User login
Temper tantrums, bullying colleagues: How to avert physician misbehavior?
Daniel Freedman, DO, a pediatric neurologist in Austin, Tex., remembers being flabbergasted when a surgeon threw an instrument across the room in medical school.
“I remember thinking, ‘I can’t believe people actually do this, a grown man in his 50s having a temper tantrum,’” Dr. Freedman said in an interview. But it certainly wasn’t the last time he witnessed bad behavior by one of his peers.
The results of Medscape’s recent report, Physicians Behaving Badly: Stress and Hardship Trigger Misconduct, suggest he has plenty of company. More than 4 in 10 respondents (41%) observed inappropriate behavior in the workplace in 2022, an uptick from 35% in 2021, according to the report, which polled more than 1,500 physicians about inappropriate behavior on and off the clock.
Of course, 38% of respondents have not seen any instances of misbehavior; and many of the instances that were seen were mild or infrequent. Additionally, instances of bad behavior have declined significantly over the past 5 years.
Dr. Freedman said he learned a lesson from his mentor and program director during training that has stuck with him throughout his career. “If you couldn’t act that way at any job, whether at McDonald’s or any other possible place, you shouldn’t act that way in medicine.” But he recognizes one limitation of that advice. “A lot of the people that behave badly may not have ever worked in a different environment before,” he said.
“They only perceive that they’re at the top of the food chain, so they can behave badly without repercussions.”
What Dr. Freedman described is formally called disruptive physician behavior, one of several categories of inappropriate behavior in medicine, according to Charles Samenow, MD, MPH, an associate professor of psychiatry and behavioral sciences at George Washington University, Washington, who has studied this phenomenon for years.
“Disruptive physician behavior compromises the safety of the workplace,” Dr. Samenow explained. The behavior can occur at work, outside of work, or on social media. It can hinder operations, threaten patient and staff safety, and affect workplace morale.
“The question is trying to understand where that bad behavior is coming from and the impact of that bad behavior,” Dr. Samenow said in an interview.
One reason is fairly simple: doctors are human, and humans have a wide range of behavior. Plus, as the Medscape survey showed,
Self-selecting traits become an Achilles heel
“Any human put in a position of power over other humans has the potential to be disruptive, harass, etc, if they have certain personality traits,” said David Gorski, MD, a professor of surgery at Wayne State University, Detroit. That jibes with Dr. Samenow’s research.
Classic disruptive behavior isn’t usually associated with depression, mania, psychosis, or similar characteristics, Dr. Samenow explained. Rather, it tends to be personality driven. “Physicians are not immune to the normal problems every human being faces,” he said.
In the Medscape report, physicians cited personal arrogance as one of the leading reasons physicians engaged in inappropriate behavior (56%), followed closely by personal problems outside of work (52%), a social shift in accepting more casual behavior (50%), and job-related stress (46%). (Respondents could choose more than one answer).
One factor contributing to misbehavior that Dr. Samenow has consistently identified in his research is a history of adverse childhood experiences or family dysfunction: People who grew up in homes with physical or verbal abuse learned anger as a coping skill instead of positive, assertive communication. It’s likely that some physicians, as well as the overall population, learned anger as a coping skill for that reason.
How to help avert disruptive behavior in medical settings
Dr. Samenow said that coaching is a “wonderful tool” in teaching the interpersonal skills that medical school often doesn’t address.
In some case, interventions can be very helpful. For example, programs that teach effective communication strategies and teamwork through a combination of culturally sensitive dialectical and cognitive-behavioral therapy and other modalities have been successful, Dr. Samenow said. Although they are more about treating an illness than addressing “misbehavior,” programs for substance use that have been developed by and for doctors are very effective, too.
Fewer resources are available, however, for addressing racism, classism, misogyny, and other forms of bigotry, Dr. Samenow noted. “There’s implicit bias training, but not at the level of what exists for disruptive physicians and those with addiction. “That’s an area we need to work on.” Racist language was the third most commonly observed bad behavior cited in the Medscape survey, behind only bullying of staff and mocking or disparaging of patients. It was reported frequently outside of work as well.
The Medscape report found an increase in observed behavior at work and on social media, although it’s hard to determine prevalence trends over time, Dr. Samenow said. “The tolerance for this behavior has really gone down,” likely leading to more reporting, he said, and more systems for reporting bad behavior exist today than in the past.
However, Dr. Freedman said inadequate regulation, disciplinary action, and follow-through remain a problem.
“There are lots of limitations to our reporting system and to our follow-through with those reports,” including hospitals that, whether for fear of litigation or other reasons, allow physicians to quietly resign and move to another institution, even with positive recommendations, Dr. Freedman said.
Indeed, only a third of observed misbehavior in the Medscape report resulted in disciplinary action. Half the respondents believed a verbal warning was a necessary consequence, followed by a conversation from management and being reported to a supervisor or human resources. Though only 10% thought a report to the medical board was warranted, it likely depends on the offense and its frequency.
“I think going from paternalism to more patient-centered care and having patients involved in those conversations is a nice shift that makes doctors more human and relatable, and hopefully makes the public more forgiving, that we’re going to make mistakes and nobody’s perfect,” Freedman said. But he added that physicians should be held accountable when a mistake or two becomes a pattern.
Misinformation is professional misconduct
Sufficient accountability is especially absent, these doctors said, for a subset of professional misconduct: spreading misinformation.
While more “conventional” bad behaviors include fraud, dishonesty, abuse of underlings, and incompetence, bad behavior should also include “selling quackery and antivaccine misinformation, the way some doctors did with various nostrums for COVID-19,” said Dr. Gorski, who frequently blogs about doctors’ spreading misinformation.
Taylor Nichols, MD, an emergency medicine physician based in Sacramento, cites the desire for attention and clout as motivations. “Saying things that are wildly, provably false is professional misconduct,” Nichols said. He distinguished such statements from scientific, academic, or clinical disagreement that is necessary within medicine.
Yet there’s been a “long tradition of looking the other way or letting people with fancy titles get away with saying nonsense just because they’re respected,” Jonathan Howard, MD, an associate professor of psychiatry and neurology at New York University said in an interview.
“We have a duty to be trusted members of the community,” Dr. Howard said. “People listen when we say things, and we have an obligation to try to be accurate and humble and as honest as possible and admit mistakes when we inevitably make them.”
That extends to social media, which Dr. Nichols said has magnified the problem of promoting quackery and misinformation. He thinks medical boards and professional credentialing bodies should pay attention to what’s happening in the public conversation and understand that our professional responsibility extends beyond the walls of the hospital or clinic. Physicians must represent themselves professionally and uphold the standards that the profession expects.
On the one hand, Medscape respondents agreed: 70% said one doctor’s misbehavior taints the whole profession. Yet, at the same time, 58% of respondents believed physicians should be able to “keep their private lives private” in 2022. But that’s not the reality of the profession when the lines between private life and behavior away from work get blurred, Dr. Samenow said.
“The way a physician behaves in public represents you,” he said. “What happens in Vegas doesn’t always stay in Vegas.”
A version of this article first appeared on Medscape.com.
Daniel Freedman, DO, a pediatric neurologist in Austin, Tex., remembers being flabbergasted when a surgeon threw an instrument across the room in medical school.
“I remember thinking, ‘I can’t believe people actually do this, a grown man in his 50s having a temper tantrum,’” Dr. Freedman said in an interview. But it certainly wasn’t the last time he witnessed bad behavior by one of his peers.
The results of Medscape’s recent report, Physicians Behaving Badly: Stress and Hardship Trigger Misconduct, suggest he has plenty of company. More than 4 in 10 respondents (41%) observed inappropriate behavior in the workplace in 2022, an uptick from 35% in 2021, according to the report, which polled more than 1,500 physicians about inappropriate behavior on and off the clock.
Of course, 38% of respondents have not seen any instances of misbehavior; and many of the instances that were seen were mild or infrequent. Additionally, instances of bad behavior have declined significantly over the past 5 years.
Dr. Freedman said he learned a lesson from his mentor and program director during training that has stuck with him throughout his career. “If you couldn’t act that way at any job, whether at McDonald’s or any other possible place, you shouldn’t act that way in medicine.” But he recognizes one limitation of that advice. “A lot of the people that behave badly may not have ever worked in a different environment before,” he said.
“They only perceive that they’re at the top of the food chain, so they can behave badly without repercussions.”
What Dr. Freedman described is formally called disruptive physician behavior, one of several categories of inappropriate behavior in medicine, according to Charles Samenow, MD, MPH, an associate professor of psychiatry and behavioral sciences at George Washington University, Washington, who has studied this phenomenon for years.
“Disruptive physician behavior compromises the safety of the workplace,” Dr. Samenow explained. The behavior can occur at work, outside of work, or on social media. It can hinder operations, threaten patient and staff safety, and affect workplace morale.
“The question is trying to understand where that bad behavior is coming from and the impact of that bad behavior,” Dr. Samenow said in an interview.
One reason is fairly simple: doctors are human, and humans have a wide range of behavior. Plus, as the Medscape survey showed,
Self-selecting traits become an Achilles heel
“Any human put in a position of power over other humans has the potential to be disruptive, harass, etc, if they have certain personality traits,” said David Gorski, MD, a professor of surgery at Wayne State University, Detroit. That jibes with Dr. Samenow’s research.
Classic disruptive behavior isn’t usually associated with depression, mania, psychosis, or similar characteristics, Dr. Samenow explained. Rather, it tends to be personality driven. “Physicians are not immune to the normal problems every human being faces,” he said.
In the Medscape report, physicians cited personal arrogance as one of the leading reasons physicians engaged in inappropriate behavior (56%), followed closely by personal problems outside of work (52%), a social shift in accepting more casual behavior (50%), and job-related stress (46%). (Respondents could choose more than one answer).
One factor contributing to misbehavior that Dr. Samenow has consistently identified in his research is a history of adverse childhood experiences or family dysfunction: People who grew up in homes with physical or verbal abuse learned anger as a coping skill instead of positive, assertive communication. It’s likely that some physicians, as well as the overall population, learned anger as a coping skill for that reason.
How to help avert disruptive behavior in medical settings
Dr. Samenow said that coaching is a “wonderful tool” in teaching the interpersonal skills that medical school often doesn’t address.
In some case, interventions can be very helpful. For example, programs that teach effective communication strategies and teamwork through a combination of culturally sensitive dialectical and cognitive-behavioral therapy and other modalities have been successful, Dr. Samenow said. Although they are more about treating an illness than addressing “misbehavior,” programs for substance use that have been developed by and for doctors are very effective, too.
Fewer resources are available, however, for addressing racism, classism, misogyny, and other forms of bigotry, Dr. Samenow noted. “There’s implicit bias training, but not at the level of what exists for disruptive physicians and those with addiction. “That’s an area we need to work on.” Racist language was the third most commonly observed bad behavior cited in the Medscape survey, behind only bullying of staff and mocking or disparaging of patients. It was reported frequently outside of work as well.
The Medscape report found an increase in observed behavior at work and on social media, although it’s hard to determine prevalence trends over time, Dr. Samenow said. “The tolerance for this behavior has really gone down,” likely leading to more reporting, he said, and more systems for reporting bad behavior exist today than in the past.
However, Dr. Freedman said inadequate regulation, disciplinary action, and follow-through remain a problem.
“There are lots of limitations to our reporting system and to our follow-through with those reports,” including hospitals that, whether for fear of litigation or other reasons, allow physicians to quietly resign and move to another institution, even with positive recommendations, Dr. Freedman said.
Indeed, only a third of observed misbehavior in the Medscape report resulted in disciplinary action. Half the respondents believed a verbal warning was a necessary consequence, followed by a conversation from management and being reported to a supervisor or human resources. Though only 10% thought a report to the medical board was warranted, it likely depends on the offense and its frequency.
“I think going from paternalism to more patient-centered care and having patients involved in those conversations is a nice shift that makes doctors more human and relatable, and hopefully makes the public more forgiving, that we’re going to make mistakes and nobody’s perfect,” Freedman said. But he added that physicians should be held accountable when a mistake or two becomes a pattern.
Misinformation is professional misconduct
Sufficient accountability is especially absent, these doctors said, for a subset of professional misconduct: spreading misinformation.
While more “conventional” bad behaviors include fraud, dishonesty, abuse of underlings, and incompetence, bad behavior should also include “selling quackery and antivaccine misinformation, the way some doctors did with various nostrums for COVID-19,” said Dr. Gorski, who frequently blogs about doctors’ spreading misinformation.
Taylor Nichols, MD, an emergency medicine physician based in Sacramento, cites the desire for attention and clout as motivations. “Saying things that are wildly, provably false is professional misconduct,” Nichols said. He distinguished such statements from scientific, academic, or clinical disagreement that is necessary within medicine.
Yet there’s been a “long tradition of looking the other way or letting people with fancy titles get away with saying nonsense just because they’re respected,” Jonathan Howard, MD, an associate professor of psychiatry and neurology at New York University said in an interview.
“We have a duty to be trusted members of the community,” Dr. Howard said. “People listen when we say things, and we have an obligation to try to be accurate and humble and as honest as possible and admit mistakes when we inevitably make them.”
That extends to social media, which Dr. Nichols said has magnified the problem of promoting quackery and misinformation. He thinks medical boards and professional credentialing bodies should pay attention to what’s happening in the public conversation and understand that our professional responsibility extends beyond the walls of the hospital or clinic. Physicians must represent themselves professionally and uphold the standards that the profession expects.
On the one hand, Medscape respondents agreed: 70% said one doctor’s misbehavior taints the whole profession. Yet, at the same time, 58% of respondents believed physicians should be able to “keep their private lives private” in 2022. But that’s not the reality of the profession when the lines between private life and behavior away from work get blurred, Dr. Samenow said.
“The way a physician behaves in public represents you,” he said. “What happens in Vegas doesn’t always stay in Vegas.”
A version of this article first appeared on Medscape.com.
Daniel Freedman, DO, a pediatric neurologist in Austin, Tex., remembers being flabbergasted when a surgeon threw an instrument across the room in medical school.
“I remember thinking, ‘I can’t believe people actually do this, a grown man in his 50s having a temper tantrum,’” Dr. Freedman said in an interview. But it certainly wasn’t the last time he witnessed bad behavior by one of his peers.
The results of Medscape’s recent report, Physicians Behaving Badly: Stress and Hardship Trigger Misconduct, suggest he has plenty of company. More than 4 in 10 respondents (41%) observed inappropriate behavior in the workplace in 2022, an uptick from 35% in 2021, according to the report, which polled more than 1,500 physicians about inappropriate behavior on and off the clock.
Of course, 38% of respondents have not seen any instances of misbehavior; and many of the instances that were seen were mild or infrequent. Additionally, instances of bad behavior have declined significantly over the past 5 years.
Dr. Freedman said he learned a lesson from his mentor and program director during training that has stuck with him throughout his career. “If you couldn’t act that way at any job, whether at McDonald’s or any other possible place, you shouldn’t act that way in medicine.” But he recognizes one limitation of that advice. “A lot of the people that behave badly may not have ever worked in a different environment before,” he said.
“They only perceive that they’re at the top of the food chain, so they can behave badly without repercussions.”
What Dr. Freedman described is formally called disruptive physician behavior, one of several categories of inappropriate behavior in medicine, according to Charles Samenow, MD, MPH, an associate professor of psychiatry and behavioral sciences at George Washington University, Washington, who has studied this phenomenon for years.
“Disruptive physician behavior compromises the safety of the workplace,” Dr. Samenow explained. The behavior can occur at work, outside of work, or on social media. It can hinder operations, threaten patient and staff safety, and affect workplace morale.
“The question is trying to understand where that bad behavior is coming from and the impact of that bad behavior,” Dr. Samenow said in an interview.
One reason is fairly simple: doctors are human, and humans have a wide range of behavior. Plus, as the Medscape survey showed,
Self-selecting traits become an Achilles heel
“Any human put in a position of power over other humans has the potential to be disruptive, harass, etc, if they have certain personality traits,” said David Gorski, MD, a professor of surgery at Wayne State University, Detroit. That jibes with Dr. Samenow’s research.
Classic disruptive behavior isn’t usually associated with depression, mania, psychosis, or similar characteristics, Dr. Samenow explained. Rather, it tends to be personality driven. “Physicians are not immune to the normal problems every human being faces,” he said.
In the Medscape report, physicians cited personal arrogance as one of the leading reasons physicians engaged in inappropriate behavior (56%), followed closely by personal problems outside of work (52%), a social shift in accepting more casual behavior (50%), and job-related stress (46%). (Respondents could choose more than one answer).
One factor contributing to misbehavior that Dr. Samenow has consistently identified in his research is a history of adverse childhood experiences or family dysfunction: People who grew up in homes with physical or verbal abuse learned anger as a coping skill instead of positive, assertive communication. It’s likely that some physicians, as well as the overall population, learned anger as a coping skill for that reason.
How to help avert disruptive behavior in medical settings
Dr. Samenow said that coaching is a “wonderful tool” in teaching the interpersonal skills that medical school often doesn’t address.
In some case, interventions can be very helpful. For example, programs that teach effective communication strategies and teamwork through a combination of culturally sensitive dialectical and cognitive-behavioral therapy and other modalities have been successful, Dr. Samenow said. Although they are more about treating an illness than addressing “misbehavior,” programs for substance use that have been developed by and for doctors are very effective, too.
Fewer resources are available, however, for addressing racism, classism, misogyny, and other forms of bigotry, Dr. Samenow noted. “There’s implicit bias training, but not at the level of what exists for disruptive physicians and those with addiction. “That’s an area we need to work on.” Racist language was the third most commonly observed bad behavior cited in the Medscape survey, behind only bullying of staff and mocking or disparaging of patients. It was reported frequently outside of work as well.
The Medscape report found an increase in observed behavior at work and on social media, although it’s hard to determine prevalence trends over time, Dr. Samenow said. “The tolerance for this behavior has really gone down,” likely leading to more reporting, he said, and more systems for reporting bad behavior exist today than in the past.
However, Dr. Freedman said inadequate regulation, disciplinary action, and follow-through remain a problem.
“There are lots of limitations to our reporting system and to our follow-through with those reports,” including hospitals that, whether for fear of litigation or other reasons, allow physicians to quietly resign and move to another institution, even with positive recommendations, Dr. Freedman said.
Indeed, only a third of observed misbehavior in the Medscape report resulted in disciplinary action. Half the respondents believed a verbal warning was a necessary consequence, followed by a conversation from management and being reported to a supervisor or human resources. Though only 10% thought a report to the medical board was warranted, it likely depends on the offense and its frequency.
“I think going from paternalism to more patient-centered care and having patients involved in those conversations is a nice shift that makes doctors more human and relatable, and hopefully makes the public more forgiving, that we’re going to make mistakes and nobody’s perfect,” Freedman said. But he added that physicians should be held accountable when a mistake or two becomes a pattern.
Misinformation is professional misconduct
Sufficient accountability is especially absent, these doctors said, for a subset of professional misconduct: spreading misinformation.
While more “conventional” bad behaviors include fraud, dishonesty, abuse of underlings, and incompetence, bad behavior should also include “selling quackery and antivaccine misinformation, the way some doctors did with various nostrums for COVID-19,” said Dr. Gorski, who frequently blogs about doctors’ spreading misinformation.
Taylor Nichols, MD, an emergency medicine physician based in Sacramento, cites the desire for attention and clout as motivations. “Saying things that are wildly, provably false is professional misconduct,” Nichols said. He distinguished such statements from scientific, academic, or clinical disagreement that is necessary within medicine.
Yet there’s been a “long tradition of looking the other way or letting people with fancy titles get away with saying nonsense just because they’re respected,” Jonathan Howard, MD, an associate professor of psychiatry and neurology at New York University said in an interview.
“We have a duty to be trusted members of the community,” Dr. Howard said. “People listen when we say things, and we have an obligation to try to be accurate and humble and as honest as possible and admit mistakes when we inevitably make them.”
That extends to social media, which Dr. Nichols said has magnified the problem of promoting quackery and misinformation. He thinks medical boards and professional credentialing bodies should pay attention to what’s happening in the public conversation and understand that our professional responsibility extends beyond the walls of the hospital or clinic. Physicians must represent themselves professionally and uphold the standards that the profession expects.
On the one hand, Medscape respondents agreed: 70% said one doctor’s misbehavior taints the whole profession. Yet, at the same time, 58% of respondents believed physicians should be able to “keep their private lives private” in 2022. But that’s not the reality of the profession when the lines between private life and behavior away from work get blurred, Dr. Samenow said.
“The way a physician behaves in public represents you,” he said. “What happens in Vegas doesn’t always stay in Vegas.”
A version of this article first appeared on Medscape.com.
Breakthrough COVID studies lend support to use of new boosters in immunosuppressed patients
People with immune-mediated inflammatory diseases who are taking immunosuppressants don’t mount as strong of an immune defense against the Omicron variant as they did against the original SARS-CoV-2 wild-type virus, according to two studies published in Annals of the Rheumatic Diseases. One of the studies further showed that vaccinated individuals taking immunosuppressants have poorer cross-neutralizing responses to Omicron than do healthy vaccinated individuals, even after three doses of the COVID-19 mRNA vaccines.
“We carefully suggest that if Omicron-specific vaccination can be administered, it may be an effective way to reduce the risk of breakthrough infections in patients with autoimmune rheumatic disease,” Sang Tae Choi, MD, PhD, of the University College of Medicine, Seoul, Korea, and one of the authors of the study on cross-neutralizing protection, told this news organization. “However, further research is needed on Omicron-specific vaccine effectiveness in patients with immune dysfunctions. We believe that these study results can be of great benefit in determining the strategy of vaccination in the future.”
The earlier study, published in July, examined the ability of COVID-19 vaccines to induce cross-reactive antibody responses against Omicron infections in patients with autoimmune rheumatic diseases (ARDs). The observational study involved 149 patients with ARDs and 94 health care workers as controls, all of whom provided blood samples a median 15 weeks after their second COVID vaccine dose or a median 8 weeks after their third dose. A little more than two-thirds of the patients (68.5%) had received a third mRNA vaccine dose. None of the participants previously had COVID-19.
The researchers compared the rate of breakthrough infections with the Omicron variant to the neutralizing responses in patients’ blood, specifically the cross-neutralizing antibody responses because the original mRNA vaccines targeted a different variant than Omicron. Breakthrough infections were assessed by survey questions.
“Our findings suggested that neither primary series vaccinations nor booster doses are sufficient to induce Omicron-neutralizing responses above the threshold in patients with ARDs, although responses were noticeably increased following the third dose of an mRNA vaccine,” write Woo-Joong Kim, of the Chung-Ang University College of Medicine, Seoul, Korea, and his colleagues. “This impairment of cross-neutralization responses across most of our patients contrasts starkly with a potent elicitation of the Omicron-neutralizing responses after the third vaccination in healthy recipients.”
The average neutralizing responses against the original SARS-CoV-2 strain were similar in both groups: 76% in patients with ARDs and 72% in health care workers after the second dose. The mean response after a third dose was 97% in health care workers and 88% in patients.
The average cross-neutralizing response against the Omicron variant was far lower, particularly in those with rheumatic disease: only 11.5%, which rose to 27% after the third dose. Only 39% of the patient sera showed neutralization of Omicron, even after the third dose. Meanwhile, the mean cross-neutralizing response in health care workers was 18% after the second dose and 50% after the third.
When the researchers compared seropositivity rates against the original virus to neutralizing responses against Omicron, the association between these was stronger in health care workers than in those with ARDs. In fact, among patients with ARDs who seroconverted, only 41% showed any response against Omicron. Among all the patients, most of those who didn’t respond to Omicron (93.5%) had initially seroconverted.
The researchers also looked at the ability to neutralize Omicron on the basis of disease in those who received three doses of the vaccine. About half of those with lupus (52%) showed any neutralization against Omicron, compared with 25% of those with rheumatoid arthritis, 37.5% of those with ankylosing spondylitis, 33% of those with Behçet snydrome, and all of those with adult-onset Still’s disease.
The rate of breakthrough infections was lower in patients (19%) than in health care workers (33%). A similar pattern was seen in the more recent study published Sept. 5. Researchers used data from a prospective cohort study in the Netherlands to examine incidence and severity of Omicron breakthrough infections in patients with immune-mediated inflammatory diseases. The researchers compared infection rates and severity among 1,593 vaccinated patients with inflammatory disease who were taking immunosuppressants and 579 vaccinated controls (418 patients with inflammatory disease not on immunosuppressants and 161 healthy controls).
One in five patients with inflammatory disease (21%) were taking immunosuppressants that substantially impair antibodies, such as anti-CD20 therapy, S1P modulators, or mycophenolate mofetil combination therapy, and 48% of these patients seroconverted after primary vaccination, compared with 96% of patients taking other immunosuppressants and 98% of controls.
Breakthrough infection rates were similar between the control group (31%) and those taking immunosuppressants (30%). Only three participants had severe disease requiring hospitalization: one control and two patients taking immunosuppressants.
“In both studies, the controls had similar or higher rates of breakthrough infections, compared with the immunosuppressed,” noted Alfred Kim, MD, an assistant professor of medicine at Washington University, St Louis, but he added, “one has to consider differences in mitigation strategies, such as masking, that may explain these findings.” That is, patients taking immunosuppressants may be taking fewer risks in the community or have fewer potential exposures, especially in the Korean study, wherein the controls were health care workers.
A greater disparity in infections occurred when considering seroconversion rates. Breakthrough incidence was 38% among those taking immunosuppressants who did not seroconvert, compared with 29% among those who did. A similar trend was seen in breakthrough incidence between those taking strongly antibody-impairing immunosuppressants (36% breakthrough rate) and those taking other immunosuppressants (28%).
Among those taking immunosuppressants who seroconverted, a primary series of vaccination reduced the risk of a breakthrough infection by 29%. Protection became more robust with a booster or prior infection, both of which reduced breakthrough infection risk by 39% in those taking immunosuppressants who seroconverted.
“We demonstrate in patients with immune-mediated inflammatory diseases on immunosuppressants that additional vaccinations are associated with decreased risk of SARS-CoV-2 Omicron breakthrough infections,” wrote Eileen W. Stalman, MD, PhD, of Amsterdam UMC in the Netherlands, and her colleagues.
Though neither study broke down immune response or breakthrough infection based on individual medications, Kim said that previous research allows one to extrapolate “that prior culprits of poor vaccine responses [such as B-cell depleting drugs, mycophenolate, and TNF [tumor necrosis factor] inhibitors will continue to bear the greatest burden in breakthrough infection, including Omicron.”
Overall, he found the data from both studies relatively consistent with one another.
“Those on immunosuppression, particularly mechanisms that have been established as risk factors for poor vaccine responses, are at risk of breakthrough infection during the era of Omicron,” Dr. Kim said.
The earlier study from Korea also found that “the median time between the third-dose vaccination and the date of confirmed breakthrough infection in patients with ARDs was significantly shorter, compared with that in health care workers” at just 93 days in patients versus 122 days in health care workers. They postulated that this population’s limited neutralization of Omicron explained this short-lived protection.
Most of the patients with breakthrough infections (74%) in that study showed no neutralization against Omicron, including the only two hospitalized patients, both of whom had strong responses against the original SARS-CoV-2 strain. The significant decline over time of neutralization against Omicron suggested “the potential for a substantial loss of the protection from breakthrough infection,” the authors write.
“The third dose of an mRNA vaccine could improve the cross-neutralization of the SARS-CoV-2 Omicron variant in patients with autoimmune rheumatic disease [although] more than half of the patients failed to generate Omicron-neutralizing antibodies,” Tae Choi said in an interview. “Our study sheds light on the relative deficiency of the Omicron-specific neutralizing responses in patients with autoimmune rheumatic disease and their anticipated vulnerability to breakthrough infection.”
The message for clinicians, Dr. Kim said, is to “continue to urge our patients to maintain additional and boosting doses per guidance, use pre-exposure prophylaxis such as Evusheld, and continue other mitigation strategies as they have done.”
The Dutch study was funded by The Netherlands Organization for Health Research and Development; the Korean study used no external funding.
The authors of the Korean study had no disclosures. The Dutch study’s authors reported a wide range of disclosures involving more than a dozen pharmaceutical companies but not including Pfizer or Moderna. Dr. Kim’s industry disclosures include Alexion, ANI, AstraZeneca, Aurinia, Exagen, Foghorn Therapeutics, GlaxoSmithKline, Kypha, and Pfizer.
A version of this article first appeared on Medscape.com.
People with immune-mediated inflammatory diseases who are taking immunosuppressants don’t mount as strong of an immune defense against the Omicron variant as they did against the original SARS-CoV-2 wild-type virus, according to two studies published in Annals of the Rheumatic Diseases. One of the studies further showed that vaccinated individuals taking immunosuppressants have poorer cross-neutralizing responses to Omicron than do healthy vaccinated individuals, even after three doses of the COVID-19 mRNA vaccines.
“We carefully suggest that if Omicron-specific vaccination can be administered, it may be an effective way to reduce the risk of breakthrough infections in patients with autoimmune rheumatic disease,” Sang Tae Choi, MD, PhD, of the University College of Medicine, Seoul, Korea, and one of the authors of the study on cross-neutralizing protection, told this news organization. “However, further research is needed on Omicron-specific vaccine effectiveness in patients with immune dysfunctions. We believe that these study results can be of great benefit in determining the strategy of vaccination in the future.”
The earlier study, published in July, examined the ability of COVID-19 vaccines to induce cross-reactive antibody responses against Omicron infections in patients with autoimmune rheumatic diseases (ARDs). The observational study involved 149 patients with ARDs and 94 health care workers as controls, all of whom provided blood samples a median 15 weeks after their second COVID vaccine dose or a median 8 weeks after their third dose. A little more than two-thirds of the patients (68.5%) had received a third mRNA vaccine dose. None of the participants previously had COVID-19.
The researchers compared the rate of breakthrough infections with the Omicron variant to the neutralizing responses in patients’ blood, specifically the cross-neutralizing antibody responses because the original mRNA vaccines targeted a different variant than Omicron. Breakthrough infections were assessed by survey questions.
“Our findings suggested that neither primary series vaccinations nor booster doses are sufficient to induce Omicron-neutralizing responses above the threshold in patients with ARDs, although responses were noticeably increased following the third dose of an mRNA vaccine,” write Woo-Joong Kim, of the Chung-Ang University College of Medicine, Seoul, Korea, and his colleagues. “This impairment of cross-neutralization responses across most of our patients contrasts starkly with a potent elicitation of the Omicron-neutralizing responses after the third vaccination in healthy recipients.”
The average neutralizing responses against the original SARS-CoV-2 strain were similar in both groups: 76% in patients with ARDs and 72% in health care workers after the second dose. The mean response after a third dose was 97% in health care workers and 88% in patients.
The average cross-neutralizing response against the Omicron variant was far lower, particularly in those with rheumatic disease: only 11.5%, which rose to 27% after the third dose. Only 39% of the patient sera showed neutralization of Omicron, even after the third dose. Meanwhile, the mean cross-neutralizing response in health care workers was 18% after the second dose and 50% after the third.
When the researchers compared seropositivity rates against the original virus to neutralizing responses against Omicron, the association between these was stronger in health care workers than in those with ARDs. In fact, among patients with ARDs who seroconverted, only 41% showed any response against Omicron. Among all the patients, most of those who didn’t respond to Omicron (93.5%) had initially seroconverted.
The researchers also looked at the ability to neutralize Omicron on the basis of disease in those who received three doses of the vaccine. About half of those with lupus (52%) showed any neutralization against Omicron, compared with 25% of those with rheumatoid arthritis, 37.5% of those with ankylosing spondylitis, 33% of those with Behçet snydrome, and all of those with adult-onset Still’s disease.
The rate of breakthrough infections was lower in patients (19%) than in health care workers (33%). A similar pattern was seen in the more recent study published Sept. 5. Researchers used data from a prospective cohort study in the Netherlands to examine incidence and severity of Omicron breakthrough infections in patients with immune-mediated inflammatory diseases. The researchers compared infection rates and severity among 1,593 vaccinated patients with inflammatory disease who were taking immunosuppressants and 579 vaccinated controls (418 patients with inflammatory disease not on immunosuppressants and 161 healthy controls).
One in five patients with inflammatory disease (21%) were taking immunosuppressants that substantially impair antibodies, such as anti-CD20 therapy, S1P modulators, or mycophenolate mofetil combination therapy, and 48% of these patients seroconverted after primary vaccination, compared with 96% of patients taking other immunosuppressants and 98% of controls.
Breakthrough infection rates were similar between the control group (31%) and those taking immunosuppressants (30%). Only three participants had severe disease requiring hospitalization: one control and two patients taking immunosuppressants.
“In both studies, the controls had similar or higher rates of breakthrough infections, compared with the immunosuppressed,” noted Alfred Kim, MD, an assistant professor of medicine at Washington University, St Louis, but he added, “one has to consider differences in mitigation strategies, such as masking, that may explain these findings.” That is, patients taking immunosuppressants may be taking fewer risks in the community or have fewer potential exposures, especially in the Korean study, wherein the controls were health care workers.
A greater disparity in infections occurred when considering seroconversion rates. Breakthrough incidence was 38% among those taking immunosuppressants who did not seroconvert, compared with 29% among those who did. A similar trend was seen in breakthrough incidence between those taking strongly antibody-impairing immunosuppressants (36% breakthrough rate) and those taking other immunosuppressants (28%).
Among those taking immunosuppressants who seroconverted, a primary series of vaccination reduced the risk of a breakthrough infection by 29%. Protection became more robust with a booster or prior infection, both of which reduced breakthrough infection risk by 39% in those taking immunosuppressants who seroconverted.
“We demonstrate in patients with immune-mediated inflammatory diseases on immunosuppressants that additional vaccinations are associated with decreased risk of SARS-CoV-2 Omicron breakthrough infections,” wrote Eileen W. Stalman, MD, PhD, of Amsterdam UMC in the Netherlands, and her colleagues.
Though neither study broke down immune response or breakthrough infection based on individual medications, Kim said that previous research allows one to extrapolate “that prior culprits of poor vaccine responses [such as B-cell depleting drugs, mycophenolate, and TNF [tumor necrosis factor] inhibitors will continue to bear the greatest burden in breakthrough infection, including Omicron.”
Overall, he found the data from both studies relatively consistent with one another.
“Those on immunosuppression, particularly mechanisms that have been established as risk factors for poor vaccine responses, are at risk of breakthrough infection during the era of Omicron,” Dr. Kim said.
The earlier study from Korea also found that “the median time between the third-dose vaccination and the date of confirmed breakthrough infection in patients with ARDs was significantly shorter, compared with that in health care workers” at just 93 days in patients versus 122 days in health care workers. They postulated that this population’s limited neutralization of Omicron explained this short-lived protection.
Most of the patients with breakthrough infections (74%) in that study showed no neutralization against Omicron, including the only two hospitalized patients, both of whom had strong responses against the original SARS-CoV-2 strain. The significant decline over time of neutralization against Omicron suggested “the potential for a substantial loss of the protection from breakthrough infection,” the authors write.
“The third dose of an mRNA vaccine could improve the cross-neutralization of the SARS-CoV-2 Omicron variant in patients with autoimmune rheumatic disease [although] more than half of the patients failed to generate Omicron-neutralizing antibodies,” Tae Choi said in an interview. “Our study sheds light on the relative deficiency of the Omicron-specific neutralizing responses in patients with autoimmune rheumatic disease and their anticipated vulnerability to breakthrough infection.”
The message for clinicians, Dr. Kim said, is to “continue to urge our patients to maintain additional and boosting doses per guidance, use pre-exposure prophylaxis such as Evusheld, and continue other mitigation strategies as they have done.”
The Dutch study was funded by The Netherlands Organization for Health Research and Development; the Korean study used no external funding.
The authors of the Korean study had no disclosures. The Dutch study’s authors reported a wide range of disclosures involving more than a dozen pharmaceutical companies but not including Pfizer or Moderna. Dr. Kim’s industry disclosures include Alexion, ANI, AstraZeneca, Aurinia, Exagen, Foghorn Therapeutics, GlaxoSmithKline, Kypha, and Pfizer.
A version of this article first appeared on Medscape.com.
People with immune-mediated inflammatory diseases who are taking immunosuppressants don’t mount as strong of an immune defense against the Omicron variant as they did against the original SARS-CoV-2 wild-type virus, according to two studies published in Annals of the Rheumatic Diseases. One of the studies further showed that vaccinated individuals taking immunosuppressants have poorer cross-neutralizing responses to Omicron than do healthy vaccinated individuals, even after three doses of the COVID-19 mRNA vaccines.
“We carefully suggest that if Omicron-specific vaccination can be administered, it may be an effective way to reduce the risk of breakthrough infections in patients with autoimmune rheumatic disease,” Sang Tae Choi, MD, PhD, of the University College of Medicine, Seoul, Korea, and one of the authors of the study on cross-neutralizing protection, told this news organization. “However, further research is needed on Omicron-specific vaccine effectiveness in patients with immune dysfunctions. We believe that these study results can be of great benefit in determining the strategy of vaccination in the future.”
The earlier study, published in July, examined the ability of COVID-19 vaccines to induce cross-reactive antibody responses against Omicron infections in patients with autoimmune rheumatic diseases (ARDs). The observational study involved 149 patients with ARDs and 94 health care workers as controls, all of whom provided blood samples a median 15 weeks after their second COVID vaccine dose or a median 8 weeks after their third dose. A little more than two-thirds of the patients (68.5%) had received a third mRNA vaccine dose. None of the participants previously had COVID-19.
The researchers compared the rate of breakthrough infections with the Omicron variant to the neutralizing responses in patients’ blood, specifically the cross-neutralizing antibody responses because the original mRNA vaccines targeted a different variant than Omicron. Breakthrough infections were assessed by survey questions.
“Our findings suggested that neither primary series vaccinations nor booster doses are sufficient to induce Omicron-neutralizing responses above the threshold in patients with ARDs, although responses were noticeably increased following the third dose of an mRNA vaccine,” write Woo-Joong Kim, of the Chung-Ang University College of Medicine, Seoul, Korea, and his colleagues. “This impairment of cross-neutralization responses across most of our patients contrasts starkly with a potent elicitation of the Omicron-neutralizing responses after the third vaccination in healthy recipients.”
The average neutralizing responses against the original SARS-CoV-2 strain were similar in both groups: 76% in patients with ARDs and 72% in health care workers after the second dose. The mean response after a third dose was 97% in health care workers and 88% in patients.
The average cross-neutralizing response against the Omicron variant was far lower, particularly in those with rheumatic disease: only 11.5%, which rose to 27% after the third dose. Only 39% of the patient sera showed neutralization of Omicron, even after the third dose. Meanwhile, the mean cross-neutralizing response in health care workers was 18% after the second dose and 50% after the third.
When the researchers compared seropositivity rates against the original virus to neutralizing responses against Omicron, the association between these was stronger in health care workers than in those with ARDs. In fact, among patients with ARDs who seroconverted, only 41% showed any response against Omicron. Among all the patients, most of those who didn’t respond to Omicron (93.5%) had initially seroconverted.
The researchers also looked at the ability to neutralize Omicron on the basis of disease in those who received three doses of the vaccine. About half of those with lupus (52%) showed any neutralization against Omicron, compared with 25% of those with rheumatoid arthritis, 37.5% of those with ankylosing spondylitis, 33% of those with Behçet snydrome, and all of those with adult-onset Still’s disease.
The rate of breakthrough infections was lower in patients (19%) than in health care workers (33%). A similar pattern was seen in the more recent study published Sept. 5. Researchers used data from a prospective cohort study in the Netherlands to examine incidence and severity of Omicron breakthrough infections in patients with immune-mediated inflammatory diseases. The researchers compared infection rates and severity among 1,593 vaccinated patients with inflammatory disease who were taking immunosuppressants and 579 vaccinated controls (418 patients with inflammatory disease not on immunosuppressants and 161 healthy controls).
One in five patients with inflammatory disease (21%) were taking immunosuppressants that substantially impair antibodies, such as anti-CD20 therapy, S1P modulators, or mycophenolate mofetil combination therapy, and 48% of these patients seroconverted after primary vaccination, compared with 96% of patients taking other immunosuppressants and 98% of controls.
Breakthrough infection rates were similar between the control group (31%) and those taking immunosuppressants (30%). Only three participants had severe disease requiring hospitalization: one control and two patients taking immunosuppressants.
“In both studies, the controls had similar or higher rates of breakthrough infections, compared with the immunosuppressed,” noted Alfred Kim, MD, an assistant professor of medicine at Washington University, St Louis, but he added, “one has to consider differences in mitigation strategies, such as masking, that may explain these findings.” That is, patients taking immunosuppressants may be taking fewer risks in the community or have fewer potential exposures, especially in the Korean study, wherein the controls were health care workers.
A greater disparity in infections occurred when considering seroconversion rates. Breakthrough incidence was 38% among those taking immunosuppressants who did not seroconvert, compared with 29% among those who did. A similar trend was seen in breakthrough incidence between those taking strongly antibody-impairing immunosuppressants (36% breakthrough rate) and those taking other immunosuppressants (28%).
Among those taking immunosuppressants who seroconverted, a primary series of vaccination reduced the risk of a breakthrough infection by 29%. Protection became more robust with a booster or prior infection, both of which reduced breakthrough infection risk by 39% in those taking immunosuppressants who seroconverted.
“We demonstrate in patients with immune-mediated inflammatory diseases on immunosuppressants that additional vaccinations are associated with decreased risk of SARS-CoV-2 Omicron breakthrough infections,” wrote Eileen W. Stalman, MD, PhD, of Amsterdam UMC in the Netherlands, and her colleagues.
Though neither study broke down immune response or breakthrough infection based on individual medications, Kim said that previous research allows one to extrapolate “that prior culprits of poor vaccine responses [such as B-cell depleting drugs, mycophenolate, and TNF [tumor necrosis factor] inhibitors will continue to bear the greatest burden in breakthrough infection, including Omicron.”
Overall, he found the data from both studies relatively consistent with one another.
“Those on immunosuppression, particularly mechanisms that have been established as risk factors for poor vaccine responses, are at risk of breakthrough infection during the era of Omicron,” Dr. Kim said.
The earlier study from Korea also found that “the median time between the third-dose vaccination and the date of confirmed breakthrough infection in patients with ARDs was significantly shorter, compared with that in health care workers” at just 93 days in patients versus 122 days in health care workers. They postulated that this population’s limited neutralization of Omicron explained this short-lived protection.
Most of the patients with breakthrough infections (74%) in that study showed no neutralization against Omicron, including the only two hospitalized patients, both of whom had strong responses against the original SARS-CoV-2 strain. The significant decline over time of neutralization against Omicron suggested “the potential for a substantial loss of the protection from breakthrough infection,” the authors write.
“The third dose of an mRNA vaccine could improve the cross-neutralization of the SARS-CoV-2 Omicron variant in patients with autoimmune rheumatic disease [although] more than half of the patients failed to generate Omicron-neutralizing antibodies,” Tae Choi said in an interview. “Our study sheds light on the relative deficiency of the Omicron-specific neutralizing responses in patients with autoimmune rheumatic disease and their anticipated vulnerability to breakthrough infection.”
The message for clinicians, Dr. Kim said, is to “continue to urge our patients to maintain additional and boosting doses per guidance, use pre-exposure prophylaxis such as Evusheld, and continue other mitigation strategies as they have done.”
The Dutch study was funded by The Netherlands Organization for Health Research and Development; the Korean study used no external funding.
The authors of the Korean study had no disclosures. The Dutch study’s authors reported a wide range of disclosures involving more than a dozen pharmaceutical companies but not including Pfizer or Moderna. Dr. Kim’s industry disclosures include Alexion, ANI, AstraZeneca, Aurinia, Exagen, Foghorn Therapeutics, GlaxoSmithKline, Kypha, and Pfizer.
A version of this article first appeared on Medscape.com.
Air pollution linked to increased IBS incidence
Increased levels of air pollution were linked to a slight uptick in new diagnoses of irritable bowel syndrome (IBS) in California residents, according to an ecologic study published in Clinical Gastroenterology and Hepatology.
“These data provide support for the role of environmental pollutants, especially air pollutants, in the development of IBS,” Philip N. Okafor, MD, MPH, of Stanford (Calif.) University, and colleagues wrote. “In contrast, we found no significant relationships between the seven environmental exposures and the ZIP-code level incidence of functional dyspepsia, ulcerative colitis, Crohn’s disease, and eosinophilic esophagitis.”
John I. Allen MD, MBA, a retired clinical professor medicine at the University of Michigan, Ann Arbor, said the findings were somewhat surprising, but he was impressed with the “fascinating and well-constructed” study.
“The differentiation between GI disorders that are linked to environmental pollutants [such as IBS] and those that are not [such as inflammatory bowel disease and eosinophilic esophagitis] is quite interesting and lends further credibility to the conclusions,” Dr. Allen said in an interview. “While definitive causal conclusions cannot rest on retrospective, population-level, studies alone, this extraordinarily detailed analysis should prompt further studies investigating root causes for these correlations,” such as gut epithelial changes secondary to ingested pollutants, for example.
The researchers noted that an “epidemiological shift in gastrointestinal diseases is underway,” with increasing incidence of inflammatory bowel disease (IBD), eosinophilic esophagitis (EoE), and disorders related to gut-brain interaction.
“While the underlying causes of this shift remain unclear, the association with industrialization suggests that environmental triggers may play a role in disease pathogenesis,” the authors wrote. Data to support that possibility, however, are lacking, Dr. Okafor said in an interview.
One potential mechanism to explain such an association could be local or systemic inflammation resulting from pollution exposure and leading to tissue injury. Others could include alterations in the gut microbiome or direct damage to the mucosal epithelial barrier from pollutants, which then results in epithelial cell death and subsequently increased intestinal permeability.
To explore whether any such associations exist, the researchers analyzed the incidence of IBS, functional dyspepsia, ulcerative colitis, Crohn’s disease, and eosinophilic esophagitis in different California ZIP codes with regard to each area’s levels of seven different pollutant markers. They used claims data for patients with Optum insurance to identify new diagnoses by ZIP code for nearly 2.9 million adult patients between 2009 and 2014 (ICD-9 era) and nearly 2.5 million patients between 2016 and 2019 (ICD-10 era). Preexisting diagnoses were excluded. The analysis included 1,365 different ZIP codes.
The measures of pollutants they assessed included the following: ozone, particulate matter less than 2.5 mcm (PM2.5), diesel emissions, drinking water contaminants, pesticides, toxic releases from industrial facilities, and traffic density. They used shoulder dislocations as a negative control in comparing incidence, and they adjusted the analysis to account for socioeconomic markers, patient-level sampling estimates, and county-level fixed effects.
Socioeconomic markers included not only income and race/ethnicity but also health insurance status, educational level, proportion of owner-occupied homes, median house prices, and the proportion of households receiving food stamps or meeting criteria for food insecurity. Given the number of potential confounders, the authors also made statistical adjustment (Bonferroni correction) to account for many multiple comparisons and reduce the likelihood of inflated statistical significance for any one finding.
The researchers found that the incidence of IBS per ZIP code was associated with the levels of PM2.5 and industrial airborne toxic releases during both time periods. An increase of 1 mcg/m3 of PM2.5 or additional 1% in toxic releases correlated with an additional 0.02 cases of IBS per 100 person-years (adjusted incidence rate ratios approximately 1.03 for IBS associated with both pollutants during both time periods).
”These associations were maintained across extensive adjustment for residual confounding and sensitivity analyses,” the authors added.
That increase in the total incidence of IBS in this study is very minor, but it’s not known how high environmental toxin levels may become in the future, Rishi D. Naik, MD, MSCI, assistant professor of medicine at Vanderbilt University Medical Center’s Esophageal Center in Nashville, Tenn., said in an interview.
“Though the increase on an absolute number currently is trivial, the percent increase if toxin releases dramatically increased can have an impact on our patients,” Dr. Naik said. “Public health policies should be in place to monitor these changes and future studies should be done prospectively to understand if this relationship is linear or has upper limits for absolute increases of incidence of IBS.”
Like the authors, however, Dr. Naik cautioned that these findings do not show causation and require further investigation. At least one potential confounder not considered in the study, Dr. Naik said, is that an increase in pharmacological therapy for IBS – which requires proper coding for insurance approval – increased during the time period as well.
Unlike EoE and IBD, IBS lacks objective pathological biomarkers for diagnosis that allow verification that “these patients truly had the disease versus were labeled with the diagnosis based on symptoms and need to obtain therapy,” Dr. Naik said. “Adjusting for prescription use and separating based on IBS-diarrhea and IBS-constipation would also help with the etiologies.”
Although the researchers also identified an association between IBS incidence and both traffic density and drinking water contaminants, these did not reach statistical significance after adjustment for multiple comparisons. Similarly, diesel particulate matter emissions were associated with functional dyspepsia and IBS until the statistical correction for multiple comparisons. None of the other conditions’ incidence was associated with any pollutant measured included in the study.
“It is important to highlight that our findings are not proof that environmental pollution causes irritable bowel syndrome but provide evidence to support further research on this topic,” Dr. Okafor said. “Our results are hypothesis generating. It would be helpful to better collect environmental hazards at a population level in a more systematic, reproducible manner so better ecological studies can be performed in the future to close knowledge gaps and improve our understanding of these diseases.”
Dr. Okafor said it would be valuable to explore potential associations between GI diseases and environmental pollutants in other states, but it would depend on how thorough data collection of pollutants is in other states. “Our study is the first step to exploring these interactions,” he noted.
“Though interesting data, the lack of patient-level data, dose response, treatment with an intervention, and the use of claims data prevent generalizability to larger populations both from a geographic perspective and also from ones based on gender, ethnicity, or socioeconomic factors,” Dr. Naik said. “Prospective studies showing incidence changes and interventions based on pollution control would help support their findings.”
Future studies could also further break down IBS incidence into IBS-diarrhea versus IBS-constipation and consider antibiotic exposure, treatment for symptoms, and symptom resolution, Dr. Naik said. “To support their association, patient-level trafficking of those who move to low and high rates of PM2.5 would help determine if individual symptoms improve with the sole intervention of geographic location,” he added.
Though it would be premature for the study to prompt any clinical changes in practice, Dr. Allen pointed out that the findings should raise clinicians’ awareness about the value of considering patients’ living areas and pollution exposure when evaluating GI symptoms.
“These data would lend support to the inclusive approach to an IBS diagnosis as opposed to a ‘rule-out’ diagnosis,” Dr. Allen said. “Additionally, we should investigate possible behavioral changes for patients exposed to environmental pollutants.”
He emphasized the importance of asking patients about their socioeconomic and environmental factors while helping them deal with GI disorders.
“These are complex and difficult histories to elicit during brief clinic encounters,” Dr. Allen said. “We need better ways to help patients understand their GI disorders in the context of their specific life stresses and avoid ordering multiple diagnostic tests when a different approach is needed to solve patients’ issues.”
The study’s biggest limitation is its ecologic design, which cannot link individual people’s exposures to their specific diagnosis. They also could not consider seasonal changes in pollutant levels or the possible interaction or cumulative effects of different pollutants. The authors also noted a number of other pollution exposures that they did not measure at all in this study, such as nitrogen dioxide, sulfur dioxide, heavy metals, or bacteria.
“Ecologic studies using claims data without a prespecified singular outcome, even when corrected for multiple comparisons, is at risk of confounding and bias,” Dr. Naik said. “This study will hopefully help with future environmental studies to understand the role of the environment and GI health.”
Dr. Okafor further cautioned that it’s likely premature to advocate for policy change right now based on these findings.
“We will need better temporal data to associate exposure to airborne pollutants and GI disease incidence and even severity,” Dr. Okafor said. “If it is possible to demonstrate this reliably, it may impact our ability to provide better care for our patients.”
As more research like this is conducted, however, it has the potential to improve how clinicians care for patients, Dr. Allen suggested.
“As we begin to understand the complex interactions of environment, social determinants of health, individual life stresses, and a person’s unique reaction to stress, we will be much better at helping patients live with GI symptoms and disorders,” Dr. Allen said. “We also can assign accountability for the externalities [costs] that environmental pollution causes.”
Dr. Allen, Dr. Naik, and the authors reported no conflicts of interest. The research was funded by the National Institutes of Health and Stanford University.
Increased levels of air pollution were linked to a slight uptick in new diagnoses of irritable bowel syndrome (IBS) in California residents, according to an ecologic study published in Clinical Gastroenterology and Hepatology.
“These data provide support for the role of environmental pollutants, especially air pollutants, in the development of IBS,” Philip N. Okafor, MD, MPH, of Stanford (Calif.) University, and colleagues wrote. “In contrast, we found no significant relationships between the seven environmental exposures and the ZIP-code level incidence of functional dyspepsia, ulcerative colitis, Crohn’s disease, and eosinophilic esophagitis.”
John I. Allen MD, MBA, a retired clinical professor medicine at the University of Michigan, Ann Arbor, said the findings were somewhat surprising, but he was impressed with the “fascinating and well-constructed” study.
“The differentiation between GI disorders that are linked to environmental pollutants [such as IBS] and those that are not [such as inflammatory bowel disease and eosinophilic esophagitis] is quite interesting and lends further credibility to the conclusions,” Dr. Allen said in an interview. “While definitive causal conclusions cannot rest on retrospective, population-level, studies alone, this extraordinarily detailed analysis should prompt further studies investigating root causes for these correlations,” such as gut epithelial changes secondary to ingested pollutants, for example.
The researchers noted that an “epidemiological shift in gastrointestinal diseases is underway,” with increasing incidence of inflammatory bowel disease (IBD), eosinophilic esophagitis (EoE), and disorders related to gut-brain interaction.
“While the underlying causes of this shift remain unclear, the association with industrialization suggests that environmental triggers may play a role in disease pathogenesis,” the authors wrote. Data to support that possibility, however, are lacking, Dr. Okafor said in an interview.
One potential mechanism to explain such an association could be local or systemic inflammation resulting from pollution exposure and leading to tissue injury. Others could include alterations in the gut microbiome or direct damage to the mucosal epithelial barrier from pollutants, which then results in epithelial cell death and subsequently increased intestinal permeability.
To explore whether any such associations exist, the researchers analyzed the incidence of IBS, functional dyspepsia, ulcerative colitis, Crohn’s disease, and eosinophilic esophagitis in different California ZIP codes with regard to each area’s levels of seven different pollutant markers. They used claims data for patients with Optum insurance to identify new diagnoses by ZIP code for nearly 2.9 million adult patients between 2009 and 2014 (ICD-9 era) and nearly 2.5 million patients between 2016 and 2019 (ICD-10 era). Preexisting diagnoses were excluded. The analysis included 1,365 different ZIP codes.
The measures of pollutants they assessed included the following: ozone, particulate matter less than 2.5 mcm (PM2.5), diesel emissions, drinking water contaminants, pesticides, toxic releases from industrial facilities, and traffic density. They used shoulder dislocations as a negative control in comparing incidence, and they adjusted the analysis to account for socioeconomic markers, patient-level sampling estimates, and county-level fixed effects.
Socioeconomic markers included not only income and race/ethnicity but also health insurance status, educational level, proportion of owner-occupied homes, median house prices, and the proportion of households receiving food stamps or meeting criteria for food insecurity. Given the number of potential confounders, the authors also made statistical adjustment (Bonferroni correction) to account for many multiple comparisons and reduce the likelihood of inflated statistical significance for any one finding.
The researchers found that the incidence of IBS per ZIP code was associated with the levels of PM2.5 and industrial airborne toxic releases during both time periods. An increase of 1 mcg/m3 of PM2.5 or additional 1% in toxic releases correlated with an additional 0.02 cases of IBS per 100 person-years (adjusted incidence rate ratios approximately 1.03 for IBS associated with both pollutants during both time periods).
”These associations were maintained across extensive adjustment for residual confounding and sensitivity analyses,” the authors added.
That increase in the total incidence of IBS in this study is very minor, but it’s not known how high environmental toxin levels may become in the future, Rishi D. Naik, MD, MSCI, assistant professor of medicine at Vanderbilt University Medical Center’s Esophageal Center in Nashville, Tenn., said in an interview.
“Though the increase on an absolute number currently is trivial, the percent increase if toxin releases dramatically increased can have an impact on our patients,” Dr. Naik said. “Public health policies should be in place to monitor these changes and future studies should be done prospectively to understand if this relationship is linear or has upper limits for absolute increases of incidence of IBS.”
Like the authors, however, Dr. Naik cautioned that these findings do not show causation and require further investigation. At least one potential confounder not considered in the study, Dr. Naik said, is that an increase in pharmacological therapy for IBS – which requires proper coding for insurance approval – increased during the time period as well.
Unlike EoE and IBD, IBS lacks objective pathological biomarkers for diagnosis that allow verification that “these patients truly had the disease versus were labeled with the diagnosis based on symptoms and need to obtain therapy,” Dr. Naik said. “Adjusting for prescription use and separating based on IBS-diarrhea and IBS-constipation would also help with the etiologies.”
Although the researchers also identified an association between IBS incidence and both traffic density and drinking water contaminants, these did not reach statistical significance after adjustment for multiple comparisons. Similarly, diesel particulate matter emissions were associated with functional dyspepsia and IBS until the statistical correction for multiple comparisons. None of the other conditions’ incidence was associated with any pollutant measured included in the study.
“It is important to highlight that our findings are not proof that environmental pollution causes irritable bowel syndrome but provide evidence to support further research on this topic,” Dr. Okafor said. “Our results are hypothesis generating. It would be helpful to better collect environmental hazards at a population level in a more systematic, reproducible manner so better ecological studies can be performed in the future to close knowledge gaps and improve our understanding of these diseases.”
Dr. Okafor said it would be valuable to explore potential associations between GI diseases and environmental pollutants in other states, but it would depend on how thorough data collection of pollutants is in other states. “Our study is the first step to exploring these interactions,” he noted.
“Though interesting data, the lack of patient-level data, dose response, treatment with an intervention, and the use of claims data prevent generalizability to larger populations both from a geographic perspective and also from ones based on gender, ethnicity, or socioeconomic factors,” Dr. Naik said. “Prospective studies showing incidence changes and interventions based on pollution control would help support their findings.”
Future studies could also further break down IBS incidence into IBS-diarrhea versus IBS-constipation and consider antibiotic exposure, treatment for symptoms, and symptom resolution, Dr. Naik said. “To support their association, patient-level trafficking of those who move to low and high rates of PM2.5 would help determine if individual symptoms improve with the sole intervention of geographic location,” he added.
Though it would be premature for the study to prompt any clinical changes in practice, Dr. Allen pointed out that the findings should raise clinicians’ awareness about the value of considering patients’ living areas and pollution exposure when evaluating GI symptoms.
“These data would lend support to the inclusive approach to an IBS diagnosis as opposed to a ‘rule-out’ diagnosis,” Dr. Allen said. “Additionally, we should investigate possible behavioral changes for patients exposed to environmental pollutants.”
He emphasized the importance of asking patients about their socioeconomic and environmental factors while helping them deal with GI disorders.
“These are complex and difficult histories to elicit during brief clinic encounters,” Dr. Allen said. “We need better ways to help patients understand their GI disorders in the context of their specific life stresses and avoid ordering multiple diagnostic tests when a different approach is needed to solve patients’ issues.”
The study’s biggest limitation is its ecologic design, which cannot link individual people’s exposures to their specific diagnosis. They also could not consider seasonal changes in pollutant levels or the possible interaction or cumulative effects of different pollutants. The authors also noted a number of other pollution exposures that they did not measure at all in this study, such as nitrogen dioxide, sulfur dioxide, heavy metals, or bacteria.
“Ecologic studies using claims data without a prespecified singular outcome, even when corrected for multiple comparisons, is at risk of confounding and bias,” Dr. Naik said. “This study will hopefully help with future environmental studies to understand the role of the environment and GI health.”
Dr. Okafor further cautioned that it’s likely premature to advocate for policy change right now based on these findings.
“We will need better temporal data to associate exposure to airborne pollutants and GI disease incidence and even severity,” Dr. Okafor said. “If it is possible to demonstrate this reliably, it may impact our ability to provide better care for our patients.”
As more research like this is conducted, however, it has the potential to improve how clinicians care for patients, Dr. Allen suggested.
“As we begin to understand the complex interactions of environment, social determinants of health, individual life stresses, and a person’s unique reaction to stress, we will be much better at helping patients live with GI symptoms and disorders,” Dr. Allen said. “We also can assign accountability for the externalities [costs] that environmental pollution causes.”
Dr. Allen, Dr. Naik, and the authors reported no conflicts of interest. The research was funded by the National Institutes of Health and Stanford University.
Increased levels of air pollution were linked to a slight uptick in new diagnoses of irritable bowel syndrome (IBS) in California residents, according to an ecologic study published in Clinical Gastroenterology and Hepatology.
“These data provide support for the role of environmental pollutants, especially air pollutants, in the development of IBS,” Philip N. Okafor, MD, MPH, of Stanford (Calif.) University, and colleagues wrote. “In contrast, we found no significant relationships between the seven environmental exposures and the ZIP-code level incidence of functional dyspepsia, ulcerative colitis, Crohn’s disease, and eosinophilic esophagitis.”
John I. Allen MD, MBA, a retired clinical professor medicine at the University of Michigan, Ann Arbor, said the findings were somewhat surprising, but he was impressed with the “fascinating and well-constructed” study.
“The differentiation between GI disorders that are linked to environmental pollutants [such as IBS] and those that are not [such as inflammatory bowel disease and eosinophilic esophagitis] is quite interesting and lends further credibility to the conclusions,” Dr. Allen said in an interview. “While definitive causal conclusions cannot rest on retrospective, population-level, studies alone, this extraordinarily detailed analysis should prompt further studies investigating root causes for these correlations,” such as gut epithelial changes secondary to ingested pollutants, for example.
The researchers noted that an “epidemiological shift in gastrointestinal diseases is underway,” with increasing incidence of inflammatory bowel disease (IBD), eosinophilic esophagitis (EoE), and disorders related to gut-brain interaction.
“While the underlying causes of this shift remain unclear, the association with industrialization suggests that environmental triggers may play a role in disease pathogenesis,” the authors wrote. Data to support that possibility, however, are lacking, Dr. Okafor said in an interview.
One potential mechanism to explain such an association could be local or systemic inflammation resulting from pollution exposure and leading to tissue injury. Others could include alterations in the gut microbiome or direct damage to the mucosal epithelial barrier from pollutants, which then results in epithelial cell death and subsequently increased intestinal permeability.
To explore whether any such associations exist, the researchers analyzed the incidence of IBS, functional dyspepsia, ulcerative colitis, Crohn’s disease, and eosinophilic esophagitis in different California ZIP codes with regard to each area’s levels of seven different pollutant markers. They used claims data for patients with Optum insurance to identify new diagnoses by ZIP code for nearly 2.9 million adult patients between 2009 and 2014 (ICD-9 era) and nearly 2.5 million patients between 2016 and 2019 (ICD-10 era). Preexisting diagnoses were excluded. The analysis included 1,365 different ZIP codes.
The measures of pollutants they assessed included the following: ozone, particulate matter less than 2.5 mcm (PM2.5), diesel emissions, drinking water contaminants, pesticides, toxic releases from industrial facilities, and traffic density. They used shoulder dislocations as a negative control in comparing incidence, and they adjusted the analysis to account for socioeconomic markers, patient-level sampling estimates, and county-level fixed effects.
Socioeconomic markers included not only income and race/ethnicity but also health insurance status, educational level, proportion of owner-occupied homes, median house prices, and the proportion of households receiving food stamps or meeting criteria for food insecurity. Given the number of potential confounders, the authors also made statistical adjustment (Bonferroni correction) to account for many multiple comparisons and reduce the likelihood of inflated statistical significance for any one finding.
The researchers found that the incidence of IBS per ZIP code was associated with the levels of PM2.5 and industrial airborne toxic releases during both time periods. An increase of 1 mcg/m3 of PM2.5 or additional 1% in toxic releases correlated with an additional 0.02 cases of IBS per 100 person-years (adjusted incidence rate ratios approximately 1.03 for IBS associated with both pollutants during both time periods).
”These associations were maintained across extensive adjustment for residual confounding and sensitivity analyses,” the authors added.
That increase in the total incidence of IBS in this study is very minor, but it’s not known how high environmental toxin levels may become in the future, Rishi D. Naik, MD, MSCI, assistant professor of medicine at Vanderbilt University Medical Center’s Esophageal Center in Nashville, Tenn., said in an interview.
“Though the increase on an absolute number currently is trivial, the percent increase if toxin releases dramatically increased can have an impact on our patients,” Dr. Naik said. “Public health policies should be in place to monitor these changes and future studies should be done prospectively to understand if this relationship is linear or has upper limits for absolute increases of incidence of IBS.”
Like the authors, however, Dr. Naik cautioned that these findings do not show causation and require further investigation. At least one potential confounder not considered in the study, Dr. Naik said, is that an increase in pharmacological therapy for IBS – which requires proper coding for insurance approval – increased during the time period as well.
Unlike EoE and IBD, IBS lacks objective pathological biomarkers for diagnosis that allow verification that “these patients truly had the disease versus were labeled with the diagnosis based on symptoms and need to obtain therapy,” Dr. Naik said. “Adjusting for prescription use and separating based on IBS-diarrhea and IBS-constipation would also help with the etiologies.”
Although the researchers also identified an association between IBS incidence and both traffic density and drinking water contaminants, these did not reach statistical significance after adjustment for multiple comparisons. Similarly, diesel particulate matter emissions were associated with functional dyspepsia and IBS until the statistical correction for multiple comparisons. None of the other conditions’ incidence was associated with any pollutant measured included in the study.
“It is important to highlight that our findings are not proof that environmental pollution causes irritable bowel syndrome but provide evidence to support further research on this topic,” Dr. Okafor said. “Our results are hypothesis generating. It would be helpful to better collect environmental hazards at a population level in a more systematic, reproducible manner so better ecological studies can be performed in the future to close knowledge gaps and improve our understanding of these diseases.”
Dr. Okafor said it would be valuable to explore potential associations between GI diseases and environmental pollutants in other states, but it would depend on how thorough data collection of pollutants is in other states. “Our study is the first step to exploring these interactions,” he noted.
“Though interesting data, the lack of patient-level data, dose response, treatment with an intervention, and the use of claims data prevent generalizability to larger populations both from a geographic perspective and also from ones based on gender, ethnicity, or socioeconomic factors,” Dr. Naik said. “Prospective studies showing incidence changes and interventions based on pollution control would help support their findings.”
Future studies could also further break down IBS incidence into IBS-diarrhea versus IBS-constipation and consider antibiotic exposure, treatment for symptoms, and symptom resolution, Dr. Naik said. “To support their association, patient-level trafficking of those who move to low and high rates of PM2.5 would help determine if individual symptoms improve with the sole intervention of geographic location,” he added.
Though it would be premature for the study to prompt any clinical changes in practice, Dr. Allen pointed out that the findings should raise clinicians’ awareness about the value of considering patients’ living areas and pollution exposure when evaluating GI symptoms.
“These data would lend support to the inclusive approach to an IBS diagnosis as opposed to a ‘rule-out’ diagnosis,” Dr. Allen said. “Additionally, we should investigate possible behavioral changes for patients exposed to environmental pollutants.”
He emphasized the importance of asking patients about their socioeconomic and environmental factors while helping them deal with GI disorders.
“These are complex and difficult histories to elicit during brief clinic encounters,” Dr. Allen said. “We need better ways to help patients understand their GI disorders in the context of their specific life stresses and avoid ordering multiple diagnostic tests when a different approach is needed to solve patients’ issues.”
The study’s biggest limitation is its ecologic design, which cannot link individual people’s exposures to their specific diagnosis. They also could not consider seasonal changes in pollutant levels or the possible interaction or cumulative effects of different pollutants. The authors also noted a number of other pollution exposures that they did not measure at all in this study, such as nitrogen dioxide, sulfur dioxide, heavy metals, or bacteria.
“Ecologic studies using claims data without a prespecified singular outcome, even when corrected for multiple comparisons, is at risk of confounding and bias,” Dr. Naik said. “This study will hopefully help with future environmental studies to understand the role of the environment and GI health.”
Dr. Okafor further cautioned that it’s likely premature to advocate for policy change right now based on these findings.
“We will need better temporal data to associate exposure to airborne pollutants and GI disease incidence and even severity,” Dr. Okafor said. “If it is possible to demonstrate this reliably, it may impact our ability to provide better care for our patients.”
As more research like this is conducted, however, it has the potential to improve how clinicians care for patients, Dr. Allen suggested.
“As we begin to understand the complex interactions of environment, social determinants of health, individual life stresses, and a person’s unique reaction to stress, we will be much better at helping patients live with GI symptoms and disorders,” Dr. Allen said. “We also can assign accountability for the externalities [costs] that environmental pollution causes.”
Dr. Allen, Dr. Naik, and the authors reported no conflicts of interest. The research was funded by the National Institutes of Health and Stanford University.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Pandemic-related CRC screening delays affect older adults most
A 1- or 2-year delay in recommended colorectal cancer (CRC) screenings had little effect on most people’s risk of illness or death from cancer, provided they eventually got screened, according to a modeling study of the impact of pandemic-related screening delays.
Most patients whose screening was delayed still benefited through a reduction in risk of cancer or death, but that benefit was lower than it would have been had they been screened on time, particularly for 65-year-olds who hadn’t ever been screened for CRC.
Extending the upper ages for undergoing screening or substituting fecal immunochemical testing (FIT) for colonoscopies blunted some of this negative effect for 50-year-olds who had never been screened and for previously screened 60-year-olds, but those mitigation strategies weren’t as helpful for never-screened 65-year-olds, report Soham Sinha, MS, of Weill Cornell Medicine, and his colleagues.
Because older patients lose the most benefit from delayed CRC screenings, Mr. Sinha and his colleagues suggest, they should be prioritized when access is reduced.
The findings were published online in Gastroenterology.
Modeling the impact of missed screenings
CRC screenings dropped by as much as 82% at the start of the pandemic, Mr. Sinha and his co-authors note, and screening rates haven’t yet recovered as new COVID variants arise.
The researchers therefore sought to evaluate the potential clinical impact of screenings that were missed because of the pandemic on three groups of people who were at average risk of CRC: people who were 50 years old and had never been screened, people who were 65 and had never been screened, and people who had been screened by age 50 but were due for a colonoscopy screening at age 60.
They modeled the incidence and mortality of colorectal cancer for a 1-year and a 2-year delay in screening, compared with on-time screening with a colonoscopy or an annual FIT through age 75, or colonoscopy surveillance through age 80.
Among never-screened 50-year-olds, waiting a year or two to start colonoscopy screening resulted in a 69% reduction in colorectal cancer incidence instead of the 70% reduction that would have occurred with on-time screening. Similarly, the reduction in risk of death from delayed screening was 75% instead of 76% with on-time screening.
A 1- or 2-year delay in starting FIT screening in this group led to a reduction in the benefit of lower risk by one percentage point: Patients had a 57% lower risk of cancer from a 1-year screening delay and a 56% reduction in risk from a 2-year delay, compared with a 58% reduction in risk without any delays. In terms of mortality, benefit fell by one absolute percentage point for each year of delay.
Restoring the benefits of screening
The most effective way to mitigate each of those lost percentage points from colonoscopy delays was to combine two rescue strategies: using FIT screening instead of colonoscopy when colonoscopy access was reduced and extending the upper ages of colonoscopy screening to age 76-77 and colonoscopy surveillance to age 81-82.
Solely extending the ages for undergoing screening and surveillance was more effective than solely substituting FIT screening for colonoscopies. To offset the impact of an FIT delay, extending the upper age of the screening or surveillance period was effective.
The negative effect of delayed colonoscopy screenings was greater for never-screened 65-year-olds, whose reduction in risk of developing CRC fell to 53%-54%, rather than the 66% reduction in risk they would have had with on-time screening. The reduction in risk of mortality from CRC was 60% instead of 74% if screenings were delayed instead of occurring on time.
“Starting at age 65 afforded individuals two lifetime colonoscopies, as opposed to one at age 66 or later, given that colorectal screening ended at age 75,” the authors write. “Rescue strategies decreased but did not negate the impact of pandemic-related colorectal screening delays.”
For never-screened 65-year-olds who experienced delays in FIT, undergoing screening 1 year late equated to a 41% reduction in cancer risk, and undergoing screening 2 years late resulted in a 38% reduction, compared with a 44% reduction with on-time FIT screening. The reduction in mortality fell from 60% with on-time screening to 57% with a 1-year delay and 54% with a 2-year delay. Though extending the upper age limited reduced this negative effect, it did not eliminate it.
The researchers found that delaying screening by 1 or 2 years among 60-year-olds who had had a colonoscopy at age 50 only modestly reduced the benefit of reduced risk of CRC or death.
“Rescue strategies mitigated or negated impact from colorectal screening delays and included FIT-based screening when colonoscopy was unavailable, with or without extended screening through ages 75 or 76,” the authors report.
One limitation of the study was its lack of cost-effectiveness calculations, which made it impossible to evaluate the economic implications of either the delays in screening or the proposed mitigation strategies.
“Our work suggests that among the 20% of the U.S. population aged 50-75 who are unscreened for colorectal cancer, older adults would experience the most clinical benefit from colorectal cancer screening if resources were limited during the COVID-19 pandemic,” the authors write.
Younger people who hadn’t yet been screened and those who had been screened at least once with a colonoscopy would not experience as dramatic a reduction in benefit once they underwent screening, they conclude.
One author was supported by the National Cancer Institute. One author has advised Universal Dx and Lean Medical and has consulted for Clinical Genomics, Medtronic, Guardant Health, and Freenome. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
A 1- or 2-year delay in recommended colorectal cancer (CRC) screenings had little effect on most people’s risk of illness or death from cancer, provided they eventually got screened, according to a modeling study of the impact of pandemic-related screening delays.
Most patients whose screening was delayed still benefited through a reduction in risk of cancer or death, but that benefit was lower than it would have been had they been screened on time, particularly for 65-year-olds who hadn’t ever been screened for CRC.
Extending the upper ages for undergoing screening or substituting fecal immunochemical testing (FIT) for colonoscopies blunted some of this negative effect for 50-year-olds who had never been screened and for previously screened 60-year-olds, but those mitigation strategies weren’t as helpful for never-screened 65-year-olds, report Soham Sinha, MS, of Weill Cornell Medicine, and his colleagues.
Because older patients lose the most benefit from delayed CRC screenings, Mr. Sinha and his colleagues suggest, they should be prioritized when access is reduced.
The findings were published online in Gastroenterology.
Modeling the impact of missed screenings
CRC screenings dropped by as much as 82% at the start of the pandemic, Mr. Sinha and his co-authors note, and screening rates haven’t yet recovered as new COVID variants arise.
The researchers therefore sought to evaluate the potential clinical impact of screenings that were missed because of the pandemic on three groups of people who were at average risk of CRC: people who were 50 years old and had never been screened, people who were 65 and had never been screened, and people who had been screened by age 50 but were due for a colonoscopy screening at age 60.
They modeled the incidence and mortality of colorectal cancer for a 1-year and a 2-year delay in screening, compared with on-time screening with a colonoscopy or an annual FIT through age 75, or colonoscopy surveillance through age 80.
Among never-screened 50-year-olds, waiting a year or two to start colonoscopy screening resulted in a 69% reduction in colorectal cancer incidence instead of the 70% reduction that would have occurred with on-time screening. Similarly, the reduction in risk of death from delayed screening was 75% instead of 76% with on-time screening.
A 1- or 2-year delay in starting FIT screening in this group led to a reduction in the benefit of lower risk by one percentage point: Patients had a 57% lower risk of cancer from a 1-year screening delay and a 56% reduction in risk from a 2-year delay, compared with a 58% reduction in risk without any delays. In terms of mortality, benefit fell by one absolute percentage point for each year of delay.
Restoring the benefits of screening
The most effective way to mitigate each of those lost percentage points from colonoscopy delays was to combine two rescue strategies: using FIT screening instead of colonoscopy when colonoscopy access was reduced and extending the upper ages of colonoscopy screening to age 76-77 and colonoscopy surveillance to age 81-82.
Solely extending the ages for undergoing screening and surveillance was more effective than solely substituting FIT screening for colonoscopies. To offset the impact of an FIT delay, extending the upper age of the screening or surveillance period was effective.
The negative effect of delayed colonoscopy screenings was greater for never-screened 65-year-olds, whose reduction in risk of developing CRC fell to 53%-54%, rather than the 66% reduction in risk they would have had with on-time screening. The reduction in risk of mortality from CRC was 60% instead of 74% if screenings were delayed instead of occurring on time.
“Starting at age 65 afforded individuals two lifetime colonoscopies, as opposed to one at age 66 or later, given that colorectal screening ended at age 75,” the authors write. “Rescue strategies decreased but did not negate the impact of pandemic-related colorectal screening delays.”
For never-screened 65-year-olds who experienced delays in FIT, undergoing screening 1 year late equated to a 41% reduction in cancer risk, and undergoing screening 2 years late resulted in a 38% reduction, compared with a 44% reduction with on-time FIT screening. The reduction in mortality fell from 60% with on-time screening to 57% with a 1-year delay and 54% with a 2-year delay. Though extending the upper age limited reduced this negative effect, it did not eliminate it.
The researchers found that delaying screening by 1 or 2 years among 60-year-olds who had had a colonoscopy at age 50 only modestly reduced the benefit of reduced risk of CRC or death.
“Rescue strategies mitigated or negated impact from colorectal screening delays and included FIT-based screening when colonoscopy was unavailable, with or without extended screening through ages 75 or 76,” the authors report.
One limitation of the study was its lack of cost-effectiveness calculations, which made it impossible to evaluate the economic implications of either the delays in screening or the proposed mitigation strategies.
“Our work suggests that among the 20% of the U.S. population aged 50-75 who are unscreened for colorectal cancer, older adults would experience the most clinical benefit from colorectal cancer screening if resources were limited during the COVID-19 pandemic,” the authors write.
Younger people who hadn’t yet been screened and those who had been screened at least once with a colonoscopy would not experience as dramatic a reduction in benefit once they underwent screening, they conclude.
One author was supported by the National Cancer Institute. One author has advised Universal Dx and Lean Medical and has consulted for Clinical Genomics, Medtronic, Guardant Health, and Freenome. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
A 1- or 2-year delay in recommended colorectal cancer (CRC) screenings had little effect on most people’s risk of illness or death from cancer, provided they eventually got screened, according to a modeling study of the impact of pandemic-related screening delays.
Most patients whose screening was delayed still benefited through a reduction in risk of cancer or death, but that benefit was lower than it would have been had they been screened on time, particularly for 65-year-olds who hadn’t ever been screened for CRC.
Extending the upper ages for undergoing screening or substituting fecal immunochemical testing (FIT) for colonoscopies blunted some of this negative effect for 50-year-olds who had never been screened and for previously screened 60-year-olds, but those mitigation strategies weren’t as helpful for never-screened 65-year-olds, report Soham Sinha, MS, of Weill Cornell Medicine, and his colleagues.
Because older patients lose the most benefit from delayed CRC screenings, Mr. Sinha and his colleagues suggest, they should be prioritized when access is reduced.
The findings were published online in Gastroenterology.
Modeling the impact of missed screenings
CRC screenings dropped by as much as 82% at the start of the pandemic, Mr. Sinha and his co-authors note, and screening rates haven’t yet recovered as new COVID variants arise.
The researchers therefore sought to evaluate the potential clinical impact of screenings that were missed because of the pandemic on three groups of people who were at average risk of CRC: people who were 50 years old and had never been screened, people who were 65 and had never been screened, and people who had been screened by age 50 but were due for a colonoscopy screening at age 60.
They modeled the incidence and mortality of colorectal cancer for a 1-year and a 2-year delay in screening, compared with on-time screening with a colonoscopy or an annual FIT through age 75, or colonoscopy surveillance through age 80.
Among never-screened 50-year-olds, waiting a year or two to start colonoscopy screening resulted in a 69% reduction in colorectal cancer incidence instead of the 70% reduction that would have occurred with on-time screening. Similarly, the reduction in risk of death from delayed screening was 75% instead of 76% with on-time screening.
A 1- or 2-year delay in starting FIT screening in this group led to a reduction in the benefit of lower risk by one percentage point: Patients had a 57% lower risk of cancer from a 1-year screening delay and a 56% reduction in risk from a 2-year delay, compared with a 58% reduction in risk without any delays. In terms of mortality, benefit fell by one absolute percentage point for each year of delay.
Restoring the benefits of screening
The most effective way to mitigate each of those lost percentage points from colonoscopy delays was to combine two rescue strategies: using FIT screening instead of colonoscopy when colonoscopy access was reduced and extending the upper ages of colonoscopy screening to age 76-77 and colonoscopy surveillance to age 81-82.
Solely extending the ages for undergoing screening and surveillance was more effective than solely substituting FIT screening for colonoscopies. To offset the impact of an FIT delay, extending the upper age of the screening or surveillance period was effective.
The negative effect of delayed colonoscopy screenings was greater for never-screened 65-year-olds, whose reduction in risk of developing CRC fell to 53%-54%, rather than the 66% reduction in risk they would have had with on-time screening. The reduction in risk of mortality from CRC was 60% instead of 74% if screenings were delayed instead of occurring on time.
“Starting at age 65 afforded individuals two lifetime colonoscopies, as opposed to one at age 66 or later, given that colorectal screening ended at age 75,” the authors write. “Rescue strategies decreased but did not negate the impact of pandemic-related colorectal screening delays.”
For never-screened 65-year-olds who experienced delays in FIT, undergoing screening 1 year late equated to a 41% reduction in cancer risk, and undergoing screening 2 years late resulted in a 38% reduction, compared with a 44% reduction with on-time FIT screening. The reduction in mortality fell from 60% with on-time screening to 57% with a 1-year delay and 54% with a 2-year delay. Though extending the upper age limited reduced this negative effect, it did not eliminate it.
The researchers found that delaying screening by 1 or 2 years among 60-year-olds who had had a colonoscopy at age 50 only modestly reduced the benefit of reduced risk of CRC or death.
“Rescue strategies mitigated or negated impact from colorectal screening delays and included FIT-based screening when colonoscopy was unavailable, with or without extended screening through ages 75 or 76,” the authors report.
One limitation of the study was its lack of cost-effectiveness calculations, which made it impossible to evaluate the economic implications of either the delays in screening or the proposed mitigation strategies.
“Our work suggests that among the 20% of the U.S. population aged 50-75 who are unscreened for colorectal cancer, older adults would experience the most clinical benefit from colorectal cancer screening if resources were limited during the COVID-19 pandemic,” the authors write.
Younger people who hadn’t yet been screened and those who had been screened at least once with a colonoscopy would not experience as dramatic a reduction in benefit once they underwent screening, they conclude.
One author was supported by the National Cancer Institute. One author has advised Universal Dx and Lean Medical and has consulted for Clinical Genomics, Medtronic, Guardant Health, and Freenome. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
Even small changes can make endoscopy more sustainable: Study
Moving recycling bins and providing education to staff led to a reduction in the carbon footprint at a Portuguese hospital’s endoscopy unit, according to a study published in Gut.
“Sustainable endoscopy regarding waste handling was achievable and sustained over time, did not compromise productivity, and may be cost-effective for stakeholders,” wrote João A Cunha Neves, MD, MMSc, of Algarve University Hospital Centre in Portimão, Portugal, and his colleagues.
Although other work has shown that several of the strategies for reducing endoscopic waste are ‘easy wins,’ the authors noted that “lack of awareness by most endoscopy staff regarding the expenses and correct categorisation of endoscopic waste is the primary barrier to recycling in many endoscopy units.”
The four-stage prospective study took place at the Portimão endoscopy unit of Algarve University Hospital Centre in Portugal. It began with a 4-week audit that involved weighing regulated medical waste (“material fully contaminated with blood or body fluids or containing infectious agents”) and landfill waste (nonrecyclable material that isn’t fully contaminated). The researchers excluded from the analysis all waste from sharps containers, pre- and postprocedure activities, and endoscope reprocessing.
The second stage was one week of medical, nursing, and auxiliary team education about handling waste, in part based on observations collected during the first stage. Each endoscopy generates an estimated 1.5 kg of plastic waste, but recycling bins often are not available for the 0.3 kg of waste that’s recyclable. During the second stage, recycling bins were placed in endoscopy rooms while regulated medical waste and landfill bins were moved elsewhere.
The final two stages involved weighing both types of waste 1 month after the training and then 4 months after the training. For their calculations, the researchers assumed that 1 kg of landfill waste equated to 1 kg of carbon dioxide and 1 kg of regulated medical waste equated to 3 kg of carbon dioxide.
At the third stage, mean total waste fell by 12.9%, albeit not statistically significantly (P = .16), while the 41.4% regulated medical waste reduction was significant (P = .01). Landfill waste had increased 12.3% and both paper (0 to 1.2 kg) and plastic (0 to 2.1 kg) recycling waste increased. Mean endoscopy load had not significantly changed (46.2 vs. 44.5). Overall carbon dioxide was reduced by 31.6%, from 109.7 kg of carbon dioxide to 74.9 kg (P = .018), equating to an annual decrease of 1,665.6 kg. At four months postintervention, these effects remained.
“In both assessment periods, total waste produced by diagnostic standard endoscopic procedures was similar, but both regulated medical waste and overall carbon footprint were reduced,” the authors reported.
In a four-question assessment of the intervention with staff, “the entire team agreed that the study did not interfere with the daily work routine and was helpful in raising awareness about waste sorting within the unit,” the authors reported. The staff “also acknowledged that recycling waste allowed for more sustainable activity within the endoscopy unit, and that the achievements of the study were to be maintained in the future.”
How feasible is change?
The authors noted that health care accounts for 4.4% of the world’s carbon footprint and that endoscopy is the third largest generator of hospital medical waste, primarily because of single-use consumables. However, 71% of that health care carbon footprint comes from supply chain issues, particularly transportation, John I. Allen, MD, MBA, a retired clinical professor of medicine at the University Michigan, Ann Arbor, said in an interview. “Facility emissions add 17% and heating/cooling add 12%,” he said. “So, the actual footprint of endoscopy is quite small.”
Reducing single-use equipment and disposables by a third is a small overall impact considering the “labor-intensive education and monitoring system,” said Dr. Allen, who was not involved in the study. “That said, this paper and numerous others remind us of small steps that we can take – mostly to raise awareness about new technologies and more sustainable processes that are available or should be studied – to help transition us from the current [terrible] state to a more climate-friendly style of practice and life.”
One of the study’s limitations was the lack of a cost-benefit or impact analysis, according to Dr. Allen. Climate policies claiming to have local impact can be problematic when they “ignore both externalities and the actual wider impact on gas or temperature mitigation,” he added.
But he noted that “many health care systems are already implementing new ways of working with temperature- and carbon-mitigation in mind,” such as his own institution’s pledge to become carbon-neutral within a year. One step on that path has included transitioning more than 30% of their clinic visits to virtual visits, “thus saving [literally] millions of miles in travel and altering our parking construction plans,” Dr. Allen said.
“Reduction in climate impact will come from new ways to manufacture endoscopes, less reliance on single-use equipment, and increasing use of materials that encourage recycling,” Dr. Allen said. “In order to achieve meaningful climate impact, we need research into what current regulations and processes are necessary to protect patients and staff from infection transmission while creating an environmentally favorable workflow.”
Where does making a difference begin?
Another limitation was simply the small size of the department itself, which limits how much impact the intervention can have, but the study also showed the feasibility of getting buy-in from a department to make meaningful changes, according to Bishr Omary, MD, PhD, professor of medicine at Rutgers University’s Robert Wood Johnson Medical School, Piscataway, N.J. He was not involved in the study.
“Culture is an important aspect of this, but that’s where education comes in,” Dr. Omary said in an interview. “Leadership has to try to encourage and incentivize different units, not just endoscopy, but other surgery, too. I think the most effective approach is going to be top-down, where hospitals and health systems buy into this.”
One challenge to that buy-in is that climate change has become political, said Linda Anh B. Nguyen, MD, clinical professor of medicine and vice chief of clinical operations in Stanford (Calif.) University’s division of gastroenterology and hepatology.
“There may be resistance to implementation by those who do not see the value of reducing waste,” Dr. Nguyen, who was not involved in this study, said in an interview. “Successful implementation requires a culture change and reducing the physical barriers to make waste reduction easier. Having an advocate for the program embedded within the endoscopy unit will help with implementation.”
One of the advantages of the intervention in this study, Dr. Nguyen said, was its relative ease of implementation.
“The next step would be identifying which of the items that go into landfill can be replaced with reusable products,” Dr. Nguyen added.
Dr. Omary pointed to Practice Greenhealth as an example of an organization working toward the goal of climate change mitigation through a wide range of initiatives, including ones he has written about. The responsibility for reducing carbon footprints should be shared among individuals, institutions, and systems, Dr. Omary said, adding that individuals’ travel, such as to medical meetings, is a major contributor to greenhouse gas emissions.
A forthcoming publication from the four major gastroenterology medical organizations will outline additional ways gastroenterology can address climate change mitigation, Dr. Omary noted.
Dr. Nguyen said that gastroenterologists, as well as the entire health care industry, have a responsibility to combat climate change through waste reduction and that it can be done without sacrificing individual patient safety.
“Climate change must be at the forefront of our priorities for present and future generations,” Dr. Nguyen said. “We need to leave this world better than when we entered.”
But much of that change must especially occur at levels far higher than individual physicians or institutions, Dr. Allen said.
“Major responsibility for altering gastroenterology practices in order to mitigate climate change must originate in regulatory agencies and the manufacturers of our equipment,” Dr. Allen said. “Regulations must be based on demonstrated positive impact that is cost-effective for practices and health care systems.”
The research did not use external funding, and the authors reported no financial disclosures or conflicts of interests. Dr. Allen has consulted for Topography Health, OSHI Health, and Lynxmd. Dr. Nguyen has consulted for Alnylam, Ardelyx, Eli Lilly, Evoke Pharma, Ironwood, Pendulum, Phathom, Neurogastx, Sanofi, and Takeda; has served on the advisory board of Gemelli Biotech; and has received grants from Bold Health and Vanda. Dr. Omary had no disclosures.
Moving recycling bins and providing education to staff led to a reduction in the carbon footprint at a Portuguese hospital’s endoscopy unit, according to a study published in Gut.
“Sustainable endoscopy regarding waste handling was achievable and sustained over time, did not compromise productivity, and may be cost-effective for stakeholders,” wrote João A Cunha Neves, MD, MMSc, of Algarve University Hospital Centre in Portimão, Portugal, and his colleagues.
Although other work has shown that several of the strategies for reducing endoscopic waste are ‘easy wins,’ the authors noted that “lack of awareness by most endoscopy staff regarding the expenses and correct categorisation of endoscopic waste is the primary barrier to recycling in many endoscopy units.”
The four-stage prospective study took place at the Portimão endoscopy unit of Algarve University Hospital Centre in Portugal. It began with a 4-week audit that involved weighing regulated medical waste (“material fully contaminated with blood or body fluids or containing infectious agents”) and landfill waste (nonrecyclable material that isn’t fully contaminated). The researchers excluded from the analysis all waste from sharps containers, pre- and postprocedure activities, and endoscope reprocessing.
The second stage was one week of medical, nursing, and auxiliary team education about handling waste, in part based on observations collected during the first stage. Each endoscopy generates an estimated 1.5 kg of plastic waste, but recycling bins often are not available for the 0.3 kg of waste that’s recyclable. During the second stage, recycling bins were placed in endoscopy rooms while regulated medical waste and landfill bins were moved elsewhere.
The final two stages involved weighing both types of waste 1 month after the training and then 4 months after the training. For their calculations, the researchers assumed that 1 kg of landfill waste equated to 1 kg of carbon dioxide and 1 kg of regulated medical waste equated to 3 kg of carbon dioxide.
At the third stage, mean total waste fell by 12.9%, albeit not statistically significantly (P = .16), while the 41.4% regulated medical waste reduction was significant (P = .01). Landfill waste had increased 12.3% and both paper (0 to 1.2 kg) and plastic (0 to 2.1 kg) recycling waste increased. Mean endoscopy load had not significantly changed (46.2 vs. 44.5). Overall carbon dioxide was reduced by 31.6%, from 109.7 kg of carbon dioxide to 74.9 kg (P = .018), equating to an annual decrease of 1,665.6 kg. At four months postintervention, these effects remained.
“In both assessment periods, total waste produced by diagnostic standard endoscopic procedures was similar, but both regulated medical waste and overall carbon footprint were reduced,” the authors reported.
In a four-question assessment of the intervention with staff, “the entire team agreed that the study did not interfere with the daily work routine and was helpful in raising awareness about waste sorting within the unit,” the authors reported. The staff “also acknowledged that recycling waste allowed for more sustainable activity within the endoscopy unit, and that the achievements of the study were to be maintained in the future.”
How feasible is change?
The authors noted that health care accounts for 4.4% of the world’s carbon footprint and that endoscopy is the third largest generator of hospital medical waste, primarily because of single-use consumables. However, 71% of that health care carbon footprint comes from supply chain issues, particularly transportation, John I. Allen, MD, MBA, a retired clinical professor of medicine at the University Michigan, Ann Arbor, said in an interview. “Facility emissions add 17% and heating/cooling add 12%,” he said. “So, the actual footprint of endoscopy is quite small.”
Reducing single-use equipment and disposables by a third is a small overall impact considering the “labor-intensive education and monitoring system,” said Dr. Allen, who was not involved in the study. “That said, this paper and numerous others remind us of small steps that we can take – mostly to raise awareness about new technologies and more sustainable processes that are available or should be studied – to help transition us from the current [terrible] state to a more climate-friendly style of practice and life.”
One of the study’s limitations was the lack of a cost-benefit or impact analysis, according to Dr. Allen. Climate policies claiming to have local impact can be problematic when they “ignore both externalities and the actual wider impact on gas or temperature mitigation,” he added.
But he noted that “many health care systems are already implementing new ways of working with temperature- and carbon-mitigation in mind,” such as his own institution’s pledge to become carbon-neutral within a year. One step on that path has included transitioning more than 30% of their clinic visits to virtual visits, “thus saving [literally] millions of miles in travel and altering our parking construction plans,” Dr. Allen said.
“Reduction in climate impact will come from new ways to manufacture endoscopes, less reliance on single-use equipment, and increasing use of materials that encourage recycling,” Dr. Allen said. “In order to achieve meaningful climate impact, we need research into what current regulations and processes are necessary to protect patients and staff from infection transmission while creating an environmentally favorable workflow.”
Where does making a difference begin?
Another limitation was simply the small size of the department itself, which limits how much impact the intervention can have, but the study also showed the feasibility of getting buy-in from a department to make meaningful changes, according to Bishr Omary, MD, PhD, professor of medicine at Rutgers University’s Robert Wood Johnson Medical School, Piscataway, N.J. He was not involved in the study.
“Culture is an important aspect of this, but that’s where education comes in,” Dr. Omary said in an interview. “Leadership has to try to encourage and incentivize different units, not just endoscopy, but other surgery, too. I think the most effective approach is going to be top-down, where hospitals and health systems buy into this.”
One challenge to that buy-in is that climate change has become political, said Linda Anh B. Nguyen, MD, clinical professor of medicine and vice chief of clinical operations in Stanford (Calif.) University’s division of gastroenterology and hepatology.
“There may be resistance to implementation by those who do not see the value of reducing waste,” Dr. Nguyen, who was not involved in this study, said in an interview. “Successful implementation requires a culture change and reducing the physical barriers to make waste reduction easier. Having an advocate for the program embedded within the endoscopy unit will help with implementation.”
One of the advantages of the intervention in this study, Dr. Nguyen said, was its relative ease of implementation.
“The next step would be identifying which of the items that go into landfill can be replaced with reusable products,” Dr. Nguyen added.
Dr. Omary pointed to Practice Greenhealth as an example of an organization working toward the goal of climate change mitigation through a wide range of initiatives, including ones he has written about. The responsibility for reducing carbon footprints should be shared among individuals, institutions, and systems, Dr. Omary said, adding that individuals’ travel, such as to medical meetings, is a major contributor to greenhouse gas emissions.
A forthcoming publication from the four major gastroenterology medical organizations will outline additional ways gastroenterology can address climate change mitigation, Dr. Omary noted.
Dr. Nguyen said that gastroenterologists, as well as the entire health care industry, have a responsibility to combat climate change through waste reduction and that it can be done without sacrificing individual patient safety.
“Climate change must be at the forefront of our priorities for present and future generations,” Dr. Nguyen said. “We need to leave this world better than when we entered.”
But much of that change must especially occur at levels far higher than individual physicians or institutions, Dr. Allen said.
“Major responsibility for altering gastroenterology practices in order to mitigate climate change must originate in regulatory agencies and the manufacturers of our equipment,” Dr. Allen said. “Regulations must be based on demonstrated positive impact that is cost-effective for practices and health care systems.”
The research did not use external funding, and the authors reported no financial disclosures or conflicts of interests. Dr. Allen has consulted for Topography Health, OSHI Health, and Lynxmd. Dr. Nguyen has consulted for Alnylam, Ardelyx, Eli Lilly, Evoke Pharma, Ironwood, Pendulum, Phathom, Neurogastx, Sanofi, and Takeda; has served on the advisory board of Gemelli Biotech; and has received grants from Bold Health and Vanda. Dr. Omary had no disclosures.
Moving recycling bins and providing education to staff led to a reduction in the carbon footprint at a Portuguese hospital’s endoscopy unit, according to a study published in Gut.
“Sustainable endoscopy regarding waste handling was achievable and sustained over time, did not compromise productivity, and may be cost-effective for stakeholders,” wrote João A Cunha Neves, MD, MMSc, of Algarve University Hospital Centre in Portimão, Portugal, and his colleagues.
Although other work has shown that several of the strategies for reducing endoscopic waste are ‘easy wins,’ the authors noted that “lack of awareness by most endoscopy staff regarding the expenses and correct categorisation of endoscopic waste is the primary barrier to recycling in many endoscopy units.”
The four-stage prospective study took place at the Portimão endoscopy unit of Algarve University Hospital Centre in Portugal. It began with a 4-week audit that involved weighing regulated medical waste (“material fully contaminated with blood or body fluids or containing infectious agents”) and landfill waste (nonrecyclable material that isn’t fully contaminated). The researchers excluded from the analysis all waste from sharps containers, pre- and postprocedure activities, and endoscope reprocessing.
The second stage was one week of medical, nursing, and auxiliary team education about handling waste, in part based on observations collected during the first stage. Each endoscopy generates an estimated 1.5 kg of plastic waste, but recycling bins often are not available for the 0.3 kg of waste that’s recyclable. During the second stage, recycling bins were placed in endoscopy rooms while regulated medical waste and landfill bins were moved elsewhere.
The final two stages involved weighing both types of waste 1 month after the training and then 4 months after the training. For their calculations, the researchers assumed that 1 kg of landfill waste equated to 1 kg of carbon dioxide and 1 kg of regulated medical waste equated to 3 kg of carbon dioxide.
At the third stage, mean total waste fell by 12.9%, albeit not statistically significantly (P = .16), while the 41.4% regulated medical waste reduction was significant (P = .01). Landfill waste had increased 12.3% and both paper (0 to 1.2 kg) and plastic (0 to 2.1 kg) recycling waste increased. Mean endoscopy load had not significantly changed (46.2 vs. 44.5). Overall carbon dioxide was reduced by 31.6%, from 109.7 kg of carbon dioxide to 74.9 kg (P = .018), equating to an annual decrease of 1,665.6 kg. At four months postintervention, these effects remained.
“In both assessment periods, total waste produced by diagnostic standard endoscopic procedures was similar, but both regulated medical waste and overall carbon footprint were reduced,” the authors reported.
In a four-question assessment of the intervention with staff, “the entire team agreed that the study did not interfere with the daily work routine and was helpful in raising awareness about waste sorting within the unit,” the authors reported. The staff “also acknowledged that recycling waste allowed for more sustainable activity within the endoscopy unit, and that the achievements of the study were to be maintained in the future.”
How feasible is change?
The authors noted that health care accounts for 4.4% of the world’s carbon footprint and that endoscopy is the third largest generator of hospital medical waste, primarily because of single-use consumables. However, 71% of that health care carbon footprint comes from supply chain issues, particularly transportation, John I. Allen, MD, MBA, a retired clinical professor of medicine at the University Michigan, Ann Arbor, said in an interview. “Facility emissions add 17% and heating/cooling add 12%,” he said. “So, the actual footprint of endoscopy is quite small.”
Reducing single-use equipment and disposables by a third is a small overall impact considering the “labor-intensive education and monitoring system,” said Dr. Allen, who was not involved in the study. “That said, this paper and numerous others remind us of small steps that we can take – mostly to raise awareness about new technologies and more sustainable processes that are available or should be studied – to help transition us from the current [terrible] state to a more climate-friendly style of practice and life.”
One of the study’s limitations was the lack of a cost-benefit or impact analysis, according to Dr. Allen. Climate policies claiming to have local impact can be problematic when they “ignore both externalities and the actual wider impact on gas or temperature mitigation,” he added.
But he noted that “many health care systems are already implementing new ways of working with temperature- and carbon-mitigation in mind,” such as his own institution’s pledge to become carbon-neutral within a year. One step on that path has included transitioning more than 30% of their clinic visits to virtual visits, “thus saving [literally] millions of miles in travel and altering our parking construction plans,” Dr. Allen said.
“Reduction in climate impact will come from new ways to manufacture endoscopes, less reliance on single-use equipment, and increasing use of materials that encourage recycling,” Dr. Allen said. “In order to achieve meaningful climate impact, we need research into what current regulations and processes are necessary to protect patients and staff from infection transmission while creating an environmentally favorable workflow.”
Where does making a difference begin?
Another limitation was simply the small size of the department itself, which limits how much impact the intervention can have, but the study also showed the feasibility of getting buy-in from a department to make meaningful changes, according to Bishr Omary, MD, PhD, professor of medicine at Rutgers University’s Robert Wood Johnson Medical School, Piscataway, N.J. He was not involved in the study.
“Culture is an important aspect of this, but that’s where education comes in,” Dr. Omary said in an interview. “Leadership has to try to encourage and incentivize different units, not just endoscopy, but other surgery, too. I think the most effective approach is going to be top-down, where hospitals and health systems buy into this.”
One challenge to that buy-in is that climate change has become political, said Linda Anh B. Nguyen, MD, clinical professor of medicine and vice chief of clinical operations in Stanford (Calif.) University’s division of gastroenterology and hepatology.
“There may be resistance to implementation by those who do not see the value of reducing waste,” Dr. Nguyen, who was not involved in this study, said in an interview. “Successful implementation requires a culture change and reducing the physical barriers to make waste reduction easier. Having an advocate for the program embedded within the endoscopy unit will help with implementation.”
One of the advantages of the intervention in this study, Dr. Nguyen said, was its relative ease of implementation.
“The next step would be identifying which of the items that go into landfill can be replaced with reusable products,” Dr. Nguyen added.
Dr. Omary pointed to Practice Greenhealth as an example of an organization working toward the goal of climate change mitigation through a wide range of initiatives, including ones he has written about. The responsibility for reducing carbon footprints should be shared among individuals, institutions, and systems, Dr. Omary said, adding that individuals’ travel, such as to medical meetings, is a major contributor to greenhouse gas emissions.
A forthcoming publication from the four major gastroenterology medical organizations will outline additional ways gastroenterology can address climate change mitigation, Dr. Omary noted.
Dr. Nguyen said that gastroenterologists, as well as the entire health care industry, have a responsibility to combat climate change through waste reduction and that it can be done without sacrificing individual patient safety.
“Climate change must be at the forefront of our priorities for present and future generations,” Dr. Nguyen said. “We need to leave this world better than when we entered.”
But much of that change must especially occur at levels far higher than individual physicians or institutions, Dr. Allen said.
“Major responsibility for altering gastroenterology practices in order to mitigate climate change must originate in regulatory agencies and the manufacturers of our equipment,” Dr. Allen said. “Regulations must be based on demonstrated positive impact that is cost-effective for practices and health care systems.”
The research did not use external funding, and the authors reported no financial disclosures or conflicts of interests. Dr. Allen has consulted for Topography Health, OSHI Health, and Lynxmd. Dr. Nguyen has consulted for Alnylam, Ardelyx, Eli Lilly, Evoke Pharma, Ironwood, Pendulum, Phathom, Neurogastx, Sanofi, and Takeda; has served on the advisory board of Gemelli Biotech; and has received grants from Bold Health and Vanda. Dr. Omary had no disclosures.
FROM GUT
10-year delay in one-third of EoE diagnoses has persisted for decades
It takes at least 10 years for one-third of patients with eosinophilic esophagitis (EoE) to receive a diagnosis and a median of 4 years for patients overall to get their diagnosis – numbers that haven’t budged in 3 decades, according to a study published online in the American Journal of Gastroenterology.
This delay has persisted despite more than 2,000 publications on the condition since 2014 and a variety of educational events about it, reported Fritz R. Murray, MD, of the department of gastroenterology and hepatology at University Hospital Zurich and his colleagues.
“Bearing in mind that eosinophilic esophagitis is a chronic and progressive disease, that, if left untreated, leads to esophageal structuring ultimately causing food impaction, the results of our analysis are a cause for concern,” the authors wrote.
“Substantial efforts are warranted to increase awareness for eosinophilic esophagitis and its hallmark symptom, solid-food dysphagia, as an age-independent red-flag symptom … in order to lower risk of long-term complications,” they added.
The researchers retrospectively analyzed prospectively collected data from 1,152 patients in a Swiss database. The patients (74% male; median age, 38 years) had all been diagnosed with EoE according to established criteria. The authors calculated the diagnostic delay from 1989 to 2021 and at three key time points: 1993 – first description of the condition, 2007 – first consensus recommendations, and 2011 – updated consensus recommendations
The median diagnostic delay over the 3 decades studied was 4 years overall and was at least 10 years in nearly one-third (32%) of the population. Diagnostic delay did not significantly change throughout the study period, year by year, or at or after any of the milestones included in the analysis, retaining the minimum 10-year delay in about one-third of all patients.
The median age at symptom onset was 30 years, with 51% of patients first experiencing symptoms between 10 and 30 years of age.
“Age at diagnosis showed a normal distribution with its peak between 30 and 40 years with 25% of the study population being diagnosed with EoE during that period,” the authors reported.
Although diagnostic delay did not differ between sexes, the length of time before diagnosis did vary on the basis of the patient’s age at diagnosis, increasing from a median of 0 years for those aged 10 years or younger to 5 years for those aged 31-40 years.
“When examining variation in diagnostic delay based on age at symptom onset, we observed an inverse association of age at symptom onset and diagnostic delay, with longest diagnostic delay observed in children,” they wrote.
Diagnostic delay was longer in those who needed an endoscopic disimpaction – a median of 6 years – before being diagnosed, compared with those who did not require this procedure, who had a median delay of 3 years. Nearly one-third (31%) of participants had at least one food impaction requiring endoscopic removal before receiving their diagnosis.
Three in four participants (74%) had a confirmed atopic condition besides eosinophilic esophagitis, with 13% not having an atopic comorbidity and another 13% lacking information on whether they did or didn’t. Those with atopic conditions were younger (median age, 29 years) when symptoms began than were those without atopic conditions (median age, 34 years).
Similarly, those with atopic conditions were younger (median age, 38 years) than those without these conditions (median age, 41 years) at the time of diagnosis. Diagnostic delay was a median 2 years shorter – 3 years vs. 5 years – for patients with concomitant atopic conditions.
“Importantly, the length of diagnosis delay (untreated disease) directly correlates with the occurrence of esophageal strictures,” the authors wrote, citing previous research finding that the prevalence of strictures rose from 17% in patients with a delay of up to 2 years to 71% in patients with a delay of more than 20 years.
“Esophageal strictures were present in around 38% of patients with a delay between 8-11 years” in that study, “a delay that is prevalent in about one third of our study population,” the authors wrote. “However, even a median delay of 4 years resulted in strictures in around 31% of untreated patients.”
Other research has found that the risk for esophageal strictures increases an estimated 9% each year that eosinophilic esophagitis goes untreated.
The authors suggested that patients’ denying symptoms or attempting to address their symptoms with changes in diet or eating behavior may be one reason for the long diagnostic delay, given other findings showing that patient-dependent delay was 18 months, compared with 6 months for physician-dependent delay. Although the authors didn’t have the information in their dataset to assess patient- vs. physician-dependent delay, a subgroup analysis revealed that patients and nongastroenterologist doctors combined made up the largest proportion of diagnosis delay.
“This fact indicates that future efforts should target the general population, and potentially primary physicians, to strengthen the awareness for eosinophilic esophagitis as a potential underlying condition in patients with dysphagia,” the authors wrote.
“A change in eating behavior, especially in cases with prolonged chewing, slow swallowing or even the necessity of drinking fluids after swallowing of solid food, should raise suspicion also in the general population,” they added.
Dr. Murray received travel support from Janssen, and 9 of the other 11 authors reported consulting, speaking, research and/or travel fees from 23 various pharmaceutical and related companies.
A version of this article first appeared on Medscape.com.
It takes at least 10 years for one-third of patients with eosinophilic esophagitis (EoE) to receive a diagnosis and a median of 4 years for patients overall to get their diagnosis – numbers that haven’t budged in 3 decades, according to a study published online in the American Journal of Gastroenterology.
This delay has persisted despite more than 2,000 publications on the condition since 2014 and a variety of educational events about it, reported Fritz R. Murray, MD, of the department of gastroenterology and hepatology at University Hospital Zurich and his colleagues.
“Bearing in mind that eosinophilic esophagitis is a chronic and progressive disease, that, if left untreated, leads to esophageal structuring ultimately causing food impaction, the results of our analysis are a cause for concern,” the authors wrote.
“Substantial efforts are warranted to increase awareness for eosinophilic esophagitis and its hallmark symptom, solid-food dysphagia, as an age-independent red-flag symptom … in order to lower risk of long-term complications,” they added.
The researchers retrospectively analyzed prospectively collected data from 1,152 patients in a Swiss database. The patients (74% male; median age, 38 years) had all been diagnosed with EoE according to established criteria. The authors calculated the diagnostic delay from 1989 to 2021 and at three key time points: 1993 – first description of the condition, 2007 – first consensus recommendations, and 2011 – updated consensus recommendations
The median diagnostic delay over the 3 decades studied was 4 years overall and was at least 10 years in nearly one-third (32%) of the population. Diagnostic delay did not significantly change throughout the study period, year by year, or at or after any of the milestones included in the analysis, retaining the minimum 10-year delay in about one-third of all patients.
The median age at symptom onset was 30 years, with 51% of patients first experiencing symptoms between 10 and 30 years of age.
“Age at diagnosis showed a normal distribution with its peak between 30 and 40 years with 25% of the study population being diagnosed with EoE during that period,” the authors reported.
Although diagnostic delay did not differ between sexes, the length of time before diagnosis did vary on the basis of the patient’s age at diagnosis, increasing from a median of 0 years for those aged 10 years or younger to 5 years for those aged 31-40 years.
“When examining variation in diagnostic delay based on age at symptom onset, we observed an inverse association of age at symptom onset and diagnostic delay, with longest diagnostic delay observed in children,” they wrote.
Diagnostic delay was longer in those who needed an endoscopic disimpaction – a median of 6 years – before being diagnosed, compared with those who did not require this procedure, who had a median delay of 3 years. Nearly one-third (31%) of participants had at least one food impaction requiring endoscopic removal before receiving their diagnosis.
Three in four participants (74%) had a confirmed atopic condition besides eosinophilic esophagitis, with 13% not having an atopic comorbidity and another 13% lacking information on whether they did or didn’t. Those with atopic conditions were younger (median age, 29 years) when symptoms began than were those without atopic conditions (median age, 34 years).
Similarly, those with atopic conditions were younger (median age, 38 years) than those without these conditions (median age, 41 years) at the time of diagnosis. Diagnostic delay was a median 2 years shorter – 3 years vs. 5 years – for patients with concomitant atopic conditions.
“Importantly, the length of diagnosis delay (untreated disease) directly correlates with the occurrence of esophageal strictures,” the authors wrote, citing previous research finding that the prevalence of strictures rose from 17% in patients with a delay of up to 2 years to 71% in patients with a delay of more than 20 years.
“Esophageal strictures were present in around 38% of patients with a delay between 8-11 years” in that study, “a delay that is prevalent in about one third of our study population,” the authors wrote. “However, even a median delay of 4 years resulted in strictures in around 31% of untreated patients.”
Other research has found that the risk for esophageal strictures increases an estimated 9% each year that eosinophilic esophagitis goes untreated.
The authors suggested that patients’ denying symptoms or attempting to address their symptoms with changes in diet or eating behavior may be one reason for the long diagnostic delay, given other findings showing that patient-dependent delay was 18 months, compared with 6 months for physician-dependent delay. Although the authors didn’t have the information in their dataset to assess patient- vs. physician-dependent delay, a subgroup analysis revealed that patients and nongastroenterologist doctors combined made up the largest proportion of diagnosis delay.
“This fact indicates that future efforts should target the general population, and potentially primary physicians, to strengthen the awareness for eosinophilic esophagitis as a potential underlying condition in patients with dysphagia,” the authors wrote.
“A change in eating behavior, especially in cases with prolonged chewing, slow swallowing or even the necessity of drinking fluids after swallowing of solid food, should raise suspicion also in the general population,” they added.
Dr. Murray received travel support from Janssen, and 9 of the other 11 authors reported consulting, speaking, research and/or travel fees from 23 various pharmaceutical and related companies.
A version of this article first appeared on Medscape.com.
It takes at least 10 years for one-third of patients with eosinophilic esophagitis (EoE) to receive a diagnosis and a median of 4 years for patients overall to get their diagnosis – numbers that haven’t budged in 3 decades, according to a study published online in the American Journal of Gastroenterology.
This delay has persisted despite more than 2,000 publications on the condition since 2014 and a variety of educational events about it, reported Fritz R. Murray, MD, of the department of gastroenterology and hepatology at University Hospital Zurich and his colleagues.
“Bearing in mind that eosinophilic esophagitis is a chronic and progressive disease, that, if left untreated, leads to esophageal structuring ultimately causing food impaction, the results of our analysis are a cause for concern,” the authors wrote.
“Substantial efforts are warranted to increase awareness for eosinophilic esophagitis and its hallmark symptom, solid-food dysphagia, as an age-independent red-flag symptom … in order to lower risk of long-term complications,” they added.
The researchers retrospectively analyzed prospectively collected data from 1,152 patients in a Swiss database. The patients (74% male; median age, 38 years) had all been diagnosed with EoE according to established criteria. The authors calculated the diagnostic delay from 1989 to 2021 and at three key time points: 1993 – first description of the condition, 2007 – first consensus recommendations, and 2011 – updated consensus recommendations
The median diagnostic delay over the 3 decades studied was 4 years overall and was at least 10 years in nearly one-third (32%) of the population. Diagnostic delay did not significantly change throughout the study period, year by year, or at or after any of the milestones included in the analysis, retaining the minimum 10-year delay in about one-third of all patients.
The median age at symptom onset was 30 years, with 51% of patients first experiencing symptoms between 10 and 30 years of age.
“Age at diagnosis showed a normal distribution with its peak between 30 and 40 years with 25% of the study population being diagnosed with EoE during that period,” the authors reported.
Although diagnostic delay did not differ between sexes, the length of time before diagnosis did vary on the basis of the patient’s age at diagnosis, increasing from a median of 0 years for those aged 10 years or younger to 5 years for those aged 31-40 years.
“When examining variation in diagnostic delay based on age at symptom onset, we observed an inverse association of age at symptom onset and diagnostic delay, with longest diagnostic delay observed in children,” they wrote.
Diagnostic delay was longer in those who needed an endoscopic disimpaction – a median of 6 years – before being diagnosed, compared with those who did not require this procedure, who had a median delay of 3 years. Nearly one-third (31%) of participants had at least one food impaction requiring endoscopic removal before receiving their diagnosis.
Three in four participants (74%) had a confirmed atopic condition besides eosinophilic esophagitis, with 13% not having an atopic comorbidity and another 13% lacking information on whether they did or didn’t. Those with atopic conditions were younger (median age, 29 years) when symptoms began than were those without atopic conditions (median age, 34 years).
Similarly, those with atopic conditions were younger (median age, 38 years) than those without these conditions (median age, 41 years) at the time of diagnosis. Diagnostic delay was a median 2 years shorter – 3 years vs. 5 years – for patients with concomitant atopic conditions.
“Importantly, the length of diagnosis delay (untreated disease) directly correlates with the occurrence of esophageal strictures,” the authors wrote, citing previous research finding that the prevalence of strictures rose from 17% in patients with a delay of up to 2 years to 71% in patients with a delay of more than 20 years.
“Esophageal strictures were present in around 38% of patients with a delay between 8-11 years” in that study, “a delay that is prevalent in about one third of our study population,” the authors wrote. “However, even a median delay of 4 years resulted in strictures in around 31% of untreated patients.”
Other research has found that the risk for esophageal strictures increases an estimated 9% each year that eosinophilic esophagitis goes untreated.
The authors suggested that patients’ denying symptoms or attempting to address their symptoms with changes in diet or eating behavior may be one reason for the long diagnostic delay, given other findings showing that patient-dependent delay was 18 months, compared with 6 months for physician-dependent delay. Although the authors didn’t have the information in their dataset to assess patient- vs. physician-dependent delay, a subgroup analysis revealed that patients and nongastroenterologist doctors combined made up the largest proportion of diagnosis delay.
“This fact indicates that future efforts should target the general population, and potentially primary physicians, to strengthen the awareness for eosinophilic esophagitis as a potential underlying condition in patients with dysphagia,” the authors wrote.
“A change in eating behavior, especially in cases with prolonged chewing, slow swallowing or even the necessity of drinking fluids after swallowing of solid food, should raise suspicion also in the general population,” they added.
Dr. Murray received travel support from Janssen, and 9 of the other 11 authors reported consulting, speaking, research and/or travel fees from 23 various pharmaceutical and related companies.
A version of this article first appeared on Medscape.com.
FROM AMERICAN JOURNAL OF GASTROENTEROLOGY
State of the science in PCOS: Emerging neuroendocrine involvement driving research
Polycystic ovary syndrome (PCOS) affects an estimated 8%-13% of women, and yet “it has been quite a black box for many years,” as Margo Hudson, MD, an assistant professor of endocrinology, diabetes, and hypertension at Harvard Medical School, Boston, puts it. That black box encompasses not only uncertainty about the etiology and pathophysiology of the condition but even what constitutes a diagnosis.
Even the international guidelines on PCOS management endorsed by the American Society for Reproductive Medicine – a document developed over 15 months with the input of 37 medical organizations covering 71 countries – notes that PCOS diagnosis is “controversial and assessment and management are inconsistent.” The result, the guidelines note, is that “the needs of women with PCOS are not being adequately met.”
One of the earliest diagnostic criteria, defined in 1990 by the National Institutes of Health, required only hyperandrogenism and irregular menstruation. Then the 2003 Rotterdam Criteria added presence of polycystic ovaries on ultrasound as a third criterion. Then the Androgen Excess Society determined that PCOS required presence of hyperandrogenism with either polycystic ovaries or oligo/amenorrhea anovulation. Yet the Endocrine Society notes that excess androgen levels are seen in 60%-80% of those with PCOS, suggesting it’s not an essential requirement for diagnosis, leaving most to diagnose it in people who have two of the three key criteria. The only real agreement on diagnosis is the need to eliminate other potential diagnoses first, making PCOS always a diagnosis of exclusion.
Further, though PCOS is known as the leading cause of infertility in women, it is more than a reproductive condition, with metabolic and psychological features as well. Then there is the range of comorbidities, none of which occur in all patients with PCOS but all of which occur in a majority and which are themselves interrelated. Insulin resistance is a common feature, occurring in 50%-70% of people with PCOS. Accordingly, metabolic syndrome occurs in at least a third of people with PCOS and type 2 diabetes prevalence is higher in those with PCOS as well.
Obesity occurs in an estimated 80% of women with PCOS in the United States, though it affects only about 50% of women with PCOS outside the United States, and those with PCOS have an increased risk of hypertension. Mood disorders, particularly anxiety and depression but also, to a lesser extent, bipolar disorder and obsessive-compulsive disorder, are more likely in people with PCOS. And given that these comorbidities are all cardiovascular risk factors, it’s unsurprising that recent studies are finding those with PCOS to be at greater risk for cardiometabolic disease and major cardiovascular events.
“The reality is that PCOS is a heterogenous entity. It’s not one thing – it’s a syndrome,” Lubna Pal, MBBS, a professor of ob.gyn. and director of the PCOS Program at Yale University, New Haven, Conn., said in an interview. A whole host of factors are likely playing a role in the causes of PCOS, and those factors interact differently within different people. “We’re looking at things like lipid metabolism, fetal origins, the gut microbiome, genetics, epigenetics, and then dietary and environmental factors,” Nichole Tyson, MD, division chief of pediatric and adolescent gynecology and a clinical associate professor at Stanford (Calif.) Medicine Children’s Health, said in an interview. And most studies have identified associations that may or may not be causal. Take, for example, endocrine disruptors. BPA levels have been shown to be higher in women with PCOS than women without, but that correlation may or may not be related to the etiology of the condition.
The hypothalamic-pituitary-gonadal axis
In trying to understand the pathophysiology of the condition, much of the latest research has zeroed in on potential mechanisms in the hypothalamic-pituitary-gonadal axis. “A consistent feature of PCOS is disordered gonadotropin secretion with elevated mean LH [luteinizing hormone], low or low normal FSH [follicle-stimulating hormone], and a persistently rapid frequency of GnRH [gonadotropin-releasing hormone] pulse secretion,” wrote authors of a scientific statement on aspects of PCOS.
“I think the balance is heading more to central neurologic control of the reproductive system and that disturbances there impact the GnRH cells in the hypothalamus, which then go on to give us the findings that we can measure peripherally with the LH-FSH ratio,” Dr. Hudson said in an interview.
The increased LH levels are thought to be a major driver of increased androgen levels. Current thinking suggests that the primary driver of increased LH is GnRH pulsatility, supported not only by human studies but by animal models as well. This leads to the question of what drives GnRH dysregulation. One hypothesis posits that GABA neurons play a role here, given findings that GABA levels in cerebrospinal fluid were higher in women with PCOS than those with normal ovulation.
But the culprit garnering the most attention is kisspeptin, a protein encoded by the KISS1 gene that stimulates GnRH neurons and has been linked to regulation of LH and FSH secretion. Kisspeptin, along with neurokinin B and dynorphin, is part of the triumvirate that comprises KNDy neurons, also recently implicated in menopausal vasomotor symptoms. Multiple systematic reviewsand meta-analyses have found a correlation between higher kisspeptin levels in the blood and higher circulating LH levels, regardless of body mass index. While kisspeptin is expressed in several tissues, including liver, pancreas, gonad, and adipose, it’s neural kisspeptin signaling that appears most likely to play a role in activating GnRH hormones and disrupting normal function of the hypothalamic-pituitary-gonadal axis.
But as noted, in at least one systematic review of kisspeptin and PCOS, “findings from animal studies suggest that kisspeptin levels are not increased in all subtypes of PCOS.” And another review found “altered” levels of kisspeptin levels in non-PCOS patients who had obesity, potentially raising questions about any associations between kisspeptin and obesity or insulin resistance.
Remaining chicken-and-egg questions
A hallmark of PCOS has long been, and continues to be, the string of chicken-or-egg questions that plague understanding of it. One of these is how depression and anxiety fit into the etiology of PCOS. Exploring the role of specific neurons that may overstimulate GnRH pulsatility may hold clues to a common underlying mechanism for the involvement of depression and anxiety in patients with PCOS, Dr. Hudson speculated. While previous assumptions often attributed depression and anxiety in PCOS to the symptoms – such as thin scalp hair and increased facial hair, excess weight, acne, and irregular periods – Dr. Hudson pointed out that women can address many of these symptoms with laser hair removal, weight loss, acne treatment, and similar interventions, yet they still have a lot of underlying mental health issues.
It’s also unclear whether metabolic factors so common with PCOS, particularly insulin resistance and obesity, are a result of the condition or are contributors to it. Is insulin resistance contributing to dysregulation in the neurons that interferes with normal functioning of the hypothalamic-pituitary-adrenal axis? Is abnormal functioning along this axis contributing to insulin resistance? Or neither? Or both? Or does it depend? The authors of one paper wrote that “insulin may play both direct and indirect roles in the pathogenesis of androgen excess in PCOS,” since insulin can “stimulate ovarian androgen production” and “enhance ovarian growth and follicular cyst formation in rats.”
Dr. Pal noted that “obesity itself can evolve into a PCOS-like picture,” raising questions about whether obesity or insulin resistance might be part of the causal pathway to PCOS, or whether either can trigger its development in those genetically predisposed.
“Obesity does appear to exacerbate many aspects of the PCOS phenotype, particularly those risk factors related to metabolic syndrome,” wrote the authors of a scientific statement on aspects of PCOS, but they add that “it is currently debated whether obesity per se can cause PCOS.” While massive weight loss in those with PCOS and obesity has improved multiple reproductive and metabolic issues, it hasn’t resolved all of them, they write.
Dr. Hudson said she expects there’s “some degree of appetite dysregulation and metabolic dysregulation” that contributes, but then there are other women who don’t have much of an appetite or overeat and still struggle with their weight. Evidence has also found insulin resistance in women of normal weight with PCOS. “There may be some kind of metabolic dysregulation that they have at some level, and others are clearly bothered by overeating,” Dr. Hudson said.
Similarly, it’s not clear whether the recent discovery of increased cardiovascular risks in people with PCOS is a result of the comorbidities so common with PCOS, such as obesity, or whether an underlying mechanism links the cardiovascular risk and the dysregulation of hormones. Dr. Pal would argue that, again, it’s probably both, depending on the patient.
Then there is the key feature of hyperandrogenemia. “An outstanding debate is whether the elevated androgens in PCOS women are merely a downstream endocrine response to hyperactive GnRH and LH secretion driving the ovary, or do the elevated androgens themselves act in the brain (or pituitary) during development and/or adulthood to sculpt and maintain the hypersecretion of GnRH and LH?” wrote Eulalia A. Coutinho, PhD, and Alexander S. Kauffman, PhD, in a 2019 review of the brain’s role in PCOS.
These problems may be bidirectional or part of various feedback loops. Sleep apnea is more common in people with PCOS, Dr. Tyson noted, but sleep apnea is also linked to cardiovascular, metabolic, and depression risks, and depression can play a role in obesity, which increases the risk of obstructive sleep apnea. “So you’re in this vicious cycle,” Dr. Tyson said. That’s why she also believes it’s important to change the dialogue and perspective on PCOS, to reduce the stigma attached to it, and work with patients to empower them in treating its symptoms and reducing their risk of comorbidities.
Recent and upcoming changes in treatment
Current treatment of PCOS already changes according to the symptoms posing the greatest problems at each stage of a person’s life, Dr. Hudson said. Younger women tend to be more bothered about the cosmetic effects of PCOS, including hair growth patterns and acne, but as they grow out of adolescence and into their 20s and 30s, infertility becomes a bigger concern for many. Then, as they start approaching menopause, metabolic and cardiovascular issues take the lead, with more of a focus on lipids, diabetes risk, and heart health.
In some ways, management of PCOS hasn’t changed much in the past several decades, except in an increased awareness of the metabolic and cardiovascular risks, which has led to more frequent screening to catch potential conditions earlier in life. What has changed, however, is improvements in the treatments used for symptoms, such as expanded bariatric surgery options and GLP-1 agonists for treating obesity. Other examples include better options for menstrual management, such as new progesterone IUDs, and optimized fertility treatments, Dr. Tyson said.
“I think with more of these large-scale studies about the pathophysiology of PCOS and how it may look in different people and the different outcomes, we may be able to tailor our treatments even further,” Dr. Tyson said. She emphasized the importance of identifying the condition early, particularly in adolescents, even if it’s identifying young people at risk for the condition rather than actually having it yet.
Early identification “gives us this chance to do a lot of preventative care and motivate older teens to have a great lifestyle, work on their diet and exercise, and manage cardiovascular” risk factors, Dr. Tyson said.
“What we do know and recognize is that there’s so many spokes to this PCOS wheel that there really should be a multidisciplinary approach to care,” Dr. Tyson said. “When I think about who would be the real doctors for patients with PCOS, these would be gynecologists, endocrinologists, dermatologists, nutritionists, psychologists, sleep specialists, and primary care at a minimum.”
Dr. Pal worries that the label of PCOS leaves it in the laps of ob.gyns. whereas, “if it was called something else, everybody would be involved in being vigilant and managing those patients.” She frequently reiterated that the label of PCOS is less important than ensuring clinicians treat the symptoms that most bother the patient.
And even if kisspeptin does play a causal role in PCOS for some patients, it’s only a subset of individuals with PCOS who would benefit from therapies developed to target it. Given the complexity of the syndrome and its many manifestations, a “galaxy of pathways” are involved in different potential subtypes of the condition. “You can’t treat PCOS as one entity,” Dr. Pal said.
Still, Dr. Hudson is optimistic that the research into potential neuroendocrine contributions to PCOS will yield therapies that go beyond just managing symptoms.
“There aren’t a lot of treatments available yet, but there may be some on the horizon,” Dr. Hudson said. “We’re still in this very primitive stage in terms of therapeutics, where we’re only addressing specific symptoms, and we haven’t been able to really address the underlying cause because we haven’t understood it as well and because we don’t have therapies that can target it,” Dr. Hudson said. “But once there are therapies developed that will target some of these central mechanisms, I think it will change completely the approach to treating PCOS for patients.”
This story was updated on Sept. 6, 2022.
Polycystic ovary syndrome (PCOS) affects an estimated 8%-13% of women, and yet “it has been quite a black box for many years,” as Margo Hudson, MD, an assistant professor of endocrinology, diabetes, and hypertension at Harvard Medical School, Boston, puts it. That black box encompasses not only uncertainty about the etiology and pathophysiology of the condition but even what constitutes a diagnosis.
Even the international guidelines on PCOS management endorsed by the American Society for Reproductive Medicine – a document developed over 15 months with the input of 37 medical organizations covering 71 countries – notes that PCOS diagnosis is “controversial and assessment and management are inconsistent.” The result, the guidelines note, is that “the needs of women with PCOS are not being adequately met.”
One of the earliest diagnostic criteria, defined in 1990 by the National Institutes of Health, required only hyperandrogenism and irregular menstruation. Then the 2003 Rotterdam Criteria added presence of polycystic ovaries on ultrasound as a third criterion. Then the Androgen Excess Society determined that PCOS required presence of hyperandrogenism with either polycystic ovaries or oligo/amenorrhea anovulation. Yet the Endocrine Society notes that excess androgen levels are seen in 60%-80% of those with PCOS, suggesting it’s not an essential requirement for diagnosis, leaving most to diagnose it in people who have two of the three key criteria. The only real agreement on diagnosis is the need to eliminate other potential diagnoses first, making PCOS always a diagnosis of exclusion.
Further, though PCOS is known as the leading cause of infertility in women, it is more than a reproductive condition, with metabolic and psychological features as well. Then there is the range of comorbidities, none of which occur in all patients with PCOS but all of which occur in a majority and which are themselves interrelated. Insulin resistance is a common feature, occurring in 50%-70% of people with PCOS. Accordingly, metabolic syndrome occurs in at least a third of people with PCOS and type 2 diabetes prevalence is higher in those with PCOS as well.
Obesity occurs in an estimated 80% of women with PCOS in the United States, though it affects only about 50% of women with PCOS outside the United States, and those with PCOS have an increased risk of hypertension. Mood disorders, particularly anxiety and depression but also, to a lesser extent, bipolar disorder and obsessive-compulsive disorder, are more likely in people with PCOS. And given that these comorbidities are all cardiovascular risk factors, it’s unsurprising that recent studies are finding those with PCOS to be at greater risk for cardiometabolic disease and major cardiovascular events.
“The reality is that PCOS is a heterogenous entity. It’s not one thing – it’s a syndrome,” Lubna Pal, MBBS, a professor of ob.gyn. and director of the PCOS Program at Yale University, New Haven, Conn., said in an interview. A whole host of factors are likely playing a role in the causes of PCOS, and those factors interact differently within different people. “We’re looking at things like lipid metabolism, fetal origins, the gut microbiome, genetics, epigenetics, and then dietary and environmental factors,” Nichole Tyson, MD, division chief of pediatric and adolescent gynecology and a clinical associate professor at Stanford (Calif.) Medicine Children’s Health, said in an interview. And most studies have identified associations that may or may not be causal. Take, for example, endocrine disruptors. BPA levels have been shown to be higher in women with PCOS than women without, but that correlation may or may not be related to the etiology of the condition.
The hypothalamic-pituitary-gonadal axis
In trying to understand the pathophysiology of the condition, much of the latest research has zeroed in on potential mechanisms in the hypothalamic-pituitary-gonadal axis. “A consistent feature of PCOS is disordered gonadotropin secretion with elevated mean LH [luteinizing hormone], low or low normal FSH [follicle-stimulating hormone], and a persistently rapid frequency of GnRH [gonadotropin-releasing hormone] pulse secretion,” wrote authors of a scientific statement on aspects of PCOS.
“I think the balance is heading more to central neurologic control of the reproductive system and that disturbances there impact the GnRH cells in the hypothalamus, which then go on to give us the findings that we can measure peripherally with the LH-FSH ratio,” Dr. Hudson said in an interview.
The increased LH levels are thought to be a major driver of increased androgen levels. Current thinking suggests that the primary driver of increased LH is GnRH pulsatility, supported not only by human studies but by animal models as well. This leads to the question of what drives GnRH dysregulation. One hypothesis posits that GABA neurons play a role here, given findings that GABA levels in cerebrospinal fluid were higher in women with PCOS than those with normal ovulation.
But the culprit garnering the most attention is kisspeptin, a protein encoded by the KISS1 gene that stimulates GnRH neurons and has been linked to regulation of LH and FSH secretion. Kisspeptin, along with neurokinin B and dynorphin, is part of the triumvirate that comprises KNDy neurons, also recently implicated in menopausal vasomotor symptoms. Multiple systematic reviewsand meta-analyses have found a correlation between higher kisspeptin levels in the blood and higher circulating LH levels, regardless of body mass index. While kisspeptin is expressed in several tissues, including liver, pancreas, gonad, and adipose, it’s neural kisspeptin signaling that appears most likely to play a role in activating GnRH hormones and disrupting normal function of the hypothalamic-pituitary-gonadal axis.
But as noted, in at least one systematic review of kisspeptin and PCOS, “findings from animal studies suggest that kisspeptin levels are not increased in all subtypes of PCOS.” And another review found “altered” levels of kisspeptin levels in non-PCOS patients who had obesity, potentially raising questions about any associations between kisspeptin and obesity or insulin resistance.
Remaining chicken-and-egg questions
A hallmark of PCOS has long been, and continues to be, the string of chicken-or-egg questions that plague understanding of it. One of these is how depression and anxiety fit into the etiology of PCOS. Exploring the role of specific neurons that may overstimulate GnRH pulsatility may hold clues to a common underlying mechanism for the involvement of depression and anxiety in patients with PCOS, Dr. Hudson speculated. While previous assumptions often attributed depression and anxiety in PCOS to the symptoms – such as thin scalp hair and increased facial hair, excess weight, acne, and irregular periods – Dr. Hudson pointed out that women can address many of these symptoms with laser hair removal, weight loss, acne treatment, and similar interventions, yet they still have a lot of underlying mental health issues.
It’s also unclear whether metabolic factors so common with PCOS, particularly insulin resistance and obesity, are a result of the condition or are contributors to it. Is insulin resistance contributing to dysregulation in the neurons that interferes with normal functioning of the hypothalamic-pituitary-adrenal axis? Is abnormal functioning along this axis contributing to insulin resistance? Or neither? Or both? Or does it depend? The authors of one paper wrote that “insulin may play both direct and indirect roles in the pathogenesis of androgen excess in PCOS,” since insulin can “stimulate ovarian androgen production” and “enhance ovarian growth and follicular cyst formation in rats.”
Dr. Pal noted that “obesity itself can evolve into a PCOS-like picture,” raising questions about whether obesity or insulin resistance might be part of the causal pathway to PCOS, or whether either can trigger its development in those genetically predisposed.
“Obesity does appear to exacerbate many aspects of the PCOS phenotype, particularly those risk factors related to metabolic syndrome,” wrote the authors of a scientific statement on aspects of PCOS, but they add that “it is currently debated whether obesity per se can cause PCOS.” While massive weight loss in those with PCOS and obesity has improved multiple reproductive and metabolic issues, it hasn’t resolved all of them, they write.
Dr. Hudson said she expects there’s “some degree of appetite dysregulation and metabolic dysregulation” that contributes, but then there are other women who don’t have much of an appetite or overeat and still struggle with their weight. Evidence has also found insulin resistance in women of normal weight with PCOS. “There may be some kind of metabolic dysregulation that they have at some level, and others are clearly bothered by overeating,” Dr. Hudson said.
Similarly, it’s not clear whether the recent discovery of increased cardiovascular risks in people with PCOS is a result of the comorbidities so common with PCOS, such as obesity, or whether an underlying mechanism links the cardiovascular risk and the dysregulation of hormones. Dr. Pal would argue that, again, it’s probably both, depending on the patient.
Then there is the key feature of hyperandrogenemia. “An outstanding debate is whether the elevated androgens in PCOS women are merely a downstream endocrine response to hyperactive GnRH and LH secretion driving the ovary, or do the elevated androgens themselves act in the brain (or pituitary) during development and/or adulthood to sculpt and maintain the hypersecretion of GnRH and LH?” wrote Eulalia A. Coutinho, PhD, and Alexander S. Kauffman, PhD, in a 2019 review of the brain’s role in PCOS.
These problems may be bidirectional or part of various feedback loops. Sleep apnea is more common in people with PCOS, Dr. Tyson noted, but sleep apnea is also linked to cardiovascular, metabolic, and depression risks, and depression can play a role in obesity, which increases the risk of obstructive sleep apnea. “So you’re in this vicious cycle,” Dr. Tyson said. That’s why she also believes it’s important to change the dialogue and perspective on PCOS, to reduce the stigma attached to it, and work with patients to empower them in treating its symptoms and reducing their risk of comorbidities.
Recent and upcoming changes in treatment
Current treatment of PCOS already changes according to the symptoms posing the greatest problems at each stage of a person’s life, Dr. Hudson said. Younger women tend to be more bothered about the cosmetic effects of PCOS, including hair growth patterns and acne, but as they grow out of adolescence and into their 20s and 30s, infertility becomes a bigger concern for many. Then, as they start approaching menopause, metabolic and cardiovascular issues take the lead, with more of a focus on lipids, diabetes risk, and heart health.
In some ways, management of PCOS hasn’t changed much in the past several decades, except in an increased awareness of the metabolic and cardiovascular risks, which has led to more frequent screening to catch potential conditions earlier in life. What has changed, however, is improvements in the treatments used for symptoms, such as expanded bariatric surgery options and GLP-1 agonists for treating obesity. Other examples include better options for menstrual management, such as new progesterone IUDs, and optimized fertility treatments, Dr. Tyson said.
“I think with more of these large-scale studies about the pathophysiology of PCOS and how it may look in different people and the different outcomes, we may be able to tailor our treatments even further,” Dr. Tyson said. She emphasized the importance of identifying the condition early, particularly in adolescents, even if it’s identifying young people at risk for the condition rather than actually having it yet.
Early identification “gives us this chance to do a lot of preventative care and motivate older teens to have a great lifestyle, work on their diet and exercise, and manage cardiovascular” risk factors, Dr. Tyson said.
“What we do know and recognize is that there’s so many spokes to this PCOS wheel that there really should be a multidisciplinary approach to care,” Dr. Tyson said. “When I think about who would be the real doctors for patients with PCOS, these would be gynecologists, endocrinologists, dermatologists, nutritionists, psychologists, sleep specialists, and primary care at a minimum.”
Dr. Pal worries that the label of PCOS leaves it in the laps of ob.gyns. whereas, “if it was called something else, everybody would be involved in being vigilant and managing those patients.” She frequently reiterated that the label of PCOS is less important than ensuring clinicians treat the symptoms that most bother the patient.
And even if kisspeptin does play a causal role in PCOS for some patients, it’s only a subset of individuals with PCOS who would benefit from therapies developed to target it. Given the complexity of the syndrome and its many manifestations, a “galaxy of pathways” are involved in different potential subtypes of the condition. “You can’t treat PCOS as one entity,” Dr. Pal said.
Still, Dr. Hudson is optimistic that the research into potential neuroendocrine contributions to PCOS will yield therapies that go beyond just managing symptoms.
“There aren’t a lot of treatments available yet, but there may be some on the horizon,” Dr. Hudson said. “We’re still in this very primitive stage in terms of therapeutics, where we’re only addressing specific symptoms, and we haven’t been able to really address the underlying cause because we haven’t understood it as well and because we don’t have therapies that can target it,” Dr. Hudson said. “But once there are therapies developed that will target some of these central mechanisms, I think it will change completely the approach to treating PCOS for patients.”
This story was updated on Sept. 6, 2022.
Polycystic ovary syndrome (PCOS) affects an estimated 8%-13% of women, and yet “it has been quite a black box for many years,” as Margo Hudson, MD, an assistant professor of endocrinology, diabetes, and hypertension at Harvard Medical School, Boston, puts it. That black box encompasses not only uncertainty about the etiology and pathophysiology of the condition but even what constitutes a diagnosis.
Even the international guidelines on PCOS management endorsed by the American Society for Reproductive Medicine – a document developed over 15 months with the input of 37 medical organizations covering 71 countries – notes that PCOS diagnosis is “controversial and assessment and management are inconsistent.” The result, the guidelines note, is that “the needs of women with PCOS are not being adequately met.”
One of the earliest diagnostic criteria, defined in 1990 by the National Institutes of Health, required only hyperandrogenism and irregular menstruation. Then the 2003 Rotterdam Criteria added presence of polycystic ovaries on ultrasound as a third criterion. Then the Androgen Excess Society determined that PCOS required presence of hyperandrogenism with either polycystic ovaries or oligo/amenorrhea anovulation. Yet the Endocrine Society notes that excess androgen levels are seen in 60%-80% of those with PCOS, suggesting it’s not an essential requirement for diagnosis, leaving most to diagnose it in people who have two of the three key criteria. The only real agreement on diagnosis is the need to eliminate other potential diagnoses first, making PCOS always a diagnosis of exclusion.
Further, though PCOS is known as the leading cause of infertility in women, it is more than a reproductive condition, with metabolic and psychological features as well. Then there is the range of comorbidities, none of which occur in all patients with PCOS but all of which occur in a majority and which are themselves interrelated. Insulin resistance is a common feature, occurring in 50%-70% of people with PCOS. Accordingly, metabolic syndrome occurs in at least a third of people with PCOS and type 2 diabetes prevalence is higher in those with PCOS as well.
Obesity occurs in an estimated 80% of women with PCOS in the United States, though it affects only about 50% of women with PCOS outside the United States, and those with PCOS have an increased risk of hypertension. Mood disorders, particularly anxiety and depression but also, to a lesser extent, bipolar disorder and obsessive-compulsive disorder, are more likely in people with PCOS. And given that these comorbidities are all cardiovascular risk factors, it’s unsurprising that recent studies are finding those with PCOS to be at greater risk for cardiometabolic disease and major cardiovascular events.
“The reality is that PCOS is a heterogenous entity. It’s not one thing – it’s a syndrome,” Lubna Pal, MBBS, a professor of ob.gyn. and director of the PCOS Program at Yale University, New Haven, Conn., said in an interview. A whole host of factors are likely playing a role in the causes of PCOS, and those factors interact differently within different people. “We’re looking at things like lipid metabolism, fetal origins, the gut microbiome, genetics, epigenetics, and then dietary and environmental factors,” Nichole Tyson, MD, division chief of pediatric and adolescent gynecology and a clinical associate professor at Stanford (Calif.) Medicine Children’s Health, said in an interview. And most studies have identified associations that may or may not be causal. Take, for example, endocrine disruptors. BPA levels have been shown to be higher in women with PCOS than women without, but that correlation may or may not be related to the etiology of the condition.
The hypothalamic-pituitary-gonadal axis
In trying to understand the pathophysiology of the condition, much of the latest research has zeroed in on potential mechanisms in the hypothalamic-pituitary-gonadal axis. “A consistent feature of PCOS is disordered gonadotropin secretion with elevated mean LH [luteinizing hormone], low or low normal FSH [follicle-stimulating hormone], and a persistently rapid frequency of GnRH [gonadotropin-releasing hormone] pulse secretion,” wrote authors of a scientific statement on aspects of PCOS.
“I think the balance is heading more to central neurologic control of the reproductive system and that disturbances there impact the GnRH cells in the hypothalamus, which then go on to give us the findings that we can measure peripherally with the LH-FSH ratio,” Dr. Hudson said in an interview.
The increased LH levels are thought to be a major driver of increased androgen levels. Current thinking suggests that the primary driver of increased LH is GnRH pulsatility, supported not only by human studies but by animal models as well. This leads to the question of what drives GnRH dysregulation. One hypothesis posits that GABA neurons play a role here, given findings that GABA levels in cerebrospinal fluid were higher in women with PCOS than those with normal ovulation.
But the culprit garnering the most attention is kisspeptin, a protein encoded by the KISS1 gene that stimulates GnRH neurons and has been linked to regulation of LH and FSH secretion. Kisspeptin, along with neurokinin B and dynorphin, is part of the triumvirate that comprises KNDy neurons, also recently implicated in menopausal vasomotor symptoms. Multiple systematic reviewsand meta-analyses have found a correlation between higher kisspeptin levels in the blood and higher circulating LH levels, regardless of body mass index. While kisspeptin is expressed in several tissues, including liver, pancreas, gonad, and adipose, it’s neural kisspeptin signaling that appears most likely to play a role in activating GnRH hormones and disrupting normal function of the hypothalamic-pituitary-gonadal axis.
But as noted, in at least one systematic review of kisspeptin and PCOS, “findings from animal studies suggest that kisspeptin levels are not increased in all subtypes of PCOS.” And another review found “altered” levels of kisspeptin levels in non-PCOS patients who had obesity, potentially raising questions about any associations between kisspeptin and obesity or insulin resistance.
Remaining chicken-and-egg questions
A hallmark of PCOS has long been, and continues to be, the string of chicken-or-egg questions that plague understanding of it. One of these is how depression and anxiety fit into the etiology of PCOS. Exploring the role of specific neurons that may overstimulate GnRH pulsatility may hold clues to a common underlying mechanism for the involvement of depression and anxiety in patients with PCOS, Dr. Hudson speculated. While previous assumptions often attributed depression and anxiety in PCOS to the symptoms – such as thin scalp hair and increased facial hair, excess weight, acne, and irregular periods – Dr. Hudson pointed out that women can address many of these symptoms with laser hair removal, weight loss, acne treatment, and similar interventions, yet they still have a lot of underlying mental health issues.
It’s also unclear whether metabolic factors so common with PCOS, particularly insulin resistance and obesity, are a result of the condition or are contributors to it. Is insulin resistance contributing to dysregulation in the neurons that interferes with normal functioning of the hypothalamic-pituitary-adrenal axis? Is abnormal functioning along this axis contributing to insulin resistance? Or neither? Or both? Or does it depend? The authors of one paper wrote that “insulin may play both direct and indirect roles in the pathogenesis of androgen excess in PCOS,” since insulin can “stimulate ovarian androgen production” and “enhance ovarian growth and follicular cyst formation in rats.”
Dr. Pal noted that “obesity itself can evolve into a PCOS-like picture,” raising questions about whether obesity or insulin resistance might be part of the causal pathway to PCOS, or whether either can trigger its development in those genetically predisposed.
“Obesity does appear to exacerbate many aspects of the PCOS phenotype, particularly those risk factors related to metabolic syndrome,” wrote the authors of a scientific statement on aspects of PCOS, but they add that “it is currently debated whether obesity per se can cause PCOS.” While massive weight loss in those with PCOS and obesity has improved multiple reproductive and metabolic issues, it hasn’t resolved all of them, they write.
Dr. Hudson said she expects there’s “some degree of appetite dysregulation and metabolic dysregulation” that contributes, but then there are other women who don’t have much of an appetite or overeat and still struggle with their weight. Evidence has also found insulin resistance in women of normal weight with PCOS. “There may be some kind of metabolic dysregulation that they have at some level, and others are clearly bothered by overeating,” Dr. Hudson said.
Similarly, it’s not clear whether the recent discovery of increased cardiovascular risks in people with PCOS is a result of the comorbidities so common with PCOS, such as obesity, or whether an underlying mechanism links the cardiovascular risk and the dysregulation of hormones. Dr. Pal would argue that, again, it’s probably both, depending on the patient.
Then there is the key feature of hyperandrogenemia. “An outstanding debate is whether the elevated androgens in PCOS women are merely a downstream endocrine response to hyperactive GnRH and LH secretion driving the ovary, or do the elevated androgens themselves act in the brain (or pituitary) during development and/or adulthood to sculpt and maintain the hypersecretion of GnRH and LH?” wrote Eulalia A. Coutinho, PhD, and Alexander S. Kauffman, PhD, in a 2019 review of the brain’s role in PCOS.
These problems may be bidirectional or part of various feedback loops. Sleep apnea is more common in people with PCOS, Dr. Tyson noted, but sleep apnea is also linked to cardiovascular, metabolic, and depression risks, and depression can play a role in obesity, which increases the risk of obstructive sleep apnea. “So you’re in this vicious cycle,” Dr. Tyson said. That’s why she also believes it’s important to change the dialogue and perspective on PCOS, to reduce the stigma attached to it, and work with patients to empower them in treating its symptoms and reducing their risk of comorbidities.
Recent and upcoming changes in treatment
Current treatment of PCOS already changes according to the symptoms posing the greatest problems at each stage of a person’s life, Dr. Hudson said. Younger women tend to be more bothered about the cosmetic effects of PCOS, including hair growth patterns and acne, but as they grow out of adolescence and into their 20s and 30s, infertility becomes a bigger concern for many. Then, as they start approaching menopause, metabolic and cardiovascular issues take the lead, with more of a focus on lipids, diabetes risk, and heart health.
In some ways, management of PCOS hasn’t changed much in the past several decades, except in an increased awareness of the metabolic and cardiovascular risks, which has led to more frequent screening to catch potential conditions earlier in life. What has changed, however, is improvements in the treatments used for symptoms, such as expanded bariatric surgery options and GLP-1 agonists for treating obesity. Other examples include better options for menstrual management, such as new progesterone IUDs, and optimized fertility treatments, Dr. Tyson said.
“I think with more of these large-scale studies about the pathophysiology of PCOS and how it may look in different people and the different outcomes, we may be able to tailor our treatments even further,” Dr. Tyson said. She emphasized the importance of identifying the condition early, particularly in adolescents, even if it’s identifying young people at risk for the condition rather than actually having it yet.
Early identification “gives us this chance to do a lot of preventative care and motivate older teens to have a great lifestyle, work on their diet and exercise, and manage cardiovascular” risk factors, Dr. Tyson said.
“What we do know and recognize is that there’s so many spokes to this PCOS wheel that there really should be a multidisciplinary approach to care,” Dr. Tyson said. “When I think about who would be the real doctors for patients with PCOS, these would be gynecologists, endocrinologists, dermatologists, nutritionists, psychologists, sleep specialists, and primary care at a minimum.”
Dr. Pal worries that the label of PCOS leaves it in the laps of ob.gyns. whereas, “if it was called something else, everybody would be involved in being vigilant and managing those patients.” She frequently reiterated that the label of PCOS is less important than ensuring clinicians treat the symptoms that most bother the patient.
And even if kisspeptin does play a causal role in PCOS for some patients, it’s only a subset of individuals with PCOS who would benefit from therapies developed to target it. Given the complexity of the syndrome and its many manifestations, a “galaxy of pathways” are involved in different potential subtypes of the condition. “You can’t treat PCOS as one entity,” Dr. Pal said.
Still, Dr. Hudson is optimistic that the research into potential neuroendocrine contributions to PCOS will yield therapies that go beyond just managing symptoms.
“There aren’t a lot of treatments available yet, but there may be some on the horizon,” Dr. Hudson said. “We’re still in this very primitive stage in terms of therapeutics, where we’re only addressing specific symptoms, and we haven’t been able to really address the underlying cause because we haven’t understood it as well and because we don’t have therapies that can target it,” Dr. Hudson said. “But once there are therapies developed that will target some of these central mechanisms, I think it will change completely the approach to treating PCOS for patients.”
This story was updated on Sept. 6, 2022.
Large genetic study links 72 genes to autism spectrum disorders
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
FROM NATURE GENETICS
What are growing pains? Turns out no one really knows
Just about every child hears it growing up: An ache in the leg? “Growing pains.” A dull pain in the side? “Growing pains.”
The catch-all phrase for random pains that children and teens have is so common that it even inspired the name of a 1980s sitcom. Yet when scientists dug into the evidence to find out what growing pains actually are, they found out that no one really knows. The definitions were as random and all over the place as the very pains that kids complain about, the researchers report in the journal Pediatrics.
Although some studies have suggested that up to a third of children have growing pains, the term has long seemed more like folk medicine than an actual medical diagnosis. Even so, parents, teachers, and doctors frequently use it when they have no other obvious answer to a particular pain a child or teen might describe.
A group of researchers at the University of Sydney in Australia wanted to find out if there was any research offering a more precise definition or criteria. They combed through eight databases for any papers that mentioned growing pains or growth pains in children or adolescents. They found 145 studies and set out to look for common ground: Where do growing pains occur? At what age do they start? Are there any patterns? Risk factors? Common clinical features? Relationships to particular activities?
What they found was that there is “no consensus whatsoever as to what growing pains really are, what they mean, how they’re defined, and how they should be diagnosed,” coauthor Steven J. Kamper, PhD, explained in a video about the findings. “The definitions were really variable, really vague, and sometimes downright contradictory,” he said. “Some studies would suggest growing pains happen in the arms, some in the lower limbs only. Some said it was about muscles, some about joints.”
The closest thing to consistency that they found was that exactly half the studies mentioned the pain being in the lower limbs. Nearly half (48%) described it as happening in the evening or nighttime, 42% said it was recurring, 35% reported it as occurring in youths with an otherwise normal physical exam, and 31% said the pain occurred on both sides of the body. Besides these, no other common feature was mentioned in more than 30% of the studies.
“Really curiously,” Dr. Kamper said, “more than 80% said nothing about the age at which these growing pains come on.” And 93% of the studies didn’t even mention growth as being related to the pain at all.
Several studies did acknowledge that the cause of growing pains is unknown, and several others considered it a diagnosis of exclusion – that is, it’s the diagnosis when everything else has been ruled out.
But that’s hardly a satisfactory explanation for kids and their families, so the researchers drew the only reasonable conclusion they could from what they found: “We think it’s important that the term is not used without some qualification or clarification, whether by researchers or clinicians,” Dr. Kamper said.
A version of this article first appeared on WebMD.com.
Just about every child hears it growing up: An ache in the leg? “Growing pains.” A dull pain in the side? “Growing pains.”
The catch-all phrase for random pains that children and teens have is so common that it even inspired the name of a 1980s sitcom. Yet when scientists dug into the evidence to find out what growing pains actually are, they found out that no one really knows. The definitions were as random and all over the place as the very pains that kids complain about, the researchers report in the journal Pediatrics.
Although some studies have suggested that up to a third of children have growing pains, the term has long seemed more like folk medicine than an actual medical diagnosis. Even so, parents, teachers, and doctors frequently use it when they have no other obvious answer to a particular pain a child or teen might describe.
A group of researchers at the University of Sydney in Australia wanted to find out if there was any research offering a more precise definition or criteria. They combed through eight databases for any papers that mentioned growing pains or growth pains in children or adolescents. They found 145 studies and set out to look for common ground: Where do growing pains occur? At what age do they start? Are there any patterns? Risk factors? Common clinical features? Relationships to particular activities?
What they found was that there is “no consensus whatsoever as to what growing pains really are, what they mean, how they’re defined, and how they should be diagnosed,” coauthor Steven J. Kamper, PhD, explained in a video about the findings. “The definitions were really variable, really vague, and sometimes downright contradictory,” he said. “Some studies would suggest growing pains happen in the arms, some in the lower limbs only. Some said it was about muscles, some about joints.”
The closest thing to consistency that they found was that exactly half the studies mentioned the pain being in the lower limbs. Nearly half (48%) described it as happening in the evening or nighttime, 42% said it was recurring, 35% reported it as occurring in youths with an otherwise normal physical exam, and 31% said the pain occurred on both sides of the body. Besides these, no other common feature was mentioned in more than 30% of the studies.
“Really curiously,” Dr. Kamper said, “more than 80% said nothing about the age at which these growing pains come on.” And 93% of the studies didn’t even mention growth as being related to the pain at all.
Several studies did acknowledge that the cause of growing pains is unknown, and several others considered it a diagnosis of exclusion – that is, it’s the diagnosis when everything else has been ruled out.
But that’s hardly a satisfactory explanation for kids and their families, so the researchers drew the only reasonable conclusion they could from what they found: “We think it’s important that the term is not used without some qualification or clarification, whether by researchers or clinicians,” Dr. Kamper said.
A version of this article first appeared on WebMD.com.
Just about every child hears it growing up: An ache in the leg? “Growing pains.” A dull pain in the side? “Growing pains.”
The catch-all phrase for random pains that children and teens have is so common that it even inspired the name of a 1980s sitcom. Yet when scientists dug into the evidence to find out what growing pains actually are, they found out that no one really knows. The definitions were as random and all over the place as the very pains that kids complain about, the researchers report in the journal Pediatrics.
Although some studies have suggested that up to a third of children have growing pains, the term has long seemed more like folk medicine than an actual medical diagnosis. Even so, parents, teachers, and doctors frequently use it when they have no other obvious answer to a particular pain a child or teen might describe.
A group of researchers at the University of Sydney in Australia wanted to find out if there was any research offering a more precise definition or criteria. They combed through eight databases for any papers that mentioned growing pains or growth pains in children or adolescents. They found 145 studies and set out to look for common ground: Where do growing pains occur? At what age do they start? Are there any patterns? Risk factors? Common clinical features? Relationships to particular activities?
What they found was that there is “no consensus whatsoever as to what growing pains really are, what they mean, how they’re defined, and how they should be diagnosed,” coauthor Steven J. Kamper, PhD, explained in a video about the findings. “The definitions were really variable, really vague, and sometimes downright contradictory,” he said. “Some studies would suggest growing pains happen in the arms, some in the lower limbs only. Some said it was about muscles, some about joints.”
The closest thing to consistency that they found was that exactly half the studies mentioned the pain being in the lower limbs. Nearly half (48%) described it as happening in the evening or nighttime, 42% said it was recurring, 35% reported it as occurring in youths with an otherwise normal physical exam, and 31% said the pain occurred on both sides of the body. Besides these, no other common feature was mentioned in more than 30% of the studies.
“Really curiously,” Dr. Kamper said, “more than 80% said nothing about the age at which these growing pains come on.” And 93% of the studies didn’t even mention growth as being related to the pain at all.
Several studies did acknowledge that the cause of growing pains is unknown, and several others considered it a diagnosis of exclusion – that is, it’s the diagnosis when everything else has been ruled out.
But that’s hardly a satisfactory explanation for kids and their families, so the researchers drew the only reasonable conclusion they could from what they found: “We think it’s important that the term is not used without some qualification or clarification, whether by researchers or clinicians,” Dr. Kamper said.
A version of this article first appeared on WebMD.com.
Drug-resistant epilepsy needs earlier surgical referral
, according to expert consensus recommendations from the International League Against Epilepsy (ILAE) published in the journal Epilepsia.
Comprehensive epilepsy care
Such a referral is not ”a commitment to undergo brain surgery,” wrote the authors of the new recommendations study, but surgical evaluations offer patients an opportunity to learn about the range of therapies available to them and to have their diagnosis verified, as well as learning about the cause and type of epilepsy they have, even if they ultimately do not pursue surgery.
”In fact, most patients with drug-resistant epilepsy do not end up undergoing surgery after referral, but still benefit from comprehensive epilepsy care improving quality of life and lowering mortality,” wrote lead author Lara Jehi, MD, professor of neurology and epilepsy specialist at Cleveland Clinic, and her colleagues. “A better characterization of the epilepsy can also help optimize medical therapy and address somatic, cognitive, behavioral, and psychiatric comorbidities.”
Is the diagnosis correct?
They noted that about one-third of patients referred to epilepsy centers with an apparent diagnosis of drug-resistant epilepsy actually have psychogenic nonepileptic seizures (PNES) – not epilepsy – and an early, accurate diagnosis of PNES can ensure they receive psychotherapy, stop taking antiseizure medications, and have better outcomes.
“These recommendations are necessary, as the delay to surgery and the overall underutilization of surgery have not improved much over the last 20 years,” said Selim R. Benbadis, MD, professor of neurology and director of the comprehensive epilepsy program at the University of South Florida and Tampa General Hospital. “Comprehensive epilepsy centers offer more than surgery, including correct and precise diagnosis, drug options, three [Food and Drug Administration]–approved neurostimulation options, and more,” said Dr. Benbadis, who was not involved in the development of these recommendations.
Consensus recommendations
On behalf of the the ILAE’s Surgical Therapies Commission, the authors used the Delphi consensus process to develop expert consensus recommendations on when to refer patients with epilepsy to surgery. They conducted three Delphi rounds on 51 clinical scenarios with 61 epileptologists (38% of participants), epilepsy neurosurgeons (34%), neurologists (23%), neuropsychiatrists (2%), and neuropsychologists (3%) from 28 countries. Most of clinicians focused on adults (39%) or adults and children (41%) while 20% focused only on pediatric epilepsy.
The physicians involved had a median 22 years of practice and represented all six ILAE regions: 30% from North America, 28% from Europe, 18% from Asia/Oceania, 13% from Latin America, 7% from the Eastern Mediterranean, and 4% from Africa.
The result of these rounds were three key recommendations arising from the consensus of experts consulted. First, every patient up to 70 years old who has drug-resistant epilepsy should be offered the option of a surgical evaluation as soon as it’s apparent that they have drug resistance. The option for surgical evaluation should be provided independent of their sex or socioeconomic status and regardless of how long they have had epilepsy, their seizure type, their epilepsy type, localization, and their comorbidities, ”including severe psychiatric comorbidity like psychogenic nonepileptic seizures (PNES) or substance abuse if patients are cooperative with management,” the authors wrote.
”Resective surgery can improve quality of life and cognitive outcomes and is the only treatment demonstrated to improve survival and reverse excess mortality attributed to drug-resistant epilepsy,” the authors wrote. Evidence supports that surgical evaluation is the most cost-effective approach to treating drug-resistant epilepsy, they added. Yet, it still takes about 20 years with epilepsy before an adult patient might be referred, ”and the neurology community remains ambivalent due to ongoing barriers and misconceptions about epilepsy surgery,” they wrote.
The second recommendation is to consider a surgical referral for older patients with drug-resistant epilepsy who have no surgical contraindication. Physicians can also consider a referral for patients of any age who are seizure free while taking one to two antiseizure drugs but who have a brain lesion in the noneloquent cortex.
The third recommendation is not to offer surgery if a patient has an active substance dependency and is not cooperative with management.
“Although there is some evidence that seizure outcomes are no different in individuals with active substance use disorder who have epilepsy surgery, the literature suggests increased perioperative surgical and anesthetic risk in this cohort,” the authors wrote. ”Patients with active substance abuse are more likely to be nonadherent with their seizure medications, and to leave the hospital against medical advice.”
One area where the participants did not reach consensus was regarding whether to refer patients who did not become seizure-free after trying just one “tolerated and appropriately chosen” antiseizure medication. Half (49%) said they would be unlikely to refer or would never refer that patient while 44% said they would likely or always refer them, and 7% weren’t sure.
The ‘next level’ of epilepsy care
“Similar recommendations have been published before, by the National Association of Epilepsy Centers, more than once, and have not changed the referral patterns,” Dr. Benbadis said. “They are not implemented by the average general neurologist.” While there are many reasons for this, one with a relativity simple fix is to adjust the language doctors use to when talking with patients about getting an evaluation, Dr. Benbadis said. ”The key is to rephrase: Instead of referrals ‘for surgery,’ which can be scary to many neurologists and patients, we should use more general terms, like referrals for the ‘next level of care by epilepsy specialists,’ ” said Dr. Benbadis, who advocated for this change in terminology in a 2019 editorial. Such language is less frightening and can ease patients’ concerns about going to an epilepsy center where they can learn about more options than just surgery.
Further, surgical options have expanded in recent years, including the development of laser interstitial thermal therapy and neuromodulation. “Identifying candidacy for any of these approaches starts with a surgical referral, so a timely evaluation is key,” the authors wrote.
Referral delays persist
Despite the strong evidence for timely referrals, delays have persisted for decades, said Dr. Benbadis, echoing what the authors describe. ”Despite the results of two randomized controlled trials showing that surgery for temporal lobe epilepsy in adults, and resective surgery in children, is superior to continued antiseizure medications both in terms of seizure freedom and improved quality of life, the mean epilepsy duration to temporal lobe resection has persisted at over 20 years,” the authors wrote. ”Although drug resistance is reached with a mean latency of 9 years in epilepsy surgery candidates, these patients have experienced a decade of unabating seizures with detrimental effects including cognitive and psychiatric comorbidities, poor psychosocial outcomes, potential injuries, and risk of death.”
Surgery is not a ‘dangerous last resort’
The authors point out a variety of likely reasons for these delays, including patients experiencing temporary remissions with a new drug, lack of adequate health care access, overestimating surgery risks, and underestimating the seriousness and risk of death from ongoing seizures.
Dr. Benbadis agreed, referring to a “combination of lack of knowledge and unrealistic views about surgery outcomes and complications.” Patients and their neurologists think surgery is a “dangerous last resort, fraught with complications, and they don’t know the outcome, so it’s mainly that they are not very well-educated about epilepsy surgery,” he said. Complacency about a patient’s infrequent seizures plays a role as well, he added. “Their patient is having one seizure every 2 months, and they might say, ‘well, that’s okay, that’s not that bad,’ but it is when we can cure it.”
Similar factors are barriers to epilepsy surgery: “lack of knowledge or misconceptions about surgical risks, negative behaviors, or cultural issues and access issues.”
Another major barrier, both within neurology and throughout medicine in general, is that large academic centers that accept referrals, including epilepsy centers, have poor communication, follow-up, and scheduling, Dr. Benbadis said.
The authors provided a table with suggestions on potential solutions to those barriers, including identifying online resources to help doctors identify possible surgery candidates, such as www.toolsforepilepsy.com, and a range of educational resources. Ways to improve access and cost include mobile clinics, telehealth, coordinating with an epilepsy organization, and employing a multidisciplinary team that includes a social worker to help with support such as transportation and health insurance.
, according to expert consensus recommendations from the International League Against Epilepsy (ILAE) published in the journal Epilepsia.
Comprehensive epilepsy care
Such a referral is not ”a commitment to undergo brain surgery,” wrote the authors of the new recommendations study, but surgical evaluations offer patients an opportunity to learn about the range of therapies available to them and to have their diagnosis verified, as well as learning about the cause and type of epilepsy they have, even if they ultimately do not pursue surgery.
”In fact, most patients with drug-resistant epilepsy do not end up undergoing surgery after referral, but still benefit from comprehensive epilepsy care improving quality of life and lowering mortality,” wrote lead author Lara Jehi, MD, professor of neurology and epilepsy specialist at Cleveland Clinic, and her colleagues. “A better characterization of the epilepsy can also help optimize medical therapy and address somatic, cognitive, behavioral, and psychiatric comorbidities.”
Is the diagnosis correct?
They noted that about one-third of patients referred to epilepsy centers with an apparent diagnosis of drug-resistant epilepsy actually have psychogenic nonepileptic seizures (PNES) – not epilepsy – and an early, accurate diagnosis of PNES can ensure they receive psychotherapy, stop taking antiseizure medications, and have better outcomes.
“These recommendations are necessary, as the delay to surgery and the overall underutilization of surgery have not improved much over the last 20 years,” said Selim R. Benbadis, MD, professor of neurology and director of the comprehensive epilepsy program at the University of South Florida and Tampa General Hospital. “Comprehensive epilepsy centers offer more than surgery, including correct and precise diagnosis, drug options, three [Food and Drug Administration]–approved neurostimulation options, and more,” said Dr. Benbadis, who was not involved in the development of these recommendations.
Consensus recommendations
On behalf of the the ILAE’s Surgical Therapies Commission, the authors used the Delphi consensus process to develop expert consensus recommendations on when to refer patients with epilepsy to surgery. They conducted three Delphi rounds on 51 clinical scenarios with 61 epileptologists (38% of participants), epilepsy neurosurgeons (34%), neurologists (23%), neuropsychiatrists (2%), and neuropsychologists (3%) from 28 countries. Most of clinicians focused on adults (39%) or adults and children (41%) while 20% focused only on pediatric epilepsy.
The physicians involved had a median 22 years of practice and represented all six ILAE regions: 30% from North America, 28% from Europe, 18% from Asia/Oceania, 13% from Latin America, 7% from the Eastern Mediterranean, and 4% from Africa.
The result of these rounds were three key recommendations arising from the consensus of experts consulted. First, every patient up to 70 years old who has drug-resistant epilepsy should be offered the option of a surgical evaluation as soon as it’s apparent that they have drug resistance. The option for surgical evaluation should be provided independent of their sex or socioeconomic status and regardless of how long they have had epilepsy, their seizure type, their epilepsy type, localization, and their comorbidities, ”including severe psychiatric comorbidity like psychogenic nonepileptic seizures (PNES) or substance abuse if patients are cooperative with management,” the authors wrote.
”Resective surgery can improve quality of life and cognitive outcomes and is the only treatment demonstrated to improve survival and reverse excess mortality attributed to drug-resistant epilepsy,” the authors wrote. Evidence supports that surgical evaluation is the most cost-effective approach to treating drug-resistant epilepsy, they added. Yet, it still takes about 20 years with epilepsy before an adult patient might be referred, ”and the neurology community remains ambivalent due to ongoing barriers and misconceptions about epilepsy surgery,” they wrote.
The second recommendation is to consider a surgical referral for older patients with drug-resistant epilepsy who have no surgical contraindication. Physicians can also consider a referral for patients of any age who are seizure free while taking one to two antiseizure drugs but who have a brain lesion in the noneloquent cortex.
The third recommendation is not to offer surgery if a patient has an active substance dependency and is not cooperative with management.
“Although there is some evidence that seizure outcomes are no different in individuals with active substance use disorder who have epilepsy surgery, the literature suggests increased perioperative surgical and anesthetic risk in this cohort,” the authors wrote. ”Patients with active substance abuse are more likely to be nonadherent with their seizure medications, and to leave the hospital against medical advice.”
One area where the participants did not reach consensus was regarding whether to refer patients who did not become seizure-free after trying just one “tolerated and appropriately chosen” antiseizure medication. Half (49%) said they would be unlikely to refer or would never refer that patient while 44% said they would likely or always refer them, and 7% weren’t sure.
The ‘next level’ of epilepsy care
“Similar recommendations have been published before, by the National Association of Epilepsy Centers, more than once, and have not changed the referral patterns,” Dr. Benbadis said. “They are not implemented by the average general neurologist.” While there are many reasons for this, one with a relativity simple fix is to adjust the language doctors use to when talking with patients about getting an evaluation, Dr. Benbadis said. ”The key is to rephrase: Instead of referrals ‘for surgery,’ which can be scary to many neurologists and patients, we should use more general terms, like referrals for the ‘next level of care by epilepsy specialists,’ ” said Dr. Benbadis, who advocated for this change in terminology in a 2019 editorial. Such language is less frightening and can ease patients’ concerns about going to an epilepsy center where they can learn about more options than just surgery.
Further, surgical options have expanded in recent years, including the development of laser interstitial thermal therapy and neuromodulation. “Identifying candidacy for any of these approaches starts with a surgical referral, so a timely evaluation is key,” the authors wrote.
Referral delays persist
Despite the strong evidence for timely referrals, delays have persisted for decades, said Dr. Benbadis, echoing what the authors describe. ”Despite the results of two randomized controlled trials showing that surgery for temporal lobe epilepsy in adults, and resective surgery in children, is superior to continued antiseizure medications both in terms of seizure freedom and improved quality of life, the mean epilepsy duration to temporal lobe resection has persisted at over 20 years,” the authors wrote. ”Although drug resistance is reached with a mean latency of 9 years in epilepsy surgery candidates, these patients have experienced a decade of unabating seizures with detrimental effects including cognitive and psychiatric comorbidities, poor psychosocial outcomes, potential injuries, and risk of death.”
Surgery is not a ‘dangerous last resort’
The authors point out a variety of likely reasons for these delays, including patients experiencing temporary remissions with a new drug, lack of adequate health care access, overestimating surgery risks, and underestimating the seriousness and risk of death from ongoing seizures.
Dr. Benbadis agreed, referring to a “combination of lack of knowledge and unrealistic views about surgery outcomes and complications.” Patients and their neurologists think surgery is a “dangerous last resort, fraught with complications, and they don’t know the outcome, so it’s mainly that they are not very well-educated about epilepsy surgery,” he said. Complacency about a patient’s infrequent seizures plays a role as well, he added. “Their patient is having one seizure every 2 months, and they might say, ‘well, that’s okay, that’s not that bad,’ but it is when we can cure it.”
Similar factors are barriers to epilepsy surgery: “lack of knowledge or misconceptions about surgical risks, negative behaviors, or cultural issues and access issues.”
Another major barrier, both within neurology and throughout medicine in general, is that large academic centers that accept referrals, including epilepsy centers, have poor communication, follow-up, and scheduling, Dr. Benbadis said.
The authors provided a table with suggestions on potential solutions to those barriers, including identifying online resources to help doctors identify possible surgery candidates, such as www.toolsforepilepsy.com, and a range of educational resources. Ways to improve access and cost include mobile clinics, telehealth, coordinating with an epilepsy organization, and employing a multidisciplinary team that includes a social worker to help with support such as transportation and health insurance.
, according to expert consensus recommendations from the International League Against Epilepsy (ILAE) published in the journal Epilepsia.
Comprehensive epilepsy care
Such a referral is not ”a commitment to undergo brain surgery,” wrote the authors of the new recommendations study, but surgical evaluations offer patients an opportunity to learn about the range of therapies available to them and to have their diagnosis verified, as well as learning about the cause and type of epilepsy they have, even if they ultimately do not pursue surgery.
”In fact, most patients with drug-resistant epilepsy do not end up undergoing surgery after referral, but still benefit from comprehensive epilepsy care improving quality of life and lowering mortality,” wrote lead author Lara Jehi, MD, professor of neurology and epilepsy specialist at Cleveland Clinic, and her colleagues. “A better characterization of the epilepsy can also help optimize medical therapy and address somatic, cognitive, behavioral, and psychiatric comorbidities.”
Is the diagnosis correct?
They noted that about one-third of patients referred to epilepsy centers with an apparent diagnosis of drug-resistant epilepsy actually have psychogenic nonepileptic seizures (PNES) – not epilepsy – and an early, accurate diagnosis of PNES can ensure they receive psychotherapy, stop taking antiseizure medications, and have better outcomes.
“These recommendations are necessary, as the delay to surgery and the overall underutilization of surgery have not improved much over the last 20 years,” said Selim R. Benbadis, MD, professor of neurology and director of the comprehensive epilepsy program at the University of South Florida and Tampa General Hospital. “Comprehensive epilepsy centers offer more than surgery, including correct and precise diagnosis, drug options, three [Food and Drug Administration]–approved neurostimulation options, and more,” said Dr. Benbadis, who was not involved in the development of these recommendations.
Consensus recommendations
On behalf of the the ILAE’s Surgical Therapies Commission, the authors used the Delphi consensus process to develop expert consensus recommendations on when to refer patients with epilepsy to surgery. They conducted three Delphi rounds on 51 clinical scenarios with 61 epileptologists (38% of participants), epilepsy neurosurgeons (34%), neurologists (23%), neuropsychiatrists (2%), and neuropsychologists (3%) from 28 countries. Most of clinicians focused on adults (39%) or adults and children (41%) while 20% focused only on pediatric epilepsy.
The physicians involved had a median 22 years of practice and represented all six ILAE regions: 30% from North America, 28% from Europe, 18% from Asia/Oceania, 13% from Latin America, 7% from the Eastern Mediterranean, and 4% from Africa.
The result of these rounds were three key recommendations arising from the consensus of experts consulted. First, every patient up to 70 years old who has drug-resistant epilepsy should be offered the option of a surgical evaluation as soon as it’s apparent that they have drug resistance. The option for surgical evaluation should be provided independent of their sex or socioeconomic status and regardless of how long they have had epilepsy, their seizure type, their epilepsy type, localization, and their comorbidities, ”including severe psychiatric comorbidity like psychogenic nonepileptic seizures (PNES) or substance abuse if patients are cooperative with management,” the authors wrote.
”Resective surgery can improve quality of life and cognitive outcomes and is the only treatment demonstrated to improve survival and reverse excess mortality attributed to drug-resistant epilepsy,” the authors wrote. Evidence supports that surgical evaluation is the most cost-effective approach to treating drug-resistant epilepsy, they added. Yet, it still takes about 20 years with epilepsy before an adult patient might be referred, ”and the neurology community remains ambivalent due to ongoing barriers and misconceptions about epilepsy surgery,” they wrote.
The second recommendation is to consider a surgical referral for older patients with drug-resistant epilepsy who have no surgical contraindication. Physicians can also consider a referral for patients of any age who are seizure free while taking one to two antiseizure drugs but who have a brain lesion in the noneloquent cortex.
The third recommendation is not to offer surgery if a patient has an active substance dependency and is not cooperative with management.
“Although there is some evidence that seizure outcomes are no different in individuals with active substance use disorder who have epilepsy surgery, the literature suggests increased perioperative surgical and anesthetic risk in this cohort,” the authors wrote. ”Patients with active substance abuse are more likely to be nonadherent with their seizure medications, and to leave the hospital against medical advice.”
One area where the participants did not reach consensus was regarding whether to refer patients who did not become seizure-free after trying just one “tolerated and appropriately chosen” antiseizure medication. Half (49%) said they would be unlikely to refer or would never refer that patient while 44% said they would likely or always refer them, and 7% weren’t sure.
The ‘next level’ of epilepsy care
“Similar recommendations have been published before, by the National Association of Epilepsy Centers, more than once, and have not changed the referral patterns,” Dr. Benbadis said. “They are not implemented by the average general neurologist.” While there are many reasons for this, one with a relativity simple fix is to adjust the language doctors use to when talking with patients about getting an evaluation, Dr. Benbadis said. ”The key is to rephrase: Instead of referrals ‘for surgery,’ which can be scary to many neurologists and patients, we should use more general terms, like referrals for the ‘next level of care by epilepsy specialists,’ ” said Dr. Benbadis, who advocated for this change in terminology in a 2019 editorial. Such language is less frightening and can ease patients’ concerns about going to an epilepsy center where they can learn about more options than just surgery.
Further, surgical options have expanded in recent years, including the development of laser interstitial thermal therapy and neuromodulation. “Identifying candidacy for any of these approaches starts with a surgical referral, so a timely evaluation is key,” the authors wrote.
Referral delays persist
Despite the strong evidence for timely referrals, delays have persisted for decades, said Dr. Benbadis, echoing what the authors describe. ”Despite the results of two randomized controlled trials showing that surgery for temporal lobe epilepsy in adults, and resective surgery in children, is superior to continued antiseizure medications both in terms of seizure freedom and improved quality of life, the mean epilepsy duration to temporal lobe resection has persisted at over 20 years,” the authors wrote. ”Although drug resistance is reached with a mean latency of 9 years in epilepsy surgery candidates, these patients have experienced a decade of unabating seizures with detrimental effects including cognitive and psychiatric comorbidities, poor psychosocial outcomes, potential injuries, and risk of death.”
Surgery is not a ‘dangerous last resort’
The authors point out a variety of likely reasons for these delays, including patients experiencing temporary remissions with a new drug, lack of adequate health care access, overestimating surgery risks, and underestimating the seriousness and risk of death from ongoing seizures.
Dr. Benbadis agreed, referring to a “combination of lack of knowledge and unrealistic views about surgery outcomes and complications.” Patients and their neurologists think surgery is a “dangerous last resort, fraught with complications, and they don’t know the outcome, so it’s mainly that they are not very well-educated about epilepsy surgery,” he said. Complacency about a patient’s infrequent seizures plays a role as well, he added. “Their patient is having one seizure every 2 months, and they might say, ‘well, that’s okay, that’s not that bad,’ but it is when we can cure it.”
Similar factors are barriers to epilepsy surgery: “lack of knowledge or misconceptions about surgical risks, negative behaviors, or cultural issues and access issues.”
Another major barrier, both within neurology and throughout medicine in general, is that large academic centers that accept referrals, including epilepsy centers, have poor communication, follow-up, and scheduling, Dr. Benbadis said.
The authors provided a table with suggestions on potential solutions to those barriers, including identifying online resources to help doctors identify possible surgery candidates, such as www.toolsforepilepsy.com, and a range of educational resources. Ways to improve access and cost include mobile clinics, telehealth, coordinating with an epilepsy organization, and employing a multidisciplinary team that includes a social worker to help with support such as transportation and health insurance.
FROM EPILEPSIA