Emergency department visits in the United States climbed by 15% overall from 2006 to 2014. Over the same time period, ED visits by people with mental health issues soared by 44%, according to a report from the Agency for Health Care Research & Quality.

©Getty Images

“The extent to which ERs are now flooded with patients with mental illness is unprecedented,” David R. Rubinow, MD, chairman of the department of psychiatry at the University of North Carolina, Chapel Hill, said in an interview with CNN.

This overflow is “having a really destructive effect on health care delivery in general,” Dr. Rubinow said. “There are ERs now that are repeatedly on diversion – which means they can’t see any more patients – because there are so many patients with mental illness or behavioral problems [who] are populating the ER.”

Physicians such as Mark D. Pearlmutter, MD, are convinced that EDs have become the medical refuge for many people with mental illness. “We are the safety net,” said Dr. Pearlmutter, an emergency physician affiliated with Steward Health Care in Brighton, Mass. Dr. Pearlmutter said some patients he has seen in the ED often have dual diagnoses, such as “substance abuse and depression, for example.”

As a result of this situation, patients with psychiatric needs might not receive the care that they really need, and care might be delayed for patients with other life-threatening conditions. “The ER is not a great place if you’re a mental health patient; the cardiac patients get put in front of you, and you could end up being there for a really long time, said David Morris, PhD, a psychologist at the O’Donnell Brain Institute in Dallas.

One solution to the overcrowding issue might be to do a better job at integrating mental health into medical practice, Dr. Pearlmutter suggested. After all, increasingly, primary care physicians are providing mental health care.

Twists on New Year’s resolutions

Some people bring in each new year by shifting their perspectives – without making resolutions.

Tim Ferriss, an entrepreneur known for blogs and podcasts on work and life, engages in what he calls “past year reviews,” where accomplishments are tallied frequently throughout the year in terms of their positive or negative effect, with the latter being ruled out for the coming year. Over a few years, he hopes, the list of negatives will shrink and the positive items will increase, according to a post on the NBC News website.

Instead of making resolutions, Oprah Winfrey keeps a journal that is updated nightly with five things that spark gratitude. “I live in the present moment. I try to find the good that’s going on in any given situation,” Ms. Winfrey said in a 2017 interview. The practice has taught her to be careful in her personal wishes.

Melinda Gates starts the new year with a single word to provide guidance. Past examples include “gentle,” “spacious,” and, last year, “grace.” Her selections, she said, have helped her sharpen her focus on the really important aspects of her life.

“[Grace] even helped me find a beam of peace through the sadness of a friend’s funeral. When I was upset or distressed, I whispered to myself: ‘Grace.’ That’s the power of a well-chosen word of the year. It makes the year better – and it helps me be better, too, she wrote in a recent LinkedIn post.
 

20-somethings facing challenges

A recent article in the Guardian lamented a life that is not progressing as expected.

“I am 25 and a half, single, unable to pay my rent, and the closest thing I own to a car is a broken skateboard,” wrote Juliana Piskorz. “I’m in the throes of a quarter-life crisis.”

Ms. Piskorz, who said she suffers from anxiety attacks, said her experience of this crisis manifests itself by making her want to run away, start all over, or distract herself from reality.

She is not alone. According to LinkedIn, about three-quarters of people aged 25-33 share this kind of insecurity and doubt. Low self-esteem is an important culprit, according to James Arkell, MD, a psychiatrist affiliated with the Nightingale Hospital London. “Very often, 20-somethings I see here are beautiful, talented, and have the world on a plate, but they don’t like themselves and that’s got to be about society making them feel as if they have to keep up with these unrelenting standards.”

There are other reasons for millennial despair, Ms. Piskorz speculated.

“Our childhood visions for our lives ... are no longer realistic,” she wrote. “Due to unaffordable housing, less job security, and lower incomes, the traditional ‘markers’ of adulthood, such as owning a home, getting married, and having children, are being pushed back. This has left a vacuum between our teenage years and late 20s with many of us feeling we’re navigating a no man’s land with zero clue when we’ll reach the other side.”

Seeking optimism, Ms. Piskorz noted that, as a community, millennials share many positive characteristics that should serve them well.

“We are not afraid to talk about how we feel, although we should probably talk more,” she wrote. “We stand up for the causes that we think matter; we are not afraid to try new things, and we are not willing to live a life half lived.”

Apps monitor teen angst, depression

The smartphone, often seen as a tool that fuels angst, might be a resource that could identify teenagers in trouble.

According to an article in the Washington Post, research is underway on smartphone apps that can decipher the digital footprints left by users during their Internet ramblings.

“As teens scroll through Instagram or Snapchat, tap out texts, or watch YouTube videos, they also leave digital footprints that might offer clues to their psychological well-being,” wrote article author Lindsey Tanner, of the Associated Press. “Changes in typing speed, voice tone, word choice, and how often kids stay home could signal trouble.”

“We are tracking the equivalent of a heartbeat for the human brain,” said Alex Leow, MD, PhD, an app developer, and associate professor of psychiatry and bioengineering at the University of Illinois at Chicago.

The technology is not ready for deployment because of technical glitches and, more importantly, ethical issues concerning the recording and scrutiny of a user’s personal data being roadblocks. Still, with the permission of the user, mood-detecting apps might one day be a smartphone feature. “[Users] could withdraw permission at any time, said Nick B. Allen, PhD, a psychologist at the University of Oregon, Portland, who has helped create an app that is being tested on young people who have attempted suicide.

He said the biggest hurdle is figuring out “what’s the signal and what’s the noise – what is in this enormous amount of data that people accumulate on their phone that is indicative of a mental health crisis.”
 

Virtues of “intellectual humility”

Intellectual humility is neither a character flaw nor a sign of being a pushover.

Instead, wrote science reporter Brian Resnick in an article posted on Vox.com, “it’s a method of thinking. It’s about entertaining the possibility that you may be wrong and being open to learning from the experience of others. Intellectual humility is about being actively curious about your blind spots.”

In an effort to promote intellectual humility in psychology, two researchers, Tal Yarkoni, PhD, and Christopher F. Chabris, PhD, launched the Loss-of-Confidence project. The project is a safe space where researchers who doubt a previous finding in psychology can recalibrate. “I do think it’s a cultural issue that people are not willing to admit mistakes,” said Julia M. Rohrer, a PhD candidate and personality psychologist at the Max Planck Institute for Human Development in Berlin who joined the team in 2017. “Our broader goal is to gently nudge the whole scientific system and psychology toward a different culture where it’s okay, normalized, and expected for researchers to admit past mistakes and not get penalized for it.”

Put another way, the aim is to foster a culture where intellectually humble, honest, and curious people can thrive. For that to occur, “we all, even the smartest among us, need to better appreciate our cognitive blind spots,” Mr. Resnick wrote. “Our minds are more imperfect and imprecise than we’d often like to admit.”

In a recent paper, Ms. Rohrer and her associates said the Loss-of-Confidence project grew out of an online discussion in the wake of a post by Dana R. Carney, PhD, and associates on power poses. In that post, Dr. Carney explains why she changed her position on the value of power poses, concluding that the data gathered by her lab at the time leading to the power poses theory (Psychol Sci. 2010 Oct 21 [10]:1363-8) were real but flimsy. “My views have been updated to reflect the evidence,” she wrote. “As such, I do not believe that ‘power pose’ effects are real.”

In the Vox.com article, Mr. Resnick wrote that intellectual humility is needed for two reasons. “One is that our culture promotes and rewards overconfidence and arrogance. At the same time, when we are wrong – out of ignorance or error – and realize it, our culture doesn’t make it easy to admit it. Humbling moments too easily can turn into moments of humiliation.”

Emergency department visits in the United States climbed by 15% overall from 2006 to 2014. Over the same time period, ED visits by people with mental health issues soared by 44%, according to a report from the Agency for Health Care Research & Quality.

©Getty Images

“The extent to which ERs are now flooded with patients with mental illness is unprecedented,” David R. Rubinow, MD, chairman of the department of psychiatry at the University of North Carolina, Chapel Hill, said in an interview with CNN.

This overflow is “having a really destructive effect on health care delivery in general,” Dr. Rubinow said. “There are ERs now that are repeatedly on diversion – which means they can’t see any more patients – because there are so many patients with mental illness or behavioral problems [who] are populating the ER.”

Physicians such as Mark D. Pearlmutter, MD, are convinced that EDs have become the medical refuge for many people with mental illness. “We are the safety net,” said Dr. Pearlmutter, an emergency physician affiliated with Steward Health Care in Brighton, Mass. Dr. Pearlmutter said some patients he has seen in the ED often have dual diagnoses, such as “substance abuse and depression, for example.”

As a result of this situation, patients with psychiatric needs might not receive the care that they really need, and care might be delayed for patients with other life-threatening conditions. “The ER is not a great place if you’re a mental health patient; the cardiac patients get put in front of you, and you could end up being there for a really long time, said David Morris, PhD, a psychologist at the O’Donnell Brain Institute in Dallas.

One solution to the overcrowding issue might be to do a better job at integrating mental health into medical practice, Dr. Pearlmutter suggested. After all, increasingly, primary care physicians are providing mental health care.

Twists on New Year’s resolutions

Some people bring in each new year by shifting their perspectives – without making resolutions.

Tim Ferriss, an entrepreneur known for blogs and podcasts on work and life, engages in what he calls “past year reviews,” where accomplishments are tallied frequently throughout the year in terms of their positive or negative effect, with the latter being ruled out for the coming year. Over a few years, he hopes, the list of negatives will shrink and the positive items will increase, according to a post on the NBC News website.

Instead of making resolutions, Oprah Winfrey keeps a journal that is updated nightly with five things that spark gratitude. “I live in the present moment. I try to find the good that’s going on in any given situation,” Ms. Winfrey said in a 2017 interview. The practice has taught her to be careful in her personal wishes.

Melinda Gates starts the new year with a single word to provide guidance. Past examples include “gentle,” “spacious,” and, last year, “grace.” Her selections, she said, have helped her sharpen her focus on the really important aspects of her life.

“[Grace] even helped me find a beam of peace through the sadness of a friend’s funeral. When I was upset or distressed, I whispered to myself: ‘Grace.’ That’s the power of a well-chosen word of the year. It makes the year better – and it helps me be better, too, she wrote in a recent LinkedIn post.
 

20-somethings facing challenges

A recent article in the Guardian lamented a life that is not progressing as expected.

“I am 25 and a half, single, unable to pay my rent, and the closest thing I own to a car is a broken skateboard,” wrote Juliana Piskorz. “I’m in the throes of a quarter-life crisis.”

Ms. Piskorz, who said she suffers from anxiety attacks, said her experience of this crisis manifests itself by making her want to run away, start all over, or distract herself from reality.

She is not alone. According to LinkedIn, about three-quarters of people aged 25-33 share this kind of insecurity and doubt. Low self-esteem is an important culprit, according to James Arkell, MD, a psychiatrist affiliated with the Nightingale Hospital London. “Very often, 20-somethings I see here are beautiful, talented, and have the world on a plate, but they don’t like themselves and that’s got to be about society making them feel as if they have to keep up with these unrelenting standards.”

There are other reasons for millennial despair, Ms. Piskorz speculated.

“Our childhood visions for our lives ... are no longer realistic,” she wrote. “Due to unaffordable housing, less job security, and lower incomes, the traditional ‘markers’ of adulthood, such as owning a home, getting married, and having children, are being pushed back. This has left a vacuum between our teenage years and late 20s with many of us feeling we’re navigating a no man’s land with zero clue when we’ll reach the other side.”

Seeking optimism, Ms. Piskorz noted that, as a community, millennials share many positive characteristics that should serve them well.

“We are not afraid to talk about how we feel, although we should probably talk more,” she wrote. “We stand up for the causes that we think matter; we are not afraid to try new things, and we are not willing to live a life half lived.”

Apps monitor teen angst, depression

The smartphone, often seen as a tool that fuels angst, might be a resource that could identify teenagers in trouble.

According to an article in the Washington Post, research is underway on smartphone apps that can decipher the digital footprints left by users during their Internet ramblings.

“As teens scroll through Instagram or Snapchat, tap out texts, or watch YouTube videos, they also leave digital footprints that might offer clues to their psychological well-being,” wrote article author Lindsey Tanner, of the Associated Press. “Changes in typing speed, voice tone, word choice, and how often kids stay home could signal trouble.”

“We are tracking the equivalent of a heartbeat for the human brain,” said Alex Leow, MD, PhD, an app developer, and associate professor of psychiatry and bioengineering at the University of Illinois at Chicago.

The technology is not ready for deployment because of technical glitches and, more importantly, ethical issues concerning the recording and scrutiny of a user’s personal data being roadblocks. Still, with the permission of the user, mood-detecting apps might one day be a smartphone feature. “[Users] could withdraw permission at any time, said Nick B. Allen, PhD, a psychologist at the University of Oregon, Portland, who has helped create an app that is being tested on young people who have attempted suicide.

He said the biggest hurdle is figuring out “what’s the signal and what’s the noise – what is in this enormous amount of data that people accumulate on their phone that is indicative of a mental health crisis.”
 

Virtues of “intellectual humility”

Intellectual humility is neither a character flaw nor a sign of being a pushover.

Instead, wrote science reporter Brian Resnick in an article posted on Vox.com, “it’s a method of thinking. It’s about entertaining the possibility that you may be wrong and being open to learning from the experience of others. Intellectual humility is about being actively curious about your blind spots.”

In an effort to promote intellectual humility in psychology, two researchers, Tal Yarkoni, PhD, and Christopher F. Chabris, PhD, launched the Loss-of-Confidence project. The project is a safe space where researchers who doubt a previous finding in psychology can recalibrate. “I do think it’s a cultural issue that people are not willing to admit mistakes,” said Julia M. Rohrer, a PhD candidate and personality psychologist at the Max Planck Institute for Human Development in Berlin who joined the team in 2017. “Our broader goal is to gently nudge the whole scientific system and psychology toward a different culture where it’s okay, normalized, and expected for researchers to admit past mistakes and not get penalized for it.”

Put another way, the aim is to foster a culture where intellectually humble, honest, and curious people can thrive. For that to occur, “we all, even the smartest among us, need to better appreciate our cognitive blind spots,” Mr. Resnick wrote. “Our minds are more imperfect and imprecise than we’d often like to admit.”

In a recent paper, Ms. Rohrer and her associates said the Loss-of-Confidence project grew out of an online discussion in the wake of a post by Dana R. Carney, PhD, and associates on power poses. In that post, Dr. Carney explains why she changed her position on the value of power poses, concluding that the data gathered by her lab at the time leading to the power poses theory (Psychol Sci. 2010 Oct 21 [10]:1363-8) were real but flimsy. “My views have been updated to reflect the evidence,” she wrote. “As such, I do not believe that ‘power pose’ effects are real.”

In the Vox.com article, Mr. Resnick wrote that intellectual humility is needed for two reasons. “One is that our culture promotes and rewards overconfidence and arrogance. At the same time, when we are wrong – out of ignorance or error – and realize it, our culture doesn’t make it easy to admit it. Humbling moments too easily can turn into moments of humiliation.”

Emergency department visits in the United States climbed by 15% overall from 2006 to 2014. Over the same time period, ED visits by people with mental health issues soared by 44%, according to a report from the Agency for Health Care Research & Quality.

©Getty Images

“The extent to which ERs are now flooded with patients with mental illness is unprecedented,” David R. Rubinow, MD, chairman of the department of psychiatry at the University of North Carolina, Chapel Hill, said in an interview with CNN.

This overflow is “having a really destructive effect on health care delivery in general,” Dr. Rubinow said. “There are ERs now that are repeatedly on diversion – which means they can’t see any more patients – because there are so many patients with mental illness or behavioral problems [who] are populating the ER.”

Physicians such as Mark D. Pearlmutter, MD, are convinced that EDs have become the medical refuge for many people with mental illness. “We are the safety net,” said Dr. Pearlmutter, an emergency physician affiliated with Steward Health Care in Brighton, Mass. Dr. Pearlmutter said some patients he has seen in the ED often have dual diagnoses, such as “substance abuse and depression, for example.”

As a result of this situation, patients with psychiatric needs might not receive the care that they really need, and care might be delayed for patients with other life-threatening conditions. “The ER is not a great place if you’re a mental health patient; the cardiac patients get put in front of you, and you could end up being there for a really long time, said David Morris, PhD, a psychologist at the O’Donnell Brain Institute in Dallas.

One solution to the overcrowding issue might be to do a better job at integrating mental health into medical practice, Dr. Pearlmutter suggested. After all, increasingly, primary care physicians are providing mental health care.

Twists on New Year’s resolutions

Some people bring in each new year by shifting their perspectives – without making resolutions.

Tim Ferriss, an entrepreneur known for blogs and podcasts on work and life, engages in what he calls “past year reviews,” where accomplishments are tallied frequently throughout the year in terms of their positive or negative effect, with the latter being ruled out for the coming year. Over a few years, he hopes, the list of negatives will shrink and the positive items will increase, according to a post on the NBC News website.

Instead of making resolutions, Oprah Winfrey keeps a journal that is updated nightly with five things that spark gratitude. “I live in the present moment. I try to find the good that’s going on in any given situation,” Ms. Winfrey said in a 2017 interview. The practice has taught her to be careful in her personal wishes.

Melinda Gates starts the new year with a single word to provide guidance. Past examples include “gentle,” “spacious,” and, last year, “grace.” Her selections, she said, have helped her sharpen her focus on the really important aspects of her life.

“[Grace] even helped me find a beam of peace through the sadness of a friend’s funeral. When I was upset or distressed, I whispered to myself: ‘Grace.’ That’s the power of a well-chosen word of the year. It makes the year better – and it helps me be better, too, she wrote in a recent LinkedIn post.
 

20-somethings facing challenges

A recent article in the Guardian lamented a life that is not progressing as expected.

“I am 25 and a half, single, unable to pay my rent, and the closest thing I own to a car is a broken skateboard,” wrote Juliana Piskorz. “I’m in the throes of a quarter-life crisis.”

Ms. Piskorz, who said she suffers from anxiety attacks, said her experience of this crisis manifests itself by making her want to run away, start all over, or distract herself from reality.

She is not alone. According to LinkedIn, about three-quarters of people aged 25-33 share this kind of insecurity and doubt. Low self-esteem is an important culprit, according to James Arkell, MD, a psychiatrist affiliated with the Nightingale Hospital London. “Very often, 20-somethings I see here are beautiful, talented, and have the world on a plate, but they don’t like themselves and that’s got to be about society making them feel as if they have to keep up with these unrelenting standards.”

There are other reasons for millennial despair, Ms. Piskorz speculated.

“Our childhood visions for our lives ... are no longer realistic,” she wrote. “Due to unaffordable housing, less job security, and lower incomes, the traditional ‘markers’ of adulthood, such as owning a home, getting married, and having children, are being pushed back. This has left a vacuum between our teenage years and late 20s with many of us feeling we’re navigating a no man’s land with zero clue when we’ll reach the other side.”

Seeking optimism, Ms. Piskorz noted that, as a community, millennials share many positive characteristics that should serve them well.

“We are not afraid to talk about how we feel, although we should probably talk more,” she wrote. “We stand up for the causes that we think matter; we are not afraid to try new things, and we are not willing to live a life half lived.”

Apps monitor teen angst, depression

The smartphone, often seen as a tool that fuels angst, might be a resource that could identify teenagers in trouble.

According to an article in the Washington Post, research is underway on smartphone apps that can decipher the digital footprints left by users during their Internet ramblings.

“As teens scroll through Instagram or Snapchat, tap out texts, or watch YouTube videos, they also leave digital footprints that might offer clues to their psychological well-being,” wrote article author Lindsey Tanner, of the Associated Press. “Changes in typing speed, voice tone, word choice, and how often kids stay home could signal trouble.”

“We are tracking the equivalent of a heartbeat for the human brain,” said Alex Leow, MD, PhD, an app developer, and associate professor of psychiatry and bioengineering at the University of Illinois at Chicago.

The technology is not ready for deployment because of technical glitches and, more importantly, ethical issues concerning the recording and scrutiny of a user’s personal data being roadblocks. Still, with the permission of the user, mood-detecting apps might one day be a smartphone feature. “[Users] could withdraw permission at any time, said Nick B. Allen, PhD, a psychologist at the University of Oregon, Portland, who has helped create an app that is being tested on young people who have attempted suicide.

He said the biggest hurdle is figuring out “what’s the signal and what’s the noise – what is in this enormous amount of data that people accumulate on their phone that is indicative of a mental health crisis.”
 

Virtues of “intellectual humility”

Intellectual humility is neither a character flaw nor a sign of being a pushover.

Instead, wrote science reporter Brian Resnick in an article posted on Vox.com, “it’s a method of thinking. It’s about entertaining the possibility that you may be wrong and being open to learning from the experience of others. Intellectual humility is about being actively curious about your blind spots.”

In an effort to promote intellectual humility in psychology, two researchers, Tal Yarkoni, PhD, and Christopher F. Chabris, PhD, launched the Loss-of-Confidence project. The project is a safe space where researchers who doubt a previous finding in psychology can recalibrate. “I do think it’s a cultural issue that people are not willing to admit mistakes,” said Julia M. Rohrer, a PhD candidate and personality psychologist at the Max Planck Institute for Human Development in Berlin who joined the team in 2017. “Our broader goal is to gently nudge the whole scientific system and psychology toward a different culture where it’s okay, normalized, and expected for researchers to admit past mistakes and not get penalized for it.”

Put another way, the aim is to foster a culture where intellectually humble, honest, and curious people can thrive. For that to occur, “we all, even the smartest among us, need to better appreciate our cognitive blind spots,” Mr. Resnick wrote. “Our minds are more imperfect and imprecise than we’d often like to admit.”

In a recent paper, Ms. Rohrer and her associates said the Loss-of-Confidence project grew out of an online discussion in the wake of a post by Dana R. Carney, PhD, and associates on power poses. In that post, Dr. Carney explains why she changed her position on the value of power poses, concluding that the data gathered by her lab at the time leading to the power poses theory (Psychol Sci. 2010 Oct 21 [10]:1363-8) were real but flimsy. “My views have been updated to reflect the evidence,” she wrote. “As such, I do not believe that ‘power pose’ effects are real.”

In the Vox.com article, Mr. Resnick wrote that intellectual humility is needed for two reasons. “One is that our culture promotes and rewards overconfidence and arrogance. At the same time, when we are wrong – out of ignorance or error – and realize it, our culture doesn’t make it easy to admit it. Humbling moments too easily can turn into moments of humiliation.”

LOS ANGELES – In some individuals, reduced degradation of insulin by the liver is the cause of type 2 diabetes mellitus.

Doug Brunk/MDedge News

That’s a hypothesis that Richard N. Bergman, PhD, and his colleagues are testing in his lab at the Sports Spectacular Diabetes and Obesity Wellness and Research Center at Cedars-Sinai Medical Center, Los Angeles.

“More than 50% of insulin secreted into the portal vein is degraded by the liver and never enters the systemic circulation,” Dr. Bergman said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “We have found that if you make an animal insulin resistant with a high fat diet, they degrade less of the insulin. Why is that? They deliver a higher fraction of the insulin into the systemic circulation. One of the answers is that the liver is a gateway for insulin delivery to the systemic circulation.” In fact, when he and his colleagues tested a population of normal dogs, they found wide variability in the ability of the liver to take up and degrade insulin (Diabetes. 2018 67[8]:1495-503).

“It ranged from 20% to 70%; I didn’t believe these data,” said Dr. Bergman, who is also chair in diabetes research at Cedars-Sinai. “We had to redo the study and the same thing was true. There’s a wide variation in what fraction of insulin that enters the liver is degraded. That led to the idea that this could be true in humans.”

[email protected]

LOS ANGELES – In some individuals, reduced degradation of insulin by the liver is the cause of type 2 diabetes mellitus.

Doug Brunk/MDedge News

That’s a hypothesis that Richard N. Bergman, PhD, and his colleagues are testing in his lab at the Sports Spectacular Diabetes and Obesity Wellness and Research Center at Cedars-Sinai Medical Center, Los Angeles.

“More than 50% of insulin secreted into the portal vein is degraded by the liver and never enters the systemic circulation,” Dr. Bergman said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “We have found that if you make an animal insulin resistant with a high fat diet, they degrade less of the insulin. Why is that? They deliver a higher fraction of the insulin into the systemic circulation. One of the answers is that the liver is a gateway for insulin delivery to the systemic circulation.” In fact, when he and his colleagues tested a population of normal dogs, they found wide variability in the ability of the liver to take up and degrade insulin (Diabetes. 2018 67[8]:1495-503).

“It ranged from 20% to 70%; I didn’t believe these data,” said Dr. Bergman, who is also chair in diabetes research at Cedars-Sinai. “We had to redo the study and the same thing was true. There’s a wide variation in what fraction of insulin that enters the liver is degraded. That led to the idea that this could be true in humans.”

[email protected]

LOS ANGELES – In some individuals, reduced degradation of insulin by the liver is the cause of type 2 diabetes mellitus.

Doug Brunk/MDedge News

That’s a hypothesis that Richard N. Bergman, PhD, and his colleagues are testing in his lab at the Sports Spectacular Diabetes and Obesity Wellness and Research Center at Cedars-Sinai Medical Center, Los Angeles.

“More than 50% of insulin secreted into the portal vein is degraded by the liver and never enters the systemic circulation,” Dr. Bergman said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “We have found that if you make an animal insulin resistant with a high fat diet, they degrade less of the insulin. Why is that? They deliver a higher fraction of the insulin into the systemic circulation. One of the answers is that the liver is a gateway for insulin delivery to the systemic circulation.” In fact, when he and his colleagues tested a population of normal dogs, they found wide variability in the ability of the liver to take up and degrade insulin (Diabetes. 2018 67[8]:1495-503).

“It ranged from 20% to 70%; I didn’t believe these data,” said Dr. Bergman, who is also chair in diabetes research at Cedars-Sinai. “We had to redo the study and the same thing was true. There’s a wide variation in what fraction of insulin that enters the liver is degraded. That led to the idea that this could be true in humans.”

[email protected]

Adiposity changes during adolescence are more strongly associated with ovarian cancer risk than changes in adiposity during adulthood, according to data from the Nurses’ Health Study.

Among the 133,526 women followed prospectively in the observational study, investigators documented 562 incident ovarian cancers in the first cohort (1980-2012) and 226 in the second cohort (1989-2013) during 32 years of follow-up. Body mass index (BMI) changes that occurred between age 10 and 18 years was strongly positively associated with ovarian cancer risk (hazard Ratio, 1.24; 95% confidence interval, 1.11-1.39; P = .0002), compared with a slight association with risk for BMI change after age 18 years (HR, 1.06; 95% CI, 0.99-1.14; P = .10), Tianyi Huang, ScD, of Harvard Medical School, Boston, and his associates reported in Annals of Oncology.

The association between adolescent BMI changes and ovarian cancer risk was stronger for premenopausal cases (HR, 2.41; 95% CI, 1.38-4.19; P = .002), compared with postmenopausal cases (HR, 1.31; 95% CI, 0.90-1.92; P = .16), and suggestively stronger for nonserous tumors versus serous ovarian tumors.

For BMI change between age 10 and 18 years, the HR for every 5 kg/m² increase was 1.35 (1.10, 1.65) for nonserous cancer and 1.08 (0.90, 1.28) for serous cancer (P = .10).

“This study provides additional evidence to support that maintaining a healthy weight throughout the life course may have moderate benefits on ovarian cancer prevention, particularly nonserous subtypes diagnosed during premenopausal years,” the authors wrote. “Further studies are needed to understand the specific mechanisms linking peripubertal adiposity and adult ovarian cancer risk.”

SOURCE: Huang T et al. Ann Oncol. 2018 Dec 21. doi: 10.1093/annonc/mdy546.

Adiposity changes during adolescence are more strongly associated with ovarian cancer risk than changes in adiposity during adulthood, according to data from the Nurses’ Health Study.

Among the 133,526 women followed prospectively in the observational study, investigators documented 562 incident ovarian cancers in the first cohort (1980-2012) and 226 in the second cohort (1989-2013) during 32 years of follow-up. Body mass index (BMI) changes that occurred between age 10 and 18 years was strongly positively associated with ovarian cancer risk (hazard Ratio, 1.24; 95% confidence interval, 1.11-1.39; P = .0002), compared with a slight association with risk for BMI change after age 18 years (HR, 1.06; 95% CI, 0.99-1.14; P = .10), Tianyi Huang, ScD, of Harvard Medical School, Boston, and his associates reported in Annals of Oncology.

The association between adolescent BMI changes and ovarian cancer risk was stronger for premenopausal cases (HR, 2.41; 95% CI, 1.38-4.19; P = .002), compared with postmenopausal cases (HR, 1.31; 95% CI, 0.90-1.92; P = .16), and suggestively stronger for nonserous tumors versus serous ovarian tumors.

For BMI change between age 10 and 18 years, the HR for every 5 kg/m² increase was 1.35 (1.10, 1.65) for nonserous cancer and 1.08 (0.90, 1.28) for serous cancer (P = .10).

“This study provides additional evidence to support that maintaining a healthy weight throughout the life course may have moderate benefits on ovarian cancer prevention, particularly nonserous subtypes diagnosed during premenopausal years,” the authors wrote. “Further studies are needed to understand the specific mechanisms linking peripubertal adiposity and adult ovarian cancer risk.”

SOURCE: Huang T et al. Ann Oncol. 2018 Dec 21. doi: 10.1093/annonc/mdy546.

Adiposity changes during adolescence are more strongly associated with ovarian cancer risk than changes in adiposity during adulthood, according to data from the Nurses’ Health Study.

Among the 133,526 women followed prospectively in the observational study, investigators documented 562 incident ovarian cancers in the first cohort (1980-2012) and 226 in the second cohort (1989-2013) during 32 years of follow-up. Body mass index (BMI) changes that occurred between age 10 and 18 years was strongly positively associated with ovarian cancer risk (hazard Ratio, 1.24; 95% confidence interval, 1.11-1.39; P = .0002), compared with a slight association with risk for BMI change after age 18 years (HR, 1.06; 95% CI, 0.99-1.14; P = .10), Tianyi Huang, ScD, of Harvard Medical School, Boston, and his associates reported in Annals of Oncology.

The association between adolescent BMI changes and ovarian cancer risk was stronger for premenopausal cases (HR, 2.41; 95% CI, 1.38-4.19; P = .002), compared with postmenopausal cases (HR, 1.31; 95% CI, 0.90-1.92; P = .16), and suggestively stronger for nonserous tumors versus serous ovarian tumors.

For BMI change between age 10 and 18 years, the HR for every 5 kg/m² increase was 1.35 (1.10, 1.65) for nonserous cancer and 1.08 (0.90, 1.28) for serous cancer (P = .10).

“This study provides additional evidence to support that maintaining a healthy weight throughout the life course may have moderate benefits on ovarian cancer prevention, particularly nonserous subtypes diagnosed during premenopausal years,” the authors wrote. “Further studies are needed to understand the specific mechanisms linking peripubertal adiposity and adult ovarian cancer risk.”

SOURCE: Huang T et al. Ann Oncol. 2018 Dec 21. doi: 10.1093/annonc/mdy546.

The FP recognized this as squamous cell carcinoma (SCC) of the penis.

The FP knew that a biopsy would be needed to confirm his clinical impression and obtained informed consent for a shave biopsy of a portion of the lesion. While the FP was taught in medical school to never use epinephrine on the penis, he realized that this was merely a myth (see “Biopsies for skin cancer detection: Dispelling the myths”). He injected 1% lidocaine with epinephrine into the lesion for anesthesia and to minimize bleeding during the shave biopsy. (See the Watch & Learn video on “Shave biopsy.”) The FP performed a shave biopsy of a small portion of the lesion farthest from the urethra.

Aluminum chloride was used to stop most of the bleeding, but since the penis is very vascular, some electrocoagulation was needed to stop all of the bleeding. The pathology came back as an invasive SCC. Due to the location of the lesion on the glans and around the urethra, the patient was referred to Urology.

A partial penectomy was performed and clear surgical margins were achieved. If the lesion had been on the shaft of the penis (rather than the glans penis), a Mohs surgeon would have attempted to save the whole penis with tissue sparing surgery.

‌

Photo courtesy of Jeff Meffert, MD, and text courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP recognized this as squamous cell carcinoma (SCC) of the penis.

The FP knew that a biopsy would be needed to confirm his clinical impression and obtained informed consent for a shave biopsy of a portion of the lesion. While the FP was taught in medical school to never use epinephrine on the penis, he realized that this was merely a myth (see “Biopsies for skin cancer detection: Dispelling the myths”). He injected 1% lidocaine with epinephrine into the lesion for anesthesia and to minimize bleeding during the shave biopsy. (See the Watch & Learn video on “Shave biopsy.”) The FP performed a shave biopsy of a small portion of the lesion farthest from the urethra.

Aluminum chloride was used to stop most of the bleeding, but since the penis is very vascular, some electrocoagulation was needed to stop all of the bleeding. The pathology came back as an invasive SCC. Due to the location of the lesion on the glans and around the urethra, the patient was referred to Urology.

A partial penectomy was performed and clear surgical margins were achieved. If the lesion had been on the shaft of the penis (rather than the glans penis), a Mohs surgeon would have attempted to save the whole penis with tissue sparing surgery.

‌

Photo courtesy of Jeff Meffert, MD, and text courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP recognized this as squamous cell carcinoma (SCC) of the penis.

The FP knew that a biopsy would be needed to confirm his clinical impression and obtained informed consent for a shave biopsy of a portion of the lesion. While the FP was taught in medical school to never use epinephrine on the penis, he realized that this was merely a myth (see “Biopsies for skin cancer detection: Dispelling the myths”). He injected 1% lidocaine with epinephrine into the lesion for anesthesia and to minimize bleeding during the shave biopsy. (See the Watch & Learn video on “Shave biopsy.”) The FP performed a shave biopsy of a small portion of the lesion farthest from the urethra.

Aluminum chloride was used to stop most of the bleeding, but since the penis is very vascular, some electrocoagulation was needed to stop all of the bleeding. The pathology came back as an invasive SCC. Due to the location of the lesion on the glans and around the urethra, the patient was referred to Urology.

A partial penectomy was performed and clear surgical margins were achieved. If the lesion had been on the shaft of the penis (rather than the glans penis), a Mohs surgeon would have attempted to save the whole penis with tissue sparing surgery.

‌

Photo courtesy of Jeff Meffert, MD, and text courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

Consider thinking outside the lower body for pelvic pain. Also today, treating obstructive sleep apnea with positive airway pressure decreased amyloid levels, spending on medical marketing increased by more than $12 billion over that past two decades, and one expert has advice on how you can get your work published.

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Consider thinking outside the lower body for pelvic pain. Also today, treating obstructive sleep apnea with positive airway pressure decreased amyloid levels, spending on medical marketing increased by more than $12 billion over that past two decades, and one expert has advice on how you can get your work published.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Consider thinking outside the lower body for pelvic pain. Also today, treating obstructive sleep apnea with positive airway pressure decreased amyloid levels, spending on medical marketing increased by more than $12 billion over that past two decades, and one expert has advice on how you can get your work published.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

Torrent Pharmaceuticals is expanding its recall of losartan potassium tablets from 2 lots to 12 lots, according to a Safety Alert from the Food and Drug Administration.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The recall was based on the discovery of N-nitrosodiethylamine (NDEA) above recommended levels in seven 100-mg lots of losartan, four 50-mg lots, and one 25-mg lot. NDEA is a naturally occurring substance that has been classified as a probable human carcinogen by the International Agency for Research on Cancer. Torrent Pharmaceuticals has not reported any adverse events related to the recall.

Losartan currently is indicated to treat hypertension, hypertensive patients with left ventricular hypertrophy, and nephropathy in type 2 diabetic patients. Patients who are taking losartan should continue to do so, as stopping treatment without an alternative could represent a greater health risk.

“Patients should contact their pharmacist or physician who can advise them about an alternative treatment prior to returning their medication,” the FDA said in the press release.

Find the full press release on the FDA website.

[email protected]

Torrent Pharmaceuticals is expanding its recall of losartan potassium tablets from 2 lots to 12 lots, according to a Safety Alert from the Food and Drug Administration.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The recall was based on the discovery of N-nitrosodiethylamine (NDEA) above recommended levels in seven 100-mg lots of losartan, four 50-mg lots, and one 25-mg lot. NDEA is a naturally occurring substance that has been classified as a probable human carcinogen by the International Agency for Research on Cancer. Torrent Pharmaceuticals has not reported any adverse events related to the recall.

Losartan currently is indicated to treat hypertension, hypertensive patients with left ventricular hypertrophy, and nephropathy in type 2 diabetic patients. Patients who are taking losartan should continue to do so, as stopping treatment without an alternative could represent a greater health risk.

“Patients should contact their pharmacist or physician who can advise them about an alternative treatment prior to returning their medication,” the FDA said in the press release.

Find the full press release on the FDA website.

[email protected]

Torrent Pharmaceuticals is expanding its recall of losartan potassium tablets from 2 lots to 12 lots, according to a Safety Alert from the Food and Drug Administration.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The recall was based on the discovery of N-nitrosodiethylamine (NDEA) above recommended levels in seven 100-mg lots of losartan, four 50-mg lots, and one 25-mg lot. NDEA is a naturally occurring substance that has been classified as a probable human carcinogen by the International Agency for Research on Cancer. Torrent Pharmaceuticals has not reported any adverse events related to the recall.

Losartan currently is indicated to treat hypertension, hypertensive patients with left ventricular hypertrophy, and nephropathy in type 2 diabetic patients. Patients who are taking losartan should continue to do so, as stopping treatment without an alternative could represent a greater health risk.

“Patients should contact their pharmacist or physician who can advise them about an alternative treatment prior to returning their medication,” the FDA said in the press release.

Find the full press release on the FDA website.

[email protected]

Negligent management of labor is the top cause of lawsuits against ob.gyns, a study of legal claims shows.

Researchers with national medical liability insurer, Coverys, analyzed 472 ob.gyn.–related claims from their database that closed between 2013 and 2017. Of the claims, 37% stemmed from alleged negligence during labor management, while 14% resulted from inappropriate management of pregnancy, and 12% were associated with negligent patient monitoring. And 11% resulted from an alleged delay in performing cesarean section, according to the report.

More than half of the obstetric-related claims involved patients with at least one known comorbidity (58%), most commonly diabetes and obesity. Hypertension was the third most frequent risk factor associated with patient claims, followed by post-40 week gestation and macrosomia. Vaginal births were responsible for more claims than cesarean sections (52% vs. 45%); vaginal births also resulted in more than three times as many claims as did emergency cesareans.

Nearly all obstetrics claims resulted in injuries or death to babies (90%), with 41% of claims associated with neurologic injuries, 37% related to shoulder dystocia/brachial plexus injuries, and 34% ending in fetal demise, including stillbirth. Other claims included congenital injuries, chorioamnionitis, and lacerations/contusions.

Of 60 claims that included communication breakdowns as a key factor, 28% were associated with communication failures between physicians, while 28% were associated with communication breakdowns between doctors and nurses. Of the communication mishap cases, 17% were associated with communication failures among physicians and mid-level providers and 10% were associated with breakdowns in communication between physicians and patients.

The Coverys report includes guidance for ob.gyns. on reducing their legal risk when caring for patients in labor. Some primary tips include:

• Require fetal heart rate (FHR) interpretation training. All obstetric providers and staff should undergo training on the interpretation of FHR patterns before treating obstetric patients.
• Strengthen communication. Health professionals should use the same language when describing electronic fetal-monitoring patterns. Such terminology should be used consistently through all medical record entries and communications regarding patient cases.
• Craft and maintain fetal-monitoring policies. Develop evidence-based policies and procedures around fetal monitoring during labor that outline when each type of monitoring should be used based on each patient case and circumstance.
• Keep doctors informed. Develop protocols that ensure physicians remain in the loop regarding the condition of the patient and which includes communication strategies for contacting doctors when the patient’s condition changes or requires oversight.

Negligent management of labor is the top cause of lawsuits against ob.gyns, a study of legal claims shows.

Researchers with national medical liability insurer, Coverys, analyzed 472 ob.gyn.–related claims from their database that closed between 2013 and 2017. Of the claims, 37% stemmed from alleged negligence during labor management, while 14% resulted from inappropriate management of pregnancy, and 12% were associated with negligent patient monitoring. And 11% resulted from an alleged delay in performing cesarean section, according to the report.

More than half of the obstetric-related claims involved patients with at least one known comorbidity (58%), most commonly diabetes and obesity. Hypertension was the third most frequent risk factor associated with patient claims, followed by post-40 week gestation and macrosomia. Vaginal births were responsible for more claims than cesarean sections (52% vs. 45%); vaginal births also resulted in more than three times as many claims as did emergency cesareans.

Nearly all obstetrics claims resulted in injuries or death to babies (90%), with 41% of claims associated with neurologic injuries, 37% related to shoulder dystocia/brachial plexus injuries, and 34% ending in fetal demise, including stillbirth. Other claims included congenital injuries, chorioamnionitis, and lacerations/contusions.

Of 60 claims that included communication breakdowns as a key factor, 28% were associated with communication failures between physicians, while 28% were associated with communication breakdowns between doctors and nurses. Of the communication mishap cases, 17% were associated with communication failures among physicians and mid-level providers and 10% were associated with breakdowns in communication between physicians and patients.

The Coverys report includes guidance for ob.gyns. on reducing their legal risk when caring for patients in labor. Some primary tips include:

• Require fetal heart rate (FHR) interpretation training. All obstetric providers and staff should undergo training on the interpretation of FHR patterns before treating obstetric patients.
• Strengthen communication. Health professionals should use the same language when describing electronic fetal-monitoring patterns. Such terminology should be used consistently through all medical record entries and communications regarding patient cases.
• Craft and maintain fetal-monitoring policies. Develop evidence-based policies and procedures around fetal monitoring during labor that outline when each type of monitoring should be used based on each patient case and circumstance.
• Keep doctors informed. Develop protocols that ensure physicians remain in the loop regarding the condition of the patient and which includes communication strategies for contacting doctors when the patient’s condition changes or requires oversight.

Negligent management of labor is the top cause of lawsuits against ob.gyns, a study of legal claims shows.

Researchers with national medical liability insurer, Coverys, analyzed 472 ob.gyn.–related claims from their database that closed between 2013 and 2017. Of the claims, 37% stemmed from alleged negligence during labor management, while 14% resulted from inappropriate management of pregnancy, and 12% were associated with negligent patient monitoring. And 11% resulted from an alleged delay in performing cesarean section, according to the report.

More than half of the obstetric-related claims involved patients with at least one known comorbidity (58%), most commonly diabetes and obesity. Hypertension was the third most frequent risk factor associated with patient claims, followed by post-40 week gestation and macrosomia. Vaginal births were responsible for more claims than cesarean sections (52% vs. 45%); vaginal births also resulted in more than three times as many claims as did emergency cesareans.

Nearly all obstetrics claims resulted in injuries or death to babies (90%), with 41% of claims associated with neurologic injuries, 37% related to shoulder dystocia/brachial plexus injuries, and 34% ending in fetal demise, including stillbirth. Other claims included congenital injuries, chorioamnionitis, and lacerations/contusions.

Of 60 claims that included communication breakdowns as a key factor, 28% were associated with communication failures between physicians, while 28% were associated with communication breakdowns between doctors and nurses. Of the communication mishap cases, 17% were associated with communication failures among physicians and mid-level providers and 10% were associated with breakdowns in communication between physicians and patients.

The Coverys report includes guidance for ob.gyns. on reducing their legal risk when caring for patients in labor. Some primary tips include:

• Require fetal heart rate (FHR) interpretation training. All obstetric providers and staff should undergo training on the interpretation of FHR patterns before treating obstetric patients.
• Strengthen communication. Health professionals should use the same language when describing electronic fetal-monitoring patterns. Such terminology should be used consistently through all medical record entries and communications regarding patient cases.
• Craft and maintain fetal-monitoring policies. Develop evidence-based policies and procedures around fetal monitoring during labor that outline when each type of monitoring should be used based on each patient case and circumstance.
• Keep doctors informed. Develop protocols that ensure physicians remain in the loop regarding the condition of the patient and which includes communication strategies for contacting doctors when the patient’s condition changes or requires oversight.

Low-dose treatment with plerixafor, a CXC chemokine receptor 4 antagonist, was well tolerated and markedly improved severe presentations of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome in three patients who could not receive granulocyte colony-stimulating factor therapy, investigators reported.

“Myelofibrosis, panleukopenia, anemia, and thrombocytopenia were ameliorated, the wart burden and frequency of infection declined, human papillomavirus–associated oropharyngeal squamous-cell carcinoma stabilized, and quality of life improved markedly,” David H. McDermott, MD, of the National Institute of Allergy and Infectious Diseases and his colleagues wrote in the New England Journal of Medicine.

WHIM syndrome is a primary immunodeficiency disorder characterized by panleukopenia and caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (CXCR4). Granulocyte colony-stimulating factor (G-CSF) therapy improves neutropenia in these patients, but not other cytopenias.

Previously, the investigators treated three WHIM syndrome patients with plerixafor (Mozobil), which was well tolerated and led to sustained increases in circulating neutrophils, lymphocytes, and monocytes. The current report is of three patients with advanced WHIM syndrome who received open-label plerixafor because they were ineligible for a randomized trial of this drug.

After treatment initiation, infection frequency dropped by 85% in one patient and declined markedly in all three patients. Lymphocyte counts improved the most in two patients while neutrophils were most responsive in the third patient. Warts partially resolved in two patients, of which one patient also experienced partial resolution of head and neck squamous cell carcinoma. This patient later died of a multidrug-resistant Pseudomonas aeruginosa infection after undergoing a 9-hour surgery.

In the third patient, plerixafor therapy led to clearance of TSPyV and 17 human papillomavirus (HPV) infections, with consequent resolution of chronic, progressive, multifocal eczematoid and follicular lesions, the researchers reported. The study dose was relatively low – about 10% of the stem-cell mobilization dose – and did not cause bone pain or other treatment-emergent adverse events, despite the relatively long treatment course (19-52 months).

A separate, phase 3 trial (NCT02231879) has enrolled 19 patients. Primary results are expected in 2020.

The National Institutes of Health funded the work. Dr. McDermott reported a pending patent to reduce CXCR4 expression and/or function to enhance engraftment of hematopoietic stem cells.

SOURCE: McDermott DH et al. N Engl J Med. 2019;380:163-70.
 

Low-dose treatment with plerixafor, a CXC chemokine receptor 4 antagonist, was well tolerated and markedly improved severe presentations of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome in three patients who could not receive granulocyte colony-stimulating factor therapy, investigators reported.

“Myelofibrosis, panleukopenia, anemia, and thrombocytopenia were ameliorated, the wart burden and frequency of infection declined, human papillomavirus–associated oropharyngeal squamous-cell carcinoma stabilized, and quality of life improved markedly,” David H. McDermott, MD, of the National Institute of Allergy and Infectious Diseases and his colleagues wrote in the New England Journal of Medicine.

WHIM syndrome is a primary immunodeficiency disorder characterized by panleukopenia and caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (CXCR4). Granulocyte colony-stimulating factor (G-CSF) therapy improves neutropenia in these patients, but not other cytopenias.

Previously, the investigators treated three WHIM syndrome patients with plerixafor (Mozobil), which was well tolerated and led to sustained increases in circulating neutrophils, lymphocytes, and monocytes. The current report is of three patients with advanced WHIM syndrome who received open-label plerixafor because they were ineligible for a randomized trial of this drug.

After treatment initiation, infection frequency dropped by 85% in one patient and declined markedly in all three patients. Lymphocyte counts improved the most in two patients while neutrophils were most responsive in the third patient. Warts partially resolved in two patients, of which one patient also experienced partial resolution of head and neck squamous cell carcinoma. This patient later died of a multidrug-resistant Pseudomonas aeruginosa infection after undergoing a 9-hour surgery.

In the third patient, plerixafor therapy led to clearance of TSPyV and 17 human papillomavirus (HPV) infections, with consequent resolution of chronic, progressive, multifocal eczematoid and follicular lesions, the researchers reported. The study dose was relatively low – about 10% of the stem-cell mobilization dose – and did not cause bone pain or other treatment-emergent adverse events, despite the relatively long treatment course (19-52 months).

A separate, phase 3 trial (NCT02231879) has enrolled 19 patients. Primary results are expected in 2020.

The National Institutes of Health funded the work. Dr. McDermott reported a pending patent to reduce CXCR4 expression and/or function to enhance engraftment of hematopoietic stem cells.

SOURCE: McDermott DH et al. N Engl J Med. 2019;380:163-70.
 

Low-dose treatment with plerixafor, a CXC chemokine receptor 4 antagonist, was well tolerated and markedly improved severe presentations of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome in three patients who could not receive granulocyte colony-stimulating factor therapy, investigators reported.

“Myelofibrosis, panleukopenia, anemia, and thrombocytopenia were ameliorated, the wart burden and frequency of infection declined, human papillomavirus–associated oropharyngeal squamous-cell carcinoma stabilized, and quality of life improved markedly,” David H. McDermott, MD, of the National Institute of Allergy and Infectious Diseases and his colleagues wrote in the New England Journal of Medicine.

WHIM syndrome is a primary immunodeficiency disorder characterized by panleukopenia and caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (CXCR4). Granulocyte colony-stimulating factor (G-CSF) therapy improves neutropenia in these patients, but not other cytopenias.

Previously, the investigators treated three WHIM syndrome patients with plerixafor (Mozobil), which was well tolerated and led to sustained increases in circulating neutrophils, lymphocytes, and monocytes. The current report is of three patients with advanced WHIM syndrome who received open-label plerixafor because they were ineligible for a randomized trial of this drug.

After treatment initiation, infection frequency dropped by 85% in one patient and declined markedly in all three patients. Lymphocyte counts improved the most in two patients while neutrophils were most responsive in the third patient. Warts partially resolved in two patients, of which one patient also experienced partial resolution of head and neck squamous cell carcinoma. This patient later died of a multidrug-resistant Pseudomonas aeruginosa infection after undergoing a 9-hour surgery.

In the third patient, plerixafor therapy led to clearance of TSPyV and 17 human papillomavirus (HPV) infections, with consequent resolution of chronic, progressive, multifocal eczematoid and follicular lesions, the researchers reported. The study dose was relatively low – about 10% of the stem-cell mobilization dose – and did not cause bone pain or other treatment-emergent adverse events, despite the relatively long treatment course (19-52 months).

A separate, phase 3 trial (NCT02231879) has enrolled 19 patients. Primary results are expected in 2020.

The National Institutes of Health funded the work. Dr. McDermott reported a pending patent to reduce CXCR4 expression and/or function to enhance engraftment of hematopoietic stem cells.

SOURCE: McDermott DH et al. N Engl J Med. 2019;380:163-70.
 

MONTREAL – For the second time in the past year, an anticoagulant failed to show superiority when it was compared with aspirin for preventing a second stroke in patients who had had an index embolic stroke of undetermined source (ESUS). But the most recent results gave a tantalizing suggestion that the anticoagulant approach might be effective for older patients, those at least 75 years old, possibly because these patients have the highest incidence of atrial fibrillation.

Mitchel L. Zoler/MDedge News

“The fact that we saw a treatment benefit in patients 75 and older [in a post hoc, subgroup analysis] means that development of atrial fibrillation (AF) is probably the most important factor,” Hans-Christoph Diener, MD, said at the World Stroke Congress. Another clue that incident AF drove a treatment benefit hidden in the new trial’s overall neutral result was that a post hoc, landmark analysis showed that, while the rate of second strokes was identical during the first year of follow-up in patients on either aspirin or the anticoagulant dabigatran (Pradaxa) after an index ESUS, patients on dabigatran had significantly fewer second strokes during subsequent follow-up.

More follow-up time was needed to see a benefit from anticoagulation because “it takes time for AF to develop, and then once a patient has AF, it takes time for a stroke to occur,” explained Dr. Diener, professor of neurology at the University of Duisburg-Essen in Essen, Germany.

The RE-SPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source) trial randomized 5,390 patients at more than 500 sites in 41 countries, including the United States, within 6 months of an index ESUS who had no history of AF and no severe renal impairment. All enrollees had to have less than 6 minutes of AF episodes during at least 20 hours of cardiac monitoring, and they had to be free of flow-limiting stenoses (50% or more) in arteries supplying their stroke region. Patients received either 150 mg or 110 mg of dabigatran twice daily depending on their age and renal function or 100 mg of aspirin daily. About a quarter of patients randomized to dabigatran received the lower dosage. The enrolled patients averaged 66 years old, almost two-thirds were men, and they started treatment a median of 44 days after their index stroke.

During a median 19 months’ follow-up, the incidence of a second stroke of any type was 4.1%/year among the patients on dabigatran and 4.8%/year among those on aspirin, a difference that was not statistically significant. However, the post hoc landmark analysis showed a significant reduction in second strokes with dabigatran treatment after the first year. In addition, a post hoc subgroup analysis showed that, among patients aged at least 75 years old, treatment with dabigatran linked with a statistically significant 37% reduction in second strokes, compared with treatment with aspirin, Dr. Diener reported.

The primary safety endpoint was major bleeds, as defined by the International Society on Thrombosis and Haemostasis, which occurred in 1.7%/year of patients on dabigatran and 1.4%/year of those on aspirin, a difference that was not statistically significant. Patients on dabigatran had a significant excess of major bleeds combined with clinically significant nonmajor bleeds: 3.3%/year versus 2.3%/year among those on aspirin.

A little over 4 months before Dr. Diener’s report, a separate research group published primary results from the NAVIGATE ESUS (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) trial, which compared the anticoagulant rivaroxaban (Xarelto) with aspirin for prevention of a second stroke in 7,213 ESUS patients. The results showed no significant efficacy difference between rivaroxaban and aspirin (N Engl J Med. 2018 June 7;378[23]:2191-2201).

RE-SPECT ESUS was funded by Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Diener has been a consultant to and has received research funding from Boehringer Ingelheim, as well as several other companies.

[email protected]

SOURCE: Diener H-C et al. Int J Stroke. 2018;13(2_suppl):27. Abstract 100.

MONTREAL – For the second time in the past year, an anticoagulant failed to show superiority when it was compared with aspirin for preventing a second stroke in patients who had had an index embolic stroke of undetermined source (ESUS). But the most recent results gave a tantalizing suggestion that the anticoagulant approach might be effective for older patients, those at least 75 years old, possibly because these patients have the highest incidence of atrial fibrillation.

Mitchel L. Zoler/MDedge News

“The fact that we saw a treatment benefit in patients 75 and older [in a post hoc, subgroup analysis] means that development of atrial fibrillation (AF) is probably the most important factor,” Hans-Christoph Diener, MD, said at the World Stroke Congress. Another clue that incident AF drove a treatment benefit hidden in the new trial’s overall neutral result was that a post hoc, landmark analysis showed that, while the rate of second strokes was identical during the first year of follow-up in patients on either aspirin or the anticoagulant dabigatran (Pradaxa) after an index ESUS, patients on dabigatran had significantly fewer second strokes during subsequent follow-up.

More follow-up time was needed to see a benefit from anticoagulation because “it takes time for AF to develop, and then once a patient has AF, it takes time for a stroke to occur,” explained Dr. Diener, professor of neurology at the University of Duisburg-Essen in Essen, Germany.

The RE-SPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source) trial randomized 5,390 patients at more than 500 sites in 41 countries, including the United States, within 6 months of an index ESUS who had no history of AF and no severe renal impairment. All enrollees had to have less than 6 minutes of AF episodes during at least 20 hours of cardiac monitoring, and they had to be free of flow-limiting stenoses (50% or more) in arteries supplying their stroke region. Patients received either 150 mg or 110 mg of dabigatran twice daily depending on their age and renal function or 100 mg of aspirin daily. About a quarter of patients randomized to dabigatran received the lower dosage. The enrolled patients averaged 66 years old, almost two-thirds were men, and they started treatment a median of 44 days after their index stroke.

During a median 19 months’ follow-up, the incidence of a second stroke of any type was 4.1%/year among the patients on dabigatran and 4.8%/year among those on aspirin, a difference that was not statistically significant. However, the post hoc landmark analysis showed a significant reduction in second strokes with dabigatran treatment after the first year. In addition, a post hoc subgroup analysis showed that, among patients aged at least 75 years old, treatment with dabigatran linked with a statistically significant 37% reduction in second strokes, compared with treatment with aspirin, Dr. Diener reported.

The primary safety endpoint was major bleeds, as defined by the International Society on Thrombosis and Haemostasis, which occurred in 1.7%/year of patients on dabigatran and 1.4%/year of those on aspirin, a difference that was not statistically significant. Patients on dabigatran had a significant excess of major bleeds combined with clinically significant nonmajor bleeds: 3.3%/year versus 2.3%/year among those on aspirin.

A little over 4 months before Dr. Diener’s report, a separate research group published primary results from the NAVIGATE ESUS (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) trial, which compared the anticoagulant rivaroxaban (Xarelto) with aspirin for prevention of a second stroke in 7,213 ESUS patients. The results showed no significant efficacy difference between rivaroxaban and aspirin (N Engl J Med. 2018 June 7;378[23]:2191-2201).

RE-SPECT ESUS was funded by Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Diener has been a consultant to and has received research funding from Boehringer Ingelheim, as well as several other companies.

[email protected]

SOURCE: Diener H-C et al. Int J Stroke. 2018;13(2_suppl):27. Abstract 100.

MONTREAL – For the second time in the past year, an anticoagulant failed to show superiority when it was compared with aspirin for preventing a second stroke in patients who had had an index embolic stroke of undetermined source (ESUS). But the most recent results gave a tantalizing suggestion that the anticoagulant approach might be effective for older patients, those at least 75 years old, possibly because these patients have the highest incidence of atrial fibrillation.

Mitchel L. Zoler/MDedge News

“The fact that we saw a treatment benefit in patients 75 and older [in a post hoc, subgroup analysis] means that development of atrial fibrillation (AF) is probably the most important factor,” Hans-Christoph Diener, MD, said at the World Stroke Congress. Another clue that incident AF drove a treatment benefit hidden in the new trial’s overall neutral result was that a post hoc, landmark analysis showed that, while the rate of second strokes was identical during the first year of follow-up in patients on either aspirin or the anticoagulant dabigatran (Pradaxa) after an index ESUS, patients on dabigatran had significantly fewer second strokes during subsequent follow-up.

More follow-up time was needed to see a benefit from anticoagulation because “it takes time for AF to develop, and then once a patient has AF, it takes time for a stroke to occur,” explained Dr. Diener, professor of neurology at the University of Duisburg-Essen in Essen, Germany.

The RE-SPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source) trial randomized 5,390 patients at more than 500 sites in 41 countries, including the United States, within 6 months of an index ESUS who had no history of AF and no severe renal impairment. All enrollees had to have less than 6 minutes of AF episodes during at least 20 hours of cardiac monitoring, and they had to be free of flow-limiting stenoses (50% or more) in arteries supplying their stroke region. Patients received either 150 mg or 110 mg of dabigatran twice daily depending on their age and renal function or 100 mg of aspirin daily. About a quarter of patients randomized to dabigatran received the lower dosage. The enrolled patients averaged 66 years old, almost two-thirds were men, and they started treatment a median of 44 days after their index stroke.

During a median 19 months’ follow-up, the incidence of a second stroke of any type was 4.1%/year among the patients on dabigatran and 4.8%/year among those on aspirin, a difference that was not statistically significant. However, the post hoc landmark analysis showed a significant reduction in second strokes with dabigatran treatment after the first year. In addition, a post hoc subgroup analysis showed that, among patients aged at least 75 years old, treatment with dabigatran linked with a statistically significant 37% reduction in second strokes, compared with treatment with aspirin, Dr. Diener reported.

The primary safety endpoint was major bleeds, as defined by the International Society on Thrombosis and Haemostasis, which occurred in 1.7%/year of patients on dabigatran and 1.4%/year of those on aspirin, a difference that was not statistically significant. Patients on dabigatran had a significant excess of major bleeds combined with clinically significant nonmajor bleeds: 3.3%/year versus 2.3%/year among those on aspirin.

A little over 4 months before Dr. Diener’s report, a separate research group published primary results from the NAVIGATE ESUS (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) trial, which compared the anticoagulant rivaroxaban (Xarelto) with aspirin for prevention of a second stroke in 7,213 ESUS patients. The results showed no significant efficacy difference between rivaroxaban and aspirin (N Engl J Med. 2018 June 7;378[23]:2191-2201).

RE-SPECT ESUS was funded by Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Diener has been a consultant to and has received research funding from Boehringer Ingelheim, as well as several other companies.

[email protected]

SOURCE: Diener H-C et al. Int J Stroke. 2018;13(2_suppl):27. Abstract 100.