantos noted that there were no differences in education attained or apolipoprotein-E gene status between the patients with and without a history of psychosis, and, within the subgroups of individual psychiatric disorders, there were no differences between patients with past and current or formal and informal diagnoses.

“When we split the cohort into quintiles based on age of Alzheimer’s disease onset, we find an inverse correlation between the amount of depression, anxiety, and PTSD endorsed and their ages of onset,” Ms. Eijansantos said. For example, the youngest quintile had a greater than 50% rate of depression while the oldest quintile had a depression rate around 36%. A similar spread was found with anxiety: a rate around 46% in the youngest quantile versus around 25% in the oldest, whereas rates of PTSD, BPD, and schizophrenia were similar across the five age-of-onset groups.

Patients with a history of multiple psychiatric disorders had an even younger age of onset. “We see that those with two psychiatric disorder are younger than those with one, and those with three psychiatric disorders are younger still,” Ms. Eijansantos said. “And we find that the Alzheimer’s disease age-at-onset reduction doubles with each additional psychiatric disorder.” Multiple disorders also adversely impacted survival, she said.

Because they found no difference between patients with past versus active symptoms and informal versus formal diagnosis, Ms. Eijansantos explained that they further studied the National Alzheimer’s Coordinating Center cohort of 8,267 patients with Alzheimer’s disease and found a similar relationship between psychiatric history and age of onset among patients with depression or anxiety or both. This cohort also documented symptom severity, she noted. “So when we look at depression and anxiety we find similar reductions in the Alzheimer’s disease age of onset with each increasing degree of symptom severity,” she said.

“Does this mean that psychiatric disease is a risk factor for Alzheimr’s disease?” Ms. Eijansantos said. “We can’t answer that with this study because it was only designed to see if the psychiatric factors modulate the age of onset in those that have Alzheimer’s disease, but taken together we believe that these results fit the framework that there are pathophysiological and profound differences between earlier and later presentations of Alzheimer’s disease.”

She pointed to reports that early-onset Alzheimer’s disease is associated with more aggressive tau pathology and that depression is associated with tau. However, the evidence supporting a link between amyloid and psychiatric disease is less certain, she said.
 

Preliminary and speculative findings

Senior study author Zachary Miller, MD, an assistant professor in the UCSF Memory and Aging Center, explained the significance of the study findings of potential links between depression and autoimmunity, and anxiety and seizure. “There may be distinct underlying pathophysiological mechanisms in patients with Alzheimer’s disease who have symptoms of depression versus anxiety,” he said, acknowledging the findings “are quite preliminary and our interpretations quite speculative.”

The findings raise the question that the symptomatic presentation of greater amounts of depression in early-onset Alzheimer’s disease may be moderated by an underlying neuroinflammatory insult, he said. “If so, depression symptomatology could then be seen as a possible clinical marker of this inflammatory response and possibly be used in testing clinical endpoints for future intervention trials,” Dr. Miller said. “Similarly, if neuronal hyperexcitability in Alzheimer’s disease manifests itself as either seizure and/or anxiety, this would have significant impact for therapeutic monitoring and treatment.”

He said a multicenter study of Alzheimer’s disease cohorts would validate the findings. “At the same time, we are also interested in looking deeper into these findings, investigating the potential cognitive and neuroanatomical correlates associated with these conditions,” Dr. Miller said.

Clinical phenotyping may provide more insight into the relationship between psychosis and age of Alzheimer’s disease onset, said Vijay K. Ramanan, MD, PhD, an assistant professor of neurology at Mayo Clinic in Rochester, Minn.

People with clinically diagnosed depression and anxiety may be prone to developing Alzheimer’s disease at a younger age than other people, and those with a history of posttraumatic stress disorder may be prone to Alzheimer’s disease onset even earlier in life, according to findings from a review of 1,500 patients with Alzheimer’s disease from a single-center population.

“Could psychosis symptoms be the proverbial canary in a coal mine?” Emily Eijansantos, a medical student at the University of California, San Francisco, said in reporting results of the chart review at the 2021 annual meeting of the American Academy of Neurology. “Previously in this cohort it was found that neurodevelopmental factors as well as chronic insults such as autoimmunity and seizure were also associated with an early age of onset in Alzheimer’s disease.”

The link between depression and autoimmunity, and anxiety and seizure “beg more questions about underlying pathophysiology,” she said. The study included 750 patients with early-onset Alzheimer’s disease and a similar number of late-onset patients from the UCSF Memory and Aging Center.
 

An inverse correlation between psychiatric disorders and age of Alzheimer’s onset

In the total study population, 43.5% (n = 652) had a previous diagnosis of depression and 32.3% (n = 485) had been diagnosed with anxiety. That, Ms. Eijansantos said, falls into similar ranges that other studies have reported.

“When we look at individual psychiatric disorders, we find that those with depression, anxiety, or PTSD are younger on average,” she said. “Patients with depression and anxiety are more [likely] female and have less vascular risk factors, and we observed an association between depression and autoimmunity, anxiety, and seizures.”

Specifically, patients with a history of depression were 2.2 years younger, on average, at the age of onset than patients without such history (P = .01); those with anxiety were 3 years younger on average (P = .01); and those with PTSD were 6.8 years younger on average, although only 1% (n = 15) of study subjects had PTSD, making for a small sample to study. These age-of-onset disparities didn’t appear among patients with previously diagnosed bipolar disorder (BPD) or schizophrenia.

Ms. Eijansantos noted that there were no differences in education attained or apolipoprotein-E gene status between the patients with and without a history of psychosis, and, within the subgroups of individual psychiatric disorders, there were no differences between patients with past and current or formal and informal diagnoses.

“When we split the cohort into quintiles based on age of Alzheimer’s disease onset, we find an inverse correlation between the amount of depression, anxiety, and PTSD endorsed and their ages of onset,” Ms. Eijansantos said. For example, the youngest quintile had a greater than 50% rate of depression while the oldest quintile had a depression rate around 36%. A similar spread was found with anxiety: a rate around 46% in the youngest quantile versus around 25% in the oldest, whereas rates of PTSD, BPD, and schizophrenia were similar across the five age-of-onset groups.

Patients with a history of multiple psychiatric disorders had an even younger age of onset. “We see that those with two psychiatric disorder are younger than those with one, and those with three psychiatric disorders are younger still,” Ms. Eijansantos said. “And we find that the Alzheimer’s disease age-at-onset reduction doubles with each additional psychiatric disorder.” Multiple disorders also adversely impacted survival, she said.

Because they found no difference between patients with past versus active symptoms and informal versus formal diagnosis, Ms. Eijansantos explained that they further studied the National Alzheimer’s Coordinating Center cohort of 8,267 patients with Alzheimer’s disease and found a similar relationship between psychiatric history and age of onset among patients with depression or anxiety or both. This cohort also documented symptom severity, she noted. “So when we look at depression and anxiety we find similar reductions in the Alzheimer’s disease age of onset with each increasing degree of symptom severity,” she said.

“Does this mean that psychiatric disease is a risk factor for Alzheimr’s disease?” Ms. Eijansantos said. “We can’t answer that with this study because it was only designed to see if the psychiatric factors modulate the age of onset in those that have Alzheimer’s disease, but taken together we believe that these results fit the framework that there are pathophysiological and profound differences between earlier and later presentations of Alzheimer’s disease.”

She pointed to reports that early-onset Alzheimer’s disease is associated with more aggressive tau pathology and that depression is associated with tau. However, the evidence supporting a link between amyloid and psychiatric disease is less certain, she said.
 

Preliminary and speculative findings

Senior study author Zachary Miller, MD, an assistant professor in the UCSF Memory and Aging Center, explained the significance of the study findings of potential links between depression and autoimmunity, and anxiety and seizure. “There may be distinct underlying pathophysiological mechanisms in patients with Alzheimer’s disease who have symptoms of depression versus anxiety,” he said, acknowledging the findings “are quite preliminary and our interpretations quite speculative.”

The findings raise the question that the symptomatic presentation of greater amounts of depression in early-onset Alzheimer’s disease may be moderated by an underlying neuroinflammatory insult, he said. “If so, depression symptomatology could then be seen as a possible clinical marker of this inflammatory response and possibly be used in testing clinical endpoints for future intervention trials,” Dr. Miller said. “Similarly, if neuronal hyperexcitability in Alzheimer’s disease manifests itself as either seizure and/or anxiety, this would have significant impact for therapeutic monitoring and treatment.”

He said a multicenter study of Alzheimer’s disease cohorts would validate the findings. “At the same time, we are also interested in looking deeper into these findings, investigating the potential cognitive and neuroanatomical correlates associated with these conditions,” Dr. Miller said.

Clinical phenotyping may provide more insight into the relationship between psychosis and age of Alzheimer’s disease onset, said Vijay K. Ramanan, MD, PhD, an assistant professor of neurology at Mayo Clinic in Rochester, Minn.

Universal multigene panel testing of colorectal cancer patients can detect heritable mutations that would not have been discovered with guideline-based testing, according to new research.

A prospective study of universal genetic testing suggested that one in six colorectal cancer patients have an inherited genetic predisposition to the cancer. More than half of the patients with genetic mutations identified in this study would have been missed if the patients had undergone genetic testing based on current practice. In 11% of patients, the genetic findings led to a change in treatment, including the type of surgery or targeted cancer therapy.

These results were presented at the American College of Medical Genetics and Genomics annual meeting and published in Clinical Gastroenterology and Hepatology.

“This study shows the limitations of relying on current clinical practice guidelines for genetic evaluation, which prioritize age of cancer diagnosis and family cancer history,” said investigator Niloy Jewel Samadder, MD, of the Mayo Clinic in Phoenix.

“We were surprised that more than 50% of the patients with a genetic mutation would not have been identified had we relied on national practice guidelines or only used a small colon cancer-specific gene panel, as is commonly employed in clinical practice. The fact that more than 10% of patients actually had changes in the type of surgery or chemo/immunotherapy they received gives the strongest indicator of how genetics can revolutionize and individualize cancer care,” Dr. Samadder said.

He added that identifying a germline predisposition has multiple values, including understanding the reason patients and their family members develop specific cancers, preventing the development of new cancers in patients and family members by providing targeted prevention and screening for those at genetic risk, and improving survival in patients with a genetic driver of cancer via targeted therapy.
 

Study details

The researchers used a next-generation sequencing platform with more than 80 genes in colorectal cancer patients (not selected for age or family history) receiving care at Mayo Clinic Cancer Centers between April 1, 2018, and March 31, 2020.

The study included 361 patients with a median age of 57 years. Pathogenic germline variants were identified in 56 patients (15.5%), including 44 patients with moderate and high penetrance cancer susceptibility genes.

Younger age (under 50 years old) was associated with having a germline mutation, but “more importantly, gender, family cancer history, and stage of cancer were not,” Dr. Samadder said.

“The current clinical guidelines rely heavily on these characteristics to determine who should and should not be referred for genetic testing,” he continued. “Our study suggests that even older patients with colorectal cancer have a high rate of having pathogenic germline mutations [12%], so restricting genetic testing to only those under age 50 will miss a substantial portion of patients who might benefit from this test.”
 

Genetic testing for all

“Our findings support the broad use of genetic testing in all colorectal cancer patients, regardless of age, gender, ethnicity, family cancer history, or stage of cancer,” Dr. Samadder said.

“This study adds to a growing body of literature that provides evidence that cancer susceptibility due to variants in single genes is more common than previously appreciated,” said Marc S. Williams, MD, president of the American College of Medical Genetics and Genomics. “Current testing guidelines seem to be relatively insensitive and miss opportunities for testing of patients.”

Dr. Williams noted that 11% of patients in this study had a change in disease management related to a genetic testing result, which is “a relatively modest impact.”

“Another potential advantage of [universal] testing was the opportunity to test at-risk relatives,” Dr. Williams added. “However, only 16% of eligible individuals pursued testing. This is consistent with other studies and represents an opportunity for testing new ways to improve uptake of cascade screening.”

Dr. Williams said rigorous prospective studies enrolling large numbers of patients from diverse backgrounds are needed to inform the development and updating of genetic testing guidelines.

He disclosed no conflicts of interest. Dr. Samadder disclosed relationships with Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals. The research was funded by the Mayo Clinic, Desert Mountain Members’ CARE Foundation, David and Twila Woods Foundation, and the Gerstner Foundation.

Universal multigene panel testing of colorectal cancer patients can detect heritable mutations that would not have been discovered with guideline-based testing, according to new research.

A prospective study of universal genetic testing suggested that one in six colorectal cancer patients have an inherited genetic predisposition to the cancer. More than half of the patients with genetic mutations identified in this study would have been missed if the patients had undergone genetic testing based on current practice. In 11% of patients, the genetic findings led to a change in treatment, including the type of surgery or targeted cancer therapy.

These results were presented at the American College of Medical Genetics and Genomics annual meeting and published in Clinical Gastroenterology and Hepatology.

“This study shows the limitations of relying on current clinical practice guidelines for genetic evaluation, which prioritize age of cancer diagnosis and family cancer history,” said investigator Niloy Jewel Samadder, MD, of the Mayo Clinic in Phoenix.

“We were surprised that more than 50% of the patients with a genetic mutation would not have been identified had we relied on national practice guidelines or only used a small colon cancer-specific gene panel, as is commonly employed in clinical practice. The fact that more than 10% of patients actually had changes in the type of surgery or chemo/immunotherapy they received gives the strongest indicator of how genetics can revolutionize and individualize cancer care,” Dr. Samadder said.

He added that identifying a germline predisposition has multiple values, including understanding the reason patients and their family members develop specific cancers, preventing the development of new cancers in patients and family members by providing targeted prevention and screening for those at genetic risk, and improving survival in patients with a genetic driver of cancer via targeted therapy.
 

Study details

The researchers used a next-generation sequencing platform with more than 80 genes in colorectal cancer patients (not selected for age or family history) receiving care at Mayo Clinic Cancer Centers between April 1, 2018, and March 31, 2020.

The study included 361 patients with a median age of 57 years. Pathogenic germline variants were identified in 56 patients (15.5%), including 44 patients with moderate and high penetrance cancer susceptibility genes.

Younger age (under 50 years old) was associated with having a germline mutation, but “more importantly, gender, family cancer history, and stage of cancer were not,” Dr. Samadder said.

“The current clinical guidelines rely heavily on these characteristics to determine who should and should not be referred for genetic testing,” he continued. “Our study suggests that even older patients with colorectal cancer have a high rate of having pathogenic germline mutations [12%], so restricting genetic testing to only those under age 50 will miss a substantial portion of patients who might benefit from this test.”
 

Genetic testing for all

“Our findings support the broad use of genetic testing in all colorectal cancer patients, regardless of age, gender, ethnicity, family cancer history, or stage of cancer,” Dr. Samadder said.

“This study adds to a growing body of literature that provides evidence that cancer susceptibility due to variants in single genes is more common than previously appreciated,” said Marc S. Williams, MD, president of the American College of Medical Genetics and Genomics. “Current testing guidelines seem to be relatively insensitive and miss opportunities for testing of patients.”

Dr. Williams noted that 11% of patients in this study had a change in disease management related to a genetic testing result, which is “a relatively modest impact.”

“Another potential advantage of [universal] testing was the opportunity to test at-risk relatives,” Dr. Williams added. “However, only 16% of eligible individuals pursued testing. This is consistent with other studies and represents an opportunity for testing new ways to improve uptake of cascade screening.”

Dr. Williams said rigorous prospective studies enrolling large numbers of patients from diverse backgrounds are needed to inform the development and updating of genetic testing guidelines.

He disclosed no conflicts of interest. Dr. Samadder disclosed relationships with Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals. The research was funded by the Mayo Clinic, Desert Mountain Members’ CARE Foundation, David and Twila Woods Foundation, and the Gerstner Foundation.

Universal multigene panel testing of colorectal cancer patients can detect heritable mutations that would not have been discovered with guideline-based testing, according to new research.

A prospective study of universal genetic testing suggested that one in six colorectal cancer patients have an inherited genetic predisposition to the cancer. More than half of the patients with genetic mutations identified in this study would have been missed if the patients had undergone genetic testing based on current practice. In 11% of patients, the genetic findings led to a change in treatment, including the type of surgery or targeted cancer therapy.

These results were presented at the American College of Medical Genetics and Genomics annual meeting and published in Clinical Gastroenterology and Hepatology.

“This study shows the limitations of relying on current clinical practice guidelines for genetic evaluation, which prioritize age of cancer diagnosis and family cancer history,” said investigator Niloy Jewel Samadder, MD, of the Mayo Clinic in Phoenix.

“We were surprised that more than 50% of the patients with a genetic mutation would not have been identified had we relied on national practice guidelines or only used a small colon cancer-specific gene panel, as is commonly employed in clinical practice. The fact that more than 10% of patients actually had changes in the type of surgery or chemo/immunotherapy they received gives the strongest indicator of how genetics can revolutionize and individualize cancer care,” Dr. Samadder said.

He added that identifying a germline predisposition has multiple values, including understanding the reason patients and their family members develop specific cancers, preventing the development of new cancers in patients and family members by providing targeted prevention and screening for those at genetic risk, and improving survival in patients with a genetic driver of cancer via targeted therapy.
 

Study details

The researchers used a next-generation sequencing platform with more than 80 genes in colorectal cancer patients (not selected for age or family history) receiving care at Mayo Clinic Cancer Centers between April 1, 2018, and March 31, 2020.

The study included 361 patients with a median age of 57 years. Pathogenic germline variants were identified in 56 patients (15.5%), including 44 patients with moderate and high penetrance cancer susceptibility genes.

Younger age (under 50 years old) was associated with having a germline mutation, but “more importantly, gender, family cancer history, and stage of cancer were not,” Dr. Samadder said.

“The current clinical guidelines rely heavily on these characteristics to determine who should and should not be referred for genetic testing,” he continued. “Our study suggests that even older patients with colorectal cancer have a high rate of having pathogenic germline mutations [12%], so restricting genetic testing to only those under age 50 will miss a substantial portion of patients who might benefit from this test.”
 

Genetic testing for all

“Our findings support the broad use of genetic testing in all colorectal cancer patients, regardless of age, gender, ethnicity, family cancer history, or stage of cancer,” Dr. Samadder said.

“This study adds to a growing body of literature that provides evidence that cancer susceptibility due to variants in single genes is more common than previously appreciated,” said Marc S. Williams, MD, president of the American College of Medical Genetics and Genomics. “Current testing guidelines seem to be relatively insensitive and miss opportunities for testing of patients.”

Dr. Williams noted that 11% of patients in this study had a change in disease management related to a genetic testing result, which is “a relatively modest impact.”

“Another potential advantage of [universal] testing was the opportunity to test at-risk relatives,” Dr. Williams added. “However, only 16% of eligible individuals pursued testing. This is consistent with other studies and represents an opportunity for testing new ways to improve uptake of cascade screening.”

Dr. Williams said rigorous prospective studies enrolling large numbers of patients from diverse backgrounds are needed to inform the development and updating of genetic testing guidelines.

He disclosed no conflicts of interest. Dr. Samadder disclosed relationships with Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals. The research was funded by the Mayo Clinic, Desert Mountain Members’ CARE Foundation, David and Twila Woods Foundation, and the Gerstner Foundation.

Nivolumab continues to demonstrate a substantial survival benefit over docetaxel at 5 years in advanced non-small cell lung cancer (NSCLC) patients who progressed on platinum-based therapies, according to a pooled analysis of two phase 3 trials published in the Journal of Clinical Oncology.

Across the two studies – CheckMate 017 and 057 – 854 patients were randomized 1:1 following progression on platinum therapy to either nivolumab at 3 mg/kg once every 2 weeks or docetaxel at 75 mg/m² once every 3 weeks until further progression or unacceptable toxicity. Previously reported overall survival (OS) outcomes favored nivolumab.

At a minimum follow-up of 5.4 years, 50 nivolumab-treated patients and 9 docetaxel-treated patients were still alive.

The 5-year OS rates were 13.4% in the nivolumab arm and 2.6% in the docetaxel arm. The 5-year progression-free survival (PFS) rates were 8% and 0%, respectively.

There were no new safety signals with nivolumab, and there was no evidence of select late-onset grade 3-4 adverse events.

According to the study authors, this analysis is the longest phase 3 follow-up to date of a PD-1 inhibitor in previously treated, advanced NSCLC, and it suggests that “long-term survival beyond 5 years may ... be possible in NSCLC.”

“The results indicate that some patients with NSCLC can have long-lasting benefit from checkpoint inhibitors. We have seen similar results in terms of long-term OS with pembrolizumab,” said investigator Hossein Borghaei, DO, chief of thoracic medical oncology at the Fox Chase Cancer Center in Philadelphia.

Dr. Borghaei said the question now is “how to identify the population that really benefits from these treatments. We think PD-L1–high [patients] have a better chance, [as do patients with] tumors that have a higher percentage of tumor-infiltrating lymphocytes, but there’s nothing concrete beyond that.”

No baseline clinical or tumor factors emerged to distinguish between long-and short-term survivors, but the 5-year OS rate was 18.3% among nivolumab-treated patients with PD-L1 expression at or above 1% versus 8% among patients with expression below 1%.

The optimal duration of nivolumab treatment beyond 1 year is also uncertain.

The median duration of therapy was 36.9 months in the 5-year survivors treated with nivolumab, and 36% of patients (18/50) were still on nivolumab at the 5-year mark.

The median duration of time off treatment was 41.9 months among patients who discontinued nivolumab. Five patients (10%) were off treatment with no subsequent therapy and had not progressed at 5 years, “suggesting benefit even for patients who stopped nivolumab treatment,” the researchers wrote.

They also found that nivolumab-treated patients who remained alive at 3 years appeared to stabilize and plateau thereafter, with early response suggesting better long-term outcomes. The majority of patients without disease progression at 2, 3, and 4 years, for instance, remained progression free at 5 years. Nearly one-third of patients who achieved an objective response with nivolumab – but none of the patients who responded to docetaxel – had ongoing responses at 5 years.

Similarly, nivolumab-treated patients without disease progression at 2 years and 3 years had an 82% and 93% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression free at 5 years.

This research was funded by Bristol-Myers Squibb. Dr. Borghaei and coauthors disclosed numerous ties to the company, including employment.

[email protected]

Nivolumab continues to demonstrate a substantial survival benefit over docetaxel at 5 years in advanced non-small cell lung cancer (NSCLC) patients who progressed on platinum-based therapies, according to a pooled analysis of two phase 3 trials published in the Journal of Clinical Oncology.

Across the two studies – CheckMate 017 and 057 – 854 patients were randomized 1:1 following progression on platinum therapy to either nivolumab at 3 mg/kg once every 2 weeks or docetaxel at 75 mg/m² once every 3 weeks until further progression or unacceptable toxicity. Previously reported overall survival (OS) outcomes favored nivolumab.

At a minimum follow-up of 5.4 years, 50 nivolumab-treated patients and 9 docetaxel-treated patients were still alive.

The 5-year OS rates were 13.4% in the nivolumab arm and 2.6% in the docetaxel arm. The 5-year progression-free survival (PFS) rates were 8% and 0%, respectively.

There were no new safety signals with nivolumab, and there was no evidence of select late-onset grade 3-4 adverse events.

According to the study authors, this analysis is the longest phase 3 follow-up to date of a PD-1 inhibitor in previously treated, advanced NSCLC, and it suggests that “long-term survival beyond 5 years may ... be possible in NSCLC.”

“The results indicate that some patients with NSCLC can have long-lasting benefit from checkpoint inhibitors. We have seen similar results in terms of long-term OS with pembrolizumab,” said investigator Hossein Borghaei, DO, chief of thoracic medical oncology at the Fox Chase Cancer Center in Philadelphia.

Dr. Borghaei said the question now is “how to identify the population that really benefits from these treatments. We think PD-L1–high [patients] have a better chance, [as do patients with] tumors that have a higher percentage of tumor-infiltrating lymphocytes, but there’s nothing concrete beyond that.”

No baseline clinical or tumor factors emerged to distinguish between long-and short-term survivors, but the 5-year OS rate was 18.3% among nivolumab-treated patients with PD-L1 expression at or above 1% versus 8% among patients with expression below 1%.

The optimal duration of nivolumab treatment beyond 1 year is also uncertain.

The median duration of therapy was 36.9 months in the 5-year survivors treated with nivolumab, and 36% of patients (18/50) were still on nivolumab at the 5-year mark.

The median duration of time off treatment was 41.9 months among patients who discontinued nivolumab. Five patients (10%) were off treatment with no subsequent therapy and had not progressed at 5 years, “suggesting benefit even for patients who stopped nivolumab treatment,” the researchers wrote.

They also found that nivolumab-treated patients who remained alive at 3 years appeared to stabilize and plateau thereafter, with early response suggesting better long-term outcomes. The majority of patients without disease progression at 2, 3, and 4 years, for instance, remained progression free at 5 years. Nearly one-third of patients who achieved an objective response with nivolumab – but none of the patients who responded to docetaxel – had ongoing responses at 5 years.

Similarly, nivolumab-treated patients without disease progression at 2 years and 3 years had an 82% and 93% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression free at 5 years.

This research was funded by Bristol-Myers Squibb. Dr. Borghaei and coauthors disclosed numerous ties to the company, including employment.

[email protected]

Nivolumab continues to demonstrate a substantial survival benefit over docetaxel at 5 years in advanced non-small cell lung cancer (NSCLC) patients who progressed on platinum-based therapies, according to a pooled analysis of two phase 3 trials published in the Journal of Clinical Oncology.

Across the two studies – CheckMate 017 and 057 – 854 patients were randomized 1:1 following progression on platinum therapy to either nivolumab at 3 mg/kg once every 2 weeks or docetaxel at 75 mg/m² once every 3 weeks until further progression or unacceptable toxicity. Previously reported overall survival (OS) outcomes favored nivolumab.

At a minimum follow-up of 5.4 years, 50 nivolumab-treated patients and 9 docetaxel-treated patients were still alive.

The 5-year OS rates were 13.4% in the nivolumab arm and 2.6% in the docetaxel arm. The 5-year progression-free survival (PFS) rates were 8% and 0%, respectively.

There were no new safety signals with nivolumab, and there was no evidence of select late-onset grade 3-4 adverse events.

According to the study authors, this analysis is the longest phase 3 follow-up to date of a PD-1 inhibitor in previously treated, advanced NSCLC, and it suggests that “long-term survival beyond 5 years may ... be possible in NSCLC.”

“The results indicate that some patients with NSCLC can have long-lasting benefit from checkpoint inhibitors. We have seen similar results in terms of long-term OS with pembrolizumab,” said investigator Hossein Borghaei, DO, chief of thoracic medical oncology at the Fox Chase Cancer Center in Philadelphia.

Dr. Borghaei said the question now is “how to identify the population that really benefits from these treatments. We think PD-L1–high [patients] have a better chance, [as do patients with] tumors that have a higher percentage of tumor-infiltrating lymphocytes, but there’s nothing concrete beyond that.”

No baseline clinical or tumor factors emerged to distinguish between long-and short-term survivors, but the 5-year OS rate was 18.3% among nivolumab-treated patients with PD-L1 expression at or above 1% versus 8% among patients with expression below 1%.

The optimal duration of nivolumab treatment beyond 1 year is also uncertain.

The median duration of therapy was 36.9 months in the 5-year survivors treated with nivolumab, and 36% of patients (18/50) were still on nivolumab at the 5-year mark.

The median duration of time off treatment was 41.9 months among patients who discontinued nivolumab. Five patients (10%) were off treatment with no subsequent therapy and had not progressed at 5 years, “suggesting benefit even for patients who stopped nivolumab treatment,” the researchers wrote.

They also found that nivolumab-treated patients who remained alive at 3 years appeared to stabilize and plateau thereafter, with early response suggesting better long-term outcomes. The majority of patients without disease progression at 2, 3, and 4 years, for instance, remained progression free at 5 years. Nearly one-third of patients who achieved an objective response with nivolumab – but none of the patients who responded to docetaxel – had ongoing responses at 5 years.

Similarly, nivolumab-treated patients without disease progression at 2 years and 3 years had an 82% and 93% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression free at 5 years.

This research was funded by Bristol-Myers Squibb. Dr. Borghaei and coauthors disclosed numerous ties to the company, including employment.

[email protected]

Use of the Johnson & Johnson COVID-19 vaccine should resume in the United States for all adults, the Food and Drug Administration and Centers for Disease Contol and Prevention said April 23, although health care providers should warn patients of the risk of developing the rare and serious blood clots that caused the agencies to pause the vaccine’s distribution earlier this month.

Johnson &amp; Johnson

Use of the Johnson & Johnson COVID-19 vaccine should resume in the United States for all adults, the Food and Drug Administration and Centers for Disease Contol and Prevention said April 23, although health care providers should warn patients of the risk of developing the rare and serious blood clots that caused the agencies to pause the vaccine’s distribution earlier this month.

Johnson &amp; Johnson

Use of the Johnson & Johnson COVID-19 vaccine should resume in the United States for all adults, the Food and Drug Administration and Centers for Disease Contol and Prevention said April 23, although health care providers should warn patients of the risk of developing the rare and serious blood clots that caused the agencies to pause the vaccine’s distribution earlier this month.

Johnson &amp; Johnson

Female nurses are at significantly greater risk of dying by suicide than physicians in findings that contradict previous research suggesting doctors are at greatest risk.

pondsaksit/Getty Images

Results of a large retrospective cohort study show that nurses of both sexes were 18% more likely to die by suicide, compared with individuals in the general population. In addition, compared with female physicians, the suicide risk among female nurses was 70% higher.

“The main takeaway is that the risk of suicide among nurses is twice that of the general population and even higher than that among physicians, a population known to be at high risk,” lead author Matthew Davis, MPH, PhD, associate professor, department of systems, populations, and leadership, University of Michigan, Ann Arbor, said in an interview.

The study was published online April 14, 2021, in JAMA Psychiatry.
 

Focus on physicians

Compared with the general public, health care workers are at higher risk for suicide, but most studies of suicide have focused on physicians, Dr. Davis said.

Although “there were several older studies hinting that there might be a difference in suicide risk among nurses,” the data were insufficient to “make an overall conclusion,” he noted.

For that reason, his group “set out to make the best estimates possible” by using a large dataset from the National Violent Death Reporting System of the Centers for Disease Control and Prevention spanning the years 2007-2018 and focusing on suicides by individuals aged 30 years and older (n = 159,372 suicides).

Additional workforce data were acquired from the Bureau of Labor Statistics and the Association of Medical Colleges State Physician Workforce Data.

An important area of focus was method of suicide.

“The reason we looked at this is because people who work in healthcare have easier access to medications and know how to use them to overdose, which also increases their risk,” Dr. Davis said in a press release.
 

Enormous job strain

The researchers identified 2,374 suicides among nurses, 857 suicides among physicians, and 156,141 suicides in the general population.

Compared with the general population, nurses who died by suicide were more likely to be women, less racially diverse (non-Hispanic White), and more likely to have been married.

pondsaksit/Getty Images

Rates of suicide were higher among nurses than among the general population, with a sex-adjusted incidence for 2017-2018 of 23.8 per 100,000 versus 20.1 per 100,000 (relative risk, 1.18; 95% confidence interval, 1.03-1.36).

The difference between suicide rates among female nurses and among women in the general population was even more striking: In 2017-2018, the suicide incidence among nurses was 17.1 per 100,000 versus 8.6 per 100,000 in the population at large (RR, 1.99; 95% CI, 1.82-2.18).

“In absolute terms, being a female nurse was associated with an additional 8.5 suicides per 100,000 (7.0-10.0), compared with the general population,” the authors reported.

In contrast, overall physician suicide rates were not statistically different from those of the general population (RR, 1.01; 95% CI, 0.79-1.30) except during the period 2011-2012 (11.7 per 100,000; 95% CI, 6.6-16.8 vs. 7.5 per 100,000; 95% CI, 7.2-7.7).

Clinicians of both sexes were more likely to use poisoning and less likely to use a firearm, compared with individuals in the general population who died by suicide. For example, 24.9% (23.5%-26.4%) of nurse suicides involved poisoning, compared to 16.8% (16.6%-17.0%) of suicides in the general population.

Toxicology reports showed that the presence of antidepressants, benzodiazepines, barbiturates, and opiates was more common in clinician suicides than suicides in the general population.

Dr. Davis suggested the higher risk for suicide among nurses, compared with physicians, might be attributed to “high job demands – for example, nurses provide the majority of bedside care, work long shifts in stressful environments, and have less autonomy.

“Health care workers and friends and family of health care workers need to be aware of mental health issues and suicide risk that can be associated with the job and, most importantly, recognize those who may be struggling and encourage them to get help by calling the National Suicide Prevention Lifeline,” he said.

Other potential contributors include “avoidance of mental health services due to stigma and greater access to the means to commit suicide via medication,” Dr. Davis noted.
 

Benchmark research

Commenting on the study, Constance Guille, MD, MSCR, professor in the department of psychiatry and behavioral science, Medical University of South Carolina, Charleston, noted that nurses are “predominantly female” and that women tend to be twice as likely as men to experience depression, which is a major risk factor for suicide. Thus, this population is particularly vulnerable.

One reason the investigators did not find that suicide rates were higher among physicians is that the health care professionals whom the researchers studied were older than 30 years. Thus, the study “excludes younger physicians in early practice or training, who likely do have higher suicide rates than the general population,” she suggested.

Dr. Guille, who is the author of an accompanying editorial and was not involved with the study, recommended “taking a public health approach, implementing preventative interventions, identifying people at high risk, providing treatment for health care professionals struggling with mental health problems, and destigmatizing help seeking.”

She encouraged clinicians to “reach out to colleagues who are struggling in a way to help them seek services and check in with them because it’s helpful when peers reach out.”

Dr. Davis noted that these disturbing trends will likely increase in the aftermath of the COVID-19 pandemic. “The pandemic has placed enormous strain on the health care workforce, and we fear this may have made the situation even worse.”

The current findings “will serve as a benchmark for future comparisons,” he said.

No source of funding for the study was reported. Dr. Davis has received consulting fees as a statistical reviewer for the journal Regional Anesthesia and Pain Medicine. His coauthors disclosed no relevant financial relationships. Dr. Guille has received grants from the National Institute on Drug Abuse, the American Foundation on Suicide Prevention, and the Duke Endowment and serves on the advisory board and speakers bureau of Sage Therapeutics.

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

Female nurses are at significantly greater risk of dying by suicide than physicians in findings that contradict previous research suggesting doctors are at greatest risk.

pondsaksit/Getty Images

Results of a large retrospective cohort study show that nurses of both sexes were 18% more likely to die by suicide, compared with individuals in the general population. In addition, compared with female physicians, the suicide risk among female nurses was 70% higher.

“The main takeaway is that the risk of suicide among nurses is twice that of the general population and even higher than that among physicians, a population known to be at high risk,” lead author Matthew Davis, MPH, PhD, associate professor, department of systems, populations, and leadership, University of Michigan, Ann Arbor, said in an interview.

The study was published online April 14, 2021, in JAMA Psychiatry.
 

Focus on physicians

Compared with the general public, health care workers are at higher risk for suicide, but most studies of suicide have focused on physicians, Dr. Davis said.

Although “there were several older studies hinting that there might be a difference in suicide risk among nurses,” the data were insufficient to “make an overall conclusion,” he noted.

For that reason, his group “set out to make the best estimates possible” by using a large dataset from the National Violent Death Reporting System of the Centers for Disease Control and Prevention spanning the years 2007-2018 and focusing on suicides by individuals aged 30 years and older (n = 159,372 suicides).

Additional workforce data were acquired from the Bureau of Labor Statistics and the Association of Medical Colleges State Physician Workforce Data.

An important area of focus was method of suicide.

“The reason we looked at this is because people who work in healthcare have easier access to medications and know how to use them to overdose, which also increases their risk,” Dr. Davis said in a press release.
 

Enormous job strain

The researchers identified 2,374 suicides among nurses, 857 suicides among physicians, and 156,141 suicides in the general population.

Compared with the general population, nurses who died by suicide were more likely to be women, less racially diverse (non-Hispanic White), and more likely to have been married.

pondsaksit/Getty Images

Rates of suicide were higher among nurses than among the general population, with a sex-adjusted incidence for 2017-2018 of 23.8 per 100,000 versus 20.1 per 100,000 (relative risk, 1.18; 95% confidence interval, 1.03-1.36).

The difference between suicide rates among female nurses and among women in the general population was even more striking: In 2017-2018, the suicide incidence among nurses was 17.1 per 100,000 versus 8.6 per 100,000 in the population at large (RR, 1.99; 95% CI, 1.82-2.18).

“In absolute terms, being a female nurse was associated with an additional 8.5 suicides per 100,000 (7.0-10.0), compared with the general population,” the authors reported.

In contrast, overall physician suicide rates were not statistically different from those of the general population (RR, 1.01; 95% CI, 0.79-1.30) except during the period 2011-2012 (11.7 per 100,000; 95% CI, 6.6-16.8 vs. 7.5 per 100,000; 95% CI, 7.2-7.7).

Clinicians of both sexes were more likely to use poisoning and less likely to use a firearm, compared with individuals in the general population who died by suicide. For example, 24.9% (23.5%-26.4%) of nurse suicides involved poisoning, compared to 16.8% (16.6%-17.0%) of suicides in the general population.

Toxicology reports showed that the presence of antidepressants, benzodiazepines, barbiturates, and opiates was more common in clinician suicides than suicides in the general population.

Dr. Davis suggested the higher risk for suicide among nurses, compared with physicians, might be attributed to “high job demands – for example, nurses provide the majority of bedside care, work long shifts in stressful environments, and have less autonomy.

“Health care workers and friends and family of health care workers need to be aware of mental health issues and suicide risk that can be associated with the job and, most importantly, recognize those who may be struggling and encourage them to get help by calling the National Suicide Prevention Lifeline,” he said.

Other potential contributors include “avoidance of mental health services due to stigma and greater access to the means to commit suicide via medication,” Dr. Davis noted.
 

Benchmark research

Commenting on the study, Constance Guille, MD, MSCR, professor in the department of psychiatry and behavioral science, Medical University of South Carolina, Charleston, noted that nurses are “predominantly female” and that women tend to be twice as likely as men to experience depression, which is a major risk factor for suicide. Thus, this population is particularly vulnerable.

One reason the investigators did not find that suicide rates were higher among physicians is that the health care professionals whom the researchers studied were older than 30 years. Thus, the study “excludes younger physicians in early practice or training, who likely do have higher suicide rates than the general population,” she suggested.

Dr. Guille, who is the author of an accompanying editorial and was not involved with the study, recommended “taking a public health approach, implementing preventative interventions, identifying people at high risk, providing treatment for health care professionals struggling with mental health problems, and destigmatizing help seeking.”

She encouraged clinicians to “reach out to colleagues who are struggling in a way to help them seek services and check in with them because it’s helpful when peers reach out.”

Dr. Davis noted that these disturbing trends will likely increase in the aftermath of the COVID-19 pandemic. “The pandemic has placed enormous strain on the health care workforce, and we fear this may have made the situation even worse.”

The current findings “will serve as a benchmark for future comparisons,” he said.

No source of funding for the study was reported. Dr. Davis has received consulting fees as a statistical reviewer for the journal Regional Anesthesia and Pain Medicine. His coauthors disclosed no relevant financial relationships. Dr. Guille has received grants from the National Institute on Drug Abuse, the American Foundation on Suicide Prevention, and the Duke Endowment and serves on the advisory board and speakers bureau of Sage Therapeutics.

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

Female nurses are at significantly greater risk of dying by suicide than physicians in findings that contradict previous research suggesting doctors are at greatest risk.

pondsaksit/Getty Images

Results of a large retrospective cohort study show that nurses of both sexes were 18% more likely to die by suicide, compared with individuals in the general population. In addition, compared with female physicians, the suicide risk among female nurses was 70% higher.

“The main takeaway is that the risk of suicide among nurses is twice that of the general population and even higher than that among physicians, a population known to be at high risk,” lead author Matthew Davis, MPH, PhD, associate professor, department of systems, populations, and leadership, University of Michigan, Ann Arbor, said in an interview.

The study was published online April 14, 2021, in JAMA Psychiatry.
 

Focus on physicians

Compared with the general public, health care workers are at higher risk for suicide, but most studies of suicide have focused on physicians, Dr. Davis said.

Although “there were several older studies hinting that there might be a difference in suicide risk among nurses,” the data were insufficient to “make an overall conclusion,” he noted.

For that reason, his group “set out to make the best estimates possible” by using a large dataset from the National Violent Death Reporting System of the Centers for Disease Control and Prevention spanning the years 2007-2018 and focusing on suicides by individuals aged 30 years and older (n = 159,372 suicides).

Additional workforce data were acquired from the Bureau of Labor Statistics and the Association of Medical Colleges State Physician Workforce Data.

An important area of focus was method of suicide.

“The reason we looked at this is because people who work in healthcare have easier access to medications and know how to use them to overdose, which also increases their risk,” Dr. Davis said in a press release.
 

Enormous job strain

The researchers identified 2,374 suicides among nurses, 857 suicides among physicians, and 156,141 suicides in the general population.

Compared with the general population, nurses who died by suicide were more likely to be women, less racially diverse (non-Hispanic White), and more likely to have been married.

pondsaksit/Getty Images

Rates of suicide were higher among nurses than among the general population, with a sex-adjusted incidence for 2017-2018 of 23.8 per 100,000 versus 20.1 per 100,000 (relative risk, 1.18; 95% confidence interval, 1.03-1.36).

The difference between suicide rates among female nurses and among women in the general population was even more striking: In 2017-2018, the suicide incidence among nurses was 17.1 per 100,000 versus 8.6 per 100,000 in the population at large (RR, 1.99; 95% CI, 1.82-2.18).

“In absolute terms, being a female nurse was associated with an additional 8.5 suicides per 100,000 (7.0-10.0), compared with the general population,” the authors reported.

In contrast, overall physician suicide rates were not statistically different from those of the general population (RR, 1.01; 95% CI, 0.79-1.30) except during the period 2011-2012 (11.7 per 100,000; 95% CI, 6.6-16.8 vs. 7.5 per 100,000; 95% CI, 7.2-7.7).

Clinicians of both sexes were more likely to use poisoning and less likely to use a firearm, compared with individuals in the general population who died by suicide. For example, 24.9% (23.5%-26.4%) of nurse suicides involved poisoning, compared to 16.8% (16.6%-17.0%) of suicides in the general population.

Toxicology reports showed that the presence of antidepressants, benzodiazepines, barbiturates, and opiates was more common in clinician suicides than suicides in the general population.

Dr. Davis suggested the higher risk for suicide among nurses, compared with physicians, might be attributed to “high job demands – for example, nurses provide the majority of bedside care, work long shifts in stressful environments, and have less autonomy.

“Health care workers and friends and family of health care workers need to be aware of mental health issues and suicide risk that can be associated with the job and, most importantly, recognize those who may be struggling and encourage them to get help by calling the National Suicide Prevention Lifeline,” he said.

Other potential contributors include “avoidance of mental health services due to stigma and greater access to the means to commit suicide via medication,” Dr. Davis noted.
 

Benchmark research

Commenting on the study, Constance Guille, MD, MSCR, professor in the department of psychiatry and behavioral science, Medical University of South Carolina, Charleston, noted that nurses are “predominantly female” and that women tend to be twice as likely as men to experience depression, which is a major risk factor for suicide. Thus, this population is particularly vulnerable.

One reason the investigators did not find that suicide rates were higher among physicians is that the health care professionals whom the researchers studied were older than 30 years. Thus, the study “excludes younger physicians in early practice or training, who likely do have higher suicide rates than the general population,” she suggested.

Dr. Guille, who is the author of an accompanying editorial and was not involved with the study, recommended “taking a public health approach, implementing preventative interventions, identifying people at high risk, providing treatment for health care professionals struggling with mental health problems, and destigmatizing help seeking.”

She encouraged clinicians to “reach out to colleagues who are struggling in a way to help them seek services and check in with them because it’s helpful when peers reach out.”

Dr. Davis noted that these disturbing trends will likely increase in the aftermath of the COVID-19 pandemic. “The pandemic has placed enormous strain on the health care workforce, and we fear this may have made the situation even worse.”

The current findings “will serve as a benchmark for future comparisons,” he said.

No source of funding for the study was reported. Dr. Davis has received consulting fees as a statistical reviewer for the journal Regional Anesthesia and Pain Medicine. His coauthors disclosed no relevant financial relationships. Dr. Guille has received grants from the National Institute on Drug Abuse, the American Foundation on Suicide Prevention, and the Duke Endowment and serves on the advisory board and speakers bureau of Sage Therapeutics.

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

With the introduction of new technology to vaccinate the world with the Pfizer and Moderna mRNA vaccines, I considered other health conditions that could benefit from new modalities. Unplanned pregnancies are a public health crisis, yet the burden falls solely on women to solve, burdening them with contraceptive practices to prevent unplanned pregnancy. With the insurrection of Row v. Wade and the new bills being pushed through states that are limiting abortion, perhaps the time has come for males to accept the responsibility for contraception to prevent unplanned pregnancy. The methods that currently exist for males are condoms and vasectomy. Other options are being explored – both nonhormonal and reversible contraception including daily pills, gels, and long-acting injections.

The pill for men has been under preliminary trials with promising results. This contraceptive pill contains dimethandrolone undecanoate, which is an androgen anabolic steroid progesterone once-daily pill that suppresses FSH and LH, causing a decrease in the production of testosterone and consequently sperm production.¹ (Long, Lee, & Blithe, 2019). This pill is in long-term trials to determine the efficacy and side effects, including the impact on libido, liver, and kidney disease.

The injectable male contraceptive in trials now includes two different options. The first was a long-acting progestin, testosterone, and androgen combination. The male participants received an intramuscular injection every 8 weeks. Although the results of the study were promising – sperm production was effectively reduced, the side effects were too severe for participants to continue use. Side effects much like those of the female Depo-Provera injections included acne and mood disorders. Men experienced erectile dysfunction while at the same time having an increase in sex drive.² (Em, 2018).

Recently, researchers in India have studied a nonhormonal injectable with promising outcomes. It prevented pregnancy in more than 97% of participants. This injectable polymer gel is placed into the male’s vas deferens to block sperm from leaving the body. This product inactivates sperm, essentially creating temporary sterilization for men. The benefit of this product, called RISUG (reversible inhibition of sperm under guidance), is a single injection that can be effective for 13 years. It can be reversed earlier if needed by injecting a dissolving gel into the male’s vas deferens.^1,2 In the United States, there is an identical product called Vasalgel – a polymer injected into the vas deferens – also being studied for temporary infertility.

Another synthetic implanted androgen product being studied is 7 alpha-methyl-19-nortestosterone (MENT), a synthetic steroid that resembles testosterone but does not convert into testosterone and, consequently, does not stimulate prostate growth. It is administered via two subdermal implants and is effective for 12 months. The first subdermal implant releases the synthetic androgen, which is more potent than testosterone, and the other emits LH-releasing hormone.³ Studies demonstrate that MENT suppresses sperm production.¹

Finally, studies are underway using transdermal gel applications to suppress sperm concentrations. The daily gel is absorbed through the skin after application to two different areas of the man’s body: the shoulders and upper arms. The daily application of the progestin product, Nestorone, and testosterone gel has been found to reduce sperm concentrations to < 1 x 10⁶/mL. Studies measured gonadal concentrations after 4 weeks.¹ Users were happy with the use of a topical gel, with minimal side effects such as lower libido, weight gain, and changes in cholesterol, yet inconsistent use of the product resulted in lower than anticipated results.⁴

Male contraceptive options are long overdue to dramatically reduce the rate of unplanned pregnancies and the burden of contraception placed on women. Getting these products to market will be half the battle – getting men to commit to using these options and women to trust male compliance may further impede acceptance. Men have not had to carry the burden and economics of single parenting. Men interested in casual sex may now need to accept more responsibility for unplanned pregnancy and be proactive with prevention, particularly as abortion laws are being challenged.

Ms. Thew is medical director of the department of pediatrics division of adolescent medicine at the Medical College of Wisconsin in Milwaukee. She is a member of the editorial board for Pediatric News and has no relevant disclosures.

References

1. Long J E et al. Clin Chem. 2019;65(1):153-60.

2. Male birth control: Current options and new breakthroughs, SingleCare: Health Education. Aug. 6, 2018.

3. Sundaram K et al. Ann Med. 1993;25(2):199-205.

4. Anawalt BD et al. Andrology. 2019;7(6):878-87.

With the introduction of new technology to vaccinate the world with the Pfizer and Moderna mRNA vaccines, I considered other health conditions that could benefit from new modalities. Unplanned pregnancies are a public health crisis, yet the burden falls solely on women to solve, burdening them with contraceptive practices to prevent unplanned pregnancy. With the insurrection of Row v. Wade and the new bills being pushed through states that are limiting abortion, perhaps the time has come for males to accept the responsibility for contraception to prevent unplanned pregnancy. The methods that currently exist for males are condoms and vasectomy. Other options are being explored – both nonhormonal and reversible contraception including daily pills, gels, and long-acting injections.

The pill for men has been under preliminary trials with promising results. This contraceptive pill contains dimethandrolone undecanoate, which is an androgen anabolic steroid progesterone once-daily pill that suppresses FSH and LH, causing a decrease in the production of testosterone and consequently sperm production.¹ (Long, Lee, & Blithe, 2019). This pill is in long-term trials to determine the efficacy and side effects, including the impact on libido, liver, and kidney disease.

The injectable male contraceptive in trials now includes two different options. The first was a long-acting progestin, testosterone, and androgen combination. The male participants received an intramuscular injection every 8 weeks. Although the results of the study were promising – sperm production was effectively reduced, the side effects were too severe for participants to continue use. Side effects much like those of the female Depo-Provera injections included acne and mood disorders. Men experienced erectile dysfunction while at the same time having an increase in sex drive.² (Em, 2018).

Recently, researchers in India have studied a nonhormonal injectable with promising outcomes. It prevented pregnancy in more than 97% of participants. This injectable polymer gel is placed into the male’s vas deferens to block sperm from leaving the body. This product inactivates sperm, essentially creating temporary sterilization for men. The benefit of this product, called RISUG (reversible inhibition of sperm under guidance), is a single injection that can be effective for 13 years. It can be reversed earlier if needed by injecting a dissolving gel into the male’s vas deferens.^1,2 In the United States, there is an identical product called Vasalgel – a polymer injected into the vas deferens – also being studied for temporary infertility.

Another synthetic implanted androgen product being studied is 7 alpha-methyl-19-nortestosterone (MENT), a synthetic steroid that resembles testosterone but does not convert into testosterone and, consequently, does not stimulate prostate growth. It is administered via two subdermal implants and is effective for 12 months. The first subdermal implant releases the synthetic androgen, which is more potent than testosterone, and the other emits LH-releasing hormone.³ Studies demonstrate that MENT suppresses sperm production.¹

Finally, studies are underway using transdermal gel applications to suppress sperm concentrations. The daily gel is absorbed through the skin after application to two different areas of the man’s body: the shoulders and upper arms. The daily application of the progestin product, Nestorone, and testosterone gel has been found to reduce sperm concentrations to < 1 x 10⁶/mL. Studies measured gonadal concentrations after 4 weeks.¹ Users were happy with the use of a topical gel, with minimal side effects such as lower libido, weight gain, and changes in cholesterol, yet inconsistent use of the product resulted in lower than anticipated results.⁴

Male contraceptive options are long overdue to dramatically reduce the rate of unplanned pregnancies and the burden of contraception placed on women. Getting these products to market will be half the battle – getting men to commit to using these options and women to trust male compliance may further impede acceptance. Men have not had to carry the burden and economics of single parenting. Men interested in casual sex may now need to accept more responsibility for unplanned pregnancy and be proactive with prevention, particularly as abortion laws are being challenged.

Ms. Thew is medical director of the department of pediatrics division of adolescent medicine at the Medical College of Wisconsin in Milwaukee. She is a member of the editorial board for Pediatric News and has no relevant disclosures.

References

1. Long J E et al. Clin Chem. 2019;65(1):153-60.

2. Male birth control: Current options and new breakthroughs, SingleCare: Health Education. Aug. 6, 2018.

3. Sundaram K et al. Ann Med. 1993;25(2):199-205.

4. Anawalt BD et al. Andrology. 2019;7(6):878-87.

With the introduction of new technology to vaccinate the world with the Pfizer and Moderna mRNA vaccines, I considered other health conditions that could benefit from new modalities. Unplanned pregnancies are a public health crisis, yet the burden falls solely on women to solve, burdening them with contraceptive practices to prevent unplanned pregnancy. With the insurrection of Row v. Wade and the new bills being pushed through states that are limiting abortion, perhaps the time has come for males to accept the responsibility for contraception to prevent unplanned pregnancy. The methods that currently exist for males are condoms and vasectomy. Other options are being explored – both nonhormonal and reversible contraception including daily pills, gels, and long-acting injections.

The pill for men has been under preliminary trials with promising results. This contraceptive pill contains dimethandrolone undecanoate, which is an androgen anabolic steroid progesterone once-daily pill that suppresses FSH and LH, causing a decrease in the production of testosterone and consequently sperm production.¹ (Long, Lee, & Blithe, 2019). This pill is in long-term trials to determine the efficacy and side effects, including the impact on libido, liver, and kidney disease.

The injectable male contraceptive in trials now includes two different options. The first was a long-acting progestin, testosterone, and androgen combination. The male participants received an intramuscular injection every 8 weeks. Although the results of the study were promising – sperm production was effectively reduced, the side effects were too severe for participants to continue use. Side effects much like those of the female Depo-Provera injections included acne and mood disorders. Men experienced erectile dysfunction while at the same time having an increase in sex drive.² (Em, 2018).

Recently, researchers in India have studied a nonhormonal injectable with promising outcomes. It prevented pregnancy in more than 97% of participants. This injectable polymer gel is placed into the male’s vas deferens to block sperm from leaving the body. This product inactivates sperm, essentially creating temporary sterilization for men. The benefit of this product, called RISUG (reversible inhibition of sperm under guidance), is a single injection that can be effective for 13 years. It can be reversed earlier if needed by injecting a dissolving gel into the male’s vas deferens.^1,2 In the United States, there is an identical product called Vasalgel – a polymer injected into the vas deferens – also being studied for temporary infertility.

Another synthetic implanted androgen product being studied is 7 alpha-methyl-19-nortestosterone (MENT), a synthetic steroid that resembles testosterone but does not convert into testosterone and, consequently, does not stimulate prostate growth. It is administered via two subdermal implants and is effective for 12 months. The first subdermal implant releases the synthetic androgen, which is more potent than testosterone, and the other emits LH-releasing hormone.³ Studies demonstrate that MENT suppresses sperm production.¹

Finally, studies are underway using transdermal gel applications to suppress sperm concentrations. The daily gel is absorbed through the skin after application to two different areas of the man’s body: the shoulders and upper arms. The daily application of the progestin product, Nestorone, and testosterone gel has been found to reduce sperm concentrations to < 1 x 10⁶/mL. Studies measured gonadal concentrations after 4 weeks.¹ Users were happy with the use of a topical gel, with minimal side effects such as lower libido, weight gain, and changes in cholesterol, yet inconsistent use of the product resulted in lower than anticipated results.⁴

Male contraceptive options are long overdue to dramatically reduce the rate of unplanned pregnancies and the burden of contraception placed on women. Getting these products to market will be half the battle – getting men to commit to using these options and women to trust male compliance may further impede acceptance. Men have not had to carry the burden and economics of single parenting. Men interested in casual sex may now need to accept more responsibility for unplanned pregnancy and be proactive with prevention, particularly as abortion laws are being challenged.

Ms. Thew is medical director of the department of pediatrics division of adolescent medicine at the Medical College of Wisconsin in Milwaukee. She is a member of the editorial board for Pediatric News and has no relevant disclosures.

References

1. Long J E et al. Clin Chem. 2019;65(1):153-60.

2. Male birth control: Current options and new breakthroughs, SingleCare: Health Education. Aug. 6, 2018.

3. Sundaram K et al. Ann Med. 1993;25(2):199-205.

4. Anawalt BD et al. Andrology. 2019;7(6):878-87.

Long-haul COVID-19 patients face many health threats – including a higher chance of dying – up to 6 months after they catch the virus, according to a massive study published in the journal Nature.

Researchers examined more than 87,000 COVID-19 patients and nearly 5 million control patients in a federal database. They found COVID-19 patients had a 59% higher risk of death up to 6 months after infection, compared with noninfected people.

Those findings translate into about 8 extra deaths per 1,000 patients over 6 months, because many deaths caused by long-term COVID complications are not recorded as COVID-19 deaths, the researchers said. Among patients who were hospitalized and died after more than 30 days, there were 29 excess deaths per 1,000 patients over 6 months.

“As far as total pandemic death toll, these numbers suggest that the deaths we’re counting due to the immediate viral infection are only the tip of the iceberg,” Ziyad Al-Aly, MD, the senior author of the study and a director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System, said in a news release from the Washington University, St. Louis.

Johns Hopkins University in Baltimore says more than 3 million people worldwide and about 570,000 people in the United States have died of coronavirus-related reasons.

Long-haul COVID patients also had a much higher chance of getting sick, and not just in the respiratory system, according to the study.

The patients had a high rate of stroke and other nervous system ailments, mental health problems such as depression, the onset of diabetes, heart disease and other coronary problems, diarrhea and digestive disorders, kidney disease, blood clots, joint pain, hair loss, and general fatigue.

Patients often had clusters of these ailments. And the more severe the case of COVID-19, the higher the chance of long-term health problems, the study said.

Researchers based their study on health care databases of the U.S. Department of Veterans Affairs. Besides the 87,000 COVID patients, the database included about 5 million patients who didn’t catch COVID. The veterans in the study were about 88% men, but the large sample size included 8,880 women with confirmed cases, the news release said.

Dr. Al-Aly, an assistant professor at Washington University, said the study shows that long-haul COVID-19 could be “America’s next big health crisis.”

“Our study demonstrates that, up to 6 months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity,” he said. “Given that more than 30 million Americans have been infected with this virus, and given that the burden of long COVID-19 is substantial, the lingering effects of this disease will reverberate for many years and even decades.”

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

Long-haul COVID-19 patients face many health threats – including a higher chance of dying – up to 6 months after they catch the virus, according to a massive study published in the journal Nature.

Researchers examined more than 87,000 COVID-19 patients and nearly 5 million control patients in a federal database. They found COVID-19 patients had a 59% higher risk of death up to 6 months after infection, compared with noninfected people.

Those findings translate into about 8 extra deaths per 1,000 patients over 6 months, because many deaths caused by long-term COVID complications are not recorded as COVID-19 deaths, the researchers said. Among patients who were hospitalized and died after more than 30 days, there were 29 excess deaths per 1,000 patients over 6 months.

“As far as total pandemic death toll, these numbers suggest that the deaths we’re counting due to the immediate viral infection are only the tip of the iceberg,” Ziyad Al-Aly, MD, the senior author of the study and a director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System, said in a news release from the Washington University, St. Louis.

Johns Hopkins University in Baltimore says more than 3 million people worldwide and about 570,000 people in the United States have died of coronavirus-related reasons.

Long-haul COVID patients also had a much higher chance of getting sick, and not just in the respiratory system, according to the study.

The patients had a high rate of stroke and other nervous system ailments, mental health problems such as depression, the onset of diabetes, heart disease and other coronary problems, diarrhea and digestive disorders, kidney disease, blood clots, joint pain, hair loss, and general fatigue.

Patients often had clusters of these ailments. And the more severe the case of COVID-19, the higher the chance of long-term health problems, the study said.

Researchers based their study on health care databases of the U.S. Department of Veterans Affairs. Besides the 87,000 COVID patients, the database included about 5 million patients who didn’t catch COVID. The veterans in the study were about 88% men, but the large sample size included 8,880 women with confirmed cases, the news release said.

Dr. Al-Aly, an assistant professor at Washington University, said the study shows that long-haul COVID-19 could be “America’s next big health crisis.”

“Our study demonstrates that, up to 6 months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity,” he said. “Given that more than 30 million Americans have been infected with this virus, and given that the burden of long COVID-19 is substantial, the lingering effects of this disease will reverberate for many years and even decades.”

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

Long-haul COVID-19 patients face many health threats – including a higher chance of dying – up to 6 months after they catch the virus, according to a massive study published in the journal Nature.

Researchers examined more than 87,000 COVID-19 patients and nearly 5 million control patients in a federal database. They found COVID-19 patients had a 59% higher risk of death up to 6 months after infection, compared with noninfected people.

Those findings translate into about 8 extra deaths per 1,000 patients over 6 months, because many deaths caused by long-term COVID complications are not recorded as COVID-19 deaths, the researchers said. Among patients who were hospitalized and died after more than 30 days, there were 29 excess deaths per 1,000 patients over 6 months.

“As far as total pandemic death toll, these numbers suggest that the deaths we’re counting due to the immediate viral infection are only the tip of the iceberg,” Ziyad Al-Aly, MD, the senior author of the study and a director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System, said in a news release from the Washington University, St. Louis.

Johns Hopkins University in Baltimore says more than 3 million people worldwide and about 570,000 people in the United States have died of coronavirus-related reasons.

Long-haul COVID patients also had a much higher chance of getting sick, and not just in the respiratory system, according to the study.

The patients had a high rate of stroke and other nervous system ailments, mental health problems such as depression, the onset of diabetes, heart disease and other coronary problems, diarrhea and digestive disorders, kidney disease, blood clots, joint pain, hair loss, and general fatigue.

Patients often had clusters of these ailments. And the more severe the case of COVID-19, the higher the chance of long-term health problems, the study said.

Researchers based their study on health care databases of the U.S. Department of Veterans Affairs. Besides the 87,000 COVID patients, the database included about 5 million patients who didn’t catch COVID. The veterans in the study were about 88% men, but the large sample size included 8,880 women with confirmed cases, the news release said.

Dr. Al-Aly, an assistant professor at Washington University, said the study shows that long-haul COVID-19 could be “America’s next big health crisis.”

“Our study demonstrates that, up to 6 months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity,” he said. “Given that more than 30 million Americans have been infected with this virus, and given that the burden of long COVID-19 is substantial, the lingering effects of this disease will reverberate for many years and even decades.”

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

The percentage of physicians in the United States who are Black has increased only 4% in the past 120 years, and the number of Black male doctors has not changed at all since 1940, according to a new study.

In 1900, 1.3% of physicians were Black. In 1940, 2.8% of physicians were Black, and by 2018 – when almost 13% of the population was Black – 5.4% of doctors were Black, reports Dan Ly, MD, PhD, MPP, an assistant professor of medicine at the University of California, Los Angeles, in a study published online April 19, 2021, in the Journal of General Internal Medicine.

The proportion of male Black physicians was 2.7% in 1940 and 2.6% in 2018.

Dr. Ly also found a significant wage gap. The median income earned by White doctors was $50,000 more than the median income of Black physicians in 2018. Dr. Ly based his findings on the U.S. Census Decennial Census long form, accessed via IPUMS, a free database funded by the National Institutes of Health and other organizations.

“If we care about the health of the population, particularly the health of Black patients, we should care about how small the proportion of our physicians who are Black is and the extremely slow progress we have made as a medical system in increasing that proportion,” Dr. Ly said in an interview.

Dr. Ly said he took on this research in part because previous studies have shown that Black patients are more likely to seek preventive care from Black doctors. Thus, increasing the numbers of Black physicians could narrow gaps in life expectancy between Whites and Blacks.

He also wanted to see whether progress had been made as a result of various medical organizations and the Association of American Medical Colleges undertaking initiatives to increase workforce diversity. There has been “very, very little” progress, he said.

Norma Poll-Hunter, PhD, the AAMC’s senior director of workforce diversity, said Dr. Ly’s report “was not surprising at all.”

The AAMC reported in 2014 that the number of Black men who apply to and matriculate into medical schools has been declining since 1978. That year, there were 1,410 Black male applicants and 542 Black enrollees. In 2014, there were 1,337 applicants and 515 enrollees.

Since 2014, Black male enrollment has increased slightly, rising from 2.4% in the 2014-2015 school year to 2.9% in the 2019-2020 year, the AAMC reported last year.

In addition, among other historically underrepresented minorities, “we really have seen very small progress” despite the increase in the number of medical schools, Dr. Poll-Hunter said in an interview.

The AAMC and the National Medical Association consider the lack of Black male applicants and matriculants to be a national crisis. The two groups started an alliance in 2020 aimed at finding ways to amplify and support Black men’s interest in medicine and the biomedical sciences and to “develop systems-based solutions to address exclusionary practices that create barriers for Black men and prevent them from having equitable opportunities to successfully enroll in medical school.”

Solutions include requiring medical school admissions committees and application screeners to undergo implicit bias awareness and mitigation training, adopting holistic admissions reviews, and incentivizing institutions of higher learning to partner with Black communities in urban and rural school systems to establish K-12 health sciences academies, said NMA President Leon McDougle, MD, MPH.

“There are the systems factors, and racism is a big one that we have to tackle,” said Dr. Poll-Hunter.

Diversity isn’t just about numbers, said Dr. McDougle, a professor of family medicine and associate dean for diversity and inclusion at Ohio State University, Columbus. “We know that medical school graduates who are African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native are more likely to serve those communities as practicing physicians.

“The COVID-19 pandemic highlighted the urgent need for more African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native physicians,” he said. “Inadequate access to culturally competent care has exacerbated existing health disparities, resulting in death and hospitalization rates up to three to four times the rates of European American or White people.”

Dr. Poll-Hunter also said that studies have shown that diversity in the classroom creates a more enriched learning environment and increases civic mindedness and cognitive complexity, “as well as helps us understand people who are different than ourselves.”

The diversity goal “is not about quotas, it’s about excellence,” she said. “We know that there’s talent that exists, and we want to make sure that everyone has an opportunity to be successful.”

Dr. Ly has disclosed no relevant financial relationships.

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