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Minimally invasive vs. open surgery in pancreatic cancer
, suggest results from the international DIPLOMA study.
In the trial, around 260 patients were randomly assigned to undergo either open surgery or minimally invasive laparoscopic or robot-assisted surgery. Rates of complete tumor removal were comparable between the groups.
In addition, the disease-free and overall survival rates at 3 years were nearly identical.
“For pancreatic cancer, we have proven for the first time that minimally invasive distal pancreatectomy is as good as open surgery,” commented principal investigator Mohammad Abu Hilal, MD, PhD, surgical director at the Instituto Ospedaliero Fondazione Poliambulanza in Brescia, Italy.
“Our research provides reassurance for surgeons and can help patients by giving them the information they need to have a conversation with their doctor about how they want to be treated,” he added.
Dr. Hilal was speaking at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented (abstract 4163) on June 5.
The study was not able to show that there was a benefit in terms of shorter hospital stays or greater functional recovery with the minimally invasive approach, Dr. Hilal noted, but he suggested that this could be because of differences in postoperative procedures between the participating centers.
He said in an interview that minimally invasive surgery is becoming “very common all over the world,” particularly in the United States, and that randomized controlled trials are “always the last step” in convincing people to use the technique.
He also emphasized that the “best results are obtained in high-volume centers where surgeons do more than at least 50 pancreatic resections a year,” because the minimally invasive approach is “quite complex and difficult,” more so than open surgery.
“This confirmatory study proves that minimally invasive surgical techniques are a safe and effective option for resectable pancreatic cancer,” commented ASCO expert Jennifer F. Tseng, MD, chair of surgery at Boston University and surgeon-in-chief at the Boston Medical Center. It may also “provide benefits like faster recovery time and less infection risk, without increasing cancer risk.”
The results from this trial “will help both surgeons and patients feel comfortable that minimally invasive surgery, in expert hands, is not inferior to open surgery,” she commented in a statement.
Minimally invasive surgery
Only around 12% of patients with pancreatic cancer are diagnosed when the disease is at an early enough stage for surgical resection to be a possibility, Dr. Hilal noted. Minimally invasive pancreatectomy, particularly the distal procedure, was introduced around 25 years ago, but it was initially used only for benign tumors or borderline malignancies.
It took another 10 years before it was considered in cases of confirmed malignancies, “and the main reason for this delay was concerns about the oncological efficiency” of MIDP in terms of its ability to achieve radical resection and an adequate lymph node yield. At the same time, some concerns about minimally invasive surgery for cancer were raised because of results from randomized trials in other cancer types, such as hysterectomy for cervical cancer. Some studies showed worse survival after minimally invasive surgery than after open surgery.
In recent years, use of minimally invasive techniques for pancreatic cancer has become an increasingly “hot topic in many surgical forums,” Dr. Hilal said.
So his team set out to investigate the approach in a phase 3 noninferiority trial. The investigators focused on patients who had an indication for elective distal pancreatectomy plus splenectomy because of proven or highly suspected pancreatic ductal adenocarcinoma in the pancreatic body or tail.
Patients from 35 centers in 12 countries were recruited between May 2018 and May 2021 and were randomly assigned to undergo either MIDP or open distal pancreatectomy.
Patients, nurses, and pathologists were blinded to the surgical procedure by covering of the abdominal wall.
None of the patients underwent adjuvant or neoadjuvant chemotherapy.
Following the procedure, the patients were followed up at 2 weeks and at 1, 3, 6, and 12 months, and a CT scan was performed at 12 months. A range of assessments was performed at each visit, including quality of life measures.
From 1,146 patients initially screened, 261 patients were included.
A few patients withdrew; 131 patients underwent MIDP, and 127 underwent open surgery and were included in the intention-to-treat analysis. Of those, 129 and 125, respectively, were included in the follow-up analysis.
The results confirmed the noninferiority of MIDP, compared with open surgery, with a rate of R0 radical resection (defined as ≥ 1 mm distance between the tumor and the surgical margin) of 73% vs. 69% (P = .039).
In addition, the lymph node yield was comparable between the two approaches, at an average of 22 nodes for MIDP vs. 23 for open surgery (P = .89), and the time to functional recovery was identical, at 5 days for both (P = .22).
The rate of intraperitoneal recurrence was found to be 41% with MIDP, compared with 38% for patients who underwent open surgery.
Dr. Hilal also showed that the rate of serious adverse events, such as bleeding or organ damage, was similar between the two procedures, at 18% with minimally invasive surgery vs. 22% for the open procedure.
Turning to the survival curves, he noted that it is “very clear” that the two procedures achieved near-identical results, at a hazard ratio of 0.99 (P = .94) for overall survival and 0.97 (P = .88) for disease-free survival when comparing MIDP with open surgery.
The researchers will continue to follow up the patients for 3-5 years and will analyze the lymph nodes retrieved to determine whether removal of the spleen is necessary.
The study was funded by Medtronic and Ethicon. Dr. Hilal has relationships with Ethicon and Medtronic. Dr. Tseng has relationships with Aegerion, Amgen, AstraZeneca, Bristol-Myers Squibb, Cubist, Curadel Surgical Innovations, Daiichi Sankyo/Lilly, GlaxoSmithKline, Intarcia Therapeutics, Merck, MyoKardia, PanTher Therapeutics, Pfizer, Quest Diagnostics, Sanofi, Vertex, and Zeus.
A version of this article first appeared on Medscape.com.
, suggest results from the international DIPLOMA study.
In the trial, around 260 patients were randomly assigned to undergo either open surgery or minimally invasive laparoscopic or robot-assisted surgery. Rates of complete tumor removal were comparable between the groups.
In addition, the disease-free and overall survival rates at 3 years were nearly identical.
“For pancreatic cancer, we have proven for the first time that minimally invasive distal pancreatectomy is as good as open surgery,” commented principal investigator Mohammad Abu Hilal, MD, PhD, surgical director at the Instituto Ospedaliero Fondazione Poliambulanza in Brescia, Italy.
“Our research provides reassurance for surgeons and can help patients by giving them the information they need to have a conversation with their doctor about how they want to be treated,” he added.
Dr. Hilal was speaking at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented (abstract 4163) on June 5.
The study was not able to show that there was a benefit in terms of shorter hospital stays or greater functional recovery with the minimally invasive approach, Dr. Hilal noted, but he suggested that this could be because of differences in postoperative procedures between the participating centers.
He said in an interview that minimally invasive surgery is becoming “very common all over the world,” particularly in the United States, and that randomized controlled trials are “always the last step” in convincing people to use the technique.
He also emphasized that the “best results are obtained in high-volume centers where surgeons do more than at least 50 pancreatic resections a year,” because the minimally invasive approach is “quite complex and difficult,” more so than open surgery.
“This confirmatory study proves that minimally invasive surgical techniques are a safe and effective option for resectable pancreatic cancer,” commented ASCO expert Jennifer F. Tseng, MD, chair of surgery at Boston University and surgeon-in-chief at the Boston Medical Center. It may also “provide benefits like faster recovery time and less infection risk, without increasing cancer risk.”
The results from this trial “will help both surgeons and patients feel comfortable that minimally invasive surgery, in expert hands, is not inferior to open surgery,” she commented in a statement.
Minimally invasive surgery
Only around 12% of patients with pancreatic cancer are diagnosed when the disease is at an early enough stage for surgical resection to be a possibility, Dr. Hilal noted. Minimally invasive pancreatectomy, particularly the distal procedure, was introduced around 25 years ago, but it was initially used only for benign tumors or borderline malignancies.
It took another 10 years before it was considered in cases of confirmed malignancies, “and the main reason for this delay was concerns about the oncological efficiency” of MIDP in terms of its ability to achieve radical resection and an adequate lymph node yield. At the same time, some concerns about minimally invasive surgery for cancer were raised because of results from randomized trials in other cancer types, such as hysterectomy for cervical cancer. Some studies showed worse survival after minimally invasive surgery than after open surgery.
In recent years, use of minimally invasive techniques for pancreatic cancer has become an increasingly “hot topic in many surgical forums,” Dr. Hilal said.
So his team set out to investigate the approach in a phase 3 noninferiority trial. The investigators focused on patients who had an indication for elective distal pancreatectomy plus splenectomy because of proven or highly suspected pancreatic ductal adenocarcinoma in the pancreatic body or tail.
Patients from 35 centers in 12 countries were recruited between May 2018 and May 2021 and were randomly assigned to undergo either MIDP or open distal pancreatectomy.
Patients, nurses, and pathologists were blinded to the surgical procedure by covering of the abdominal wall.
None of the patients underwent adjuvant or neoadjuvant chemotherapy.
Following the procedure, the patients were followed up at 2 weeks and at 1, 3, 6, and 12 months, and a CT scan was performed at 12 months. A range of assessments was performed at each visit, including quality of life measures.
From 1,146 patients initially screened, 261 patients were included.
A few patients withdrew; 131 patients underwent MIDP, and 127 underwent open surgery and were included in the intention-to-treat analysis. Of those, 129 and 125, respectively, were included in the follow-up analysis.
The results confirmed the noninferiority of MIDP, compared with open surgery, with a rate of R0 radical resection (defined as ≥ 1 mm distance between the tumor and the surgical margin) of 73% vs. 69% (P = .039).
In addition, the lymph node yield was comparable between the two approaches, at an average of 22 nodes for MIDP vs. 23 for open surgery (P = .89), and the time to functional recovery was identical, at 5 days for both (P = .22).
The rate of intraperitoneal recurrence was found to be 41% with MIDP, compared with 38% for patients who underwent open surgery.
Dr. Hilal also showed that the rate of serious adverse events, such as bleeding or organ damage, was similar between the two procedures, at 18% with minimally invasive surgery vs. 22% for the open procedure.
Turning to the survival curves, he noted that it is “very clear” that the two procedures achieved near-identical results, at a hazard ratio of 0.99 (P = .94) for overall survival and 0.97 (P = .88) for disease-free survival when comparing MIDP with open surgery.
The researchers will continue to follow up the patients for 3-5 years and will analyze the lymph nodes retrieved to determine whether removal of the spleen is necessary.
The study was funded by Medtronic and Ethicon. Dr. Hilal has relationships with Ethicon and Medtronic. Dr. Tseng has relationships with Aegerion, Amgen, AstraZeneca, Bristol-Myers Squibb, Cubist, Curadel Surgical Innovations, Daiichi Sankyo/Lilly, GlaxoSmithKline, Intarcia Therapeutics, Merck, MyoKardia, PanTher Therapeutics, Pfizer, Quest Diagnostics, Sanofi, Vertex, and Zeus.
A version of this article first appeared on Medscape.com.
, suggest results from the international DIPLOMA study.
In the trial, around 260 patients were randomly assigned to undergo either open surgery or minimally invasive laparoscopic or robot-assisted surgery. Rates of complete tumor removal were comparable between the groups.
In addition, the disease-free and overall survival rates at 3 years were nearly identical.
“For pancreatic cancer, we have proven for the first time that minimally invasive distal pancreatectomy is as good as open surgery,” commented principal investigator Mohammad Abu Hilal, MD, PhD, surgical director at the Instituto Ospedaliero Fondazione Poliambulanza in Brescia, Italy.
“Our research provides reassurance for surgeons and can help patients by giving them the information they need to have a conversation with their doctor about how they want to be treated,” he added.
Dr. Hilal was speaking at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented (abstract 4163) on June 5.
The study was not able to show that there was a benefit in terms of shorter hospital stays or greater functional recovery with the minimally invasive approach, Dr. Hilal noted, but he suggested that this could be because of differences in postoperative procedures between the participating centers.
He said in an interview that minimally invasive surgery is becoming “very common all over the world,” particularly in the United States, and that randomized controlled trials are “always the last step” in convincing people to use the technique.
He also emphasized that the “best results are obtained in high-volume centers where surgeons do more than at least 50 pancreatic resections a year,” because the minimally invasive approach is “quite complex and difficult,” more so than open surgery.
“This confirmatory study proves that minimally invasive surgical techniques are a safe and effective option for resectable pancreatic cancer,” commented ASCO expert Jennifer F. Tseng, MD, chair of surgery at Boston University and surgeon-in-chief at the Boston Medical Center. It may also “provide benefits like faster recovery time and less infection risk, without increasing cancer risk.”
The results from this trial “will help both surgeons and patients feel comfortable that minimally invasive surgery, in expert hands, is not inferior to open surgery,” she commented in a statement.
Minimally invasive surgery
Only around 12% of patients with pancreatic cancer are diagnosed when the disease is at an early enough stage for surgical resection to be a possibility, Dr. Hilal noted. Minimally invasive pancreatectomy, particularly the distal procedure, was introduced around 25 years ago, but it was initially used only for benign tumors or borderline malignancies.
It took another 10 years before it was considered in cases of confirmed malignancies, “and the main reason for this delay was concerns about the oncological efficiency” of MIDP in terms of its ability to achieve radical resection and an adequate lymph node yield. At the same time, some concerns about minimally invasive surgery for cancer were raised because of results from randomized trials in other cancer types, such as hysterectomy for cervical cancer. Some studies showed worse survival after minimally invasive surgery than after open surgery.
In recent years, use of minimally invasive techniques for pancreatic cancer has become an increasingly “hot topic in many surgical forums,” Dr. Hilal said.
So his team set out to investigate the approach in a phase 3 noninferiority trial. The investigators focused on patients who had an indication for elective distal pancreatectomy plus splenectomy because of proven or highly suspected pancreatic ductal adenocarcinoma in the pancreatic body or tail.
Patients from 35 centers in 12 countries were recruited between May 2018 and May 2021 and were randomly assigned to undergo either MIDP or open distal pancreatectomy.
Patients, nurses, and pathologists were blinded to the surgical procedure by covering of the abdominal wall.
None of the patients underwent adjuvant or neoadjuvant chemotherapy.
Following the procedure, the patients were followed up at 2 weeks and at 1, 3, 6, and 12 months, and a CT scan was performed at 12 months. A range of assessments was performed at each visit, including quality of life measures.
From 1,146 patients initially screened, 261 patients were included.
A few patients withdrew; 131 patients underwent MIDP, and 127 underwent open surgery and were included in the intention-to-treat analysis. Of those, 129 and 125, respectively, were included in the follow-up analysis.
The results confirmed the noninferiority of MIDP, compared with open surgery, with a rate of R0 radical resection (defined as ≥ 1 mm distance between the tumor and the surgical margin) of 73% vs. 69% (P = .039).
In addition, the lymph node yield was comparable between the two approaches, at an average of 22 nodes for MIDP vs. 23 for open surgery (P = .89), and the time to functional recovery was identical, at 5 days for both (P = .22).
The rate of intraperitoneal recurrence was found to be 41% with MIDP, compared with 38% for patients who underwent open surgery.
Dr. Hilal also showed that the rate of serious adverse events, such as bleeding or organ damage, was similar between the two procedures, at 18% with minimally invasive surgery vs. 22% for the open procedure.
Turning to the survival curves, he noted that it is “very clear” that the two procedures achieved near-identical results, at a hazard ratio of 0.99 (P = .94) for overall survival and 0.97 (P = .88) for disease-free survival when comparing MIDP with open surgery.
The researchers will continue to follow up the patients for 3-5 years and will analyze the lymph nodes retrieved to determine whether removal of the spleen is necessary.
The study was funded by Medtronic and Ethicon. Dr. Hilal has relationships with Ethicon and Medtronic. Dr. Tseng has relationships with Aegerion, Amgen, AstraZeneca, Bristol-Myers Squibb, Cubist, Curadel Surgical Innovations, Daiichi Sankyo/Lilly, GlaxoSmithKline, Intarcia Therapeutics, Merck, MyoKardia, PanTher Therapeutics, Pfizer, Quest Diagnostics, Sanofi, Vertex, and Zeus.
A version of this article first appeared on Medscape.com.
FROM ASCO 2023
Family placement better for deprived kids than institutions
SAN FRANCISCO – results of a new study suggest.
The study shows that sustained recovery is possible after severe, early-life adversity, study author Kathryn L. Humphreys, PhD, assistant professor, department of psychology and human development, Vanderbilt University, Nashville, Tenn., said in an interview.
“Given the strong evidence from the present study, I hope physicians will play a role in promoting family placements as an alternative to institutional care for children who have been orphaned,” she said.
The findings were presented at the annual meeting of the American Psychiatric Association and were published online in the American Journal of Psychiatry.
Millions of children around the world experience psychosocial deprivation while living in institutions, and many more are neglected in their families of origin. In addition, about 6.7 million children lost a parent or caregiver during the COVID-19 pandemic.
In particular, Romania has a history of institutionalizing children. Through decades of repressive policies from the Romanian dictator Nicolae Ceausescu, child abandonment became a national disaster. Families couldn’t afford to keep their children and were encouraged to turn them over to the state.
The current study was part of the Bucharest Early Intervention Project, initiated in 2001 to examine the impact of high-quality, family-based care on development. It included 136 Romanian children (mean age, about 22 months) who were abandoned at or shortly after birth and were placed in an institution.
Researchers randomly assigned each toddler to 1 of 56 foster families or to continue living in an institution (care as usual). The researchers had to create a foster care network, because such care was extremely limited at the start of the study.
Providing stimulating care
Foster parents in the study received regular support from social workers and U.S.-based psychologists. They were encouraged to “make a commitment to treat the child as if it was their own, providing sensitive, stimulating, and nurturing care, not just in the short term but for their whole life,” said Dr. Humphreys.
Foster care programs in the United States have been criticized for focusing on short-term care, she said. “It’s really just a bed to sleep on, clothes to wear, and food to eat rather than the psychological component we think is really important for child development.”
For the study, the researchers assessed the children across multiple developmental domains at baseline and at ages 30, 42, and 54 months. They conducted additional assessments when the kids were aged 8, 12, and 16-18 years.
The primary outcomes were cognitive functioning (IQ), physical growth (height, weight, head circumference), brain electrical activity (relative electroencephalography power in the alpha frequency band), and symptoms of five types of psychopathology (disinhibited social engagement disorder, reactive attachment disorder, ADHD symptoms, externalizing symptoms, and internalizing symptoms).
From over 7,000 observations analyzed across follow-ups, the investigators found that the intervention had an overall significant effect on cognitive, physical, and neural outcomes when considered collectively across waves (beta, 0.26; 95% confidence interval, 0.07-0.46; P = .012). Compared to children who received care as usual, those in foster homes had significantly higher average IQ scores (P < .001) and physical size (P = .008).
The intervention had an overall beneficial effect in regard to psychopathology. The greatest impact involved a reduction in symptoms of reactive attachment disorder (P < .001).
“There are a few forms of psychopathology that seem to almost entirely occur after severe neglect, including reactive attachment disorder; we think of these as disorders of social relatedness that derive from aberrant or insufficient early caregiving experiences,” said Dr. Humphreys. “Being placed in a family reduced the symptoms of reactive attachment disorder to pretty much nonexistent.”
To a lesser extent, the intervention reduced symptoms of disinhibited social engagement disorder. The foster care group also had significantly fewer internalizing symptoms than did children in the care-as-usual group.
But there was no significant overall effect of the intervention on symptoms of ADHD or externalizing problems.
Positive effects persisted
For the most part, the positive effects of the intervention on children’s functioning persisted during nearly 2 decades of follow-up. The impact of the intervention “can be described as rapidly apparent by age 30 months and sustained through late adolescence,” wrote the authors.
Regarding the impact of age at the time of placement, the study found that, compared with children placed into foster care later, those who entered foster care earlier (younger than 33 months) had significantly higher IQ scores and relative alpha power, but there was no difference in physical growth.
For some outcomes, the benefits of earlier placement were apparent in early childhood but faded by adolescence. But Dr. Humphreys noted all placements were early by most definitions.
The researchers also assessed stability of foster care placements. Children were considered “stable” if they remained with their original foster family; they were considered “disrupted” if they no longer resided with the family.
Here, the study found some “striking results,” said Dr. Humphreys. The effect of placement stability was largest in adolescence, when, overall, those who had remained with their original foster family had better cognitive and physical outcomes and less severe symptoms of psychopathology compared to those who experienced placement disruptions.
As for sex differences, “it’s a mixed bag,” said Dr. Humphreys, although overall, “we didn’t see strong evidence of sex differences” in terms of outcomes.
The investigators were unable to examine trajectories of children’s functioning, which would have provided important information on aspects such as rate of growth and the shape of growth curves. Specific features of the institutional or foster care environment in Bucharest during the study may limit the generalizability of the findings to other settings.
Absolutely unique project
The study examined an “absolutely unique project” and had “very exciting” results that should have “important clinical implications,” commented the American Journal of Psychiatry editor-in-chief Ned Kalin, MD, Hedberg Professor and chair, department of psychiatry, University of Wisconsin–Madison.
The findings are “pretty dramatic,” added Dr. Kalin. “This is probably the study to be thinking about when considering the future of treatment and interventions in children who have suffered from this type of neglect, which is unfortunately extremely common worldwide, including in the U.S.”
In particular, the findings regarding improved psychopathology “bode well for the future,” said Dr. Kalin. “We know these types of problems are risk factors for the later development of depression and anxiety disorders. It will be really interesting to find out, but my guess is these kids will be protected as they mature further.”
The study was supported by the NIH, the John D. and Catherine T. MacArthur Foundation, the Palix Foundation, and the Jacobs Foundation. Dr. Humphreys has received research funding from the Brain and Behavior Research Foundation, the Caplan Foundation, the Jacobs Foundation, the National Science Foundation, the NIH, the Vanderbilt Institute for Clinical and Translational Research, the Vanderbilt Kennedy Center, and Vanderbilt University; she has received honoraria from the Journal of Clinical Child and Adolescent Psychology Future Directions Forum, Learning Grove, the University of Iowa, the University of Texas at Austin, and ZERO TO THREE.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – results of a new study suggest.
The study shows that sustained recovery is possible after severe, early-life adversity, study author Kathryn L. Humphreys, PhD, assistant professor, department of psychology and human development, Vanderbilt University, Nashville, Tenn., said in an interview.
“Given the strong evidence from the present study, I hope physicians will play a role in promoting family placements as an alternative to institutional care for children who have been orphaned,” she said.
The findings were presented at the annual meeting of the American Psychiatric Association and were published online in the American Journal of Psychiatry.
Millions of children around the world experience psychosocial deprivation while living in institutions, and many more are neglected in their families of origin. In addition, about 6.7 million children lost a parent or caregiver during the COVID-19 pandemic.
In particular, Romania has a history of institutionalizing children. Through decades of repressive policies from the Romanian dictator Nicolae Ceausescu, child abandonment became a national disaster. Families couldn’t afford to keep their children and were encouraged to turn them over to the state.
The current study was part of the Bucharest Early Intervention Project, initiated in 2001 to examine the impact of high-quality, family-based care on development. It included 136 Romanian children (mean age, about 22 months) who were abandoned at or shortly after birth and were placed in an institution.
Researchers randomly assigned each toddler to 1 of 56 foster families or to continue living in an institution (care as usual). The researchers had to create a foster care network, because such care was extremely limited at the start of the study.
Providing stimulating care
Foster parents in the study received regular support from social workers and U.S.-based psychologists. They were encouraged to “make a commitment to treat the child as if it was their own, providing sensitive, stimulating, and nurturing care, not just in the short term but for their whole life,” said Dr. Humphreys.
Foster care programs in the United States have been criticized for focusing on short-term care, she said. “It’s really just a bed to sleep on, clothes to wear, and food to eat rather than the psychological component we think is really important for child development.”
For the study, the researchers assessed the children across multiple developmental domains at baseline and at ages 30, 42, and 54 months. They conducted additional assessments when the kids were aged 8, 12, and 16-18 years.
The primary outcomes were cognitive functioning (IQ), physical growth (height, weight, head circumference), brain electrical activity (relative electroencephalography power in the alpha frequency band), and symptoms of five types of psychopathology (disinhibited social engagement disorder, reactive attachment disorder, ADHD symptoms, externalizing symptoms, and internalizing symptoms).
From over 7,000 observations analyzed across follow-ups, the investigators found that the intervention had an overall significant effect on cognitive, physical, and neural outcomes when considered collectively across waves (beta, 0.26; 95% confidence interval, 0.07-0.46; P = .012). Compared to children who received care as usual, those in foster homes had significantly higher average IQ scores (P < .001) and physical size (P = .008).
The intervention had an overall beneficial effect in regard to psychopathology. The greatest impact involved a reduction in symptoms of reactive attachment disorder (P < .001).
“There are a few forms of psychopathology that seem to almost entirely occur after severe neglect, including reactive attachment disorder; we think of these as disorders of social relatedness that derive from aberrant or insufficient early caregiving experiences,” said Dr. Humphreys. “Being placed in a family reduced the symptoms of reactive attachment disorder to pretty much nonexistent.”
To a lesser extent, the intervention reduced symptoms of disinhibited social engagement disorder. The foster care group also had significantly fewer internalizing symptoms than did children in the care-as-usual group.
But there was no significant overall effect of the intervention on symptoms of ADHD or externalizing problems.
Positive effects persisted
For the most part, the positive effects of the intervention on children’s functioning persisted during nearly 2 decades of follow-up. The impact of the intervention “can be described as rapidly apparent by age 30 months and sustained through late adolescence,” wrote the authors.
Regarding the impact of age at the time of placement, the study found that, compared with children placed into foster care later, those who entered foster care earlier (younger than 33 months) had significantly higher IQ scores and relative alpha power, but there was no difference in physical growth.
For some outcomes, the benefits of earlier placement were apparent in early childhood but faded by adolescence. But Dr. Humphreys noted all placements were early by most definitions.
The researchers also assessed stability of foster care placements. Children were considered “stable” if they remained with their original foster family; they were considered “disrupted” if they no longer resided with the family.
Here, the study found some “striking results,” said Dr. Humphreys. The effect of placement stability was largest in adolescence, when, overall, those who had remained with their original foster family had better cognitive and physical outcomes and less severe symptoms of psychopathology compared to those who experienced placement disruptions.
As for sex differences, “it’s a mixed bag,” said Dr. Humphreys, although overall, “we didn’t see strong evidence of sex differences” in terms of outcomes.
The investigators were unable to examine trajectories of children’s functioning, which would have provided important information on aspects such as rate of growth and the shape of growth curves. Specific features of the institutional or foster care environment in Bucharest during the study may limit the generalizability of the findings to other settings.
Absolutely unique project
The study examined an “absolutely unique project” and had “very exciting” results that should have “important clinical implications,” commented the American Journal of Psychiatry editor-in-chief Ned Kalin, MD, Hedberg Professor and chair, department of psychiatry, University of Wisconsin–Madison.
The findings are “pretty dramatic,” added Dr. Kalin. “This is probably the study to be thinking about when considering the future of treatment and interventions in children who have suffered from this type of neglect, which is unfortunately extremely common worldwide, including in the U.S.”
In particular, the findings regarding improved psychopathology “bode well for the future,” said Dr. Kalin. “We know these types of problems are risk factors for the later development of depression and anxiety disorders. It will be really interesting to find out, but my guess is these kids will be protected as they mature further.”
The study was supported by the NIH, the John D. and Catherine T. MacArthur Foundation, the Palix Foundation, and the Jacobs Foundation. Dr. Humphreys has received research funding from the Brain and Behavior Research Foundation, the Caplan Foundation, the Jacobs Foundation, the National Science Foundation, the NIH, the Vanderbilt Institute for Clinical and Translational Research, the Vanderbilt Kennedy Center, and Vanderbilt University; she has received honoraria from the Journal of Clinical Child and Adolescent Psychology Future Directions Forum, Learning Grove, the University of Iowa, the University of Texas at Austin, and ZERO TO THREE.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – results of a new study suggest.
The study shows that sustained recovery is possible after severe, early-life adversity, study author Kathryn L. Humphreys, PhD, assistant professor, department of psychology and human development, Vanderbilt University, Nashville, Tenn., said in an interview.
“Given the strong evidence from the present study, I hope physicians will play a role in promoting family placements as an alternative to institutional care for children who have been orphaned,” she said.
The findings were presented at the annual meeting of the American Psychiatric Association and were published online in the American Journal of Psychiatry.
Millions of children around the world experience psychosocial deprivation while living in institutions, and many more are neglected in their families of origin. In addition, about 6.7 million children lost a parent or caregiver during the COVID-19 pandemic.
In particular, Romania has a history of institutionalizing children. Through decades of repressive policies from the Romanian dictator Nicolae Ceausescu, child abandonment became a national disaster. Families couldn’t afford to keep their children and were encouraged to turn them over to the state.
The current study was part of the Bucharest Early Intervention Project, initiated in 2001 to examine the impact of high-quality, family-based care on development. It included 136 Romanian children (mean age, about 22 months) who were abandoned at or shortly after birth and were placed in an institution.
Researchers randomly assigned each toddler to 1 of 56 foster families or to continue living in an institution (care as usual). The researchers had to create a foster care network, because such care was extremely limited at the start of the study.
Providing stimulating care
Foster parents in the study received regular support from social workers and U.S.-based psychologists. They were encouraged to “make a commitment to treat the child as if it was their own, providing sensitive, stimulating, and nurturing care, not just in the short term but for their whole life,” said Dr. Humphreys.
Foster care programs in the United States have been criticized for focusing on short-term care, she said. “It’s really just a bed to sleep on, clothes to wear, and food to eat rather than the psychological component we think is really important for child development.”
For the study, the researchers assessed the children across multiple developmental domains at baseline and at ages 30, 42, and 54 months. They conducted additional assessments when the kids were aged 8, 12, and 16-18 years.
The primary outcomes were cognitive functioning (IQ), physical growth (height, weight, head circumference), brain electrical activity (relative electroencephalography power in the alpha frequency band), and symptoms of five types of psychopathology (disinhibited social engagement disorder, reactive attachment disorder, ADHD symptoms, externalizing symptoms, and internalizing symptoms).
From over 7,000 observations analyzed across follow-ups, the investigators found that the intervention had an overall significant effect on cognitive, physical, and neural outcomes when considered collectively across waves (beta, 0.26; 95% confidence interval, 0.07-0.46; P = .012). Compared to children who received care as usual, those in foster homes had significantly higher average IQ scores (P < .001) and physical size (P = .008).
The intervention had an overall beneficial effect in regard to psychopathology. The greatest impact involved a reduction in symptoms of reactive attachment disorder (P < .001).
“There are a few forms of psychopathology that seem to almost entirely occur after severe neglect, including reactive attachment disorder; we think of these as disorders of social relatedness that derive from aberrant or insufficient early caregiving experiences,” said Dr. Humphreys. “Being placed in a family reduced the symptoms of reactive attachment disorder to pretty much nonexistent.”
To a lesser extent, the intervention reduced symptoms of disinhibited social engagement disorder. The foster care group also had significantly fewer internalizing symptoms than did children in the care-as-usual group.
But there was no significant overall effect of the intervention on symptoms of ADHD or externalizing problems.
Positive effects persisted
For the most part, the positive effects of the intervention on children’s functioning persisted during nearly 2 decades of follow-up. The impact of the intervention “can be described as rapidly apparent by age 30 months and sustained through late adolescence,” wrote the authors.
Regarding the impact of age at the time of placement, the study found that, compared with children placed into foster care later, those who entered foster care earlier (younger than 33 months) had significantly higher IQ scores and relative alpha power, but there was no difference in physical growth.
For some outcomes, the benefits of earlier placement were apparent in early childhood but faded by adolescence. But Dr. Humphreys noted all placements were early by most definitions.
The researchers also assessed stability of foster care placements. Children were considered “stable” if they remained with their original foster family; they were considered “disrupted” if they no longer resided with the family.
Here, the study found some “striking results,” said Dr. Humphreys. The effect of placement stability was largest in adolescence, when, overall, those who had remained with their original foster family had better cognitive and physical outcomes and less severe symptoms of psychopathology compared to those who experienced placement disruptions.
As for sex differences, “it’s a mixed bag,” said Dr. Humphreys, although overall, “we didn’t see strong evidence of sex differences” in terms of outcomes.
The investigators were unable to examine trajectories of children’s functioning, which would have provided important information on aspects such as rate of growth and the shape of growth curves. Specific features of the institutional or foster care environment in Bucharest during the study may limit the generalizability of the findings to other settings.
Absolutely unique project
The study examined an “absolutely unique project” and had “very exciting” results that should have “important clinical implications,” commented the American Journal of Psychiatry editor-in-chief Ned Kalin, MD, Hedberg Professor and chair, department of psychiatry, University of Wisconsin–Madison.
The findings are “pretty dramatic,” added Dr. Kalin. “This is probably the study to be thinking about when considering the future of treatment and interventions in children who have suffered from this type of neglect, which is unfortunately extremely common worldwide, including in the U.S.”
In particular, the findings regarding improved psychopathology “bode well for the future,” said Dr. Kalin. “We know these types of problems are risk factors for the later development of depression and anxiety disorders. It will be really interesting to find out, but my guess is these kids will be protected as they mature further.”
The study was supported by the NIH, the John D. and Catherine T. MacArthur Foundation, the Palix Foundation, and the Jacobs Foundation. Dr. Humphreys has received research funding from the Brain and Behavior Research Foundation, the Caplan Foundation, the Jacobs Foundation, the National Science Foundation, the NIH, the Vanderbilt Institute for Clinical and Translational Research, the Vanderbilt Kennedy Center, and Vanderbilt University; she has received honoraria from the Journal of Clinical Child and Adolescent Psychology Future Directions Forum, Learning Grove, the University of Iowa, the University of Texas at Austin, and ZERO TO THREE.
A version of this article first appeared on Medscape.com.
AT APA 2023
ECG implant tightens AFib management, improves outcomes in MONITOR-AF
Chronic conditions like diabetes or hypertension “often require long-term care through long-term monitoring,” observed a researcher, and “we know that continuous monitoring is superior to intermittent monitoring for long-term outcomes.”
So maybe practice should rely more on continuous ECG monitoring for patients with atrial fibrillation (AFib), also a chronic condition, proposed Dhanunjaya R. Lakkireddy, MD, of the Kansas City Heart Rhythm Institute, Overland Park, Kan., in presenting a new analysis at the annual scientific sessions of the Heart Rhythm Society.
(ILRs), compared with standard care. The latter could include intermittent 12-lead ECG, Holter, or other intermittent monitoring at physicians’ discretion.
Patients with AFib and the ECG implants in the MONITOR-AF study, which was not randomized and therefore only suggestive, were managed “more efficiently” with greater access to electrophysiologists (P < .01) and adherence to oral anticoagulants (P = .020) and other medications.
Followed for a mean of 2 years, patients with ILRs were more likely to undergo catheter ablation, and their time to a catheter ablation “was impressively shorter, 153 days versus 426 days” (P < .001), Dr. Lakkireddy said.
The ILR group also had fewer strokes and bleeding complications and were less likely to be hospitalized for AFib-related reasons, he said, because “a lot of these patients were caught ahead of time through the remote monitoring.”
For example, ILR patients had fewer heart failure (HF) hospitalizations, likely because “you’re not allowing these patients to remain with untreated rapid ventricular rates for a long period of time. You intervene early, thereby mitigating the onset of heart failure.”
Indeed, Dr. Lakkireddy said, their cumulative rate of any cardiovascular complication was “dramatically lower” – 3.4 versus 10.4 events per 100 person-years (P < .001).
Certainly, a routine recommendation to consider AFib patients for continuous monitoring would require randomized-trial evidence, he acknowledged. “This is an observation registry and proof of concept from a very heterogeneous cohort of patients. There were no obvious set criteria for ILR implantation.”
Nonetheless, “continuous and dynamic monitoring enabled quicker decision-making and patient management,” Dr. Lakkireddy said. “Especially in those patients who may have silent atrial fibrillation, an ILR could significantly mitigate the risk of complications from stroke and heart failure exacerbations.”
Several randomized trials have supported “earlier, more aggressive treatment” for AFib, including EAST-AFNET4, EARLY-AF, and CABANA, observed Daniel Morin, MD, MPH, of Ochsner Medical Center, New Orleans, as the invited discussant for Dr. Lakkireddy’s presentation.
So, he continued, if the goal is to “get every single AFib patient to ablation just as soon as possible,” then maybe MONITOR-AF supports the use of ILRs in such cases.
Indeed, it is “certainly possible” that the continuous stream of data from ILRs “allows faster progression of therapy and possibly even better outcomes” as MONITOR-AF suggests, said Dr. Morin, who is director of electrophysiology research at his center.
Moreover, ILR data could potentially “support shared decision-making perhaps by convincing the patient, and maybe their insurers, that we should move forward with ablation.”
But given the study’s observational, registry-based nature, the MONITOR-AF analysis is limited by potential confounders that complicate its interpretation.
For example, Dr. Morin continued, all ILR patients but only 60% of those on standard care˙ had access to an electrophysiologist (P = .001). That means “less access to some antiarrhythmic medications and certainly far less access to ablation therapy.”
Moreover, “during shared decision-making, a patient who sees the results of their ILR monitoring may be more prone to seek out or to accept earlier, more definitive therapy via ablation,” he said. “The presence of an ILR may then be a good way to move the needle toward ablation.”
Of note, an overwhelming majority of ILR patients received ablation, 93.5%, compared with 58.6% of standard-care patients. “It’s unclear how much of that association was caused by the ILR’s presence vs. other factors, such as physician availability, physician aggressiveness, or patient willingness for intervention,” Dr. Morin noted.
MONITOR-AF included 2,458 patients with paroxysmal or persistent AFib who either were implanted with or did not receive an ILR from 2018 to 2021 and were followed for at least 12 months.
The two groups were similar, Dr. Lakkireddy reported, with respect to demographics and baseline history AFib, hypertension, hyperlipidemia, diabetes, coronary disease, neurovascular events, peripheral artery disease, and obstructive sleep apnea.
Dr. Lakkireddy said a subgroup analysis is forthcoming, but that he’d “intuitively” think that the 15%-20% of AFib patients who are asymptomatic would gain the most from the ILR monitoring approach. There is already evidence that such patients tend to have the worst AFib outcomes, often receiving an AFib diagnosis only after presenting with consequences such as stroke or heart failure.
Dr. Lakkireddy disclosed receiving research grants, modest honoraria, or consulting fees from Abbott, Janssen, Boston Scientific, Johnson & Johnson, Biotronik, Bristol-Myers Squibb, Pfizer, Atricure, Northeast Scientific, and Acutus. Dr. Morin disclosed receiving research grants, honoraria, or consulting fees from Abbott and serving on a speakers’ bureau for Boston Scientific, Medtronic, and Zoll Medical.
A version of this article first appeared on Medscape.com.
Chronic conditions like diabetes or hypertension “often require long-term care through long-term monitoring,” observed a researcher, and “we know that continuous monitoring is superior to intermittent monitoring for long-term outcomes.”
So maybe practice should rely more on continuous ECG monitoring for patients with atrial fibrillation (AFib), also a chronic condition, proposed Dhanunjaya R. Lakkireddy, MD, of the Kansas City Heart Rhythm Institute, Overland Park, Kan., in presenting a new analysis at the annual scientific sessions of the Heart Rhythm Society.
(ILRs), compared with standard care. The latter could include intermittent 12-lead ECG, Holter, or other intermittent monitoring at physicians’ discretion.
Patients with AFib and the ECG implants in the MONITOR-AF study, which was not randomized and therefore only suggestive, were managed “more efficiently” with greater access to electrophysiologists (P < .01) and adherence to oral anticoagulants (P = .020) and other medications.
Followed for a mean of 2 years, patients with ILRs were more likely to undergo catheter ablation, and their time to a catheter ablation “was impressively shorter, 153 days versus 426 days” (P < .001), Dr. Lakkireddy said.
The ILR group also had fewer strokes and bleeding complications and were less likely to be hospitalized for AFib-related reasons, he said, because “a lot of these patients were caught ahead of time through the remote monitoring.”
For example, ILR patients had fewer heart failure (HF) hospitalizations, likely because “you’re not allowing these patients to remain with untreated rapid ventricular rates for a long period of time. You intervene early, thereby mitigating the onset of heart failure.”
Indeed, Dr. Lakkireddy said, their cumulative rate of any cardiovascular complication was “dramatically lower” – 3.4 versus 10.4 events per 100 person-years (P < .001).
Certainly, a routine recommendation to consider AFib patients for continuous monitoring would require randomized-trial evidence, he acknowledged. “This is an observation registry and proof of concept from a very heterogeneous cohort of patients. There were no obvious set criteria for ILR implantation.”
Nonetheless, “continuous and dynamic monitoring enabled quicker decision-making and patient management,” Dr. Lakkireddy said. “Especially in those patients who may have silent atrial fibrillation, an ILR could significantly mitigate the risk of complications from stroke and heart failure exacerbations.”
Several randomized trials have supported “earlier, more aggressive treatment” for AFib, including EAST-AFNET4, EARLY-AF, and CABANA, observed Daniel Morin, MD, MPH, of Ochsner Medical Center, New Orleans, as the invited discussant for Dr. Lakkireddy’s presentation.
So, he continued, if the goal is to “get every single AFib patient to ablation just as soon as possible,” then maybe MONITOR-AF supports the use of ILRs in such cases.
Indeed, it is “certainly possible” that the continuous stream of data from ILRs “allows faster progression of therapy and possibly even better outcomes” as MONITOR-AF suggests, said Dr. Morin, who is director of electrophysiology research at his center.
Moreover, ILR data could potentially “support shared decision-making perhaps by convincing the patient, and maybe their insurers, that we should move forward with ablation.”
But given the study’s observational, registry-based nature, the MONITOR-AF analysis is limited by potential confounders that complicate its interpretation.
For example, Dr. Morin continued, all ILR patients but only 60% of those on standard care˙ had access to an electrophysiologist (P = .001). That means “less access to some antiarrhythmic medications and certainly far less access to ablation therapy.”
Moreover, “during shared decision-making, a patient who sees the results of their ILR monitoring may be more prone to seek out or to accept earlier, more definitive therapy via ablation,” he said. “The presence of an ILR may then be a good way to move the needle toward ablation.”
Of note, an overwhelming majority of ILR patients received ablation, 93.5%, compared with 58.6% of standard-care patients. “It’s unclear how much of that association was caused by the ILR’s presence vs. other factors, such as physician availability, physician aggressiveness, or patient willingness for intervention,” Dr. Morin noted.
MONITOR-AF included 2,458 patients with paroxysmal or persistent AFib who either were implanted with or did not receive an ILR from 2018 to 2021 and were followed for at least 12 months.
The two groups were similar, Dr. Lakkireddy reported, with respect to demographics and baseline history AFib, hypertension, hyperlipidemia, diabetes, coronary disease, neurovascular events, peripheral artery disease, and obstructive sleep apnea.
Dr. Lakkireddy said a subgroup analysis is forthcoming, but that he’d “intuitively” think that the 15%-20% of AFib patients who are asymptomatic would gain the most from the ILR monitoring approach. There is already evidence that such patients tend to have the worst AFib outcomes, often receiving an AFib diagnosis only after presenting with consequences such as stroke or heart failure.
Dr. Lakkireddy disclosed receiving research grants, modest honoraria, or consulting fees from Abbott, Janssen, Boston Scientific, Johnson & Johnson, Biotronik, Bristol-Myers Squibb, Pfizer, Atricure, Northeast Scientific, and Acutus. Dr. Morin disclosed receiving research grants, honoraria, or consulting fees from Abbott and serving on a speakers’ bureau for Boston Scientific, Medtronic, and Zoll Medical.
A version of this article first appeared on Medscape.com.
Chronic conditions like diabetes or hypertension “often require long-term care through long-term monitoring,” observed a researcher, and “we know that continuous monitoring is superior to intermittent monitoring for long-term outcomes.”
So maybe practice should rely more on continuous ECG monitoring for patients with atrial fibrillation (AFib), also a chronic condition, proposed Dhanunjaya R. Lakkireddy, MD, of the Kansas City Heart Rhythm Institute, Overland Park, Kan., in presenting a new analysis at the annual scientific sessions of the Heart Rhythm Society.
(ILRs), compared with standard care. The latter could include intermittent 12-lead ECG, Holter, or other intermittent monitoring at physicians’ discretion.
Patients with AFib and the ECG implants in the MONITOR-AF study, which was not randomized and therefore only suggestive, were managed “more efficiently” with greater access to electrophysiologists (P < .01) and adherence to oral anticoagulants (P = .020) and other medications.
Followed for a mean of 2 years, patients with ILRs were more likely to undergo catheter ablation, and their time to a catheter ablation “was impressively shorter, 153 days versus 426 days” (P < .001), Dr. Lakkireddy said.
The ILR group also had fewer strokes and bleeding complications and were less likely to be hospitalized for AFib-related reasons, he said, because “a lot of these patients were caught ahead of time through the remote monitoring.”
For example, ILR patients had fewer heart failure (HF) hospitalizations, likely because “you’re not allowing these patients to remain with untreated rapid ventricular rates for a long period of time. You intervene early, thereby mitigating the onset of heart failure.”
Indeed, Dr. Lakkireddy said, their cumulative rate of any cardiovascular complication was “dramatically lower” – 3.4 versus 10.4 events per 100 person-years (P < .001).
Certainly, a routine recommendation to consider AFib patients for continuous monitoring would require randomized-trial evidence, he acknowledged. “This is an observation registry and proof of concept from a very heterogeneous cohort of patients. There were no obvious set criteria for ILR implantation.”
Nonetheless, “continuous and dynamic monitoring enabled quicker decision-making and patient management,” Dr. Lakkireddy said. “Especially in those patients who may have silent atrial fibrillation, an ILR could significantly mitigate the risk of complications from stroke and heart failure exacerbations.”
Several randomized trials have supported “earlier, more aggressive treatment” for AFib, including EAST-AFNET4, EARLY-AF, and CABANA, observed Daniel Morin, MD, MPH, of Ochsner Medical Center, New Orleans, as the invited discussant for Dr. Lakkireddy’s presentation.
So, he continued, if the goal is to “get every single AFib patient to ablation just as soon as possible,” then maybe MONITOR-AF supports the use of ILRs in such cases.
Indeed, it is “certainly possible” that the continuous stream of data from ILRs “allows faster progression of therapy and possibly even better outcomes” as MONITOR-AF suggests, said Dr. Morin, who is director of electrophysiology research at his center.
Moreover, ILR data could potentially “support shared decision-making perhaps by convincing the patient, and maybe their insurers, that we should move forward with ablation.”
But given the study’s observational, registry-based nature, the MONITOR-AF analysis is limited by potential confounders that complicate its interpretation.
For example, Dr. Morin continued, all ILR patients but only 60% of those on standard care˙ had access to an electrophysiologist (P = .001). That means “less access to some antiarrhythmic medications and certainly far less access to ablation therapy.”
Moreover, “during shared decision-making, a patient who sees the results of their ILR monitoring may be more prone to seek out or to accept earlier, more definitive therapy via ablation,” he said. “The presence of an ILR may then be a good way to move the needle toward ablation.”
Of note, an overwhelming majority of ILR patients received ablation, 93.5%, compared with 58.6% of standard-care patients. “It’s unclear how much of that association was caused by the ILR’s presence vs. other factors, such as physician availability, physician aggressiveness, or patient willingness for intervention,” Dr. Morin noted.
MONITOR-AF included 2,458 patients with paroxysmal or persistent AFib who either were implanted with or did not receive an ILR from 2018 to 2021 and were followed for at least 12 months.
The two groups were similar, Dr. Lakkireddy reported, with respect to demographics and baseline history AFib, hypertension, hyperlipidemia, diabetes, coronary disease, neurovascular events, peripheral artery disease, and obstructive sleep apnea.
Dr. Lakkireddy said a subgroup analysis is forthcoming, but that he’d “intuitively” think that the 15%-20% of AFib patients who are asymptomatic would gain the most from the ILR monitoring approach. There is already evidence that such patients tend to have the worst AFib outcomes, often receiving an AFib diagnosis only after presenting with consequences such as stroke or heart failure.
Dr. Lakkireddy disclosed receiving research grants, modest honoraria, or consulting fees from Abbott, Janssen, Boston Scientific, Johnson & Johnson, Biotronik, Bristol-Myers Squibb, Pfizer, Atricure, Northeast Scientific, and Acutus. Dr. Morin disclosed receiving research grants, honoraria, or consulting fees from Abbott and serving on a speakers’ bureau for Boston Scientific, Medtronic, and Zoll Medical.
A version of this article first appeared on Medscape.com.
FROM HEART RHYTHM 2023
Significant increase in vitamin D deficiency in kids with major depressive disorder
SAN FRANCISCO – , according to new findings that suggest spending more time indoors may have fueled this uptick.
“We suspect that this may be due to the COVID lockdowns and kids schooling from home and having less time outside,” study investigator Oluwatomiwa Babade, MD, MPH, with Virginia Tech Carilion School of Medicine, Roanoke, Va., said in an interview.
The study was presented at the annual meeting of the American Psychiatric Association.
Anecdotal observation confirmed
During the pandemic, investigators noticed an uptick in the number of children and adolescents attending their clinic for psychiatric hospitalization who had low vitamin D levels.
To investigate, they analyzed the records of all patients aged 6-17 years with psychiatric diagnoses and vitamin D level assessment who were admitted into the inpatient psychiatry unit from March 18, 2020, to June 30, 2021.
Among 599 unique patients, 275 (83% female) had a diagnosis of MDD and 226 of these patients were vitamin D deficient (< 30 ng/mL) – a prevalence rate of roughly 82%. Among 246 patients with psychiatric disorders other than MDD, the prevalence of vitamin D deficiency was 76%.
“This was very surprising and much higher than prior to the pandemic. Prior to COVID, the prevalence of vitamin D deficiency was around 14% in similar patients,” Dr. Babade said.
“Now that we are post-lockdown, it would be good to repeat the study. I think the prevalence should drop. That’s my guess,” he added.
Important research, no surprises
In a comment, Cemre Robinson, MD, director of the Mount Sinai Pediatric Bone Health and Calcium Metabolism Clinic, New York, said that although the study’s findings aren’t surprising, “it’s important to present such data in adolescents with major depression.”
“These findings reiterate the importance of screening for vitamin D deficiency in children and adolescents, with or without depression, particularly during winter, which is associated with less sun exposure,” Dr. Robinson, assistant professor of pediatrics, endocrinology, and diabetes at Icahn School of Medicine at Mount Sinai, said.
She noted that vitamin D deficiency is prevalent in the general population, and it can be easily corrected with supplementation.
“Vitamin D is important for bone growth, mineralization, and accretion as well as calcium absorption. Adolescence, in particular, is a period of rapid physical, cognitive, and psychosocial growth,” Dr. Robinson said.
“The requirement of all minerals and vitamins changes in this phase of life. Therefore, it is important to have sufficient vitamin D levels during adolescence for several health benefits,” she noted.
Dr. Robinson said that “more research is needed to validate the present findings in adolescents with major depression, and larger studies, including randomized control trials, are required to establish a causal association between MDD and vitamin D deficiency.”
The study had no specific funding. Dr. Babade and Dr. Robinson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , according to new findings that suggest spending more time indoors may have fueled this uptick.
“We suspect that this may be due to the COVID lockdowns and kids schooling from home and having less time outside,” study investigator Oluwatomiwa Babade, MD, MPH, with Virginia Tech Carilion School of Medicine, Roanoke, Va., said in an interview.
The study was presented at the annual meeting of the American Psychiatric Association.
Anecdotal observation confirmed
During the pandemic, investigators noticed an uptick in the number of children and adolescents attending their clinic for psychiatric hospitalization who had low vitamin D levels.
To investigate, they analyzed the records of all patients aged 6-17 years with psychiatric diagnoses and vitamin D level assessment who were admitted into the inpatient psychiatry unit from March 18, 2020, to June 30, 2021.
Among 599 unique patients, 275 (83% female) had a diagnosis of MDD and 226 of these patients were vitamin D deficient (< 30 ng/mL) – a prevalence rate of roughly 82%. Among 246 patients with psychiatric disorders other than MDD, the prevalence of vitamin D deficiency was 76%.
“This was very surprising and much higher than prior to the pandemic. Prior to COVID, the prevalence of vitamin D deficiency was around 14% in similar patients,” Dr. Babade said.
“Now that we are post-lockdown, it would be good to repeat the study. I think the prevalence should drop. That’s my guess,” he added.
Important research, no surprises
In a comment, Cemre Robinson, MD, director of the Mount Sinai Pediatric Bone Health and Calcium Metabolism Clinic, New York, said that although the study’s findings aren’t surprising, “it’s important to present such data in adolescents with major depression.”
“These findings reiterate the importance of screening for vitamin D deficiency in children and adolescents, with or without depression, particularly during winter, which is associated with less sun exposure,” Dr. Robinson, assistant professor of pediatrics, endocrinology, and diabetes at Icahn School of Medicine at Mount Sinai, said.
She noted that vitamin D deficiency is prevalent in the general population, and it can be easily corrected with supplementation.
“Vitamin D is important for bone growth, mineralization, and accretion as well as calcium absorption. Adolescence, in particular, is a period of rapid physical, cognitive, and psychosocial growth,” Dr. Robinson said.
“The requirement of all minerals and vitamins changes in this phase of life. Therefore, it is important to have sufficient vitamin D levels during adolescence for several health benefits,” she noted.
Dr. Robinson said that “more research is needed to validate the present findings in adolescents with major depression, and larger studies, including randomized control trials, are required to establish a causal association between MDD and vitamin D deficiency.”
The study had no specific funding. Dr. Babade and Dr. Robinson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , according to new findings that suggest spending more time indoors may have fueled this uptick.
“We suspect that this may be due to the COVID lockdowns and kids schooling from home and having less time outside,” study investigator Oluwatomiwa Babade, MD, MPH, with Virginia Tech Carilion School of Medicine, Roanoke, Va., said in an interview.
The study was presented at the annual meeting of the American Psychiatric Association.
Anecdotal observation confirmed
During the pandemic, investigators noticed an uptick in the number of children and adolescents attending their clinic for psychiatric hospitalization who had low vitamin D levels.
To investigate, they analyzed the records of all patients aged 6-17 years with psychiatric diagnoses and vitamin D level assessment who were admitted into the inpatient psychiatry unit from March 18, 2020, to June 30, 2021.
Among 599 unique patients, 275 (83% female) had a diagnosis of MDD and 226 of these patients were vitamin D deficient (< 30 ng/mL) – a prevalence rate of roughly 82%. Among 246 patients with psychiatric disorders other than MDD, the prevalence of vitamin D deficiency was 76%.
“This was very surprising and much higher than prior to the pandemic. Prior to COVID, the prevalence of vitamin D deficiency was around 14% in similar patients,” Dr. Babade said.
“Now that we are post-lockdown, it would be good to repeat the study. I think the prevalence should drop. That’s my guess,” he added.
Important research, no surprises
In a comment, Cemre Robinson, MD, director of the Mount Sinai Pediatric Bone Health and Calcium Metabolism Clinic, New York, said that although the study’s findings aren’t surprising, “it’s important to present such data in adolescents with major depression.”
“These findings reiterate the importance of screening for vitamin D deficiency in children and adolescents, with or without depression, particularly during winter, which is associated with less sun exposure,” Dr. Robinson, assistant professor of pediatrics, endocrinology, and diabetes at Icahn School of Medicine at Mount Sinai, said.
She noted that vitamin D deficiency is prevalent in the general population, and it can be easily corrected with supplementation.
“Vitamin D is important for bone growth, mineralization, and accretion as well as calcium absorption. Adolescence, in particular, is a period of rapid physical, cognitive, and psychosocial growth,” Dr. Robinson said.
“The requirement of all minerals and vitamins changes in this phase of life. Therefore, it is important to have sufficient vitamin D levels during adolescence for several health benefits,” she noted.
Dr. Robinson said that “more research is needed to validate the present findings in adolescents with major depression, and larger studies, including randomized control trials, are required to establish a causal association between MDD and vitamin D deficiency.”
The study had no specific funding. Dr. Babade and Dr. Robinson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT APA 2023
Abortion restrictions linked to less evidence-based care for miscarriages
BALTIMORE – , according to a cross-sectional study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists and published in Obstetrics & Gynecology.
The results revealed that “abortion restrictions have far-reaching effects on early pregnancy loss care and on resident education,” the researchers concluded.
“Abortion restrictions don’t just affect people seeking abortions; they affect people also suffering from early pregnancy loss,” Aurora Phillips, MD, an ob.gyn. resident at Albany (N.Y.) Medical Center, said in an interview. “It’s harder to make that diagnosis and to be able to offer interventions, and these institutions that had restrictions also were less likely to have mifepristone or office based human aspiration, which are the most efficient and cost-effective interventions that we have.”
For example, less than half the programs surveyed offered mifepristone to help manage a miscarriage, “with availability varying inversely with abortion restrictions,” they found. After considering all characteristics of residency programs, “institutional abortion restrictions and bans were more important than state policies or religious affiliation in determining whether evidence-based early pregnancy loss treatments were available,” the researchers found, though their findings predated the Supreme Court’s Dobbs ruling that overturned Roe v. Wade. “Training institutions with a commitment to evidence-based family planning care and education are able to ensure access to the most evidence-based, cost-effective, and timely treatments for pregnancy loss even in the face of state abortion restrictions, thereby preserving patient safety, physician competency, and health care system sustainability,” they wrote.
Reduced access leads to higher risk interventions
An estimated 10%-20% of pregnancies result in early miscarriage, totaling more than one million cases in the U.S. each year. But since treatments for miscarriage often overlap with those for abortion, the researchers wondered whether differences existed in how providers managed miscarriages in states or institutions with strict abortion restrictions versus management in hospitals without restrictions.
They also looked at how closely the management strategies adhered to ACOG’s recommendations, which advise that providers consider both ultrasound imaging and other factors, including clinical reasoning and patient preferences, before diagnosing early pregnancy loss and considering possible interventions.
For imaging guidelines, ACOG endorses the criteria established for ultrasound diagnosis of first trimester pregnancy loss from the Society of Radiologists in 2012. But, the authors note, these guidelines are very conservative, exceeding previous measurements that had a 99%-100% predictive value for pregnancy loss, in the interest of “[prioritizing preservation of] fetal potential over facilitating expeditious care.” Hence the reason ACOG advises providers to include clinical judgment and patient preferences in their approach to care.
”In places where abortion is heavily regulated, clinicians managing miscarriages may cautiously rely on the strictest criteria to differentiate early pregnancy loss from potentially viable pregnancy and may not offer certain treatments commonly associated with abortion,” the authors noted. ACOG recommends surgical aspiration and medical treatment with both mifepristone and misoprostol as the safest and most effective options in managing miscarriages.
“Treating early pregnancy loss without the use of mifepristone is more likely to fail, is more likely to require an unscheduled procedure, and people who choose medication management for their miscarriages are usually trying to avoid a procedure, so that is the downside of not using mifepristone,” coauthor Rachel M. Flink-Bochacki, MD, an associate professor at Albany (N.Y.) Medical Center, said in an interview.
“Office-based uterine aspiration has the same safety profile as uterine aspiration in the operating room minus the risks of anesthesia and also helps patients get in faster because they don’t need to wait for OR time,” Dr. Flink-Bochacki explained. “So again, for a patient who wants an aspiration and does not want to pass the pregnancy at home, not having access to office-based aspiration could lead them to miscarry at home, which has higher risks and is not what they wanted.”
Reduced access to miscarriage care options in ‘hostile’ states
Among all 296 U.S. ob.gyn. residency programs that were contacted between November 2021 and January 2022, half (50.3%) responded to the researchers’ survey about their institutional practices around miscarriage, including location of diagnosis, use of ultrasound diagnostic guidelines, treatment options offered by their institution, and institutional restrictions on abortions based on indication.
The survey also collected characteristics of each program, including its state, setting, religious affiliation, and affiliation with the Ryan Training Program in Abortion and Family Planning. The responding sample had similar geographic distribution and state abortion policies as those who did not respond, but the responding programs were slightly more likely to be academic programs and to be affiliated with the Ryan program.
At the time of the study, prior to the Dobbs ruling, more than half the U.S. states had legislation restricting abortion care, and 57% of national teaching hospitals had internal restrictions that limited care based on gestational age and indication, particularly if the indication was elective, the authors reported. The researchers relied on designations from the Guttmacher Institute in December 2020 to categorize states as “hostile” to abortion (very hostile, hostile, and leans hostile) or non-hostile (neutral, leans supportive, supportive, and very supportive).
Most of the programs (80%) had no religious affiliation, but 11% had a Catholic affiliation and 5% had a different Christian affiliation. Institutional policies either had no restrictions on abortion care (38%), had restrictions (39%) based on certain maternal or fetal indications, or completely banned abortion services unless the mother’s life was threatened (23%). Among the Christian-affiliated programs, 60% had bans and 40% had restrictions.
Half (49.7%) of the responding programs relied rigidly on ultrasound criteria before offering any intervention for suspected early pregnancy loss, regardless of patient preferences. The other half (50.3%) incorporated ultrasound criteria and other factors, including clinical judgment and patient preferences, into a holistic determination of what options to present to the patient.
Before accounting for other factors, the researchers found that only a third (33%) of programs in states with severe abortion restrictions considered additional factors besides imaging when offering patients options for miscarriage management. In states without such abortion restrictions, 79% of programs considered both imaging and other factors (P < .001).
In states with “hostile abortion legislation,” only 32% of the programs used mifepristone for miscarriage management, compared with 75% of the programs in states without onerous abortion restrictions (P < .001). The results were similar for use of office-based suction aspiration: Just under half the programs (48%) in states with severe abortion restrictions included this technique as part of standard miscarriage management, compared with 68% of programs in states without such restrictions (P = .014).
Those findings match up with the experience of Cara Heuser, MD, a maternal-fetal medicine specialist from Salt Lake City, who was not involved in this study.
“We had a lot of restrictions even before Roe fell,” including heavy regulation of mifepristone, Dr. Heuser said in an interview. “In non-restricted states, it’s pretty easy to get, but even before Roe in our state, it was very, very difficult to get institutions and individual doctor’s offices to carry mifepristone to treat miscarriages. They were still treating miscarriages in a way that was known to be less effective.” Adding mifepristone to misoprostol reduces the risk of needing an evacuation surgery procedure, she explained, “so adding the mifepristone makes it safer.”
Institutional policies had the strongest impact
Before accounting for the state a hospital was in, 27% of institutions with restrictive abortion policies looked at more than imaging in determining how to proceed, compared with 88% of institutions without abortion restrictions that included clinical judgment and patient preferences in their management.
After controlling for state policies and affiliation with a family planning training program or a religious entity, the odds of an institution relying solely on imaging guidelines were over 12 times greater for institutions with abortion restrictions or bans (odds ratio, 12.3; 95% confidence interval, 3.2-47.9). Specifically, the odds were 9 times greater for institutions with restrictions and 27 times greater for institutions with bans.
Only 12% of the institutions without restrictions relied solely on ultrasound criteria, compared with 67% of the institutions with restrictions and 82% of the institutions that banned all abortions except to save the life of the pregnant individual (P < .001).
Only one in four (25%) of the programs with institutional abortion restrictions used mifepristone, compared with 86% of unrestricted programs (P < .001), and 40% of programs with institutional abortion restrictions used office-based aspiration, compared with 81% of unrestricted programs (P < .001).
Without access to all evidence-based treatments, doctors are often forced to choose expectant management for miscarriages. “So you’re kind of forced to have them to pass the pregnancy at home, which can be traumatic for patients” if that’s not what they wanted, Dr. Phillips said.
Dr. Flink-Bochacki further noted that this patient population is already particularly vulnerable.
“Especially for patients with early pregnancy loss, it’s such a feeling of powerlessness already, so the mental state that many of these patients are in is already quite fraught,” Dr. Flink-Bochacki said. “Then to not even have power to choose the interventions that you want or to be able to access interventions in a timely fashion because you’re being held to some arbitrary guideline further takes away the power and further exacerbates the trauma of the experience.”
The biggest factor likely driving the reduced access to those interventions is the fear that the care could be confused with providing an abortion instead of simply managing a miscarriage, Dr. Flink-Bochacki said. “I think that’s why a lot of these programs don’t have mifepristone and don’t offer outpatient uterine aspiration,” she said. “Because those are so widely used in abortion and the connotation is with abortion, they’re just kind of steering clear of it, but meanwhile, patients with pregnancy loss are suffering because they’re being unnecessarily restrictive.”
The research did not use any external funding, and the authors and Dr. Heuser had no disclosures.
BALTIMORE – , according to a cross-sectional study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists and published in Obstetrics & Gynecology.
The results revealed that “abortion restrictions have far-reaching effects on early pregnancy loss care and on resident education,” the researchers concluded.
“Abortion restrictions don’t just affect people seeking abortions; they affect people also suffering from early pregnancy loss,” Aurora Phillips, MD, an ob.gyn. resident at Albany (N.Y.) Medical Center, said in an interview. “It’s harder to make that diagnosis and to be able to offer interventions, and these institutions that had restrictions also were less likely to have mifepristone or office based human aspiration, which are the most efficient and cost-effective interventions that we have.”
For example, less than half the programs surveyed offered mifepristone to help manage a miscarriage, “with availability varying inversely with abortion restrictions,” they found. After considering all characteristics of residency programs, “institutional abortion restrictions and bans were more important than state policies or religious affiliation in determining whether evidence-based early pregnancy loss treatments were available,” the researchers found, though their findings predated the Supreme Court’s Dobbs ruling that overturned Roe v. Wade. “Training institutions with a commitment to evidence-based family planning care and education are able to ensure access to the most evidence-based, cost-effective, and timely treatments for pregnancy loss even in the face of state abortion restrictions, thereby preserving patient safety, physician competency, and health care system sustainability,” they wrote.
Reduced access leads to higher risk interventions
An estimated 10%-20% of pregnancies result in early miscarriage, totaling more than one million cases in the U.S. each year. But since treatments for miscarriage often overlap with those for abortion, the researchers wondered whether differences existed in how providers managed miscarriages in states or institutions with strict abortion restrictions versus management in hospitals without restrictions.
They also looked at how closely the management strategies adhered to ACOG’s recommendations, which advise that providers consider both ultrasound imaging and other factors, including clinical reasoning and patient preferences, before diagnosing early pregnancy loss and considering possible interventions.
For imaging guidelines, ACOG endorses the criteria established for ultrasound diagnosis of first trimester pregnancy loss from the Society of Radiologists in 2012. But, the authors note, these guidelines are very conservative, exceeding previous measurements that had a 99%-100% predictive value for pregnancy loss, in the interest of “[prioritizing preservation of] fetal potential over facilitating expeditious care.” Hence the reason ACOG advises providers to include clinical judgment and patient preferences in their approach to care.
”In places where abortion is heavily regulated, clinicians managing miscarriages may cautiously rely on the strictest criteria to differentiate early pregnancy loss from potentially viable pregnancy and may not offer certain treatments commonly associated with abortion,” the authors noted. ACOG recommends surgical aspiration and medical treatment with both mifepristone and misoprostol as the safest and most effective options in managing miscarriages.
“Treating early pregnancy loss without the use of mifepristone is more likely to fail, is more likely to require an unscheduled procedure, and people who choose medication management for their miscarriages are usually trying to avoid a procedure, so that is the downside of not using mifepristone,” coauthor Rachel M. Flink-Bochacki, MD, an associate professor at Albany (N.Y.) Medical Center, said in an interview.
“Office-based uterine aspiration has the same safety profile as uterine aspiration in the operating room minus the risks of anesthesia and also helps patients get in faster because they don’t need to wait for OR time,” Dr. Flink-Bochacki explained. “So again, for a patient who wants an aspiration and does not want to pass the pregnancy at home, not having access to office-based aspiration could lead them to miscarry at home, which has higher risks and is not what they wanted.”
Reduced access to miscarriage care options in ‘hostile’ states
Among all 296 U.S. ob.gyn. residency programs that were contacted between November 2021 and January 2022, half (50.3%) responded to the researchers’ survey about their institutional practices around miscarriage, including location of diagnosis, use of ultrasound diagnostic guidelines, treatment options offered by their institution, and institutional restrictions on abortions based on indication.
The survey also collected characteristics of each program, including its state, setting, religious affiliation, and affiliation with the Ryan Training Program in Abortion and Family Planning. The responding sample had similar geographic distribution and state abortion policies as those who did not respond, but the responding programs were slightly more likely to be academic programs and to be affiliated with the Ryan program.
At the time of the study, prior to the Dobbs ruling, more than half the U.S. states had legislation restricting abortion care, and 57% of national teaching hospitals had internal restrictions that limited care based on gestational age and indication, particularly if the indication was elective, the authors reported. The researchers relied on designations from the Guttmacher Institute in December 2020 to categorize states as “hostile” to abortion (very hostile, hostile, and leans hostile) or non-hostile (neutral, leans supportive, supportive, and very supportive).
Most of the programs (80%) had no religious affiliation, but 11% had a Catholic affiliation and 5% had a different Christian affiliation. Institutional policies either had no restrictions on abortion care (38%), had restrictions (39%) based on certain maternal or fetal indications, or completely banned abortion services unless the mother’s life was threatened (23%). Among the Christian-affiliated programs, 60% had bans and 40% had restrictions.
Half (49.7%) of the responding programs relied rigidly on ultrasound criteria before offering any intervention for suspected early pregnancy loss, regardless of patient preferences. The other half (50.3%) incorporated ultrasound criteria and other factors, including clinical judgment and patient preferences, into a holistic determination of what options to present to the patient.
Before accounting for other factors, the researchers found that only a third (33%) of programs in states with severe abortion restrictions considered additional factors besides imaging when offering patients options for miscarriage management. In states without such abortion restrictions, 79% of programs considered both imaging and other factors (P < .001).
In states with “hostile abortion legislation,” only 32% of the programs used mifepristone for miscarriage management, compared with 75% of the programs in states without onerous abortion restrictions (P < .001). The results were similar for use of office-based suction aspiration: Just under half the programs (48%) in states with severe abortion restrictions included this technique as part of standard miscarriage management, compared with 68% of programs in states without such restrictions (P = .014).
Those findings match up with the experience of Cara Heuser, MD, a maternal-fetal medicine specialist from Salt Lake City, who was not involved in this study.
“We had a lot of restrictions even before Roe fell,” including heavy regulation of mifepristone, Dr. Heuser said in an interview. “In non-restricted states, it’s pretty easy to get, but even before Roe in our state, it was very, very difficult to get institutions and individual doctor’s offices to carry mifepristone to treat miscarriages. They were still treating miscarriages in a way that was known to be less effective.” Adding mifepristone to misoprostol reduces the risk of needing an evacuation surgery procedure, she explained, “so adding the mifepristone makes it safer.”
Institutional policies had the strongest impact
Before accounting for the state a hospital was in, 27% of institutions with restrictive abortion policies looked at more than imaging in determining how to proceed, compared with 88% of institutions without abortion restrictions that included clinical judgment and patient preferences in their management.
After controlling for state policies and affiliation with a family planning training program or a religious entity, the odds of an institution relying solely on imaging guidelines were over 12 times greater for institutions with abortion restrictions or bans (odds ratio, 12.3; 95% confidence interval, 3.2-47.9). Specifically, the odds were 9 times greater for institutions with restrictions and 27 times greater for institutions with bans.
Only 12% of the institutions without restrictions relied solely on ultrasound criteria, compared with 67% of the institutions with restrictions and 82% of the institutions that banned all abortions except to save the life of the pregnant individual (P < .001).
Only one in four (25%) of the programs with institutional abortion restrictions used mifepristone, compared with 86% of unrestricted programs (P < .001), and 40% of programs with institutional abortion restrictions used office-based aspiration, compared with 81% of unrestricted programs (P < .001).
Without access to all evidence-based treatments, doctors are often forced to choose expectant management for miscarriages. “So you’re kind of forced to have them to pass the pregnancy at home, which can be traumatic for patients” if that’s not what they wanted, Dr. Phillips said.
Dr. Flink-Bochacki further noted that this patient population is already particularly vulnerable.
“Especially for patients with early pregnancy loss, it’s such a feeling of powerlessness already, so the mental state that many of these patients are in is already quite fraught,” Dr. Flink-Bochacki said. “Then to not even have power to choose the interventions that you want or to be able to access interventions in a timely fashion because you’re being held to some arbitrary guideline further takes away the power and further exacerbates the trauma of the experience.”
The biggest factor likely driving the reduced access to those interventions is the fear that the care could be confused with providing an abortion instead of simply managing a miscarriage, Dr. Flink-Bochacki said. “I think that’s why a lot of these programs don’t have mifepristone and don’t offer outpatient uterine aspiration,” she said. “Because those are so widely used in abortion and the connotation is with abortion, they’re just kind of steering clear of it, but meanwhile, patients with pregnancy loss are suffering because they’re being unnecessarily restrictive.”
The research did not use any external funding, and the authors and Dr. Heuser had no disclosures.
BALTIMORE – , according to a cross-sectional study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists and published in Obstetrics & Gynecology.
The results revealed that “abortion restrictions have far-reaching effects on early pregnancy loss care and on resident education,” the researchers concluded.
“Abortion restrictions don’t just affect people seeking abortions; they affect people also suffering from early pregnancy loss,” Aurora Phillips, MD, an ob.gyn. resident at Albany (N.Y.) Medical Center, said in an interview. “It’s harder to make that diagnosis and to be able to offer interventions, and these institutions that had restrictions also were less likely to have mifepristone or office based human aspiration, which are the most efficient and cost-effective interventions that we have.”
For example, less than half the programs surveyed offered mifepristone to help manage a miscarriage, “with availability varying inversely with abortion restrictions,” they found. After considering all characteristics of residency programs, “institutional abortion restrictions and bans were more important than state policies or religious affiliation in determining whether evidence-based early pregnancy loss treatments were available,” the researchers found, though their findings predated the Supreme Court’s Dobbs ruling that overturned Roe v. Wade. “Training institutions with a commitment to evidence-based family planning care and education are able to ensure access to the most evidence-based, cost-effective, and timely treatments for pregnancy loss even in the face of state abortion restrictions, thereby preserving patient safety, physician competency, and health care system sustainability,” they wrote.
Reduced access leads to higher risk interventions
An estimated 10%-20% of pregnancies result in early miscarriage, totaling more than one million cases in the U.S. each year. But since treatments for miscarriage often overlap with those for abortion, the researchers wondered whether differences existed in how providers managed miscarriages in states or institutions with strict abortion restrictions versus management in hospitals without restrictions.
They also looked at how closely the management strategies adhered to ACOG’s recommendations, which advise that providers consider both ultrasound imaging and other factors, including clinical reasoning and patient preferences, before diagnosing early pregnancy loss and considering possible interventions.
For imaging guidelines, ACOG endorses the criteria established for ultrasound diagnosis of first trimester pregnancy loss from the Society of Radiologists in 2012. But, the authors note, these guidelines are very conservative, exceeding previous measurements that had a 99%-100% predictive value for pregnancy loss, in the interest of “[prioritizing preservation of] fetal potential over facilitating expeditious care.” Hence the reason ACOG advises providers to include clinical judgment and patient preferences in their approach to care.
”In places where abortion is heavily regulated, clinicians managing miscarriages may cautiously rely on the strictest criteria to differentiate early pregnancy loss from potentially viable pregnancy and may not offer certain treatments commonly associated with abortion,” the authors noted. ACOG recommends surgical aspiration and medical treatment with both mifepristone and misoprostol as the safest and most effective options in managing miscarriages.
“Treating early pregnancy loss without the use of mifepristone is more likely to fail, is more likely to require an unscheduled procedure, and people who choose medication management for their miscarriages are usually trying to avoid a procedure, so that is the downside of not using mifepristone,” coauthor Rachel M. Flink-Bochacki, MD, an associate professor at Albany (N.Y.) Medical Center, said in an interview.
“Office-based uterine aspiration has the same safety profile as uterine aspiration in the operating room minus the risks of anesthesia and also helps patients get in faster because they don’t need to wait for OR time,” Dr. Flink-Bochacki explained. “So again, for a patient who wants an aspiration and does not want to pass the pregnancy at home, not having access to office-based aspiration could lead them to miscarry at home, which has higher risks and is not what they wanted.”
Reduced access to miscarriage care options in ‘hostile’ states
Among all 296 U.S. ob.gyn. residency programs that were contacted between November 2021 and January 2022, half (50.3%) responded to the researchers’ survey about their institutional practices around miscarriage, including location of diagnosis, use of ultrasound diagnostic guidelines, treatment options offered by their institution, and institutional restrictions on abortions based on indication.
The survey also collected characteristics of each program, including its state, setting, religious affiliation, and affiliation with the Ryan Training Program in Abortion and Family Planning. The responding sample had similar geographic distribution and state abortion policies as those who did not respond, but the responding programs were slightly more likely to be academic programs and to be affiliated with the Ryan program.
At the time of the study, prior to the Dobbs ruling, more than half the U.S. states had legislation restricting abortion care, and 57% of national teaching hospitals had internal restrictions that limited care based on gestational age and indication, particularly if the indication was elective, the authors reported. The researchers relied on designations from the Guttmacher Institute in December 2020 to categorize states as “hostile” to abortion (very hostile, hostile, and leans hostile) or non-hostile (neutral, leans supportive, supportive, and very supportive).
Most of the programs (80%) had no religious affiliation, but 11% had a Catholic affiliation and 5% had a different Christian affiliation. Institutional policies either had no restrictions on abortion care (38%), had restrictions (39%) based on certain maternal or fetal indications, or completely banned abortion services unless the mother’s life was threatened (23%). Among the Christian-affiliated programs, 60% had bans and 40% had restrictions.
Half (49.7%) of the responding programs relied rigidly on ultrasound criteria before offering any intervention for suspected early pregnancy loss, regardless of patient preferences. The other half (50.3%) incorporated ultrasound criteria and other factors, including clinical judgment and patient preferences, into a holistic determination of what options to present to the patient.
Before accounting for other factors, the researchers found that only a third (33%) of programs in states with severe abortion restrictions considered additional factors besides imaging when offering patients options for miscarriage management. In states without such abortion restrictions, 79% of programs considered both imaging and other factors (P < .001).
In states with “hostile abortion legislation,” only 32% of the programs used mifepristone for miscarriage management, compared with 75% of the programs in states without onerous abortion restrictions (P < .001). The results were similar for use of office-based suction aspiration: Just under half the programs (48%) in states with severe abortion restrictions included this technique as part of standard miscarriage management, compared with 68% of programs in states without such restrictions (P = .014).
Those findings match up with the experience of Cara Heuser, MD, a maternal-fetal medicine specialist from Salt Lake City, who was not involved in this study.
“We had a lot of restrictions even before Roe fell,” including heavy regulation of mifepristone, Dr. Heuser said in an interview. “In non-restricted states, it’s pretty easy to get, but even before Roe in our state, it was very, very difficult to get institutions and individual doctor’s offices to carry mifepristone to treat miscarriages. They were still treating miscarriages in a way that was known to be less effective.” Adding mifepristone to misoprostol reduces the risk of needing an evacuation surgery procedure, she explained, “so adding the mifepristone makes it safer.”
Institutional policies had the strongest impact
Before accounting for the state a hospital was in, 27% of institutions with restrictive abortion policies looked at more than imaging in determining how to proceed, compared with 88% of institutions without abortion restrictions that included clinical judgment and patient preferences in their management.
After controlling for state policies and affiliation with a family planning training program or a religious entity, the odds of an institution relying solely on imaging guidelines were over 12 times greater for institutions with abortion restrictions or bans (odds ratio, 12.3; 95% confidence interval, 3.2-47.9). Specifically, the odds were 9 times greater for institutions with restrictions and 27 times greater for institutions with bans.
Only 12% of the institutions without restrictions relied solely on ultrasound criteria, compared with 67% of the institutions with restrictions and 82% of the institutions that banned all abortions except to save the life of the pregnant individual (P < .001).
Only one in four (25%) of the programs with institutional abortion restrictions used mifepristone, compared with 86% of unrestricted programs (P < .001), and 40% of programs with institutional abortion restrictions used office-based aspiration, compared with 81% of unrestricted programs (P < .001).
Without access to all evidence-based treatments, doctors are often forced to choose expectant management for miscarriages. “So you’re kind of forced to have them to pass the pregnancy at home, which can be traumatic for patients” if that’s not what they wanted, Dr. Phillips said.
Dr. Flink-Bochacki further noted that this patient population is already particularly vulnerable.
“Especially for patients with early pregnancy loss, it’s such a feeling of powerlessness already, so the mental state that many of these patients are in is already quite fraught,” Dr. Flink-Bochacki said. “Then to not even have power to choose the interventions that you want or to be able to access interventions in a timely fashion because you’re being held to some arbitrary guideline further takes away the power and further exacerbates the trauma of the experience.”
The biggest factor likely driving the reduced access to those interventions is the fear that the care could be confused with providing an abortion instead of simply managing a miscarriage, Dr. Flink-Bochacki said. “I think that’s why a lot of these programs don’t have mifepristone and don’t offer outpatient uterine aspiration,” she said. “Because those are so widely used in abortion and the connotation is with abortion, they’re just kind of steering clear of it, but meanwhile, patients with pregnancy loss are suffering because they’re being unnecessarily restrictive.”
The research did not use any external funding, and the authors and Dr. Heuser had no disclosures.
AT ACOG 2023
New treatments under study for celiac disease
CHICAGO –
There are a number of clinical trials underway, including one for the investigational drug TPM502, which carries three gluten-specific antigenic peptides with overlapping T-cell epitopes for the HLA-DQ2.5 gene. And, research is underway for the novel KAN-101, which aims to restore the immune tolerance of gluten by targeting receptors on the liver. It received Fast Track designation by the Food and Drug Administration in 2022.
During the annual Digestive Disease Week® (DDW), researchers shared the results from a new proof-of-concept study for DONQ52, a bispecific antibody that targets HLA-DQ2.5. DONQ52 was found to be highly effective in blocking gluten-specific T cells, said investigator Jason A. Tye-Din, PhD, a researcher with The Walter and Eliza Hall Institute of Medical Research, Melbourne, and an investigator with Chugai Pharmaceutical, which is funding the DONQ52 research which has since advanced to a phase 1 study of 56 patients.
There are no existing drug therapies for celiac disease, which leaves patients with a lifelong, and strict, gluten-free diet as treatment. This strategy, however, often fails to induce mucosal healing or symptom control, and has stimulated a search for novel therapies, said Melinda Y. Hardy, PhD, a postdoctoral researcher with the University of Melbourne, and the first author of the DONQ52 study. While targeting the gluten-specific immune response is highly attractive, it presents safety and pharmacokinetic challenges, so a better alternative would be to develop antibodies that selectively bind to HLA-DQ2.5, which is found in 80%-90% of celiac disease patients, she said. DONQ52 blocks at least 25 gluten peptides, and binds specifically to complexes of HLA-DQ2.5 and a range of immunogenic gluten peptides.
The study included 20 patients who consumed wheat bread for 3 days. Blood samples were taken 1 day before the start of the trial and 6 days after it concluded. Twenty patients were found to be wheat challenged, 10 were barley challenged, and 14 were rye challenged.
All were tested for gluten-specific T-cell responses in the presence or absence of DONQ52, which was designed to reduce the wheat-specific T-cell response because 90% of gluten intake is from wheat. “If you have celiac disease, you have a reservoir of these gluten-specific T cells. When you eat gluten, they’ll be activated and switched on and that’s what we want to block,” Dr. Tye-Din said.
The main assessment – a day 6 wheat challenge among 15 responders – revealed a more than 80% reduction in T-cell responses to a peptide cocktail. DONQ52 also reduced barley and rye T cell responses in a day 6 challenge, although to a lesser degree (40%/80%).
“DONQ52 is designed to target individual peptides that trigger the disease, and we showed that it did it very well to the wheat peptides, well over 80%. That’s a very impressive reduction in responses,” he said. A further test among 20 samples showed that DONQ52 did not activate T-cells nonspecifically. “You don’t want to trigger an unnecessary response,” Dr. Tye-Din added.
“DONQ52 effectively reduces activation of wheat gluten-specific T cells. It also has broad reactivity extending to barley and rye T-cell epitopes,” said Dr. Hardy.
The study was funded by Chugai Pharmaceutical. Dr. Hardy is a coinventor on a provisional patent describing oats peptides in celiac disease therapeutics and diagnostics. Dr. Tye-Din disclosed associations with Chugai, Genentech, Janssen, and Takeda, among others.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
CHICAGO –
There are a number of clinical trials underway, including one for the investigational drug TPM502, which carries three gluten-specific antigenic peptides with overlapping T-cell epitopes for the HLA-DQ2.5 gene. And, research is underway for the novel KAN-101, which aims to restore the immune tolerance of gluten by targeting receptors on the liver. It received Fast Track designation by the Food and Drug Administration in 2022.
During the annual Digestive Disease Week® (DDW), researchers shared the results from a new proof-of-concept study for DONQ52, a bispecific antibody that targets HLA-DQ2.5. DONQ52 was found to be highly effective in blocking gluten-specific T cells, said investigator Jason A. Tye-Din, PhD, a researcher with The Walter and Eliza Hall Institute of Medical Research, Melbourne, and an investigator with Chugai Pharmaceutical, which is funding the DONQ52 research which has since advanced to a phase 1 study of 56 patients.
There are no existing drug therapies for celiac disease, which leaves patients with a lifelong, and strict, gluten-free diet as treatment. This strategy, however, often fails to induce mucosal healing or symptom control, and has stimulated a search for novel therapies, said Melinda Y. Hardy, PhD, a postdoctoral researcher with the University of Melbourne, and the first author of the DONQ52 study. While targeting the gluten-specific immune response is highly attractive, it presents safety and pharmacokinetic challenges, so a better alternative would be to develop antibodies that selectively bind to HLA-DQ2.5, which is found in 80%-90% of celiac disease patients, she said. DONQ52 blocks at least 25 gluten peptides, and binds specifically to complexes of HLA-DQ2.5 and a range of immunogenic gluten peptides.
The study included 20 patients who consumed wheat bread for 3 days. Blood samples were taken 1 day before the start of the trial and 6 days after it concluded. Twenty patients were found to be wheat challenged, 10 were barley challenged, and 14 were rye challenged.
All were tested for gluten-specific T-cell responses in the presence or absence of DONQ52, which was designed to reduce the wheat-specific T-cell response because 90% of gluten intake is from wheat. “If you have celiac disease, you have a reservoir of these gluten-specific T cells. When you eat gluten, they’ll be activated and switched on and that’s what we want to block,” Dr. Tye-Din said.
The main assessment – a day 6 wheat challenge among 15 responders – revealed a more than 80% reduction in T-cell responses to a peptide cocktail. DONQ52 also reduced barley and rye T cell responses in a day 6 challenge, although to a lesser degree (40%/80%).
“DONQ52 is designed to target individual peptides that trigger the disease, and we showed that it did it very well to the wheat peptides, well over 80%. That’s a very impressive reduction in responses,” he said. A further test among 20 samples showed that DONQ52 did not activate T-cells nonspecifically. “You don’t want to trigger an unnecessary response,” Dr. Tye-Din added.
“DONQ52 effectively reduces activation of wheat gluten-specific T cells. It also has broad reactivity extending to barley and rye T-cell epitopes,” said Dr. Hardy.
The study was funded by Chugai Pharmaceutical. Dr. Hardy is a coinventor on a provisional patent describing oats peptides in celiac disease therapeutics and diagnostics. Dr. Tye-Din disclosed associations with Chugai, Genentech, Janssen, and Takeda, among others.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
CHICAGO –
There are a number of clinical trials underway, including one for the investigational drug TPM502, which carries three gluten-specific antigenic peptides with overlapping T-cell epitopes for the HLA-DQ2.5 gene. And, research is underway for the novel KAN-101, which aims to restore the immune tolerance of gluten by targeting receptors on the liver. It received Fast Track designation by the Food and Drug Administration in 2022.
During the annual Digestive Disease Week® (DDW), researchers shared the results from a new proof-of-concept study for DONQ52, a bispecific antibody that targets HLA-DQ2.5. DONQ52 was found to be highly effective in blocking gluten-specific T cells, said investigator Jason A. Tye-Din, PhD, a researcher with The Walter and Eliza Hall Institute of Medical Research, Melbourne, and an investigator with Chugai Pharmaceutical, which is funding the DONQ52 research which has since advanced to a phase 1 study of 56 patients.
There are no existing drug therapies for celiac disease, which leaves patients with a lifelong, and strict, gluten-free diet as treatment. This strategy, however, often fails to induce mucosal healing or symptom control, and has stimulated a search for novel therapies, said Melinda Y. Hardy, PhD, a postdoctoral researcher with the University of Melbourne, and the first author of the DONQ52 study. While targeting the gluten-specific immune response is highly attractive, it presents safety and pharmacokinetic challenges, so a better alternative would be to develop antibodies that selectively bind to HLA-DQ2.5, which is found in 80%-90% of celiac disease patients, she said. DONQ52 blocks at least 25 gluten peptides, and binds specifically to complexes of HLA-DQ2.5 and a range of immunogenic gluten peptides.
The study included 20 patients who consumed wheat bread for 3 days. Blood samples were taken 1 day before the start of the trial and 6 days after it concluded. Twenty patients were found to be wheat challenged, 10 were barley challenged, and 14 were rye challenged.
All were tested for gluten-specific T-cell responses in the presence or absence of DONQ52, which was designed to reduce the wheat-specific T-cell response because 90% of gluten intake is from wheat. “If you have celiac disease, you have a reservoir of these gluten-specific T cells. When you eat gluten, they’ll be activated and switched on and that’s what we want to block,” Dr. Tye-Din said.
The main assessment – a day 6 wheat challenge among 15 responders – revealed a more than 80% reduction in T-cell responses to a peptide cocktail. DONQ52 also reduced barley and rye T cell responses in a day 6 challenge, although to a lesser degree (40%/80%).
“DONQ52 is designed to target individual peptides that trigger the disease, and we showed that it did it very well to the wheat peptides, well over 80%. That’s a very impressive reduction in responses,” he said. A further test among 20 samples showed that DONQ52 did not activate T-cells nonspecifically. “You don’t want to trigger an unnecessary response,” Dr. Tye-Din added.
“DONQ52 effectively reduces activation of wheat gluten-specific T cells. It also has broad reactivity extending to barley and rye T-cell epitopes,” said Dr. Hardy.
The study was funded by Chugai Pharmaceutical. Dr. Hardy is a coinventor on a provisional patent describing oats peptides in celiac disease therapeutics and diagnostics. Dr. Tye-Din disclosed associations with Chugai, Genentech, Janssen, and Takeda, among others.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
AT DDW 2023
Multiple successive biologic to biosimilar switches deemed safe and effective
CHICAGO – according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).
“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.
While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.
The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.
During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)
Infliximab persistence
Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).
While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.
What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.
Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.
“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.
Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
CHICAGO – according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).
“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.
While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.
The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.
During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)
Infliximab persistence
Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).
While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.
What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.
Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.
“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.
Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
CHICAGO – according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).
“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.
While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.
The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.
During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)
Infliximab persistence
Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).
While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.
What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.
Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.
“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.
Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
AT DDW 2023
Few patients take weight control medications after bariatric surgery
CHICAGO –
Obesity is a chronic, relapsing condition that must be treated as such, said the study’s author Stephen A. Firkins, MD, a fellow of gastroenterology and hepatology at the Cleveland Clinic. “Barriers to antiobesity medications must be identified.”
“If a quarter of all patients experience weight regain and another quarter experience insufficient weight loss – but only 5% are being prescribed an FDA-approved AOM – that means there’s underutilization,” Dr. Firkins said.
Data from the National Health and Nutrition Examination Survey show that 30.7% of all men and women in the United States are overweight and of these, 42.4% are obese. For the severely obese, bariatric surgery, including sleeve gastrectomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass, are viable options with differing degrees of long-term success.
And while antiobesity medications such as orlistat (Xenical, Alli), phentermine/topiramate (Qsymia), naltrexone/bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and setmelanotide (Imcivree), may be considered before bariatric surgery, there are questions about the need for its use after surgery.
“While these are often employed or considered presurgically, there is a paucity of literature describing their utilization postsurgically, particularly in regards to newer antiobesity medications such as the [glucagonlike peptide–1] receptor agonists,” Dr. Firkins said.
The aim of Dr. Firkins’ analysis of the large, publicly available IBM Explorys Electronic Health Record, which included 59,160 adult post–bariatric surgery patients, was to identify postoperative weight control medication use and trends among different populations.
He found rates of postsurgical weight control medication use at 8% for topiramate (off label), 2.9% for liraglutide, 1.03% for phentermine/topiramate, 0.95% for naltrexone/bupropion, 0.52% for semaglutide and 0.1% for orlistat. Rates of topiramate use were higher for patients in the 35- 39-year range, and for orlistat and liraglutide in the 65- to 69-year range.
The differences, Dr. Firkins said, were likely related to side-effect profiles and accumulations of comorbidities with advancing age. Black patients were more likely to be prescribed the medications. Also, further analysis showed a significantly higher use of these medications among individuals with hypertension, diabetes, and hyperlipidemia.
The analyses raised several questions for future study, Dr. Firkins said: “What is the optimal timing of antiobesity medication initiation? Is it at the plateau of peak weight loss typically seen at 1-3 years post surgery? Or, after weight is regained? What is the phenotype of patients who are going to be good responders versus poor responders to a particular medication category?”
“Upon recognition of insufficient weight loss/weight regain, a multidisciplinary strategy towards management is warranted, including behavioral and dietary counseling, and consideration of AOM early use, as well as endoscopic or surgical revision,” he said.
Dr. Firkins had no disclosures.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
CHICAGO –
Obesity is a chronic, relapsing condition that must be treated as such, said the study’s author Stephen A. Firkins, MD, a fellow of gastroenterology and hepatology at the Cleveland Clinic. “Barriers to antiobesity medications must be identified.”
“If a quarter of all patients experience weight regain and another quarter experience insufficient weight loss – but only 5% are being prescribed an FDA-approved AOM – that means there’s underutilization,” Dr. Firkins said.
Data from the National Health and Nutrition Examination Survey show that 30.7% of all men and women in the United States are overweight and of these, 42.4% are obese. For the severely obese, bariatric surgery, including sleeve gastrectomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass, are viable options with differing degrees of long-term success.
And while antiobesity medications such as orlistat (Xenical, Alli), phentermine/topiramate (Qsymia), naltrexone/bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and setmelanotide (Imcivree), may be considered before bariatric surgery, there are questions about the need for its use after surgery.
“While these are often employed or considered presurgically, there is a paucity of literature describing their utilization postsurgically, particularly in regards to newer antiobesity medications such as the [glucagonlike peptide–1] receptor agonists,” Dr. Firkins said.
The aim of Dr. Firkins’ analysis of the large, publicly available IBM Explorys Electronic Health Record, which included 59,160 adult post–bariatric surgery patients, was to identify postoperative weight control medication use and trends among different populations.
He found rates of postsurgical weight control medication use at 8% for topiramate (off label), 2.9% for liraglutide, 1.03% for phentermine/topiramate, 0.95% for naltrexone/bupropion, 0.52% for semaglutide and 0.1% for orlistat. Rates of topiramate use were higher for patients in the 35- 39-year range, and for orlistat and liraglutide in the 65- to 69-year range.
The differences, Dr. Firkins said, were likely related to side-effect profiles and accumulations of comorbidities with advancing age. Black patients were more likely to be prescribed the medications. Also, further analysis showed a significantly higher use of these medications among individuals with hypertension, diabetes, and hyperlipidemia.
The analyses raised several questions for future study, Dr. Firkins said: “What is the optimal timing of antiobesity medication initiation? Is it at the plateau of peak weight loss typically seen at 1-3 years post surgery? Or, after weight is regained? What is the phenotype of patients who are going to be good responders versus poor responders to a particular medication category?”
“Upon recognition of insufficient weight loss/weight regain, a multidisciplinary strategy towards management is warranted, including behavioral and dietary counseling, and consideration of AOM early use, as well as endoscopic or surgical revision,” he said.
Dr. Firkins had no disclosures.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
CHICAGO –
Obesity is a chronic, relapsing condition that must be treated as such, said the study’s author Stephen A. Firkins, MD, a fellow of gastroenterology and hepatology at the Cleveland Clinic. “Barriers to antiobesity medications must be identified.”
“If a quarter of all patients experience weight regain and another quarter experience insufficient weight loss – but only 5% are being prescribed an FDA-approved AOM – that means there’s underutilization,” Dr. Firkins said.
Data from the National Health and Nutrition Examination Survey show that 30.7% of all men and women in the United States are overweight and of these, 42.4% are obese. For the severely obese, bariatric surgery, including sleeve gastrectomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass, are viable options with differing degrees of long-term success.
And while antiobesity medications such as orlistat (Xenical, Alli), phentermine/topiramate (Qsymia), naltrexone/bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and setmelanotide (Imcivree), may be considered before bariatric surgery, there are questions about the need for its use after surgery.
“While these are often employed or considered presurgically, there is a paucity of literature describing their utilization postsurgically, particularly in regards to newer antiobesity medications such as the [glucagonlike peptide–1] receptor agonists,” Dr. Firkins said.
The aim of Dr. Firkins’ analysis of the large, publicly available IBM Explorys Electronic Health Record, which included 59,160 adult post–bariatric surgery patients, was to identify postoperative weight control medication use and trends among different populations.
He found rates of postsurgical weight control medication use at 8% for topiramate (off label), 2.9% for liraglutide, 1.03% for phentermine/topiramate, 0.95% for naltrexone/bupropion, 0.52% for semaglutide and 0.1% for orlistat. Rates of topiramate use were higher for patients in the 35- 39-year range, and for orlistat and liraglutide in the 65- to 69-year range.
The differences, Dr. Firkins said, were likely related to side-effect profiles and accumulations of comorbidities with advancing age. Black patients were more likely to be prescribed the medications. Also, further analysis showed a significantly higher use of these medications among individuals with hypertension, diabetes, and hyperlipidemia.
The analyses raised several questions for future study, Dr. Firkins said: “What is the optimal timing of antiobesity medication initiation? Is it at the plateau of peak weight loss typically seen at 1-3 years post surgery? Or, after weight is regained? What is the phenotype of patients who are going to be good responders versus poor responders to a particular medication category?”
“Upon recognition of insufficient weight loss/weight regain, a multidisciplinary strategy towards management is warranted, including behavioral and dietary counseling, and consideration of AOM early use, as well as endoscopic or surgical revision,” he said.
Dr. Firkins had no disclosures.
DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.
AT DDW 2023
Quick medication, better communication linked to less violence at inpatient psych unit
SAN FRANCISCO – Physically violent events at an inpatient psychiatric unit in Pennsylvania dropped by 59.8% in the months after it implemented a plan to administer antipsychotic medications to patients more quickly – both in the emergency department and in the unit – and improve handoffs between providers and nurses, researchers reported.
“We were able to significantly reduce violence,” said Michael Chen, MD, Lehigh Valley Health Network psychiatry resident and lead author of an abstract presented at the annual meeting of the American Psychiatric Association. “Furthermore, the interventions were effective in reducing episodes of violence rather than redirecting it. And the overall feeling of safety on the inpatient psychiatric unit improved.”
Violence is common in psychiatric units, although it’s not clear how often it occurs. “The data has shown that patients with a psychotic disorder such as schizophrenia or a mood disorder with psychotic features such as bipolar disorder tend to account for most of the episodes of violence on the unit,” Dr. Chen said in an interview. “This inevitably results in a higher risk for violence on inpatient psychiatric units as a large portion of patients admitted to inpatient psychiatric units have these diagnoses.”
Enlisting the pharmacy department
For the new study, investigators tracked episodes of violence – including verbal attacks – at an Allentown, Penn.–area inpatient psychiatric unit from December 2021 to September 2022. According to Dr. Chen, unit leaders implemented the new plan in May 2022 in the wake of higher levels of violence during the COVID-19 pandemic and the concurrent staff shortages.
Clinic leaders sought to identify potentially aggressive patients in the emergency department and treat them with antipsychotics prior to admission to the psychiatric unit, ensure that the pharmacy provides access to as-needed or standing medications, and develop “standardized huddles to ensure proper handoffs between providers and nurses.”
Medical staff relied on the Dynamic Appraisal of Situational Aggression scale, risk factors, and clinical judgment to determine which patients had the potential to be violent, Dr. Chen said.
As for treatment, first-line antipsychotics are typically given orally, but they can be injected if patients must be treated over their objections, he said. “We would only consider starting standing medications against objections in patients who are involuntarily committed.”
During the 5 months before the intervention was implemented versus the following 5 months, the average monthly number of physically violent events in the psychiatric unit fell from 12.4 to 4.8 (–61.1%, P = .04), and verbal threats dipped from 7.2 to 4 (–44.4%, P = .15). The total average number of violent events per month, including violence against property, fell from an average of 25.4 to 10.2 (–59.8%, P = .03).
The total patient population didn’t vary significantly over time, Dr. Chen said. “Thus, the decrease in violence was not correlated with a decrease in patient load.”
While “there were concerns that there would just be higher episodes of violence in the ED while psychiatry patients awaited placement,” Dr. Chen said, the numbers actually showed reductions in violence in that setting. The average number of physically violent events per month in the ED fell from 49.6 to 39.4 (–20.6%, P = .03). Verbal threats dropped from 38 to 34.6 (–8.9%, P = .5) and overall violent events dipped from 87.6 to 74 (–15.6%, P = .08).
Why did the interventions seem to work? “Standing doses as well as as-needed medications started for psychiatric patients in the emergency department have been crucial to prevent delay of care,” Dr. Chen said. Enlisting the pharmacy department “helped ensure all patients had appropriate as-needed medications to prevent them from decompensating on the units,” he added, and “involvement of nursing and ancillary staff in high-risk rounds allowed the treatment team to rapidly anticipate and address concerns.”
The study authors also reported that nursing staff felt safer. Scores on a perception-of-safety scale – with 1 most unsafe and 7 most safe – improved from 3.3 to 4.2 (+27%, P < .01).
Dr. Chen said there was a “minimal” increase in cost to implement the intervention, although coordination is necessary. “The emergency department and psychiatry department have to work together to initiate treatment in the ED while awaiting beds,” he said. “The treatment team needs to communicate concerns during rounds. The pharmacist and psychiatrist need to work together to ensure that proper as-needed medications are available.”
‘Good clinical practice’
In an interview, psychiatrist Mark J. Russ, MD, of NewYork-Presbyterian/Westchester Behavioral Health and Weill Cornell Medical College, said violent incidents in inpatient psychiatric units are influenced by many factors, such as history of violence, substance use, history of trauma, psychosis/paranoia, and medical problems.
The units themselves can contribute to the risk of violence through power struggles and lack of attention paid to respect and dignity, he said. “Attention to these issues is important in reducing violence,” he noted. “Generalized training for staff in de-escalation techniques and trauma-informed care is imperative. There may be value in developing specialized psychiatric ICUs where staff are meticulously trained in these and other approaches.”
The new study, Dr. Russ said, suggests that “early identification of patients at risk of engaging in violent behavior on the inpatient unit, pharmacologic treatment, and good communication helps reduce violence.” The findings, he added, suggest that “interventions known to constitute good clinical practice are indeed helpful.”
However, he cautioned that “treating all at-risk patients with antipsychotics, regardless of their psychiatric diagnosis, might well be considered chemical restraint, depending on [the] circumstances.”
There was no study funding. The study authors and Dr. Russ have no disclosures.
SAN FRANCISCO – Physically violent events at an inpatient psychiatric unit in Pennsylvania dropped by 59.8% in the months after it implemented a plan to administer antipsychotic medications to patients more quickly – both in the emergency department and in the unit – and improve handoffs between providers and nurses, researchers reported.
“We were able to significantly reduce violence,” said Michael Chen, MD, Lehigh Valley Health Network psychiatry resident and lead author of an abstract presented at the annual meeting of the American Psychiatric Association. “Furthermore, the interventions were effective in reducing episodes of violence rather than redirecting it. And the overall feeling of safety on the inpatient psychiatric unit improved.”
Violence is common in psychiatric units, although it’s not clear how often it occurs. “The data has shown that patients with a psychotic disorder such as schizophrenia or a mood disorder with psychotic features such as bipolar disorder tend to account for most of the episodes of violence on the unit,” Dr. Chen said in an interview. “This inevitably results in a higher risk for violence on inpatient psychiatric units as a large portion of patients admitted to inpatient psychiatric units have these diagnoses.”
Enlisting the pharmacy department
For the new study, investigators tracked episodes of violence – including verbal attacks – at an Allentown, Penn.–area inpatient psychiatric unit from December 2021 to September 2022. According to Dr. Chen, unit leaders implemented the new plan in May 2022 in the wake of higher levels of violence during the COVID-19 pandemic and the concurrent staff shortages.
Clinic leaders sought to identify potentially aggressive patients in the emergency department and treat them with antipsychotics prior to admission to the psychiatric unit, ensure that the pharmacy provides access to as-needed or standing medications, and develop “standardized huddles to ensure proper handoffs between providers and nurses.”
Medical staff relied on the Dynamic Appraisal of Situational Aggression scale, risk factors, and clinical judgment to determine which patients had the potential to be violent, Dr. Chen said.
As for treatment, first-line antipsychotics are typically given orally, but they can be injected if patients must be treated over their objections, he said. “We would only consider starting standing medications against objections in patients who are involuntarily committed.”
During the 5 months before the intervention was implemented versus the following 5 months, the average monthly number of physically violent events in the psychiatric unit fell from 12.4 to 4.8 (–61.1%, P = .04), and verbal threats dipped from 7.2 to 4 (–44.4%, P = .15). The total average number of violent events per month, including violence against property, fell from an average of 25.4 to 10.2 (–59.8%, P = .03).
The total patient population didn’t vary significantly over time, Dr. Chen said. “Thus, the decrease in violence was not correlated with a decrease in patient load.”
While “there were concerns that there would just be higher episodes of violence in the ED while psychiatry patients awaited placement,” Dr. Chen said, the numbers actually showed reductions in violence in that setting. The average number of physically violent events per month in the ED fell from 49.6 to 39.4 (–20.6%, P = .03). Verbal threats dropped from 38 to 34.6 (–8.9%, P = .5) and overall violent events dipped from 87.6 to 74 (–15.6%, P = .08).
Why did the interventions seem to work? “Standing doses as well as as-needed medications started for psychiatric patients in the emergency department have been crucial to prevent delay of care,” Dr. Chen said. Enlisting the pharmacy department “helped ensure all patients had appropriate as-needed medications to prevent them from decompensating on the units,” he added, and “involvement of nursing and ancillary staff in high-risk rounds allowed the treatment team to rapidly anticipate and address concerns.”
The study authors also reported that nursing staff felt safer. Scores on a perception-of-safety scale – with 1 most unsafe and 7 most safe – improved from 3.3 to 4.2 (+27%, P < .01).
Dr. Chen said there was a “minimal” increase in cost to implement the intervention, although coordination is necessary. “The emergency department and psychiatry department have to work together to initiate treatment in the ED while awaiting beds,” he said. “The treatment team needs to communicate concerns during rounds. The pharmacist and psychiatrist need to work together to ensure that proper as-needed medications are available.”
‘Good clinical practice’
In an interview, psychiatrist Mark J. Russ, MD, of NewYork-Presbyterian/Westchester Behavioral Health and Weill Cornell Medical College, said violent incidents in inpatient psychiatric units are influenced by many factors, such as history of violence, substance use, history of trauma, psychosis/paranoia, and medical problems.
The units themselves can contribute to the risk of violence through power struggles and lack of attention paid to respect and dignity, he said. “Attention to these issues is important in reducing violence,” he noted. “Generalized training for staff in de-escalation techniques and trauma-informed care is imperative. There may be value in developing specialized psychiatric ICUs where staff are meticulously trained in these and other approaches.”
The new study, Dr. Russ said, suggests that “early identification of patients at risk of engaging in violent behavior on the inpatient unit, pharmacologic treatment, and good communication helps reduce violence.” The findings, he added, suggest that “interventions known to constitute good clinical practice are indeed helpful.”
However, he cautioned that “treating all at-risk patients with antipsychotics, regardless of their psychiatric diagnosis, might well be considered chemical restraint, depending on [the] circumstances.”
There was no study funding. The study authors and Dr. Russ have no disclosures.
SAN FRANCISCO – Physically violent events at an inpatient psychiatric unit in Pennsylvania dropped by 59.8% in the months after it implemented a plan to administer antipsychotic medications to patients more quickly – both in the emergency department and in the unit – and improve handoffs between providers and nurses, researchers reported.
“We were able to significantly reduce violence,” said Michael Chen, MD, Lehigh Valley Health Network psychiatry resident and lead author of an abstract presented at the annual meeting of the American Psychiatric Association. “Furthermore, the interventions were effective in reducing episodes of violence rather than redirecting it. And the overall feeling of safety on the inpatient psychiatric unit improved.”
Violence is common in psychiatric units, although it’s not clear how often it occurs. “The data has shown that patients with a psychotic disorder such as schizophrenia or a mood disorder with psychotic features such as bipolar disorder tend to account for most of the episodes of violence on the unit,” Dr. Chen said in an interview. “This inevitably results in a higher risk for violence on inpatient psychiatric units as a large portion of patients admitted to inpatient psychiatric units have these diagnoses.”
Enlisting the pharmacy department
For the new study, investigators tracked episodes of violence – including verbal attacks – at an Allentown, Penn.–area inpatient psychiatric unit from December 2021 to September 2022. According to Dr. Chen, unit leaders implemented the new plan in May 2022 in the wake of higher levels of violence during the COVID-19 pandemic and the concurrent staff shortages.
Clinic leaders sought to identify potentially aggressive patients in the emergency department and treat them with antipsychotics prior to admission to the psychiatric unit, ensure that the pharmacy provides access to as-needed or standing medications, and develop “standardized huddles to ensure proper handoffs between providers and nurses.”
Medical staff relied on the Dynamic Appraisal of Situational Aggression scale, risk factors, and clinical judgment to determine which patients had the potential to be violent, Dr. Chen said.
As for treatment, first-line antipsychotics are typically given orally, but they can be injected if patients must be treated over their objections, he said. “We would only consider starting standing medications against objections in patients who are involuntarily committed.”
During the 5 months before the intervention was implemented versus the following 5 months, the average monthly number of physically violent events in the psychiatric unit fell from 12.4 to 4.8 (–61.1%, P = .04), and verbal threats dipped from 7.2 to 4 (–44.4%, P = .15). The total average number of violent events per month, including violence against property, fell from an average of 25.4 to 10.2 (–59.8%, P = .03).
The total patient population didn’t vary significantly over time, Dr. Chen said. “Thus, the decrease in violence was not correlated with a decrease in patient load.”
While “there were concerns that there would just be higher episodes of violence in the ED while psychiatry patients awaited placement,” Dr. Chen said, the numbers actually showed reductions in violence in that setting. The average number of physically violent events per month in the ED fell from 49.6 to 39.4 (–20.6%, P = .03). Verbal threats dropped from 38 to 34.6 (–8.9%, P = .5) and overall violent events dipped from 87.6 to 74 (–15.6%, P = .08).
Why did the interventions seem to work? “Standing doses as well as as-needed medications started for psychiatric patients in the emergency department have been crucial to prevent delay of care,” Dr. Chen said. Enlisting the pharmacy department “helped ensure all patients had appropriate as-needed medications to prevent them from decompensating on the units,” he added, and “involvement of nursing and ancillary staff in high-risk rounds allowed the treatment team to rapidly anticipate and address concerns.”
The study authors also reported that nursing staff felt safer. Scores on a perception-of-safety scale – with 1 most unsafe and 7 most safe – improved from 3.3 to 4.2 (+27%, P < .01).
Dr. Chen said there was a “minimal” increase in cost to implement the intervention, although coordination is necessary. “The emergency department and psychiatry department have to work together to initiate treatment in the ED while awaiting beds,” he said. “The treatment team needs to communicate concerns during rounds. The pharmacist and psychiatrist need to work together to ensure that proper as-needed medications are available.”
‘Good clinical practice’
In an interview, psychiatrist Mark J. Russ, MD, of NewYork-Presbyterian/Westchester Behavioral Health and Weill Cornell Medical College, said violent incidents in inpatient psychiatric units are influenced by many factors, such as history of violence, substance use, history of trauma, psychosis/paranoia, and medical problems.
The units themselves can contribute to the risk of violence through power struggles and lack of attention paid to respect and dignity, he said. “Attention to these issues is important in reducing violence,” he noted. “Generalized training for staff in de-escalation techniques and trauma-informed care is imperative. There may be value in developing specialized psychiatric ICUs where staff are meticulously trained in these and other approaches.”
The new study, Dr. Russ said, suggests that “early identification of patients at risk of engaging in violent behavior on the inpatient unit, pharmacologic treatment, and good communication helps reduce violence.” The findings, he added, suggest that “interventions known to constitute good clinical practice are indeed helpful.”
However, he cautioned that “treating all at-risk patients with antipsychotics, regardless of their psychiatric diagnosis, might well be considered chemical restraint, depending on [the] circumstances.”
There was no study funding. The study authors and Dr. Russ have no disclosures.
AT APA 2023
Overweight in heterozygous FH tied to even higher CAD risk
MANNHEIM, GERMANY – – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.
Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.
Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.
Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.
She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”
The research was presented at the annual meeting of the European Atherosclerosis Society.
Tended to be thin
Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.
However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.
In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.
As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”
Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).
Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”
In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”
Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”
Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”
The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.
Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.
Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”
Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
More with than without
Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”
Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.
Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.
They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.
Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.
For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.
Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.
Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.
In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.
Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.
Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.
Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).
Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.
Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).
The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.
No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.
A version of this article first appeared on Medscape.com.
MANNHEIM, GERMANY – – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.
Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.
Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.
Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.
She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”
The research was presented at the annual meeting of the European Atherosclerosis Society.
Tended to be thin
Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.
However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.
In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.
As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”
Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).
Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”
In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”
Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”
Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”
The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.
Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.
Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”
Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
More with than without
Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”
Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.
Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.
They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.
Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.
For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.
Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.
Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.
In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.
Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.
Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.
Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).
Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.
Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).
The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.
No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.
A version of this article first appeared on Medscape.com.
MANNHEIM, GERMANY – – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.
Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.
Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.
Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.
She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”
The research was presented at the annual meeting of the European Atherosclerosis Society.
Tended to be thin
Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.
However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.
In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.
As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”
Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).
Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”
In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”
Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”
Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”
The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.
Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.
Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”
Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
More with than without
Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”
Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.
Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.
They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.
Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.
For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.
Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.
Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.
In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.
Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.
Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.
Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).
Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.
Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).
The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.
No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.
A version of this article first appeared on Medscape.com.
AT EAS 2023