The day I interviewed at Johns Hopkins in Baltimore, like every other day of residency interviews, was a very long and draining day.

I started by meeting alone with Philip Slavney, MD, the residency director, who spoke with me about the program and gave me a schedule to follow. I was to meet with residents and psychiatrists, some of whom had graduated from my medical school, and was sent to the Bayview campus a few miles away to have lunch and attend a few meetings. By the time I boarded an Amtrak train at Baltimore Penn Station, I was tired but I liked what I had seen. By the end of the interview season, I had crossed four programs off my list and had decided to rank only three.

In 1987, there were 987 residency positions in psychiatry in the United States, and 83.6% of those positions filled with a combination of U.S. and international medical graduates. Still, this was a risky move; the programs that I decided to rank would fill, but I was matching separately for an internship year in internal medicine in New York and decided that I would rather reapply in a year than risk matching at a program I didn’t want to go to.

I wasn’t quite sure where I wanted to rank Hopkins on my list, so I called Dr. Slavney and said I wanted to come back and meet more members of the department. He did not hide his surprise and was quick to tell me that no one had ever requested a second set of interviews. I mentioned specific people I wanted to meet with, and he was kind enough to accommodate my request and set up a second day of interviews for me.

Needless to say, the residency match felt very personal – at least to me – and although I felt vulnerable, I also felt empowered. Because of the low pay, patients with stigmatized illnesses, and the rampant belief that psychiatry was not “real” medicine and the patients never got better, psychiatry was not a desired specialty.

The residency application process in psychiatry (and every other specialty) has become a much different process. In 2006, the Association of American Medical Colleges called on medical schools to increase their enrollments to address the national shortage of physicians. Soon, there were more medical schools, bigger classes, and more doctors being minted, but the Balanced Budget Act of 1997 prevented a proportional increase in residency positions.

Len Marquez, senior director of government relations at the AAMC noted: “The Resident Physician Shortage Reduction Act of 2021 (S. 834), sponsored by Sen. Robert Menendez (D-N.J.), Sen. John Boozman (R-Ark.), and Majority Leader Sen. Charles Schumer (D-N.Y.), would support 2,000 additional Medicare-supported residency positions each year for 7 years, but Congress has not yet acted on the legislation. We were very pleased that last year, Congress passed the first increase in Medicare-supported graduate medical education in 25 years by including 1,000 new slots as part of the Consolidated Appropriations Act, 2021.”

In addition, the Build Back Better Act, which is currently being debated in Congress, would provide 4,000 more graduate medical education slots, including a specific requirement that 15% of them go to “psychiatry-related residencies,” he added.

Over 90% of graduates from U.S. medical schools currently match into a residency position. That statistic for international medical graduates is notably lower, with perhaps as few as 50% of all applicants matching.

Since 2014, the number of applicants to psychiatry residencies has nearly doubled. For the 2021 match, there were 2,486 applicants applying for 1,858 positions in psychiatry – so 1.34 applicants for each slot. Of the 1,117 senior medical students at U.S. schools who applied to psychiatry residencies, 129 did not match. Overall, 99.8% of residency positions in psychiatry filled. 

“It used to be less competitive,” said Kaz J. Nelson, MD, the vice chair for education at the University of Minnesota’s department of psychiatry and behavioral sciences in Minneapolis, adding that interest in psychiatry has increased over the years. 

“Interest has skyrocketed as the word has gotten out about how great a field it is. It helps that reimbursements are better, that there is less bias and discrimination against patients with psychiatric issues, and that psychiatric care is seen as a legitimate part of medicine. It has been exciting to watch!” Dr. Nelson said.

The numbers are only one part of the story, however. 

Application submission now involves a centralized, electronic process, and it has become easier for applicants to apply to a lot of programs indiscriminately. It’s not unusual for applicants to apply to 70 or more programs. The factors that have limited applications include the cost: Electronic Residency Application Services (ERAS) charges for each application package they send to a program, and applicants traditionally pay to travel to the programs where they interview. This all changed with the 2021 cycle when in-person interviews were halted for the pandemic and interviews became virtual. While I recall applying to 7 residency programs, this year the average number of applications was 54.7 per applicant.

“It used to be that the cap on interviewing was financial,” Dr. Nelson said. “It was discriminatory and favored those who had more money to travel to interviews. There are still the ERAS fees, but COVID has been an equalizer and we are getting more applicants, and interviewing more who are not from Minnesota or the Midwest. We have been working to make our program attractive in terms of diversity, equity, inclusion, and justice. Our hospital is located a mile from where George Floyd was murdered, and it’s our responsibility to lead the effort to ensure the psychiatry workforce is diverse, and inclusive, as possible.”

Daniel E. Gih, MD, is the program director for a new psychiatry residency at the University of Nebraska, Omaha. When the program started in 2019, there were spots for four residents and the program had 588 applications. In 2020, the program grew to five positions and this year there were 553 applicants. Dr. Gih attributed the high number of applications to his program’s strong social media presence.

“Going through the applications and meeting the students are some of the most enjoyable parts of my work,” Dr. Gih said. “I feel guilty though, that I’m likely going to miss a great applicant. Each application averages 35 pages and it’s inevitable that programs have to take shortcuts. Applicants worry that they’ll be ranked by board scores. While we certainly don’t do that here, students might feel ruled out of a program if their numbers aren’t high enough. Furthermore, wealthy students can apply to more programs. The pandemic has really highlighted the inequity issues.”

Dr. Gih noted that the Zoom interview process has not been disappointing: “Two of the people we matched had never been to Omaha, and many expressed concerns about what it is like here. Of course, on Zoom you don’t catch subtle interpersonal issues, but we have been pleasantly surprised that the people we matched were consistent with what we expected. It is exciting to meet the people who will eventually replace us as psychiatrists, they will be here to deal with future challenges!” His enthusiasm was tangible. 

While the program directors remain optimistic, the system is not without its stresses, as many programs receive over 1,000 applications.

“This is difficult,” Dr. Nelson said.” It’s wonderful for the programs, but for the medical students, not matching is experienced by them as being catastrophic, so they apply to a lot of programs. Getting this many applications is a challenge, yet I don’t want to interview someone if they are going to rank our program No. 80 on their list!” 

Residencies have dealt with the deluge of applicants in a number of ways. Some specialties started a “signal” protocol wherein candidates and programs receive a certain number of tokens to indicate that each would rank the other highly, but psychiatry has not done this. Early on in the Zoom process, multiple applicants would be offered interviews simultaneously, and the interview would be given to the candidate who responded first. Students vented their frustrations on Twitter when they lost interview spots at their coveted programs because they hadn’t checked their email in time or had gone to take a shower.

“The American Association of Directors of Psychiatry Residency Training Programs issued guidelines saying that it is unacceptable to offer interview spots without allowing a reasonable time for the applicant to respond, and that it is not appropriate to offer multiple candidates one spot on a first-come, first-serve basis,” Dr. Nelson explained.

Her program has managed some of the application chaos by using a software program called Scutmonkey, codeveloped by David Ross, MD, PhD, the associate program director of the Yale Adult Psychiatry Residency Program.

“It lets us screen applications for candidates who specifically are interested in being here, and for those who qualify as part of the mission we are trying to fulfill.”

One fourth-year student at a mid-Atlantic medical school who is applying in psychiatry – who I’ll call Sacha to protect his anonymity – applied to 73 psychiatry programs and to date, has interviewed at 6. He describes a stressful, roller coaster experience:

“I got those six interviews right away and that was an amazing start, but then I didn’t get any more. The interviews I had went well, but it has been disappointing not to have more. Some were all-day interviews, while other programs had me meet with residents and attendings for 20 minutes each and it was all done after 2 hours.”

He has mixed opinions about not seeing the schools in person. “There are very heavy pros and cons. I’ve saved thousands of dollars in travel expenses that would have limited my applications, so logistically it’s a dream. On the other hand, I’ve interviewed in cities I have never been to, it’s hard to get a sense of the intangibles of a program, and the shorter interviews feel very impersonal.” 

Sacha expressed anxieties about the process. “With so many applicants, it’s difficult for someone with a nontraditional story to get a spot and it’s easier for the programs to toss applications. With all of my classmates, there is the palpable fear of not matching anywhere, it’s common enough and everyone has seen someone who has gone through this. At times, we feel powerless; we have no real agency or control. We send stuff out and then we sit in the prayer position and wait.”

I think back on my own application process with a sense of gratitude. I certainly didn’t feel powerless, and in today’s world, postinterview communications with program directors are regulated for both parties. Dr. Slavney was kind enough to humor my request, but I don’t believe this would be feasible in the current environment.

Even though it is wonderful that more doctors have figured out that careers in psychiatry are rewarding, the current situation is overwhelming for both the applicants and the programs. With over 100 applicants for every position – many of whom will have no interest in going to some of the programs they apply to – qualified candidates who go unmatched, and a roulette wheel which requires heavily indebted students to pay to apply, this is simply not sustainable in a country with a shortage of physicians – psychiatrists in particular. 

We hear that mid-level practitioners are the answer to our shortages, but perhaps we need to create a system with enough residency positions to accommodate highly trained and qualified physicians in a more inviting and targeted way.

Dinah Miller, MD, is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore. A version of this article first appeared on Medscape.com.

The day I interviewed at Johns Hopkins in Baltimore, like every other day of residency interviews, was a very long and draining day.

I started by meeting alone with Philip Slavney, MD, the residency director, who spoke with me about the program and gave me a schedule to follow. I was to meet with residents and psychiatrists, some of whom had graduated from my medical school, and was sent to the Bayview campus a few miles away to have lunch and attend a few meetings. By the time I boarded an Amtrak train at Baltimore Penn Station, I was tired but I liked what I had seen. By the end of the interview season, I had crossed four programs off my list and had decided to rank only three.

In 1987, there were 987 residency positions in psychiatry in the United States, and 83.6% of those positions filled with a combination of U.S. and international medical graduates. Still, this was a risky move; the programs that I decided to rank would fill, but I was matching separately for an internship year in internal medicine in New York and decided that I would rather reapply in a year than risk matching at a program I didn’t want to go to.

I wasn’t quite sure where I wanted to rank Hopkins on my list, so I called Dr. Slavney and said I wanted to come back and meet more members of the department. He did not hide his surprise and was quick to tell me that no one had ever requested a second set of interviews. I mentioned specific people I wanted to meet with, and he was kind enough to accommodate my request and set up a second day of interviews for me.

Needless to say, the residency match felt very personal – at least to me – and although I felt vulnerable, I also felt empowered. Because of the low pay, patients with stigmatized illnesses, and the rampant belief that psychiatry was not “real” medicine and the patients never got better, psychiatry was not a desired specialty.

The residency application process in psychiatry (and every other specialty) has become a much different process. In 2006, the Association of American Medical Colleges called on medical schools to increase their enrollments to address the national shortage of physicians. Soon, there were more medical schools, bigger classes, and more doctors being minted, but the Balanced Budget Act of 1997 prevented a proportional increase in residency positions.

Len Marquez, senior director of government relations at the AAMC noted: “The Resident Physician Shortage Reduction Act of 2021 (S. 834), sponsored by Sen. Robert Menendez (D-N.J.), Sen. John Boozman (R-Ark.), and Majority Leader Sen. Charles Schumer (D-N.Y.), would support 2,000 additional Medicare-supported residency positions each year for 7 years, but Congress has not yet acted on the legislation. We were very pleased that last year, Congress passed the first increase in Medicare-supported graduate medical education in 25 years by including 1,000 new slots as part of the Consolidated Appropriations Act, 2021.”

In addition, the Build Back Better Act, which is currently being debated in Congress, would provide 4,000 more graduate medical education slots, including a specific requirement that 15% of them go to “psychiatry-related residencies,” he added.

Over 90% of graduates from U.S. medical schools currently match into a residency position. That statistic for international medical graduates is notably lower, with perhaps as few as 50% of all applicants matching.

Since 2014, the number of applicants to psychiatry residencies has nearly doubled. For the 2021 match, there were 2,486 applicants applying for 1,858 positions in psychiatry – so 1.34 applicants for each slot. Of the 1,117 senior medical students at U.S. schools who applied to psychiatry residencies, 129 did not match. Overall, 99.8% of residency positions in psychiatry filled. 

“It used to be less competitive,” said Kaz J. Nelson, MD, the vice chair for education at the University of Minnesota’s department of psychiatry and behavioral sciences in Minneapolis, adding that interest in psychiatry has increased over the years. 

“Interest has skyrocketed as the word has gotten out about how great a field it is. It helps that reimbursements are better, that there is less bias and discrimination against patients with psychiatric issues, and that psychiatric care is seen as a legitimate part of medicine. It has been exciting to watch!” Dr. Nelson said.

The numbers are only one part of the story, however. 

Application submission now involves a centralized, electronic process, and it has become easier for applicants to apply to a lot of programs indiscriminately. It’s not unusual for applicants to apply to 70 or more programs. The factors that have limited applications include the cost: Electronic Residency Application Services (ERAS) charges for each application package they send to a program, and applicants traditionally pay to travel to the programs where they interview. This all changed with the 2021 cycle when in-person interviews were halted for the pandemic and interviews became virtual. While I recall applying to 7 residency programs, this year the average number of applications was 54.7 per applicant.

“It used to be that the cap on interviewing was financial,” Dr. Nelson said. “It was discriminatory and favored those who had more money to travel to interviews. There are still the ERAS fees, but COVID has been an equalizer and we are getting more applicants, and interviewing more who are not from Minnesota or the Midwest. We have been working to make our program attractive in terms of diversity, equity, inclusion, and justice. Our hospital is located a mile from where George Floyd was murdered, and it’s our responsibility to lead the effort to ensure the psychiatry workforce is diverse, and inclusive, as possible.”

Daniel E. Gih, MD, is the program director for a new psychiatry residency at the University of Nebraska, Omaha. When the program started in 2019, there were spots for four residents and the program had 588 applications. In 2020, the program grew to five positions and this year there were 553 applicants. Dr. Gih attributed the high number of applications to his program’s strong social media presence.

“Going through the applications and meeting the students are some of the most enjoyable parts of my work,” Dr. Gih said. “I feel guilty though, that I’m likely going to miss a great applicant. Each application averages 35 pages and it’s inevitable that programs have to take shortcuts. Applicants worry that they’ll be ranked by board scores. While we certainly don’t do that here, students might feel ruled out of a program if their numbers aren’t high enough. Furthermore, wealthy students can apply to more programs. The pandemic has really highlighted the inequity issues.”

Dr. Gih noted that the Zoom interview process has not been disappointing: “Two of the people we matched had never been to Omaha, and many expressed concerns about what it is like here. Of course, on Zoom you don’t catch subtle interpersonal issues, but we have been pleasantly surprised that the people we matched were consistent with what we expected. It is exciting to meet the people who will eventually replace us as psychiatrists, they will be here to deal with future challenges!” His enthusiasm was tangible. 

While the program directors remain optimistic, the system is not without its stresses, as many programs receive over 1,000 applications.

“This is difficult,” Dr. Nelson said.” It’s wonderful for the programs, but for the medical students, not matching is experienced by them as being catastrophic, so they apply to a lot of programs. Getting this many applications is a challenge, yet I don’t want to interview someone if they are going to rank our program No. 80 on their list!” 

Residencies have dealt with the deluge of applicants in a number of ways. Some specialties started a “signal” protocol wherein candidates and programs receive a certain number of tokens to indicate that each would rank the other highly, but psychiatry has not done this. Early on in the Zoom process, multiple applicants would be offered interviews simultaneously, and the interview would be given to the candidate who responded first. Students vented their frustrations on Twitter when they lost interview spots at their coveted programs because they hadn’t checked their email in time or had gone to take a shower.

“The American Association of Directors of Psychiatry Residency Training Programs issued guidelines saying that it is unacceptable to offer interview spots without allowing a reasonable time for the applicant to respond, and that it is not appropriate to offer multiple candidates one spot on a first-come, first-serve basis,” Dr. Nelson explained.

Her program has managed some of the application chaos by using a software program called Scutmonkey, codeveloped by David Ross, MD, PhD, the associate program director of the Yale Adult Psychiatry Residency Program.

“It lets us screen applications for candidates who specifically are interested in being here, and for those who qualify as part of the mission we are trying to fulfill.”

One fourth-year student at a mid-Atlantic medical school who is applying in psychiatry – who I’ll call Sacha to protect his anonymity – applied to 73 psychiatry programs and to date, has interviewed at 6. He describes a stressful, roller coaster experience:

“I got those six interviews right away and that was an amazing start, but then I didn’t get any more. The interviews I had went well, but it has been disappointing not to have more. Some were all-day interviews, while other programs had me meet with residents and attendings for 20 minutes each and it was all done after 2 hours.”

He has mixed opinions about not seeing the schools in person. “There are very heavy pros and cons. I’ve saved thousands of dollars in travel expenses that would have limited my applications, so logistically it’s a dream. On the other hand, I’ve interviewed in cities I have never been to, it’s hard to get a sense of the intangibles of a program, and the shorter interviews feel very impersonal.” 

Sacha expressed anxieties about the process. “With so many applicants, it’s difficult for someone with a nontraditional story to get a spot and it’s easier for the programs to toss applications. With all of my classmates, there is the palpable fear of not matching anywhere, it’s common enough and everyone has seen someone who has gone through this. At times, we feel powerless; we have no real agency or control. We send stuff out and then we sit in the prayer position and wait.”

I think back on my own application process with a sense of gratitude. I certainly didn’t feel powerless, and in today’s world, postinterview communications with program directors are regulated for both parties. Dr. Slavney was kind enough to humor my request, but I don’t believe this would be feasible in the current environment.

Even though it is wonderful that more doctors have figured out that careers in psychiatry are rewarding, the current situation is overwhelming for both the applicants and the programs. With over 100 applicants for every position – many of whom will have no interest in going to some of the programs they apply to – qualified candidates who go unmatched, and a roulette wheel which requires heavily indebted students to pay to apply, this is simply not sustainable in a country with a shortage of physicians – psychiatrists in particular. 

We hear that mid-level practitioners are the answer to our shortages, but perhaps we need to create a system with enough residency positions to accommodate highly trained and qualified physicians in a more inviting and targeted way.

Dinah Miller, MD, is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore. A version of this article first appeared on Medscape.com.

The day I interviewed at Johns Hopkins in Baltimore, like every other day of residency interviews, was a very long and draining day.

I started by meeting alone with Philip Slavney, MD, the residency director, who spoke with me about the program and gave me a schedule to follow. I was to meet with residents and psychiatrists, some of whom had graduated from my medical school, and was sent to the Bayview campus a few miles away to have lunch and attend a few meetings. By the time I boarded an Amtrak train at Baltimore Penn Station, I was tired but I liked what I had seen. By the end of the interview season, I had crossed four programs off my list and had decided to rank only three.

In 1987, there were 987 residency positions in psychiatry in the United States, and 83.6% of those positions filled with a combination of U.S. and international medical graduates. Still, this was a risky move; the programs that I decided to rank would fill, but I was matching separately for an internship year in internal medicine in New York and decided that I would rather reapply in a year than risk matching at a program I didn’t want to go to.

I wasn’t quite sure where I wanted to rank Hopkins on my list, so I called Dr. Slavney and said I wanted to come back and meet more members of the department. He did not hide his surprise and was quick to tell me that no one had ever requested a second set of interviews. I mentioned specific people I wanted to meet with, and he was kind enough to accommodate my request and set up a second day of interviews for me.

Needless to say, the residency match felt very personal – at least to me – and although I felt vulnerable, I also felt empowered. Because of the low pay, patients with stigmatized illnesses, and the rampant belief that psychiatry was not “real” medicine and the patients never got better, psychiatry was not a desired specialty.

The residency application process in psychiatry (and every other specialty) has become a much different process. In 2006, the Association of American Medical Colleges called on medical schools to increase their enrollments to address the national shortage of physicians. Soon, there were more medical schools, bigger classes, and more doctors being minted, but the Balanced Budget Act of 1997 prevented a proportional increase in residency positions.

Len Marquez, senior director of government relations at the AAMC noted: “The Resident Physician Shortage Reduction Act of 2021 (S. 834), sponsored by Sen. Robert Menendez (D-N.J.), Sen. John Boozman (R-Ark.), and Majority Leader Sen. Charles Schumer (D-N.Y.), would support 2,000 additional Medicare-supported residency positions each year for 7 years, but Congress has not yet acted on the legislation. We were very pleased that last year, Congress passed the first increase in Medicare-supported graduate medical education in 25 years by including 1,000 new slots as part of the Consolidated Appropriations Act, 2021.”

In addition, the Build Back Better Act, which is currently being debated in Congress, would provide 4,000 more graduate medical education slots, including a specific requirement that 15% of them go to “psychiatry-related residencies,” he added.

Over 90% of graduates from U.S. medical schools currently match into a residency position. That statistic for international medical graduates is notably lower, with perhaps as few as 50% of all applicants matching.

Since 2014, the number of applicants to psychiatry residencies has nearly doubled. For the 2021 match, there were 2,486 applicants applying for 1,858 positions in psychiatry – so 1.34 applicants for each slot. Of the 1,117 senior medical students at U.S. schools who applied to psychiatry residencies, 129 did not match. Overall, 99.8% of residency positions in psychiatry filled. 

“It used to be less competitive,” said Kaz J. Nelson, MD, the vice chair for education at the University of Minnesota’s department of psychiatry and behavioral sciences in Minneapolis, adding that interest in psychiatry has increased over the years. 

“Interest has skyrocketed as the word has gotten out about how great a field it is. It helps that reimbursements are better, that there is less bias and discrimination against patients with psychiatric issues, and that psychiatric care is seen as a legitimate part of medicine. It has been exciting to watch!” Dr. Nelson said.

The numbers are only one part of the story, however. 

Application submission now involves a centralized, electronic process, and it has become easier for applicants to apply to a lot of programs indiscriminately. It’s not unusual for applicants to apply to 70 or more programs. The factors that have limited applications include the cost: Electronic Residency Application Services (ERAS) charges for each application package they send to a program, and applicants traditionally pay to travel to the programs where they interview. This all changed with the 2021 cycle when in-person interviews were halted for the pandemic and interviews became virtual. While I recall applying to 7 residency programs, this year the average number of applications was 54.7 per applicant.

“It used to be that the cap on interviewing was financial,” Dr. Nelson said. “It was discriminatory and favored those who had more money to travel to interviews. There are still the ERAS fees, but COVID has been an equalizer and we are getting more applicants, and interviewing more who are not from Minnesota or the Midwest. We have been working to make our program attractive in terms of diversity, equity, inclusion, and justice. Our hospital is located a mile from where George Floyd was murdered, and it’s our responsibility to lead the effort to ensure the psychiatry workforce is diverse, and inclusive, as possible.”

Daniel E. Gih, MD, is the program director for a new psychiatry residency at the University of Nebraska, Omaha. When the program started in 2019, there were spots for four residents and the program had 588 applications. In 2020, the program grew to five positions and this year there were 553 applicants. Dr. Gih attributed the high number of applications to his program’s strong social media presence.

“Going through the applications and meeting the students are some of the most enjoyable parts of my work,” Dr. Gih said. “I feel guilty though, that I’m likely going to miss a great applicant. Each application averages 35 pages and it’s inevitable that programs have to take shortcuts. Applicants worry that they’ll be ranked by board scores. While we certainly don’t do that here, students might feel ruled out of a program if their numbers aren’t high enough. Furthermore, wealthy students can apply to more programs. The pandemic has really highlighted the inequity issues.”

Dr. Gih noted that the Zoom interview process has not been disappointing: “Two of the people we matched had never been to Omaha, and many expressed concerns about what it is like here. Of course, on Zoom you don’t catch subtle interpersonal issues, but we have been pleasantly surprised that the people we matched were consistent with what we expected. It is exciting to meet the people who will eventually replace us as psychiatrists, they will be here to deal with future challenges!” His enthusiasm was tangible. 

While the program directors remain optimistic, the system is not without its stresses, as many programs receive over 1,000 applications.

“This is difficult,” Dr. Nelson said.” It’s wonderful for the programs, but for the medical students, not matching is experienced by them as being catastrophic, so they apply to a lot of programs. Getting this many applications is a challenge, yet I don’t want to interview someone if they are going to rank our program No. 80 on their list!” 

Residencies have dealt with the deluge of applicants in a number of ways. Some specialties started a “signal” protocol wherein candidates and programs receive a certain number of tokens to indicate that each would rank the other highly, but psychiatry has not done this. Early on in the Zoom process, multiple applicants would be offered interviews simultaneously, and the interview would be given to the candidate who responded first. Students vented their frustrations on Twitter when they lost interview spots at their coveted programs because they hadn’t checked their email in time or had gone to take a shower.

“The American Association of Directors of Psychiatry Residency Training Programs issued guidelines saying that it is unacceptable to offer interview spots without allowing a reasonable time for the applicant to respond, and that it is not appropriate to offer multiple candidates one spot on a first-come, first-serve basis,” Dr. Nelson explained.

Her program has managed some of the application chaos by using a software program called Scutmonkey, codeveloped by David Ross, MD, PhD, the associate program director of the Yale Adult Psychiatry Residency Program.

“It lets us screen applications for candidates who specifically are interested in being here, and for those who qualify as part of the mission we are trying to fulfill.”

One fourth-year student at a mid-Atlantic medical school who is applying in psychiatry – who I’ll call Sacha to protect his anonymity – applied to 73 psychiatry programs and to date, has interviewed at 6. He describes a stressful, roller coaster experience:

“I got those six interviews right away and that was an amazing start, but then I didn’t get any more. The interviews I had went well, but it has been disappointing not to have more. Some were all-day interviews, while other programs had me meet with residents and attendings for 20 minutes each and it was all done after 2 hours.”

He has mixed opinions about not seeing the schools in person. “There are very heavy pros and cons. I’ve saved thousands of dollars in travel expenses that would have limited my applications, so logistically it’s a dream. On the other hand, I’ve interviewed in cities I have never been to, it’s hard to get a sense of the intangibles of a program, and the shorter interviews feel very impersonal.” 

Sacha expressed anxieties about the process. “With so many applicants, it’s difficult for someone with a nontraditional story to get a spot and it’s easier for the programs to toss applications. With all of my classmates, there is the palpable fear of not matching anywhere, it’s common enough and everyone has seen someone who has gone through this. At times, we feel powerless; we have no real agency or control. We send stuff out and then we sit in the prayer position and wait.”

I think back on my own application process with a sense of gratitude. I certainly didn’t feel powerless, and in today’s world, postinterview communications with program directors are regulated for both parties. Dr. Slavney was kind enough to humor my request, but I don’t believe this would be feasible in the current environment.

Even though it is wonderful that more doctors have figured out that careers in psychiatry are rewarding, the current situation is overwhelming for both the applicants and the programs. With over 100 applicants for every position – many of whom will have no interest in going to some of the programs they apply to – qualified candidates who go unmatched, and a roulette wheel which requires heavily indebted students to pay to apply, this is simply not sustainable in a country with a shortage of physicians – psychiatrists in particular. 

We hear that mid-level practitioners are the answer to our shortages, but perhaps we need to create a system with enough residency positions to accommodate highly trained and qualified physicians in a more inviting and targeted way.

Dinah Miller, MD, is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore. A version of this article first appeared on Medscape.com.

Older adults who participate in even light physical activity (LPA) may have a lower risk of developing dementia, new research suggests.

In a retrospective analysis of more than 62,000 individuals aged 65 or older without preexisting dementia, 6% developed dementia.

Compared with inactive individuals, “insufficiently active,” “active,” and “highly active” individuals all had a 10%, 20%, and 28% lower risk for dementia, respectively. And this association was consistent regardless of age, sex, other comorbidities, or after the researchers censored for stroke.

Even the lowest amount of LPA was associated with reduced dementia risk, investigators noted.

“In older adults, an increased physical activity level, including a low amount of LPA, was associated with a reduced risk of dementia,” Minjae Yoon, MD, division of cardiology, Severance Cardiovascular Hospital, Yonsei University, Seoul, South Korea, and colleagues wrote.

“Promotion of LPA might reduce the risk of dementia in older adults,” they added.

The findings were published online in JAMA Network Open.
 

Reverse causation?

Physical activity has been shown previously to be associated with reduced dementia risk. Current World Health Organization guidelines recommend that adults with normal cognition should engage in PA to reduce their risk for cognitive decline.

However, some studies have not yielded this result, “suggesting that previous findings showing a lower risk of dementia in physically active people could be attributed to reverse causation,” the investigators noted. Additionally, previous research regarding exercise intensity has been “inconsistent” concerning the role of LPA in reducing dementia risk.

Many older adults with frailty and comorbidity cannot perform intense or even moderate PA, therefore “these adults would have to gain the benefits of physical activity from LPA,” the researchers noted.

To clarify the potential association between PA and new-onset dementia, they focused specifically on the “dose-response association” between PA and dementia – especially LPA.

Between 2009 and 2012, the investigators enrolled 62,286 older individuals (60.4% women; mean age, 73.2 years) with available health checkup data from the National Health Insurance Service–Senior Database of Korea. All had no history of dementia.

Leisure-time PA was assessed with self-report questionnaires that used a 7-day recall method and included three questions regarding usual frequency (in days per week):

• Vigorous PA (VPA) for at least 20 minutes
• Moderate-intensity PA (MPA) for at least 30 minutes 
• LPA for at least 30 minutes

VPA was defined as “intense exercise that caused severe shortness of breath, MPA was defined as activity causing mild shortness of breath, and LPA was defined as “walking at a slow or leisurely pace.”

PA-related energy expenditure was also calculated in metabolic equivalent (MET) minutes per week by “summing the product of frequency, intensity, and duration,” the investigators noted.

Participants were stratified on the basis of their weekly total PA levels into the following groups:

• Inactive (no LPA beyond basic movements)
• Insufficiently active (less than the recommended target range of 1-499 MET-min/wk)
• Active (meeting the recommended target range of 500-999 MET-min/wk)
• Highly active (exceeding the recommended target range of at least 1,000 MET-min/wk)

Of all participants, 35% were categorized as inactive, 25% were insufficiently active, 24.4% were active, and 15.2% were highly active.
 

Controversy remains

During the total median follow-up of 42 months, 6% of participants had all-cause dementia. After the researchers excluded the first 2 years, incidence of dementia was 21.6 per 1000 person-years during follow-up. 

“The cumulative incidence of dementia was associated with a progressively decreasing trend with increasing physical activity” (P = .001 for trend), the investigators reported.

When using a competing-risk multivariable regression model, they found that higher levels of PA were associated with lower risk for dementia, compared with the inactive group.

Similar findings were obtained after censoring for stroke, and were consistent for all follow-up periods. In subgroup analysis, the association between PA level and dementia risk remained consistent, regardless of age, sex, and comorbidities.

Even a low amount of LPA (1-299 MET-min/wk) was linked to reduced risk for dementia versus total sedentary behavior (adjusted HR, 0.86; 95% CI, 0.74-0.99).

The investigators noted that some “controversy” remains regarding the possibility of reverse causation and, because their study was observational in nature, “it cannot be used to establish causal relationship.”

Nevertheless, the study had important strengths, including the large number of older adults with available data, the assessment of dose-response association between PA and dementia, and the sensitivity analyses they performed, the researchers added.
 

Piece of important evidence

Commenting on the findings, Takashi Tarumi, PhD, senior research investigator, National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan, said previous studies have suggested “an inverse association between physical activity and dementia risk, such that older adults performing a higher dose of exercise may have a greater benefit for reducing the dementia risk.”

Dr. Tarumi, an associate editor at the Journal of Alzheimer’s Disease, added the current study “significantly extends our knowledge by showing that dementia risk can also be reduced by light physical activities when they are performed for longer hours.”

This provides “another piece of important evidence” to support clinicians recommending regular physical activity for the prevention of dementia in later life, said Dr. Tarumi, who was not involved with the research.

Also commenting, Martin Underwood, MD, Warwick Medical School, Coventry, England, described the association between reduced physical inactivity and dementia as well established – and noted the current study “appears to confirm earlier observational data showing this relationship.” 

The current results have “still not been able to fully exclude the possibility of reverse causation,” said Dr. Underwood, who was also not associated with the study.

However, the finding that more physically active individuals are less likely to develop dementia “only becomes of real interest if we can show that increased physical activity prevents the onset, or slows the progression, of dementia,” he noted.

“To my knowledge this has not yet been established” in randomized clinical trials, Dr. Underwood added.

The study was supported by grants from the Patient-Centered Clinical Research Coordinating Center, funded by the Ministry of Health & Welfare, Republic of Korea; and by a research grant from Yonsei University. One coauthor reported serving as a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, and Daiichi-Sankyo, and receiving research funds from Medtronic and Abbott. No other author disclosures were reported. Dr. Tarumi and Dr. Underwood have disclosed no relevant financial relationships.

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

Older adults who participate in even light physical activity (LPA) may have a lower risk of developing dementia, new research suggests.

In a retrospective analysis of more than 62,000 individuals aged 65 or older without preexisting dementia, 6% developed dementia.

Compared with inactive individuals, “insufficiently active,” “active,” and “highly active” individuals all had a 10%, 20%, and 28% lower risk for dementia, respectively. And this association was consistent regardless of age, sex, other comorbidities, or after the researchers censored for stroke.

Even the lowest amount of LPA was associated with reduced dementia risk, investigators noted.

“In older adults, an increased physical activity level, including a low amount of LPA, was associated with a reduced risk of dementia,” Minjae Yoon, MD, division of cardiology, Severance Cardiovascular Hospital, Yonsei University, Seoul, South Korea, and colleagues wrote.

“Promotion of LPA might reduce the risk of dementia in older adults,” they added.

The findings were published online in JAMA Network Open.
 

Reverse causation?

Physical activity has been shown previously to be associated with reduced dementia risk. Current World Health Organization guidelines recommend that adults with normal cognition should engage in PA to reduce their risk for cognitive decline.

However, some studies have not yielded this result, “suggesting that previous findings showing a lower risk of dementia in physically active people could be attributed to reverse causation,” the investigators noted. Additionally, previous research regarding exercise intensity has been “inconsistent” concerning the role of LPA in reducing dementia risk.

Many older adults with frailty and comorbidity cannot perform intense or even moderate PA, therefore “these adults would have to gain the benefits of physical activity from LPA,” the researchers noted.

To clarify the potential association between PA and new-onset dementia, they focused specifically on the “dose-response association” between PA and dementia – especially LPA.

Between 2009 and 2012, the investigators enrolled 62,286 older individuals (60.4% women; mean age, 73.2 years) with available health checkup data from the National Health Insurance Service–Senior Database of Korea. All had no history of dementia.

Leisure-time PA was assessed with self-report questionnaires that used a 7-day recall method and included three questions regarding usual frequency (in days per week):

• Vigorous PA (VPA) for at least 20 minutes
• Moderate-intensity PA (MPA) for at least 30 minutes 
• LPA for at least 30 minutes

VPA was defined as “intense exercise that caused severe shortness of breath, MPA was defined as activity causing mild shortness of breath, and LPA was defined as “walking at a slow or leisurely pace.”

PA-related energy expenditure was also calculated in metabolic equivalent (MET) minutes per week by “summing the product of frequency, intensity, and duration,” the investigators noted.

Participants were stratified on the basis of their weekly total PA levels into the following groups:

• Inactive (no LPA beyond basic movements)
• Insufficiently active (less than the recommended target range of 1-499 MET-min/wk)
• Active (meeting the recommended target range of 500-999 MET-min/wk)
• Highly active (exceeding the recommended target range of at least 1,000 MET-min/wk)

Of all participants, 35% were categorized as inactive, 25% were insufficiently active, 24.4% were active, and 15.2% were highly active.
 

Controversy remains

During the total median follow-up of 42 months, 6% of participants had all-cause dementia. After the researchers excluded the first 2 years, incidence of dementia was 21.6 per 1000 person-years during follow-up. 

“The cumulative incidence of dementia was associated with a progressively decreasing trend with increasing physical activity” (P = .001 for trend), the investigators reported.

When using a competing-risk multivariable regression model, they found that higher levels of PA were associated with lower risk for dementia, compared with the inactive group.

Similar findings were obtained after censoring for stroke, and were consistent for all follow-up periods. In subgroup analysis, the association between PA level and dementia risk remained consistent, regardless of age, sex, and comorbidities.

Even a low amount of LPA (1-299 MET-min/wk) was linked to reduced risk for dementia versus total sedentary behavior (adjusted HR, 0.86; 95% CI, 0.74-0.99).

The investigators noted that some “controversy” remains regarding the possibility of reverse causation and, because their study was observational in nature, “it cannot be used to establish causal relationship.”

Nevertheless, the study had important strengths, including the large number of older adults with available data, the assessment of dose-response association between PA and dementia, and the sensitivity analyses they performed, the researchers added.
 

Piece of important evidence

Commenting on the findings, Takashi Tarumi, PhD, senior research investigator, National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan, said previous studies have suggested “an inverse association between physical activity and dementia risk, such that older adults performing a higher dose of exercise may have a greater benefit for reducing the dementia risk.”

Dr. Tarumi, an associate editor at the Journal of Alzheimer’s Disease, added the current study “significantly extends our knowledge by showing that dementia risk can also be reduced by light physical activities when they are performed for longer hours.”

This provides “another piece of important evidence” to support clinicians recommending regular physical activity for the prevention of dementia in later life, said Dr. Tarumi, who was not involved with the research.

Also commenting, Martin Underwood, MD, Warwick Medical School, Coventry, England, described the association between reduced physical inactivity and dementia as well established – and noted the current study “appears to confirm earlier observational data showing this relationship.” 

The current results have “still not been able to fully exclude the possibility of reverse causation,” said Dr. Underwood, who was also not associated with the study.

However, the finding that more physically active individuals are less likely to develop dementia “only becomes of real interest if we can show that increased physical activity prevents the onset, or slows the progression, of dementia,” he noted.

“To my knowledge this has not yet been established” in randomized clinical trials, Dr. Underwood added.

The study was supported by grants from the Patient-Centered Clinical Research Coordinating Center, funded by the Ministry of Health & Welfare, Republic of Korea; and by a research grant from Yonsei University. One coauthor reported serving as a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, and Daiichi-Sankyo, and receiving research funds from Medtronic and Abbott. No other author disclosures were reported. Dr. Tarumi and Dr. Underwood have disclosed no relevant financial relationships.

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

Older adults who participate in even light physical activity (LPA) may have a lower risk of developing dementia, new research suggests.

In a retrospective analysis of more than 62,000 individuals aged 65 or older without preexisting dementia, 6% developed dementia.

Compared with inactive individuals, “insufficiently active,” “active,” and “highly active” individuals all had a 10%, 20%, and 28% lower risk for dementia, respectively. And this association was consistent regardless of age, sex, other comorbidities, or after the researchers censored for stroke.

Even the lowest amount of LPA was associated with reduced dementia risk, investigators noted.

“In older adults, an increased physical activity level, including a low amount of LPA, was associated with a reduced risk of dementia,” Minjae Yoon, MD, division of cardiology, Severance Cardiovascular Hospital, Yonsei University, Seoul, South Korea, and colleagues wrote.

“Promotion of LPA might reduce the risk of dementia in older adults,” they added.

The findings were published online in JAMA Network Open.
 

Reverse causation?

Physical activity has been shown previously to be associated with reduced dementia risk. Current World Health Organization guidelines recommend that adults with normal cognition should engage in PA to reduce their risk for cognitive decline.

However, some studies have not yielded this result, “suggesting that previous findings showing a lower risk of dementia in physically active people could be attributed to reverse causation,” the investigators noted. Additionally, previous research regarding exercise intensity has been “inconsistent” concerning the role of LPA in reducing dementia risk.

Many older adults with frailty and comorbidity cannot perform intense or even moderate PA, therefore “these adults would have to gain the benefits of physical activity from LPA,” the researchers noted.

To clarify the potential association between PA and new-onset dementia, they focused specifically on the “dose-response association” between PA and dementia – especially LPA.

Between 2009 and 2012, the investigators enrolled 62,286 older individuals (60.4% women; mean age, 73.2 years) with available health checkup data from the National Health Insurance Service–Senior Database of Korea. All had no history of dementia.

Leisure-time PA was assessed with self-report questionnaires that used a 7-day recall method and included three questions regarding usual frequency (in days per week):

• Vigorous PA (VPA) for at least 20 minutes
• Moderate-intensity PA (MPA) for at least 30 minutes 
• LPA for at least 30 minutes

VPA was defined as “intense exercise that caused severe shortness of breath, MPA was defined as activity causing mild shortness of breath, and LPA was defined as “walking at a slow or leisurely pace.”

PA-related energy expenditure was also calculated in metabolic equivalent (MET) minutes per week by “summing the product of frequency, intensity, and duration,” the investigators noted.

Participants were stratified on the basis of their weekly total PA levels into the following groups:

• Inactive (no LPA beyond basic movements)
• Insufficiently active (less than the recommended target range of 1-499 MET-min/wk)
• Active (meeting the recommended target range of 500-999 MET-min/wk)
• Highly active (exceeding the recommended target range of at least 1,000 MET-min/wk)

Of all participants, 35% were categorized as inactive, 25% were insufficiently active, 24.4% were active, and 15.2% were highly active.
 

Controversy remains

During the total median follow-up of 42 months, 6% of participants had all-cause dementia. After the researchers excluded the first 2 years, incidence of dementia was 21.6 per 1000 person-years during follow-up. 

“The cumulative incidence of dementia was associated with a progressively decreasing trend with increasing physical activity” (P = .001 for trend), the investigators reported.

When using a competing-risk multivariable regression model, they found that higher levels of PA were associated with lower risk for dementia, compared with the inactive group.

Similar findings were obtained after censoring for stroke, and were consistent for all follow-up periods. In subgroup analysis, the association between PA level and dementia risk remained consistent, regardless of age, sex, and comorbidities.

Even a low amount of LPA (1-299 MET-min/wk) was linked to reduced risk for dementia versus total sedentary behavior (adjusted HR, 0.86; 95% CI, 0.74-0.99).

The investigators noted that some “controversy” remains regarding the possibility of reverse causation and, because their study was observational in nature, “it cannot be used to establish causal relationship.”

Nevertheless, the study had important strengths, including the large number of older adults with available data, the assessment of dose-response association between PA and dementia, and the sensitivity analyses they performed, the researchers added.
 

Piece of important evidence

Commenting on the findings, Takashi Tarumi, PhD, senior research investigator, National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan, said previous studies have suggested “an inverse association between physical activity and dementia risk, such that older adults performing a higher dose of exercise may have a greater benefit for reducing the dementia risk.”

Dr. Tarumi, an associate editor at the Journal of Alzheimer’s Disease, added the current study “significantly extends our knowledge by showing that dementia risk can also be reduced by light physical activities when they are performed for longer hours.”

This provides “another piece of important evidence” to support clinicians recommending regular physical activity for the prevention of dementia in later life, said Dr. Tarumi, who was not involved with the research.

Also commenting, Martin Underwood, MD, Warwick Medical School, Coventry, England, described the association between reduced physical inactivity and dementia as well established – and noted the current study “appears to confirm earlier observational data showing this relationship.” 

The current results have “still not been able to fully exclude the possibility of reverse causation,” said Dr. Underwood, who was also not associated with the study.

However, the finding that more physically active individuals are less likely to develop dementia “only becomes of real interest if we can show that increased physical activity prevents the onset, or slows the progression, of dementia,” he noted.

“To my knowledge this has not yet been established” in randomized clinical trials, Dr. Underwood added.

The study was supported by grants from the Patient-Centered Clinical Research Coordinating Center, funded by the Ministry of Health & Welfare, Republic of Korea; and by a research grant from Yonsei University. One coauthor reported serving as a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, and Daiichi-Sankyo, and receiving research funds from Medtronic and Abbott. No other author disclosures were reported. Dr. Tarumi and Dr. Underwood have disclosed no relevant financial relationships.

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

Severe gastrointestinal involvement can be common in children who have had COVID-19, a new study shows.

Andrea Lo Veccio, MD, PhD, with the department of translational medical sciences, section of pediatrics, University of Naples (Italy) Federico II, and colleagues retrospectively analyzed data from a large cohort of children aged 18 years and younger who had been diagnosed with COVID-19 between Feb. 25, 2020, and Jan. 20, 2021, in 54 Italian institutions.

Overall, 685 Italian children (56.4% boys; average age, 7 years) were included in the study. Of these, 628 (91.7%) were diagnosed with acute SARS-CoV-2 infection and 57 (8.3%) with multisystem inflammatory syndrome in children (MIS-C).

When children had GI symptoms, the authors found a higher risk of hospitalization (odds ratio, 2.64; 95% confidence interval, 1.89-3.69) and nearly four times the risk of ICU admission (OR, 3.90; 95% CI, 1.98-7.68).

Severe GI involvement occurred in 65 children (9.5%). The authors included the following within that category: disseminated adenomesenteritis (39.6%), appendicitis (33.5%), abdominal fluid collection (21.3%), pancreatitis (6.9%), or intussusception (4.6%). Additionally, out of these 65 children, 27 (41.5%) underwent surgery.

Older children were much more likely than preschoolers to have severe GI symptoms. Children aged 5-10 years were eight times more likely than preschoolers to show severe symptoms (OR, 8.33; 95% CI, 2.62-26.5). In those older than age 10 years, severe symptoms were six times more likely (OR, 6.37; 95% CI, 2.12-19.1).

Awareness about its frequency and presentation may help practitioners to appropriately manage children at risk of severe outcomes, the authors wrote.

The findings of this study were published online Dec. 20 in JAMA Network Open.
 

Study highlights the GI link

Reached for comment, William Balistreri, MD, with the division of gastroenterology, hepatology, and nutrition at Cincinnati Children’s Hospital Medical Center, said that it has been known that children are more likely than adults to present with GI symptoms, and also that these symptoms are especially common in children with MIS-C.

“The symptoms most commonly cited in the literature to date include diarrhea, nausea, vomiting, or abdominal pain,” he said. “What [has not been known] is the frequency, predictive markers, and clinical course of the severe GI manifestations of COVID-19.”

The findings of this study are important to clinicians to help recognize the potential for severe GI involvement, Dr. Balistreri said, adding that “the occurrence of abdominal pain, leukopenia, and elevated inflammatory markers or MIS-C should raise suspicion and lead to early evaluation.”

Margaret E. Thew, APNP, medical director in adolescent medicine and a family nurse practitioner with Medical College of Wisconsin, Milwaukee, said that news reports typically emphasize the respiratory involvement, but this study provides a detailed analysis of the link between GI symptoms and COVID-19.

“Their data show that there may be less respiratory illness with children, regardless of whether they are generally healthy kids,” she said. “They may have more GI symptoms.

“We know that COVID-19 causes a lot of inflammation, and a large percentage of these kids had inflammation in their stomach or an inflamed bowel,” she added.

Dr. Thew said primary care doctors and urgent and emergency care clinicians will benefit from the findings of this study and should be on alert when kids come in with belly pain or vomiting.

Parents will benefit too, she said, if they are waiting for respiratory illness before they suspect COVID.

“You have to have a high suspicion this is going to be COVID positive,” she said. “You have to have that as part of your thought process.”

Though the study was done in Italy, Dr. Thew added that their experiences mimic those she’s seen locally.

Dr. Lo Vecchio reported receiving fees from Pfizer as an advisory board member outside the submitted work. A coauthor reported speaker’s fees from Angelini, Sobi, and X4 Pharma outside the submitted work. No other disclosures were reported. Dr. Balistreri and Dr. Thew reported no relevant financial relationships.

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

Severe gastrointestinal involvement can be common in children who have had COVID-19, a new study shows.

Andrea Lo Veccio, MD, PhD, with the department of translational medical sciences, section of pediatrics, University of Naples (Italy) Federico II, and colleagues retrospectively analyzed data from a large cohort of children aged 18 years and younger who had been diagnosed with COVID-19 between Feb. 25, 2020, and Jan. 20, 2021, in 54 Italian institutions.

Overall, 685 Italian children (56.4% boys; average age, 7 years) were included in the study. Of these, 628 (91.7%) were diagnosed with acute SARS-CoV-2 infection and 57 (8.3%) with multisystem inflammatory syndrome in children (MIS-C).

When children had GI symptoms, the authors found a higher risk of hospitalization (odds ratio, 2.64; 95% confidence interval, 1.89-3.69) and nearly four times the risk of ICU admission (OR, 3.90; 95% CI, 1.98-7.68).

Severe GI involvement occurred in 65 children (9.5%). The authors included the following within that category: disseminated adenomesenteritis (39.6%), appendicitis (33.5%), abdominal fluid collection (21.3%), pancreatitis (6.9%), or intussusception (4.6%). Additionally, out of these 65 children, 27 (41.5%) underwent surgery.

Older children were much more likely than preschoolers to have severe GI symptoms. Children aged 5-10 years were eight times more likely than preschoolers to show severe symptoms (OR, 8.33; 95% CI, 2.62-26.5). In those older than age 10 years, severe symptoms were six times more likely (OR, 6.37; 95% CI, 2.12-19.1).

Awareness about its frequency and presentation may help practitioners to appropriately manage children at risk of severe outcomes, the authors wrote.

The findings of this study were published online Dec. 20 in JAMA Network Open.
 

Study highlights the GI link

Reached for comment, William Balistreri, MD, with the division of gastroenterology, hepatology, and nutrition at Cincinnati Children’s Hospital Medical Center, said that it has been known that children are more likely than adults to present with GI symptoms, and also that these symptoms are especially common in children with MIS-C.

“The symptoms most commonly cited in the literature to date include diarrhea, nausea, vomiting, or abdominal pain,” he said. “What [has not been known] is the frequency, predictive markers, and clinical course of the severe GI manifestations of COVID-19.”

The findings of this study are important to clinicians to help recognize the potential for severe GI involvement, Dr. Balistreri said, adding that “the occurrence of abdominal pain, leukopenia, and elevated inflammatory markers or MIS-C should raise suspicion and lead to early evaluation.”

Margaret E. Thew, APNP, medical director in adolescent medicine and a family nurse practitioner with Medical College of Wisconsin, Milwaukee, said that news reports typically emphasize the respiratory involvement, but this study provides a detailed analysis of the link between GI symptoms and COVID-19.

“Their data show that there may be less respiratory illness with children, regardless of whether they are generally healthy kids,” she said. “They may have more GI symptoms.

“We know that COVID-19 causes a lot of inflammation, and a large percentage of these kids had inflammation in their stomach or an inflamed bowel,” she added.

Dr. Thew said primary care doctors and urgent and emergency care clinicians will benefit from the findings of this study and should be on alert when kids come in with belly pain or vomiting.

Parents will benefit too, she said, if they are waiting for respiratory illness before they suspect COVID.

“You have to have a high suspicion this is going to be COVID positive,” she said. “You have to have that as part of your thought process.”

Though the study was done in Italy, Dr. Thew added that their experiences mimic those she’s seen locally.

Dr. Lo Vecchio reported receiving fees from Pfizer as an advisory board member outside the submitted work. A coauthor reported speaker’s fees from Angelini, Sobi, and X4 Pharma outside the submitted work. No other disclosures were reported. Dr. Balistreri and Dr. Thew reported no relevant financial relationships.

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

Severe gastrointestinal involvement can be common in children who have had COVID-19, a new study shows.

Andrea Lo Veccio, MD, PhD, with the department of translational medical sciences, section of pediatrics, University of Naples (Italy) Federico II, and colleagues retrospectively analyzed data from a large cohort of children aged 18 years and younger who had been diagnosed with COVID-19 between Feb. 25, 2020, and Jan. 20, 2021, in 54 Italian institutions.

Overall, 685 Italian children (56.4% boys; average age, 7 years) were included in the study. Of these, 628 (91.7%) were diagnosed with acute SARS-CoV-2 infection and 57 (8.3%) with multisystem inflammatory syndrome in children (MIS-C).

When children had GI symptoms, the authors found a higher risk of hospitalization (odds ratio, 2.64; 95% confidence interval, 1.89-3.69) and nearly four times the risk of ICU admission (OR, 3.90; 95% CI, 1.98-7.68).

Severe GI involvement occurred in 65 children (9.5%). The authors included the following within that category: disseminated adenomesenteritis (39.6%), appendicitis (33.5%), abdominal fluid collection (21.3%), pancreatitis (6.9%), or intussusception (4.6%). Additionally, out of these 65 children, 27 (41.5%) underwent surgery.

Older children were much more likely than preschoolers to have severe GI symptoms. Children aged 5-10 years were eight times more likely than preschoolers to show severe symptoms (OR, 8.33; 95% CI, 2.62-26.5). In those older than age 10 years, severe symptoms were six times more likely (OR, 6.37; 95% CI, 2.12-19.1).

Awareness about its frequency and presentation may help practitioners to appropriately manage children at risk of severe outcomes, the authors wrote.

The findings of this study were published online Dec. 20 in JAMA Network Open.
 

Study highlights the GI link

Reached for comment, William Balistreri, MD, with the division of gastroenterology, hepatology, and nutrition at Cincinnati Children’s Hospital Medical Center, said that it has been known that children are more likely than adults to present with GI symptoms, and also that these symptoms are especially common in children with MIS-C.

“The symptoms most commonly cited in the literature to date include diarrhea, nausea, vomiting, or abdominal pain,” he said. “What [has not been known] is the frequency, predictive markers, and clinical course of the severe GI manifestations of COVID-19.”

The findings of this study are important to clinicians to help recognize the potential for severe GI involvement, Dr. Balistreri said, adding that “the occurrence of abdominal pain, leukopenia, and elevated inflammatory markers or MIS-C should raise suspicion and lead to early evaluation.”

Margaret E. Thew, APNP, medical director in adolescent medicine and a family nurse practitioner with Medical College of Wisconsin, Milwaukee, said that news reports typically emphasize the respiratory involvement, but this study provides a detailed analysis of the link between GI symptoms and COVID-19.

“Their data show that there may be less respiratory illness with children, regardless of whether they are generally healthy kids,” she said. “They may have more GI symptoms.

“We know that COVID-19 causes a lot of inflammation, and a large percentage of these kids had inflammation in their stomach or an inflamed bowel,” she added.

Dr. Thew said primary care doctors and urgent and emergency care clinicians will benefit from the findings of this study and should be on alert when kids come in with belly pain or vomiting.

Parents will benefit too, she said, if they are waiting for respiratory illness before they suspect COVID.

“You have to have a high suspicion this is going to be COVID positive,” she said. “You have to have that as part of your thought process.”

Though the study was done in Italy, Dr. Thew added that their experiences mimic those she’s seen locally.

Dr. Lo Vecchio reported receiving fees from Pfizer as an advisory board member outside the submitted work. A coauthor reported speaker’s fees from Angelini, Sobi, and X4 Pharma outside the submitted work. No other disclosures were reported. Dr. Balistreri and Dr. Thew reported no relevant financial relationships.

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

Secretan syndrome (SS) represents a recurrent or chronic form of factitious lymphedema, usually affecting the dorsal aspect of the hand.^1-3 It is accepted as a subtype of Munchausen syndrome whereby the patient self-inflicts and simulates lymphedema.^1,2 Historically, many of the cases reported with the term Charcot’s oedème bleu are now believed to represent clinical variants of SS.^4-6

Case Report

A 38-year-old Turkish woman presented with progressive swelling of the right hand of 2 years’ duration that had caused difficulty in manual work and reduction in manual dexterity. She previously had sought medical treatment for this condition by visiting several hospitals. According to her medical record, the following laboratory or radiologic tests had revealed negative or normal findings, except for obvious soft-tissue edema: bacterial and fungal cultures, plain radiography, Doppler ultrasonography, lymphoscintigraphy, magnetic resonance imaging, fine needle aspiration, and punch biopsy. Reflex sympathetic dystrophy, compartment syndrome, filariasis, tuberculosis, and lymphatic and venous obstruction were all excluded by appropriate testing. Our patient was in good health prior to onset of this disorder, and her medical history was unremarkable. There was no family history of a similar condition.

Dermatologic examination revealed brawny, soft, pitting edema; erythema; and crusts affecting the dorsal aspect of the right hand and proximal parts of the fingers (Figure 1). The yellow discoloration of the skin and nails was attributed to potassium permanganate wet dressings. Under an elastic bandage at the wrist, which the patient unrolled herself, a sharp line of demarcation was evident, separating the lymphedematous and normal parts of the arm. There was no axillary lymphadenopathy.

Comment

In 1901, Henri Francois Secretan, a Swiss physician, reported workmen who had persistent hard swellings on the dorsal aspect of the hands after minor work-related trauma for which they had compensation claims.⁷ In his original report, Secretan did not suggest self-inflicted trauma in the etiology of this disorder.^5,8,9 In 1890, Jean Martin Charcot, a French neurologist, described oedème bleu, a term that is now believed to denote a condition similar to SS.^4-6 Currently, SS is attributed to self-inflicted injury and is considered a form of factitious lymphedema.⁹ As in dermatitis artefacta, most patients with SS are young women, and male patients with the condition tend to be older.^3,8

The mechanism used to provoke this factitious lymphedema might be of traumatic or obstructive nature. Secretan syndrome either is induced by intermittent or constant application of a tourniquet, ligature, cord, elastic bandage, scarf, kerchief, rubber band, or compress around the affected extremity, or by repetitive blunt trauma, force, or skin irritation.^1,4,5,8-10 There was an underlying psychopathology in all reported cases.^1,8,11 Factitious lymphedema is unconsciously motivated and consciously produced.^4,12 The affected patient often is experiencing a serious emotional conflict and is unlikely to be a malingerer, although exaggeration of symptoms may occur, as in our patient.¹² Psychiatric evaluation in SS may uncover neurosis, hysteria, frank psychosis, schizophrenia, masochism, depression, or an abnormal personality disorder.^1,12

Patients with SS present with recurrent or chronic lymphedema, usually affecting the dominant hand.¹ Involvement usually is unilateral; bilateral cases are rare.^3,6 Secretan syndrome is not solely limited to the hands; it also may involve the upper and lower extremities, including the feet.^3,11 There may be a clear line of demarcation, a ring, sulcus, distinct circumferential linear bands of erythema, discoloration, or ecchymoses, separating the normal and lymphedematous parts of the extremity.^{1,4,6,8-10,12} Patients usually attempt to hide the constricted areas from sight.¹ Over time, flexion contractures may develop due to peritendinous fibrosis.⁶ Histopathology displays a hematoma with adhesions to the extensor tendons; a hematoma surrounded by a thickened scar; or changes similar to ganglion tissue with cystic areas of mucin, fibrosis, and myxoid degeneration.^4,6

Factitious lymphedema can only be definitively diagnosed when the patient confesses or is caught self-inflicting the injury. Nevertheless, a diagnosis by exclusion is possible.⁴ Lymphangiography, lymphoscintigraphy, vascular Doppler ultrasonography, and magnetic resonance imaging may be helpful in excluding congenital and acquired causes of lymphedema and venous obstruction.^1,3,9,11 Magnetic resonance imaging may show soft tissue and tendon edema as well as diffuse peritendinous fibrosis extending to the fascia of the dorsal interosseous muscles.^3,4

Factitious lymphedema should be suspected in all patients with recurrent or chronic unilateral lymphedema without an explicable or apparent predisposing factor.^4,11,12 Patients with SS typically visit several hospitals or institutions; see many physicians; and willingly accept, request, and undergo unnecessary extensive, invasive, and costly diagnostic and therapeutic procedures and prolonged hospitalizations.^1,2,5,12 The disorder promptly responds to immobilization and elevation of the limb.^2,4 Plaster casts may prove useful in prevention of compression and thus amelioration of the lymphedema.^1,4,6 Once the diagnosis is confirmed, direct confrontation should be avoided and ideally the patient should be referred for psychiatric evaluation.^1,2,4,5,8,12 If the patient admits self-inflicting behavior, psychotherapy and/or behavior modification therapy along with psychotropic medications may be helpful to relieve emotional and behavioral symptoms.¹² Unfortunately, if the patient denies a self-inflicting role in the occurrence of lymphedema and persists in self-injurious behavior, psychotherapy or psychotropic medications will be futile.⁹

Secretan syndrome (SS) represents a recurrent or chronic form of factitious lymphedema, usually affecting the dorsal aspect of the hand.^1-3 It is accepted as a subtype of Munchausen syndrome whereby the patient self-inflicts and simulates lymphedema.^1,2 Historically, many of the cases reported with the term Charcot’s oedème bleu are now believed to represent clinical variants of SS.^4-6

Case Report

A 38-year-old Turkish woman presented with progressive swelling of the right hand of 2 years’ duration that had caused difficulty in manual work and reduction in manual dexterity. She previously had sought medical treatment for this condition by visiting several hospitals. According to her medical record, the following laboratory or radiologic tests had revealed negative or normal findings, except for obvious soft-tissue edema: bacterial and fungal cultures, plain radiography, Doppler ultrasonography, lymphoscintigraphy, magnetic resonance imaging, fine needle aspiration, and punch biopsy. Reflex sympathetic dystrophy, compartment syndrome, filariasis, tuberculosis, and lymphatic and venous obstruction were all excluded by appropriate testing. Our patient was in good health prior to onset of this disorder, and her medical history was unremarkable. There was no family history of a similar condition.

Dermatologic examination revealed brawny, soft, pitting edema; erythema; and crusts affecting the dorsal aspect of the right hand and proximal parts of the fingers (Figure 1). The yellow discoloration of the skin and nails was attributed to potassium permanganate wet dressings. Under an elastic bandage at the wrist, which the patient unrolled herself, a sharp line of demarcation was evident, separating the lymphedematous and normal parts of the arm. There was no axillary lymphadenopathy.

Comment

In 1901, Henri Francois Secretan, a Swiss physician, reported workmen who had persistent hard swellings on the dorsal aspect of the hands after minor work-related trauma for which they had compensation claims.⁷ In his original report, Secretan did not suggest self-inflicted trauma in the etiology of this disorder.^5,8,9 In 1890, Jean Martin Charcot, a French neurologist, described oedème bleu, a term that is now believed to denote a condition similar to SS.^4-6 Currently, SS is attributed to self-inflicted injury and is considered a form of factitious lymphedema.⁹ As in dermatitis artefacta, most patients with SS are young women, and male patients with the condition tend to be older.^3,8

The mechanism used to provoke this factitious lymphedema might be of traumatic or obstructive nature. Secretan syndrome either is induced by intermittent or constant application of a tourniquet, ligature, cord, elastic bandage, scarf, kerchief, rubber band, or compress around the affected extremity, or by repetitive blunt trauma, force, or skin irritation.^1,4,5,8-10 There was an underlying psychopathology in all reported cases.^1,8,11 Factitious lymphedema is unconsciously motivated and consciously produced.^4,12 The affected patient often is experiencing a serious emotional conflict and is unlikely to be a malingerer, although exaggeration of symptoms may occur, as in our patient.¹² Psychiatric evaluation in SS may uncover neurosis, hysteria, frank psychosis, schizophrenia, masochism, depression, or an abnormal personality disorder.^1,12

Patients with SS present with recurrent or chronic lymphedema, usually affecting the dominant hand.¹ Involvement usually is unilateral; bilateral cases are rare.^3,6 Secretan syndrome is not solely limited to the hands; it also may involve the upper and lower extremities, including the feet.^3,11 There may be a clear line of demarcation, a ring, sulcus, distinct circumferential linear bands of erythema, discoloration, or ecchymoses, separating the normal and lymphedematous parts of the extremity.^{1,4,6,8-10,12} Patients usually attempt to hide the constricted areas from sight.¹ Over time, flexion contractures may develop due to peritendinous fibrosis.⁶ Histopathology displays a hematoma with adhesions to the extensor tendons; a hematoma surrounded by a thickened scar; or changes similar to ganglion tissue with cystic areas of mucin, fibrosis, and myxoid degeneration.^4,6

Factitious lymphedema can only be definitively diagnosed when the patient confesses or is caught self-inflicting the injury. Nevertheless, a diagnosis by exclusion is possible.⁴ Lymphangiography, lymphoscintigraphy, vascular Doppler ultrasonography, and magnetic resonance imaging may be helpful in excluding congenital and acquired causes of lymphedema and venous obstruction.^1,3,9,11 Magnetic resonance imaging may show soft tissue and tendon edema as well as diffuse peritendinous fibrosis extending to the fascia of the dorsal interosseous muscles.^3,4

Factitious lymphedema should be suspected in all patients with recurrent or chronic unilateral lymphedema without an explicable or apparent predisposing factor.^4,11,12 Patients with SS typically visit several hospitals or institutions; see many physicians; and willingly accept, request, and undergo unnecessary extensive, invasive, and costly diagnostic and therapeutic procedures and prolonged hospitalizations.^1,2,5,12 The disorder promptly responds to immobilization and elevation of the limb.^2,4 Plaster casts may prove useful in prevention of compression and thus amelioration of the lymphedema.^1,4,6 Once the diagnosis is confirmed, direct confrontation should be avoided and ideally the patient should be referred for psychiatric evaluation.^1,2,4,5,8,12 If the patient admits self-inflicting behavior, psychotherapy and/or behavior modification therapy along with psychotropic medications may be helpful to relieve emotional and behavioral symptoms.¹² Unfortunately, if the patient denies a self-inflicting role in the occurrence of lymphedema and persists in self-injurious behavior, psychotherapy or psychotropic medications will be futile.⁹

Secretan syndrome (SS) represents a recurrent or chronic form of factitious lymphedema, usually affecting the dorsal aspect of the hand.^1-3 It is accepted as a subtype of Munchausen syndrome whereby the patient self-inflicts and simulates lymphedema.^1,2 Historically, many of the cases reported with the term Charcot’s oedème bleu are now believed to represent clinical variants of SS.^4-6

Case Report

A 38-year-old Turkish woman presented with progressive swelling of the right hand of 2 years’ duration that had caused difficulty in manual work and reduction in manual dexterity. She previously had sought medical treatment for this condition by visiting several hospitals. According to her medical record, the following laboratory or radiologic tests had revealed negative or normal findings, except for obvious soft-tissue edema: bacterial and fungal cultures, plain radiography, Doppler ultrasonography, lymphoscintigraphy, magnetic resonance imaging, fine needle aspiration, and punch biopsy. Reflex sympathetic dystrophy, compartment syndrome, filariasis, tuberculosis, and lymphatic and venous obstruction were all excluded by appropriate testing. Our patient was in good health prior to onset of this disorder, and her medical history was unremarkable. There was no family history of a similar condition.

Dermatologic examination revealed brawny, soft, pitting edema; erythema; and crusts affecting the dorsal aspect of the right hand and proximal parts of the fingers (Figure 1). The yellow discoloration of the skin and nails was attributed to potassium permanganate wet dressings. Under an elastic bandage at the wrist, which the patient unrolled herself, a sharp line of demarcation was evident, separating the lymphedematous and normal parts of the arm. There was no axillary lymphadenopathy.

Comment

In 1901, Henri Francois Secretan, a Swiss physician, reported workmen who had persistent hard swellings on the dorsal aspect of the hands after minor work-related trauma for which they had compensation claims.⁷ In his original report, Secretan did not suggest self-inflicted trauma in the etiology of this disorder.^5,8,9 In 1890, Jean Martin Charcot, a French neurologist, described oedème bleu, a term that is now believed to denote a condition similar to SS.^4-6 Currently, SS is attributed to self-inflicted injury and is considered a form of factitious lymphedema.⁹ As in dermatitis artefacta, most patients with SS are young women, and male patients with the condition tend to be older.^3,8

The mechanism used to provoke this factitious lymphedema might be of traumatic or obstructive nature. Secretan syndrome either is induced by intermittent or constant application of a tourniquet, ligature, cord, elastic bandage, scarf, kerchief, rubber band, or compress around the affected extremity, or by repetitive blunt trauma, force, or skin irritation.^1,4,5,8-10 There was an underlying psychopathology in all reported cases.^1,8,11 Factitious lymphedema is unconsciously motivated and consciously produced.^4,12 The affected patient often is experiencing a serious emotional conflict and is unlikely to be a malingerer, although exaggeration of symptoms may occur, as in our patient.¹² Psychiatric evaluation in SS may uncover neurosis, hysteria, frank psychosis, schizophrenia, masochism, depression, or an abnormal personality disorder.^1,12

Patients with SS present with recurrent or chronic lymphedema, usually affecting the dominant hand.¹ Involvement usually is unilateral; bilateral cases are rare.^3,6 Secretan syndrome is not solely limited to the hands; it also may involve the upper and lower extremities, including the feet.^3,11 There may be a clear line of demarcation, a ring, sulcus, distinct circumferential linear bands of erythema, discoloration, or ecchymoses, separating the normal and lymphedematous parts of the extremity.^{1,4,6,8-10,12} Patients usually attempt to hide the constricted areas from sight.¹ Over time, flexion contractures may develop due to peritendinous fibrosis.⁶ Histopathology displays a hematoma with adhesions to the extensor tendons; a hematoma surrounded by a thickened scar; or changes similar to ganglion tissue with cystic areas of mucin, fibrosis, and myxoid degeneration.^4,6

Factitious lymphedema can only be definitively diagnosed when the patient confesses or is caught self-inflicting the injury. Nevertheless, a diagnosis by exclusion is possible.⁴ Lymphangiography, lymphoscintigraphy, vascular Doppler ultrasonography, and magnetic resonance imaging may be helpful in excluding congenital and acquired causes of lymphedema and venous obstruction.^1,3,9,11 Magnetic resonance imaging may show soft tissue and tendon edema as well as diffuse peritendinous fibrosis extending to the fascia of the dorsal interosseous muscles.^3,4

Factitious lymphedema should be suspected in all patients with recurrent or chronic unilateral lymphedema without an explicable or apparent predisposing factor.^4,11,12 Patients with SS typically visit several hospitals or institutions; see many physicians; and willingly accept, request, and undergo unnecessary extensive, invasive, and costly diagnostic and therapeutic procedures and prolonged hospitalizations.^1,2,5,12 The disorder promptly responds to immobilization and elevation of the limb.^2,4 Plaster casts may prove useful in prevention of compression and thus amelioration of the lymphedema.^1,4,6 Once the diagnosis is confirmed, direct confrontation should be avoided and ideally the patient should be referred for psychiatric evaluation.^1,2,4,5,8,12 If the patient admits self-inflicting behavior, psychotherapy and/or behavior modification therapy along with psychotropic medications may be helpful to relieve emotional and behavioral symptoms.¹² Unfortunately, if the patient denies a self-inflicting role in the occurrence of lymphedema and persists in self-injurious behavior, psychotherapy or psychotropic medications will be futile.⁹

A “definitive study” from Johns Hopkins University researchers and others shows that convalescent plasma can cut hospital admissions for COVID-19 by 54% if therapy is administered within 8 days of symptom onset.

In the study of 1,181 adults randomly assigned to high-titer convalescent plasma or placebo, 2.9% of people receiving the therapy were hospitalized, compared with 6.3% who received placebo control plasma.

This translates to a 54% risk reduction for hospitalization with convalescent plasma.

“We have a clear difference,” principal investigator David Sullivan, MD, a professor at Johns Hopkins University, Baltimore, said during a Dec. 21 media briefing.

“This is very good news since we are in the midst of the Omicron surge, which has defeated [some of] our major monocular antibody therapies,” said Arturo Casadevall, MD, chair of the department of molecular microbiology and immunology at Johns Hopkins.

“So we have a new tool to keep people from progressing in their disease and to reduce progression or hospitalization,” Dr. Casadevall said.

The findings were published as a preprint study on Dec. 21, 2021, on medRxiv. The study has not yet been peer reviewed.

Whereas many convalescent plasma studies were done in hospitalized patients, this is one of only a handful performed in outpatients, the researchers noted.

There is a regulatory catch. The Food and Drug Administration restricted emergency use authorization (EUA) for convalescent plasma in February 2021 to include only high-dose titer plasma and to limit the therapy to hospitalized patients with early disease or for immunocompromised people who cannot mount an adequate antibody response.

Dr. Sullivan and colleagues hoped their findings will prompt the FDA to expand the EUA to include outpatients.

“We have shared this data with both the World Health Organization and the FDA,” study coauthor Kelly Gebo, MD, MPH, said during the media briefing.

“We do believe that this could be scaled up quickly,” added Dr. Gebo, professor of medicine at Johns Hopkins University. Convalescent plasma “could be used as a potential treatment as variants continue to evolve, such as we’ve seen with Omicron.”
 

Pre-Omicron results

The study was conducted at Johns Hopkins University and 23 other sites nationwide between June 2020 and October 2021. This means researchers enrolled symptomatic adults during circulation of the SARS-CoV-2 ancestral strain and the Alpha and Delta variants.

However, Dr. Sullivan said, “we think that ... plasma with high levels of antibodies can adapt faster to Omicron, although it will take us longer to get an Omicron-specific supply.”

Because of the timing of the study, 80% of participants were unvaccinated. Mean age was 44 years and 57% were women. Black and Hispanic participants each accounted for more than 12% of the study population.

On average, participants received a transfusion within 6 days of the start of symptoms.

In the study, 37 people out of 589 control group participants were hospitalized, compared with 17 of the 592 who received the convalescent plasma.

“We know antibodies work against SARS-CoV-2. The vaccines have been spectacular – producing antibodies that reduce hospitalizations and prevent transmission,” Dr. Sullivan said. “Convalescent plasma provides much of the same antibodies instantly.”
 

Convalescent and controversial

Convalescent plasma has been one of the controversial treatments for people with COVID-19 – with studies going back and forth on the potential benefits and efficacy. A National Institutes of Health–funded study published in August 2021, for example, showed no significant benefit.

“As you know, convalescent plasma has had a rocky ride,” Dr. Casadevall said.

“It was deployed with great excitement in the terrible, early days of the pandemic. Unfortunately, the early excitement and optimism was dampened with some of the randomized control trials appearing to show no benefit in reducing mortality and hospitalized patients,” he added.

In contrast, the current study shows “where convalescent plasma works using the latest, most rigorous clinical investigation tools available: a double-blinded, randomized, placebo-control trial,” Dr. Casadevall said.
 

Why a preprint, and why now?

The researchers decided to release their data in recognition of the lag time between reporting of COVID-19 cases and hospitalizations, Dr. Sullivan said. “That’s part of the reason we decided to act now with this knowledge – that it does take a couple of weeks – with cases of Omicron going up.”

Furthermore, “we thought this was actionable data for decision-makers,” he added.

A reporter asked why the Johns Hopkins researchers chose to hold a media briefing for a preprint study.

A preprint is “not so unusual given the SARS-CoV-2 pandemic,” said study senior author Daniel Hanley, MD, division director of brain injury outcomes at Johns Hopkins University.

“The data are the data,” Dr. Casadevall added. “This is not going to change from peer review.”

Peer review may change some of the wording of the manuscript, but not the numbers, he added.

“Now with the Omicron crisis and the fact that we have lost some more main monoclonal antibodies, it is essential to get this information out,” Dr. Casadevall said.
 

Plasma therapy nothing new

Donation and transfusion of convalescent plasma is highly regulated with strict criteria, said Evan Bloch, MBChB, associate director of the transfusion medicine division at Johns Hopkins University.

If the FDA opts to expand the EUA based on this or other evidence, administration of convalescent plasma could be rolled out fairly quickly, the researchers noted.

Plasma transfusion takes place in hospitals and at infusion centers every day. The infrastructure is in place in many countries, even low- and middle-resource nations, around the world to provide convalescent plasma therapy. The major difference between traditional plasma and SARS-CoV-2 convalescent plasma is the indication, Dr. Bloch added.

In addition, convalescent plasma has a polyclonal composition – a benefit compared with monoclonal antibodies, he added. “It’s more durable or adaptive [compared with] some of the targeted therapies, such as monoclonal antibodies, where we’ve witnessed this diminished efficacy with viral evolution.”

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

A “definitive study” from Johns Hopkins University researchers and others shows that convalescent plasma can cut hospital admissions for COVID-19 by 54% if therapy is administered within 8 days of symptom onset.

In the study of 1,181 adults randomly assigned to high-titer convalescent plasma or placebo, 2.9% of people receiving the therapy were hospitalized, compared with 6.3% who received placebo control plasma.

This translates to a 54% risk reduction for hospitalization with convalescent plasma.

“We have a clear difference,” principal investigator David Sullivan, MD, a professor at Johns Hopkins University, Baltimore, said during a Dec. 21 media briefing.

“This is very good news since we are in the midst of the Omicron surge, which has defeated [some of] our major monocular antibody therapies,” said Arturo Casadevall, MD, chair of the department of molecular microbiology and immunology at Johns Hopkins.

“So we have a new tool to keep people from progressing in their disease and to reduce progression or hospitalization,” Dr. Casadevall said.

The findings were published as a preprint study on Dec. 21, 2021, on medRxiv. The study has not yet been peer reviewed.

Whereas many convalescent plasma studies were done in hospitalized patients, this is one of only a handful performed in outpatients, the researchers noted.

There is a regulatory catch. The Food and Drug Administration restricted emergency use authorization (EUA) for convalescent plasma in February 2021 to include only high-dose titer plasma and to limit the therapy to hospitalized patients with early disease or for immunocompromised people who cannot mount an adequate antibody response.

Dr. Sullivan and colleagues hoped their findings will prompt the FDA to expand the EUA to include outpatients.

“We have shared this data with both the World Health Organization and the FDA,” study coauthor Kelly Gebo, MD, MPH, said during the media briefing.

“We do believe that this could be scaled up quickly,” added Dr. Gebo, professor of medicine at Johns Hopkins University. Convalescent plasma “could be used as a potential treatment as variants continue to evolve, such as we’ve seen with Omicron.”
 

Pre-Omicron results

The study was conducted at Johns Hopkins University and 23 other sites nationwide between June 2020 and October 2021. This means researchers enrolled symptomatic adults during circulation of the SARS-CoV-2 ancestral strain and the Alpha and Delta variants.

However, Dr. Sullivan said, “we think that ... plasma with high levels of antibodies can adapt faster to Omicron, although it will take us longer to get an Omicron-specific supply.”

Because of the timing of the study, 80% of participants were unvaccinated. Mean age was 44 years and 57% were women. Black and Hispanic participants each accounted for more than 12% of the study population.

On average, participants received a transfusion within 6 days of the start of symptoms.

In the study, 37 people out of 589 control group participants were hospitalized, compared with 17 of the 592 who received the convalescent plasma.

“We know antibodies work against SARS-CoV-2. The vaccines have been spectacular – producing antibodies that reduce hospitalizations and prevent transmission,” Dr. Sullivan said. “Convalescent plasma provides much of the same antibodies instantly.”
 

Convalescent and controversial

Convalescent plasma has been one of the controversial treatments for people with COVID-19 – with studies going back and forth on the potential benefits and efficacy. A National Institutes of Health–funded study published in August 2021, for example, showed no significant benefit.

“As you know, convalescent plasma has had a rocky ride,” Dr. Casadevall said.

“It was deployed with great excitement in the terrible, early days of the pandemic. Unfortunately, the early excitement and optimism was dampened with some of the randomized control trials appearing to show no benefit in reducing mortality and hospitalized patients,” he added.

In contrast, the current study shows “where convalescent plasma works using the latest, most rigorous clinical investigation tools available: a double-blinded, randomized, placebo-control trial,” Dr. Casadevall said.
 

Why a preprint, and why now?

The researchers decided to release their data in recognition of the lag time between reporting of COVID-19 cases and hospitalizations, Dr. Sullivan said. “That’s part of the reason we decided to act now with this knowledge – that it does take a couple of weeks – with cases of Omicron going up.”

Furthermore, “we thought this was actionable data for decision-makers,” he added.

A reporter asked why the Johns Hopkins researchers chose to hold a media briefing for a preprint study.

A preprint is “not so unusual given the SARS-CoV-2 pandemic,” said study senior author Daniel Hanley, MD, division director of brain injury outcomes at Johns Hopkins University.

“The data are the data,” Dr. Casadevall added. “This is not going to change from peer review.”

Peer review may change some of the wording of the manuscript, but not the numbers, he added.

“Now with the Omicron crisis and the fact that we have lost some more main monoclonal antibodies, it is essential to get this information out,” Dr. Casadevall said.
 

Plasma therapy nothing new

Donation and transfusion of convalescent plasma is highly regulated with strict criteria, said Evan Bloch, MBChB, associate director of the transfusion medicine division at Johns Hopkins University.

If the FDA opts to expand the EUA based on this or other evidence, administration of convalescent plasma could be rolled out fairly quickly, the researchers noted.

Plasma transfusion takes place in hospitals and at infusion centers every day. The infrastructure is in place in many countries, even low- and middle-resource nations, around the world to provide convalescent plasma therapy. The major difference between traditional plasma and SARS-CoV-2 convalescent plasma is the indication, Dr. Bloch added.

In addition, convalescent plasma has a polyclonal composition – a benefit compared with monoclonal antibodies, he added. “It’s more durable or adaptive [compared with] some of the targeted therapies, such as monoclonal antibodies, where we’ve witnessed this diminished efficacy with viral evolution.”

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

A “definitive study” from Johns Hopkins University researchers and others shows that convalescent plasma can cut hospital admissions for COVID-19 by 54% if therapy is administered within 8 days of symptom onset.

In the study of 1,181 adults randomly assigned to high-titer convalescent plasma or placebo, 2.9% of people receiving the therapy were hospitalized, compared with 6.3% who received placebo control plasma.

This translates to a 54% risk reduction for hospitalization with convalescent plasma.

“We have a clear difference,” principal investigator David Sullivan, MD, a professor at Johns Hopkins University, Baltimore, said during a Dec. 21 media briefing.

“This is very good news since we are in the midst of the Omicron surge, which has defeated [some of] our major monocular antibody therapies,” said Arturo Casadevall, MD, chair of the department of molecular microbiology and immunology at Johns Hopkins.

“So we have a new tool to keep people from progressing in their disease and to reduce progression or hospitalization,” Dr. Casadevall said.

The findings were published as a preprint study on Dec. 21, 2021, on medRxiv. The study has not yet been peer reviewed.

Whereas many convalescent plasma studies were done in hospitalized patients, this is one of only a handful performed in outpatients, the researchers noted.

There is a regulatory catch. The Food and Drug Administration restricted emergency use authorization (EUA) for convalescent plasma in February 2021 to include only high-dose titer plasma and to limit the therapy to hospitalized patients with early disease or for immunocompromised people who cannot mount an adequate antibody response.

Dr. Sullivan and colleagues hoped their findings will prompt the FDA to expand the EUA to include outpatients.

“We have shared this data with both the World Health Organization and the FDA,” study coauthor Kelly Gebo, MD, MPH, said during the media briefing.

“We do believe that this could be scaled up quickly,” added Dr. Gebo, professor of medicine at Johns Hopkins University. Convalescent plasma “could be used as a potential treatment as variants continue to evolve, such as we’ve seen with Omicron.”
 

Pre-Omicron results

The study was conducted at Johns Hopkins University and 23 other sites nationwide between June 2020 and October 2021. This means researchers enrolled symptomatic adults during circulation of the SARS-CoV-2 ancestral strain and the Alpha and Delta variants.

However, Dr. Sullivan said, “we think that ... plasma with high levels of antibodies can adapt faster to Omicron, although it will take us longer to get an Omicron-specific supply.”

Because of the timing of the study, 80% of participants were unvaccinated. Mean age was 44 years and 57% were women. Black and Hispanic participants each accounted for more than 12% of the study population.

On average, participants received a transfusion within 6 days of the start of symptoms.

In the study, 37 people out of 589 control group participants were hospitalized, compared with 17 of the 592 who received the convalescent plasma.

“We know antibodies work against SARS-CoV-2. The vaccines have been spectacular – producing antibodies that reduce hospitalizations and prevent transmission,” Dr. Sullivan said. “Convalescent plasma provides much of the same antibodies instantly.”
 

Convalescent and controversial

Convalescent plasma has been one of the controversial treatments for people with COVID-19 – with studies going back and forth on the potential benefits and efficacy. A National Institutes of Health–funded study published in August 2021, for example, showed no significant benefit.

“As you know, convalescent plasma has had a rocky ride,” Dr. Casadevall said.

“It was deployed with great excitement in the terrible, early days of the pandemic. Unfortunately, the early excitement and optimism was dampened with some of the randomized control trials appearing to show no benefit in reducing mortality and hospitalized patients,” he added.

In contrast, the current study shows “where convalescent plasma works using the latest, most rigorous clinical investigation tools available: a double-blinded, randomized, placebo-control trial,” Dr. Casadevall said.
 

Why a preprint, and why now?

The researchers decided to release their data in recognition of the lag time between reporting of COVID-19 cases and hospitalizations, Dr. Sullivan said. “That’s part of the reason we decided to act now with this knowledge – that it does take a couple of weeks – with cases of Omicron going up.”

Furthermore, “we thought this was actionable data for decision-makers,” he added.

A reporter asked why the Johns Hopkins researchers chose to hold a media briefing for a preprint study.

A preprint is “not so unusual given the SARS-CoV-2 pandemic,” said study senior author Daniel Hanley, MD, division director of brain injury outcomes at Johns Hopkins University.

“The data are the data,” Dr. Casadevall added. “This is not going to change from peer review.”

Peer review may change some of the wording of the manuscript, but not the numbers, he added.

“Now with the Omicron crisis and the fact that we have lost some more main monoclonal antibodies, it is essential to get this information out,” Dr. Casadevall said.
 

Plasma therapy nothing new

Donation and transfusion of convalescent plasma is highly regulated with strict criteria, said Evan Bloch, MBChB, associate director of the transfusion medicine division at Johns Hopkins University.

If the FDA opts to expand the EUA based on this or other evidence, administration of convalescent plasma could be rolled out fairly quickly, the researchers noted.

Plasma transfusion takes place in hospitals and at infusion centers every day. The infrastructure is in place in many countries, even low- and middle-resource nations, around the world to provide convalescent plasma therapy. The major difference between traditional plasma and SARS-CoV-2 convalescent plasma is the indication, Dr. Bloch added.

In addition, convalescent plasma has a polyclonal composition – a benefit compared with monoclonal antibodies, he added. “It’s more durable or adaptive [compared with] some of the targeted therapies, such as monoclonal antibodies, where we’ve witnessed this diminished efficacy with viral evolution.”

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

The International Skin Imaging Collaboration (ISIC) Artificial Intelligence Working Group has released the first-ever guidelines for developing artificial intelligence (AI) algorithms used in dermatology.

Christopher Smith

The guidelines, published in JAMA Dermatology on Dec. 1, 2021, contain a broad range of recommendations stakeholders should consider when developing and assessing image-based AI algorithms in dermatology. The recommendations are divided into categories of data, technique, technical assessment, and application. ISIC is “an academia and industry partnership designed to facilitate the application of digital skin imaging to help reduce melanoma mortality,” and is organized into different working groups, including the AI working group, according to its website.

“Our goal with these guidelines was to create higher-quality reporting of dataset and algorithm characteristics for dermatology AI,” first author Roxana Daneshjou, MD, PhD, clinical scholar in dermatology, in the department of dermatology at Stanford (Calif.) University, said in an interview. “We hope these guidelines also aid regulatory bodies around the world when they are assessing algorithms to be used in dermatology.”
 

Recommendations for data

The authors recommended that datasets used by AI algorithms have image descriptions and details on image artifacts. “For photography, these include the type of camera used; whether images were taken under standardized or varying conditions; whether they were taken by professional photographers, laymen, or health care professionals; and image quality,” they wrote. They also recommended that developers include in an image description the type of lighting used and whether the photo contains pen markings, hair, tattoos, injuries, surgical effects, or other “physical perturbations.”

Exchangeable image file format data obtained from the camera, and preprocessing procedures like color normalization and “postprocessing” of images, such as filtering, should also be disclosed. In addition, developers should disclose and justify inclusion of images that have been created by an algorithm within a dataset. Any public images used in the datasets should have references, and privately used images should be made public where possible, the authors said.

The ISIC working group guidelines also provided recommendations for patient-level metadata. Each image should include a patient’s geographical location and medical center they visited as well as their age, sex and gender, ethnicity and/or race, and skin tone. Dr. Daneshjou said this was one area where she and her colleagues found a lack of transparency in AI datasets in algorithms in a recent review. “We found that many AI papers provided sparse details about the images used to train and test their algorithms,” Dr. Daneshjou explained. “For example, only 7 out of 70 papers had any information about the skin tones in the images used for developing and/or testing AI algorithms. Understanding the diversity of images used to train and test algorithms is important because algorithms that are developed on images of predominantly white skin likely won’t work as well on Black and brown skin.”

The guideline authors also asked algorithm developers to describe the limitations of not including patient-level metadata information when it is incomplete or unavailable. In addition, “we ask that algorithm developers comment on potential biases of their algorithms,” Dr. Daneshjou said. “For example, an algorithm based only on telemedicine images may not capture the full range of diseases seen within an in-person clinic.”

When describing their AI algorithm, developers should detail their reasoning for the dataset size and partitions, inclusion and exclusion criteria for images, and use of any external samples for test sets. “Authors should consider any differences between the image characteristics used for algorithm development and those that might be encountered in the real world,” the guidelines stated.

Recommendations for technique

How the images in a dataset are labeled is a unique challenge in developing AI algorithms for dermatology, the authors noted. Developers should use histopathological diagnosis in their labeling, but this can sometimes result in label noise.

“Many of the AI algorithms in dermatology use supervised learning, which requires labeled examples to help the algorithm ‘learn’ features for discriminating between lesions. We found that some papers use consensus labeling – dermatologists providing a label – to label skin cancers; however, the standard for diagnosing skin cancer is using histopathology from a biopsy,” she said. “Dermatologists can biopsy seven to eight suspected melanomas before discovering a true melanoma, so dermatologist labeling of skin cancers is prone to label noise.”

ISIC’s guidelines stated a gold standard of labeling for dermatologic images is one area that still needs future research, but currently, “diagnoses, labels and diagnostic groups used in data repositories as well as public ontologies” such as ICD-11, AnatomyMapper, and SNOMED-CT should be included in dermatologic image datasets.

AI developers should also provide a detailed description of their algorithm, which includes methods, work flows, mathematical formulas as well as the generalizability of the algorithm across more than one dataset.
 

Recommendations for technical assessment

“Another important recommendation is that algorithm developers should provide a way for algorithms to be publicly evaluable by researchers,” Dr. Daneshjou said. “Many dermatology AI algorithms do not share either their data or their algorithm. Algorithm sharing is important for assessing reproducibility and robustness.”

Google’s recently announced AI-powered dermatology assistant tool, for example, “has made claims about its accuracy and ability to diagnose skin disease at a dermatologist level, but there is no way for researchers to independently test these claims,” she said. Other options like Model Dermatology, developed by Seung Seog Han, MD, PhD, of the Dermatology Clinic in Seoul, South Korea, and colleagues, offer an application programming interface “that allows researchers to test the algorithm,” Dr. Daneshjou said. “This kind of openness is key for assessing algorithm robustness.”

Developers should also note in their algorithm explanations how performance markers and benchmarks would translate to proposed clinical application. “In this context,” the use case – the context in which the AI application is being used – “should be clearly described – who are the intended users and under what clinical scenario are they using the algorithm,” the authors wrote.
 

Recommendations for application

The guidelines note that use case for the model should also be described by the AI developers. “Our checklist includes delineating use cases for algorithms and describing what use cases may be within the scope of the algorithm versus which use cases are out of scope,” Dr. Daneshjou said. “For example, an algorithm developed to provide decision support to dermatologists, with a human in the loop, may not be accurate enough to release directly to consumers.”

As the goal of AI algorithms in dermatology is eventual implementation for clinicians and patients, the authors asked developers to consider shortcomings and potential harms of the algorithm during implementation. “Ethical considerations and impact on vulnerable populations should also be considered and discussed,” they wrote. An algorithm “suggesting aesthetic medical treatments may have negative effects given the biased nature of beauty standards,” and “an algorithm that diagnoses basal cell carcinomas but lacks any pigmented basal cell carcinomas, which are more often seen in skin of color, will not perform equitably across populations.”

Prior to implementing an AI algorithm, the ISIC working group recommended developers perform prospective clinical trials for validation. Checklists and guidelines like SPIRIT-AI and CONSORT-AI “provide guidance on how to design clinical trials to test AI algorithms,” Dr. Daneshjou said.

After implementation, “I believe we need additional research in how we monitor algorithms after they are deployed clinically, Dr. Daneshjou said. “Currently there are no [Food and Drug Administration]–approved AI algorithms in dermatology; however, there are several applications that have CE mark in Europe, and there are no mechanisms for postmarket surveillance there.
 

'Timely' recommendations

Commenting on the ISIC working group guidelines, Justin M. Ko, MD, MBA, director and chief of medical dermatology for Stanford Health Care, who was not involved with the work, said that the recommendations are timely and provide “a framework for a ‘common language’ around AI datasets specifically tailored to dermatology.” Dr. Ko, chair of the American Academy of Dermatology’s Ad Hoc Task Force on Augmented Intelligence, noted the work by Dr. Daneshjou and colleagues “is consistent with and builds further details” on the position statement released by the AAD AI task force in 2019.

“As machine-learning capabilities and commercial efforts continue to mature, it becomes increasingly important that we are able to ‘look under the hood,’ and evaluate all the critical factors that influence development of these capabilities,” he said in an interview. “A standard set of reporting guidelines not only allows for transparency in evaluating data and performance of models and algorithms, but also forces the consideration of issues of equity, fairness, mitigation of bias, and clinically meaningful outcomes.”

One concern is the impact of AI algorithms on societal or health systems, he noted, which is brought up in the guidelines. “The last thing we would want is the development of robust AI systems that exacerbate access challenges, or generate patient anxiety/worry, or drive low-value utilization, or adds to care team burden, or create a technological barrier to care, or increases inequity in dermatologic care,” he said.

In developing AI algorithms for dermatology, a “major practical issue” is how performance on paper will translate to real-world use, Dr. Ko explained, and the ISIC guidelines “provide a critical step in empowering clinicians, practices, and our field to shape the advent of the AI and augmented intelligence tools and systems to promote and enhance meaningful clinical outcomes, and augment the core patient-clinician relationship and ensure they are grounded in principles of fairness, equity and transparency.”

This research was funded by awards and grants to individual authors from the Charina Fund, a Google Research Award, Melanoma Research Alliance, National Health and Medical Research Council, National Institutes of Health/National Cancer Institute, National Science Foundation, and the Department of Veterans Affairs. The authors disclosed relationships with governmental entities, pharmaceutical companies, technology startups, medical publishers, charitable trusts, consulting firms, dermatology training companies, providers of medical devices, manufacturers of dermatologic products, and other organizations related to the paper in the form of supplied equipment, having founded a company; receiving grants, patents, or personal fees; holding shares; and medical reporting. Dr. Ko reported that he serves as a clinical advisor for Skin Analytics, and has an ongoing research collaboration with Google.

The International Skin Imaging Collaboration (ISIC) Artificial Intelligence Working Group has released the first-ever guidelines for developing artificial intelligence (AI) algorithms used in dermatology.

Christopher Smith

The guidelines, published in JAMA Dermatology on Dec. 1, 2021, contain a broad range of recommendations stakeholders should consider when developing and assessing image-based AI algorithms in dermatology. The recommendations are divided into categories of data, technique, technical assessment, and application. ISIC is “an academia and industry partnership designed to facilitate the application of digital skin imaging to help reduce melanoma mortality,” and is organized into different working groups, including the AI working group, according to its website.

“Our goal with these guidelines was to create higher-quality reporting of dataset and algorithm characteristics for dermatology AI,” first author Roxana Daneshjou, MD, PhD, clinical scholar in dermatology, in the department of dermatology at Stanford (Calif.) University, said in an interview. “We hope these guidelines also aid regulatory bodies around the world when they are assessing algorithms to be used in dermatology.”
 

Recommendations for data

The authors recommended that datasets used by AI algorithms have image descriptions and details on image artifacts. “For photography, these include the type of camera used; whether images were taken under standardized or varying conditions; whether they were taken by professional photographers, laymen, or health care professionals; and image quality,” they wrote. They also recommended that developers include in an image description the type of lighting used and whether the photo contains pen markings, hair, tattoos, injuries, surgical effects, or other “physical perturbations.”

Exchangeable image file format data obtained from the camera, and preprocessing procedures like color normalization and “postprocessing” of images, such as filtering, should also be disclosed. In addition, developers should disclose and justify inclusion of images that have been created by an algorithm within a dataset. Any public images used in the datasets should have references, and privately used images should be made public where possible, the authors said.

The ISIC working group guidelines also provided recommendations for patient-level metadata. Each image should include a patient’s geographical location and medical center they visited as well as their age, sex and gender, ethnicity and/or race, and skin tone. Dr. Daneshjou said this was one area where she and her colleagues found a lack of transparency in AI datasets in algorithms in a recent review. “We found that many AI papers provided sparse details about the images used to train and test their algorithms,” Dr. Daneshjou explained. “For example, only 7 out of 70 papers had any information about the skin tones in the images used for developing and/or testing AI algorithms. Understanding the diversity of images used to train and test algorithms is important because algorithms that are developed on images of predominantly white skin likely won’t work as well on Black and brown skin.”

The guideline authors also asked algorithm developers to describe the limitations of not including patient-level metadata information when it is incomplete or unavailable. In addition, “we ask that algorithm developers comment on potential biases of their algorithms,” Dr. Daneshjou said. “For example, an algorithm based only on telemedicine images may not capture the full range of diseases seen within an in-person clinic.”

When describing their AI algorithm, developers should detail their reasoning for the dataset size and partitions, inclusion and exclusion criteria for images, and use of any external samples for test sets. “Authors should consider any differences between the image characteristics used for algorithm development and those that might be encountered in the real world,” the guidelines stated.

Recommendations for technique

How the images in a dataset are labeled is a unique challenge in developing AI algorithms for dermatology, the authors noted. Developers should use histopathological diagnosis in their labeling, but this can sometimes result in label noise.

“Many of the AI algorithms in dermatology use supervised learning, which requires labeled examples to help the algorithm ‘learn’ features for discriminating between lesions. We found that some papers use consensus labeling – dermatologists providing a label – to label skin cancers; however, the standard for diagnosing skin cancer is using histopathology from a biopsy,” she said. “Dermatologists can biopsy seven to eight suspected melanomas before discovering a true melanoma, so dermatologist labeling of skin cancers is prone to label noise.”

ISIC’s guidelines stated a gold standard of labeling for dermatologic images is one area that still needs future research, but currently, “diagnoses, labels and diagnostic groups used in data repositories as well as public ontologies” such as ICD-11, AnatomyMapper, and SNOMED-CT should be included in dermatologic image datasets.

AI developers should also provide a detailed description of their algorithm, which includes methods, work flows, mathematical formulas as well as the generalizability of the algorithm across more than one dataset.
 

Recommendations for technical assessment

“Another important recommendation is that algorithm developers should provide a way for algorithms to be publicly evaluable by researchers,” Dr. Daneshjou said. “Many dermatology AI algorithms do not share either their data or their algorithm. Algorithm sharing is important for assessing reproducibility and robustness.”

Google’s recently announced AI-powered dermatology assistant tool, for example, “has made claims about its accuracy and ability to diagnose skin disease at a dermatologist level, but there is no way for researchers to independently test these claims,” she said. Other options like Model Dermatology, developed by Seung Seog Han, MD, PhD, of the Dermatology Clinic in Seoul, South Korea, and colleagues, offer an application programming interface “that allows researchers to test the algorithm,” Dr. Daneshjou said. “This kind of openness is key for assessing algorithm robustness.”

Developers should also note in their algorithm explanations how performance markers and benchmarks would translate to proposed clinical application. “In this context,” the use case – the context in which the AI application is being used – “should be clearly described – who are the intended users and under what clinical scenario are they using the algorithm,” the authors wrote.
 

Recommendations for application

The guidelines note that use case for the model should also be described by the AI developers. “Our checklist includes delineating use cases for algorithms and describing what use cases may be within the scope of the algorithm versus which use cases are out of scope,” Dr. Daneshjou said. “For example, an algorithm developed to provide decision support to dermatologists, with a human in the loop, may not be accurate enough to release directly to consumers.”

As the goal of AI algorithms in dermatology is eventual implementation for clinicians and patients, the authors asked developers to consider shortcomings and potential harms of the algorithm during implementation. “Ethical considerations and impact on vulnerable populations should also be considered and discussed,” they wrote. An algorithm “suggesting aesthetic medical treatments may have negative effects given the biased nature of beauty standards,” and “an algorithm that diagnoses basal cell carcinomas but lacks any pigmented basal cell carcinomas, which are more often seen in skin of color, will not perform equitably across populations.”

Prior to implementing an AI algorithm, the ISIC working group recommended developers perform prospective clinical trials for validation. Checklists and guidelines like SPIRIT-AI and CONSORT-AI “provide guidance on how to design clinical trials to test AI algorithms,” Dr. Daneshjou said.

After implementation, “I believe we need additional research in how we monitor algorithms after they are deployed clinically, Dr. Daneshjou said. “Currently there are no [Food and Drug Administration]–approved AI algorithms in dermatology; however, there are several applications that have CE mark in Europe, and there are no mechanisms for postmarket surveillance there.
 

'Timely' recommendations

Commenting on the ISIC working group guidelines, Justin M. Ko, MD, MBA, director and chief of medical dermatology for Stanford Health Care, who was not involved with the work, said that the recommendations are timely and provide “a framework for a ‘common language’ around AI datasets specifically tailored to dermatology.” Dr. Ko, chair of the American Academy of Dermatology’s Ad Hoc Task Force on Augmented Intelligence, noted the work by Dr. Daneshjou and colleagues “is consistent with and builds further details” on the position statement released by the AAD AI task force in 2019.

“As machine-learning capabilities and commercial efforts continue to mature, it becomes increasingly important that we are able to ‘look under the hood,’ and evaluate all the critical factors that influence development of these capabilities,” he said in an interview. “A standard set of reporting guidelines not only allows for transparency in evaluating data and performance of models and algorithms, but also forces the consideration of issues of equity, fairness, mitigation of bias, and clinically meaningful outcomes.”

One concern is the impact of AI algorithms on societal or health systems, he noted, which is brought up in the guidelines. “The last thing we would want is the development of robust AI systems that exacerbate access challenges, or generate patient anxiety/worry, or drive low-value utilization, or adds to care team burden, or create a technological barrier to care, or increases inequity in dermatologic care,” he said.

In developing AI algorithms for dermatology, a “major practical issue” is how performance on paper will translate to real-world use, Dr. Ko explained, and the ISIC guidelines “provide a critical step in empowering clinicians, practices, and our field to shape the advent of the AI and augmented intelligence tools and systems to promote and enhance meaningful clinical outcomes, and augment the core patient-clinician relationship and ensure they are grounded in principles of fairness, equity and transparency.”

This research was funded by awards and grants to individual authors from the Charina Fund, a Google Research Award, Melanoma Research Alliance, National Health and Medical Research Council, National Institutes of Health/National Cancer Institute, National Science Foundation, and the Department of Veterans Affairs. The authors disclosed relationships with governmental entities, pharmaceutical companies, technology startups, medical publishers, charitable trusts, consulting firms, dermatology training companies, providers of medical devices, manufacturers of dermatologic products, and other organizations related to the paper in the form of supplied equipment, having founded a company; receiving grants, patents, or personal fees; holding shares; and medical reporting. Dr. Ko reported that he serves as a clinical advisor for Skin Analytics, and has an ongoing research collaboration with Google.

The International Skin Imaging Collaboration (ISIC) Artificial Intelligence Working Group has released the first-ever guidelines for developing artificial intelligence (AI) algorithms used in dermatology.

Christopher Smith

The guidelines, published in JAMA Dermatology on Dec. 1, 2021, contain a broad range of recommendations stakeholders should consider when developing and assessing image-based AI algorithms in dermatology. The recommendations are divided into categories of data, technique, technical assessment, and application. ISIC is “an academia and industry partnership designed to facilitate the application of digital skin imaging to help reduce melanoma mortality,” and is organized into different working groups, including the AI working group, according to its website.

“Our goal with these guidelines was to create higher-quality reporting of dataset and algorithm characteristics for dermatology AI,” first author Roxana Daneshjou, MD, PhD, clinical scholar in dermatology, in the department of dermatology at Stanford (Calif.) University, said in an interview. “We hope these guidelines also aid regulatory bodies around the world when they are assessing algorithms to be used in dermatology.”
 

Recommendations for data

The authors recommended that datasets used by AI algorithms have image descriptions and details on image artifacts. “For photography, these include the type of camera used; whether images were taken under standardized or varying conditions; whether they were taken by professional photographers, laymen, or health care professionals; and image quality,” they wrote. They also recommended that developers include in an image description the type of lighting used and whether the photo contains pen markings, hair, tattoos, injuries, surgical effects, or other “physical perturbations.”

Exchangeable image file format data obtained from the camera, and preprocessing procedures like color normalization and “postprocessing” of images, such as filtering, should also be disclosed. In addition, developers should disclose and justify inclusion of images that have been created by an algorithm within a dataset. Any public images used in the datasets should have references, and privately used images should be made public where possible, the authors said.

The ISIC working group guidelines also provided recommendations for patient-level metadata. Each image should include a patient’s geographical location and medical center they visited as well as their age, sex and gender, ethnicity and/or race, and skin tone. Dr. Daneshjou said this was one area where she and her colleagues found a lack of transparency in AI datasets in algorithms in a recent review. “We found that many AI papers provided sparse details about the images used to train and test their algorithms,” Dr. Daneshjou explained. “For example, only 7 out of 70 papers had any information about the skin tones in the images used for developing and/or testing AI algorithms. Understanding the diversity of images used to train and test algorithms is important because algorithms that are developed on images of predominantly white skin likely won’t work as well on Black and brown skin.”

The guideline authors also asked algorithm developers to describe the limitations of not including patient-level metadata information when it is incomplete or unavailable. In addition, “we ask that algorithm developers comment on potential biases of their algorithms,” Dr. Daneshjou said. “For example, an algorithm based only on telemedicine images may not capture the full range of diseases seen within an in-person clinic.”

When describing their AI algorithm, developers should detail their reasoning for the dataset size and partitions, inclusion and exclusion criteria for images, and use of any external samples for test sets. “Authors should consider any differences between the image characteristics used for algorithm development and those that might be encountered in the real world,” the guidelines stated.

Recommendations for technique

How the images in a dataset are labeled is a unique challenge in developing AI algorithms for dermatology, the authors noted. Developers should use histopathological diagnosis in their labeling, but this can sometimes result in label noise.

“Many of the AI algorithms in dermatology use supervised learning, which requires labeled examples to help the algorithm ‘learn’ features for discriminating between lesions. We found that some papers use consensus labeling – dermatologists providing a label – to label skin cancers; however, the standard for diagnosing skin cancer is using histopathology from a biopsy,” she said. “Dermatologists can biopsy seven to eight suspected melanomas before discovering a true melanoma, so dermatologist labeling of skin cancers is prone to label noise.”

ISIC’s guidelines stated a gold standard of labeling for dermatologic images is one area that still needs future research, but currently, “diagnoses, labels and diagnostic groups used in data repositories as well as public ontologies” such as ICD-11, AnatomyMapper, and SNOMED-CT should be included in dermatologic image datasets.

AI developers should also provide a detailed description of their algorithm, which includes methods, work flows, mathematical formulas as well as the generalizability of the algorithm across more than one dataset.
 

Recommendations for technical assessment

“Another important recommendation is that algorithm developers should provide a way for algorithms to be publicly evaluable by researchers,” Dr. Daneshjou said. “Many dermatology AI algorithms do not share either their data or their algorithm. Algorithm sharing is important for assessing reproducibility and robustness.”

Google’s recently announced AI-powered dermatology assistant tool, for example, “has made claims about its accuracy and ability to diagnose skin disease at a dermatologist level, but there is no way for researchers to independently test these claims,” she said. Other options like Model Dermatology, developed by Seung Seog Han, MD, PhD, of the Dermatology Clinic in Seoul, South Korea, and colleagues, offer an application programming interface “that allows researchers to test the algorithm,” Dr. Daneshjou said. “This kind of openness is key for assessing algorithm robustness.”

Developers should also note in their algorithm explanations how performance markers and benchmarks would translate to proposed clinical application. “In this context,” the use case – the context in which the AI application is being used – “should be clearly described – who are the intended users and under what clinical scenario are they using the algorithm,” the authors wrote.
 

Recommendations for application

The guidelines note that use case for the model should also be described by the AI developers. “Our checklist includes delineating use cases for algorithms and describing what use cases may be within the scope of the algorithm versus which use cases are out of scope,” Dr. Daneshjou said. “For example, an algorithm developed to provide decision support to dermatologists, with a human in the loop, may not be accurate enough to release directly to consumers.”

As the goal of AI algorithms in dermatology is eventual implementation for clinicians and patients, the authors asked developers to consider shortcomings and potential harms of the algorithm during implementation. “Ethical considerations and impact on vulnerable populations should also be considered and discussed,” they wrote. An algorithm “suggesting aesthetic medical treatments may have negative effects given the biased nature of beauty standards,” and “an algorithm that diagnoses basal cell carcinomas but lacks any pigmented basal cell carcinomas, which are more often seen in skin of color, will not perform equitably across populations.”

Prior to implementing an AI algorithm, the ISIC working group recommended developers perform prospective clinical trials for validation. Checklists and guidelines like SPIRIT-AI and CONSORT-AI “provide guidance on how to design clinical trials to test AI algorithms,” Dr. Daneshjou said.

After implementation, “I believe we need additional research in how we monitor algorithms after they are deployed clinically, Dr. Daneshjou said. “Currently there are no [Food and Drug Administration]–approved AI algorithms in dermatology; however, there are several applications that have CE mark in Europe, and there are no mechanisms for postmarket surveillance there.
 

'Timely' recommendations

Commenting on the ISIC working group guidelines, Justin M. Ko, MD, MBA, director and chief of medical dermatology for Stanford Health Care, who was not involved with the work, said that the recommendations are timely and provide “a framework for a ‘common language’ around AI datasets specifically tailored to dermatology.” Dr. Ko, chair of the American Academy of Dermatology’s Ad Hoc Task Force on Augmented Intelligence, noted the work by Dr. Daneshjou and colleagues “is consistent with and builds further details” on the position statement released by the AAD AI task force in 2019.

“As machine-learning capabilities and commercial efforts continue to mature, it becomes increasingly important that we are able to ‘look under the hood,’ and evaluate all the critical factors that influence development of these capabilities,” he said in an interview. “A standard set of reporting guidelines not only allows for transparency in evaluating data and performance of models and algorithms, but also forces the consideration of issues of equity, fairness, mitigation of bias, and clinically meaningful outcomes.”

One concern is the impact of AI algorithms on societal or health systems, he noted, which is brought up in the guidelines. “The last thing we would want is the development of robust AI systems that exacerbate access challenges, or generate patient anxiety/worry, or drive low-value utilization, or adds to care team burden, or create a technological barrier to care, or increases inequity in dermatologic care,” he said.

In developing AI algorithms for dermatology, a “major practical issue” is how performance on paper will translate to real-world use, Dr. Ko explained, and the ISIC guidelines “provide a critical step in empowering clinicians, practices, and our field to shape the advent of the AI and augmented intelligence tools and systems to promote and enhance meaningful clinical outcomes, and augment the core patient-clinician relationship and ensure they are grounded in principles of fairness, equity and transparency.”

This research was funded by awards and grants to individual authors from the Charina Fund, a Google Research Award, Melanoma Research Alliance, National Health and Medical Research Council, National Institutes of Health/National Cancer Institute, National Science Foundation, and the Department of Veterans Affairs. The authors disclosed relationships with governmental entities, pharmaceutical companies, technology startups, medical publishers, charitable trusts, consulting firms, dermatology training companies, providers of medical devices, manufacturers of dermatologic products, and other organizations related to the paper in the form of supplied equipment, having founded a company; receiving grants, patents, or personal fees; holding shares; and medical reporting. Dr. Ko reported that he serves as a clinical advisor for Skin Analytics, and has an ongoing research collaboration with Google.

The clinical value of bamlanivimab for hospitalized COVID-19 patients depends on whether patients have endogenous neutralizing antibodies at the time of treatment, according to new research.

In the randomized controlled trial, in both the group who received bamlanivimab and the group who received placebo, higher antigen and viral RNA levels were associated with a lower proportion of patients achieving recovery.

Other studies have shown that the use of monoclonal antibodies reduces hospitalization risk in outpatients with early COVID-19, and appears to promote viral load decline in the nasopharynx, wrote Jens D. Lundgren, MD, of the University of Copenhagen and colleagues in their article published in the Annals of Internal Medicine. What had been missing prior to this new research was final results from hospitalized patients, the authors said.

In the new study, the researchers randomized 314 adults hospitalized with COVID-19 but without end-organ failure to receive 7,000 mg bamlanivimab (163 patients) or a placebo (151 patients). All patients received study-supplied remdesivir unless contraindicated. The researchers compared the efficacy of bamlanivimab versus placebo, but considered remdesivir the standard of care in this study.

At baseline, 50% of patients overall had antispike endogenous neutralizing antibodies (nAbs), and 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1,000 ng/L.

The median time to sustained recovery, 19 days, was not significantly different between the bamlanivimab and placebo groups (subhazard ratio, 0.99).

“As hypothesized, among those who were negative for nAb, the difference between bamlanivimab and placebo was more evident if levels of plasma antigen or nasal-swab viral RNA were above the median entry levels,” with subhazard ratios of 1.48 and 1.89, respectively, the researchers explained.

However, the hazard ratio for death for bamlanivimab vs. placebo was 0.45 for patients negative for nAb vs. 3.53 for those positive for nAb. These differences with respect to nAb status were similar across all 90 elements of a composite safety outcome, the researchers said.

Potential benefits remain unclear

The use of neutralizing monoclonal antibodies has been extensively documented as an effective treatment for COVID-19 among ambulatory patients, corresponding author Dr. Lundgren said in an interview.

“Conversely, among admitted patients with COVID-19 pneumonia, the benefit has been questionable,” he said.

The researchers examined a hypothesis that the null finding in hospitalized patients may stem from differences in underlying mechanisms, “either from uncontrolled viral replication – which would be predicted to occur in particular among those not yet been able to mount an endogenous immune response – or from hyperinflammation among those that have mounted such a response,” Dr. Lundgren said.

 The study findings supported the stated hypothesis, said Dr. Lundgren. “However, it was surprising that not only was the neutralizing antibody without any benefit among those that had mounted an endogenous immune response, but it actually may have been harmful,” he said.

Bamlanivimab was effective against the viral strain that circulated at the time of enrollment in the study, but subsequent viral strains have appeared to be unaffected by the neutralizing activity of the antibody, said Dr. Lundgren.

From a practical standpoint, “the findings would suggest that use of neutralizing monoclonal antibodies for patients admitted to a hospital with COVID pneumonia should be restricted to those that have not yet mounted an endogenous immune response, as determined by lack of detectable neutralizing antibodies at the time of admission,” Dr. Lundgren said.

Looking ahead, studies are currently underway to examine how the findings translate to vaccinated patients, he added. Other questions to be addressed include whether the benefits and harms apply to some or all neutralizing antibody products, he said.

In addition, “our research consortium is currently doing field testing of several point-of-care test candidates to examine their reliability and functionality,” for how quickly they might identify an endogenous neutralizing antibody response in an admitted COVID pneumonia patient,” Dr. Lundgren noted.

Findings show bamlanivimab’s limits

“Based on the findings of the current study, no clear subgroup of patients could be identified who would benefit from bamlanivimab when hospitalized with COVID-19,” said Suman Pal, MD, of the University of New Mexico, Albuquerque, in an interview.

“The study findings also show possible harm of using bamlanivimab in hospitalized COVID-19 patients who were seropositive for neutralizing antibodies prior to receiving therapy,” Dr. Pal emphasized. “Moreover, the study did not include participants with COVID-19 from variant strains, such as delta and omicron, which currently account for a large number of cases.” “Therefore, the results of this study do not support the use of bamlanivimab in the clinical setting until further evidence is available to guide the selection of patients who may benefit from therapy,” he explained.

“The possible benefit of bamlanivimab does not outweigh the risks in patients hospitalized with COVID-19,” he concluded.

Dr. Pal emphasized the need for larger prospective studies to establish whether bamlanivimab may have benefits in a subgroup of patients, but “well-validated point-of-care tests to identify such patients need to be readily available before this therapy can be considered by clinicians at the bedside,” he concluded.

Diligent screening required before use

Monoclonal antibody treatment has been administered to individuals with diagnosis of COVID-19 infection as outpatients as well as for hospitalized inpatients, said Noel Deep, MD, an internist in Antigo, Wisc., in an interview. “This study is important because it helps physicians and health care institutions to evaluate whether continued use of the monoclonal antibodies would be beneficial and, if so, in what patient populations,” he said.

The findings present interesting implications for the care of COVID-19 patients, said Dr. Deep. “This study indicates that bamlanivimab does not provide the benefit that was initially envisioned when the monoclonal antibody infusions were initially initiated in the treatment of COVID-19 infections. “Serological screening of the patients would help to identify that subgroup of individuals who could benefit from this monoclonal antibody rather than administering it to every COVID-19–positive individual,” he explained.

However, “it is important to note that the emergency use authorization (EUA) for single-agent bamlanivimab has been revoked,” Dr. Deep said.

“The potential benefits of bamlanivimab can be realized only if adequate attention is paid to identifying the appropriate candidates based on serological screening, and administering bamlanivimab to those who are already producing endogenous antibodies could lead to increased risk to those individuals,” he said. Dr. Deep added that he would favor administration of bamlanivimab “in those appropriately screened and eligible candidates, and it is my opinion that the benefits outweigh the risks in those individuals.”

Although the EUA for single-agent bamlanivimab has been revoked, “alternative monoclonal antibody therapies remain available under EUA, including REGEN-COV (casirivimab and imdevimab, administered together), and bamlanivimab and etesevimab administered together, for the same uses as previously authorized for bamlanivimab alone,” Dr. Deep said. “The FDA believes that these alternative monoclonal antibody therapies remain appropriate to treat patients with COVID-19, and I would like to see some data about the benefits and risks of these agents,” he noted.

Limitations, funding, and disclosures

The main limitation of the study was the small size and the fact that it was a subgroup analysis of a trial that ended early because of futility, the researchers wrote. However, the Therapeutics for Inpatients With COVID-19 (TICO) platform will proceed with clinical evaluation of additional COVID-19 treatments, they said.

The study was supported primarily by the U.S. government Operation Warp Speed and the National Institute of Allergy and Infectious Diseases. Other funding sources included the Division of Clinical Research and Leidos Biomedical Research for the INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) Network, as well as an agreement between the National Heart, Lung, and Blood Institute and the Research Triangle Institute for the PETAL (Prevention & Early Treatment of Acute Lung Injury) Network and CTSN (Cardiothoracic Surgical Trials Network). Other support came from the U.S. Department of Veterans Affairs and the governments of Denmark (National Research Foundation), Australia (National Health and Medical Research Council), and the United Kingdom (Medical Research Council).

The medications used in the study were donated by Gilead Sciences and Eli Lilly.

The researchers had no financial conflicts do disclose. Dr. Deep and Dr. Pal had no relevant financial conflicts to disclose.

The clinical value of bamlanivimab for hospitalized COVID-19 patients depends on whether patients have endogenous neutralizing antibodies at the time of treatment, according to new research.

In the randomized controlled trial, in both the group who received bamlanivimab and the group who received placebo, higher antigen and viral RNA levels were associated with a lower proportion of patients achieving recovery.

Other studies have shown that the use of monoclonal antibodies reduces hospitalization risk in outpatients with early COVID-19, and appears to promote viral load decline in the nasopharynx, wrote Jens D. Lundgren, MD, of the University of Copenhagen and colleagues in their article published in the Annals of Internal Medicine. What had been missing prior to this new research was final results from hospitalized patients, the authors said.

In the new study, the researchers randomized 314 adults hospitalized with COVID-19 but without end-organ failure to receive 7,000 mg bamlanivimab (163 patients) or a placebo (151 patients). All patients received study-supplied remdesivir unless contraindicated. The researchers compared the efficacy of bamlanivimab versus placebo, but considered remdesivir the standard of care in this study.

At baseline, 50% of patients overall had antispike endogenous neutralizing antibodies (nAbs), and 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1,000 ng/L.

The median time to sustained recovery, 19 days, was not significantly different between the bamlanivimab and placebo groups (subhazard ratio, 0.99).

“As hypothesized, among those who were negative for nAb, the difference between bamlanivimab and placebo was more evident if levels of plasma antigen or nasal-swab viral RNA were above the median entry levels,” with subhazard ratios of 1.48 and 1.89, respectively, the researchers explained.

However, the hazard ratio for death for bamlanivimab vs. placebo was 0.45 for patients negative for nAb vs. 3.53 for those positive for nAb. These differences with respect to nAb status were similar across all 90 elements of a composite safety outcome, the researchers said.

Potential benefits remain unclear

The use of neutralizing monoclonal antibodies has been extensively documented as an effective treatment for COVID-19 among ambulatory patients, corresponding author Dr. Lundgren said in an interview.

“Conversely, among admitted patients with COVID-19 pneumonia, the benefit has been questionable,” he said.

The researchers examined a hypothesis that the null finding in hospitalized patients may stem from differences in underlying mechanisms, “either from uncontrolled viral replication – which would be predicted to occur in particular among those not yet been able to mount an endogenous immune response – or from hyperinflammation among those that have mounted such a response,” Dr. Lundgren said.

 The study findings supported the stated hypothesis, said Dr. Lundgren. “However, it was surprising that not only was the neutralizing antibody without any benefit among those that had mounted an endogenous immune response, but it actually may have been harmful,” he said.

Bamlanivimab was effective against the viral strain that circulated at the time of enrollment in the study, but subsequent viral strains have appeared to be unaffected by the neutralizing activity of the antibody, said Dr. Lundgren.

From a practical standpoint, “the findings would suggest that use of neutralizing monoclonal antibodies for patients admitted to a hospital with COVID pneumonia should be restricted to those that have not yet mounted an endogenous immune response, as determined by lack of detectable neutralizing antibodies at the time of admission,” Dr. Lundgren said.

Looking ahead, studies are currently underway to examine how the findings translate to vaccinated patients, he added. Other questions to be addressed include whether the benefits and harms apply to some or all neutralizing antibody products, he said.

In addition, “our research consortium is currently doing field testing of several point-of-care test candidates to examine their reliability and functionality,” for how quickly they might identify an endogenous neutralizing antibody response in an admitted COVID pneumonia patient,” Dr. Lundgren noted.

Findings show bamlanivimab’s limits

“Based on the findings of the current study, no clear subgroup of patients could be identified who would benefit from bamlanivimab when hospitalized with COVID-19,” said Suman Pal, MD, of the University of New Mexico, Albuquerque, in an interview.

“The study findings also show possible harm of using bamlanivimab in hospitalized COVID-19 patients who were seropositive for neutralizing antibodies prior to receiving therapy,” Dr. Pal emphasized. “Moreover, the study did not include participants with COVID-19 from variant strains, such as delta and omicron, which currently account for a large number of cases.” “Therefore, the results of this study do not support the use of bamlanivimab in the clinical setting until further evidence is available to guide the selection of patients who may benefit from therapy,” he explained.

“The possible benefit of bamlanivimab does not outweigh the risks in patients hospitalized with COVID-19,” he concluded.

Dr. Pal emphasized the need for larger prospective studies to establish whether bamlanivimab may have benefits in a subgroup of patients, but “well-validated point-of-care tests to identify such patients need to be readily available before this therapy can be considered by clinicians at the bedside,” he concluded.

Diligent screening required before use

Monoclonal antibody treatment has been administered to individuals with diagnosis of COVID-19 infection as outpatients as well as for hospitalized inpatients, said Noel Deep, MD, an internist in Antigo, Wisc., in an interview. “This study is important because it helps physicians and health care institutions to evaluate whether continued use of the monoclonal antibodies would be beneficial and, if so, in what patient populations,” he said.

The findings present interesting implications for the care of COVID-19 patients, said Dr. Deep. “This study indicates that bamlanivimab does not provide the benefit that was initially envisioned when the monoclonal antibody infusions were initially initiated in the treatment of COVID-19 infections. “Serological screening of the patients would help to identify that subgroup of individuals who could benefit from this monoclonal antibody rather than administering it to every COVID-19–positive individual,” he explained.

However, “it is important to note that the emergency use authorization (EUA) for single-agent bamlanivimab has been revoked,” Dr. Deep said.

“The potential benefits of bamlanivimab can be realized only if adequate attention is paid to identifying the appropriate candidates based on serological screening, and administering bamlanivimab to those who are already producing endogenous antibodies could lead to increased risk to those individuals,” he said. Dr. Deep added that he would favor administration of bamlanivimab “in those appropriately screened and eligible candidates, and it is my opinion that the benefits outweigh the risks in those individuals.”

Although the EUA for single-agent bamlanivimab has been revoked, “alternative monoclonal antibody therapies remain available under EUA, including REGEN-COV (casirivimab and imdevimab, administered together), and bamlanivimab and etesevimab administered together, for the same uses as previously authorized for bamlanivimab alone,” Dr. Deep said. “The FDA believes that these alternative monoclonal antibody therapies remain appropriate to treat patients with COVID-19, and I would like to see some data about the benefits and risks of these agents,” he noted.

Limitations, funding, and disclosures

The main limitation of the study was the small size and the fact that it was a subgroup analysis of a trial that ended early because of futility, the researchers wrote. However, the Therapeutics for Inpatients With COVID-19 (TICO) platform will proceed with clinical evaluation of additional COVID-19 treatments, they said.

The study was supported primarily by the U.S. government Operation Warp Speed and the National Institute of Allergy and Infectious Diseases. Other funding sources included the Division of Clinical Research and Leidos Biomedical Research for the INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) Network, as well as an agreement between the National Heart, Lung, and Blood Institute and the Research Triangle Institute for the PETAL (Prevention & Early Treatment of Acute Lung Injury) Network and CTSN (Cardiothoracic Surgical Trials Network). Other support came from the U.S. Department of Veterans Affairs and the governments of Denmark (National Research Foundation), Australia (National Health and Medical Research Council), and the United Kingdom (Medical Research Council).

The medications used in the study were donated by Gilead Sciences and Eli Lilly.

The researchers had no financial conflicts do disclose. Dr. Deep and Dr. Pal had no relevant financial conflicts to disclose.

The clinical value of bamlanivimab for hospitalized COVID-19 patients depends on whether patients have endogenous neutralizing antibodies at the time of treatment, according to new research.

In the randomized controlled trial, in both the group who received bamlanivimab and the group who received placebo, higher antigen and viral RNA levels were associated with a lower proportion of patients achieving recovery.

Other studies have shown that the use of monoclonal antibodies reduces hospitalization risk in outpatients with early COVID-19, and appears to promote viral load decline in the nasopharynx, wrote Jens D. Lundgren, MD, of the University of Copenhagen and colleagues in their article published in the Annals of Internal Medicine. What had been missing prior to this new research was final results from hospitalized patients, the authors said.

In the new study, the researchers randomized 314 adults hospitalized with COVID-19 but without end-organ failure to receive 7,000 mg bamlanivimab (163 patients) or a placebo (151 patients). All patients received study-supplied remdesivir unless contraindicated. The researchers compared the efficacy of bamlanivimab versus placebo, but considered remdesivir the standard of care in this study.

At baseline, 50% of patients overall had antispike endogenous neutralizing antibodies (nAbs), and 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1,000 ng/L.

The median time to sustained recovery, 19 days, was not significantly different between the bamlanivimab and placebo groups (subhazard ratio, 0.99).

“As hypothesized, among those who were negative for nAb, the difference between bamlanivimab and placebo was more evident if levels of plasma antigen or nasal-swab viral RNA were above the median entry levels,” with subhazard ratios of 1.48 and 1.89, respectively, the researchers explained.

However, the hazard ratio for death for bamlanivimab vs. placebo was 0.45 for patients negative for nAb vs. 3.53 for those positive for nAb. These differences with respect to nAb status were similar across all 90 elements of a composite safety outcome, the researchers said.

Potential benefits remain unclear

The use of neutralizing monoclonal antibodies has been extensively documented as an effective treatment for COVID-19 among ambulatory patients, corresponding author Dr. Lundgren said in an interview.

“Conversely, among admitted patients with COVID-19 pneumonia, the benefit has been questionable,” he said.

The researchers examined a hypothesis that the null finding in hospitalized patients may stem from differences in underlying mechanisms, “either from uncontrolled viral replication – which would be predicted to occur in particular among those not yet been able to mount an endogenous immune response – or from hyperinflammation among those that have mounted such a response,” Dr. Lundgren said.

 The study findings supported the stated hypothesis, said Dr. Lundgren. “However, it was surprising that not only was the neutralizing antibody without any benefit among those that had mounted an endogenous immune response, but it actually may have been harmful,” he said.

Bamlanivimab was effective against the viral strain that circulated at the time of enrollment in the study, but subsequent viral strains have appeared to be unaffected by the neutralizing activity of the antibody, said Dr. Lundgren.

From a practical standpoint, “the findings would suggest that use of neutralizing monoclonal antibodies for patients admitted to a hospital with COVID pneumonia should be restricted to those that have not yet mounted an endogenous immune response, as determined by lack of detectable neutralizing antibodies at the time of admission,” Dr. Lundgren said.

Looking ahead, studies are currently underway to examine how the findings translate to vaccinated patients, he added. Other questions to be addressed include whether the benefits and harms apply to some or all neutralizing antibody products, he said.

In addition, “our research consortium is currently doing field testing of several point-of-care test candidates to examine their reliability and functionality,” for how quickly they might identify an endogenous neutralizing antibody response in an admitted COVID pneumonia patient,” Dr. Lundgren noted.

Findings show bamlanivimab’s limits

“Based on the findings of the current study, no clear subgroup of patients could be identified who would benefit from bamlanivimab when hospitalized with COVID-19,” said Suman Pal, MD, of the University of New Mexico, Albuquerque, in an interview.

“The study findings also show possible harm of using bamlanivimab in hospitalized COVID-19 patients who were seropositive for neutralizing antibodies prior to receiving therapy,” Dr. Pal emphasized. “Moreover, the study did not include participants with COVID-19 from variant strains, such as delta and omicron, which currently account for a large number of cases.” “Therefore, the results of this study do not support the use of bamlanivimab in the clinical setting until further evidence is available to guide the selection of patients who may benefit from therapy,” he explained.

“The possible benefit of bamlanivimab does not outweigh the risks in patients hospitalized with COVID-19,” he concluded.

Dr. Pal emphasized the need for larger prospective studies to establish whether bamlanivimab may have benefits in a subgroup of patients, but “well-validated point-of-care tests to identify such patients need to be readily available before this therapy can be considered by clinicians at the bedside,” he concluded.

Diligent screening required before use

Monoclonal antibody treatment has been administered to individuals with diagnosis of COVID-19 infection as outpatients as well as for hospitalized inpatients, said Noel Deep, MD, an internist in Antigo, Wisc., in an interview. “This study is important because it helps physicians and health care institutions to evaluate whether continued use of the monoclonal antibodies would be beneficial and, if so, in what patient populations,” he said.

The findings present interesting implications for the care of COVID-19 patients, said Dr. Deep. “This study indicates that bamlanivimab does not provide the benefit that was initially envisioned when the monoclonal antibody infusions were initially initiated in the treatment of COVID-19 infections. “Serological screening of the patients would help to identify that subgroup of individuals who could benefit from this monoclonal antibody rather than administering it to every COVID-19–positive individual,” he explained.

However, “it is important to note that the emergency use authorization (EUA) for single-agent bamlanivimab has been revoked,” Dr. Deep said.

“The potential benefits of bamlanivimab can be realized only if adequate attention is paid to identifying the appropriate candidates based on serological screening, and administering bamlanivimab to those who are already producing endogenous antibodies could lead to increased risk to those individuals,” he said. Dr. Deep added that he would favor administration of bamlanivimab “in those appropriately screened and eligible candidates, and it is my opinion that the benefits outweigh the risks in those individuals.”

Although the EUA for single-agent bamlanivimab has been revoked, “alternative monoclonal antibody therapies remain available under EUA, including REGEN-COV (casirivimab and imdevimab, administered together), and bamlanivimab and etesevimab administered together, for the same uses as previously authorized for bamlanivimab alone,” Dr. Deep said. “The FDA believes that these alternative monoclonal antibody therapies remain appropriate to treat patients with COVID-19, and I would like to see some data about the benefits and risks of these agents,” he noted.

Limitations, funding, and disclosures

The main limitation of the study was the small size and the fact that it was a subgroup analysis of a trial that ended early because of futility, the researchers wrote. However, the Therapeutics for Inpatients With COVID-19 (TICO) platform will proceed with clinical evaluation of additional COVID-19 treatments, they said.

The study was supported primarily by the U.S. government Operation Warp Speed and the National Institute of Allergy and Infectious Diseases. Other funding sources included the Division of Clinical Research and Leidos Biomedical Research for the INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) Network, as well as an agreement between the National Heart, Lung, and Blood Institute and the Research Triangle Institute for the PETAL (Prevention & Early Treatment of Acute Lung Injury) Network and CTSN (Cardiothoracic Surgical Trials Network). Other support came from the U.S. Department of Veterans Affairs and the governments of Denmark (National Research Foundation), Australia (National Health and Medical Research Council), and the United Kingdom (Medical Research Council).

The medications used in the study were donated by Gilead Sciences and Eli Lilly.

The researchers had no financial conflicts do disclose. Dr. Deep and Dr. Pal had no relevant financial conflicts to disclose.

New COVID-19 vaccinations in children were down by almost 24% in the last week as new cases rose by just 3.5%, based on new data.

That fairly low number suggests the latest case count from the American Academy of Pediatrics and the Children’s Hospital Association has not caught up yet to the reality of the Omicron variant, which has sent new cases climbing among all ages and now represents the majority of COVID-19 infections nationwide, the Centers for Disease Control and Prevention said.

Meanwhile, in the midst of the latest surge, the United States just passed yet another sobering COVID milestone: 1,000 deaths in children aged 17 and under. The total as of Dec. 20 was 1,015, according to the CDC, with the largest share, almost 32%, occurring in children less than 5 years of age.

The 3.5% increase in child cases brought the total to nearly 170,000 for the week of Dec. 10-16, the fifth such rise in the last 6 weeks and the 19th consecutive week with a count of over 100,000 dating back to mid-August. Regionally, the majority of that increase came in the Northeast, with a small rise in the South and decreases in the Midwest and West, the AAP and CHA said in their weekly COVID report.

At the state level, the largest percent increases in cases over the past 2 weeks were seen in Maine and New Hampshire, as well as Vermont, which has the nation’s highest vaccination rates for children aged 5-11 (51%) and 12-17 (84%), the AAP said in its vaccination trends report.

Nationally, new COVID vaccinations in children continue to trend downward. The number of children aged 5-17 years who had received at least one dose increased by about 498,000 for the week of Dec. 13-19, down from 654,000 (–23.9%) the previous week. Children aged 5-11 years still represented the largest share (22.7%) of all vaccine initiators in the last 2 weeks, but that proportion was 42.8% just before Thanksgiving, according to data from the CDC.

On a more positive note, children aged 5-11 made up 51% of all Americans who completed the vaccine regimen during the 2 weeks ending Dec. 20. The cumulative completion count is 3.6 million in that age group, along with almost 13.4 million children aged 12-17, and the CDC data show that 6.1 million children aged 5-11 and 15.9 million children aged 12-17 have received at least one dose.

On a less positive note, however, that means almost half (47%) of 12- to 17-year-olds still are not fully vaccinated and that over a third (37%) have received no vaccine at all, according to the COVID Data Tracker.

[email protected]

New COVID-19 vaccinations in children were down by almost 24% in the last week as new cases rose by just 3.5%, based on new data.

That fairly low number suggests the latest case count from the American Academy of Pediatrics and the Children’s Hospital Association has not caught up yet to the reality of the Omicron variant, which has sent new cases climbing among all ages and now represents the majority of COVID-19 infections nationwide, the Centers for Disease Control and Prevention said.

Meanwhile, in the midst of the latest surge, the United States just passed yet another sobering COVID milestone: 1,000 deaths in children aged 17 and under. The total as of Dec. 20 was 1,015, according to the CDC, with the largest share, almost 32%, occurring in children less than 5 years of age.

The 3.5% increase in child cases brought the total to nearly 170,000 for the week of Dec. 10-16, the fifth such rise in the last 6 weeks and the 19th consecutive week with a count of over 100,000 dating back to mid-August. Regionally, the majority of that increase came in the Northeast, with a small rise in the South and decreases in the Midwest and West, the AAP and CHA said in their weekly COVID report.

At the state level, the largest percent increases in cases over the past 2 weeks were seen in Maine and New Hampshire, as well as Vermont, which has the nation’s highest vaccination rates for children aged 5-11 (51%) and 12-17 (84%), the AAP said in its vaccination trends report.

Nationally, new COVID vaccinations in children continue to trend downward. The number of children aged 5-17 years who had received at least one dose increased by about 498,000 for the week of Dec. 13-19, down from 654,000 (–23.9%) the previous week. Children aged 5-11 years still represented the largest share (22.7%) of all vaccine initiators in the last 2 weeks, but that proportion was 42.8% just before Thanksgiving, according to data from the CDC.

On a more positive note, children aged 5-11 made up 51% of all Americans who completed the vaccine regimen during the 2 weeks ending Dec. 20. The cumulative completion count is 3.6 million in that age group, along with almost 13.4 million children aged 12-17, and the CDC data show that 6.1 million children aged 5-11 and 15.9 million children aged 12-17 have received at least one dose.

On a less positive note, however, that means almost half (47%) of 12- to 17-year-olds still are not fully vaccinated and that over a third (37%) have received no vaccine at all, according to the COVID Data Tracker.

[email protected]

New COVID-19 vaccinations in children were down by almost 24% in the last week as new cases rose by just 3.5%, based on new data.

That fairly low number suggests the latest case count from the American Academy of Pediatrics and the Children’s Hospital Association has not caught up yet to the reality of the Omicron variant, which has sent new cases climbing among all ages and now represents the majority of COVID-19 infections nationwide, the Centers for Disease Control and Prevention said.

Meanwhile, in the midst of the latest surge, the United States just passed yet another sobering COVID milestone: 1,000 deaths in children aged 17 and under. The total as of Dec. 20 was 1,015, according to the CDC, with the largest share, almost 32%, occurring in children less than 5 years of age.

The 3.5% increase in child cases brought the total to nearly 170,000 for the week of Dec. 10-16, the fifth such rise in the last 6 weeks and the 19th consecutive week with a count of over 100,000 dating back to mid-August. Regionally, the majority of that increase came in the Northeast, with a small rise in the South and decreases in the Midwest and West, the AAP and CHA said in their weekly COVID report.

At the state level, the largest percent increases in cases over the past 2 weeks were seen in Maine and New Hampshire, as well as Vermont, which has the nation’s highest vaccination rates for children aged 5-11 (51%) and 12-17 (84%), the AAP said in its vaccination trends report.

Nationally, new COVID vaccinations in children continue to trend downward. The number of children aged 5-17 years who had received at least one dose increased by about 498,000 for the week of Dec. 13-19, down from 654,000 (–23.9%) the previous week. Children aged 5-11 years still represented the largest share (22.7%) of all vaccine initiators in the last 2 weeks, but that proportion was 42.8% just before Thanksgiving, according to data from the CDC.

On a more positive note, children aged 5-11 made up 51% of all Americans who completed the vaccine regimen during the 2 weeks ending Dec. 20. The cumulative completion count is 3.6 million in that age group, along with almost 13.4 million children aged 12-17, and the CDC data show that 6.1 million children aged 5-11 and 15.9 million children aged 12-17 have received at least one dose.

On a less positive note, however, that means almost half (47%) of 12- to 17-year-olds still are not fully vaccinated and that over a third (37%) have received no vaccine at all, according to the COVID Data Tracker.

[email protected]

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) on December 17 recommended approval of linzagolix (Yselty, ObsEva), an oral gonadotropin-releasing hormone (GnRH) antagonist, for the management of moderate to severe symptoms of uterine fibroids (UF) in adult women of reproductive age.

If approved, linzagolix – which is taken once per day – would become the first GnRH receptor antagonist with a nonhormonal option to reach the market. The U.S. Food and Drug Administration in November accepted ObsEva’s new drug application for the medication, with a decision expected by September 2022.

“The positive CHMP opinion is an important milestone for millions of women in the EU living with UF to address the diverse medical needs of the women who suffer from this condition,” said Brian O’Callaghan, CEO of ObsEva, in a statement. “We will continue our productive, ongoing dialogue with [the] EMA toward potential marketing authorization in the EU and, in parallel, continue to work with the FDA to advance linzagolix through the U.S. regulatory process.”

The committee’s positive opinion was based on 52-week results from PRIMROSE 1 and PRIMROSE 2 phase 3 trials, involving more than 1,000 patients in the United States and Europe, as well as results from 76-week follow-up studies of patients in those trials. The two phase 3 trials assessed a 200-mg and 100-mg dose of linzagolix, with and without hormone add-back therapy (ABT; 1 mg estradiol and 0.5 mg norethisterone acetate).

According to ObsEVA, both trials met their primary endpoints, with all doses showing statistically significant and clinically relevant reductions in heavy menstrual bleeding (HMB) compared to placebo. The trials also achieved several secondary endpoints, including reduction in pain, rates of amenorrhea, time to reduced HMB, and amenorrhea and for the high dose without ABT, reductions in uterine and fibroid volume, the company said.

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

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) on December 17 recommended approval of linzagolix (Yselty, ObsEva), an oral gonadotropin-releasing hormone (GnRH) antagonist, for the management of moderate to severe symptoms of uterine fibroids (UF) in adult women of reproductive age.

If approved, linzagolix – which is taken once per day – would become the first GnRH receptor antagonist with a nonhormonal option to reach the market. The U.S. Food and Drug Administration in November accepted ObsEva’s new drug application for the medication, with a decision expected by September 2022.

“The positive CHMP opinion is an important milestone for millions of women in the EU living with UF to address the diverse medical needs of the women who suffer from this condition,” said Brian O’Callaghan, CEO of ObsEva, in a statement. “We will continue our productive, ongoing dialogue with [the] EMA toward potential marketing authorization in the EU and, in parallel, continue to work with the FDA to advance linzagolix through the U.S. regulatory process.”

The committee’s positive opinion was based on 52-week results from PRIMROSE 1 and PRIMROSE 2 phase 3 trials, involving more than 1,000 patients in the United States and Europe, as well as results from 76-week follow-up studies of patients in those trials. The two phase 3 trials assessed a 200-mg and 100-mg dose of linzagolix, with and without hormone add-back therapy (ABT; 1 mg estradiol and 0.5 mg norethisterone acetate).

According to ObsEVA, both trials met their primary endpoints, with all doses showing statistically significant and clinically relevant reductions in heavy menstrual bleeding (HMB) compared to placebo. The trials also achieved several secondary endpoints, including reduction in pain, rates of amenorrhea, time to reduced HMB, and amenorrhea and for the high dose without ABT, reductions in uterine and fibroid volume, the company said.

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

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) on December 17 recommended approval of linzagolix (Yselty, ObsEva), an oral gonadotropin-releasing hormone (GnRH) antagonist, for the management of moderate to severe symptoms of uterine fibroids (UF) in adult women of reproductive age.

If approved, linzagolix – which is taken once per day – would become the first GnRH receptor antagonist with a nonhormonal option to reach the market. The U.S. Food and Drug Administration in November accepted ObsEva’s new drug application for the medication, with a decision expected by September 2022.

“The positive CHMP opinion is an important milestone for millions of women in the EU living with UF to address the diverse medical needs of the women who suffer from this condition,” said Brian O’Callaghan, CEO of ObsEva, in a statement. “We will continue our productive, ongoing dialogue with [the] EMA toward potential marketing authorization in the EU and, in parallel, continue to work with the FDA to advance linzagolix through the U.S. regulatory process.”

The committee’s positive opinion was based on 52-week results from PRIMROSE 1 and PRIMROSE 2 phase 3 trials, involving more than 1,000 patients in the United States and Europe, as well as results from 76-week follow-up studies of patients in those trials. The two phase 3 trials assessed a 200-mg and 100-mg dose of linzagolix, with and without hormone add-back therapy (ABT; 1 mg estradiol and 0.5 mg norethisterone acetate).

According to ObsEVA, both trials met their primary endpoints, with all doses showing statistically significant and clinically relevant reductions in heavy menstrual bleeding (HMB) compared to placebo. The trials also achieved several secondary endpoints, including reduction in pain, rates of amenorrhea, time to reduced HMB, and amenorrhea and for the high dose without ABT, reductions in uterine and fibroid volume, the company said.

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

Fish oil supplementation does not help prevent depression or boost mood, new research suggests.

The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.

In fact, there was a small increase found in risk for depression or depressive symptoms with omega-3 supplements.

“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.

The findings were published online Dec. 21 in JAMA.
 

Assessing general population risk

For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.

“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.

The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.

Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.

“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
 

No significant benefit

Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.

The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).

There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).

“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.

“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.

“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.

Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
 

Cautionary notes

Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.

First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.

He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.

Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”

VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.

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

Fish oil supplementation does not help prevent depression or boost mood, new research suggests.

The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.

In fact, there was a small increase found in risk for depression or depressive symptoms with omega-3 supplements.

“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.

The findings were published online Dec. 21 in JAMA.
 

Assessing general population risk

For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.

“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.

The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.

Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.

“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
 

No significant benefit

Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.

The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).

There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).

“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.

“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.

“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.

Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
 

Cautionary notes

Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.

First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.

He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.

Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”

VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.

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

Fish oil supplementation does not help prevent depression or boost mood, new research suggests.

The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.

In fact, there was a small increase found in risk for depression or depressive symptoms with omega-3 supplements.

“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.

The findings were published online Dec. 21 in JAMA.
 

Assessing general population risk

For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.

“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.

The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.

Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.

“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
 

No significant benefit

Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.

The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).

There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).

“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.

“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.

“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.

Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
 

Cautionary notes

Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.

First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.

He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.

Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”

VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.

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