Ob.Gyn. News

Having a sore throat is becoming a dominant symptom of COVID-19 infection, with fever and loss of smell becoming less common, according to recent reports in the United Kingdom.

The shift could be a cause of concern for the fall. As the main symptoms of the coronavirus change, people could spread the virus without realizing it.

“Many people are still using the government guidelines about symptoms, which are wrong,” Tim Spector, a professor of genetic epidemiology at King’s College London, told the Independent.

Prof. Spector cofounded the COVID ZOE app, which is part of the world’s largest COVID-19 study. Throughout the pandemic, researchers have used data from the app to track changes in symptoms.

“At the moment, COVID starts in two-thirds of people with a sore throat,” he said. “Fever and loss of smell are really rare now, so many old people may not think they’ve got COVID. They’d say it’s a cold and not be tested.”

COVID-19 infections in the United Kingdom increased 14% at the end of September, according to data from the U.K.’s Office for National Statistics. More than 1.1 million people tested positive during the week ending Sept. 20, up from 927,000 cases the week before. The numbers continue to increase in England and Wales, with an uncertain trend in Northern Ireland and Scotland.

The fall wave of infections has likely arrived in the United Kingdom, Prof. Spector told the Independent. Omicron variants continue to evolve and are escaping immunity from previous infection and vaccination, which he expects to continue into the winter.

But with reduced testing and surveillance of new variants, public health experts have voiced concerns about tracking the latest variants and COVID-19 trends.

“We can only detect variants or know what’s coming by doing sequencing from PCR testing, and that’s not going on anywhere near the extent it was a year ago,” Lawrence Young, a professor of virology at the University of Warwick, Coventry, England, told the Independent.

“People are going to get various infections over the winter but won’t know what they are because free tests aren’t available,” he said. “It’s going to be a problem.” 

COVID-19 cases are also increasing across Europe, which could mark the first regional spike since the BA.5 wave, according to the latest data from the European CDC. (In the past, increases in Europe have signaled a trend to come in other regions.)

People aged 65 and older have been hit the hardest, the data shows, with cases rising 9% from the previous week. Hospitalizations remain stable for now, although 14 of 27 countries in the European region have noted an upward trend.

“Changes in population mixing following the summer break are likely to be the main driver of these increases, with no indication of changes in the distribution of circulating variants,” the European CDC said.

For now, most COVID-19 numbers are still falling in the United States, according to a weekly CDC update published Sept. 30. About 47,000 cases are being reported each day, marking a 13% decrease from the week before. Hospitalizations dropped 7%, and deaths dropped 6%.

At the same time, test positivity rose slightly last week, from 9.6% to 9.8%. Wastewater surveillance indicates that 53% of sites in the United States reported a decrease in virus levels, while 41% reported an increase last week.

The CDC encouraged people to get the updated Omicron-targeted booster shot for the fall. About 7.5 million Americans have received the updated vaccine. Half of the eligible population in the United States hasn’t received any booster dose yet.

“Bivalent boosters help restore protection that might have gone down since your last dose – and they also give extra protection for you and those around you against all lineages of the Omicron variant,” the CDC wrote. “The more people who stay up to date on vaccinations, the better chance we have of avoiding a possible surge in COVID-19 illness later this fall and winter.”

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

Having a sore throat is becoming a dominant symptom of COVID-19 infection, with fever and loss of smell becoming less common, according to recent reports in the United Kingdom.

The shift could be a cause of concern for the fall. As the main symptoms of the coronavirus change, people could spread the virus without realizing it.

“Many people are still using the government guidelines about symptoms, which are wrong,” Tim Spector, a professor of genetic epidemiology at King’s College London, told the Independent.

Prof. Spector cofounded the COVID ZOE app, which is part of the world’s largest COVID-19 study. Throughout the pandemic, researchers have used data from the app to track changes in symptoms.

“At the moment, COVID starts in two-thirds of people with a sore throat,” he said. “Fever and loss of smell are really rare now, so many old people may not think they’ve got COVID. They’d say it’s a cold and not be tested.”

COVID-19 infections in the United Kingdom increased 14% at the end of September, according to data from the U.K.’s Office for National Statistics. More than 1.1 million people tested positive during the week ending Sept. 20, up from 927,000 cases the week before. The numbers continue to increase in England and Wales, with an uncertain trend in Northern Ireland and Scotland.

The fall wave of infections has likely arrived in the United Kingdom, Prof. Spector told the Independent. Omicron variants continue to evolve and are escaping immunity from previous infection and vaccination, which he expects to continue into the winter.

But with reduced testing and surveillance of new variants, public health experts have voiced concerns about tracking the latest variants and COVID-19 trends.

“We can only detect variants or know what’s coming by doing sequencing from PCR testing, and that’s not going on anywhere near the extent it was a year ago,” Lawrence Young, a professor of virology at the University of Warwick, Coventry, England, told the Independent.

“People are going to get various infections over the winter but won’t know what they are because free tests aren’t available,” he said. “It’s going to be a problem.” 

COVID-19 cases are also increasing across Europe, which could mark the first regional spike since the BA.5 wave, according to the latest data from the European CDC. (In the past, increases in Europe have signaled a trend to come in other regions.)

People aged 65 and older have been hit the hardest, the data shows, with cases rising 9% from the previous week. Hospitalizations remain stable for now, although 14 of 27 countries in the European region have noted an upward trend.

“Changes in population mixing following the summer break are likely to be the main driver of these increases, with no indication of changes in the distribution of circulating variants,” the European CDC said.

For now, most COVID-19 numbers are still falling in the United States, according to a weekly CDC update published Sept. 30. About 47,000 cases are being reported each day, marking a 13% decrease from the week before. Hospitalizations dropped 7%, and deaths dropped 6%.

At the same time, test positivity rose slightly last week, from 9.6% to 9.8%. Wastewater surveillance indicates that 53% of sites in the United States reported a decrease in virus levels, while 41% reported an increase last week.

The CDC encouraged people to get the updated Omicron-targeted booster shot for the fall. About 7.5 million Americans have received the updated vaccine. Half of the eligible population in the United States hasn’t received any booster dose yet.

“Bivalent boosters help restore protection that might have gone down since your last dose – and they also give extra protection for you and those around you against all lineages of the Omicron variant,” the CDC wrote. “The more people who stay up to date on vaccinations, the better chance we have of avoiding a possible surge in COVID-19 illness later this fall and winter.”

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

Having a sore throat is becoming a dominant symptom of COVID-19 infection, with fever and loss of smell becoming less common, according to recent reports in the United Kingdom.

The shift could be a cause of concern for the fall. As the main symptoms of the coronavirus change, people could spread the virus without realizing it.

“Many people are still using the government guidelines about symptoms, which are wrong,” Tim Spector, a professor of genetic epidemiology at King’s College London, told the Independent.

Prof. Spector cofounded the COVID ZOE app, which is part of the world’s largest COVID-19 study. Throughout the pandemic, researchers have used data from the app to track changes in symptoms.

“At the moment, COVID starts in two-thirds of people with a sore throat,” he said. “Fever and loss of smell are really rare now, so many old people may not think they’ve got COVID. They’d say it’s a cold and not be tested.”

COVID-19 infections in the United Kingdom increased 14% at the end of September, according to data from the U.K.’s Office for National Statistics. More than 1.1 million people tested positive during the week ending Sept. 20, up from 927,000 cases the week before. The numbers continue to increase in England and Wales, with an uncertain trend in Northern Ireland and Scotland.

The fall wave of infections has likely arrived in the United Kingdom, Prof. Spector told the Independent. Omicron variants continue to evolve and are escaping immunity from previous infection and vaccination, which he expects to continue into the winter.

But with reduced testing and surveillance of new variants, public health experts have voiced concerns about tracking the latest variants and COVID-19 trends.

“We can only detect variants or know what’s coming by doing sequencing from PCR testing, and that’s not going on anywhere near the extent it was a year ago,” Lawrence Young, a professor of virology at the University of Warwick, Coventry, England, told the Independent.

“People are going to get various infections over the winter but won’t know what they are because free tests aren’t available,” he said. “It’s going to be a problem.” 

COVID-19 cases are also increasing across Europe, which could mark the first regional spike since the BA.5 wave, according to the latest data from the European CDC. (In the past, increases in Europe have signaled a trend to come in other regions.)

People aged 65 and older have been hit the hardest, the data shows, with cases rising 9% from the previous week. Hospitalizations remain stable for now, although 14 of 27 countries in the European region have noted an upward trend.

“Changes in population mixing following the summer break are likely to be the main driver of these increases, with no indication of changes in the distribution of circulating variants,” the European CDC said.

For now, most COVID-19 numbers are still falling in the United States, according to a weekly CDC update published Sept. 30. About 47,000 cases are being reported each day, marking a 13% decrease from the week before. Hospitalizations dropped 7%, and deaths dropped 6%.

At the same time, test positivity rose slightly last week, from 9.6% to 9.8%. Wastewater surveillance indicates that 53% of sites in the United States reported a decrease in virus levels, while 41% reported an increase last week.

The CDC encouraged people to get the updated Omicron-targeted booster shot for the fall. About 7.5 million Americans have received the updated vaccine. Half of the eligible population in the United States hasn’t received any booster dose yet.

“Bivalent boosters help restore protection that might have gone down since your last dose – and they also give extra protection for you and those around you against all lineages of the Omicron variant,” the CDC wrote. “The more people who stay up to date on vaccinations, the better chance we have of avoiding a possible surge in COVID-19 illness later this fall and winter.”

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

For Yuk Ming Dennis Lo, BM BCh, DPhil, a 1996 paper showing the detection of tumor DNA in blood plasma would prove a turning point.

Since the 1960s, clinicians had been searching for a way to glimpse into a fetus’ genetic makeup without disturbing the pregnancy – a fascination Dr. Lo, at the time a graduate student in the United Kingdom, shared.

But the article triggered a thought. If cancer cells could release their DNA into blood plasma, then maybe fetuses could, too. “I had the strange thought that the cancer growing in the patients is a little bit like the placenta that has implanted into the uterus,” he told The New York Times.

The answer was yes. In 1997, having returned home to Hong Kong, Dr. Lo published a seminal article showing that cell-free fetal DNA could be detected in maternal blood. 

He went on to devise methods to detect markers for Down syndrome, creating a noninvasive test that is more than 99% accurate for ruling out the disorder, along with screenings for trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome), and other chromosome abnormalities.

With the commercial launch of noninvasive prenatal testing (NIPT) in 2011, health care centers around the world quickly embraced the technology as a safe alternative to more invasive methods, such as amniocentesis, for identifying fetal abnormalities. NIPT is now available in over 60 countries and is widely used by clinicians, according to the Lasker Foundation, which granted him the 2022 Lasker DeBakey Clinical Medical Research Award, along with a $250,000 prize.

“I am pleased that since its launch, noninvasive prenatal testing has become a standard of care,” Dr. Lo, chair of the department of chemical pathology at The Chinese University of Hong Kong, said in a video on the Lasker website. “It has also stimulated a global interest in the diagnostic applications of plasma DNA, especially in the area of cancer liquid biopsies and transplantation monitoring. I look forward to seeing these and other yet to be developed applications improving health care worldwide.” 

Dr. Lo’s work has inspired clinical advances and applications, including Rh factor assessments, innovations in cancer technology, transplantation, and beyond, according to Lasker.

Iris Krishna, MD, MPH, director of Perinatal Quality in the Emory Perinatal Center at Emory University School of Medicine, Atlanta, said Dr. Lo’s work has also provided opportunities to screen for other genetic disorders, such as microdeletion syndromes and single gene disorders

“As we continue to learn about the possibilities of this technology, it is imperative for the clinician to be knowledgeable of the benefits and limitations of cell-free DNA screening to be able to counsel their patients appropriately,” Dr. Krishna said.
 

A COVID clearinghouse

Lauren Gardner, PhD, professor in the department of civil and systems engineering at Johns Hopkins University, Baltimore, received the Lasker Bloomberg Public Service Award for her work on the Johns Hopkins’ COVID-19 dashboard, a critical tool for the dissemination of public health data in real time.

According to the Los Angeles Times, Ensheng Dong, Dr. Gardner’s graduate student, approached her about tracking cases of the emerging infection in his home country of China. Mr. Dong mined Chinese websites for early cases of COVID-19 and created online maps using the information. At Dr. Gardner’s suggestion, he expanded the database to include global data.

At the time, according to Lasker, no other institution was providing this information. The World Health Organization created summaries of daily COVID-19 counts, but the data were not as accessible. Dr. Gardner said timely and obtainable information was crucial to craft nimble and rational strategies for combating the pandemic.

“Given the amount of misinformation in circulation and the highly politicized nature of the COVID-19 public health crisis, our work enabled individuals to access the information they needed to make informed decisions to protect themselves, which was especially critical in those locations with delayed or nonexistent policies in place,” Dr. Gardner said in a statement.

Dr. Gardner said she was excited to pursue additional data-centric projects. “I am optimistic that in the future, timely public health information will become increasingly available, especially in times of crisis,” she said. “Moving forward, I am excited to build on our learnings from COVID-19 and transfer that knowledge to address other problems facing societies.”
 

New knowledge of cells, immunology, and disease

The 2022 Albert Lasker Basic Research Award honored three scientists who helped identify a family of proteins that connect cells and assist the immune system in attaching to its targets. The proteins, called integrins, are needed for cells to interact with each other to build complex structures in the body. They are also key to the process T cells undergo to recognize and attack cancer cells.

Awardees Richard O. Hynes, MA, PhD, distinguished professor of cancer research at Massachusetts Institute of Technology; Erkki Ruoslahti, MD, PhD, distinguished professor emeritus at Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California; and Timothy A. Springer, PhD, professor of biological chemistry and molecular biology at Boston Children’s Hospital and Harvard Medical School, independently identified a cell-surface–associated protein that helps cells attach to the extracellular matrix.

“Many of the mysteries of how integrins work are only being discovered today,” Dr. Springer said in his acceptance remarks online.

The discoveries related to integrins have led to several clinical advances, including the development of drugs like the eyedrops lifitegrast, the biologic agent vedolizumab (made using integrins Springer discovered), and tirofiban, a medication used to hamper clotting in cardiovascular diseases.

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

For Yuk Ming Dennis Lo, BM BCh, DPhil, a 1996 paper showing the detection of tumor DNA in blood plasma would prove a turning point.

Since the 1960s, clinicians had been searching for a way to glimpse into a fetus’ genetic makeup without disturbing the pregnancy – a fascination Dr. Lo, at the time a graduate student in the United Kingdom, shared.

But the article triggered a thought. If cancer cells could release their DNA into blood plasma, then maybe fetuses could, too. “I had the strange thought that the cancer growing in the patients is a little bit like the placenta that has implanted into the uterus,” he told The New York Times.

The answer was yes. In 1997, having returned home to Hong Kong, Dr. Lo published a seminal article showing that cell-free fetal DNA could be detected in maternal blood. 

He went on to devise methods to detect markers for Down syndrome, creating a noninvasive test that is more than 99% accurate for ruling out the disorder, along with screenings for trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome), and other chromosome abnormalities.

With the commercial launch of noninvasive prenatal testing (NIPT) in 2011, health care centers around the world quickly embraced the technology as a safe alternative to more invasive methods, such as amniocentesis, for identifying fetal abnormalities. NIPT is now available in over 60 countries and is widely used by clinicians, according to the Lasker Foundation, which granted him the 2022 Lasker DeBakey Clinical Medical Research Award, along with a $250,000 prize.

“I am pleased that since its launch, noninvasive prenatal testing has become a standard of care,” Dr. Lo, chair of the department of chemical pathology at The Chinese University of Hong Kong, said in a video on the Lasker website. “It has also stimulated a global interest in the diagnostic applications of plasma DNA, especially in the area of cancer liquid biopsies and transplantation monitoring. I look forward to seeing these and other yet to be developed applications improving health care worldwide.” 

Dr. Lo’s work has inspired clinical advances and applications, including Rh factor assessments, innovations in cancer technology, transplantation, and beyond, according to Lasker.

Iris Krishna, MD, MPH, director of Perinatal Quality in the Emory Perinatal Center at Emory University School of Medicine, Atlanta, said Dr. Lo’s work has also provided opportunities to screen for other genetic disorders, such as microdeletion syndromes and single gene disorders

“As we continue to learn about the possibilities of this technology, it is imperative for the clinician to be knowledgeable of the benefits and limitations of cell-free DNA screening to be able to counsel their patients appropriately,” Dr. Krishna said.
 

A COVID clearinghouse

Lauren Gardner, PhD, professor in the department of civil and systems engineering at Johns Hopkins University, Baltimore, received the Lasker Bloomberg Public Service Award for her work on the Johns Hopkins’ COVID-19 dashboard, a critical tool for the dissemination of public health data in real time.

According to the Los Angeles Times, Ensheng Dong, Dr. Gardner’s graduate student, approached her about tracking cases of the emerging infection in his home country of China. Mr. Dong mined Chinese websites for early cases of COVID-19 and created online maps using the information. At Dr. Gardner’s suggestion, he expanded the database to include global data.

At the time, according to Lasker, no other institution was providing this information. The World Health Organization created summaries of daily COVID-19 counts, but the data were not as accessible. Dr. Gardner said timely and obtainable information was crucial to craft nimble and rational strategies for combating the pandemic.

“Given the amount of misinformation in circulation and the highly politicized nature of the COVID-19 public health crisis, our work enabled individuals to access the information they needed to make informed decisions to protect themselves, which was especially critical in those locations with delayed or nonexistent policies in place,” Dr. Gardner said in a statement.

Dr. Gardner said she was excited to pursue additional data-centric projects. “I am optimistic that in the future, timely public health information will become increasingly available, especially in times of crisis,” she said. “Moving forward, I am excited to build on our learnings from COVID-19 and transfer that knowledge to address other problems facing societies.”
 

New knowledge of cells, immunology, and disease

The 2022 Albert Lasker Basic Research Award honored three scientists who helped identify a family of proteins that connect cells and assist the immune system in attaching to its targets. The proteins, called integrins, are needed for cells to interact with each other to build complex structures in the body. They are also key to the process T cells undergo to recognize and attack cancer cells.

Awardees Richard O. Hynes, MA, PhD, distinguished professor of cancer research at Massachusetts Institute of Technology; Erkki Ruoslahti, MD, PhD, distinguished professor emeritus at Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California; and Timothy A. Springer, PhD, professor of biological chemistry and molecular biology at Boston Children’s Hospital and Harvard Medical School, independently identified a cell-surface–associated protein that helps cells attach to the extracellular matrix.

“Many of the mysteries of how integrins work are only being discovered today,” Dr. Springer said in his acceptance remarks online.

The discoveries related to integrins have led to several clinical advances, including the development of drugs like the eyedrops lifitegrast, the biologic agent vedolizumab (made using integrins Springer discovered), and tirofiban, a medication used to hamper clotting in cardiovascular diseases.

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

For Yuk Ming Dennis Lo, BM BCh, DPhil, a 1996 paper showing the detection of tumor DNA in blood plasma would prove a turning point.

Since the 1960s, clinicians had been searching for a way to glimpse into a fetus’ genetic makeup without disturbing the pregnancy – a fascination Dr. Lo, at the time a graduate student in the United Kingdom, shared.

But the article triggered a thought. If cancer cells could release their DNA into blood plasma, then maybe fetuses could, too. “I had the strange thought that the cancer growing in the patients is a little bit like the placenta that has implanted into the uterus,” he told The New York Times.

The answer was yes. In 1997, having returned home to Hong Kong, Dr. Lo published a seminal article showing that cell-free fetal DNA could be detected in maternal blood. 

He went on to devise methods to detect markers for Down syndrome, creating a noninvasive test that is more than 99% accurate for ruling out the disorder, along with screenings for trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome), and other chromosome abnormalities.

With the commercial launch of noninvasive prenatal testing (NIPT) in 2011, health care centers around the world quickly embraced the technology as a safe alternative to more invasive methods, such as amniocentesis, for identifying fetal abnormalities. NIPT is now available in over 60 countries and is widely used by clinicians, according to the Lasker Foundation, which granted him the 2022 Lasker DeBakey Clinical Medical Research Award, along with a $250,000 prize.

“I am pleased that since its launch, noninvasive prenatal testing has become a standard of care,” Dr. Lo, chair of the department of chemical pathology at The Chinese University of Hong Kong, said in a video on the Lasker website. “It has also stimulated a global interest in the diagnostic applications of plasma DNA, especially in the area of cancer liquid biopsies and transplantation monitoring. I look forward to seeing these and other yet to be developed applications improving health care worldwide.” 

Dr. Lo’s work has inspired clinical advances and applications, including Rh factor assessments, innovations in cancer technology, transplantation, and beyond, according to Lasker.

Iris Krishna, MD, MPH, director of Perinatal Quality in the Emory Perinatal Center at Emory University School of Medicine, Atlanta, said Dr. Lo’s work has also provided opportunities to screen for other genetic disorders, such as microdeletion syndromes and single gene disorders

“As we continue to learn about the possibilities of this technology, it is imperative for the clinician to be knowledgeable of the benefits and limitations of cell-free DNA screening to be able to counsel their patients appropriately,” Dr. Krishna said.
 

A COVID clearinghouse

Lauren Gardner, PhD, professor in the department of civil and systems engineering at Johns Hopkins University, Baltimore, received the Lasker Bloomberg Public Service Award for her work on the Johns Hopkins’ COVID-19 dashboard, a critical tool for the dissemination of public health data in real time.

According to the Los Angeles Times, Ensheng Dong, Dr. Gardner’s graduate student, approached her about tracking cases of the emerging infection in his home country of China. Mr. Dong mined Chinese websites for early cases of COVID-19 and created online maps using the information. At Dr. Gardner’s suggestion, he expanded the database to include global data.

At the time, according to Lasker, no other institution was providing this information. The World Health Organization created summaries of daily COVID-19 counts, but the data were not as accessible. Dr. Gardner said timely and obtainable information was crucial to craft nimble and rational strategies for combating the pandemic.

“Given the amount of misinformation in circulation and the highly politicized nature of the COVID-19 public health crisis, our work enabled individuals to access the information they needed to make informed decisions to protect themselves, which was especially critical in those locations with delayed or nonexistent policies in place,” Dr. Gardner said in a statement.

Dr. Gardner said she was excited to pursue additional data-centric projects. “I am optimistic that in the future, timely public health information will become increasingly available, especially in times of crisis,” she said. “Moving forward, I am excited to build on our learnings from COVID-19 and transfer that knowledge to address other problems facing societies.”
 

New knowledge of cells, immunology, and disease

The 2022 Albert Lasker Basic Research Award honored three scientists who helped identify a family of proteins that connect cells and assist the immune system in attaching to its targets. The proteins, called integrins, are needed for cells to interact with each other to build complex structures in the body. They are also key to the process T cells undergo to recognize and attack cancer cells.

Awardees Richard O. Hynes, MA, PhD, distinguished professor of cancer research at Massachusetts Institute of Technology; Erkki Ruoslahti, MD, PhD, distinguished professor emeritus at Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California; and Timothy A. Springer, PhD, professor of biological chemistry and molecular biology at Boston Children’s Hospital and Harvard Medical School, independently identified a cell-surface–associated protein that helps cells attach to the extracellular matrix.

“Many of the mysteries of how integrins work are only being discovered today,” Dr. Springer said in his acceptance remarks online.

The discoveries related to integrins have led to several clinical advances, including the development of drugs like the eyedrops lifitegrast, the biologic agent vedolizumab (made using integrins Springer discovered), and tirofiban, a medication used to hamper clotting in cardiovascular diseases.

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

Daniel Freedman, DO, a pediatric neurologist in Austin, Tex., remembers being flabbergasted when a surgeon threw an instrument across the room in medical school.

“I remember thinking, ‘I can’t believe people actually do this, a grown man in his 50s having a temper tantrum,’” Dr. Freedman said in an interview. But it certainly wasn’t the last time he witnessed bad behavior by one of his peers.

The results of Medscape’s recent report, Physicians Behaving Badly: Stress and Hardship Trigger Misconduct, suggest he has plenty of company. More than 4 in 10 respondents (41%) observed inappropriate behavior in the workplace in 2022, an uptick from 35% in 2021, according to the report, which polled more than 1,500 physicians about inappropriate behavior on and off the clock.

Of course, 38% of respondents have not seen any instances of misbehavior; and many of the instances that were seen were mild or infrequent. Additionally, instances of bad behavior have declined significantly over the past 5 years.

Dr. Freedman said he learned a lesson from his mentor and program director during training that has stuck with him throughout his career. “If you couldn’t act that way at any job, whether at McDonald’s or any other possible place, you shouldn’t act that way in medicine.” But he recognizes one limitation of that advice. “A lot of the people that behave badly may not have ever worked in a different environment before,” he said.

“They only perceive that they’re at the top of the food chain, so they can behave badly without repercussions.”

What Dr. Freedman described is formally called disruptive physician behavior, one of several categories of inappropriate behavior in medicine, according to Charles Samenow, MD, MPH, an associate professor of psychiatry and behavioral sciences at George Washington University, Washington, who has studied this phenomenon for years.

“Disruptive physician behavior compromises the safety of the workplace,” Dr. Samenow explained. The behavior can occur at work, outside of work, or on social media. It can hinder operations, threaten patient and staff safety, and affect workplace morale.

“The question is trying to understand where that bad behavior is coming from and the impact of that bad behavior,” Dr. Samenow said in an interview.

One reason is fairly simple: doctors are human, and humans have a wide range of behavior. Plus, as the Medscape survey showed, the tension, stress, dangerous conditions during COVID, burnout, and other problems have made many physicians tired, frustrated, depressed, and more reactive to situations around them.
 

Self-selecting traits become an Achilles heel

“Any human put in a position of power over other humans has the potential to be disruptive, harass, etc, if they have certain personality traits,” said David Gorski, MD, a professor of surgery at Wayne State University, Detroit. That jibes with Dr. Samenow’s research.

Classic disruptive behavior isn’t usually associated with depression, mania, psychosis, or similar characteristics, Dr. Samenow explained. Rather, it tends to be personality driven. “Physicians are not immune to the normal problems every human being faces,” he said.

In the Medscape report, physicians cited personal arrogance as one of the leading reasons physicians engaged in inappropriate behavior (56%), followed closely by personal problems outside of work (52%), a social shift in accepting more casual behavior (50%), and job-related stress (46%). (Respondents could choose more than one answer).

One factor contributing to misbehavior that Dr. Samenow has consistently identified in his research is a history of adverse childhood experiences or family dysfunction: People who grew up in homes with physical or verbal abuse learned anger as a coping skill instead of positive, assertive communication. It’s likely that some physicians, as well as the overall population, learned anger as a coping skill for that reason.
 

How to help avert disruptive behavior in medical settings

Dr. Samenow said that coaching is a “wonderful tool” in teaching the interpersonal skills that medical school often doesn’t address.

In some case, interventions can be very helpful. For example, programs that teach effective communication strategies and teamwork through a combination of culturally sensitive dialectical and cognitive-behavioral therapy and other modalities have been successful, Dr. Samenow said. Although they are more about treating an illness than addressing “misbehavior,” programs for substance use that have been developed by and for doctors are very effective, too.

Fewer resources are available, however, for addressing racism, classism, misogyny, and other forms of bigotry, Dr. Samenow noted. “There’s implicit bias training, but not at the level of what exists for disruptive physicians and those with addiction. “That’s an area we need to work on.” Racist language was the third most commonly observed bad behavior cited in the Medscape survey, behind only bullying of staff and mocking or disparaging of patients. It was reported frequently outside of work as well.

The Medscape report found an increase in observed behavior at work and on social media, although it’s hard to determine prevalence trends over time, Dr. Samenow said. “The tolerance for this behavior has really gone down,” likely leading to more reporting, he said, and more systems for reporting bad behavior exist today than in the past.

However, Dr. Freedman said inadequate regulation, disciplinary action, and follow-through remain a problem.

“There are lots of limitations to our reporting system and to our follow-through with those reports,” including hospitals that, whether for fear of litigation or other reasons, allow physicians to quietly resign and move to another institution, even with positive recommendations, Dr. Freedman said.

Indeed, only a third of observed misbehavior in the Medscape report resulted in disciplinary action. Half the respondents believed a verbal warning was a necessary consequence, followed by a conversation from management and being reported to a supervisor or human resources. Though only 10% thought a report to the medical board was warranted, it likely depends on the offense and its frequency.

“I think going from paternalism to more patient-centered care and having patients involved in those conversations is a nice shift that makes doctors more human and relatable, and hopefully makes the public more forgiving, that we’re going to make mistakes and nobody’s perfect,” Freedman said. But he added that physicians should be held accountable when a mistake or two becomes a pattern.
 

Misinformation is professional misconduct

Sufficient accountability is especially absent, these doctors said, for a subset of professional misconduct: spreading misinformation.

While more “conventional” bad behaviors include fraud, dishonesty, abuse of underlings, and incompetence, bad behavior should also include “selling quackery and antivaccine misinformation, the way some doctors did with various nostrums for COVID-19,” said Dr. Gorski, who frequently blogs about doctors’ spreading misinformation.

Taylor Nichols, MD, an emergency medicine physician based in Sacramento, cites the desire for attention and clout as motivations. “Saying things that are wildly, provably false is professional misconduct,” Nichols said. He distinguished such statements from scientific, academic, or clinical disagreement that is necessary within medicine.

Yet there’s been a “long tradition of looking the other way or letting people with fancy titles get away with saying nonsense just because they’re respected,” Jonathan Howard, MD, an associate professor of psychiatry and neurology at New York University said in an interview.

“We have a duty to be trusted members of the community,” Dr. Howard said. “People listen when we say things, and we have an obligation to try to be accurate and humble and as honest as possible and admit mistakes when we inevitably make them.”

That extends to social media, which Dr. Nichols said has magnified the problem of promoting quackery and misinformation. He thinks medical boards and professional credentialing bodies should pay attention to what’s happening in the public conversation and understand that our professional responsibility extends beyond the walls of the hospital or clinic. Physicians must represent themselves professionally and uphold the standards that the profession expects.

On the one hand, Medscape respondents agreed: 70% said one doctor’s misbehavior taints the whole profession. Yet, at the same time, 58% of respondents believed physicians should be able to “keep their private lives private” in 2022. But that’s not the reality of the profession when the lines between private life and behavior away from work get blurred, Dr. Samenow said.

“The way a physician behaves in public represents you,” he said. “What happens in Vegas doesn’t always stay in Vegas.”

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

Daniel Freedman, DO, a pediatric neurologist in Austin, Tex., remembers being flabbergasted when a surgeon threw an instrument across the room in medical school.

“I remember thinking, ‘I can’t believe people actually do this, a grown man in his 50s having a temper tantrum,’” Dr. Freedman said in an interview. But it certainly wasn’t the last time he witnessed bad behavior by one of his peers.

The results of Medscape’s recent report, Physicians Behaving Badly: Stress and Hardship Trigger Misconduct, suggest he has plenty of company. More than 4 in 10 respondents (41%) observed inappropriate behavior in the workplace in 2022, an uptick from 35% in 2021, according to the report, which polled more than 1,500 physicians about inappropriate behavior on and off the clock.

Of course, 38% of respondents have not seen any instances of misbehavior; and many of the instances that were seen were mild or infrequent. Additionally, instances of bad behavior have declined significantly over the past 5 years.

Dr. Freedman said he learned a lesson from his mentor and program director during training that has stuck with him throughout his career. “If you couldn’t act that way at any job, whether at McDonald’s or any other possible place, you shouldn’t act that way in medicine.” But he recognizes one limitation of that advice. “A lot of the people that behave badly may not have ever worked in a different environment before,” he said.

“They only perceive that they’re at the top of the food chain, so they can behave badly without repercussions.”

What Dr. Freedman described is formally called disruptive physician behavior, one of several categories of inappropriate behavior in medicine, according to Charles Samenow, MD, MPH, an associate professor of psychiatry and behavioral sciences at George Washington University, Washington, who has studied this phenomenon for years.

“Disruptive physician behavior compromises the safety of the workplace,” Dr. Samenow explained. The behavior can occur at work, outside of work, or on social media. It can hinder operations, threaten patient and staff safety, and affect workplace morale.

“The question is trying to understand where that bad behavior is coming from and the impact of that bad behavior,” Dr. Samenow said in an interview.

One reason is fairly simple: doctors are human, and humans have a wide range of behavior. Plus, as the Medscape survey showed, the tension, stress, dangerous conditions during COVID, burnout, and other problems have made many physicians tired, frustrated, depressed, and more reactive to situations around them.
 

Self-selecting traits become an Achilles heel

“Any human put in a position of power over other humans has the potential to be disruptive, harass, etc, if they have certain personality traits,” said David Gorski, MD, a professor of surgery at Wayne State University, Detroit. That jibes with Dr. Samenow’s research.

Classic disruptive behavior isn’t usually associated with depression, mania, psychosis, or similar characteristics, Dr. Samenow explained. Rather, it tends to be personality driven. “Physicians are not immune to the normal problems every human being faces,” he said.

In the Medscape report, physicians cited personal arrogance as one of the leading reasons physicians engaged in inappropriate behavior (56%), followed closely by personal problems outside of work (52%), a social shift in accepting more casual behavior (50%), and job-related stress (46%). (Respondents could choose more than one answer).

One factor contributing to misbehavior that Dr. Samenow has consistently identified in his research is a history of adverse childhood experiences or family dysfunction: People who grew up in homes with physical or verbal abuse learned anger as a coping skill instead of positive, assertive communication. It’s likely that some physicians, as well as the overall population, learned anger as a coping skill for that reason.
 

How to help avert disruptive behavior in medical settings

Dr. Samenow said that coaching is a “wonderful tool” in teaching the interpersonal skills that medical school often doesn’t address.

In some case, interventions can be very helpful. For example, programs that teach effective communication strategies and teamwork through a combination of culturally sensitive dialectical and cognitive-behavioral therapy and other modalities have been successful, Dr. Samenow said. Although they are more about treating an illness than addressing “misbehavior,” programs for substance use that have been developed by and for doctors are very effective, too.

Fewer resources are available, however, for addressing racism, classism, misogyny, and other forms of bigotry, Dr. Samenow noted. “There’s implicit bias training, but not at the level of what exists for disruptive physicians and those with addiction. “That’s an area we need to work on.” Racist language was the third most commonly observed bad behavior cited in the Medscape survey, behind only bullying of staff and mocking or disparaging of patients. It was reported frequently outside of work as well.

The Medscape report found an increase in observed behavior at work and on social media, although it’s hard to determine prevalence trends over time, Dr. Samenow said. “The tolerance for this behavior has really gone down,” likely leading to more reporting, he said, and more systems for reporting bad behavior exist today than in the past.

However, Dr. Freedman said inadequate regulation, disciplinary action, and follow-through remain a problem.

“There are lots of limitations to our reporting system and to our follow-through with those reports,” including hospitals that, whether for fear of litigation or other reasons, allow physicians to quietly resign and move to another institution, even with positive recommendations, Dr. Freedman said.

Indeed, only a third of observed misbehavior in the Medscape report resulted in disciplinary action. Half the respondents believed a verbal warning was a necessary consequence, followed by a conversation from management and being reported to a supervisor or human resources. Though only 10% thought a report to the medical board was warranted, it likely depends on the offense and its frequency.

“I think going from paternalism to more patient-centered care and having patients involved in those conversations is a nice shift that makes doctors more human and relatable, and hopefully makes the public more forgiving, that we’re going to make mistakes and nobody’s perfect,” Freedman said. But he added that physicians should be held accountable when a mistake or two becomes a pattern.
 

Misinformation is professional misconduct

Sufficient accountability is especially absent, these doctors said, for a subset of professional misconduct: spreading misinformation.

While more “conventional” bad behaviors include fraud, dishonesty, abuse of underlings, and incompetence, bad behavior should also include “selling quackery and antivaccine misinformation, the way some doctors did with various nostrums for COVID-19,” said Dr. Gorski, who frequently blogs about doctors’ spreading misinformation.

Taylor Nichols, MD, an emergency medicine physician based in Sacramento, cites the desire for attention and clout as motivations. “Saying things that are wildly, provably false is professional misconduct,” Nichols said. He distinguished such statements from scientific, academic, or clinical disagreement that is necessary within medicine.

Yet there’s been a “long tradition of looking the other way or letting people with fancy titles get away with saying nonsense just because they’re respected,” Jonathan Howard, MD, an associate professor of psychiatry and neurology at New York University said in an interview.

“We have a duty to be trusted members of the community,” Dr. Howard said. “People listen when we say things, and we have an obligation to try to be accurate and humble and as honest as possible and admit mistakes when we inevitably make them.”

That extends to social media, which Dr. Nichols said has magnified the problem of promoting quackery and misinformation. He thinks medical boards and professional credentialing bodies should pay attention to what’s happening in the public conversation and understand that our professional responsibility extends beyond the walls of the hospital or clinic. Physicians must represent themselves professionally and uphold the standards that the profession expects.

On the one hand, Medscape respondents agreed: 70% said one doctor’s misbehavior taints the whole profession. Yet, at the same time, 58% of respondents believed physicians should be able to “keep their private lives private” in 2022. But that’s not the reality of the profession when the lines between private life and behavior away from work get blurred, Dr. Samenow said.

“The way a physician behaves in public represents you,” he said. “What happens in Vegas doesn’t always stay in Vegas.”

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

Daniel Freedman, DO, a pediatric neurologist in Austin, Tex., remembers being flabbergasted when a surgeon threw an instrument across the room in medical school.

“I remember thinking, ‘I can’t believe people actually do this, a grown man in his 50s having a temper tantrum,’” Dr. Freedman said in an interview. But it certainly wasn’t the last time he witnessed bad behavior by one of his peers.

The results of Medscape’s recent report, Physicians Behaving Badly: Stress and Hardship Trigger Misconduct, suggest he has plenty of company. More than 4 in 10 respondents (41%) observed inappropriate behavior in the workplace in 2022, an uptick from 35% in 2021, according to the report, which polled more than 1,500 physicians about inappropriate behavior on and off the clock.

Of course, 38% of respondents have not seen any instances of misbehavior; and many of the instances that were seen were mild or infrequent. Additionally, instances of bad behavior have declined significantly over the past 5 years.

Dr. Freedman said he learned a lesson from his mentor and program director during training that has stuck with him throughout his career. “If you couldn’t act that way at any job, whether at McDonald’s or any other possible place, you shouldn’t act that way in medicine.” But he recognizes one limitation of that advice. “A lot of the people that behave badly may not have ever worked in a different environment before,” he said.

“They only perceive that they’re at the top of the food chain, so they can behave badly without repercussions.”

What Dr. Freedman described is formally called disruptive physician behavior, one of several categories of inappropriate behavior in medicine, according to Charles Samenow, MD, MPH, an associate professor of psychiatry and behavioral sciences at George Washington University, Washington, who has studied this phenomenon for years.

“Disruptive physician behavior compromises the safety of the workplace,” Dr. Samenow explained. The behavior can occur at work, outside of work, or on social media. It can hinder operations, threaten patient and staff safety, and affect workplace morale.

“The question is trying to understand where that bad behavior is coming from and the impact of that bad behavior,” Dr. Samenow said in an interview.

One reason is fairly simple: doctors are human, and humans have a wide range of behavior. Plus, as the Medscape survey showed, the tension, stress, dangerous conditions during COVID, burnout, and other problems have made many physicians tired, frustrated, depressed, and more reactive to situations around them.
 

Self-selecting traits become an Achilles heel

“Any human put in a position of power over other humans has the potential to be disruptive, harass, etc, if they have certain personality traits,” said David Gorski, MD, a professor of surgery at Wayne State University, Detroit. That jibes with Dr. Samenow’s research.

Classic disruptive behavior isn’t usually associated with depression, mania, psychosis, or similar characteristics, Dr. Samenow explained. Rather, it tends to be personality driven. “Physicians are not immune to the normal problems every human being faces,” he said.

In the Medscape report, physicians cited personal arrogance as one of the leading reasons physicians engaged in inappropriate behavior (56%), followed closely by personal problems outside of work (52%), a social shift in accepting more casual behavior (50%), and job-related stress (46%). (Respondents could choose more than one answer).

One factor contributing to misbehavior that Dr. Samenow has consistently identified in his research is a history of adverse childhood experiences or family dysfunction: People who grew up in homes with physical or verbal abuse learned anger as a coping skill instead of positive, assertive communication. It’s likely that some physicians, as well as the overall population, learned anger as a coping skill for that reason.
 

How to help avert disruptive behavior in medical settings

Dr. Samenow said that coaching is a “wonderful tool” in teaching the interpersonal skills that medical school often doesn’t address.

In some case, interventions can be very helpful. For example, programs that teach effective communication strategies and teamwork through a combination of culturally sensitive dialectical and cognitive-behavioral therapy and other modalities have been successful, Dr. Samenow said. Although they are more about treating an illness than addressing “misbehavior,” programs for substance use that have been developed by and for doctors are very effective, too.

Fewer resources are available, however, for addressing racism, classism, misogyny, and other forms of bigotry, Dr. Samenow noted. “There’s implicit bias training, but not at the level of what exists for disruptive physicians and those with addiction. “That’s an area we need to work on.” Racist language was the third most commonly observed bad behavior cited in the Medscape survey, behind only bullying of staff and mocking or disparaging of patients. It was reported frequently outside of work as well.

The Medscape report found an increase in observed behavior at work and on social media, although it’s hard to determine prevalence trends over time, Dr. Samenow said. “The tolerance for this behavior has really gone down,” likely leading to more reporting, he said, and more systems for reporting bad behavior exist today than in the past.

However, Dr. Freedman said inadequate regulation, disciplinary action, and follow-through remain a problem.

“There are lots of limitations to our reporting system and to our follow-through with those reports,” including hospitals that, whether for fear of litigation or other reasons, allow physicians to quietly resign and move to another institution, even with positive recommendations, Dr. Freedman said.

Indeed, only a third of observed misbehavior in the Medscape report resulted in disciplinary action. Half the respondents believed a verbal warning was a necessary consequence, followed by a conversation from management and being reported to a supervisor or human resources. Though only 10% thought a report to the medical board was warranted, it likely depends on the offense and its frequency.

“I think going from paternalism to more patient-centered care and having patients involved in those conversations is a nice shift that makes doctors more human and relatable, and hopefully makes the public more forgiving, that we’re going to make mistakes and nobody’s perfect,” Freedman said. But he added that physicians should be held accountable when a mistake or two becomes a pattern.
 

Misinformation is professional misconduct

Sufficient accountability is especially absent, these doctors said, for a subset of professional misconduct: spreading misinformation.

While more “conventional” bad behaviors include fraud, dishonesty, abuse of underlings, and incompetence, bad behavior should also include “selling quackery and antivaccine misinformation, the way some doctors did with various nostrums for COVID-19,” said Dr. Gorski, who frequently blogs about doctors’ spreading misinformation.

Taylor Nichols, MD, an emergency medicine physician based in Sacramento, cites the desire for attention and clout as motivations. “Saying things that are wildly, provably false is professional misconduct,” Nichols said. He distinguished such statements from scientific, academic, or clinical disagreement that is necessary within medicine.

Yet there’s been a “long tradition of looking the other way or letting people with fancy titles get away with saying nonsense just because they’re respected,” Jonathan Howard, MD, an associate professor of psychiatry and neurology at New York University said in an interview.

“We have a duty to be trusted members of the community,” Dr. Howard said. “People listen when we say things, and we have an obligation to try to be accurate and humble and as honest as possible and admit mistakes when we inevitably make them.”

That extends to social media, which Dr. Nichols said has magnified the problem of promoting quackery and misinformation. He thinks medical boards and professional credentialing bodies should pay attention to what’s happening in the public conversation and understand that our professional responsibility extends beyond the walls of the hospital or clinic. Physicians must represent themselves professionally and uphold the standards that the profession expects.

On the one hand, Medscape respondents agreed: 70% said one doctor’s misbehavior taints the whole profession. Yet, at the same time, 58% of respondents believed physicians should be able to “keep their private lives private” in 2022. But that’s not the reality of the profession when the lines between private life and behavior away from work get blurred, Dr. Samenow said.

“The way a physician behaves in public represents you,” he said. “What happens in Vegas doesn’t always stay in Vegas.”

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

Miscarriages are a devastating, if natural, occurrence. Nearly 1 million pregnant people in the United States experience a miscarriage every year, according to the National Advocates for Pregnant Women. New research could lend insight into the causes of some types of early pregnancy loss and maybe one day help prevent miscarriages. 

In the bioengineering breakthrough, scientists created a mouse embryo in a lab without using sperm or eggs. The experimental embryo, called a model, was grown out of stem cells and developed further than any earlier experiments, with a beating heart and the foundation of a brain within a yolk sac, according to the researchers. 

The experiment, while conducted with mouse stem cells, could help explain why some human pregnancies fail. Miscarriages occur in up to 15% of pregnancies confirmed by doctors, according to some studies, and also for many pregnant people before they even knew of the pregnancy. This experiment gives researchers a glimpse of a critical developmental stage for the first time. 

“We are building mouse embryo models, but they have exactly the same principle as real human embryos,” says lead researcher Magdalena Zernicka-Goetz, PhD, professor in mammalian development and stem cell biology at Cambridge (England) University. “That’s why they tell us about real pregnancy.”

With the new mouse models, the researchers can study implantation, the stage when embryos embed themselves in the mother’s body – a stage that’s often difficult for embryos to survive. The same process happens in mouse embryos, which develop very similarly to human embryos at this early stage of life.

Six years ago, researchers from the University of Cambridge and the California Institute of Technology set out to create models that would allow them to study fetal development in three-dimensional form but without the need for human embryos. 

“We are trying to understand the major principles of time and space that have to be fulfilled” to form a successful pregnancy, Dr. Zernicka-Goetz explains. “If those principles are not fulfilled, the pregnancies are terminated, even before women know they’re pregnant.” 

There are limits on using human embryos for research, and previous experiments have tended to replicate only one aspect of development. That led to two-dimensional experiments: flat cells on the bottom of a petri dish that lack the structural organization of real tissue. 

The new models are three-dimensional with beating hearts and the yolk sacs in which embryos feed and grow. The models even progressed to forming the beginning of a brain – a research first. 

The scientists used the foundational cellular “building blocks” called stem cells and managed to get the cells to communicate along a timeline that mimicked natural development, simulating those developmental stages, says Dr. Zernicka-Goetz. Those “building blocks” are actually three types of stem cells: pluripotent stem cells that build body tissue, and two other types of stem cells that build the placenta and the amniotic sac. 

Completing the experiment required the right quantity of each stem cell type. The researchers also needed to understand how those cells exchange information before they can begin to grow. The researchers were able to “decipher the code” of how the cells talk to each other, Dr. Zernicka-Goetz says.

Initially, the three types of stem cells combine, almost like a soup, but when the timing is right, they have to recognize each other and sort themselves. Next, each stem cell type must start building a different structure necessary for fetal development. Dr. Zernicka-Goetz thinks of this construction as the architecture of human tissue. 

With the new technique, researchers can continue investigating the implantation stage and beyond. And they did – tweaking the experiment to create a genetically flawed embryo on purpose.

Dr. Zernicka-Goetz and her team eliminated a certain gene known to regulate how cells establish their own identities. Doing so resulted in the same brain development flaws as in human embryos, providing “a proof of concept” that the experimental models can be used to study other genetic mysteries, she says. 

Scientists are still in the dark about what some genes do, as well as the point when they become critical to brain development. 

“Many genes have very early roles in specifying, for example, the position of the head and also how our brain will function,” Dr. Zernicka-Goetz says. “We can now use this model system to assess the function of those genes.” 

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

Miscarriages are a devastating, if natural, occurrence. Nearly 1 million pregnant people in the United States experience a miscarriage every year, according to the National Advocates for Pregnant Women. New research could lend insight into the causes of some types of early pregnancy loss and maybe one day help prevent miscarriages. 

In the bioengineering breakthrough, scientists created a mouse embryo in a lab without using sperm or eggs. The experimental embryo, called a model, was grown out of stem cells and developed further than any earlier experiments, with a beating heart and the foundation of a brain within a yolk sac, according to the researchers. 

The experiment, while conducted with mouse stem cells, could help explain why some human pregnancies fail. Miscarriages occur in up to 15% of pregnancies confirmed by doctors, according to some studies, and also for many pregnant people before they even knew of the pregnancy. This experiment gives researchers a glimpse of a critical developmental stage for the first time. 

“We are building mouse embryo models, but they have exactly the same principle as real human embryos,” says lead researcher Magdalena Zernicka-Goetz, PhD, professor in mammalian development and stem cell biology at Cambridge (England) University. “That’s why they tell us about real pregnancy.”

With the new mouse models, the researchers can study implantation, the stage when embryos embed themselves in the mother’s body – a stage that’s often difficult for embryos to survive. The same process happens in mouse embryos, which develop very similarly to human embryos at this early stage of life.

Six years ago, researchers from the University of Cambridge and the California Institute of Technology set out to create models that would allow them to study fetal development in three-dimensional form but without the need for human embryos. 

“We are trying to understand the major principles of time and space that have to be fulfilled” to form a successful pregnancy, Dr. Zernicka-Goetz explains. “If those principles are not fulfilled, the pregnancies are terminated, even before women know they’re pregnant.” 

There are limits on using human embryos for research, and previous experiments have tended to replicate only one aspect of development. That led to two-dimensional experiments: flat cells on the bottom of a petri dish that lack the structural organization of real tissue. 

The new models are three-dimensional with beating hearts and the yolk sacs in which embryos feed and grow. The models even progressed to forming the beginning of a brain – a research first. 

The scientists used the foundational cellular “building blocks” called stem cells and managed to get the cells to communicate along a timeline that mimicked natural development, simulating those developmental stages, says Dr. Zernicka-Goetz. Those “building blocks” are actually three types of stem cells: pluripotent stem cells that build body tissue, and two other types of stem cells that build the placenta and the amniotic sac. 

Completing the experiment required the right quantity of each stem cell type. The researchers also needed to understand how those cells exchange information before they can begin to grow. The researchers were able to “decipher the code” of how the cells talk to each other, Dr. Zernicka-Goetz says.

Initially, the three types of stem cells combine, almost like a soup, but when the timing is right, they have to recognize each other and sort themselves. Next, each stem cell type must start building a different structure necessary for fetal development. Dr. Zernicka-Goetz thinks of this construction as the architecture of human tissue. 

With the new technique, researchers can continue investigating the implantation stage and beyond. And they did – tweaking the experiment to create a genetically flawed embryo on purpose.

Dr. Zernicka-Goetz and her team eliminated a certain gene known to regulate how cells establish their own identities. Doing so resulted in the same brain development flaws as in human embryos, providing “a proof of concept” that the experimental models can be used to study other genetic mysteries, she says. 

Scientists are still in the dark about what some genes do, as well as the point when they become critical to brain development. 

“Many genes have very early roles in specifying, for example, the position of the head and also how our brain will function,” Dr. Zernicka-Goetz says. “We can now use this model system to assess the function of those genes.” 

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

Miscarriages are a devastating, if natural, occurrence. Nearly 1 million pregnant people in the United States experience a miscarriage every year, according to the National Advocates for Pregnant Women. New research could lend insight into the causes of some types of early pregnancy loss and maybe one day help prevent miscarriages. 

In the bioengineering breakthrough, scientists created a mouse embryo in a lab without using sperm or eggs. The experimental embryo, called a model, was grown out of stem cells and developed further than any earlier experiments, with a beating heart and the foundation of a brain within a yolk sac, according to the researchers. 

The experiment, while conducted with mouse stem cells, could help explain why some human pregnancies fail. Miscarriages occur in up to 15% of pregnancies confirmed by doctors, according to some studies, and also for many pregnant people before they even knew of the pregnancy. This experiment gives researchers a glimpse of a critical developmental stage for the first time. 

“We are building mouse embryo models, but they have exactly the same principle as real human embryos,” says lead researcher Magdalena Zernicka-Goetz, PhD, professor in mammalian development and stem cell biology at Cambridge (England) University. “That’s why they tell us about real pregnancy.”

With the new mouse models, the researchers can study implantation, the stage when embryos embed themselves in the mother’s body – a stage that’s often difficult for embryos to survive. The same process happens in mouse embryos, which develop very similarly to human embryos at this early stage of life.

Six years ago, researchers from the University of Cambridge and the California Institute of Technology set out to create models that would allow them to study fetal development in three-dimensional form but without the need for human embryos. 

“We are trying to understand the major principles of time and space that have to be fulfilled” to form a successful pregnancy, Dr. Zernicka-Goetz explains. “If those principles are not fulfilled, the pregnancies are terminated, even before women know they’re pregnant.” 

There are limits on using human embryos for research, and previous experiments have tended to replicate only one aspect of development. That led to two-dimensional experiments: flat cells on the bottom of a petri dish that lack the structural organization of real tissue. 

The new models are three-dimensional with beating hearts and the yolk sacs in which embryos feed and grow. The models even progressed to forming the beginning of a brain – a research first. 

The scientists used the foundational cellular “building blocks” called stem cells and managed to get the cells to communicate along a timeline that mimicked natural development, simulating those developmental stages, says Dr. Zernicka-Goetz. Those “building blocks” are actually three types of stem cells: pluripotent stem cells that build body tissue, and two other types of stem cells that build the placenta and the amniotic sac. 

Completing the experiment required the right quantity of each stem cell type. The researchers also needed to understand how those cells exchange information before they can begin to grow. The researchers were able to “decipher the code” of how the cells talk to each other, Dr. Zernicka-Goetz says.

Initially, the three types of stem cells combine, almost like a soup, but when the timing is right, they have to recognize each other and sort themselves. Next, each stem cell type must start building a different structure necessary for fetal development. Dr. Zernicka-Goetz thinks of this construction as the architecture of human tissue. 

With the new technique, researchers can continue investigating the implantation stage and beyond. And they did – tweaking the experiment to create a genetically flawed embryo on purpose.

Dr. Zernicka-Goetz and her team eliminated a certain gene known to regulate how cells establish their own identities. Doing so resulted in the same brain development flaws as in human embryos, providing “a proof of concept” that the experimental models can be used to study other genetic mysteries, she says. 

Scientists are still in the dark about what some genes do, as well as the point when they become critical to brain development. 

“Many genes have very early roles in specifying, for example, the position of the head and also how our brain will function,” Dr. Zernicka-Goetz says. “We can now use this model system to assess the function of those genes.” 

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

Several leading medical groups on Oct. 3 called on U.S. Attorney General Merrick Garland to investigate and prosecute those responsible for a recent spate of threats and attacks against hospitals and physicians who are providing gender-affirming care.

In an Oct. 3 letter, the American Academy of Pediatrics (AAP), the American Medical Association (AMA), and the Children’s Hospital Association detailed the risk posed by these threats to physicians, patients, and the federally protected right to health care.

The letter comes during a campaign of intimidation and misinformation that has disrupted gender-related care in Seattle, Akron, Ohio, Nashville, Tenn., and Boston in the past few weeks. Hospitals across the country and their ambulatory sites have been forced to substantially increase protection, and “some providers have needed 24/7 security,” according to the letter.

Not only do the threats bully physicians providing gender-affirming care and the patients who receive that care, but “they have also disrupted many other services to families seeking care,” the letter claims.

According to STAT, many hospitals that provide gender-affirming care have responded to the threats by removing information about the treatment from their websites.

At one hospital, a new mother was separated from her preterm infant because the facility’s neonatal intensive care unit was locked down as the result of a bomb threat. (It’s not clear whether that incident is the same as a similar threat that led to the arrest of a 37-year-old Massachusetts woman, who is facing criminal charges in the episode.)

“The attacks are rooted in an intentional campaign of disinformation” by high-profile social media users, according to the letter. The medical organizations have also called on major tech companies, including TikTok, Twitter, and Meta, to do more to prevent the coordination of disinformation campaigns and violence against health care providers and patients.

“We now urge your office to take swift action to investigate and prosecute all organizations, individuals, and entities responsible,” the letter states.

“We cannot stand by as threats of violence against our members and their patients proliferate with little consequence. We call on the Department of Justice to investigate these attacks and social media platforms to reduce the spread of the misinformation enabling them,” AAP President Moira Szilagyi, MD, PhD, FAAP, said in a press release.

In addition to physical threats at their workplace, providers face threats on their personal social media accounts and harassment via phone and email. The letter notes that these unchecked attacks are coming after health care workers spent 3 years working on the front lines of a pandemic.

“Individuals in all workplaces have the right to a safe environment, out of harm’s way and free of intimidation or reprisal,” AMA President Jack Resneck Jr, MD, said in a statement. “The AMA will continue to work with federal, state, and local law enforcement officials to develop and implement strategies that protect hard-working, law-abiding physicians and other health care workers from senseless acts of violence, abuse, and intimidation.”

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

Several leading medical groups on Oct. 3 called on U.S. Attorney General Merrick Garland to investigate and prosecute those responsible for a recent spate of threats and attacks against hospitals and physicians who are providing gender-affirming care.

In an Oct. 3 letter, the American Academy of Pediatrics (AAP), the American Medical Association (AMA), and the Children’s Hospital Association detailed the risk posed by these threats to physicians, patients, and the federally protected right to health care.

The letter comes during a campaign of intimidation and misinformation that has disrupted gender-related care in Seattle, Akron, Ohio, Nashville, Tenn., and Boston in the past few weeks. Hospitals across the country and their ambulatory sites have been forced to substantially increase protection, and “some providers have needed 24/7 security,” according to the letter.

Not only do the threats bully physicians providing gender-affirming care and the patients who receive that care, but “they have also disrupted many other services to families seeking care,” the letter claims.

According to STAT, many hospitals that provide gender-affirming care have responded to the threats by removing information about the treatment from their websites.

At one hospital, a new mother was separated from her preterm infant because the facility’s neonatal intensive care unit was locked down as the result of a bomb threat. (It’s not clear whether that incident is the same as a similar threat that led to the arrest of a 37-year-old Massachusetts woman, who is facing criminal charges in the episode.)

“The attacks are rooted in an intentional campaign of disinformation” by high-profile social media users, according to the letter. The medical organizations have also called on major tech companies, including TikTok, Twitter, and Meta, to do more to prevent the coordination of disinformation campaigns and violence against health care providers and patients.

“We now urge your office to take swift action to investigate and prosecute all organizations, individuals, and entities responsible,” the letter states.

“We cannot stand by as threats of violence against our members and their patients proliferate with little consequence. We call on the Department of Justice to investigate these attacks and social media platforms to reduce the spread of the misinformation enabling them,” AAP President Moira Szilagyi, MD, PhD, FAAP, said in a press release.

In addition to physical threats at their workplace, providers face threats on their personal social media accounts and harassment via phone and email. The letter notes that these unchecked attacks are coming after health care workers spent 3 years working on the front lines of a pandemic.

“Individuals in all workplaces have the right to a safe environment, out of harm’s way and free of intimidation or reprisal,” AMA President Jack Resneck Jr, MD, said in a statement. “The AMA will continue to work with federal, state, and local law enforcement officials to develop and implement strategies that protect hard-working, law-abiding physicians and other health care workers from senseless acts of violence, abuse, and intimidation.”

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

Several leading medical groups on Oct. 3 called on U.S. Attorney General Merrick Garland to investigate and prosecute those responsible for a recent spate of threats and attacks against hospitals and physicians who are providing gender-affirming care.

In an Oct. 3 letter, the American Academy of Pediatrics (AAP), the American Medical Association (AMA), and the Children’s Hospital Association detailed the risk posed by these threats to physicians, patients, and the federally protected right to health care.

The letter comes during a campaign of intimidation and misinformation that has disrupted gender-related care in Seattle, Akron, Ohio, Nashville, Tenn., and Boston in the past few weeks. Hospitals across the country and their ambulatory sites have been forced to substantially increase protection, and “some providers have needed 24/7 security,” according to the letter.

Not only do the threats bully physicians providing gender-affirming care and the patients who receive that care, but “they have also disrupted many other services to families seeking care,” the letter claims.

According to STAT, many hospitals that provide gender-affirming care have responded to the threats by removing information about the treatment from their websites.

At one hospital, a new mother was separated from her preterm infant because the facility’s neonatal intensive care unit was locked down as the result of a bomb threat. (It’s not clear whether that incident is the same as a similar threat that led to the arrest of a 37-year-old Massachusetts woman, who is facing criminal charges in the episode.)

“The attacks are rooted in an intentional campaign of disinformation” by high-profile social media users, according to the letter. The medical organizations have also called on major tech companies, including TikTok, Twitter, and Meta, to do more to prevent the coordination of disinformation campaigns and violence against health care providers and patients.

“We now urge your office to take swift action to investigate and prosecute all organizations, individuals, and entities responsible,” the letter states.

“We cannot stand by as threats of violence against our members and their patients proliferate with little consequence. We call on the Department of Justice to investigate these attacks and social media platforms to reduce the spread of the misinformation enabling them,” AAP President Moira Szilagyi, MD, PhD, FAAP, said in a press release.

In addition to physical threats at their workplace, providers face threats on their personal social media accounts and harassment via phone and email. The letter notes that these unchecked attacks are coming after health care workers spent 3 years working on the front lines of a pandemic.

“Individuals in all workplaces have the right to a safe environment, out of harm’s way and free of intimidation or reprisal,” AMA President Jack Resneck Jr, MD, said in a statement. “The AMA will continue to work with federal, state, and local law enforcement officials to develop and implement strategies that protect hard-working, law-abiding physicians and other health care workers from senseless acts of violence, abuse, and intimidation.”

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

Prescription folic acid, a synthetic form of vitamin B₉, may provide a safe and effective approach for decreasing suicidal ideation, new research suggests.

After adjusting for multiple factors, results from a large pharmaco-epidemiological study showed taking folic acid was associated with a 44% reduction in suicide events.

“These results are really putting folic acid squarely on the map as a potential for large-scale, population-level prevention,” lead author Robert D. Gibbons, PhD, professor of biostatistics, Center for Health Statistics, University of Chicago, said in an interview.

University of Chicago

“Folic acid is safe, inexpensive, and generally available, and if future randomized controlled trials show this association is beyond a shadow of a doubt causal, we have a new tool in the arsenal,” Dr. Gibbons said.

Having such a tool would be extremely important given that suicide is such a significant public health crisis worldwide, he added.

The findings were published online in JAMA Psychiatry.
 

Previous research ‘fairly thin’

Folate, the naturally occurring form of B₉, is essential for neurogenesis, nucleotide synthesis, and methylation of homocysteine. Past research has suggested that taking folate can prevent neural tube and heart defects in the fetus during pregnancy – and may prevent strokes and reduce age-related hearing loss in adults.

In psychiatry, the role of folate has been recognized for more than a decade. It may enhance the effects of antidepressants; and folate deficiency can predict poorer response to SSRIs.

This has led to recommendations for folate augmentation in patients with low or normal levels at the start of depression treatment.

Although previous research has shown a link between folic acid and suicidality, the findings have been “fairly thin,” with studies being “generally small, and many are case series,” Dr. Gibbons said.

The current study follows an earlier analysis that used a novel statistical methodology for generating drug safety signals that was developed by Dr. Gibbons and colleagues. That study compared rates of suicide attempts before and after initiation of 922 drugs with at least 3,000 prescriptions.

Its results showed 10 drugs were associated with increased risk after exposure, with the strongest associations for alprazolam, butalbital, hydrocodone, and combination codeine/promethazine. In addition, 44 drugs were associated with decreased risk, many of which were antidepressants and antipsychotics.

“One of the most interesting findings in terms of the decreased risk was for folic acid,” said Dr. Gibbons.

He and his colleagues initially thought this was because of women taking folic acid during pregnancy. But when restricting the analysis to men, they found the same effect.

Their next step was to carry out the current large-scale pharmaco-epidemiological study.
 

Prescriptions for pain

The researchers used a health claims database that included 164 million enrollees. The study cohort was comprised of 866,586 adults with private health insurance (81.3% women; 10.4% aged 60 years and older) who filled a folic acid prescription between 2012 and 2017.

More than half of the folic acid prescriptions were associated with pain disorders. About 48% were for a single agent at a dosage of 1 mg/d, which is the upper tolerable limit for adults – including in pregnancy and lactation.

Other single-agent daily dosages ranging from 0.4 mg to 5 mg accounted for 0.11% of prescriptions. The remainder were multivitamins.

The participants were followed for 24 months. The within-person analysis compared suicide attempts or self-harm events resulting in an outpatient visit or inpatient admission during periods of folic acid treatment versus during periods without treatment.

During the study period, the overall suicidal event rate was 133 per 100,000 population, which is one-fourth the national rate reported by the National Institutes of Health of 600 per 100,000.

After adjusting for age, sex, diagnoses related to suicidal behavior and folic acid deficiency, history of folate-reducing medications, and history of suicidal events, the estimated hazard ratio for suicide events when taking folic acid was 0.56 (95% confidence interal, 0.48-0.65) – which indicates a 44% reduction in suicide events.

“This is a very large decrease and is extremely significant and exciting,” Dr. Gibbons said.

He noted the decrease in suicidal events may have been even greater considering the study captured only prescription folic acid, and participants may also have also taken over-the-counter products.

“The 44% reduction in suicide attempts may actually be an underestimate,” said Dr. Gibbons.

Age and sex did not moderate the association between folic acid and suicide attempts, and a similar association was found in women of childbearing age.
 

Provocative results?

The investigators also assessed a negative control group of 236,610 individuals using cyanocobalamin during the study period. Cyanocobalamin is a form of vitamin B₁₂ that is essential for metabolism, blood cell synthesis, and the nervous system. It does not contain folic acid and is commonly used to treat anemia.

Results showed no association between cyanocobalamin and suicidal events in the adjusted analysis (HR, 1.01; 95% CI, 0.80-1.27) or unadjusted analysis (HR, 1.02; 95% CI, 0.80-1.28).

Dr. Gibbons noted this result boosts the argument that the association between folic acid and reduced suicidal attempts “isn’t just about health-seeking behavior like taking vitamin supplements.”

Another sensitivity analysis showed every additional month of treatment was associated with a 5% reduction in the suicidal event rate.

“This means the longer you take folic acid, the greater the benefit, which is what you would expect to see if there was a real association between a treatment and an outcome,” said Dr. Gibbons.

The new results “are so provocative that they really mandate the need for a well-controlled randomized controlled trial of folic acid and suicide events,” possibly in a high-risk population such as veterans, he noted.

Such a study could use longitudinal assessments of suicidal events, such as the validated Computerized Adaptive Test Suicide Scale, he added. This continuous scale of suicidality ranges from subclinical, signifying helplessness, hopelessness, and loss of pleasure, to suicide attempts and completion.

As for study limitations, the investigators noted that this study was observational, so there could be selection effects. And using claims data likely underrepresented the number of suicidal events because of incomplete reporting. As the researchers pointed out, the rate of suicidal events in this study was much lower than the national rate.

Other limitations cited were that the association between folic acid and suicidal events may be explained by healthy user bias; and although the investigators conducted a sensitivity analysis in women of childbearing age, they did not have data on women actively planning for a pregnancy.
 

‘Impressive, encouraging’

In a comment, Shirley Yen, PhD, associate professor of psychology, Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, described the new findings as “quite impressive” and “extremely encouraging.”

However, she noted “it’s too premature” to suggest widespread use of folic acid in patients with depressive symptoms.

Dr. Yen, who has researched suicide risks previously, was not involved with the current study.

She did agree with the investigators that the results call for “more robustly controlled studies. These could include double-blind, randomized, controlled trials that could “more formally assess” all folic acid usage as opposed to prescriptions only, Dr. Yen said.

The study was funded by the NIH, the Agency for Healthcare Research and Quality, and the Center of Excellence for Suicide Prevention. Dr. Gibbons reported serving as an expert witness in cases for the Department of Justice; receiving expert witness fees from Merck, GlaxoSmithKline, Pfizer, and Wyeth; and having founded Adaptive Testing Technologies, which distributes the Computerized Adaptive Test Suicide Scale. Dr. Yen reported no relevant financial relationships.

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

Prescription folic acid, a synthetic form of vitamin B₉, may provide a safe and effective approach for decreasing suicidal ideation, new research suggests.

After adjusting for multiple factors, results from a large pharmaco-epidemiological study showed taking folic acid was associated with a 44% reduction in suicide events.

“These results are really putting folic acid squarely on the map as a potential for large-scale, population-level prevention,” lead author Robert D. Gibbons, PhD, professor of biostatistics, Center for Health Statistics, University of Chicago, said in an interview.

University of Chicago

“Folic acid is safe, inexpensive, and generally available, and if future randomized controlled trials show this association is beyond a shadow of a doubt causal, we have a new tool in the arsenal,” Dr. Gibbons said.

Having such a tool would be extremely important given that suicide is such a significant public health crisis worldwide, he added.

The findings were published online in JAMA Psychiatry.
 

Previous research ‘fairly thin’

Folate, the naturally occurring form of B₉, is essential for neurogenesis, nucleotide synthesis, and methylation of homocysteine. Past research has suggested that taking folate can prevent neural tube and heart defects in the fetus during pregnancy – and may prevent strokes and reduce age-related hearing loss in adults.

In psychiatry, the role of folate has been recognized for more than a decade. It may enhance the effects of antidepressants; and folate deficiency can predict poorer response to SSRIs.

This has led to recommendations for folate augmentation in patients with low or normal levels at the start of depression treatment.

Although previous research has shown a link between folic acid and suicidality, the findings have been “fairly thin,” with studies being “generally small, and many are case series,” Dr. Gibbons said.

The current study follows an earlier analysis that used a novel statistical methodology for generating drug safety signals that was developed by Dr. Gibbons and colleagues. That study compared rates of suicide attempts before and after initiation of 922 drugs with at least 3,000 prescriptions.

Its results showed 10 drugs were associated with increased risk after exposure, with the strongest associations for alprazolam, butalbital, hydrocodone, and combination codeine/promethazine. In addition, 44 drugs were associated with decreased risk, many of which were antidepressants and antipsychotics.

“One of the most interesting findings in terms of the decreased risk was for folic acid,” said Dr. Gibbons.

He and his colleagues initially thought this was because of women taking folic acid during pregnancy. But when restricting the analysis to men, they found the same effect.

Their next step was to carry out the current large-scale pharmaco-epidemiological study.
 

Prescriptions for pain

The researchers used a health claims database that included 164 million enrollees. The study cohort was comprised of 866,586 adults with private health insurance (81.3% women; 10.4% aged 60 years and older) who filled a folic acid prescription between 2012 and 2017.

More than half of the folic acid prescriptions were associated with pain disorders. About 48% were for a single agent at a dosage of 1 mg/d, which is the upper tolerable limit for adults – including in pregnancy and lactation.

Other single-agent daily dosages ranging from 0.4 mg to 5 mg accounted for 0.11% of prescriptions. The remainder were multivitamins.

The participants were followed for 24 months. The within-person analysis compared suicide attempts or self-harm events resulting in an outpatient visit or inpatient admission during periods of folic acid treatment versus during periods without treatment.

During the study period, the overall suicidal event rate was 133 per 100,000 population, which is one-fourth the national rate reported by the National Institutes of Health of 600 per 100,000.

After adjusting for age, sex, diagnoses related to suicidal behavior and folic acid deficiency, history of folate-reducing medications, and history of suicidal events, the estimated hazard ratio for suicide events when taking folic acid was 0.56 (95% confidence interal, 0.48-0.65) – which indicates a 44% reduction in suicide events.

“This is a very large decrease and is extremely significant and exciting,” Dr. Gibbons said.

He noted the decrease in suicidal events may have been even greater considering the study captured only prescription folic acid, and participants may also have also taken over-the-counter products.

“The 44% reduction in suicide attempts may actually be an underestimate,” said Dr. Gibbons.

Age and sex did not moderate the association between folic acid and suicide attempts, and a similar association was found in women of childbearing age.
 

Provocative results?

The investigators also assessed a negative control group of 236,610 individuals using cyanocobalamin during the study period. Cyanocobalamin is a form of vitamin B₁₂ that is essential for metabolism, blood cell synthesis, and the nervous system. It does not contain folic acid and is commonly used to treat anemia.

Results showed no association between cyanocobalamin and suicidal events in the adjusted analysis (HR, 1.01; 95% CI, 0.80-1.27) or unadjusted analysis (HR, 1.02; 95% CI, 0.80-1.28).

Dr. Gibbons noted this result boosts the argument that the association between folic acid and reduced suicidal attempts “isn’t just about health-seeking behavior like taking vitamin supplements.”

Another sensitivity analysis showed every additional month of treatment was associated with a 5% reduction in the suicidal event rate.

“This means the longer you take folic acid, the greater the benefit, which is what you would expect to see if there was a real association between a treatment and an outcome,” said Dr. Gibbons.

The new results “are so provocative that they really mandate the need for a well-controlled randomized controlled trial of folic acid and suicide events,” possibly in a high-risk population such as veterans, he noted.

Such a study could use longitudinal assessments of suicidal events, such as the validated Computerized Adaptive Test Suicide Scale, he added. This continuous scale of suicidality ranges from subclinical, signifying helplessness, hopelessness, and loss of pleasure, to suicide attempts and completion.

As for study limitations, the investigators noted that this study was observational, so there could be selection effects. And using claims data likely underrepresented the number of suicidal events because of incomplete reporting. As the researchers pointed out, the rate of suicidal events in this study was much lower than the national rate.

Other limitations cited were that the association between folic acid and suicidal events may be explained by healthy user bias; and although the investigators conducted a sensitivity analysis in women of childbearing age, they did not have data on women actively planning for a pregnancy.
 

‘Impressive, encouraging’

In a comment, Shirley Yen, PhD, associate professor of psychology, Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, described the new findings as “quite impressive” and “extremely encouraging.”

However, she noted “it’s too premature” to suggest widespread use of folic acid in patients with depressive symptoms.

Dr. Yen, who has researched suicide risks previously, was not involved with the current study.

She did agree with the investigators that the results call for “more robustly controlled studies. These could include double-blind, randomized, controlled trials that could “more formally assess” all folic acid usage as opposed to prescriptions only, Dr. Yen said.

The study was funded by the NIH, the Agency for Healthcare Research and Quality, and the Center of Excellence for Suicide Prevention. Dr. Gibbons reported serving as an expert witness in cases for the Department of Justice; receiving expert witness fees from Merck, GlaxoSmithKline, Pfizer, and Wyeth; and having founded Adaptive Testing Technologies, which distributes the Computerized Adaptive Test Suicide Scale. Dr. Yen reported no relevant financial relationships.

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

Prescription folic acid, a synthetic form of vitamin B₉, may provide a safe and effective approach for decreasing suicidal ideation, new research suggests.

After adjusting for multiple factors, results from a large pharmaco-epidemiological study showed taking folic acid was associated with a 44% reduction in suicide events.

“These results are really putting folic acid squarely on the map as a potential for large-scale, population-level prevention,” lead author Robert D. Gibbons, PhD, professor of biostatistics, Center for Health Statistics, University of Chicago, said in an interview.

University of Chicago

“Folic acid is safe, inexpensive, and generally available, and if future randomized controlled trials show this association is beyond a shadow of a doubt causal, we have a new tool in the arsenal,” Dr. Gibbons said.

Having such a tool would be extremely important given that suicide is such a significant public health crisis worldwide, he added.

The findings were published online in JAMA Psychiatry.
 

Previous research ‘fairly thin’

Folate, the naturally occurring form of B₉, is essential for neurogenesis, nucleotide synthesis, and methylation of homocysteine. Past research has suggested that taking folate can prevent neural tube and heart defects in the fetus during pregnancy – and may prevent strokes and reduce age-related hearing loss in adults.

In psychiatry, the role of folate has been recognized for more than a decade. It may enhance the effects of antidepressants; and folate deficiency can predict poorer response to SSRIs.

This has led to recommendations for folate augmentation in patients with low or normal levels at the start of depression treatment.

Although previous research has shown a link between folic acid and suicidality, the findings have been “fairly thin,” with studies being “generally small, and many are case series,” Dr. Gibbons said.

The current study follows an earlier analysis that used a novel statistical methodology for generating drug safety signals that was developed by Dr. Gibbons and colleagues. That study compared rates of suicide attempts before and after initiation of 922 drugs with at least 3,000 prescriptions.

Its results showed 10 drugs were associated with increased risk after exposure, with the strongest associations for alprazolam, butalbital, hydrocodone, and combination codeine/promethazine. In addition, 44 drugs were associated with decreased risk, many of which were antidepressants and antipsychotics.

“One of the most interesting findings in terms of the decreased risk was for folic acid,” said Dr. Gibbons.

He and his colleagues initially thought this was because of women taking folic acid during pregnancy. But when restricting the analysis to men, they found the same effect.

Their next step was to carry out the current large-scale pharmaco-epidemiological study.
 

Prescriptions for pain

The researchers used a health claims database that included 164 million enrollees. The study cohort was comprised of 866,586 adults with private health insurance (81.3% women; 10.4% aged 60 years and older) who filled a folic acid prescription between 2012 and 2017.

More than half of the folic acid prescriptions were associated with pain disorders. About 48% were for a single agent at a dosage of 1 mg/d, which is the upper tolerable limit for adults – including in pregnancy and lactation.

Other single-agent daily dosages ranging from 0.4 mg to 5 mg accounted for 0.11% of prescriptions. The remainder were multivitamins.

The participants were followed for 24 months. The within-person analysis compared suicide attempts or self-harm events resulting in an outpatient visit or inpatient admission during periods of folic acid treatment versus during periods without treatment.

During the study period, the overall suicidal event rate was 133 per 100,000 population, which is one-fourth the national rate reported by the National Institutes of Health of 600 per 100,000.

After adjusting for age, sex, diagnoses related to suicidal behavior and folic acid deficiency, history of folate-reducing medications, and history of suicidal events, the estimated hazard ratio for suicide events when taking folic acid was 0.56 (95% confidence interal, 0.48-0.65) – which indicates a 44% reduction in suicide events.

“This is a very large decrease and is extremely significant and exciting,” Dr. Gibbons said.

He noted the decrease in suicidal events may have been even greater considering the study captured only prescription folic acid, and participants may also have also taken over-the-counter products.

“The 44% reduction in suicide attempts may actually be an underestimate,” said Dr. Gibbons.

Age and sex did not moderate the association between folic acid and suicide attempts, and a similar association was found in women of childbearing age.
 

Provocative results?

The investigators also assessed a negative control group of 236,610 individuals using cyanocobalamin during the study period. Cyanocobalamin is a form of vitamin B₁₂ that is essential for metabolism, blood cell synthesis, and the nervous system. It does not contain folic acid and is commonly used to treat anemia.

Results showed no association between cyanocobalamin and suicidal events in the adjusted analysis (HR, 1.01; 95% CI, 0.80-1.27) or unadjusted analysis (HR, 1.02; 95% CI, 0.80-1.28).

Dr. Gibbons noted this result boosts the argument that the association between folic acid and reduced suicidal attempts “isn’t just about health-seeking behavior like taking vitamin supplements.”

Another sensitivity analysis showed every additional month of treatment was associated with a 5% reduction in the suicidal event rate.

“This means the longer you take folic acid, the greater the benefit, which is what you would expect to see if there was a real association between a treatment and an outcome,” said Dr. Gibbons.

The new results “are so provocative that they really mandate the need for a well-controlled randomized controlled trial of folic acid and suicide events,” possibly in a high-risk population such as veterans, he noted.

Such a study could use longitudinal assessments of suicidal events, such as the validated Computerized Adaptive Test Suicide Scale, he added. This continuous scale of suicidality ranges from subclinical, signifying helplessness, hopelessness, and loss of pleasure, to suicide attempts and completion.

As for study limitations, the investigators noted that this study was observational, so there could be selection effects. And using claims data likely underrepresented the number of suicidal events because of incomplete reporting. As the researchers pointed out, the rate of suicidal events in this study was much lower than the national rate.

Other limitations cited were that the association between folic acid and suicidal events may be explained by healthy user bias; and although the investigators conducted a sensitivity analysis in women of childbearing age, they did not have data on women actively planning for a pregnancy.
 

‘Impressive, encouraging’

In a comment, Shirley Yen, PhD, associate professor of psychology, Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, described the new findings as “quite impressive” and “extremely encouraging.”

However, she noted “it’s too premature” to suggest widespread use of folic acid in patients with depressive symptoms.

Dr. Yen, who has researched suicide risks previously, was not involved with the current study.

She did agree with the investigators that the results call for “more robustly controlled studies. These could include double-blind, randomized, controlled trials that could “more formally assess” all folic acid usage as opposed to prescriptions only, Dr. Yen said.

The study was funded by the NIH, the Agency for Healthcare Research and Quality, and the Center of Excellence for Suicide Prevention. Dr. Gibbons reported serving as an expert witness in cases for the Department of Justice; receiving expert witness fees from Merck, GlaxoSmithKline, Pfizer, and Wyeth; and having founded Adaptive Testing Technologies, which distributes the Computerized Adaptive Test Suicide Scale. Dr. Yen reported no relevant financial relationships.

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

For Tara Lagu, MD, the realization that the health care system was broken for patients with disabilities came when a woman she had been treating seemed to keep ignoring Dr. Lagu’s request to see a urologist.

When Dr. Lagu asked the patient’s two attentive daughters about the delay, their response surprised her. The women said they couldn’t find a urologist who was willing to see a patient in a wheelchair.

Ingram/thinkstock

Surprised and a bit doubtful, Dr. Lagu checked around. She found that, indeed, the only way to get her patient in to see the type of physician required was to send her by ambulance.

“It opened my eyes to how hard it is for patients with disabilities to navigate the health care system,” Dr. Lagu said.

Dr. Lagu, director of the Center for Health Services and Outcomes Research at Northwestern University in Chicago, decided to take a closer look at how her colleagues in medicine care for – or not, as the case proved – the roughly one in four American adults, and millions of children, with disabilities.

In a series of three focus groups, Dr. Lagu and colleagues identified a range of obstacles – including some physician attitudes – that prevent people with disabilities from getting adequate care.

Lack of experience, logistics often cited

Some physicians admitted that limited resources and training left them without the space and necessary knowledge to properly care for patients with disabilities. They felt they lacked the expertise or exposure to care for individuals with disabilities, nor did they have enough time and space to properly accommodate these patients, according to the researchers. Some said they struggled to coordinate care for individuals with disabilities and did not know which types of accessible equipment, such as adjustable tables and chair scales, were needed or how to use them.

Several physicians also noted that they are inadequately reimbursed for the special accommodations – including additional staff, equipment, and time – required to care for these patients. One primary care physician said he hired a sign-language interpreter for a patient but the bill for the services exceeded the amount insurance reimbursed. As a result, he said, he spent $30 of his own money per visit to see the patient.

Because of these limitations, some physicians in the focus groups said they try to turn away patients with disabilities. Both specialists and general practitioners said they had told patients with disabilities that they didn’t feel they could provide the care needed, and suggested they look elsewhere. A few were surprisingly – even upsettingly – honest, Dr. Lagu said, making statements such as: “I am not the doctor for you.”
 

‘We really need a rewrite’

Previous work has shown that people with disabilities have worse health outcomes, such as undetected cancer, obesity, and cardiovascular disease.

But “the disability itself isn’t what leads to worse outcomes,” said Allison Kessler, MD, section chief of the Renée Crown Center for Spinal Cord Innovation and associate director of the Shirley Ryan AbilityLab in Chicago*. This study does a good job at highlighting “the need for change on multiple levels,” said Dr. Kessler, who was not a member of the study team.

“People with disabilities have all these disparities in access and outcomes. We’ve never understood why. I think the why is complicated,” Dr. Lagu added. “I think this study suggests some of the negative outcomes are due to explicit bias.”

“It’s also clear that the current framework of health care in the United States does not lend to allowing physicians and medical providers the time needed to adequately address patient issues – those with disabilities or just multiple complex problems,” Colin O’Reilly, DO, vice president and chief medical officer at Children’s Specialized Hospital, an acute rehabilitation facility affiliated with RWJBarnabas Health, in New Brunswick, N.J. “We really need a rewrite.”

However, Dr. O’Reilly said, such a small study population with no control group and no mention of physician resources makes it difficult to come to a strong conclusion about physician bias and discriminatory attitudes against individuals with disabilities.

Dr. Lagu agreed, saying this research “is not conclusive in any way.” The excuses doctors use to discharge patients with disabilities, such as “we don’t accept your insurance,” “we aren’t taking new patients,” and “we can’t provide you with the appropriate care,” could be legitimate, the study authors wrote. But the “disparities in care for people with disabilities suggest that there is a pattern of more frequently denying care to them than people without a disability,” they added.

Dr. Kessler said many of her patients have told her they experience barriers to care. Some say finding an office with the necessary equipment is a challenge or that they often don’t feel welcome.

The Americans With Disabilities Act (ADA) is a federal civil rights law that prohibits discrimination against individuals with disabilities in all public and private places that are open to the general public, including medical offices.

“It is difficult to enforce the ADA in medical settings,” the researchers noted. “Explanations physicians gave in this study could, for any single case of denying care, be legitimate.” Knowing whether a particular instance of denial of care represents discrimination related to disability is “nearly impossible,” they wrote.

All the experts agreed that the study adds valuable insight into an ongoing health disparity. And while system and policy changes are required, Dr. Kessler said, individual physicians can take steps to improve the situation.

A physician in an academic setting can look at the curriculum and the medical school and see about increasing exposure to patients with disabilities earlier in training. In a practice, physicians can retrain staff to ask every patient if an accommodation is needed. “Each one of those changes can only help us move our system in the right direction,” Dr. Kessler said.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

*Correction, 10/5/22: This article includes a corrected title for Dr. Allison Kessler.

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

For Tara Lagu, MD, the realization that the health care system was broken for patients with disabilities came when a woman she had been treating seemed to keep ignoring Dr. Lagu’s request to see a urologist.

When Dr. Lagu asked the patient’s two attentive daughters about the delay, their response surprised her. The women said they couldn’t find a urologist who was willing to see a patient in a wheelchair.

Ingram/thinkstock

Surprised and a bit doubtful, Dr. Lagu checked around. She found that, indeed, the only way to get her patient in to see the type of physician required was to send her by ambulance.

“It opened my eyes to how hard it is for patients with disabilities to navigate the health care system,” Dr. Lagu said.

Dr. Lagu, director of the Center for Health Services and Outcomes Research at Northwestern University in Chicago, decided to take a closer look at how her colleagues in medicine care for – or not, as the case proved – the roughly one in four American adults, and millions of children, with disabilities.

In a series of three focus groups, Dr. Lagu and colleagues identified a range of obstacles – including some physician attitudes – that prevent people with disabilities from getting adequate care.

Lack of experience, logistics often cited

Some physicians admitted that limited resources and training left them without the space and necessary knowledge to properly care for patients with disabilities. They felt they lacked the expertise or exposure to care for individuals with disabilities, nor did they have enough time and space to properly accommodate these patients, according to the researchers. Some said they struggled to coordinate care for individuals with disabilities and did not know which types of accessible equipment, such as adjustable tables and chair scales, were needed or how to use them.

Several physicians also noted that they are inadequately reimbursed for the special accommodations – including additional staff, equipment, and time – required to care for these patients. One primary care physician said he hired a sign-language interpreter for a patient but the bill for the services exceeded the amount insurance reimbursed. As a result, he said, he spent $30 of his own money per visit to see the patient.

Because of these limitations, some physicians in the focus groups said they try to turn away patients with disabilities. Both specialists and general practitioners said they had told patients with disabilities that they didn’t feel they could provide the care needed, and suggested they look elsewhere. A few were surprisingly – even upsettingly – honest, Dr. Lagu said, making statements such as: “I am not the doctor for you.”
 

‘We really need a rewrite’

Previous work has shown that people with disabilities have worse health outcomes, such as undetected cancer, obesity, and cardiovascular disease.

But “the disability itself isn’t what leads to worse outcomes,” said Allison Kessler, MD, section chief of the Renée Crown Center for Spinal Cord Innovation and associate director of the Shirley Ryan AbilityLab in Chicago*. This study does a good job at highlighting “the need for change on multiple levels,” said Dr. Kessler, who was not a member of the study team.

“People with disabilities have all these disparities in access and outcomes. We’ve never understood why. I think the why is complicated,” Dr. Lagu added. “I think this study suggests some of the negative outcomes are due to explicit bias.”

“It’s also clear that the current framework of health care in the United States does not lend to allowing physicians and medical providers the time needed to adequately address patient issues – those with disabilities or just multiple complex problems,” Colin O’Reilly, DO, vice president and chief medical officer at Children’s Specialized Hospital, an acute rehabilitation facility affiliated with RWJBarnabas Health, in New Brunswick, N.J. “We really need a rewrite.”

However, Dr. O’Reilly said, such a small study population with no control group and no mention of physician resources makes it difficult to come to a strong conclusion about physician bias and discriminatory attitudes against individuals with disabilities.

Dr. Lagu agreed, saying this research “is not conclusive in any way.” The excuses doctors use to discharge patients with disabilities, such as “we don’t accept your insurance,” “we aren’t taking new patients,” and “we can’t provide you with the appropriate care,” could be legitimate, the study authors wrote. But the “disparities in care for people with disabilities suggest that there is a pattern of more frequently denying care to them than people without a disability,” they added.

Dr. Kessler said many of her patients have told her they experience barriers to care. Some say finding an office with the necessary equipment is a challenge or that they often don’t feel welcome.

The Americans With Disabilities Act (ADA) is a federal civil rights law that prohibits discrimination against individuals with disabilities in all public and private places that are open to the general public, including medical offices.

“It is difficult to enforce the ADA in medical settings,” the researchers noted. “Explanations physicians gave in this study could, for any single case of denying care, be legitimate.” Knowing whether a particular instance of denial of care represents discrimination related to disability is “nearly impossible,” they wrote.

All the experts agreed that the study adds valuable insight into an ongoing health disparity. And while system and policy changes are required, Dr. Kessler said, individual physicians can take steps to improve the situation.

A physician in an academic setting can look at the curriculum and the medical school and see about increasing exposure to patients with disabilities earlier in training. In a practice, physicians can retrain staff to ask every patient if an accommodation is needed. “Each one of those changes can only help us move our system in the right direction,” Dr. Kessler said.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

*Correction, 10/5/22: This article includes a corrected title for Dr. Allison Kessler.

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

For Tara Lagu, MD, the realization that the health care system was broken for patients with disabilities came when a woman she had been treating seemed to keep ignoring Dr. Lagu’s request to see a urologist.

When Dr. Lagu asked the patient’s two attentive daughters about the delay, their response surprised her. The women said they couldn’t find a urologist who was willing to see a patient in a wheelchair.

Ingram/thinkstock

Surprised and a bit doubtful, Dr. Lagu checked around. She found that, indeed, the only way to get her patient in to see the type of physician required was to send her by ambulance.

“It opened my eyes to how hard it is for patients with disabilities to navigate the health care system,” Dr. Lagu said.

Dr. Lagu, director of the Center for Health Services and Outcomes Research at Northwestern University in Chicago, decided to take a closer look at how her colleagues in medicine care for – or not, as the case proved – the roughly one in four American adults, and millions of children, with disabilities.

In a series of three focus groups, Dr. Lagu and colleagues identified a range of obstacles – including some physician attitudes – that prevent people with disabilities from getting adequate care.

Lack of experience, logistics often cited

Some physicians admitted that limited resources and training left them without the space and necessary knowledge to properly care for patients with disabilities. They felt they lacked the expertise or exposure to care for individuals with disabilities, nor did they have enough time and space to properly accommodate these patients, according to the researchers. Some said they struggled to coordinate care for individuals with disabilities and did not know which types of accessible equipment, such as adjustable tables and chair scales, were needed or how to use them.

Several physicians also noted that they are inadequately reimbursed for the special accommodations – including additional staff, equipment, and time – required to care for these patients. One primary care physician said he hired a sign-language interpreter for a patient but the bill for the services exceeded the amount insurance reimbursed. As a result, he said, he spent $30 of his own money per visit to see the patient.

Because of these limitations, some physicians in the focus groups said they try to turn away patients with disabilities. Both specialists and general practitioners said they had told patients with disabilities that they didn’t feel they could provide the care needed, and suggested they look elsewhere. A few were surprisingly – even upsettingly – honest, Dr. Lagu said, making statements such as: “I am not the doctor for you.”
 

‘We really need a rewrite’

Previous work has shown that people with disabilities have worse health outcomes, such as undetected cancer, obesity, and cardiovascular disease.

But “the disability itself isn’t what leads to worse outcomes,” said Allison Kessler, MD, section chief of the Renée Crown Center for Spinal Cord Innovation and associate director of the Shirley Ryan AbilityLab in Chicago*. This study does a good job at highlighting “the need for change on multiple levels,” said Dr. Kessler, who was not a member of the study team.

“People with disabilities have all these disparities in access and outcomes. We’ve never understood why. I think the why is complicated,” Dr. Lagu added. “I think this study suggests some of the negative outcomes are due to explicit bias.”

“It’s also clear that the current framework of health care in the United States does not lend to allowing physicians and medical providers the time needed to adequately address patient issues – those with disabilities or just multiple complex problems,” Colin O’Reilly, DO, vice president and chief medical officer at Children’s Specialized Hospital, an acute rehabilitation facility affiliated with RWJBarnabas Health, in New Brunswick, N.J. “We really need a rewrite.”

However, Dr. O’Reilly said, such a small study population with no control group and no mention of physician resources makes it difficult to come to a strong conclusion about physician bias and discriminatory attitudes against individuals with disabilities.

Dr. Lagu agreed, saying this research “is not conclusive in any way.” The excuses doctors use to discharge patients with disabilities, such as “we don’t accept your insurance,” “we aren’t taking new patients,” and “we can’t provide you with the appropriate care,” could be legitimate, the study authors wrote. But the “disparities in care for people with disabilities suggest that there is a pattern of more frequently denying care to them than people without a disability,” they added.

Dr. Kessler said many of her patients have told her they experience barriers to care. Some say finding an office with the necessary equipment is a challenge or that they often don’t feel welcome.

The Americans With Disabilities Act (ADA) is a federal civil rights law that prohibits discrimination against individuals with disabilities in all public and private places that are open to the general public, including medical offices.

“It is difficult to enforce the ADA in medical settings,” the researchers noted. “Explanations physicians gave in this study could, for any single case of denying care, be legitimate.” Knowing whether a particular instance of denial of care represents discrimination related to disability is “nearly impossible,” they wrote.

All the experts agreed that the study adds valuable insight into an ongoing health disparity. And while system and policy changes are required, Dr. Kessler said, individual physicians can take steps to improve the situation.

A physician in an academic setting can look at the curriculum and the medical school and see about increasing exposure to patients with disabilities earlier in training. In a practice, physicians can retrain staff to ask every patient if an accommodation is needed. “Each one of those changes can only help us move our system in the right direction,” Dr. Kessler said.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

*Correction, 10/5/22: This article includes a corrected title for Dr. Allison Kessler.

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

Prenatal exposure to high-dose folic acid is associated with a greater than twofold increased risk for cancer in children of mothers with epilepsy, new data from a Scandinavian registry of more than 3 million pregnancies suggests.

The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).

There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.

The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.

“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.

The study was published online in JAMA Neurology.
 

Risks and benefits

Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.

To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.

Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).

The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.

Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.

In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).

There was no association between any specific ASM and childhood cancer.

“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.

They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.

“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
 

Practice changing?

Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”

“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.

Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.

“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.

The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.

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

Prenatal exposure to high-dose folic acid is associated with a greater than twofold increased risk for cancer in children of mothers with epilepsy, new data from a Scandinavian registry of more than 3 million pregnancies suggests.

The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).

There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.

The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.

“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.

The study was published online in JAMA Neurology.
 

Risks and benefits

Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.

To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.

Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).

The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.

Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.

In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).

There was no association between any specific ASM and childhood cancer.

“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.

They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.

“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
 

Practice changing?

Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”

“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.

Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.

“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.

The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.

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

Prenatal exposure to high-dose folic acid is associated with a greater than twofold increased risk for cancer in children of mothers with epilepsy, new data from a Scandinavian registry of more than 3 million pregnancies suggests.

The increased risk for cancer did not change after considering other factors that could explain the risk, such as use of antiseizure medication (ASM).

There was no increased risk for cancer in children of mothers without epilepsy who used high-dose folic acid.

The results of this study “should be considered when the risks and benefits of folic acid supplements for women with epilepsy are discussed and before decisions about optimal dose recommendations are made,” the authors write.

“Although we believe that the association between prescription fills for high-dose folic acid and cancer in children born to mothers with epilepsy is robust, it is important to underline that these are the findings of one study only,” first author Håkon Magne Vegrim, MD, with University of Bergen (Norway) told this news organization.

The study was published online in JAMA Neurology.
 

Risks and benefits

Women with epilepsy are advised to take high doses of folic acid before and during pregnancy owing to the risk for congenital malformations associated with ASM. Whether high-dose folic acid is associated with increases in the risk for childhood cancer is unknown.

To investigate, the researchers analyzed registry data from Denmark, Norway, and Sweden for 3.3 million children followed to a median age of 7.3 years.

Among the 27,784 children born to mothers with epilepsy, 5,934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with a cancer incidence rate of 42.5 per 100,000 person-years in 18 exposed cancer cases compared with 18.4 per 100,000 person-years in 29 unexposed cancer cases – yielding an adjusted hazard ratio of 2.7 (95% confidence interval, 1.2-6.3).

The absolute risk with exposure was 1.5% (95% CI, 0.5%-3.5%) in children of mothers with epilepsy compared with 0.6% (95% CI, 0.3%-1.1%) in children of mothers with epilepsy who were not exposed high-dose folic acid.

Prenatal exposure to high-dose folic acid was not associated with an increased risk for cancer in children of mothers without epilepsy.

In children of mothers without epilepsy, 46,646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg). There were 69 exposed and 4,927 unexposed cancer cases and an aHR for cancer of 1.1 (95% CI, 0.9-1.4) and absolute risk for cancer of 0.4% (95% CI, 0.3%-0.5%).

There was no association between any specific ASM and childhood cancer.

“Removing mothers with any prescription fills for carbamazepine and valproate was not associated with the point estimate. Hence, these two ASMs were not important effect modifiers for the cancer association,” the investigators note in their study.

They also note that the most common childhood cancer types in children among mothers with epilepsy who took high-dose folic acid did not differ from the distribution in the general population.

“We need to get more knowledge about the potential mechanisms behind high-dose folic acid and childhood cancer, and it is important to identify the optimal dose to balance risks and benefits – and whether folic acid supplementation should be more individualized, based on factors like the serum level of folate and what type of antiseizure medication that is being used,” said Dr. Vegrim.
 

Practice changing?

Weighing in on the study, Elizabeth E. Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said, “There are known benefits of folic acid supplementation during pregnancy including a decreased risk of neural tube defects in the general population and improved neurodevelopmental outcomes in children born to mothers with and without epilepsy.”

“However, despite some expert guidelines recommending high-dose folic acid supplementation, there is a lack of certainty surrounding the ‘just right’ dose for patients with epilepsy who may become pregnant,” said Dr. Gerard, who wasn’t involved in the study.

Dr. Gerard, a member of the American Epilepsy Society, noted that other epidemiologic studies of folic acid supplementation and cancer have had “contradictory results, thus further research on this association will be needed. Additionally, differences in maternal/fetal folate metabolism and blood levels may be an important factor to study in the future.

“That said, this study definitely should cause us to pause and reevaluate the common practice of high-dose folic acid supplementation for patients with epilepsy who are considering pregnancy,” said Dr. Gerard.

The study was supported by the NordForsk Nordic Program on Health and Welfare. Dr. Vegrim and Dr. Gerard report no relevant financial relationships.

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

New models can help predict whether women having a hysterectomy for benign conditions are likely to have major complications, according to researchers.

The models, which use routinely collected data, are meant to aid surgeons in counseling women before surgery and help guide shared decision-making. The tools may lead to referrals for centers with greater surgical experience or may result in seeking nonsurgical treatment options, the researchers indicate.

The tools are not applicable to patients having hysterectomy for malignant disease.

Findings of the study, led by Krupa Madhvani, MD, of Barts and the London School of Medicine and Dentistry in London, are published online in the Canadian Medical Association Journal.

Calculators complement surgeons’ intuition

“Our aim was to generate prediction models that can be used in conjunction with a surgeon’s intuition to enhance preoperative patient counseling and match the advances made in the technical aspects of surgery,” the authors write.

“Internal–external cross-validation and external validation showed moderate discrimination,” they note.

The study included 68,599 patients who had laparoscopic hysterectomies and 125,971 patients who had an abdominal hysterectomy, all English National Health System patients between 2011 and 2018.

Among their findings were that major complications occurred in 4.4% of laparoscopic and 4.9% of abdominal hysterectomies. Major complications in this study included ureteric, gastrointestinal, and vascular injury and wound complications.

Adhesions biggest predictors of complications

Adhesions were most predictive of complications – with double the odds – in both models (laparoscopic: odds ratio, 1.92; 95% confidence interval, 1.73-2.13; abdominal: OR, 2.46; 95% CI, 2.27-2.66). That finding was consistent with previous literature.

“Adhesions should be suspected if there is a previous history of laparotomy, cesarean section, pelvic infection, or endometriosis, and can be reliably diagnosed preoperatively using ultrasonography,” the authors write. “As the global rate of cesarean sections continues to rise, this will undoubtedly remain a key determinant of major complications.”

Other factors that best predicted complications included adenomyosis in the laparoscopic model, and Asian ethnicity and diabetes in the abdominal model. Diabetes was not a predictive factor for complications in laparoscopic hysterectomy as it was in a previous study.

Obesity was not a significant predictor of major complications for either form of hysterectomy.

Factors protective against major complications included younger age and diagnosed menstrual disorders or benign adnexal mass (both models) and diagnosis of fibroids in the abdominal model.

Models miss surgeon experience

Jon Ivar Einarsson MD, PhD, MPH, founder of the division of minimally invasive gynecologic surgery at Brigham and Women’s Hospital, Boston, said it’s good to have these models to estimate risk as “there’s possibly a tendency to underestimate the risk by the surgeon.”

However, he told this publication that, though these models are based on a very large data set, the models are missing some key variables – often a problem with database studies – that are more indicative of complications. The most important factor missing, he said, is surgeon experience.

“We’ve shown in our publications that there’s a correlation between that and the risk of complications,“ Dr. Einarsson said.

Among other variables missing, he noted, are some that the authors list when acknowledging the limitations: severity of endometriosis and severity of adhesions.

He said his team wouldn’t use such models because they rely on their own data for gauging risk. He encourages other surgeons to track their own data and outcomes as well.

“I think the external validity here is nonexistent because we’re dealing with a different patient population in a different country with different surgeons [who] have various degrees of expertise,” Dr. Einarsson said.

“But if surgeons have not collected their own data, then this could be useful,” he said.

Links to online calculators

The online calculator can be found at www.evidencio.com (laparoscopic, www.evidencio.com/models/show/2551; abdominal, www.evidencio.com/models/show/2552).

The large, national multi-institutional database helps with generalizability of findings, the authors write. Additionally, patients had a unique identifier number so if patients were admitted to a different hospital after surgery, they were not lost to follow-up.

Limitations, in addition to those mentioned, include gaps in detailed clinical information, such as exact body mass index, and location, type, and size of leiomyoma, the authors write.

“Further research should focus on improving the discriminatory ability of these tools by including factors other than patient characteristics, including surgeon volume, as this has been shown to reduce complications,” they write.

Dr. Madhvani has received article-processing fees from Elly Charity (East London International Women’s Health Charity). No other competing interests were declared. Dr. Einarsson reports no relevant financial relationships. The acquisition of the data was funded by the British Society for Gynaecological Endoscopy. They were not involved in the study design, analysis, interpretation of data, the writing of the report, or the decision to submit the article for publication. Coauthor Khalid Khan, MD is a distinguished investigator funded by the Beatriz Galindo Program grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Government of Spain.

New models can help predict whether women having a hysterectomy for benign conditions are likely to have major complications, according to researchers.

The models, which use routinely collected data, are meant to aid surgeons in counseling women before surgery and help guide shared decision-making. The tools may lead to referrals for centers with greater surgical experience or may result in seeking nonsurgical treatment options, the researchers indicate.

The tools are not applicable to patients having hysterectomy for malignant disease.

Findings of the study, led by Krupa Madhvani, MD, of Barts and the London School of Medicine and Dentistry in London, are published online in the Canadian Medical Association Journal.

Calculators complement surgeons’ intuition

“Our aim was to generate prediction models that can be used in conjunction with a surgeon’s intuition to enhance preoperative patient counseling and match the advances made in the technical aspects of surgery,” the authors write.

“Internal–external cross-validation and external validation showed moderate discrimination,” they note.

The study included 68,599 patients who had laparoscopic hysterectomies and 125,971 patients who had an abdominal hysterectomy, all English National Health System patients between 2011 and 2018.

Among their findings were that major complications occurred in 4.4% of laparoscopic and 4.9% of abdominal hysterectomies. Major complications in this study included ureteric, gastrointestinal, and vascular injury and wound complications.

Adhesions biggest predictors of complications

Adhesions were most predictive of complications – with double the odds – in both models (laparoscopic: odds ratio, 1.92; 95% confidence interval, 1.73-2.13; abdominal: OR, 2.46; 95% CI, 2.27-2.66). That finding was consistent with previous literature.

“Adhesions should be suspected if there is a previous history of laparotomy, cesarean section, pelvic infection, or endometriosis, and can be reliably diagnosed preoperatively using ultrasonography,” the authors write. “As the global rate of cesarean sections continues to rise, this will undoubtedly remain a key determinant of major complications.”

Other factors that best predicted complications included adenomyosis in the laparoscopic model, and Asian ethnicity and diabetes in the abdominal model. Diabetes was not a predictive factor for complications in laparoscopic hysterectomy as it was in a previous study.

Obesity was not a significant predictor of major complications for either form of hysterectomy.

Factors protective against major complications included younger age and diagnosed menstrual disorders or benign adnexal mass (both models) and diagnosis of fibroids in the abdominal model.

Models miss surgeon experience

Jon Ivar Einarsson MD, PhD, MPH, founder of the division of minimally invasive gynecologic surgery at Brigham and Women’s Hospital, Boston, said it’s good to have these models to estimate risk as “there’s possibly a tendency to underestimate the risk by the surgeon.”

However, he told this publication that, though these models are based on a very large data set, the models are missing some key variables – often a problem with database studies – that are more indicative of complications. The most important factor missing, he said, is surgeon experience.

“We’ve shown in our publications that there’s a correlation between that and the risk of complications,“ Dr. Einarsson said.

Among other variables missing, he noted, are some that the authors list when acknowledging the limitations: severity of endometriosis and severity of adhesions.

He said his team wouldn’t use such models because they rely on their own data for gauging risk. He encourages other surgeons to track their own data and outcomes as well.

“I think the external validity here is nonexistent because we’re dealing with a different patient population in a different country with different surgeons [who] have various degrees of expertise,” Dr. Einarsson said.

“But if surgeons have not collected their own data, then this could be useful,” he said.

Links to online calculators

The online calculator can be found at www.evidencio.com (laparoscopic, www.evidencio.com/models/show/2551; abdominal, www.evidencio.com/models/show/2552).

The large, national multi-institutional database helps with generalizability of findings, the authors write. Additionally, patients had a unique identifier number so if patients were admitted to a different hospital after surgery, they were not lost to follow-up.

Limitations, in addition to those mentioned, include gaps in detailed clinical information, such as exact body mass index, and location, type, and size of leiomyoma, the authors write.

“Further research should focus on improving the discriminatory ability of these tools by including factors other than patient characteristics, including surgeon volume, as this has been shown to reduce complications,” they write.

Dr. Madhvani has received article-processing fees from Elly Charity (East London International Women’s Health Charity). No other competing interests were declared. Dr. Einarsson reports no relevant financial relationships. The acquisition of the data was funded by the British Society for Gynaecological Endoscopy. They were not involved in the study design, analysis, interpretation of data, the writing of the report, or the decision to submit the article for publication. Coauthor Khalid Khan, MD is a distinguished investigator funded by the Beatriz Galindo Program grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Government of Spain.

New models can help predict whether women having a hysterectomy for benign conditions are likely to have major complications, according to researchers.

The models, which use routinely collected data, are meant to aid surgeons in counseling women before surgery and help guide shared decision-making. The tools may lead to referrals for centers with greater surgical experience or may result in seeking nonsurgical treatment options, the researchers indicate.

The tools are not applicable to patients having hysterectomy for malignant disease.

Findings of the study, led by Krupa Madhvani, MD, of Barts and the London School of Medicine and Dentistry in London, are published online in the Canadian Medical Association Journal.

Calculators complement surgeons’ intuition

“Our aim was to generate prediction models that can be used in conjunction with a surgeon’s intuition to enhance preoperative patient counseling and match the advances made in the technical aspects of surgery,” the authors write.

“Internal–external cross-validation and external validation showed moderate discrimination,” they note.

The study included 68,599 patients who had laparoscopic hysterectomies and 125,971 patients who had an abdominal hysterectomy, all English National Health System patients between 2011 and 2018.

Among their findings were that major complications occurred in 4.4% of laparoscopic and 4.9% of abdominal hysterectomies. Major complications in this study included ureteric, gastrointestinal, and vascular injury and wound complications.

Adhesions biggest predictors of complications

Adhesions were most predictive of complications – with double the odds – in both models (laparoscopic: odds ratio, 1.92; 95% confidence interval, 1.73-2.13; abdominal: OR, 2.46; 95% CI, 2.27-2.66). That finding was consistent with previous literature.

“Adhesions should be suspected if there is a previous history of laparotomy, cesarean section, pelvic infection, or endometriosis, and can be reliably diagnosed preoperatively using ultrasonography,” the authors write. “As the global rate of cesarean sections continues to rise, this will undoubtedly remain a key determinant of major complications.”

Other factors that best predicted complications included adenomyosis in the laparoscopic model, and Asian ethnicity and diabetes in the abdominal model. Diabetes was not a predictive factor for complications in laparoscopic hysterectomy as it was in a previous study.

Obesity was not a significant predictor of major complications for either form of hysterectomy.

Factors protective against major complications included younger age and diagnosed menstrual disorders or benign adnexal mass (both models) and diagnosis of fibroids in the abdominal model.

Models miss surgeon experience

Jon Ivar Einarsson MD, PhD, MPH, founder of the division of minimally invasive gynecologic surgery at Brigham and Women’s Hospital, Boston, said it’s good to have these models to estimate risk as “there’s possibly a tendency to underestimate the risk by the surgeon.”

However, he told this publication that, though these models are based on a very large data set, the models are missing some key variables – often a problem with database studies – that are more indicative of complications. The most important factor missing, he said, is surgeon experience.

“We’ve shown in our publications that there’s a correlation between that and the risk of complications,“ Dr. Einarsson said.

Among other variables missing, he noted, are some that the authors list when acknowledging the limitations: severity of endometriosis and severity of adhesions.

He said his team wouldn’t use such models because they rely on their own data for gauging risk. He encourages other surgeons to track their own data and outcomes as well.

“I think the external validity here is nonexistent because we’re dealing with a different patient population in a different country with different surgeons [who] have various degrees of expertise,” Dr. Einarsson said.

“But if surgeons have not collected their own data, then this could be useful,” he said.

Links to online calculators

The online calculator can be found at www.evidencio.com (laparoscopic, www.evidencio.com/models/show/2551; abdominal, www.evidencio.com/models/show/2552).

The large, national multi-institutional database helps with generalizability of findings, the authors write. Additionally, patients had a unique identifier number so if patients were admitted to a different hospital after surgery, they were not lost to follow-up.

Limitations, in addition to those mentioned, include gaps in detailed clinical information, such as exact body mass index, and location, type, and size of leiomyoma, the authors write.

“Further research should focus on improving the discriminatory ability of these tools by including factors other than patient characteristics, including surgeon volume, as this has been shown to reduce complications,” they write.

Dr. Madhvani has received article-processing fees from Elly Charity (East London International Women’s Health Charity). No other competing interests were declared. Dr. Einarsson reports no relevant financial relationships. The acquisition of the data was funded by the British Society for Gynaecological Endoscopy. They were not involved in the study design, analysis, interpretation of data, the writing of the report, or the decision to submit the article for publication. Coauthor Khalid Khan, MD is a distinguished investigator funded by the Beatriz Galindo Program grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Government of Spain.