Doctors are more likely to miss appendicitis in patients who are Black, research shows.

This phenomenon, first described in children, occurs in adults as well, according to a study published in JAMA Surgery.

Some hospitals fare better than others: Those with more diverse patient populations were less likely to have missed the diagnosis, the researchers found.

“We don’t think the amount of melanin in your skin predicts how you present with appendicitis,” said Jonathan Carter, MD, professor of surgery at the University of California, San Francisco. “There’s no biological explanation,” Dr. Carter, who wrote an invited commentary on the research, said in an interview. “It’s really what’s going on in the social environment of those emergency rooms.”

For the study, Anne Stey, MD, assistant professor of surgery at Northwestern University in Chicago and her colleagues analyzed data from more than 80,000 men and women in four states – Florida, Maryland, New York, and Wisconsin – who underwent appendectomy in 2016-2017.

They identified those who had been seen for abdominal complaints at a hospital in the week before surgery but did not receive a diagnosis of appendicitis at that time, indicating a missed opportunity to intervene sooner.

Among Black patients, the proportion who had experienced this type of delay was 3.6%, whereas for White patients, it was 2.5%. For Hispanic patients, the share was 2.4%, while for Asian or Pacific Islander patients, the figure was 1.5%.

An analysis that controlled for patient and hospital variables found that among non-Hispanic Black patients, the rate of delayed diagnosis was 1.41 times higher than for non-Hispanic White patients (95% confidence interval, 1.21-1.63).

Other patient factors associated with delayed diagnosis included female sex, comorbidities, and living in a low-income zip code.

A key factor was where patients sought care. A delayed diagnosis of appendicitis was 3.51 times more likely for patients who went to hospitals where most patients are insured by Medicaid. Prior research has shown that “safety-net hospitals have fewer resources and may provide lower-quality care than hospitals with a larger private payer population,” Dr. Stey’s group writes.

On the other hand, going to a hospital with a more diverse patient population reduced the odds of a delayed diagnosis.

“Patients presenting to hospitals with a greater than 50% Black and Hispanic population were 0.73 (95% CI, 0.59-0.91) times less likely to have a delayed diagnosis, compared with patients presenting to hospitals with a less than 25% Black and Hispanic population,” the researchers report.

In the 30 days after discharge following appendectomy, Black patients returned to the hospital at a higher rate than White patients did (17.5% vs. 11.4%), indicating worse outcomes.

“Delayed diagnosis may account for some of the racial and ethnic disparities observed in outcomes after appendicitis,” according to the authors.

“It may be hospitals that are more used to serving racial-ethnic minority patients are better at diagnosing them, because they’re more culturally informed and have a better understanding of these patients,” Dr. Stey said in a news release about their findings.
 

Great masquerader

Diagnosing appendicitis can be challenging, Dr. Carter said. The early signs can be subtle, and the condition is sometimes called the great masquerader. It is not uncommon for patients to be diagnosed with gastroenteritis or pain associated with their menstrual period, for example, and sent home.

Scoring systems based on patients’ symptoms and liberal use of imaging have improved detection of appendicitis, but “no physician or health care system is perfect in the diagnosis,” he said.

The increased odds of delayed diagnosis for Black patients remained when the researchers focused on healthier patients who had fewer comorbidities, and it also held when they considered patients with private insurance in high-income areas, Dr. Carter noted.

“Once again, with this study we see the association of structural and systematic racism with access to health care, especially for Black patients, in emergency departments and hospitals,” he wrote. “We must redouble our efforts to become anti-racist in ourselves, our institutions, and our profession.”
 

‘Our health care system itself’

Elizabeth Garner, MD, MPH, a pharmaceutical executive who was not involved in the study, commented on Twitter that the study points to an underlying issue that has existed in medicine “for quite some time.”

“Minority populations are not taken as seriously as their white counterparts,” she wrote. “This needs to change.”

Measures of hospital quality need to be tied to health equity, according to Mofya Diallo, MD, MPH, of the department of anesthesiology at the Children’s Hospital Los Angeles and the University of Southern California, Los Angeles.

“Top hospitals should take pride in outcomes that do not vary based on race, income or literacy,” she tweeted in response to the study.

To better understand possible reasons for delayed diagnosis, future researchers could assess whether patients who are Black are less likely to receive a surgical consultation, imaging studies, or lab work, Dr. Carter told this news organization. He pointed to a recent analysis of patients insured by Medicare that found that Black patients were less likely than White patients to receive a surgical consultation after they were admitted with colorectal, general abdominal, hepatopancreatobiliary, intestinal obstruction, or upper gastrointestinal diagnoses.

While social determinants of health, such as income, education, housing, early childhood development, employment, and social inclusion, may account for a substantial portion of health outcomes, “Our health care system itself can be viewed as another social determinant of health,” Dr. Carter wrote. “Insurance coverage, health care professional availability, health care professional linguistic and cultural competency, and quality of care all have an effect on health outcomes.”

Dr. Stey was supported by grants from the American College of Surgeons and the National Institutes of Health.

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

Doctors are more likely to miss appendicitis in patients who are Black, research shows.

This phenomenon, first described in children, occurs in adults as well, according to a study published in JAMA Surgery.

Some hospitals fare better than others: Those with more diverse patient populations were less likely to have missed the diagnosis, the researchers found.

“We don’t think the amount of melanin in your skin predicts how you present with appendicitis,” said Jonathan Carter, MD, professor of surgery at the University of California, San Francisco. “There’s no biological explanation,” Dr. Carter, who wrote an invited commentary on the research, said in an interview. “It’s really what’s going on in the social environment of those emergency rooms.”

For the study, Anne Stey, MD, assistant professor of surgery at Northwestern University in Chicago and her colleagues analyzed data from more than 80,000 men and women in four states – Florida, Maryland, New York, and Wisconsin – who underwent appendectomy in 2016-2017.

They identified those who had been seen for abdominal complaints at a hospital in the week before surgery but did not receive a diagnosis of appendicitis at that time, indicating a missed opportunity to intervene sooner.

Among Black patients, the proportion who had experienced this type of delay was 3.6%, whereas for White patients, it was 2.5%. For Hispanic patients, the share was 2.4%, while for Asian or Pacific Islander patients, the figure was 1.5%.

An analysis that controlled for patient and hospital variables found that among non-Hispanic Black patients, the rate of delayed diagnosis was 1.41 times higher than for non-Hispanic White patients (95% confidence interval, 1.21-1.63).

Other patient factors associated with delayed diagnosis included female sex, comorbidities, and living in a low-income zip code.

A key factor was where patients sought care. A delayed diagnosis of appendicitis was 3.51 times more likely for patients who went to hospitals where most patients are insured by Medicaid. Prior research has shown that “safety-net hospitals have fewer resources and may provide lower-quality care than hospitals with a larger private payer population,” Dr. Stey’s group writes.

On the other hand, going to a hospital with a more diverse patient population reduced the odds of a delayed diagnosis.

“Patients presenting to hospitals with a greater than 50% Black and Hispanic population were 0.73 (95% CI, 0.59-0.91) times less likely to have a delayed diagnosis, compared with patients presenting to hospitals with a less than 25% Black and Hispanic population,” the researchers report.

In the 30 days after discharge following appendectomy, Black patients returned to the hospital at a higher rate than White patients did (17.5% vs. 11.4%), indicating worse outcomes.

“Delayed diagnosis may account for some of the racial and ethnic disparities observed in outcomes after appendicitis,” according to the authors.

“It may be hospitals that are more used to serving racial-ethnic minority patients are better at diagnosing them, because they’re more culturally informed and have a better understanding of these patients,” Dr. Stey said in a news release about their findings.
 

Great masquerader

Diagnosing appendicitis can be challenging, Dr. Carter said. The early signs can be subtle, and the condition is sometimes called the great masquerader. It is not uncommon for patients to be diagnosed with gastroenteritis or pain associated with their menstrual period, for example, and sent home.

Scoring systems based on patients’ symptoms and liberal use of imaging have improved detection of appendicitis, but “no physician or health care system is perfect in the diagnosis,” he said.

The increased odds of delayed diagnosis for Black patients remained when the researchers focused on healthier patients who had fewer comorbidities, and it also held when they considered patients with private insurance in high-income areas, Dr. Carter noted.

“Once again, with this study we see the association of structural and systematic racism with access to health care, especially for Black patients, in emergency departments and hospitals,” he wrote. “We must redouble our efforts to become anti-racist in ourselves, our institutions, and our profession.”
 

‘Our health care system itself’

Elizabeth Garner, MD, MPH, a pharmaceutical executive who was not involved in the study, commented on Twitter that the study points to an underlying issue that has existed in medicine “for quite some time.”

“Minority populations are not taken as seriously as their white counterparts,” she wrote. “This needs to change.”

Measures of hospital quality need to be tied to health equity, according to Mofya Diallo, MD, MPH, of the department of anesthesiology at the Children’s Hospital Los Angeles and the University of Southern California, Los Angeles.

“Top hospitals should take pride in outcomes that do not vary based on race, income or literacy,” she tweeted in response to the study.

To better understand possible reasons for delayed diagnosis, future researchers could assess whether patients who are Black are less likely to receive a surgical consultation, imaging studies, or lab work, Dr. Carter told this news organization. He pointed to a recent analysis of patients insured by Medicare that found that Black patients were less likely than White patients to receive a surgical consultation after they were admitted with colorectal, general abdominal, hepatopancreatobiliary, intestinal obstruction, or upper gastrointestinal diagnoses.

While social determinants of health, such as income, education, housing, early childhood development, employment, and social inclusion, may account for a substantial portion of health outcomes, “Our health care system itself can be viewed as another social determinant of health,” Dr. Carter wrote. “Insurance coverage, health care professional availability, health care professional linguistic and cultural competency, and quality of care all have an effect on health outcomes.”

Dr. Stey was supported by grants from the American College of Surgeons and the National Institutes of Health.

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

Doctors are more likely to miss appendicitis in patients who are Black, research shows.

This phenomenon, first described in children, occurs in adults as well, according to a study published in JAMA Surgery.

Some hospitals fare better than others: Those with more diverse patient populations were less likely to have missed the diagnosis, the researchers found.

“We don’t think the amount of melanin in your skin predicts how you present with appendicitis,” said Jonathan Carter, MD, professor of surgery at the University of California, San Francisco. “There’s no biological explanation,” Dr. Carter, who wrote an invited commentary on the research, said in an interview. “It’s really what’s going on in the social environment of those emergency rooms.”

For the study, Anne Stey, MD, assistant professor of surgery at Northwestern University in Chicago and her colleagues analyzed data from more than 80,000 men and women in four states – Florida, Maryland, New York, and Wisconsin – who underwent appendectomy in 2016-2017.

They identified those who had been seen for abdominal complaints at a hospital in the week before surgery but did not receive a diagnosis of appendicitis at that time, indicating a missed opportunity to intervene sooner.

Among Black patients, the proportion who had experienced this type of delay was 3.6%, whereas for White patients, it was 2.5%. For Hispanic patients, the share was 2.4%, while for Asian or Pacific Islander patients, the figure was 1.5%.

An analysis that controlled for patient and hospital variables found that among non-Hispanic Black patients, the rate of delayed diagnosis was 1.41 times higher than for non-Hispanic White patients (95% confidence interval, 1.21-1.63).

Other patient factors associated with delayed diagnosis included female sex, comorbidities, and living in a low-income zip code.

A key factor was where patients sought care. A delayed diagnosis of appendicitis was 3.51 times more likely for patients who went to hospitals where most patients are insured by Medicaid. Prior research has shown that “safety-net hospitals have fewer resources and may provide lower-quality care than hospitals with a larger private payer population,” Dr. Stey’s group writes.

On the other hand, going to a hospital with a more diverse patient population reduced the odds of a delayed diagnosis.

“Patients presenting to hospitals with a greater than 50% Black and Hispanic population were 0.73 (95% CI, 0.59-0.91) times less likely to have a delayed diagnosis, compared with patients presenting to hospitals with a less than 25% Black and Hispanic population,” the researchers report.

In the 30 days after discharge following appendectomy, Black patients returned to the hospital at a higher rate than White patients did (17.5% vs. 11.4%), indicating worse outcomes.

“Delayed diagnosis may account for some of the racial and ethnic disparities observed in outcomes after appendicitis,” according to the authors.

“It may be hospitals that are more used to serving racial-ethnic minority patients are better at diagnosing them, because they’re more culturally informed and have a better understanding of these patients,” Dr. Stey said in a news release about their findings.
 

Great masquerader

Diagnosing appendicitis can be challenging, Dr. Carter said. The early signs can be subtle, and the condition is sometimes called the great masquerader. It is not uncommon for patients to be diagnosed with gastroenteritis or pain associated with their menstrual period, for example, and sent home.

Scoring systems based on patients’ symptoms and liberal use of imaging have improved detection of appendicitis, but “no physician or health care system is perfect in the diagnosis,” he said.

The increased odds of delayed diagnosis for Black patients remained when the researchers focused on healthier patients who had fewer comorbidities, and it also held when they considered patients with private insurance in high-income areas, Dr. Carter noted.

“Once again, with this study we see the association of structural and systematic racism with access to health care, especially for Black patients, in emergency departments and hospitals,” he wrote. “We must redouble our efforts to become anti-racist in ourselves, our institutions, and our profession.”
 

‘Our health care system itself’

Elizabeth Garner, MD, MPH, a pharmaceutical executive who was not involved in the study, commented on Twitter that the study points to an underlying issue that has existed in medicine “for quite some time.”

“Minority populations are not taken as seriously as their white counterparts,” she wrote. “This needs to change.”

Measures of hospital quality need to be tied to health equity, according to Mofya Diallo, MD, MPH, of the department of anesthesiology at the Children’s Hospital Los Angeles and the University of Southern California, Los Angeles.

“Top hospitals should take pride in outcomes that do not vary based on race, income or literacy,” she tweeted in response to the study.

To better understand possible reasons for delayed diagnosis, future researchers could assess whether patients who are Black are less likely to receive a surgical consultation, imaging studies, or lab work, Dr. Carter told this news organization. He pointed to a recent analysis of patients insured by Medicare that found that Black patients were less likely than White patients to receive a surgical consultation after they were admitted with colorectal, general abdominal, hepatopancreatobiliary, intestinal obstruction, or upper gastrointestinal diagnoses.

While social determinants of health, such as income, education, housing, early childhood development, employment, and social inclusion, may account for a substantial portion of health outcomes, “Our health care system itself can be viewed as another social determinant of health,” Dr. Carter wrote. “Insurance coverage, health care professional availability, health care professional linguistic and cultural competency, and quality of care all have an effect on health outcomes.”

Dr. Stey was supported by grants from the American College of Surgeons and the National Institutes of Health.

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

In a recent, tragic case, a newborn died from being crushed by its mother, who fell asleep from the fatigue of numerous hours of labor. The case has brought the issue of obstetric violence (OV) to the attention of the Italian media. OV is defined as neglect, physical abuse, or disrespect during childbirth, according to the World Health Organization. The WHO outlined fundamental actions to be taken at various levels for its prevention, especially by health care systems, in a 2014 position paper.

Gender-based abuse

Considered a form of gender-based abuse, OV was first described in Latin America in the early 2000s. It is widespread and is increasing in European countries.

From the scientific literature on the subject, OV seems to be strongly associated with a lack of communication between health care personnel and pregnant women. It appears to have more to do with authoritarian and paternalistic behavior than actual real-life medical issues. Actively involving women in decision-making regarding childbirth and postpartum care seems to reduce the incidence of OV. Pregnant women who are more involved appear to trust health care professionals more and are therefore less likely to report disrespectful and abusive behavior.

Estimates of the prevalence of OV vary, depending on the country, the childbirth facility, and its definition. In Italy, inspired by the web campaign “#Bastatacere: le madri hanno voce [#EnoughSilence: mothers have a voice],” in 2017, the Obstetric Violence Database (OVO) investigated perceptions of having been a victim of OV in a representative sample of Italian women aged 18-54 years who had at least one child.

In 2017, just over 20% of the women interviewed considered themselves victims of OV; 33% felt they had not received adequate care; and around 35% reported serious problems concerning privacy or trust. Following the treatment received, approximately 15% of the women decided not to return to the same health care facility, and 6% did not want to proceed with further pregnancies.

At the time of publication, the results sparked a debate among relevant medical associations (the Association of Obstetricians and Gynecologists of Italian Hospitals, the Italian Society of Gynecology and Obstetrics, and the Association of Italian University Gynecologists), which immediately recognized the importance of the topic and accepted an invitation for further discussion on physician-patient relationships. They expressed reservations concerning the methodologies used by the OVO for data collection, especially regarding the representativeness of the sample.
 

Lack of communication

“In general, women who claim to have suffered from obstetric violence do not do so because they have been denied an aspect of care but because they have had an overall experience that, for whatever reason, did not conform with their expectations,” said Irene Cetin, MD, PhD, professor of obstetrics and gynecology at the University of Milan and director of the obstetrics and gynecology unit of the Buzzi Hospital in Milan. “Following the OVO’s exposé, the Italian Society of Gynecology and Obstetrics also conducted a large-scale study throughout Italy on all women who had given birth within a 3-month period. That investigation painted a very different picture. It wasn’t the case that no instances of obstetric violence were found, but the results were more contained. This is a very delicate subject, given that every report that we receive in hospital is always valued and looked into in detail, and women come to speak to us about errors and things that were missed.”

She added, “Experience leads me to say that complaints about what happens in the delivery room are extremely rare. What we hear more of, but still not often, are problems experienced during days spent in hospital immediately after childbirth.” There are never enough resources, which is the reason behind most problems. “The real hardships are found in the wards,” continued Dr. Cetin, “where the midwife-to-bed ratio is one or two to 30, and therefore this is where it is more difficult to feel like you’re being listened to. With COVID-19, the situation has gotten even worse, even though in my hospital we have always guaranteed, not without struggle, the presence of the partner in the delivery room.”

Only relatively recently have women’s partners been allowed into the hospital. In addition, a number of services, such as having the right beds and giving the correct explanations and information on how to establish a relationship with the child, are now being offered. These steps are necessary to guarantee what is referred to as a “humanizing birth,” a process in which the woman is at the center of the experience and is the main protagonist of the birth.
 

Lack of resources

This trend also is observed at the systemic level, where there is a lack of organization and resources. Few staff members are in the ward, even fewer specialists are in the psychological field, and contact is almost nonexistent after discharge from many hospitals and in many regions across Italy. There are, however, some positive aspects and hope for the future. “Just think,” said Dr. Cetin, “of how degree courses in obstetrics have changed over time, with a large part of teaching and training now being centered around the emotional aspects of birth.” From the gynecologist’s side, “most of the problems have been inherited from the past,” said Dr. Cetin. “Let’s not forget that we have only recently been giving birth in hospital. The so-called medicalization of childbirth has been responsible for a decline in the death rate and morbidity rate of pregnant women, but initially, there was little interest or care in how women felt in this situation, including with regard to physical pain. Since the 1970s, with Leboyer from France and Miraglia from Italy [promoters of so-called sweet birth], a path was cleared for a different line of thought. For this reason, I believe that the situation will improve over time.

“To continuously improve physician-patient communication,” concluded Dr. Cetin, “it would perhaps be appropriate to make sure that, even in the preparatory phase, women are well aware of possible complications and of the necessary and rapid emergency procedures that must be implemented by health care personnel. This way, a trusting relationship could be maintained, and the perception of having suffered abuse due to not being involved in strictly medical decisions could be stemmed.”

This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.

In a recent, tragic case, a newborn died from being crushed by its mother, who fell asleep from the fatigue of numerous hours of labor. The case has brought the issue of obstetric violence (OV) to the attention of the Italian media. OV is defined as neglect, physical abuse, or disrespect during childbirth, according to the World Health Organization. The WHO outlined fundamental actions to be taken at various levels for its prevention, especially by health care systems, in a 2014 position paper.

Gender-based abuse

Considered a form of gender-based abuse, OV was first described in Latin America in the early 2000s. It is widespread and is increasing in European countries.

From the scientific literature on the subject, OV seems to be strongly associated with a lack of communication between health care personnel and pregnant women. It appears to have more to do with authoritarian and paternalistic behavior than actual real-life medical issues. Actively involving women in decision-making regarding childbirth and postpartum care seems to reduce the incidence of OV. Pregnant women who are more involved appear to trust health care professionals more and are therefore less likely to report disrespectful and abusive behavior.

Estimates of the prevalence of OV vary, depending on the country, the childbirth facility, and its definition. In Italy, inspired by the web campaign “#Bastatacere: le madri hanno voce [#EnoughSilence: mothers have a voice],” in 2017, the Obstetric Violence Database (OVO) investigated perceptions of having been a victim of OV in a representative sample of Italian women aged 18-54 years who had at least one child.

In 2017, just over 20% of the women interviewed considered themselves victims of OV; 33% felt they had not received adequate care; and around 35% reported serious problems concerning privacy or trust. Following the treatment received, approximately 15% of the women decided not to return to the same health care facility, and 6% did not want to proceed with further pregnancies.

At the time of publication, the results sparked a debate among relevant medical associations (the Association of Obstetricians and Gynecologists of Italian Hospitals, the Italian Society of Gynecology and Obstetrics, and the Association of Italian University Gynecologists), which immediately recognized the importance of the topic and accepted an invitation for further discussion on physician-patient relationships. They expressed reservations concerning the methodologies used by the OVO for data collection, especially regarding the representativeness of the sample.
 

Lack of communication

“In general, women who claim to have suffered from obstetric violence do not do so because they have been denied an aspect of care but because they have had an overall experience that, for whatever reason, did not conform with their expectations,” said Irene Cetin, MD, PhD, professor of obstetrics and gynecology at the University of Milan and director of the obstetrics and gynecology unit of the Buzzi Hospital in Milan. “Following the OVO’s exposé, the Italian Society of Gynecology and Obstetrics also conducted a large-scale study throughout Italy on all women who had given birth within a 3-month period. That investigation painted a very different picture. It wasn’t the case that no instances of obstetric violence were found, but the results were more contained. This is a very delicate subject, given that every report that we receive in hospital is always valued and looked into in detail, and women come to speak to us about errors and things that were missed.”

She added, “Experience leads me to say that complaints about what happens in the delivery room are extremely rare. What we hear more of, but still not often, are problems experienced during days spent in hospital immediately after childbirth.” There are never enough resources, which is the reason behind most problems. “The real hardships are found in the wards,” continued Dr. Cetin, “where the midwife-to-bed ratio is one or two to 30, and therefore this is where it is more difficult to feel like you’re being listened to. With COVID-19, the situation has gotten even worse, even though in my hospital we have always guaranteed, not without struggle, the presence of the partner in the delivery room.”

Only relatively recently have women’s partners been allowed into the hospital. In addition, a number of services, such as having the right beds and giving the correct explanations and information on how to establish a relationship with the child, are now being offered. These steps are necessary to guarantee what is referred to as a “humanizing birth,” a process in which the woman is at the center of the experience and is the main protagonist of the birth.
 

Lack of resources

This trend also is observed at the systemic level, where there is a lack of organization and resources. Few staff members are in the ward, even fewer specialists are in the psychological field, and contact is almost nonexistent after discharge from many hospitals and in many regions across Italy. There are, however, some positive aspects and hope for the future. “Just think,” said Dr. Cetin, “of how degree courses in obstetrics have changed over time, with a large part of teaching and training now being centered around the emotional aspects of birth.” From the gynecologist’s side, “most of the problems have been inherited from the past,” said Dr. Cetin. “Let’s not forget that we have only recently been giving birth in hospital. The so-called medicalization of childbirth has been responsible for a decline in the death rate and morbidity rate of pregnant women, but initially, there was little interest or care in how women felt in this situation, including with regard to physical pain. Since the 1970s, with Leboyer from France and Miraglia from Italy [promoters of so-called sweet birth], a path was cleared for a different line of thought. For this reason, I believe that the situation will improve over time.

“To continuously improve physician-patient communication,” concluded Dr. Cetin, “it would perhaps be appropriate to make sure that, even in the preparatory phase, women are well aware of possible complications and of the necessary and rapid emergency procedures that must be implemented by health care personnel. This way, a trusting relationship could be maintained, and the perception of having suffered abuse due to not being involved in strictly medical decisions could be stemmed.”

This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.

In a recent, tragic case, a newborn died from being crushed by its mother, who fell asleep from the fatigue of numerous hours of labor. The case has brought the issue of obstetric violence (OV) to the attention of the Italian media. OV is defined as neglect, physical abuse, or disrespect during childbirth, according to the World Health Organization. The WHO outlined fundamental actions to be taken at various levels for its prevention, especially by health care systems, in a 2014 position paper.

Gender-based abuse

Considered a form of gender-based abuse, OV was first described in Latin America in the early 2000s. It is widespread and is increasing in European countries.

From the scientific literature on the subject, OV seems to be strongly associated with a lack of communication between health care personnel and pregnant women. It appears to have more to do with authoritarian and paternalistic behavior than actual real-life medical issues. Actively involving women in decision-making regarding childbirth and postpartum care seems to reduce the incidence of OV. Pregnant women who are more involved appear to trust health care professionals more and are therefore less likely to report disrespectful and abusive behavior.

Estimates of the prevalence of OV vary, depending on the country, the childbirth facility, and its definition. In Italy, inspired by the web campaign “#Bastatacere: le madri hanno voce [#EnoughSilence: mothers have a voice],” in 2017, the Obstetric Violence Database (OVO) investigated perceptions of having been a victim of OV in a representative sample of Italian women aged 18-54 years who had at least one child.

In 2017, just over 20% of the women interviewed considered themselves victims of OV; 33% felt they had not received adequate care; and around 35% reported serious problems concerning privacy or trust. Following the treatment received, approximately 15% of the women decided not to return to the same health care facility, and 6% did not want to proceed with further pregnancies.

At the time of publication, the results sparked a debate among relevant medical associations (the Association of Obstetricians and Gynecologists of Italian Hospitals, the Italian Society of Gynecology and Obstetrics, and the Association of Italian University Gynecologists), which immediately recognized the importance of the topic and accepted an invitation for further discussion on physician-patient relationships. They expressed reservations concerning the methodologies used by the OVO for data collection, especially regarding the representativeness of the sample.
 

Lack of communication

“In general, women who claim to have suffered from obstetric violence do not do so because they have been denied an aspect of care but because they have had an overall experience that, for whatever reason, did not conform with their expectations,” said Irene Cetin, MD, PhD, professor of obstetrics and gynecology at the University of Milan and director of the obstetrics and gynecology unit of the Buzzi Hospital in Milan. “Following the OVO’s exposé, the Italian Society of Gynecology and Obstetrics also conducted a large-scale study throughout Italy on all women who had given birth within a 3-month period. That investigation painted a very different picture. It wasn’t the case that no instances of obstetric violence were found, but the results were more contained. This is a very delicate subject, given that every report that we receive in hospital is always valued and looked into in detail, and women come to speak to us about errors and things that were missed.”

She added, “Experience leads me to say that complaints about what happens in the delivery room are extremely rare. What we hear more of, but still not often, are problems experienced during days spent in hospital immediately after childbirth.” There are never enough resources, which is the reason behind most problems. “The real hardships are found in the wards,” continued Dr. Cetin, “where the midwife-to-bed ratio is one or two to 30, and therefore this is where it is more difficult to feel like you’re being listened to. With COVID-19, the situation has gotten even worse, even though in my hospital we have always guaranteed, not without struggle, the presence of the partner in the delivery room.”

Only relatively recently have women’s partners been allowed into the hospital. In addition, a number of services, such as having the right beds and giving the correct explanations and information on how to establish a relationship with the child, are now being offered. These steps are necessary to guarantee what is referred to as a “humanizing birth,” a process in which the woman is at the center of the experience and is the main protagonist of the birth.
 

Lack of resources

This trend also is observed at the systemic level, where there is a lack of organization and resources. Few staff members are in the ward, even fewer specialists are in the psychological field, and contact is almost nonexistent after discharge from many hospitals and in many regions across Italy. There are, however, some positive aspects and hope for the future. “Just think,” said Dr. Cetin, “of how degree courses in obstetrics have changed over time, with a large part of teaching and training now being centered around the emotional aspects of birth.” From the gynecologist’s side, “most of the problems have been inherited from the past,” said Dr. Cetin. “Let’s not forget that we have only recently been giving birth in hospital. The so-called medicalization of childbirth has been responsible for a decline in the death rate and morbidity rate of pregnant women, but initially, there was little interest or care in how women felt in this situation, including with regard to physical pain. Since the 1970s, with Leboyer from France and Miraglia from Italy [promoters of so-called sweet birth], a path was cleared for a different line of thought. For this reason, I believe that the situation will improve over time.

“To continuously improve physician-patient communication,” concluded Dr. Cetin, “it would perhaps be appropriate to make sure that, even in the preparatory phase, women are well aware of possible complications and of the necessary and rapid emergency procedures that must be implemented by health care personnel. This way, a trusting relationship could be maintained, and the perception of having suffered abuse due to not being involved in strictly medical decisions could be stemmed.”

This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.

Dilating eye drops may delay – and perhaps even prevent – the onset of myopia in children, according to findings from a study published in JAMA. The study was conducted by researchers in Hong Kong.

Myopia is irreversible once it takes root and can contribute to other vision problems, such as macular degeneration, retinal detachment, glaucoma, and cataracts. The incidence of nearsightedness has nearly doubled since the 1970s, rising from 25% of the U.S. population to nearly 42%. Children have been particularly affected by the increase; reasons may include spending more time indoors looking at screens, experts say.

“Myopia is an ongoing and growing worldwide concern. This is of particular importance because of the change in children’s lifestyle, such as decreased outdoor time and increased screen time during and after the COVID-19 pandemic,” Jason C. Yam, MPH, of the department of ophthalmology and visual services at the Chinese University of Hong Kong, said in an interview.

Mr. Yam said that, while encouraging children to engage more in outdoor activity and spend less time using screens would help delay myopia, pharmaceutical interventions are needed, given myopia’s potential lifelong effects.
 

Putting eye drops to the test

In 2020, Mr. Yam and colleagues reported results of the Low-Concentration Atropine for Myopia Progression (LAMP) study, which showed that eye drops containing a solution of 0.05% atropine worked best at slowing the progression of myopia in 4- to 12-year-olds who already had the condition. Atropine relaxes eye muscles, causing dilation.

In that study, Mr. Yam and colleagues measured the rate of change in the eye’s ability to see at a great distance using a unit of measure known as the diopter. The higher the diopter, the more myopic a person’s vision. The 0.05% atropine solution was better at slowing this decline than placebo or solutions that contained a lower concentration of the substance.

The new study enrolled 474 children who were evenly divided by sex. None of the children had myopia when the trial began. Of that starting group, 353 children (age, 4-9 years) completed the study, which involved receiving eye drops once nightly in both eyes for 2 years.

Some children (n = 116) received 0.05% atropine, others (n = 122) received 0.01% atropine, and the rest (n = 115) received placebo drops. Mr. Yam and colleagues assessed how many children in each group had myopia after 2 years, as measured by a decline of at least a half diopter in one eye.

At the 2-year mark, more than half of children who received the placebo drops (61/115) had developed myopia, as had nearly half of those given 0.01% atropine (56/122). But fewer than one-third of children (33/116, 28.4%) who had received the drops with 0.05% atropine developed myopia during that period, the researchers reported.

The percentage of children with myopia in the placebo group (39/128, 30.5%) was larger by the end of the first year of the study than was the share of children in the 0.05% atropine group by the end of the trial. (Between 12 months and 24 months, 13 children in the placebo group left the study.) The main adverse event, in all treatment groups, was discomfort when exposed to bright light, according to the researchers.

“We are continuing the current study with the total intended follow-up duration of at least 6years,” added Mr. Yam, who hopes to determine whether the 0.05% atropine solution not only delays myopia but also prevents it altogether. While myopia is a concern worldwide, the condition is particularly prevalent in East Asia.

Mark A. Bullimore, MCOptom, PhD, FAAO, an adjunct professor at the University of Houston, and a consultant to ophthalmologic companies, called the trial “a landmark study. Finding children who are eligible and parents who are willing to deal with 2 years of drops is no small feat.

“The 0.05% atropine, on average, delays onset of myopia by a year,” Dr. Bullimore noted. He pointed to the similar percentages of myopia with placebo at 12 months, compared with 0.05% atropine 1 year later. He added that few clinicians in the United States use higher than 0.05% atropine for control of myopia because doing so can lead to excessive dilation and difficulty focusing.

While preventing myopia altogether would be ideal, simply delaying its onset can also be of tangible benefit, Bullimore said. In an article published in January, Dr. Bullimore and Noel A. Brennan of Johnson & Johnson Vision showed that delaying the onset of myopia reduces its severity.

“Optometrists prescribe low-concentration atropine already for myopia control, and there’s no reason now – in the light of this study – that they wouldn’t also do it to delay onset,” Dr. Bullimore said.

But in an editorial accompanying the journal article David A. Berntsen, OD, PhD, and Jeffrey J. Walline, OD, PhD, both of the University of Houston, wrote that a change in practice would be premature.

“The evidence presented does not yet warrant a change in the standard care of children because we do not yet know the long-term effects of delaying the onset of myopia with low-concentration atropine,” they wrote.

Identifying which children to consider for treatment is “a challenge,” they noted, because those who are not nearsighted typically do not undergo routine examination unless they have failed a vision test.

“Ultimately, the implementation of vision screenings that include determining a child’s prescription will likely be needed to identify children most likely to become myopic who may benefit from low-concentration atropine,” Dr. Berntsen and Dr. Walline wrote.

Mr. Yam and coinvestigators have applied for a patent on a 0.05% atropine solution. Dr. Bullimore reported relationships with Alcon Research,CooperVision, CorneaGen, EssilorLuxottica, Eyenovia, Genentech, Johnson & Johnson Vision, Lentechs, Novartis, and Vyluma, and is the sole owner of Ridgevue Publishing and Ridgevue Vision.

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

Dilating eye drops may delay – and perhaps even prevent – the onset of myopia in children, according to findings from a study published in JAMA. The study was conducted by researchers in Hong Kong.

Myopia is irreversible once it takes root and can contribute to other vision problems, such as macular degeneration, retinal detachment, glaucoma, and cataracts. The incidence of nearsightedness has nearly doubled since the 1970s, rising from 25% of the U.S. population to nearly 42%. Children have been particularly affected by the increase; reasons may include spending more time indoors looking at screens, experts say.

“Myopia is an ongoing and growing worldwide concern. This is of particular importance because of the change in children’s lifestyle, such as decreased outdoor time and increased screen time during and after the COVID-19 pandemic,” Jason C. Yam, MPH, of the department of ophthalmology and visual services at the Chinese University of Hong Kong, said in an interview.

Mr. Yam said that, while encouraging children to engage more in outdoor activity and spend less time using screens would help delay myopia, pharmaceutical interventions are needed, given myopia’s potential lifelong effects.
 

Putting eye drops to the test

In 2020, Mr. Yam and colleagues reported results of the Low-Concentration Atropine for Myopia Progression (LAMP) study, which showed that eye drops containing a solution of 0.05% atropine worked best at slowing the progression of myopia in 4- to 12-year-olds who already had the condition. Atropine relaxes eye muscles, causing dilation.

In that study, Mr. Yam and colleagues measured the rate of change in the eye’s ability to see at a great distance using a unit of measure known as the diopter. The higher the diopter, the more myopic a person’s vision. The 0.05% atropine solution was better at slowing this decline than placebo or solutions that contained a lower concentration of the substance.

The new study enrolled 474 children who were evenly divided by sex. None of the children had myopia when the trial began. Of that starting group, 353 children (age, 4-9 years) completed the study, which involved receiving eye drops once nightly in both eyes for 2 years.

Some children (n = 116) received 0.05% atropine, others (n = 122) received 0.01% atropine, and the rest (n = 115) received placebo drops. Mr. Yam and colleagues assessed how many children in each group had myopia after 2 years, as measured by a decline of at least a half diopter in one eye.

At the 2-year mark, more than half of children who received the placebo drops (61/115) had developed myopia, as had nearly half of those given 0.01% atropine (56/122). But fewer than one-third of children (33/116, 28.4%) who had received the drops with 0.05% atropine developed myopia during that period, the researchers reported.

The percentage of children with myopia in the placebo group (39/128, 30.5%) was larger by the end of the first year of the study than was the share of children in the 0.05% atropine group by the end of the trial. (Between 12 months and 24 months, 13 children in the placebo group left the study.) The main adverse event, in all treatment groups, was discomfort when exposed to bright light, according to the researchers.

“We are continuing the current study with the total intended follow-up duration of at least 6years,” added Mr. Yam, who hopes to determine whether the 0.05% atropine solution not only delays myopia but also prevents it altogether. While myopia is a concern worldwide, the condition is particularly prevalent in East Asia.

Mark A. Bullimore, MCOptom, PhD, FAAO, an adjunct professor at the University of Houston, and a consultant to ophthalmologic companies, called the trial “a landmark study. Finding children who are eligible and parents who are willing to deal with 2 years of drops is no small feat.

“The 0.05% atropine, on average, delays onset of myopia by a year,” Dr. Bullimore noted. He pointed to the similar percentages of myopia with placebo at 12 months, compared with 0.05% atropine 1 year later. He added that few clinicians in the United States use higher than 0.05% atropine for control of myopia because doing so can lead to excessive dilation and difficulty focusing.

While preventing myopia altogether would be ideal, simply delaying its onset can also be of tangible benefit, Bullimore said. In an article published in January, Dr. Bullimore and Noel A. Brennan of Johnson & Johnson Vision showed that delaying the onset of myopia reduces its severity.

“Optometrists prescribe low-concentration atropine already for myopia control, and there’s no reason now – in the light of this study – that they wouldn’t also do it to delay onset,” Dr. Bullimore said.

But in an editorial accompanying the journal article David A. Berntsen, OD, PhD, and Jeffrey J. Walline, OD, PhD, both of the University of Houston, wrote that a change in practice would be premature.

“The evidence presented does not yet warrant a change in the standard care of children because we do not yet know the long-term effects of delaying the onset of myopia with low-concentration atropine,” they wrote.

Identifying which children to consider for treatment is “a challenge,” they noted, because those who are not nearsighted typically do not undergo routine examination unless they have failed a vision test.

“Ultimately, the implementation of vision screenings that include determining a child’s prescription will likely be needed to identify children most likely to become myopic who may benefit from low-concentration atropine,” Dr. Berntsen and Dr. Walline wrote.

Mr. Yam and coinvestigators have applied for a patent on a 0.05% atropine solution. Dr. Bullimore reported relationships with Alcon Research,CooperVision, CorneaGen, EssilorLuxottica, Eyenovia, Genentech, Johnson & Johnson Vision, Lentechs, Novartis, and Vyluma, and is the sole owner of Ridgevue Publishing and Ridgevue Vision.

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

Dilating eye drops may delay – and perhaps even prevent – the onset of myopia in children, according to findings from a study published in JAMA. The study was conducted by researchers in Hong Kong.

Myopia is irreversible once it takes root and can contribute to other vision problems, such as macular degeneration, retinal detachment, glaucoma, and cataracts. The incidence of nearsightedness has nearly doubled since the 1970s, rising from 25% of the U.S. population to nearly 42%. Children have been particularly affected by the increase; reasons may include spending more time indoors looking at screens, experts say.

“Myopia is an ongoing and growing worldwide concern. This is of particular importance because of the change in children’s lifestyle, such as decreased outdoor time and increased screen time during and after the COVID-19 pandemic,” Jason C. Yam, MPH, of the department of ophthalmology and visual services at the Chinese University of Hong Kong, said in an interview.

Mr. Yam said that, while encouraging children to engage more in outdoor activity and spend less time using screens would help delay myopia, pharmaceutical interventions are needed, given myopia’s potential lifelong effects.
 

Putting eye drops to the test

In 2020, Mr. Yam and colleagues reported results of the Low-Concentration Atropine for Myopia Progression (LAMP) study, which showed that eye drops containing a solution of 0.05% atropine worked best at slowing the progression of myopia in 4- to 12-year-olds who already had the condition. Atropine relaxes eye muscles, causing dilation.

In that study, Mr. Yam and colleagues measured the rate of change in the eye’s ability to see at a great distance using a unit of measure known as the diopter. The higher the diopter, the more myopic a person’s vision. The 0.05% atropine solution was better at slowing this decline than placebo or solutions that contained a lower concentration of the substance.

The new study enrolled 474 children who were evenly divided by sex. None of the children had myopia when the trial began. Of that starting group, 353 children (age, 4-9 years) completed the study, which involved receiving eye drops once nightly in both eyes for 2 years.

Some children (n = 116) received 0.05% atropine, others (n = 122) received 0.01% atropine, and the rest (n = 115) received placebo drops. Mr. Yam and colleagues assessed how many children in each group had myopia after 2 years, as measured by a decline of at least a half diopter in one eye.

At the 2-year mark, more than half of children who received the placebo drops (61/115) had developed myopia, as had nearly half of those given 0.01% atropine (56/122). But fewer than one-third of children (33/116, 28.4%) who had received the drops with 0.05% atropine developed myopia during that period, the researchers reported.

The percentage of children with myopia in the placebo group (39/128, 30.5%) was larger by the end of the first year of the study than was the share of children in the 0.05% atropine group by the end of the trial. (Between 12 months and 24 months, 13 children in the placebo group left the study.) The main adverse event, in all treatment groups, was discomfort when exposed to bright light, according to the researchers.

“We are continuing the current study with the total intended follow-up duration of at least 6years,” added Mr. Yam, who hopes to determine whether the 0.05% atropine solution not only delays myopia but also prevents it altogether. While myopia is a concern worldwide, the condition is particularly prevalent in East Asia.

Mark A. Bullimore, MCOptom, PhD, FAAO, an adjunct professor at the University of Houston, and a consultant to ophthalmologic companies, called the trial “a landmark study. Finding children who are eligible and parents who are willing to deal with 2 years of drops is no small feat.

“The 0.05% atropine, on average, delays onset of myopia by a year,” Dr. Bullimore noted. He pointed to the similar percentages of myopia with placebo at 12 months, compared with 0.05% atropine 1 year later. He added that few clinicians in the United States use higher than 0.05% atropine for control of myopia because doing so can lead to excessive dilation and difficulty focusing.

While preventing myopia altogether would be ideal, simply delaying its onset can also be of tangible benefit, Bullimore said. In an article published in January, Dr. Bullimore and Noel A. Brennan of Johnson & Johnson Vision showed that delaying the onset of myopia reduces its severity.

“Optometrists prescribe low-concentration atropine already for myopia control, and there’s no reason now – in the light of this study – that they wouldn’t also do it to delay onset,” Dr. Bullimore said.

But in an editorial accompanying the journal article David A. Berntsen, OD, PhD, and Jeffrey J. Walline, OD, PhD, both of the University of Houston, wrote that a change in practice would be premature.

“The evidence presented does not yet warrant a change in the standard care of children because we do not yet know the long-term effects of delaying the onset of myopia with low-concentration atropine,” they wrote.

Identifying which children to consider for treatment is “a challenge,” they noted, because those who are not nearsighted typically do not undergo routine examination unless they have failed a vision test.

“Ultimately, the implementation of vision screenings that include determining a child’s prescription will likely be needed to identify children most likely to become myopic who may benefit from low-concentration atropine,” Dr. Berntsen and Dr. Walline wrote.

Mr. Yam and coinvestigators have applied for a patent on a 0.05% atropine solution. Dr. Bullimore reported relationships with Alcon Research,CooperVision, CorneaGen, EssilorLuxottica, Eyenovia, Genentech, Johnson & Johnson Vision, Lentechs, Novartis, and Vyluma, and is the sole owner of Ridgevue Publishing and Ridgevue Vision.

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

Off-label use of ketamine, the anesthetic-turned-potential treatment for resistant depression, is soaring in the United States and has many experts in the psychiatric community concerned.

The number of ketamine clinics has risen dramatically, with little to no oversight. Prescriptions are being written by providers who lack training in safe ketamine use and online startups are selling the drug for at-home use, taking advantage of a temporary federal regulation that makes it easier to prescribe controlled substances without an in-person patient assessment.

All of this comes at a time when recreational use of ketamine, known on the street as “Special K,” is rising, and reports to poison control centers and drug seizures by the U.S. Drug Enforcement Agency (DEA) are climbing.

In a scenario where enthusiasm for the drug is larger than the body of evidence supporting its clinical use, support is growing for the creation of a ketamine registry to collect data on dosage, treatment frequency, adverse events, and long-term outcomes in patients receiving the therapy for depression and other mental health conditions.

“In the past, there was this question of whether a registry was even needed,” said Gerard Sanacora, MD, PhD, a professor of psychiatry at Yale University, New Haven, Conn., who has pushed for a registry for more than 5 years.

“Now, not only are people being treated with this in large numbers, but it’s also started to push the envelope with at-home dosing,” Dr. Sanacora said in an interview. “It’s come to the point that everybody agrees we do need some way to track it.”
 

An idea whose time has come

Interest in ketamine’s antidepressant effects has grown since 2000, when a small study suggested the drug rapidly improved depressive symptoms. Research now suggests ketamine reduces symptoms in patients with treatment-resistant depression (TRD).

Studies linking ketamine to relief of depressive symptoms are small and mostly retrospective, and none has offered longitudinal information on long-term outcomes, including side effects and the risk of addiction.

Still, clinicians desperate to help the one-third of patients with major depression who fail to respond to first-line treatments often prescribe the drug anyway.

In 2017, Dr. Sanacora, who also is director of the Yale Depression Research Program at the Yale School of Medicine, was the lead author of a consensus statement that sought to help physicians administer ketamine safely and appropriately in patients with severe depression and other mood disorders.

In that paper, Dr. Sanacora and his coauthors advocated for the creation of a ketamine registry. Such a database, they argued, would provide much-needed data for large, long-term studies, which could be used to develop treatment guidelines, certification programs, and possibly even accreditation standards for providers. Meanwhile, researchers and clinicians in the United Kingdom were also calling for a ketamine registry.

While there seemed to be wide consensus that such a registry was needed, there was no clear path to creating one and no clear line to an agency that would take responsibility for maintaining it.

Because the registry wouldn’t be tied to a drug indication, Dr. Sanacora was told the U.S. Food and Drug Administration wouldn’t take it on. The project also fell outside the purview of the U.S. Department of Health & Human Services, the National Institute of Mental Health (NIMH), and the DEA.

“I haven’t met anybody who has said this is a terrible idea, but nobody seems to have a clear mechanism of doing it, and it doesn’t seem to fall directly under anybody’s jurisdiction,” Dr. Sanacora said.

Dr. Sanacora and other ketamine registry advocates were met with an endless stream of questions. Who would pay for it? How would they get providers to participate? Who would run it and how would the data be shared? The barriers to implementation seemed insurmountable.
 

A changing landscape

Five years later, these barriers remain. However, advocates note support for a registry is growing, due in large part to a series of developments over the past 6 years that they believe have altered the ketamine landscape.

Chief among these was the 2019 FDA approval of esketamine, a nasal formulation of ketamine, for the treatment of resistant depression. The drug’s indication was expanded in 2020 to include major depressive disorder and acute suicidal ideation or behavior. The drug is only available through a restricted distribution system – the Spravato Risk Evaluation and Mitigation Strategy (REMS) – because of the risk for serious adverse events, including sedation and dissociation, as well as the potential for abuse or misuse.

A sharp increase in the number of ketamine prescribers and clinics has also heightened interest in a ketamine registry. In the last year alone, membership in the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP) – a nonprofit trade organization for clinicians who prescribe ketamine for mental health disorders and pain conditions – swelled from 300 individual providers to more than 500.

The number of ketamine clinics in the United States has also grown exponentially and is estimated to be anywhere from 500 to 750. A spokesperson with HHS said such clinics are not regulated by the department or any other federal agency but instead are subject to oversight by individual states.

Although recreational use of ketamine remains low overall, there are signs that illicit use is rising, including an increase in DEA seizures of illicit ketamine and reports of ketamine-related poisonings to the nation’s poison control centers. Data on recreational use is spotty, at best. The Centers for Disease Control and Prevention National Vital Statistics System – the primary source of information on drug-related mortality in the United States – does not report on ketamine.
 

At-home ketamine use soars

Perhaps the most significant development came in March 2020 in the early days of the pandemic. To ease access to therapeutic schedule II-V controlled substances, the DEA issued a waiver that relaxed restrictions in the Ryan Haight Act, legislation that requires that patients be seen at least once in person before receiving a prescription for this class of drugs.

Under the waiver, DEA-registered practitioners are allowed to prescribe these substances – including ketamine, a schedule III substance – via telemedicine, without an in-person exam.

Startup companies cropped up almost overnight to prescribe oral ketamine online for at-home use, with almost no oversight. A spokesperson with the DEA told this news organization that the agency is working to make these “temporary” regulations permanent.

Under the relaxed DEA guidelines, a prescriber only needs to have a DEA license to dispense a ketamine prescription. An alarming number of clinics and online startups are staffed by individuals with no training in ketamine use and, in some cases, no formal mental health training at all, said Lisa Harding, MD, vice president of ASKP and a clinical instructor of psychiatry at Yale School of Medicine.

“The biggest problem is not the ketamine itself, it’s that the majority of practitioners are not psychiatrists, so they don’t have mental health training,” Dr. Harding said. “The fact that an untrained person, any practitioner with no mental health training, can administer this treatment once they have a state license to give ketamine ... then how are you protecting the patients?”

That question prompted ASKP to create the first known program to train psychiatrists, and other qualified mental health practitioners who prescribe ketamine, how to use the drug safely and effectively. The program, scheduled for June, will also include discussion by leaders in the field about how a ketamine registry might address these and other patient safety concerns.

“Nobody is really investigating the standard to which these clinics and online companies should be held, and I think a registry would help with that,” she said in an interview.
 

The path forward

While ASKP leadership supports the idea of a ketamine registry, Dr. Harding said the organization would need assurances the effort would not create a barrier to treatment.

“It will take somebody bringing all of us to the table and figuring that out,” Dr. Harding said.

Conversations like that with stakeholders would be one of the first steps toward creating a registry, Dr. Sanacora said.

“The more complicated we make this registry, the less compliance we’re going to get,” Dr. Sanacora said. “Our first step is to understand the major impediments and figure out how we can make this easier for people.”

Ideally, the registry would take advantage of existing data-collection tools, such as electronic health records (EHR), and include some sort of patient data entry mechanism, Dr. Sanacora said. The effort will also require skilled biostatisticians and a database system that is easy to manage.

And, of course, the registry will need a large number of patients to gather sufficient data to conduct high-quality research to develop treatment guidelines, training, and accreditation standards. A good target would be about 10,000 patients, Dr. Sanacora said.

All of this requires funding, which is the first hurdle registry advocates must clear. Dr. Sanacora is working on identifying funding sources and said that after working on this for years, he is hopeful that progress can be made.

“I had reached a point where it felt like there was no path forward,” Dr. Sanacora said. “But now I have renewed optimism that something can be done. And something does need to be done, largely for public health reasons but also to optimize the treatment.”

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

Off-label use of ketamine, the anesthetic-turned-potential treatment for resistant depression, is soaring in the United States and has many experts in the psychiatric community concerned.

The number of ketamine clinics has risen dramatically, with little to no oversight. Prescriptions are being written by providers who lack training in safe ketamine use and online startups are selling the drug for at-home use, taking advantage of a temporary federal regulation that makes it easier to prescribe controlled substances without an in-person patient assessment.

All of this comes at a time when recreational use of ketamine, known on the street as “Special K,” is rising, and reports to poison control centers and drug seizures by the U.S. Drug Enforcement Agency (DEA) are climbing.

In a scenario where enthusiasm for the drug is larger than the body of evidence supporting its clinical use, support is growing for the creation of a ketamine registry to collect data on dosage, treatment frequency, adverse events, and long-term outcomes in patients receiving the therapy for depression and other mental health conditions.

“In the past, there was this question of whether a registry was even needed,” said Gerard Sanacora, MD, PhD, a professor of psychiatry at Yale University, New Haven, Conn., who has pushed for a registry for more than 5 years.

“Now, not only are people being treated with this in large numbers, but it’s also started to push the envelope with at-home dosing,” Dr. Sanacora said in an interview. “It’s come to the point that everybody agrees we do need some way to track it.”
 

An idea whose time has come

Interest in ketamine’s antidepressant effects has grown since 2000, when a small study suggested the drug rapidly improved depressive symptoms. Research now suggests ketamine reduces symptoms in patients with treatment-resistant depression (TRD).

Studies linking ketamine to relief of depressive symptoms are small and mostly retrospective, and none has offered longitudinal information on long-term outcomes, including side effects and the risk of addiction.

Still, clinicians desperate to help the one-third of patients with major depression who fail to respond to first-line treatments often prescribe the drug anyway.

In 2017, Dr. Sanacora, who also is director of the Yale Depression Research Program at the Yale School of Medicine, was the lead author of a consensus statement that sought to help physicians administer ketamine safely and appropriately in patients with severe depression and other mood disorders.

In that paper, Dr. Sanacora and his coauthors advocated for the creation of a ketamine registry. Such a database, they argued, would provide much-needed data for large, long-term studies, which could be used to develop treatment guidelines, certification programs, and possibly even accreditation standards for providers. Meanwhile, researchers and clinicians in the United Kingdom were also calling for a ketamine registry.

While there seemed to be wide consensus that such a registry was needed, there was no clear path to creating one and no clear line to an agency that would take responsibility for maintaining it.

Because the registry wouldn’t be tied to a drug indication, Dr. Sanacora was told the U.S. Food and Drug Administration wouldn’t take it on. The project also fell outside the purview of the U.S. Department of Health & Human Services, the National Institute of Mental Health (NIMH), and the DEA.

“I haven’t met anybody who has said this is a terrible idea, but nobody seems to have a clear mechanism of doing it, and it doesn’t seem to fall directly under anybody’s jurisdiction,” Dr. Sanacora said.

Dr. Sanacora and other ketamine registry advocates were met with an endless stream of questions. Who would pay for it? How would they get providers to participate? Who would run it and how would the data be shared? The barriers to implementation seemed insurmountable.
 

A changing landscape

Five years later, these barriers remain. However, advocates note support for a registry is growing, due in large part to a series of developments over the past 6 years that they believe have altered the ketamine landscape.

Chief among these was the 2019 FDA approval of esketamine, a nasal formulation of ketamine, for the treatment of resistant depression. The drug’s indication was expanded in 2020 to include major depressive disorder and acute suicidal ideation or behavior. The drug is only available through a restricted distribution system – the Spravato Risk Evaluation and Mitigation Strategy (REMS) – because of the risk for serious adverse events, including sedation and dissociation, as well as the potential for abuse or misuse.

A sharp increase in the number of ketamine prescribers and clinics has also heightened interest in a ketamine registry. In the last year alone, membership in the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP) – a nonprofit trade organization for clinicians who prescribe ketamine for mental health disorders and pain conditions – swelled from 300 individual providers to more than 500.

The number of ketamine clinics in the United States has also grown exponentially and is estimated to be anywhere from 500 to 750. A spokesperson with HHS said such clinics are not regulated by the department or any other federal agency but instead are subject to oversight by individual states.

Although recreational use of ketamine remains low overall, there are signs that illicit use is rising, including an increase in DEA seizures of illicit ketamine and reports of ketamine-related poisonings to the nation’s poison control centers. Data on recreational use is spotty, at best. The Centers for Disease Control and Prevention National Vital Statistics System – the primary source of information on drug-related mortality in the United States – does not report on ketamine.
 

At-home ketamine use soars

Perhaps the most significant development came in March 2020 in the early days of the pandemic. To ease access to therapeutic schedule II-V controlled substances, the DEA issued a waiver that relaxed restrictions in the Ryan Haight Act, legislation that requires that patients be seen at least once in person before receiving a prescription for this class of drugs.

Under the waiver, DEA-registered practitioners are allowed to prescribe these substances – including ketamine, a schedule III substance – via telemedicine, without an in-person exam.

Startup companies cropped up almost overnight to prescribe oral ketamine online for at-home use, with almost no oversight. A spokesperson with the DEA told this news organization that the agency is working to make these “temporary” regulations permanent.

Under the relaxed DEA guidelines, a prescriber only needs to have a DEA license to dispense a ketamine prescription. An alarming number of clinics and online startups are staffed by individuals with no training in ketamine use and, in some cases, no formal mental health training at all, said Lisa Harding, MD, vice president of ASKP and a clinical instructor of psychiatry at Yale School of Medicine.

“The biggest problem is not the ketamine itself, it’s that the majority of practitioners are not psychiatrists, so they don’t have mental health training,” Dr. Harding said. “The fact that an untrained person, any practitioner with no mental health training, can administer this treatment once they have a state license to give ketamine ... then how are you protecting the patients?”

That question prompted ASKP to create the first known program to train psychiatrists, and other qualified mental health practitioners who prescribe ketamine, how to use the drug safely and effectively. The program, scheduled for June, will also include discussion by leaders in the field about how a ketamine registry might address these and other patient safety concerns.

“Nobody is really investigating the standard to which these clinics and online companies should be held, and I think a registry would help with that,” she said in an interview.
 

The path forward

While ASKP leadership supports the idea of a ketamine registry, Dr. Harding said the organization would need assurances the effort would not create a barrier to treatment.

“It will take somebody bringing all of us to the table and figuring that out,” Dr. Harding said.

Conversations like that with stakeholders would be one of the first steps toward creating a registry, Dr. Sanacora said.

“The more complicated we make this registry, the less compliance we’re going to get,” Dr. Sanacora said. “Our first step is to understand the major impediments and figure out how we can make this easier for people.”

Ideally, the registry would take advantage of existing data-collection tools, such as electronic health records (EHR), and include some sort of patient data entry mechanism, Dr. Sanacora said. The effort will also require skilled biostatisticians and a database system that is easy to manage.

And, of course, the registry will need a large number of patients to gather sufficient data to conduct high-quality research to develop treatment guidelines, training, and accreditation standards. A good target would be about 10,000 patients, Dr. Sanacora said.

All of this requires funding, which is the first hurdle registry advocates must clear. Dr. Sanacora is working on identifying funding sources and said that after working on this for years, he is hopeful that progress can be made.

“I had reached a point where it felt like there was no path forward,” Dr. Sanacora said. “But now I have renewed optimism that something can be done. And something does need to be done, largely for public health reasons but also to optimize the treatment.”

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

Off-label use of ketamine, the anesthetic-turned-potential treatment for resistant depression, is soaring in the United States and has many experts in the psychiatric community concerned.

The number of ketamine clinics has risen dramatically, with little to no oversight. Prescriptions are being written by providers who lack training in safe ketamine use and online startups are selling the drug for at-home use, taking advantage of a temporary federal regulation that makes it easier to prescribe controlled substances without an in-person patient assessment.

All of this comes at a time when recreational use of ketamine, known on the street as “Special K,” is rising, and reports to poison control centers and drug seizures by the U.S. Drug Enforcement Agency (DEA) are climbing.

In a scenario where enthusiasm for the drug is larger than the body of evidence supporting its clinical use, support is growing for the creation of a ketamine registry to collect data on dosage, treatment frequency, adverse events, and long-term outcomes in patients receiving the therapy for depression and other mental health conditions.

“In the past, there was this question of whether a registry was even needed,” said Gerard Sanacora, MD, PhD, a professor of psychiatry at Yale University, New Haven, Conn., who has pushed for a registry for more than 5 years.

“Now, not only are people being treated with this in large numbers, but it’s also started to push the envelope with at-home dosing,” Dr. Sanacora said in an interview. “It’s come to the point that everybody agrees we do need some way to track it.”
 

An idea whose time has come

Interest in ketamine’s antidepressant effects has grown since 2000, when a small study suggested the drug rapidly improved depressive symptoms. Research now suggests ketamine reduces symptoms in patients with treatment-resistant depression (TRD).

Studies linking ketamine to relief of depressive symptoms are small and mostly retrospective, and none has offered longitudinal information on long-term outcomes, including side effects and the risk of addiction.

Still, clinicians desperate to help the one-third of patients with major depression who fail to respond to first-line treatments often prescribe the drug anyway.

In 2017, Dr. Sanacora, who also is director of the Yale Depression Research Program at the Yale School of Medicine, was the lead author of a consensus statement that sought to help physicians administer ketamine safely and appropriately in patients with severe depression and other mood disorders.

In that paper, Dr. Sanacora and his coauthors advocated for the creation of a ketamine registry. Such a database, they argued, would provide much-needed data for large, long-term studies, which could be used to develop treatment guidelines, certification programs, and possibly even accreditation standards for providers. Meanwhile, researchers and clinicians in the United Kingdom were also calling for a ketamine registry.

While there seemed to be wide consensus that such a registry was needed, there was no clear path to creating one and no clear line to an agency that would take responsibility for maintaining it.

Because the registry wouldn’t be tied to a drug indication, Dr. Sanacora was told the U.S. Food and Drug Administration wouldn’t take it on. The project also fell outside the purview of the U.S. Department of Health & Human Services, the National Institute of Mental Health (NIMH), and the DEA.

“I haven’t met anybody who has said this is a terrible idea, but nobody seems to have a clear mechanism of doing it, and it doesn’t seem to fall directly under anybody’s jurisdiction,” Dr. Sanacora said.

Dr. Sanacora and other ketamine registry advocates were met with an endless stream of questions. Who would pay for it? How would they get providers to participate? Who would run it and how would the data be shared? The barriers to implementation seemed insurmountable.
 

A changing landscape

Five years later, these barriers remain. However, advocates note support for a registry is growing, due in large part to a series of developments over the past 6 years that they believe have altered the ketamine landscape.

Chief among these was the 2019 FDA approval of esketamine, a nasal formulation of ketamine, for the treatment of resistant depression. The drug’s indication was expanded in 2020 to include major depressive disorder and acute suicidal ideation or behavior. The drug is only available through a restricted distribution system – the Spravato Risk Evaluation and Mitigation Strategy (REMS) – because of the risk for serious adverse events, including sedation and dissociation, as well as the potential for abuse or misuse.

A sharp increase in the number of ketamine prescribers and clinics has also heightened interest in a ketamine registry. In the last year alone, membership in the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP) – a nonprofit trade organization for clinicians who prescribe ketamine for mental health disorders and pain conditions – swelled from 300 individual providers to more than 500.

The number of ketamine clinics in the United States has also grown exponentially and is estimated to be anywhere from 500 to 750. A spokesperson with HHS said such clinics are not regulated by the department or any other federal agency but instead are subject to oversight by individual states.

Although recreational use of ketamine remains low overall, there are signs that illicit use is rising, including an increase in DEA seizures of illicit ketamine and reports of ketamine-related poisonings to the nation’s poison control centers. Data on recreational use is spotty, at best. The Centers for Disease Control and Prevention National Vital Statistics System – the primary source of information on drug-related mortality in the United States – does not report on ketamine.
 

At-home ketamine use soars

Perhaps the most significant development came in March 2020 in the early days of the pandemic. To ease access to therapeutic schedule II-V controlled substances, the DEA issued a waiver that relaxed restrictions in the Ryan Haight Act, legislation that requires that patients be seen at least once in person before receiving a prescription for this class of drugs.

Under the waiver, DEA-registered practitioners are allowed to prescribe these substances – including ketamine, a schedule III substance – via telemedicine, without an in-person exam.

Startup companies cropped up almost overnight to prescribe oral ketamine online for at-home use, with almost no oversight. A spokesperson with the DEA told this news organization that the agency is working to make these “temporary” regulations permanent.

Under the relaxed DEA guidelines, a prescriber only needs to have a DEA license to dispense a ketamine prescription. An alarming number of clinics and online startups are staffed by individuals with no training in ketamine use and, in some cases, no formal mental health training at all, said Lisa Harding, MD, vice president of ASKP and a clinical instructor of psychiatry at Yale School of Medicine.

“The biggest problem is not the ketamine itself, it’s that the majority of practitioners are not psychiatrists, so they don’t have mental health training,” Dr. Harding said. “The fact that an untrained person, any practitioner with no mental health training, can administer this treatment once they have a state license to give ketamine ... then how are you protecting the patients?”

That question prompted ASKP to create the first known program to train psychiatrists, and other qualified mental health practitioners who prescribe ketamine, how to use the drug safely and effectively. The program, scheduled for June, will also include discussion by leaders in the field about how a ketamine registry might address these and other patient safety concerns.

“Nobody is really investigating the standard to which these clinics and online companies should be held, and I think a registry would help with that,” she said in an interview.
 

The path forward

While ASKP leadership supports the idea of a ketamine registry, Dr. Harding said the organization would need assurances the effort would not create a barrier to treatment.

“It will take somebody bringing all of us to the table and figuring that out,” Dr. Harding said.

Conversations like that with stakeholders would be one of the first steps toward creating a registry, Dr. Sanacora said.

“The more complicated we make this registry, the less compliance we’re going to get,” Dr. Sanacora said. “Our first step is to understand the major impediments and figure out how we can make this easier for people.”

Ideally, the registry would take advantage of existing data-collection tools, such as electronic health records (EHR), and include some sort of patient data entry mechanism, Dr. Sanacora said. The effort will also require skilled biostatisticians and a database system that is easy to manage.

And, of course, the registry will need a large number of patients to gather sufficient data to conduct high-quality research to develop treatment guidelines, training, and accreditation standards. A good target would be about 10,000 patients, Dr. Sanacora said.

All of this requires funding, which is the first hurdle registry advocates must clear. Dr. Sanacora is working on identifying funding sources and said that after working on this for years, he is hopeful that progress can be made.

“I had reached a point where it felt like there was no path forward,” Dr. Sanacora said. “But now I have renewed optimism that something can be done. And something does need to be done, largely for public health reasons but also to optimize the treatment.”

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

The Food and Drug Administration will not act on Phathom Pharmaceutical’s vonoprazan new drug application (NDA) for erosive esophagitis or its postapproval supplement for Helicobacter pylori until the company addresses concerns over the presence of nitrosamine impurities.

The FDA approved the company’s two vonoprazan-based treatments for H. pylori infection, Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), last May.

The target action date of the company’s NDA for vonoprazan for the treatment of erosive esophagitis was Jan. 11, 2023.

In a news release, Phathom said it has received complete response letters from the FDA related to its erosive esophagitis NDA and H. pylori postapproval supplement.

Both letters address specifications and controls for a nitrosamine drug substance–related impurity, N-nitroso-vonoprazan (NVP), which was detected in the initial commercial launch materials of both products.

The FDA letters ask Phathom to provide “additional stability data to demonstrate that levels of the impurity previously found in vonoprazan drug product will remain at or below the daily acceptable intake throughout the proposed shelf life of the product,” Phathom said.

Phathom said it has conducted “extensive root cause investigations regarding the trace levels of the impurity since it was detected and has implemented mitigation measures to control the levels of NVP below the acceptable intake.”

The company expects to meet with the FDA before the end of March to discuss a resubmission plan and a timeline for the vonoprazan products.

Owing to the regulatory delays, Phathom said it no longer expects product launches for H. pylori or erosive esophagitis in the first quarter of 2023.

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

The Food and Drug Administration will not act on Phathom Pharmaceutical’s vonoprazan new drug application (NDA) for erosive esophagitis or its postapproval supplement for Helicobacter pylori until the company addresses concerns over the presence of nitrosamine impurities.

The FDA approved the company’s two vonoprazan-based treatments for H. pylori infection, Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), last May.

The target action date of the company’s NDA for vonoprazan for the treatment of erosive esophagitis was Jan. 11, 2023.

In a news release, Phathom said it has received complete response letters from the FDA related to its erosive esophagitis NDA and H. pylori postapproval supplement.

Both letters address specifications and controls for a nitrosamine drug substance–related impurity, N-nitroso-vonoprazan (NVP), which was detected in the initial commercial launch materials of both products.

The FDA letters ask Phathom to provide “additional stability data to demonstrate that levels of the impurity previously found in vonoprazan drug product will remain at or below the daily acceptable intake throughout the proposed shelf life of the product,” Phathom said.

Phathom said it has conducted “extensive root cause investigations regarding the trace levels of the impurity since it was detected and has implemented mitigation measures to control the levels of NVP below the acceptable intake.”

The company expects to meet with the FDA before the end of March to discuss a resubmission plan and a timeline for the vonoprazan products.

Owing to the regulatory delays, Phathom said it no longer expects product launches for H. pylori or erosive esophagitis in the first quarter of 2023.

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

The Food and Drug Administration will not act on Phathom Pharmaceutical’s vonoprazan new drug application (NDA) for erosive esophagitis or its postapproval supplement for Helicobacter pylori until the company addresses concerns over the presence of nitrosamine impurities.

The FDA approved the company’s two vonoprazan-based treatments for H. pylori infection, Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), last May.

The target action date of the company’s NDA for vonoprazan for the treatment of erosive esophagitis was Jan. 11, 2023.

In a news release, Phathom said it has received complete response letters from the FDA related to its erosive esophagitis NDA and H. pylori postapproval supplement.

Both letters address specifications and controls for a nitrosamine drug substance–related impurity, N-nitroso-vonoprazan (NVP), which was detected in the initial commercial launch materials of both products.

The FDA letters ask Phathom to provide “additional stability data to demonstrate that levels of the impurity previously found in vonoprazan drug product will remain at or below the daily acceptable intake throughout the proposed shelf life of the product,” Phathom said.

Phathom said it has conducted “extensive root cause investigations regarding the trace levels of the impurity since it was detected and has implemented mitigation measures to control the levels of NVP below the acceptable intake.”

The company expects to meet with the FDA before the end of March to discuss a resubmission plan and a timeline for the vonoprazan products.

Owing to the regulatory delays, Phathom said it no longer expects product launches for H. pylori or erosive esophagitis in the first quarter of 2023.

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

An oncologist who says she was fired for whistleblower retaliation and gender discrimination has now filed a lawsuit against her former employer.

Anne Grand’Maison, MD, was employed at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., for 5 years and was the first medical oncologist specifically trained in sarcoma to join the center since it was founded more than 130 years ago.

The lawsuit, filed on Jan. 31, alleges that she was pushed out of her job after raising numerous concerns about egregious medical misconduct and lack of patient safety at the facility.

Roswell Park Cancer Center “denies these unfounded claims, and will vigorously defend itself in this matter,” the organization said in a statement issued to this news organization.

The 75-page complaint alleges that Dr. Grand’Maison observed unacceptable conduct and treatment of patients, including sarcoma pathology reports replete with diagnostic errors, physicians who were not well educated in the latest sarcoma research, and senior doctors refusing to seek out second opinions even in difficult cases.

All of these issues put patient safety and lives at serious risk, according to the lawsuit, and Dr. Grand’Maison raised her concerns internally and attempted to create the necessary changes.

Of specific concern to Dr. Grand’Maison was the competence of Carl Morrison, MD, DVM, Roswell Park’s lead sarcoma pathologist and chair of pathology, whom she had questioned on many occasions and voiced concerns about to other senior staff. But once she made it known that she had gathered up medical records to prove that he had made numerous specific misdiagnoses that led to mistreatments, Dr. Grand’Maison was forced out of her job and the hospital, she said.

“Roswell failed the cancer patients who entrusted their lives to the hospital by ignoring risks to their safety,” Dr. Grand’Maison said in an interview. “The heart of my practice as an oncologist is the well-being of my patients and that is why I could not stay silent.

“I hope that by coming forward, Roswell will be held accountable for putting lives at risk,” she said.
 

Not up to date with best practices

Before joining Roswell, Dr. Grand’Maison had worked at the University of Texas MD Anderson Cancer Center, which is the top cancer center in the nation, noted David E. Gottlieb, a partner at Wigdor, the law firm that is representing her.

MD Anderson has set the standard for sarcoma care, as they treat the highest volume of sarcoma cases of any hospital in North America and they have the best survival outcomes for sarcoma patients, he said in an interview.

“She was bringing this knowledge and background to Roswell Park,” Mr. Gottlieb said. “She felt that Dr. Morrison was not up to date with best practices as far as diagnosing and treating sarcoma, and she raised numerous issues.

“He was not open to being critiqued and even rejected her request to send something out for a second opinion,” Mr. Gottlieb said. “Second opinions are routine in medicine, and it’s the standard of care. We are dealing with a person’s life and it’s not a personal attack – you could be wrong, and getting another opinion can save a patient’s life.”

But Dr. Morrison has been at Roswell Park for many years, is a good friend of Roswell’s president and CEO Candace Johnson, PhD, and is part of the “old guard,” and “really at the top of the organization,” Mr. Gottlieb said  “Whereas Dr. Grand’Maison was relatively new, and her opinions were not popular.”

The complaint was filed against defendants Roswell Park Comprehensive Care Center; Health Research Inc. Roswell Park Division; Candace Johnson, PhD; Carl Morrison, MD, DVM; Renier Brentjens, MD, PhD, deputy director and chair of medicine; and two other senior physicians.
 

Denial of ‘unfounded claims’

In its statement, Roswell Park pointed out that it is one of few centers in the nation recognized by the Sarcoma Alliance as a hospital with specialized expertise and resources for patients with sarcoma. “Our physician experts not only adhere strictly to national best practices in the diagnosis and care of patients with sarcoma, they determine and disseminate the standards of appropriate medical care as lead authors of national guidelines,” the center stated.

“The facts demonstrate that Roswell Park is a richly diverse and inclusive organization committed to optimizing cancer care by incorporating the expertise of teams of specialists from many subspecialties and disciplines,” according to the statement.
 

Resistance and male egos

Dr. Grand’Maison has been a licensed physician for more than 30 years, and received her MD in 1988 after graduating from Sherbrooke University in Quebec. Over the next few decades she worked in clinical medicine and research, both in Canada and the United States. In 2014, she became certified in medical oncology and then secured a clinical and research fellowship focusing on sarcoma at MD Anderson.

Two years later, after completing her fellowship, she accepted a full-time position as an assistant professor of oncology in the department of medical oncology’s sarcoma division at Roswell Park. She became the first medical oncologist with a subspecialty in sarcoma, and also brought with her the advanced techniques and aggressive treatment that had been pioneered by MD Anderson, and which had never been used at Roswell Park, according to the complaint.

However, Dr. Grand’Maison said that she began to encounter some resistance from those more familiar with Roswell’s previous standard operating procedures. For example, her practice of seeing patients on days when chemotherapy was administered was viewed by some of the advanced practice clinicians as a lack of confidence in their abilities.

According to the complaint, Dr. Grand’Maison found the sarcoma tumor board at Roswell to be “male-dominated, ego-driven, fraught with defensiveness, and rife with a lack of collegiality almost from the very beginning,” which was very different from her experience at MD Anderson.

Less than 6 months after joining Roswell, she said that Dr. Morrison began treating her in a condescending manner at the tumor board meetings when she asked him questions pertaining to a diagnosis. She viewed his “physically intimidating and aggressive conduct toward her as sexist, and it was a pattern of conduct that would persist in the years that followed.” Dr. Grand’Maison observed that Dr. Morrison never behaved that way toward the men when discussing a case.

Over time, Dr. Grand’Maison made numerous and near endless efforts to raise her concerns about patient safety and gender discrimination at Roswell Park and had reached out to her supervisor and to others in upper management, the complaint alleges. All of this appeared to fall on completely deaf ears as hospital “politics” and doctor egos took precedence. Dr. Morrison continued to try to intimidate her into “silence” and block her attempts to refine diagnoses to ensure proper treatment, and several other senior physicians enabled his behavior and ignored the risk it posed to patient safety, the complaint alleges.  

“While she raised complaints about gender discrimination, the crux of her complaint was patient safety,” Mr. Gottlieb emphasized.

Another issue was that Dr. Grand’Maison never received the proper clinical support she repeatedly requested and that was urgently needed. Thus, her patients faced other elevated safety risks as a result of the underresourced sarcoma clinic, she said.
 

Fired or resigned?

Dr. Grand’Maison left Roswell Park Cancer center last May, and has not worked since.

Although Dr. Grand’Maison stated that she was fired in retaliation for raising serious concerns, Roswell Park insists that she voluntarily resigned. Dr. Grand’Maison acknowledged that she wrote an email in January 2022 to the clinical practice plan coordinator in which she mentioned that her husband was planning to relocate back to Canada and that her last date at Roswell Park would be May 1, 2022. The coordinator never responded to that email. In the interim, her husband, also a physician with privileges at Roswell Park, made it known that he was not moving to Canada.

Dr. Grand’Maison said that, as she had not resigned, and everyone knew her husband wasn’t moving, she did not follow up on that January 2022 email, and then forgot about it.

“That email was used as the basis to force her out,”said her lawyer, Mr. Gottlieb. “The day after she put together a summary and extensively documented serious patient safety concerns, she got an email that her resignation had been accepted.”

None of the standard protocols for resignation had been completed, either by human resources or by her supervisors, Mr. Gottlieb contended. “The law says that they can’t take adverse action against her for filing a complaint, so they fired her under the guise of a resignation,” he said.

Roswell Park refused to rescind Dr. Grand’Maison’s resignation, despite multiple attempts on her part. She even contacted the CEO and stated that her January 2022 email was being used a pretext to push her out in retaliation, but she received no response, only that the matter had been referred to someone else.

“I am speaking out because time and again female doctors are unable to deliver on the promise of their medical training because of discrimination,” said Dr. Grand’Maison. “Roswell dismissed my expertise and diminished my value. While I worry that coming forward may affect my career, I am taking that risk to make the path easier for the women who will come behind me.”

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

An oncologist who says she was fired for whistleblower retaliation and gender discrimination has now filed a lawsuit against her former employer.

Anne Grand’Maison, MD, was employed at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., for 5 years and was the first medical oncologist specifically trained in sarcoma to join the center since it was founded more than 130 years ago.

The lawsuit, filed on Jan. 31, alleges that she was pushed out of her job after raising numerous concerns about egregious medical misconduct and lack of patient safety at the facility.

Roswell Park Cancer Center “denies these unfounded claims, and will vigorously defend itself in this matter,” the organization said in a statement issued to this news organization.

The 75-page complaint alleges that Dr. Grand’Maison observed unacceptable conduct and treatment of patients, including sarcoma pathology reports replete with diagnostic errors, physicians who were not well educated in the latest sarcoma research, and senior doctors refusing to seek out second opinions even in difficult cases.

All of these issues put patient safety and lives at serious risk, according to the lawsuit, and Dr. Grand’Maison raised her concerns internally and attempted to create the necessary changes.

Of specific concern to Dr. Grand’Maison was the competence of Carl Morrison, MD, DVM, Roswell Park’s lead sarcoma pathologist and chair of pathology, whom she had questioned on many occasions and voiced concerns about to other senior staff. But once she made it known that she had gathered up medical records to prove that he had made numerous specific misdiagnoses that led to mistreatments, Dr. Grand’Maison was forced out of her job and the hospital, she said.

“Roswell failed the cancer patients who entrusted their lives to the hospital by ignoring risks to their safety,” Dr. Grand’Maison said in an interview. “The heart of my practice as an oncologist is the well-being of my patients and that is why I could not stay silent.

“I hope that by coming forward, Roswell will be held accountable for putting lives at risk,” she said.
 

Not up to date with best practices

Before joining Roswell, Dr. Grand’Maison had worked at the University of Texas MD Anderson Cancer Center, which is the top cancer center in the nation, noted David E. Gottlieb, a partner at Wigdor, the law firm that is representing her.

MD Anderson has set the standard for sarcoma care, as they treat the highest volume of sarcoma cases of any hospital in North America and they have the best survival outcomes for sarcoma patients, he said in an interview.

“She was bringing this knowledge and background to Roswell Park,” Mr. Gottlieb said. “She felt that Dr. Morrison was not up to date with best practices as far as diagnosing and treating sarcoma, and she raised numerous issues.

“He was not open to being critiqued and even rejected her request to send something out for a second opinion,” Mr. Gottlieb said. “Second opinions are routine in medicine, and it’s the standard of care. We are dealing with a person’s life and it’s not a personal attack – you could be wrong, and getting another opinion can save a patient’s life.”

But Dr. Morrison has been at Roswell Park for many years, is a good friend of Roswell’s president and CEO Candace Johnson, PhD, and is part of the “old guard,” and “really at the top of the organization,” Mr. Gottlieb said  “Whereas Dr. Grand’Maison was relatively new, and her opinions were not popular.”

The complaint was filed against defendants Roswell Park Comprehensive Care Center; Health Research Inc. Roswell Park Division; Candace Johnson, PhD; Carl Morrison, MD, DVM; Renier Brentjens, MD, PhD, deputy director and chair of medicine; and two other senior physicians.
 

Denial of ‘unfounded claims’

In its statement, Roswell Park pointed out that it is one of few centers in the nation recognized by the Sarcoma Alliance as a hospital with specialized expertise and resources for patients with sarcoma. “Our physician experts not only adhere strictly to national best practices in the diagnosis and care of patients with sarcoma, they determine and disseminate the standards of appropriate medical care as lead authors of national guidelines,” the center stated.

“The facts demonstrate that Roswell Park is a richly diverse and inclusive organization committed to optimizing cancer care by incorporating the expertise of teams of specialists from many subspecialties and disciplines,” according to the statement.
 

Resistance and male egos

Dr. Grand’Maison has been a licensed physician for more than 30 years, and received her MD in 1988 after graduating from Sherbrooke University in Quebec. Over the next few decades she worked in clinical medicine and research, both in Canada and the United States. In 2014, she became certified in medical oncology and then secured a clinical and research fellowship focusing on sarcoma at MD Anderson.

Two years later, after completing her fellowship, she accepted a full-time position as an assistant professor of oncology in the department of medical oncology’s sarcoma division at Roswell Park. She became the first medical oncologist with a subspecialty in sarcoma, and also brought with her the advanced techniques and aggressive treatment that had been pioneered by MD Anderson, and which had never been used at Roswell Park, according to the complaint.

However, Dr. Grand’Maison said that she began to encounter some resistance from those more familiar with Roswell’s previous standard operating procedures. For example, her practice of seeing patients on days when chemotherapy was administered was viewed by some of the advanced practice clinicians as a lack of confidence in their abilities.

According to the complaint, Dr. Grand’Maison found the sarcoma tumor board at Roswell to be “male-dominated, ego-driven, fraught with defensiveness, and rife with a lack of collegiality almost from the very beginning,” which was very different from her experience at MD Anderson.

Less than 6 months after joining Roswell, she said that Dr. Morrison began treating her in a condescending manner at the tumor board meetings when she asked him questions pertaining to a diagnosis. She viewed his “physically intimidating and aggressive conduct toward her as sexist, and it was a pattern of conduct that would persist in the years that followed.” Dr. Grand’Maison observed that Dr. Morrison never behaved that way toward the men when discussing a case.

Over time, Dr. Grand’Maison made numerous and near endless efforts to raise her concerns about patient safety and gender discrimination at Roswell Park and had reached out to her supervisor and to others in upper management, the complaint alleges. All of this appeared to fall on completely deaf ears as hospital “politics” and doctor egos took precedence. Dr. Morrison continued to try to intimidate her into “silence” and block her attempts to refine diagnoses to ensure proper treatment, and several other senior physicians enabled his behavior and ignored the risk it posed to patient safety, the complaint alleges.  

“While she raised complaints about gender discrimination, the crux of her complaint was patient safety,” Mr. Gottlieb emphasized.

Another issue was that Dr. Grand’Maison never received the proper clinical support she repeatedly requested and that was urgently needed. Thus, her patients faced other elevated safety risks as a result of the underresourced sarcoma clinic, she said.
 

Fired or resigned?

Dr. Grand’Maison left Roswell Park Cancer center last May, and has not worked since.

Although Dr. Grand’Maison stated that she was fired in retaliation for raising serious concerns, Roswell Park insists that she voluntarily resigned. Dr. Grand’Maison acknowledged that she wrote an email in January 2022 to the clinical practice plan coordinator in which she mentioned that her husband was planning to relocate back to Canada and that her last date at Roswell Park would be May 1, 2022. The coordinator never responded to that email. In the interim, her husband, also a physician with privileges at Roswell Park, made it known that he was not moving to Canada.

Dr. Grand’Maison said that, as she had not resigned, and everyone knew her husband wasn’t moving, she did not follow up on that January 2022 email, and then forgot about it.

“That email was used as the basis to force her out,”said her lawyer, Mr. Gottlieb. “The day after she put together a summary and extensively documented serious patient safety concerns, she got an email that her resignation had been accepted.”

None of the standard protocols for resignation had been completed, either by human resources or by her supervisors, Mr. Gottlieb contended. “The law says that they can’t take adverse action against her for filing a complaint, so they fired her under the guise of a resignation,” he said.

Roswell Park refused to rescind Dr. Grand’Maison’s resignation, despite multiple attempts on her part. She even contacted the CEO and stated that her January 2022 email was being used a pretext to push her out in retaliation, but she received no response, only that the matter had been referred to someone else.

“I am speaking out because time and again female doctors are unable to deliver on the promise of their medical training because of discrimination,” said Dr. Grand’Maison. “Roswell dismissed my expertise and diminished my value. While I worry that coming forward may affect my career, I am taking that risk to make the path easier for the women who will come behind me.”

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

An oncologist who says she was fired for whistleblower retaliation and gender discrimination has now filed a lawsuit against her former employer.

Anne Grand’Maison, MD, was employed at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., for 5 years and was the first medical oncologist specifically trained in sarcoma to join the center since it was founded more than 130 years ago.

The lawsuit, filed on Jan. 31, alleges that she was pushed out of her job after raising numerous concerns about egregious medical misconduct and lack of patient safety at the facility.

Roswell Park Cancer Center “denies these unfounded claims, and will vigorously defend itself in this matter,” the organization said in a statement issued to this news organization.

The 75-page complaint alleges that Dr. Grand’Maison observed unacceptable conduct and treatment of patients, including sarcoma pathology reports replete with diagnostic errors, physicians who were not well educated in the latest sarcoma research, and senior doctors refusing to seek out second opinions even in difficult cases.

All of these issues put patient safety and lives at serious risk, according to the lawsuit, and Dr. Grand’Maison raised her concerns internally and attempted to create the necessary changes.

Of specific concern to Dr. Grand’Maison was the competence of Carl Morrison, MD, DVM, Roswell Park’s lead sarcoma pathologist and chair of pathology, whom she had questioned on many occasions and voiced concerns about to other senior staff. But once she made it known that she had gathered up medical records to prove that he had made numerous specific misdiagnoses that led to mistreatments, Dr. Grand’Maison was forced out of her job and the hospital, she said.

“Roswell failed the cancer patients who entrusted their lives to the hospital by ignoring risks to their safety,” Dr. Grand’Maison said in an interview. “The heart of my practice as an oncologist is the well-being of my patients and that is why I could not stay silent.

“I hope that by coming forward, Roswell will be held accountable for putting lives at risk,” she said.
 

Not up to date with best practices

Before joining Roswell, Dr. Grand’Maison had worked at the University of Texas MD Anderson Cancer Center, which is the top cancer center in the nation, noted David E. Gottlieb, a partner at Wigdor, the law firm that is representing her.

MD Anderson has set the standard for sarcoma care, as they treat the highest volume of sarcoma cases of any hospital in North America and they have the best survival outcomes for sarcoma patients, he said in an interview.

“She was bringing this knowledge and background to Roswell Park,” Mr. Gottlieb said. “She felt that Dr. Morrison was not up to date with best practices as far as diagnosing and treating sarcoma, and she raised numerous issues.

“He was not open to being critiqued and even rejected her request to send something out for a second opinion,” Mr. Gottlieb said. “Second opinions are routine in medicine, and it’s the standard of care. We are dealing with a person’s life and it’s not a personal attack – you could be wrong, and getting another opinion can save a patient’s life.”

But Dr. Morrison has been at Roswell Park for many years, is a good friend of Roswell’s president and CEO Candace Johnson, PhD, and is part of the “old guard,” and “really at the top of the organization,” Mr. Gottlieb said  “Whereas Dr. Grand’Maison was relatively new, and her opinions were not popular.”

The complaint was filed against defendants Roswell Park Comprehensive Care Center; Health Research Inc. Roswell Park Division; Candace Johnson, PhD; Carl Morrison, MD, DVM; Renier Brentjens, MD, PhD, deputy director and chair of medicine; and two other senior physicians.
 

Denial of ‘unfounded claims’

In its statement, Roswell Park pointed out that it is one of few centers in the nation recognized by the Sarcoma Alliance as a hospital with specialized expertise and resources for patients with sarcoma. “Our physician experts not only adhere strictly to national best practices in the diagnosis and care of patients with sarcoma, they determine and disseminate the standards of appropriate medical care as lead authors of national guidelines,” the center stated.

“The facts demonstrate that Roswell Park is a richly diverse and inclusive organization committed to optimizing cancer care by incorporating the expertise of teams of specialists from many subspecialties and disciplines,” according to the statement.
 

Resistance and male egos

Dr. Grand’Maison has been a licensed physician for more than 30 years, and received her MD in 1988 after graduating from Sherbrooke University in Quebec. Over the next few decades she worked in clinical medicine and research, both in Canada and the United States. In 2014, she became certified in medical oncology and then secured a clinical and research fellowship focusing on sarcoma at MD Anderson.

Two years later, after completing her fellowship, she accepted a full-time position as an assistant professor of oncology in the department of medical oncology’s sarcoma division at Roswell Park. She became the first medical oncologist with a subspecialty in sarcoma, and also brought with her the advanced techniques and aggressive treatment that had been pioneered by MD Anderson, and which had never been used at Roswell Park, according to the complaint.

However, Dr. Grand’Maison said that she began to encounter some resistance from those more familiar with Roswell’s previous standard operating procedures. For example, her practice of seeing patients on days when chemotherapy was administered was viewed by some of the advanced practice clinicians as a lack of confidence in their abilities.

According to the complaint, Dr. Grand’Maison found the sarcoma tumor board at Roswell to be “male-dominated, ego-driven, fraught with defensiveness, and rife with a lack of collegiality almost from the very beginning,” which was very different from her experience at MD Anderson.

Less than 6 months after joining Roswell, she said that Dr. Morrison began treating her in a condescending manner at the tumor board meetings when she asked him questions pertaining to a diagnosis. She viewed his “physically intimidating and aggressive conduct toward her as sexist, and it was a pattern of conduct that would persist in the years that followed.” Dr. Grand’Maison observed that Dr. Morrison never behaved that way toward the men when discussing a case.

Over time, Dr. Grand’Maison made numerous and near endless efforts to raise her concerns about patient safety and gender discrimination at Roswell Park and had reached out to her supervisor and to others in upper management, the complaint alleges. All of this appeared to fall on completely deaf ears as hospital “politics” and doctor egos took precedence. Dr. Morrison continued to try to intimidate her into “silence” and block her attempts to refine diagnoses to ensure proper treatment, and several other senior physicians enabled his behavior and ignored the risk it posed to patient safety, the complaint alleges.  

“While she raised complaints about gender discrimination, the crux of her complaint was patient safety,” Mr. Gottlieb emphasized.

Another issue was that Dr. Grand’Maison never received the proper clinical support she repeatedly requested and that was urgently needed. Thus, her patients faced other elevated safety risks as a result of the underresourced sarcoma clinic, she said.
 

Fired or resigned?

Dr. Grand’Maison left Roswell Park Cancer center last May, and has not worked since.

Although Dr. Grand’Maison stated that she was fired in retaliation for raising serious concerns, Roswell Park insists that she voluntarily resigned. Dr. Grand’Maison acknowledged that she wrote an email in January 2022 to the clinical practice plan coordinator in which she mentioned that her husband was planning to relocate back to Canada and that her last date at Roswell Park would be May 1, 2022. The coordinator never responded to that email. In the interim, her husband, also a physician with privileges at Roswell Park, made it known that he was not moving to Canada.

Dr. Grand’Maison said that, as she had not resigned, and everyone knew her husband wasn’t moving, she did not follow up on that January 2022 email, and then forgot about it.

“That email was used as the basis to force her out,”said her lawyer, Mr. Gottlieb. “The day after she put together a summary and extensively documented serious patient safety concerns, she got an email that her resignation had been accepted.”

None of the standard protocols for resignation had been completed, either by human resources or by her supervisors, Mr. Gottlieb contended. “The law says that they can’t take adverse action against her for filing a complaint, so they fired her under the guise of a resignation,” he said.

Roswell Park refused to rescind Dr. Grand’Maison’s resignation, despite multiple attempts on her part. She even contacted the CEO and stated that her January 2022 email was being used a pretext to push her out in retaliation, but she received no response, only that the matter had been referred to someone else.

“I am speaking out because time and again female doctors are unable to deliver on the promise of their medical training because of discrimination,” said Dr. Grand’Maison. “Roswell dismissed my expertise and diminished my value. While I worry that coming forward may affect my career, I am taking that risk to make the path easier for the women who will come behind me.”

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

For patients with locally advanced head and neck squamous cell carcinoma who cannot tolerate platinum chemotherapy, docetaxel is a sound alternative to enhance sensitivity to radiotherapy, say researchers reporting a phase 3 trial from India.

“This is the first randomized study demonstrating the benefit of an alternate radiosensitizing agent in cisplatin-ineligible patients,” they wrote.

“We found that the use of docetaxel as a radiosensitizer in cisplatin-ineligible patients,” compared with the use of radiation alone, “led to an improvement in disease-free survival, locoregional control, and overall survival without affecting the quality of life of the patients,” the team reported.

The investigators, led by Vijay Maruti Patil, MD, DM, a medical oncologist at Tata Memorial Hospital, Mumbai, noted that they stopped the trial early after the benefit from adding docetaxel became clear.

Cisplatin is the general standard of care to sensitize locally advanced head and neck tumors to radiation treatment, but up to a third of patients are ineligible because of age, diminished kidney function, hearing loss, and other problems, they wrote.

Many alternatives to cisplatin are used in such settings, but until now, there hasn’t been any level 1, phase 3 evidence to guide the selection.

Cetuximab is the alternative used most often in the United States, but evidence supporting it was generated in trials involving cisplatin-eligible patients, the investigators pointed out. There is also a high incidence of skin and other toxicities and, in some studies, nonideal survival outcomes, they noted.

The new study was published online in the Journal of Clinical Oncology.

It “demonstrates what could be presumed but was not known to be true in the cisplatin-ineligible context: Radiosensitizers improve outcomes over radiotherapy alone,” commented the authors of an accompanying editorial (J Clin Oncol. 2023 Feb 1. doi: 10.1200/JCO.22.02350).

“Docetaxel belongs in the armamentarium of go-to regimens,” wrote radiation oncologist Loren Mell, MD, of the University of California, San Diego, and medical oncologist Stuart Wong, MD, of the Medical College of Wisconsin, Milwaukee.

This study “fills an important gap in the head and neck cancer literature, but “since [docetaxel] was not compared head-to-head against” other radiosensitizing alternatives, it “should not be declared the lone standard. ... It is high time to shift the conversation from whether radiosensitizers are beneficial to which regimen (if any) provides the most benefit and should define the standard of care,” they added.

The trial randomly assigned 356 cisplatin-ineligible adults equally to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The investigators planned to enroll 600 patients but stopped the trial early when the survival benefit with docetaxel became clear.

The addition of docetaxel improved 2-year disease-free survival (42% vs. 30.3%; hazard ratio, 0.673; P = .002); 2-year overall survival (50.8% vs. 41.7%; HR, 0.747; P = .035), and the 2-year locoregional failure rate (41.8% vs. 54.7%; HR, 0.661; P = .002).

Median overall survival was 25.5 months with docetaxel versus 15.3 months with radiation alone (P = .035).

Docetaxel’s benefits were most pronounced in patients with hypopharyngeal primary sites and among the 61% of patients treated definitively. There was “possibly” a benefit in the adjuvant setting, but “further study would be required to show definitive applicability,” the investigators said.

There was a higher incidence of grade 3 or greater mucositis (49.7% vs. 22.2%), odynophagia (52.5% vs. 33.5%), and dysphagia (33%), but the “complications were manageable and did not affect the compliance” with either radiation or docetaxel, the team reported. Overall, 86% of patients received five or more cycles docetaxel.

In their editorial, Dr. Mell and Dr. Wong noted that the “majority of patients did not receive intensity-modulated radiotherapy, the standard in higher-income countries,” but added that “we do not expect the use of conventional radiotherapy would reduce the effectiveness of docetaxel.”

The trial was funded by Tata Memorial Hospital, where it was conducted. Several investigators had industry ties, including Dr. Patil, who reported research funding from Johnson & Johnson/Janssen, AstraZeneca, Intas, NATCO Pharma, Eisai Germany, and Novartis. Dr. Mell is an advisor for Cel-Sci and reported research funding from Merck and AstraZeneca. Dr. Wong disclosed research funding from Novartis and Merck.

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

For patients with locally advanced head and neck squamous cell carcinoma who cannot tolerate platinum chemotherapy, docetaxel is a sound alternative to enhance sensitivity to radiotherapy, say researchers reporting a phase 3 trial from India.

“This is the first randomized study demonstrating the benefit of an alternate radiosensitizing agent in cisplatin-ineligible patients,” they wrote.

“We found that the use of docetaxel as a radiosensitizer in cisplatin-ineligible patients,” compared with the use of radiation alone, “led to an improvement in disease-free survival, locoregional control, and overall survival without affecting the quality of life of the patients,” the team reported.

The investigators, led by Vijay Maruti Patil, MD, DM, a medical oncologist at Tata Memorial Hospital, Mumbai, noted that they stopped the trial early after the benefit from adding docetaxel became clear.

Cisplatin is the general standard of care to sensitize locally advanced head and neck tumors to radiation treatment, but up to a third of patients are ineligible because of age, diminished kidney function, hearing loss, and other problems, they wrote.

Many alternatives to cisplatin are used in such settings, but until now, there hasn’t been any level 1, phase 3 evidence to guide the selection.

Cetuximab is the alternative used most often in the United States, but evidence supporting it was generated in trials involving cisplatin-eligible patients, the investigators pointed out. There is also a high incidence of skin and other toxicities and, in some studies, nonideal survival outcomes, they noted.

The new study was published online in the Journal of Clinical Oncology.

It “demonstrates what could be presumed but was not known to be true in the cisplatin-ineligible context: Radiosensitizers improve outcomes over radiotherapy alone,” commented the authors of an accompanying editorial (J Clin Oncol. 2023 Feb 1. doi: 10.1200/JCO.22.02350).

“Docetaxel belongs in the armamentarium of go-to regimens,” wrote radiation oncologist Loren Mell, MD, of the University of California, San Diego, and medical oncologist Stuart Wong, MD, of the Medical College of Wisconsin, Milwaukee.

This study “fills an important gap in the head and neck cancer literature, but “since [docetaxel] was not compared head-to-head against” other radiosensitizing alternatives, it “should not be declared the lone standard. ... It is high time to shift the conversation from whether radiosensitizers are beneficial to which regimen (if any) provides the most benefit and should define the standard of care,” they added.

The trial randomly assigned 356 cisplatin-ineligible adults equally to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The investigators planned to enroll 600 patients but stopped the trial early when the survival benefit with docetaxel became clear.

The addition of docetaxel improved 2-year disease-free survival (42% vs. 30.3%; hazard ratio, 0.673; P = .002); 2-year overall survival (50.8% vs. 41.7%; HR, 0.747; P = .035), and the 2-year locoregional failure rate (41.8% vs. 54.7%; HR, 0.661; P = .002).

Median overall survival was 25.5 months with docetaxel versus 15.3 months with radiation alone (P = .035).

Docetaxel’s benefits were most pronounced in patients with hypopharyngeal primary sites and among the 61% of patients treated definitively. There was “possibly” a benefit in the adjuvant setting, but “further study would be required to show definitive applicability,” the investigators said.

There was a higher incidence of grade 3 or greater mucositis (49.7% vs. 22.2%), odynophagia (52.5% vs. 33.5%), and dysphagia (33%), but the “complications were manageable and did not affect the compliance” with either radiation or docetaxel, the team reported. Overall, 86% of patients received five or more cycles docetaxel.

In their editorial, Dr. Mell and Dr. Wong noted that the “majority of patients did not receive intensity-modulated radiotherapy, the standard in higher-income countries,” but added that “we do not expect the use of conventional radiotherapy would reduce the effectiveness of docetaxel.”

The trial was funded by Tata Memorial Hospital, where it was conducted. Several investigators had industry ties, including Dr. Patil, who reported research funding from Johnson & Johnson/Janssen, AstraZeneca, Intas, NATCO Pharma, Eisai Germany, and Novartis. Dr. Mell is an advisor for Cel-Sci and reported research funding from Merck and AstraZeneca. Dr. Wong disclosed research funding from Novartis and Merck.

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

For patients with locally advanced head and neck squamous cell carcinoma who cannot tolerate platinum chemotherapy, docetaxel is a sound alternative to enhance sensitivity to radiotherapy, say researchers reporting a phase 3 trial from India.

“This is the first randomized study demonstrating the benefit of an alternate radiosensitizing agent in cisplatin-ineligible patients,” they wrote.

“We found that the use of docetaxel as a radiosensitizer in cisplatin-ineligible patients,” compared with the use of radiation alone, “led to an improvement in disease-free survival, locoregional control, and overall survival without affecting the quality of life of the patients,” the team reported.

The investigators, led by Vijay Maruti Patil, MD, DM, a medical oncologist at Tata Memorial Hospital, Mumbai, noted that they stopped the trial early after the benefit from adding docetaxel became clear.

Cisplatin is the general standard of care to sensitize locally advanced head and neck tumors to radiation treatment, but up to a third of patients are ineligible because of age, diminished kidney function, hearing loss, and other problems, they wrote.

Many alternatives to cisplatin are used in such settings, but until now, there hasn’t been any level 1, phase 3 evidence to guide the selection.

Cetuximab is the alternative used most often in the United States, but evidence supporting it was generated in trials involving cisplatin-eligible patients, the investigators pointed out. There is also a high incidence of skin and other toxicities and, in some studies, nonideal survival outcomes, they noted.

The new study was published online in the Journal of Clinical Oncology.

It “demonstrates what could be presumed but was not known to be true in the cisplatin-ineligible context: Radiosensitizers improve outcomes over radiotherapy alone,” commented the authors of an accompanying editorial (J Clin Oncol. 2023 Feb 1. doi: 10.1200/JCO.22.02350).

“Docetaxel belongs in the armamentarium of go-to regimens,” wrote radiation oncologist Loren Mell, MD, of the University of California, San Diego, and medical oncologist Stuart Wong, MD, of the Medical College of Wisconsin, Milwaukee.

This study “fills an important gap in the head and neck cancer literature, but “since [docetaxel] was not compared head-to-head against” other radiosensitizing alternatives, it “should not be declared the lone standard. ... It is high time to shift the conversation from whether radiosensitizers are beneficial to which regimen (if any) provides the most benefit and should define the standard of care,” they added.

The trial randomly assigned 356 cisplatin-ineligible adults equally to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The investigators planned to enroll 600 patients but stopped the trial early when the survival benefit with docetaxel became clear.

The addition of docetaxel improved 2-year disease-free survival (42% vs. 30.3%; hazard ratio, 0.673; P = .002); 2-year overall survival (50.8% vs. 41.7%; HR, 0.747; P = .035), and the 2-year locoregional failure rate (41.8% vs. 54.7%; HR, 0.661; P = .002).

Median overall survival was 25.5 months with docetaxel versus 15.3 months with radiation alone (P = .035).

Docetaxel’s benefits were most pronounced in patients with hypopharyngeal primary sites and among the 61% of patients treated definitively. There was “possibly” a benefit in the adjuvant setting, but “further study would be required to show definitive applicability,” the investigators said.

There was a higher incidence of grade 3 or greater mucositis (49.7% vs. 22.2%), odynophagia (52.5% vs. 33.5%), and dysphagia (33%), but the “complications were manageable and did not affect the compliance” with either radiation or docetaxel, the team reported. Overall, 86% of patients received five or more cycles docetaxel.

In their editorial, Dr. Mell and Dr. Wong noted that the “majority of patients did not receive intensity-modulated radiotherapy, the standard in higher-income countries,” but added that “we do not expect the use of conventional radiotherapy would reduce the effectiveness of docetaxel.”

The trial was funded by Tata Memorial Hospital, where it was conducted. Several investigators had industry ties, including Dr. Patil, who reported research funding from Johnson & Johnson/Janssen, AstraZeneca, Intas, NATCO Pharma, Eisai Germany, and Novartis. Dr. Mell is an advisor for Cel-Sci and reported research funding from Merck and AstraZeneca. Dr. Wong disclosed research funding from Novartis and Merck.

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

Caring for a child with autism is a long haul for families and not often a smooth ride. Medications can help improve child functioning and family quality of life but the evidence may require our careful consideration.

Although I am discussing medication treatment here, the best evidence-based treatments for autism symptoms such as poor social communication and repetitive restricted behavior (RRB) are behavioral (for example, applied behavior analysis), cognitive-behavioral therapy (CBT), and parent training. These modalities also augment the effectiveness of medications in many cases. Educational adjustments and specific therapies, when indicated, such as speech-language, occupational, and physical therapy are also beneficial.

Autism symptoms change with age from early regression, later to RRB, then depression, and they are complicated by coexisting conditions. Not surprisingly then, studying the effectiveness and side effects of medications is complex and guidance is in flux as reliable data emerge.

Because of the shortage of specialists and increasing prevalence of autism, we need to be prepared to manage, monitor, and sometimes start medications for our autistic patients. With great individual differences and the hopes and fears of distressed parents making them desperate for help, we need to be as evidence-based as possible to avoid serious side effects or delay effective behavioral treatments.

Our assistance is mainly to address the many co-occurring symptoms in autism: 37%-85% ADHD, 50% anxiety, 7.3% bipolar disorder, and 54.1% depression (by age 30). Many autistic children have problematic irritability, explosive episodes, repetitive or rigid routines, difficulty with social engagement, or trouble sleeping.

We need to be clear with families about the evidence and, whenever possible, use our own time-limited trials with placebos and objective measures that target symptoms and goals for improvement. This is complicated by that fact that the child may have trouble communicating about how they feel, have hypo- or hypersensitivity to feelings, as well as confounding coexisting conditions.

The Food and Drug Administration has approved the atypical antipsychotics risperidone (ages 5-16) and aripiprazole (ages 6-17) for reducing symptoms of irritability by 25%-50% – such as agitation, stereotypy, anger outbursts, self-injurious behavior, and hyperactivity within 8 weeks. The Aberrant Behavior Checklist can be used for monitoring. These benefits are largest with behavior therapy and at doses of 1.25-1.75  mg/day (risperidone) or 2-15 mg/day (aripiprazole). Unfortunately, side effects of these medications include somnolence, increased appetite and weight gain (average of 5.1 kg), abnormal blood lipids and glucose, dyskinesia, and elevated prolactin (sometimes galactorrhea). Aripiprazole is equivalent to risperidone for irritability, has less prolactin and fewer metabolic effects, but sometimes has extrapyramidal symptoms. Other second-generation atypical antipsychotics have less evidence but may have fewer side effects. With careful monitoring, these medications can make a major difference in child behavior.

ADHD symptoms often respond to methylphenidate within 4 weeks but at a lower dose and with more side effects of irritability, social withdrawal, and emotional outbursts than for children with ADHD without autism. Formulations such as liquid (short or long acting) or dermal patch may facilitate the important small-dose adjustments and slow ramp-up we should use with checklist monitoring (for example, Vanderbilt Assessment). Atomoxetine also reduces hyperactivity, especially when used with parent training, but has associated nausea, anorexia, early awakening, and rare unpredictable liver failure. Mixed amphetamine salts have not been studied. Clonidine (oral or patch) and guanfacine extended release have also shown some effectiveness for hyperarousal, social interaction, and sleep although they can cause drowsiness/hypotension.

Sleep issues such as sleep onset, duration, and disruptions can improve with melatonin, especially combined with CBT, and it can even sometimes help with anxiety, rigidity, and communication. Use a certified brand and prevent accidental ingestion of gummy forms. Note that obstructive sleep apnea is significantly more common in children with autism spectrum disorder (ASD) and should be evaluated if there are signs. The Childhood Sleep Questionnaire can be used to monitor.

There aren’t data available for selective serotonin reuptake inhibitors in treating depression and anxiety in autistic children but CBT may help. Buspirone improved RRB (at 2.5 mg b.i.d.) but did not help mood. Mood-stabilizing antiepileptics have had mixed results (valproate reduced irritability but with serious side effects), no benefits (lamotrigine and levetiracetam), or no trials (lithium, oxcarbazepine, and topiramate). In spite of this, a Cochrane report recommends antidepressants “on a case by case basis” for children with ASD, keeping in mind the higher risks of behavioral activation (consider comorbid bipolar disorder), irritability, akathisia, and sleep disturbance. We can monitor with Short Moods and Feelings Questionnaire and Problem Behavior Checklist.

NMDA and GABA receptors are implicated in the genesis of ASD. Bumetanide, a GABA modulator, at 1 mg b.i.d., improved social communication and restricted interests, but had dose-related hypokalemia, increased urination, dehydration, loss of appetite, and asthenia. Donepezil (cholinesterase inhibitor) in small studies improved autism scores and expressive/receptive language. N-acetylcysteine, D-cycloserine, and arbaclofen did not show efficacy.

Currently, 64% of children with ASD are prescribed one psychotropic medication, 35% more than two classes, and 15% more than three. While we may look askance at polypharmacy, several medications not effective as monotherapy for children with ASD have significant effects in combination with risperidone; notably memantine, riluzole, N-acetylcysteine, amantadine, topiramate, and buspirone, compared with placebo. Memantine alone has shown benefits in 60% of autistic patients on social, language, and self-stimulatory behaviors at 2.5-30 mg; effective enough that 80% chose continuation.

Families often use complementary or alternative medicines (CAM) so we need to ask about them because CAM may interact with prescribed drugs or complicate determining the source of side effects or benefits. Oxytocin has promising but inconclusive data for improving social cognition but only for 3-8 year olds. Omega-3 fatty acid had benefits for young child stereotypy and lethargy but only by parent report. Vitamin B12, folinic acid, vitamin D3, and digestive enzymes may help but lack data. It is important that families not replace evidence-based treatments with CAM when there are significant symptoms needing treatment.

Being a person with autism, beyond the stress of rigid routines and social difficulties, may include being a target of physical or sexual abuse or bullying, which are risks for suicide. Suicide is eightfold greater in people with autism, especially those who are high functioning; thus, we need to include children with ASD in our routine suicide screening.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

References

Goel R et al. Int Rev Psychiatry. 2018;30(1):78-95.

Stepanova E et al. Dialogues Clin Neurosci. 2017;19(4):395-402.

Caring for a child with autism is a long haul for families and not often a smooth ride. Medications can help improve child functioning and family quality of life but the evidence may require our careful consideration.

Although I am discussing medication treatment here, the best evidence-based treatments for autism symptoms such as poor social communication and repetitive restricted behavior (RRB) are behavioral (for example, applied behavior analysis), cognitive-behavioral therapy (CBT), and parent training. These modalities also augment the effectiveness of medications in many cases. Educational adjustments and specific therapies, when indicated, such as speech-language, occupational, and physical therapy are also beneficial.

Autism symptoms change with age from early regression, later to RRB, then depression, and they are complicated by coexisting conditions. Not surprisingly then, studying the effectiveness and side effects of medications is complex and guidance is in flux as reliable data emerge.

Because of the shortage of specialists and increasing prevalence of autism, we need to be prepared to manage, monitor, and sometimes start medications for our autistic patients. With great individual differences and the hopes and fears of distressed parents making them desperate for help, we need to be as evidence-based as possible to avoid serious side effects or delay effective behavioral treatments.

Our assistance is mainly to address the many co-occurring symptoms in autism: 37%-85% ADHD, 50% anxiety, 7.3% bipolar disorder, and 54.1% depression (by age 30). Many autistic children have problematic irritability, explosive episodes, repetitive or rigid routines, difficulty with social engagement, or trouble sleeping.

We need to be clear with families about the evidence and, whenever possible, use our own time-limited trials with placebos and objective measures that target symptoms and goals for improvement. This is complicated by that fact that the child may have trouble communicating about how they feel, have hypo- or hypersensitivity to feelings, as well as confounding coexisting conditions.

The Food and Drug Administration has approved the atypical antipsychotics risperidone (ages 5-16) and aripiprazole (ages 6-17) for reducing symptoms of irritability by 25%-50% – such as agitation, stereotypy, anger outbursts, self-injurious behavior, and hyperactivity within 8 weeks. The Aberrant Behavior Checklist can be used for monitoring. These benefits are largest with behavior therapy and at doses of 1.25-1.75  mg/day (risperidone) or 2-15 mg/day (aripiprazole). Unfortunately, side effects of these medications include somnolence, increased appetite and weight gain (average of 5.1 kg), abnormal blood lipids and glucose, dyskinesia, and elevated prolactin (sometimes galactorrhea). Aripiprazole is equivalent to risperidone for irritability, has less prolactin and fewer metabolic effects, but sometimes has extrapyramidal symptoms. Other second-generation atypical antipsychotics have less evidence but may have fewer side effects. With careful monitoring, these medications can make a major difference in child behavior.

ADHD symptoms often respond to methylphenidate within 4 weeks but at a lower dose and with more side effects of irritability, social withdrawal, and emotional outbursts than for children with ADHD without autism. Formulations such as liquid (short or long acting) or dermal patch may facilitate the important small-dose adjustments and slow ramp-up we should use with checklist monitoring (for example, Vanderbilt Assessment). Atomoxetine also reduces hyperactivity, especially when used with parent training, but has associated nausea, anorexia, early awakening, and rare unpredictable liver failure. Mixed amphetamine salts have not been studied. Clonidine (oral or patch) and guanfacine extended release have also shown some effectiveness for hyperarousal, social interaction, and sleep although they can cause drowsiness/hypotension.

Sleep issues such as sleep onset, duration, and disruptions can improve with melatonin, especially combined with CBT, and it can even sometimes help with anxiety, rigidity, and communication. Use a certified brand and prevent accidental ingestion of gummy forms. Note that obstructive sleep apnea is significantly more common in children with autism spectrum disorder (ASD) and should be evaluated if there are signs. The Childhood Sleep Questionnaire can be used to monitor.

There aren’t data available for selective serotonin reuptake inhibitors in treating depression and anxiety in autistic children but CBT may help. Buspirone improved RRB (at 2.5 mg b.i.d.) but did not help mood. Mood-stabilizing antiepileptics have had mixed results (valproate reduced irritability but with serious side effects), no benefits (lamotrigine and levetiracetam), or no trials (lithium, oxcarbazepine, and topiramate). In spite of this, a Cochrane report recommends antidepressants “on a case by case basis” for children with ASD, keeping in mind the higher risks of behavioral activation (consider comorbid bipolar disorder), irritability, akathisia, and sleep disturbance. We can monitor with Short Moods and Feelings Questionnaire and Problem Behavior Checklist.

NMDA and GABA receptors are implicated in the genesis of ASD. Bumetanide, a GABA modulator, at 1 mg b.i.d., improved social communication and restricted interests, but had dose-related hypokalemia, increased urination, dehydration, loss of appetite, and asthenia. Donepezil (cholinesterase inhibitor) in small studies improved autism scores and expressive/receptive language. N-acetylcysteine, D-cycloserine, and arbaclofen did not show efficacy.

Currently, 64% of children with ASD are prescribed one psychotropic medication, 35% more than two classes, and 15% more than three. While we may look askance at polypharmacy, several medications not effective as monotherapy for children with ASD have significant effects in combination with risperidone; notably memantine, riluzole, N-acetylcysteine, amantadine, topiramate, and buspirone, compared with placebo. Memantine alone has shown benefits in 60% of autistic patients on social, language, and self-stimulatory behaviors at 2.5-30 mg; effective enough that 80% chose continuation.

Families often use complementary or alternative medicines (CAM) so we need to ask about them because CAM may interact with prescribed drugs or complicate determining the source of side effects or benefits. Oxytocin has promising but inconclusive data for improving social cognition but only for 3-8 year olds. Omega-3 fatty acid had benefits for young child stereotypy and lethargy but only by parent report. Vitamin B12, folinic acid, vitamin D3, and digestive enzymes may help but lack data. It is important that families not replace evidence-based treatments with CAM when there are significant symptoms needing treatment.

Being a person with autism, beyond the stress of rigid routines and social difficulties, may include being a target of physical or sexual abuse or bullying, which are risks for suicide. Suicide is eightfold greater in people with autism, especially those who are high functioning; thus, we need to include children with ASD in our routine suicide screening.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

References

Goel R et al. Int Rev Psychiatry. 2018;30(1):78-95.

Stepanova E et al. Dialogues Clin Neurosci. 2017;19(4):395-402.

Caring for a child with autism is a long haul for families and not often a smooth ride. Medications can help improve child functioning and family quality of life but the evidence may require our careful consideration.

Although I am discussing medication treatment here, the best evidence-based treatments for autism symptoms such as poor social communication and repetitive restricted behavior (RRB) are behavioral (for example, applied behavior analysis), cognitive-behavioral therapy (CBT), and parent training. These modalities also augment the effectiveness of medications in many cases. Educational adjustments and specific therapies, when indicated, such as speech-language, occupational, and physical therapy are also beneficial.

Autism symptoms change with age from early regression, later to RRB, then depression, and they are complicated by coexisting conditions. Not surprisingly then, studying the effectiveness and side effects of medications is complex and guidance is in flux as reliable data emerge.

Because of the shortage of specialists and increasing prevalence of autism, we need to be prepared to manage, monitor, and sometimes start medications for our autistic patients. With great individual differences and the hopes and fears of distressed parents making them desperate for help, we need to be as evidence-based as possible to avoid serious side effects or delay effective behavioral treatments.

Our assistance is mainly to address the many co-occurring symptoms in autism: 37%-85% ADHD, 50% anxiety, 7.3% bipolar disorder, and 54.1% depression (by age 30). Many autistic children have problematic irritability, explosive episodes, repetitive or rigid routines, difficulty with social engagement, or trouble sleeping.

We need to be clear with families about the evidence and, whenever possible, use our own time-limited trials with placebos and objective measures that target symptoms and goals for improvement. This is complicated by that fact that the child may have trouble communicating about how they feel, have hypo- or hypersensitivity to feelings, as well as confounding coexisting conditions.

The Food and Drug Administration has approved the atypical antipsychotics risperidone (ages 5-16) and aripiprazole (ages 6-17) for reducing symptoms of irritability by 25%-50% – such as agitation, stereotypy, anger outbursts, self-injurious behavior, and hyperactivity within 8 weeks. The Aberrant Behavior Checklist can be used for monitoring. These benefits are largest with behavior therapy and at doses of 1.25-1.75  mg/day (risperidone) or 2-15 mg/day (aripiprazole). Unfortunately, side effects of these medications include somnolence, increased appetite and weight gain (average of 5.1 kg), abnormal blood lipids and glucose, dyskinesia, and elevated prolactin (sometimes galactorrhea). Aripiprazole is equivalent to risperidone for irritability, has less prolactin and fewer metabolic effects, but sometimes has extrapyramidal symptoms. Other second-generation atypical antipsychotics have less evidence but may have fewer side effects. With careful monitoring, these medications can make a major difference in child behavior.

ADHD symptoms often respond to methylphenidate within 4 weeks but at a lower dose and with more side effects of irritability, social withdrawal, and emotional outbursts than for children with ADHD without autism. Formulations such as liquid (short or long acting) or dermal patch may facilitate the important small-dose adjustments and slow ramp-up we should use with checklist monitoring (for example, Vanderbilt Assessment). Atomoxetine also reduces hyperactivity, especially when used with parent training, but has associated nausea, anorexia, early awakening, and rare unpredictable liver failure. Mixed amphetamine salts have not been studied. Clonidine (oral or patch) and guanfacine extended release have also shown some effectiveness for hyperarousal, social interaction, and sleep although they can cause drowsiness/hypotension.

Sleep issues such as sleep onset, duration, and disruptions can improve with melatonin, especially combined with CBT, and it can even sometimes help with anxiety, rigidity, and communication. Use a certified brand and prevent accidental ingestion of gummy forms. Note that obstructive sleep apnea is significantly more common in children with autism spectrum disorder (ASD) and should be evaluated if there are signs. The Childhood Sleep Questionnaire can be used to monitor.

There aren’t data available for selective serotonin reuptake inhibitors in treating depression and anxiety in autistic children but CBT may help. Buspirone improved RRB (at 2.5 mg b.i.d.) but did not help mood. Mood-stabilizing antiepileptics have had mixed results (valproate reduced irritability but with serious side effects), no benefits (lamotrigine and levetiracetam), or no trials (lithium, oxcarbazepine, and topiramate). In spite of this, a Cochrane report recommends antidepressants “on a case by case basis” for children with ASD, keeping in mind the higher risks of behavioral activation (consider comorbid bipolar disorder), irritability, akathisia, and sleep disturbance. We can monitor with Short Moods and Feelings Questionnaire and Problem Behavior Checklist.

NMDA and GABA receptors are implicated in the genesis of ASD. Bumetanide, a GABA modulator, at 1 mg b.i.d., improved social communication and restricted interests, but had dose-related hypokalemia, increased urination, dehydration, loss of appetite, and asthenia. Donepezil (cholinesterase inhibitor) in small studies improved autism scores and expressive/receptive language. N-acetylcysteine, D-cycloserine, and arbaclofen did not show efficacy.

Currently, 64% of children with ASD are prescribed one psychotropic medication, 35% more than two classes, and 15% more than three. While we may look askance at polypharmacy, several medications not effective as monotherapy for children with ASD have significant effects in combination with risperidone; notably memantine, riluzole, N-acetylcysteine, amantadine, topiramate, and buspirone, compared with placebo. Memantine alone has shown benefits in 60% of autistic patients on social, language, and self-stimulatory behaviors at 2.5-30 mg; effective enough that 80% chose continuation.

Families often use complementary or alternative medicines (CAM) so we need to ask about them because CAM may interact with prescribed drugs or complicate determining the source of side effects or benefits. Oxytocin has promising but inconclusive data for improving social cognition but only for 3-8 year olds. Omega-3 fatty acid had benefits for young child stereotypy and lethargy but only by parent report. Vitamin B12, folinic acid, vitamin D3, and digestive enzymes may help but lack data. It is important that families not replace evidence-based treatments with CAM when there are significant symptoms needing treatment.

Being a person with autism, beyond the stress of rigid routines and social difficulties, may include being a target of physical or sexual abuse or bullying, which are risks for suicide. Suicide is eightfold greater in people with autism, especially those who are high functioning; thus, we need to include children with ASD in our routine suicide screening.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

References

Goel R et al. Int Rev Psychiatry. 2018;30(1):78-95.

Stepanova E et al. Dialogues Clin Neurosci. 2017;19(4):395-402.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• A few key factors predict when gallbladder cancer will be found on routine cholecystectomy, allowing for better surgical planning and treatment.

Why this matters

• More than 60% of gallbladder cancers are diagnosed incidentally following cholecystectomy for benign reasons.
• Identifying predictors allows surgeons to send high-risk individuals for oncologic evaluation beforehand and to prepare for intraoperative frozen pathology and more appropriate surgery, including extended cholecystectomy and lymph node dissection.

Study design

• The investigators analyzed 403,443 cholecystectomies in the American College of Surgeons’ NSQIP database from 2007 to 2017.
• They used multivariable logistic regression to identify risk factors for gallbladder cancers.
• Patients undergoing cholecystectomy for suspected or confirmed gallbladder cancer were excluded.

Key results

• The incidence of gallbladder cancer was 0.11% (441 of 403,443 patients).
• Preoperative factors significantly associated with gallbladder cancer included age older than 60 years (odds ratio [OR], 6.51), female sex (OR, 1.75), weight loss (OR, 2.58), and elevated alkaline phosphatase level (OR, 1.67).
• Starting with or converting to an open approach – both potential indicators of more complex disease – were associated with seven times’ higher odds of gallbladder cancer (OR, 7.33; P < .001), as were longer operative times (127 minutes vs. 70.7 minutes; P < .001).

Limitations

• There is a risk of selection bias regarding which patients were included in the database.
• Presenting symptoms, preoperative imaging findings, and pathologic staging were not available.
• The database did not record the reasons for choosing open surgery rather than laparoscopic surgery or for converting to an open approach.

Disclosures

• There was no funding for the work, and the investigators did not disclose any relevant financial relationships.

This is a summary of a preprint research study, “Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors,” led by Elizabeth Olecki of Penn State University, State College. The study has not been peer reviewed. The full text can be found at researchsquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• A few key factors predict when gallbladder cancer will be found on routine cholecystectomy, allowing for better surgical planning and treatment.

Why this matters

• More than 60% of gallbladder cancers are diagnosed incidentally following cholecystectomy for benign reasons.
• Identifying predictors allows surgeons to send high-risk individuals for oncologic evaluation beforehand and to prepare for intraoperative frozen pathology and more appropriate surgery, including extended cholecystectomy and lymph node dissection.

Study design

• The investigators analyzed 403,443 cholecystectomies in the American College of Surgeons’ NSQIP database from 2007 to 2017.
• They used multivariable logistic regression to identify risk factors for gallbladder cancers.
• Patients undergoing cholecystectomy for suspected or confirmed gallbladder cancer were excluded.

Key results

• The incidence of gallbladder cancer was 0.11% (441 of 403,443 patients).
• Preoperative factors significantly associated with gallbladder cancer included age older than 60 years (odds ratio [OR], 6.51), female sex (OR, 1.75), weight loss (OR, 2.58), and elevated alkaline phosphatase level (OR, 1.67).
• Starting with or converting to an open approach – both potential indicators of more complex disease – were associated with seven times’ higher odds of gallbladder cancer (OR, 7.33; P < .001), as were longer operative times (127 minutes vs. 70.7 minutes; P < .001).

Limitations

• There is a risk of selection bias regarding which patients were included in the database.
• Presenting symptoms, preoperative imaging findings, and pathologic staging were not available.
• The database did not record the reasons for choosing open surgery rather than laparoscopic surgery or for converting to an open approach.

Disclosures

• There was no funding for the work, and the investigators did not disclose any relevant financial relationships.

This is a summary of a preprint research study, “Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors,” led by Elizabeth Olecki of Penn State University, State College. The study has not been peer reviewed. The full text can be found at researchsquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• A few key factors predict when gallbladder cancer will be found on routine cholecystectomy, allowing for better surgical planning and treatment.

Why this matters

• More than 60% of gallbladder cancers are diagnosed incidentally following cholecystectomy for benign reasons.
• Identifying predictors allows surgeons to send high-risk individuals for oncologic evaluation beforehand and to prepare for intraoperative frozen pathology and more appropriate surgery, including extended cholecystectomy and lymph node dissection.

Study design

• The investigators analyzed 403,443 cholecystectomies in the American College of Surgeons’ NSQIP database from 2007 to 2017.
• They used multivariable logistic regression to identify risk factors for gallbladder cancers.
• Patients undergoing cholecystectomy for suspected or confirmed gallbladder cancer were excluded.

Key results

• The incidence of gallbladder cancer was 0.11% (441 of 403,443 patients).
• Preoperative factors significantly associated with gallbladder cancer included age older than 60 years (odds ratio [OR], 6.51), female sex (OR, 1.75), weight loss (OR, 2.58), and elevated alkaline phosphatase level (OR, 1.67).
• Starting with or converting to an open approach – both potential indicators of more complex disease – were associated with seven times’ higher odds of gallbladder cancer (OR, 7.33; P < .001), as were longer operative times (127 minutes vs. 70.7 minutes; P < .001).

Limitations

• There is a risk of selection bias regarding which patients were included in the database.
• Presenting symptoms, preoperative imaging findings, and pathologic staging were not available.
• The database did not record the reasons for choosing open surgery rather than laparoscopic surgery or for converting to an open approach.

Disclosures

• There was no funding for the work, and the investigators did not disclose any relevant financial relationships.

This is a summary of a preprint research study, “Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors,” led by Elizabeth Olecki of Penn State University, State College. The study has not been peer reviewed. The full text can be found at researchsquare.com. A version of this article first appeared on Medscape.com.

The increased risk for diabetes following COVID-19 infection has persisted into the Omicron era, but vaccination against SARS-CoV-2 appears to diminish that likelihood, new data suggest.

The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.

Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.

However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.

“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.

“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.

Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”

The findings were published online in JAMA Network Open.

Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.

Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.

The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).

Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).

The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).

However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.

There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.

Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”

He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”

This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.

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

The increased risk for diabetes following COVID-19 infection has persisted into the Omicron era, but vaccination against SARS-CoV-2 appears to diminish that likelihood, new data suggest.

The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.

Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.

However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.

“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.

“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.

Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”

The findings were published online in JAMA Network Open.

Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.

Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.

The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).

Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).

The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).

However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.

There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.

Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”

He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”

This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.

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

The increased risk for diabetes following COVID-19 infection has persisted into the Omicron era, but vaccination against SARS-CoV-2 appears to diminish that likelihood, new data suggest.

The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.

Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.

However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.

“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.

“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.

Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”

The findings were published online in JAMA Network Open.

Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.

Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.

The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).

Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).

The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).

However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.

There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.

Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”

He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”

This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.

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