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Increased Risk of New Rheumatic Disease Follows COVID-19 Infection
The risk of developing a new autoimmune inflammatory rheumatic disease (AIRD) is greater following a COVID-19 infection than after an influenza infection or in the general population, according to a study published March 5 in Annals of Internal Medicine. More severe COVID-19 infections were linked to a greater risk of incident rheumatic disease, but vaccination appeared protective against development of a new AIRD.
“Importantly, this study shows the value of vaccination to prevent severe disease and these types of sequelae,” Anne Davidson, MBBS, a professor in the Institute of Molecular Medicine at The Feinstein Institutes for Medical Research in Manhasset, New York, who was not involved in the study, said in an interview.
Previous research had already identified the likelihood of an association between SARS-CoV-2 infection and subsequent development of a new AIRD. This new study, however, includes much larger cohorts from two different countries and relies on more robust methodology than previous studies, experts said.
“Unique steps were taken by the study authors to make sure that what they were looking at in terms of signal was most likely true,” Alfred Kim, MD, PhD, assistant professor of medicine in rheumatology at Washington University in St. Louis, who was not involved in the study, said in an interview. Dr. Davidson agreed, noting that these authors “were a bit more rigorous with ascertainment of the autoimmune diagnosis, using two codes and also checking that appropriate medications were administered.”
More Robust and Rigorous Research
Past cohort studies finding an increased risk of rheumatic disease after COVID-19 “based their findings solely on comparisons between infected and uninfected groups, which could be influenced by ascertainment bias due to disparities in care, differences in health-seeking tendencies, and inherent risks among the groups,” Min Seo Kim, MD, of the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, and his colleagues reported. Their study, however, required at least two claims with codes for rheumatic disease and compared patients with COVID-19 to those with flu “to adjust for the potentially heightened detection of AIRD in SARS-CoV-2–infected persons owing to their interactions with the health care system.”
Dr. Alfred Kim said the fact that they used at least two claims codes “gives a little more credence that the patients were actually experiencing some sort of autoimmune inflammatory condition as opposed to a very transient issue post COVID that just went away on its own.”
He acknowledged that the previous research was reasonably strong, “especially in light of the fact that there has been so much work done on a molecular level demonstrating that COVID-19 is associated with a substantial increase in autoantibodies in a significant proportion of patients, so this always opened up the possibility that this could associate with some sort of autoimmune disease downstream.”
While the study is well done with a large population, “it still has limitations that might overestimate the effect,” Kevin W. Byram, MD, associate professor of medicine in rheumatology and immunology at Vanderbilt University Medical Center in Nashville, Tennessee, who was not involved in the study, said in an interview. “We certainly have seen individual cases of new rheumatic disease where COVID-19 infection is likely the trigger,” but the phenomenon is not new, he added.
“Many autoimmune diseases are spurred by a loss of tolerance that might be induced by a pathogen of some sort,” Dr. Byram said. “The study is right to point out different forms of bias that might be at play. One in particular that is important to consider in a study like this is the lack of case-level adjudication regarding the diagnosis of rheumatic disease” since the study relied on available ICD-10 codes and medication prescriptions.
The researchers used national claims data to compare risk of incident AIRD in 10,027,506 South Korean and 12,218,680 Japanese adults, aged 20 and older, at 1 month, 6 months, and 12 months after COVID-19 infection, influenza infection, or a matched index date for uninfected control participants. Only patients with at least two claims for AIRD were considered to have a new diagnosis.
Patients who had COVID-19 between January 2020 and December 2021, confirmed by PCR or antigen testing, were matched 1:1 with patients who had test-confirmed influenza during that time and 1:4 with uninfected control participants, whose index date was set to the infection date of their matched COVID-19 patient.
The propensity score matching was based on age, sex, household income, urban versus rural residence, and various clinical characteristics and history: body mass index; blood pressure; fasting blood glucose; glomerular filtration rate; smoking status; alcohol consumption; weekly aerobic physical activity; comorbidity index; hospitalizations and outpatient visits in the previous year; past use of diabetes, hyperlipidemia, or hypertension medication; and history of cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, or respiratory infectious disease.
Patients with a history of AIRD or with coinfection or reinfection of COVID-19 and influenza were excluded, as were patients diagnosed with rheumatic disease within a month of COVID-19 infection.
Risk Varied With Disease Severity and Vaccination Status
Among the Korean patients, 3.9% had a COVID-19 infection and 0.98% had an influenza infection. After matching, the comparison populations included 94,504 patients with COVID-19 versus 94,504 patients with flu, and 177,083 patients with COVID-19 versus 675,750 uninfected controls.
The risk of developing an AIRD at least 1 month after infection in South Korean patients with COVID-19 was 25% higher than in uninfected control participants (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.18–1.31; P < .05) and 30% higher than in influenza patients (aHR, 1.3; 95% CI, 1.02–1.59; P < .05). Specifically, risk in South Korean patients with COVID-19 was significantly increased for connective tissue disease and both treated and untreated AIRD but not for inflammatory arthritis.
Among the Japanese patients, 8.2% had COVID-19 and 0.99% had flu, resulting in matched populations of 115,003 with COVID-19 versus 110,310 with flu, and 960,849 with COVID-19 versus 1,606,873 uninfected patients. The effect size was larger in Japanese patients, with a 79% increased risk for AIRD in patients with COVID-19, compared with the general population (aHR, 1.79; 95% CI, 1.77–1.82; P < .05) and a 14% increased risk, compared with patients with influenza infection (aHR, 1.14; 95% CI, 1.10–1.17; P < .05). In Japanese patients, risk was increased across all four categories, including a doubled risk for inflammatory arthritis (aHR, 2.02; 95% CI, 1.96–2.07; P < .05), compared with the general population.
The researchers had data only from the South Korean cohort to calculate risk based on vaccination status, SARS-CoV-2 variant (wild type versus Delta), and COVID-19 severity. Researchers determined a COVID-19 infection to be moderate-to-severe based on billing codes for ICU admission or requiring oxygen therapy, extracorporeal membrane oxygenation, renal replacement, or CPR.
Infection with both the original strain and the Delta variant were linked to similar increased risks for AIRD, but moderate to severe COVID-19 infections had greater risk of subsequent AIRD (aHR, 1.42; P < .05) than mild infections (aHR, 1.22; P < .05). Vaccination was linked to a lower risk of AIRD within the COVID-19 patient population: One dose was linked to a 41% reduced risk (HR, 0.59; P < .05) and two doses were linked to a 58% reduced risk (HR, 0.42; P < .05), regardless of the vaccine type, compared with unvaccinated patients with COVID-19. The apparent protective effect of vaccination was true only for patients with mild COVID-19, not those with moderate to severe infection.
“One has to wonder whether or not these people were at much higher risk of developing autoimmune disease that just got exposed because they got COVID, so that a fraction of these would have gotten an autoimmune disease downstream,” Dr. Alfred Kim said. Regardless, one clinical implication of the findings is the reduced risk in vaccinated patients, regardless of the vaccine type, given the fact that “mRNA vaccination in particular has not been associated with any autoantibody development,” he said.
Though the correlations in the study cannot translate to causation, several mechanisms might be at play in a viral infection contributing to autoimmune risk, Dr. Davidson said. Given that viral nucleic acids also recognize self-nucleic acids, “a large load of viral nucleic acid may break tolerance,” or “viral proteins could also mimic self-proteins,” she said. “In addition, tolerance may be broken by a highly inflammatory environment associated with the release of cytokines and other inflammatory mediators.”
The association between new-onset autoimmune disease and severe COVID-19 infection suggests multiple mechanisms may be involved in excess immune stimulation, Dr. Davidson said. But she added that it’s unclear how these findings, involving the original strain and Delta variant of SARS-CoV-2, might relate to currently circulating variants.
The research was funded by the National Research Foundation of Korea, the Korea Health Industry Development Institute, and the Ministry of Food and Drug Safety of the Republic of Korea. The authors reported no relevant financial relationships with industry. Dr. Alfred Kim has sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, and Novartis; receives royalties from a patent with Kypha Inc.; and has done consulting or speaking for Amgen, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, GlaxoSmithKline, Kypha, Miltenyi Biotech, Pfizer, Rheumatology & Arthritis Learning Network, Synthekine, Techtonic Therapeutics, and UpToDate. Dr. Byram reported consulting for TenSixteen Bio. Dr. Davidson had no disclosures.
The risk of developing a new autoimmune inflammatory rheumatic disease (AIRD) is greater following a COVID-19 infection than after an influenza infection or in the general population, according to a study published March 5 in Annals of Internal Medicine. More severe COVID-19 infections were linked to a greater risk of incident rheumatic disease, but vaccination appeared protective against development of a new AIRD.
“Importantly, this study shows the value of vaccination to prevent severe disease and these types of sequelae,” Anne Davidson, MBBS, a professor in the Institute of Molecular Medicine at The Feinstein Institutes for Medical Research in Manhasset, New York, who was not involved in the study, said in an interview.
Previous research had already identified the likelihood of an association between SARS-CoV-2 infection and subsequent development of a new AIRD. This new study, however, includes much larger cohorts from two different countries and relies on more robust methodology than previous studies, experts said.
“Unique steps were taken by the study authors to make sure that what they were looking at in terms of signal was most likely true,” Alfred Kim, MD, PhD, assistant professor of medicine in rheumatology at Washington University in St. Louis, who was not involved in the study, said in an interview. Dr. Davidson agreed, noting that these authors “were a bit more rigorous with ascertainment of the autoimmune diagnosis, using two codes and also checking that appropriate medications were administered.”
More Robust and Rigorous Research
Past cohort studies finding an increased risk of rheumatic disease after COVID-19 “based their findings solely on comparisons between infected and uninfected groups, which could be influenced by ascertainment bias due to disparities in care, differences in health-seeking tendencies, and inherent risks among the groups,” Min Seo Kim, MD, of the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, and his colleagues reported. Their study, however, required at least two claims with codes for rheumatic disease and compared patients with COVID-19 to those with flu “to adjust for the potentially heightened detection of AIRD in SARS-CoV-2–infected persons owing to their interactions with the health care system.”
Dr. Alfred Kim said the fact that they used at least two claims codes “gives a little more credence that the patients were actually experiencing some sort of autoimmune inflammatory condition as opposed to a very transient issue post COVID that just went away on its own.”
He acknowledged that the previous research was reasonably strong, “especially in light of the fact that there has been so much work done on a molecular level demonstrating that COVID-19 is associated with a substantial increase in autoantibodies in a significant proportion of patients, so this always opened up the possibility that this could associate with some sort of autoimmune disease downstream.”
While the study is well done with a large population, “it still has limitations that might overestimate the effect,” Kevin W. Byram, MD, associate professor of medicine in rheumatology and immunology at Vanderbilt University Medical Center in Nashville, Tennessee, who was not involved in the study, said in an interview. “We certainly have seen individual cases of new rheumatic disease where COVID-19 infection is likely the trigger,” but the phenomenon is not new, he added.
“Many autoimmune diseases are spurred by a loss of tolerance that might be induced by a pathogen of some sort,” Dr. Byram said. “The study is right to point out different forms of bias that might be at play. One in particular that is important to consider in a study like this is the lack of case-level adjudication regarding the diagnosis of rheumatic disease” since the study relied on available ICD-10 codes and medication prescriptions.
The researchers used national claims data to compare risk of incident AIRD in 10,027,506 South Korean and 12,218,680 Japanese adults, aged 20 and older, at 1 month, 6 months, and 12 months after COVID-19 infection, influenza infection, or a matched index date for uninfected control participants. Only patients with at least two claims for AIRD were considered to have a new diagnosis.
Patients who had COVID-19 between January 2020 and December 2021, confirmed by PCR or antigen testing, were matched 1:1 with patients who had test-confirmed influenza during that time and 1:4 with uninfected control participants, whose index date was set to the infection date of their matched COVID-19 patient.
The propensity score matching was based on age, sex, household income, urban versus rural residence, and various clinical characteristics and history: body mass index; blood pressure; fasting blood glucose; glomerular filtration rate; smoking status; alcohol consumption; weekly aerobic physical activity; comorbidity index; hospitalizations and outpatient visits in the previous year; past use of diabetes, hyperlipidemia, or hypertension medication; and history of cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, or respiratory infectious disease.
Patients with a history of AIRD or with coinfection or reinfection of COVID-19 and influenza were excluded, as were patients diagnosed with rheumatic disease within a month of COVID-19 infection.
Risk Varied With Disease Severity and Vaccination Status
Among the Korean patients, 3.9% had a COVID-19 infection and 0.98% had an influenza infection. After matching, the comparison populations included 94,504 patients with COVID-19 versus 94,504 patients with flu, and 177,083 patients with COVID-19 versus 675,750 uninfected controls.
The risk of developing an AIRD at least 1 month after infection in South Korean patients with COVID-19 was 25% higher than in uninfected control participants (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.18–1.31; P < .05) and 30% higher than in influenza patients (aHR, 1.3; 95% CI, 1.02–1.59; P < .05). Specifically, risk in South Korean patients with COVID-19 was significantly increased for connective tissue disease and both treated and untreated AIRD but not for inflammatory arthritis.
Among the Japanese patients, 8.2% had COVID-19 and 0.99% had flu, resulting in matched populations of 115,003 with COVID-19 versus 110,310 with flu, and 960,849 with COVID-19 versus 1,606,873 uninfected patients. The effect size was larger in Japanese patients, with a 79% increased risk for AIRD in patients with COVID-19, compared with the general population (aHR, 1.79; 95% CI, 1.77–1.82; P < .05) and a 14% increased risk, compared with patients with influenza infection (aHR, 1.14; 95% CI, 1.10–1.17; P < .05). In Japanese patients, risk was increased across all four categories, including a doubled risk for inflammatory arthritis (aHR, 2.02; 95% CI, 1.96–2.07; P < .05), compared with the general population.
The researchers had data only from the South Korean cohort to calculate risk based on vaccination status, SARS-CoV-2 variant (wild type versus Delta), and COVID-19 severity. Researchers determined a COVID-19 infection to be moderate-to-severe based on billing codes for ICU admission or requiring oxygen therapy, extracorporeal membrane oxygenation, renal replacement, or CPR.
Infection with both the original strain and the Delta variant were linked to similar increased risks for AIRD, but moderate to severe COVID-19 infections had greater risk of subsequent AIRD (aHR, 1.42; P < .05) than mild infections (aHR, 1.22; P < .05). Vaccination was linked to a lower risk of AIRD within the COVID-19 patient population: One dose was linked to a 41% reduced risk (HR, 0.59; P < .05) and two doses were linked to a 58% reduced risk (HR, 0.42; P < .05), regardless of the vaccine type, compared with unvaccinated patients with COVID-19. The apparent protective effect of vaccination was true only for patients with mild COVID-19, not those with moderate to severe infection.
“One has to wonder whether or not these people were at much higher risk of developing autoimmune disease that just got exposed because they got COVID, so that a fraction of these would have gotten an autoimmune disease downstream,” Dr. Alfred Kim said. Regardless, one clinical implication of the findings is the reduced risk in vaccinated patients, regardless of the vaccine type, given the fact that “mRNA vaccination in particular has not been associated with any autoantibody development,” he said.
Though the correlations in the study cannot translate to causation, several mechanisms might be at play in a viral infection contributing to autoimmune risk, Dr. Davidson said. Given that viral nucleic acids also recognize self-nucleic acids, “a large load of viral nucleic acid may break tolerance,” or “viral proteins could also mimic self-proteins,” she said. “In addition, tolerance may be broken by a highly inflammatory environment associated with the release of cytokines and other inflammatory mediators.”
The association between new-onset autoimmune disease and severe COVID-19 infection suggests multiple mechanisms may be involved in excess immune stimulation, Dr. Davidson said. But she added that it’s unclear how these findings, involving the original strain and Delta variant of SARS-CoV-2, might relate to currently circulating variants.
The research was funded by the National Research Foundation of Korea, the Korea Health Industry Development Institute, and the Ministry of Food and Drug Safety of the Republic of Korea. The authors reported no relevant financial relationships with industry. Dr. Alfred Kim has sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, and Novartis; receives royalties from a patent with Kypha Inc.; and has done consulting or speaking for Amgen, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, GlaxoSmithKline, Kypha, Miltenyi Biotech, Pfizer, Rheumatology & Arthritis Learning Network, Synthekine, Techtonic Therapeutics, and UpToDate. Dr. Byram reported consulting for TenSixteen Bio. Dr. Davidson had no disclosures.
The risk of developing a new autoimmune inflammatory rheumatic disease (AIRD) is greater following a COVID-19 infection than after an influenza infection or in the general population, according to a study published March 5 in Annals of Internal Medicine. More severe COVID-19 infections were linked to a greater risk of incident rheumatic disease, but vaccination appeared protective against development of a new AIRD.
“Importantly, this study shows the value of vaccination to prevent severe disease and these types of sequelae,” Anne Davidson, MBBS, a professor in the Institute of Molecular Medicine at The Feinstein Institutes for Medical Research in Manhasset, New York, who was not involved in the study, said in an interview.
Previous research had already identified the likelihood of an association between SARS-CoV-2 infection and subsequent development of a new AIRD. This new study, however, includes much larger cohorts from two different countries and relies on more robust methodology than previous studies, experts said.
“Unique steps were taken by the study authors to make sure that what they were looking at in terms of signal was most likely true,” Alfred Kim, MD, PhD, assistant professor of medicine in rheumatology at Washington University in St. Louis, who was not involved in the study, said in an interview. Dr. Davidson agreed, noting that these authors “were a bit more rigorous with ascertainment of the autoimmune diagnosis, using two codes and also checking that appropriate medications were administered.”
More Robust and Rigorous Research
Past cohort studies finding an increased risk of rheumatic disease after COVID-19 “based their findings solely on comparisons between infected and uninfected groups, which could be influenced by ascertainment bias due to disparities in care, differences in health-seeking tendencies, and inherent risks among the groups,” Min Seo Kim, MD, of the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, and his colleagues reported. Their study, however, required at least two claims with codes for rheumatic disease and compared patients with COVID-19 to those with flu “to adjust for the potentially heightened detection of AIRD in SARS-CoV-2–infected persons owing to their interactions with the health care system.”
Dr. Alfred Kim said the fact that they used at least two claims codes “gives a little more credence that the patients were actually experiencing some sort of autoimmune inflammatory condition as opposed to a very transient issue post COVID that just went away on its own.”
He acknowledged that the previous research was reasonably strong, “especially in light of the fact that there has been so much work done on a molecular level demonstrating that COVID-19 is associated with a substantial increase in autoantibodies in a significant proportion of patients, so this always opened up the possibility that this could associate with some sort of autoimmune disease downstream.”
While the study is well done with a large population, “it still has limitations that might overestimate the effect,” Kevin W. Byram, MD, associate professor of medicine in rheumatology and immunology at Vanderbilt University Medical Center in Nashville, Tennessee, who was not involved in the study, said in an interview. “We certainly have seen individual cases of new rheumatic disease where COVID-19 infection is likely the trigger,” but the phenomenon is not new, he added.
“Many autoimmune diseases are spurred by a loss of tolerance that might be induced by a pathogen of some sort,” Dr. Byram said. “The study is right to point out different forms of bias that might be at play. One in particular that is important to consider in a study like this is the lack of case-level adjudication regarding the diagnosis of rheumatic disease” since the study relied on available ICD-10 codes and medication prescriptions.
The researchers used national claims data to compare risk of incident AIRD in 10,027,506 South Korean and 12,218,680 Japanese adults, aged 20 and older, at 1 month, 6 months, and 12 months after COVID-19 infection, influenza infection, or a matched index date for uninfected control participants. Only patients with at least two claims for AIRD were considered to have a new diagnosis.
Patients who had COVID-19 between January 2020 and December 2021, confirmed by PCR or antigen testing, were matched 1:1 with patients who had test-confirmed influenza during that time and 1:4 with uninfected control participants, whose index date was set to the infection date of their matched COVID-19 patient.
The propensity score matching was based on age, sex, household income, urban versus rural residence, and various clinical characteristics and history: body mass index; blood pressure; fasting blood glucose; glomerular filtration rate; smoking status; alcohol consumption; weekly aerobic physical activity; comorbidity index; hospitalizations and outpatient visits in the previous year; past use of diabetes, hyperlipidemia, or hypertension medication; and history of cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, or respiratory infectious disease.
Patients with a history of AIRD or with coinfection or reinfection of COVID-19 and influenza were excluded, as were patients diagnosed with rheumatic disease within a month of COVID-19 infection.
Risk Varied With Disease Severity and Vaccination Status
Among the Korean patients, 3.9% had a COVID-19 infection and 0.98% had an influenza infection. After matching, the comparison populations included 94,504 patients with COVID-19 versus 94,504 patients with flu, and 177,083 patients with COVID-19 versus 675,750 uninfected controls.
The risk of developing an AIRD at least 1 month after infection in South Korean patients with COVID-19 was 25% higher than in uninfected control participants (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.18–1.31; P < .05) and 30% higher than in influenza patients (aHR, 1.3; 95% CI, 1.02–1.59; P < .05). Specifically, risk in South Korean patients with COVID-19 was significantly increased for connective tissue disease and both treated and untreated AIRD but not for inflammatory arthritis.
Among the Japanese patients, 8.2% had COVID-19 and 0.99% had flu, resulting in matched populations of 115,003 with COVID-19 versus 110,310 with flu, and 960,849 with COVID-19 versus 1,606,873 uninfected patients. The effect size was larger in Japanese patients, with a 79% increased risk for AIRD in patients with COVID-19, compared with the general population (aHR, 1.79; 95% CI, 1.77–1.82; P < .05) and a 14% increased risk, compared with patients with influenza infection (aHR, 1.14; 95% CI, 1.10–1.17; P < .05). In Japanese patients, risk was increased across all four categories, including a doubled risk for inflammatory arthritis (aHR, 2.02; 95% CI, 1.96–2.07; P < .05), compared with the general population.
The researchers had data only from the South Korean cohort to calculate risk based on vaccination status, SARS-CoV-2 variant (wild type versus Delta), and COVID-19 severity. Researchers determined a COVID-19 infection to be moderate-to-severe based on billing codes for ICU admission or requiring oxygen therapy, extracorporeal membrane oxygenation, renal replacement, or CPR.
Infection with both the original strain and the Delta variant were linked to similar increased risks for AIRD, but moderate to severe COVID-19 infections had greater risk of subsequent AIRD (aHR, 1.42; P < .05) than mild infections (aHR, 1.22; P < .05). Vaccination was linked to a lower risk of AIRD within the COVID-19 patient population: One dose was linked to a 41% reduced risk (HR, 0.59; P < .05) and two doses were linked to a 58% reduced risk (HR, 0.42; P < .05), regardless of the vaccine type, compared with unvaccinated patients with COVID-19. The apparent protective effect of vaccination was true only for patients with mild COVID-19, not those with moderate to severe infection.
“One has to wonder whether or not these people were at much higher risk of developing autoimmune disease that just got exposed because they got COVID, so that a fraction of these would have gotten an autoimmune disease downstream,” Dr. Alfred Kim said. Regardless, one clinical implication of the findings is the reduced risk in vaccinated patients, regardless of the vaccine type, given the fact that “mRNA vaccination in particular has not been associated with any autoantibody development,” he said.
Though the correlations in the study cannot translate to causation, several mechanisms might be at play in a viral infection contributing to autoimmune risk, Dr. Davidson said. Given that viral nucleic acids also recognize self-nucleic acids, “a large load of viral nucleic acid may break tolerance,” or “viral proteins could also mimic self-proteins,” she said. “In addition, tolerance may be broken by a highly inflammatory environment associated with the release of cytokines and other inflammatory mediators.”
The association between new-onset autoimmune disease and severe COVID-19 infection suggests multiple mechanisms may be involved in excess immune stimulation, Dr. Davidson said. But she added that it’s unclear how these findings, involving the original strain and Delta variant of SARS-CoV-2, might relate to currently circulating variants.
The research was funded by the National Research Foundation of Korea, the Korea Health Industry Development Institute, and the Ministry of Food and Drug Safety of the Republic of Korea. The authors reported no relevant financial relationships with industry. Dr. Alfred Kim has sponsored research agreements with AstraZeneca, Bristol-Myers Squibb, and Novartis; receives royalties from a patent with Kypha Inc.; and has done consulting or speaking for Amgen, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, GlaxoSmithKline, Kypha, Miltenyi Biotech, Pfizer, Rheumatology & Arthritis Learning Network, Synthekine, Techtonic Therapeutics, and UpToDate. Dr. Byram reported consulting for TenSixteen Bio. Dr. Davidson had no disclosures.
FROM ANNALS OF INTERNAL MEDICINE
AAP Updates Guidance on Vaccine Communication and Hesitancy
The measles outbreak in Florida, occurring just as health officials announced an official end to Philadelphia’s measles outbreak and rising global cases, has cast attention once again on concerns about vaccine hesitancy. In the midst of Florida’s surgeon general avoiding measles vaccination recommendations for parents, the American Academy of Pediatrics has updated its clinical guidance on vaccine communication.
“Disruption to routine pediatric vaccination during the COVID-19 pandemic has left many children vulnerable to vaccine-preventable diseases and more locations susceptible to outbreaks in the United States and around the world,” Sean T. O’Leary, MD, MPH, a pediatric infectious diseases specialist and associate professor of pediatrics at the University of Colorado in Aurora, and his colleagues, wrote in the new report, published in the March issue of Pediatrics. “Geographic clustering of vaccine refusal further increases the risk of communicable disease outbreaks in certain communities even when vaccination rates at a state or national level remain high overall.”
The authors note that disease resurgence may bolster vaccine uptake, with media coverage of recent outbreaks linked to more pro-vaccine discussions and attitudes among parents. But the evidence on that remains inconclusive, and the authors point out the slow uptake in COVID-19 vaccination as parents navigate ongoing spread of both the disease and vaccine misinformation.
Conflicting Evidence on Postpandemic Attitudes
It remains unclear how parent attitudes toward vaccines have shifted, if at all, since the pandemic. A study published in Pediatrics from October 2023, which Dr. O’Leary also coauthored, analyzed data from an online survey of Colorado mothers between 2018 and 2021 and found no significant difference in vaccine hesitancy during the pandemic compared with pre-pandemic.
Among 3,553 respondents, 1 in 5 (20.4%) were vaccine hesitant overall. Though parents were twice as likely to feel uncertain in trusting vaccine information after the COVID-19 vaccines were authorized (adjusted odds ratio [aOR] 2.14), they were half as likely to be unsure about hesitancy toward childhood vaccines (aOR 0.48).
Another study in Pediatrics from October 2023 found that common concerns about COVID-19 vaccines among parents included infertility, long-term effects from the vaccines, and effects on preexisting medical conditions. But even then, participants in focus groups “expressed that they would listen to their doctor for information about COVID-19 vaccines,” wrote Aubree Honcoop, MPS, of the University of Nebraska Medical Center in Omaha, and her colleagues.
“I think what we’re seeing, very importantly, is that physicians seem to be the source people rely on,” said Walter Orenstein, MD, professor of medicine and associate director of the Emory Vaccine Center at Emory University in Atlanta. “But we need to give the physicians time and incentives to spend time with families,” such as a billing code for vaccine counseling, he said.
Dr. Orenstein was surprised to see the results from Colorado, but he noted they were from a small survey in a single state. He pointed to other findings, such as those from the University of Pennsylvania’s Annenberg Public Policy Center in November 2023, that found lower confidence overall among Americans toward vaccines.
Paul Offit, MD, director of the Vaccine Education Center and an attending infectious disease physician at Children’s Hospital of Philadelphia, where the city’s measles outbreak began, is similarly skeptical about the Colorado study’s findings that parent vaccine attitudes have changed little since the pandemic. At the AAP’s annual conference in October 2023, Dr. Offit asked pediatricians about their experiences while he signed books.
“I would ask, ‘So what’s it like out there? Are we winning or losing?’ ” he said. “I would say, to a person, everyone said they felt things were much worse now than they ever have been before.”
Clinical Guidance
The new report reviews previously published evidence on the spectrum of parental vaccine acceptance — from supporters and “go along to get along” parents to cautious acceptors and fence sitters to vaccine refusers — and the determinants that contribute to hesitancy. They also noted the social inequities that have played a role in vaccine uptake disparities.
“Distrust of health systems based on historic and ongoing discrimination and inequitable access to care are intertwined challenges that contribute to racial and ethnic disparities in vaccine uptake,” the authors wrote. “Although there has been progress in reducing racial, ethnic, and socioeconomic disparities in childhood vaccination coverage, the COVID-19 pandemic made clear how much work is yet to be done.”
The report also reviewed the societal, individual, payer and pediatric practice costs of vaccine refusal. The 1-year cost to taxpayers from the measles outbreak in New York City in 2018-2019, for example, was $8.4 million, excluding vaccination programs.
The report provides background information to equip pediatricians for conversations with parents about vaccines. Since safety is the top concern for vaccine hesitancy among parents, the authors advised pediatricians to be familiar with the process of vaccine testing, emergency use authorization, licensure, approval, recommendations, and safety monitoring, including the Vaccine Safety Datalink, the Vaccine Adverse Event Reporting System (VAERS), the FDA’s Biologics Effectiveness and Safety (BEST) system, and the CDC’s Clinical Immunization Safety Assessment Project (CISA).
“Because vaccines are generally given to healthy individuals to prevent disease, they are held to a higher safety standard than other medications,” the authors wrote before providing a summary of the process for physicians to reference. The report also includes information on vaccine ingredients and a chart of common misconceptions about vaccines with the corresponding facts.
Overcoming Hesitancy
Evidence-based strategies for increasing childhood vaccine uptake begin with a strong vaccine recommendation using a presumptive rather than participatory approach, the authors wrote. “A presumptive format is one in which the clinician asserts a position regarding vaccines using a closed-ended statement, such as ‘Sara is due for several vaccines today’ or ‘Well, we have to do some shots,’ ” the authors wrote. “This strategy is in contrast to a participatory format, in which an open-ended question is used to more explicitly invite the parent to voice an opinion, such as ‘How do you feel about vaccines today?’ ” The presumptive format and a strong recommendation are both associated with greater uptake, evidence shows.
For parents who express hesitancy, the authors provide a summary of additional evidence-based communication strategies, starting with motivational interviewing. Two other strategies they highlight include using language to re-emphasize the importance of adhering to the CDC recommended schedule — “He really needs these shots” — and bundling discussion of all recommended vaccines for a visit at once.
“Finally, clinicians can emphasize their own experiences when discussing the need for vaccination, including personal experience with vaccine-preventable diseases and the fact that they and their families are vaccinated because of their confidence in the safety and efficacy of the vaccines,” the authors wrote.
For families who refuse or delay vaccines, the authors reviewed the “ethical arguments both in favor of and against dismissal policies,” noting that nearly all pediatricians who report dismissing families who refuse vaccination are in private practice, since large systems are often unable to dismiss patients. They also point out that fewer pediatricians dismiss families for spreading out vaccines than outright refusing all vaccines.
”Dismissal of child patients of vaccine-refusing parents can be a difficult decision arrived at after considering multiple factors and documented attempts to counsel vaccine-refusing families,” they wrote. “However, if repeated attempts to help understand and address parental values and vaccine concerns fails to engender trust, move parents toward vaccine acceptance, or strengthen the therapeutic alliance, dismissal can be an acceptable option.”
Finally, the authors reminded pediatricians “that vaccine-hesitant parents are a heterogeneous group and that specific parental vaccine concerns need to be individually identified and addressed.” Working with families to discuss their questions and concerns is an opportunity to “build rapport and trust with a family,” they wrote, ”and, ultimately, protect their children from the scourge of vaccine-preventable diseases.”
The focus groups study was funded by the National Institutes of Health, and the authors reported having no disclosures. The Colorado attitudes study used no external funding, and the authors reported no disclosures. The new clinical report used no external funding, and the authors reported no disclosures. Dr. Orenstein is an uncompensated member of the Moderna Scientific Advisory Board. Dr. Offit codeveloped a licensed rotavirus vaccine, but he does not receive any royalties or own a patent for that.
The measles outbreak in Florida, occurring just as health officials announced an official end to Philadelphia’s measles outbreak and rising global cases, has cast attention once again on concerns about vaccine hesitancy. In the midst of Florida’s surgeon general avoiding measles vaccination recommendations for parents, the American Academy of Pediatrics has updated its clinical guidance on vaccine communication.
“Disruption to routine pediatric vaccination during the COVID-19 pandemic has left many children vulnerable to vaccine-preventable diseases and more locations susceptible to outbreaks in the United States and around the world,” Sean T. O’Leary, MD, MPH, a pediatric infectious diseases specialist and associate professor of pediatrics at the University of Colorado in Aurora, and his colleagues, wrote in the new report, published in the March issue of Pediatrics. “Geographic clustering of vaccine refusal further increases the risk of communicable disease outbreaks in certain communities even when vaccination rates at a state or national level remain high overall.”
The authors note that disease resurgence may bolster vaccine uptake, with media coverage of recent outbreaks linked to more pro-vaccine discussions and attitudes among parents. But the evidence on that remains inconclusive, and the authors point out the slow uptake in COVID-19 vaccination as parents navigate ongoing spread of both the disease and vaccine misinformation.
Conflicting Evidence on Postpandemic Attitudes
It remains unclear how parent attitudes toward vaccines have shifted, if at all, since the pandemic. A study published in Pediatrics from October 2023, which Dr. O’Leary also coauthored, analyzed data from an online survey of Colorado mothers between 2018 and 2021 and found no significant difference in vaccine hesitancy during the pandemic compared with pre-pandemic.
Among 3,553 respondents, 1 in 5 (20.4%) were vaccine hesitant overall. Though parents were twice as likely to feel uncertain in trusting vaccine information after the COVID-19 vaccines were authorized (adjusted odds ratio [aOR] 2.14), they were half as likely to be unsure about hesitancy toward childhood vaccines (aOR 0.48).
Another study in Pediatrics from October 2023 found that common concerns about COVID-19 vaccines among parents included infertility, long-term effects from the vaccines, and effects on preexisting medical conditions. But even then, participants in focus groups “expressed that they would listen to their doctor for information about COVID-19 vaccines,” wrote Aubree Honcoop, MPS, of the University of Nebraska Medical Center in Omaha, and her colleagues.
“I think what we’re seeing, very importantly, is that physicians seem to be the source people rely on,” said Walter Orenstein, MD, professor of medicine and associate director of the Emory Vaccine Center at Emory University in Atlanta. “But we need to give the physicians time and incentives to spend time with families,” such as a billing code for vaccine counseling, he said.
Dr. Orenstein was surprised to see the results from Colorado, but he noted they were from a small survey in a single state. He pointed to other findings, such as those from the University of Pennsylvania’s Annenberg Public Policy Center in November 2023, that found lower confidence overall among Americans toward vaccines.
Paul Offit, MD, director of the Vaccine Education Center and an attending infectious disease physician at Children’s Hospital of Philadelphia, where the city’s measles outbreak began, is similarly skeptical about the Colorado study’s findings that parent vaccine attitudes have changed little since the pandemic. At the AAP’s annual conference in October 2023, Dr. Offit asked pediatricians about their experiences while he signed books.
“I would ask, ‘So what’s it like out there? Are we winning or losing?’ ” he said. “I would say, to a person, everyone said they felt things were much worse now than they ever have been before.”
Clinical Guidance
The new report reviews previously published evidence on the spectrum of parental vaccine acceptance — from supporters and “go along to get along” parents to cautious acceptors and fence sitters to vaccine refusers — and the determinants that contribute to hesitancy. They also noted the social inequities that have played a role in vaccine uptake disparities.
“Distrust of health systems based on historic and ongoing discrimination and inequitable access to care are intertwined challenges that contribute to racial and ethnic disparities in vaccine uptake,” the authors wrote. “Although there has been progress in reducing racial, ethnic, and socioeconomic disparities in childhood vaccination coverage, the COVID-19 pandemic made clear how much work is yet to be done.”
The report also reviewed the societal, individual, payer and pediatric practice costs of vaccine refusal. The 1-year cost to taxpayers from the measles outbreak in New York City in 2018-2019, for example, was $8.4 million, excluding vaccination programs.
The report provides background information to equip pediatricians for conversations with parents about vaccines. Since safety is the top concern for vaccine hesitancy among parents, the authors advised pediatricians to be familiar with the process of vaccine testing, emergency use authorization, licensure, approval, recommendations, and safety monitoring, including the Vaccine Safety Datalink, the Vaccine Adverse Event Reporting System (VAERS), the FDA’s Biologics Effectiveness and Safety (BEST) system, and the CDC’s Clinical Immunization Safety Assessment Project (CISA).
“Because vaccines are generally given to healthy individuals to prevent disease, they are held to a higher safety standard than other medications,” the authors wrote before providing a summary of the process for physicians to reference. The report also includes information on vaccine ingredients and a chart of common misconceptions about vaccines with the corresponding facts.
Overcoming Hesitancy
Evidence-based strategies for increasing childhood vaccine uptake begin with a strong vaccine recommendation using a presumptive rather than participatory approach, the authors wrote. “A presumptive format is one in which the clinician asserts a position regarding vaccines using a closed-ended statement, such as ‘Sara is due for several vaccines today’ or ‘Well, we have to do some shots,’ ” the authors wrote. “This strategy is in contrast to a participatory format, in which an open-ended question is used to more explicitly invite the parent to voice an opinion, such as ‘How do you feel about vaccines today?’ ” The presumptive format and a strong recommendation are both associated with greater uptake, evidence shows.
For parents who express hesitancy, the authors provide a summary of additional evidence-based communication strategies, starting with motivational interviewing. Two other strategies they highlight include using language to re-emphasize the importance of adhering to the CDC recommended schedule — “He really needs these shots” — and bundling discussion of all recommended vaccines for a visit at once.
“Finally, clinicians can emphasize their own experiences when discussing the need for vaccination, including personal experience with vaccine-preventable diseases and the fact that they and their families are vaccinated because of their confidence in the safety and efficacy of the vaccines,” the authors wrote.
For families who refuse or delay vaccines, the authors reviewed the “ethical arguments both in favor of and against dismissal policies,” noting that nearly all pediatricians who report dismissing families who refuse vaccination are in private practice, since large systems are often unable to dismiss patients. They also point out that fewer pediatricians dismiss families for spreading out vaccines than outright refusing all vaccines.
”Dismissal of child patients of vaccine-refusing parents can be a difficult decision arrived at after considering multiple factors and documented attempts to counsel vaccine-refusing families,” they wrote. “However, if repeated attempts to help understand and address parental values and vaccine concerns fails to engender trust, move parents toward vaccine acceptance, or strengthen the therapeutic alliance, dismissal can be an acceptable option.”
Finally, the authors reminded pediatricians “that vaccine-hesitant parents are a heterogeneous group and that specific parental vaccine concerns need to be individually identified and addressed.” Working with families to discuss their questions and concerns is an opportunity to “build rapport and trust with a family,” they wrote, ”and, ultimately, protect their children from the scourge of vaccine-preventable diseases.”
The focus groups study was funded by the National Institutes of Health, and the authors reported having no disclosures. The Colorado attitudes study used no external funding, and the authors reported no disclosures. The new clinical report used no external funding, and the authors reported no disclosures. Dr. Orenstein is an uncompensated member of the Moderna Scientific Advisory Board. Dr. Offit codeveloped a licensed rotavirus vaccine, but he does not receive any royalties or own a patent for that.
The measles outbreak in Florida, occurring just as health officials announced an official end to Philadelphia’s measles outbreak and rising global cases, has cast attention once again on concerns about vaccine hesitancy. In the midst of Florida’s surgeon general avoiding measles vaccination recommendations for parents, the American Academy of Pediatrics has updated its clinical guidance on vaccine communication.
“Disruption to routine pediatric vaccination during the COVID-19 pandemic has left many children vulnerable to vaccine-preventable diseases and more locations susceptible to outbreaks in the United States and around the world,” Sean T. O’Leary, MD, MPH, a pediatric infectious diseases specialist and associate professor of pediatrics at the University of Colorado in Aurora, and his colleagues, wrote in the new report, published in the March issue of Pediatrics. “Geographic clustering of vaccine refusal further increases the risk of communicable disease outbreaks in certain communities even when vaccination rates at a state or national level remain high overall.”
The authors note that disease resurgence may bolster vaccine uptake, with media coverage of recent outbreaks linked to more pro-vaccine discussions and attitudes among parents. But the evidence on that remains inconclusive, and the authors point out the slow uptake in COVID-19 vaccination as parents navigate ongoing spread of both the disease and vaccine misinformation.
Conflicting Evidence on Postpandemic Attitudes
It remains unclear how parent attitudes toward vaccines have shifted, if at all, since the pandemic. A study published in Pediatrics from October 2023, which Dr. O’Leary also coauthored, analyzed data from an online survey of Colorado mothers between 2018 and 2021 and found no significant difference in vaccine hesitancy during the pandemic compared with pre-pandemic.
Among 3,553 respondents, 1 in 5 (20.4%) were vaccine hesitant overall. Though parents were twice as likely to feel uncertain in trusting vaccine information after the COVID-19 vaccines were authorized (adjusted odds ratio [aOR] 2.14), they were half as likely to be unsure about hesitancy toward childhood vaccines (aOR 0.48).
Another study in Pediatrics from October 2023 found that common concerns about COVID-19 vaccines among parents included infertility, long-term effects from the vaccines, and effects on preexisting medical conditions. But even then, participants in focus groups “expressed that they would listen to their doctor for information about COVID-19 vaccines,” wrote Aubree Honcoop, MPS, of the University of Nebraska Medical Center in Omaha, and her colleagues.
“I think what we’re seeing, very importantly, is that physicians seem to be the source people rely on,” said Walter Orenstein, MD, professor of medicine and associate director of the Emory Vaccine Center at Emory University in Atlanta. “But we need to give the physicians time and incentives to spend time with families,” such as a billing code for vaccine counseling, he said.
Dr. Orenstein was surprised to see the results from Colorado, but he noted they were from a small survey in a single state. He pointed to other findings, such as those from the University of Pennsylvania’s Annenberg Public Policy Center in November 2023, that found lower confidence overall among Americans toward vaccines.
Paul Offit, MD, director of the Vaccine Education Center and an attending infectious disease physician at Children’s Hospital of Philadelphia, where the city’s measles outbreak began, is similarly skeptical about the Colorado study’s findings that parent vaccine attitudes have changed little since the pandemic. At the AAP’s annual conference in October 2023, Dr. Offit asked pediatricians about their experiences while he signed books.
“I would ask, ‘So what’s it like out there? Are we winning or losing?’ ” he said. “I would say, to a person, everyone said they felt things were much worse now than they ever have been before.”
Clinical Guidance
The new report reviews previously published evidence on the spectrum of parental vaccine acceptance — from supporters and “go along to get along” parents to cautious acceptors and fence sitters to vaccine refusers — and the determinants that contribute to hesitancy. They also noted the social inequities that have played a role in vaccine uptake disparities.
“Distrust of health systems based on historic and ongoing discrimination and inequitable access to care are intertwined challenges that contribute to racial and ethnic disparities in vaccine uptake,” the authors wrote. “Although there has been progress in reducing racial, ethnic, and socioeconomic disparities in childhood vaccination coverage, the COVID-19 pandemic made clear how much work is yet to be done.”
The report also reviewed the societal, individual, payer and pediatric practice costs of vaccine refusal. The 1-year cost to taxpayers from the measles outbreak in New York City in 2018-2019, for example, was $8.4 million, excluding vaccination programs.
The report provides background information to equip pediatricians for conversations with parents about vaccines. Since safety is the top concern for vaccine hesitancy among parents, the authors advised pediatricians to be familiar with the process of vaccine testing, emergency use authorization, licensure, approval, recommendations, and safety monitoring, including the Vaccine Safety Datalink, the Vaccine Adverse Event Reporting System (VAERS), the FDA’s Biologics Effectiveness and Safety (BEST) system, and the CDC’s Clinical Immunization Safety Assessment Project (CISA).
“Because vaccines are generally given to healthy individuals to prevent disease, they are held to a higher safety standard than other medications,” the authors wrote before providing a summary of the process for physicians to reference. The report also includes information on vaccine ingredients and a chart of common misconceptions about vaccines with the corresponding facts.
Overcoming Hesitancy
Evidence-based strategies for increasing childhood vaccine uptake begin with a strong vaccine recommendation using a presumptive rather than participatory approach, the authors wrote. “A presumptive format is one in which the clinician asserts a position regarding vaccines using a closed-ended statement, such as ‘Sara is due for several vaccines today’ or ‘Well, we have to do some shots,’ ” the authors wrote. “This strategy is in contrast to a participatory format, in which an open-ended question is used to more explicitly invite the parent to voice an opinion, such as ‘How do you feel about vaccines today?’ ” The presumptive format and a strong recommendation are both associated with greater uptake, evidence shows.
For parents who express hesitancy, the authors provide a summary of additional evidence-based communication strategies, starting with motivational interviewing. Two other strategies they highlight include using language to re-emphasize the importance of adhering to the CDC recommended schedule — “He really needs these shots” — and bundling discussion of all recommended vaccines for a visit at once.
“Finally, clinicians can emphasize their own experiences when discussing the need for vaccination, including personal experience with vaccine-preventable diseases and the fact that they and their families are vaccinated because of their confidence in the safety and efficacy of the vaccines,” the authors wrote.
For families who refuse or delay vaccines, the authors reviewed the “ethical arguments both in favor of and against dismissal policies,” noting that nearly all pediatricians who report dismissing families who refuse vaccination are in private practice, since large systems are often unable to dismiss patients. They also point out that fewer pediatricians dismiss families for spreading out vaccines than outright refusing all vaccines.
”Dismissal of child patients of vaccine-refusing parents can be a difficult decision arrived at after considering multiple factors and documented attempts to counsel vaccine-refusing families,” they wrote. “However, if repeated attempts to help understand and address parental values and vaccine concerns fails to engender trust, move parents toward vaccine acceptance, or strengthen the therapeutic alliance, dismissal can be an acceptable option.”
Finally, the authors reminded pediatricians “that vaccine-hesitant parents are a heterogeneous group and that specific parental vaccine concerns need to be individually identified and addressed.” Working with families to discuss their questions and concerns is an opportunity to “build rapport and trust with a family,” they wrote, ”and, ultimately, protect their children from the scourge of vaccine-preventable diseases.”
The focus groups study was funded by the National Institutes of Health, and the authors reported having no disclosures. The Colorado attitudes study used no external funding, and the authors reported no disclosures. The new clinical report used no external funding, and the authors reported no disclosures. Dr. Orenstein is an uncompensated member of the Moderna Scientific Advisory Board. Dr. Offit codeveloped a licensed rotavirus vaccine, but he does not receive any royalties or own a patent for that.
FROM PEDIATRICS
GLP-1s’ Next Target: Male Infertility?
The explosion of interest in glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, has raised questions about what therapeutic effects this class of medication might have beyond their current indications for type 2 diabetes and obesity.
Recent clinical trials have recently identified benefits from GLP-1 agents for the heart, liver, and kidneys, but the current evidence base is murkier regarding how the drugs may affect male fertility.
For starters, overweight and obesity are strongly associated with male infertility in several overlapping ways. Obesity can disrupt hormones linked to fertility, increase the risk for defective sperm, adversely affect semen quality, and even make sexual intercourse more difficult due to obesity’s link to erectile dysfunction. As a result, GLP-1 RAs should at least in theory boost male fertility in men who take the drugs to lose weight.
But animal studies and a handful of small trials and observational data point to the potential for GLP-1 RAs to improve male fertility in other ways.
A recent narrative review on GLP-1 RAs and male reproductive health, published in the journal Medicina in December 2023, surveyed the potential of the drugs for male infertility and offered reason for optimism.
Hossein Sadeghi-Nejad, MD, director of urology at NYU Langone Health, New York, and a coauthor of the article, said that one reason he and his colleagues conducted their analysis was the known association between weight loss and an increase in testosterone.
“Most of the animal studies that are out there show that this class of drugs does affect testosterone levels,” Dr. Sadeghi-Nejad said; they wanted to better understand what other evidence showed about GLP-1 agonists and other fertility factors.
Link Between Obesity and Fertility
The recent paper first reviews the well-established link between obesity and poorer fertility outcomes.
“Certainly, obesity poses a significant societal problem with substantial impacts on both overall health and economic aspects,” senior author Ranjith Ramasamy, MD, associate professor of urology and director of the reproductive urology Fellowship program at the University of Miami’s Miller School of Medicine, told this news organization. “The escalating global obesity rates raise concerns, especially in the field of male infertility, where excessive body fat induces intrinsic hormonal changes leading to alterations, eventually, in semen parameters.”
The authors noted that obesity has been linked in the research to worse assisted reproductive technology (ART) outcomes and to subfecundity, taking more than 12 months to achieve pregnancy. They also referenced a systematic review that found men with obesity were more likely to have lower sperm counts and less viable sperm.
“From our standpoint, I think the key point was to raise awareness about the fact that obesity, because of the aromatization of testosterone to estradiol [from excess adipose tissue], will affect the hormonal axis and the availability of testosterone and, therefore, indirectly affects spermatogenesis,” Dr. Sadeghi-Nejad said.
Obesity is also linked to lower levels of inhibin B, which stimulates testosterone secretion in Sertoli cells, which, when combined with the proinflammatory state of obesity, “results in a less favorable environment for sperm production,” he said. Finally, the link between obesity and poorer sexual function further inhibits fertility potential, he added.
Until recently, the primary treatments for obesity in men experiencing fertility problems have been lifestyle modifications or surgical interventions. But the recent approval of GLP-1 RA drugs for obesity present an additional option depending on how these drugs affect other fertility parameters.
Direct or Indirect Effects?
Most of the available evidence on GLP-RAs and sperm parameters comes from preclinical research. One of the few clinical trials, published last year in the Journal of Clinical Medicine, investigated the effects of liraglutide in men with metabolic hypogonadism, a body mass index between (BMI) 30 and 40, and severe erectile dysfunction.
Among the 110 men enrolled in the study, only the 35 participants who said that they were not seeking fatherhood received liraglutide. After 4 months of treatment, these men had significantly improved semen concentration, motility, and morphology than did those wanting to conceive who received conventional fertility treatment. Erectile dysfunction was also more improved in the liraglutide group, according to the researchers.
Though this study demonstrated the potential for liraglutide to treat metabolic hypogonadism, the men in that group also had greater weight loss and BMI reduction than the other participants. The review cited several other studies — albeit small ones — in which weight loss was associated with improvements in sperm parameters, including one randomized controlled trial in which one group lost weight with liraglutide and the other with lifestyle modifications; both groups showed increases in the concentration and number of sperm.
One of the key questions requiring further research, then, is whether GLP-1 agents have direct effects on male fertility independent of a reduction in obesity. The randomized controlled trials comparing liraglutide and lifestyle modifications failed to find additional effects on semen in the men taking liraglutide; however, the study had only 56 participants, and results from liraglutide cannot be generalized to potential effects of semaglutide or tirzepatide, Dr. Sadeghi-Nejad said.
“Determining the relative contributions of weight loss versus direct drug actions on fertility outcomes remains challenging without robust data,” Dr. Ramasamy said. “While acknowledged that diet and physical activity positively impact fertility, confirming the synergistic role of GLP-1 receptor agonists requires evidence from well-designed randomized clinical trials.”
Rodent studies suggest that GLP-1 RAs may independently affect testicular function because GLP-1 receptors exist in Sertoli and Leydig cells of the testes. In one study, for example, obese mice who received the GLP-1 agonist exenatide for 8 weeks had “improved sperm motility, DNA integrity, and decreased expression of pro-inflammatory cytokines,” the authors of the review reported. But the precise mechanisms aren’t well understood.
“We know that there are GLP-1 receptors in the reproductive tract, but the extent of the downstream effect of stimulating those receptors, I don’t think we know well,” said John P. Lindsey II, MD, MEng, assistant professor of urology at University of California San Francisco Health.
Other hormonal effects of GLP-1 agonists, such as stimulating insulin production and better regulating blood glucose levels, are better understood, said Raevti Bole, MD, a urologist at Cleveland Clinic, in Ohio, but still other effects of the drugs may not yet be identified.
“I think the really big unknown is whether these types of drugs have effects that are not hormonal on male fertility and what those effects are, and how those affect sperm,” Dr. Bole said. “For example, we know that these drugs slow gastric emptying. Is it possible that slow gastric emptying affects some of the nutrients that you absorb, and that could affect fertility?” Similarly, she said, it’s not clear whether GLP-1 agonists would have any effects on the thyroid that could then affect fertility.
Effects on Offspring
Another open question about GLP-1 RAs and male fertility is their potential effects on the offspring, said Sriram Machineni, MBBS, associate professor of endocrinology at the Albert Einstein College of Medicine in New York City. The clinical trials involving the drugs for treating type 2 diabetes and obesity required both men and women to use contraception. If sperm contributing to a pregnancy are exposed to a GLP-1 agent, “we don’t know what the consequences could be,” Dr. Machineni said. “Just increasing the fertility of the man is not enough. We need to make sure it’s safe long-term for the fetus.”
Dr. Bole also pointed out the need for understanding potential effects in the fetus.
“We know that there are epigenetic changes that can happen to sperm that are influenced by the lifestyle and the physical health and environment of the parent,” Dr. Bole said. “So how could these drugs potentially affect those epigenetic changes that then potentially are passed on to the offspring? We don’t know that.”
An ideal source for that data would be a cohort registry of people who are taking the medication and then cause a pregnancy. “They have a registry for pregnant women,” Dr. Machineni said, “but we need something similar for men.”
Dr. Sadeghi-Nejad said that he and his coauthors are working on developing a registry for men who take GLP-1 RAs that would enable long-term tracking of multiple andrologic outcomes, including fertility and sexual dysfunction. Such a registry could theoretically be useful in tracking pregnancy and offspring outcomes as well.
Too Soon for Prescribing
Additional options for treating fertility in men with obesity would be welcome. Current treatments include the selective estrogen receptor modulator (SERM) clomiphene citrate and the aromatase inhibitor anastrozole. But these have their drawbacks, Dr. Sadeghi-Nejad pointed out; in the overweight population in particular, they “are not necessarily ideal,” he said.
“Although both are viable treatments for enhancing hormonal balance and semen parameters, clomiphene citrate has rare but documented side effects, including thromboembolism, gastrointestinal distress and occasional weight gain in men,” Dr. Sadeghi-Nejad and his colleagues wrote. “Furthermore, despite clomiphene citrate’s association with significant increases in sperm concentration, it is not universally effective, with a meta-analysis indicating a significant increase in sperm concentration in approximately 60% of men.”
For men who have obesity and oligospermia but normal levels of testosterone and estradiol, “conventional pharmaceutical approaches like clomiphene may not be suitable,” the authors wrote.
Still, GLP-1 RAs may have a role to play for this population.
“I think it is within the wheelhouse of a reproductive urologist to consider those types of medications,” Dr. Lindsey said. For example, for a patient who has overweight or obesity, “does it make sense to think about doing clomiphene therapy, which we often do for someone who has low testosterone, in conjunction [with a GLP-1 agonist]? Maybe there’s a kind of an additive effect of having both on board.”
Dr. Ramasamy similarly noted that GLP-1 agonists cannot replace SERMs but may work “synergistically” with them.
“Despite the established popularity of GLP-1 receptor agonists, there may be some reluctance among urologists and fertility specialists to prescribe them, with some others advocating for their use to enhance semen parameters,” Dr. Ramasamy said. “However, robust scientific evidence is still lacking, necessitating caution and a wait for more substantial data.”
Even if GLP-1 RAs prove to have therapeutic benefit for fertility, considerations such as availability and cost may affect prescribing.
“We do currently have safe and effective drugs that we use for male fertility, and those are generally nowhere near as expensive,” Dr. Bole said. “When we start talking about another drug that we can add, we have to think about the efficacy and the potential side effect but also, is this affordable for patients?”
Eventually, once more evidence become available, all of the urologists who spoke with this news organization said that they expect discussion about the possible therapeutic utility of GLP-1 agonists to make its way into clinical guidelines.
“Obesity is such a huge impediment for fertility in the modern environment,” Dr. Machineni said. “We will have to clarify the use of these agents, so I think this will be a part of the guidelines some point, but I think we need more information.”
The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the American Cancer Society. The review authors and other quoted physicians reported no disclosures. Dr. Machineni has consulted for Novo Nordisk and Lilly and has conducted clinical trials with semaglutide and tirzepatide for those companies.
A version of this article appeared on Medscape.com.
The explosion of interest in glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, has raised questions about what therapeutic effects this class of medication might have beyond their current indications for type 2 diabetes and obesity.
Recent clinical trials have recently identified benefits from GLP-1 agents for the heart, liver, and kidneys, but the current evidence base is murkier regarding how the drugs may affect male fertility.
For starters, overweight and obesity are strongly associated with male infertility in several overlapping ways. Obesity can disrupt hormones linked to fertility, increase the risk for defective sperm, adversely affect semen quality, and even make sexual intercourse more difficult due to obesity’s link to erectile dysfunction. As a result, GLP-1 RAs should at least in theory boost male fertility in men who take the drugs to lose weight.
But animal studies and a handful of small trials and observational data point to the potential for GLP-1 RAs to improve male fertility in other ways.
A recent narrative review on GLP-1 RAs and male reproductive health, published in the journal Medicina in December 2023, surveyed the potential of the drugs for male infertility and offered reason for optimism.
Hossein Sadeghi-Nejad, MD, director of urology at NYU Langone Health, New York, and a coauthor of the article, said that one reason he and his colleagues conducted their analysis was the known association between weight loss and an increase in testosterone.
“Most of the animal studies that are out there show that this class of drugs does affect testosterone levels,” Dr. Sadeghi-Nejad said; they wanted to better understand what other evidence showed about GLP-1 agonists and other fertility factors.
Link Between Obesity and Fertility
The recent paper first reviews the well-established link between obesity and poorer fertility outcomes.
“Certainly, obesity poses a significant societal problem with substantial impacts on both overall health and economic aspects,” senior author Ranjith Ramasamy, MD, associate professor of urology and director of the reproductive urology Fellowship program at the University of Miami’s Miller School of Medicine, told this news organization. “The escalating global obesity rates raise concerns, especially in the field of male infertility, where excessive body fat induces intrinsic hormonal changes leading to alterations, eventually, in semen parameters.”
The authors noted that obesity has been linked in the research to worse assisted reproductive technology (ART) outcomes and to subfecundity, taking more than 12 months to achieve pregnancy. They also referenced a systematic review that found men with obesity were more likely to have lower sperm counts and less viable sperm.
“From our standpoint, I think the key point was to raise awareness about the fact that obesity, because of the aromatization of testosterone to estradiol [from excess adipose tissue], will affect the hormonal axis and the availability of testosterone and, therefore, indirectly affects spermatogenesis,” Dr. Sadeghi-Nejad said.
Obesity is also linked to lower levels of inhibin B, which stimulates testosterone secretion in Sertoli cells, which, when combined with the proinflammatory state of obesity, “results in a less favorable environment for sperm production,” he said. Finally, the link between obesity and poorer sexual function further inhibits fertility potential, he added.
Until recently, the primary treatments for obesity in men experiencing fertility problems have been lifestyle modifications or surgical interventions. But the recent approval of GLP-1 RA drugs for obesity present an additional option depending on how these drugs affect other fertility parameters.
Direct or Indirect Effects?
Most of the available evidence on GLP-RAs and sperm parameters comes from preclinical research. One of the few clinical trials, published last year in the Journal of Clinical Medicine, investigated the effects of liraglutide in men with metabolic hypogonadism, a body mass index between (BMI) 30 and 40, and severe erectile dysfunction.
Among the 110 men enrolled in the study, only the 35 participants who said that they were not seeking fatherhood received liraglutide. After 4 months of treatment, these men had significantly improved semen concentration, motility, and morphology than did those wanting to conceive who received conventional fertility treatment. Erectile dysfunction was also more improved in the liraglutide group, according to the researchers.
Though this study demonstrated the potential for liraglutide to treat metabolic hypogonadism, the men in that group also had greater weight loss and BMI reduction than the other participants. The review cited several other studies — albeit small ones — in which weight loss was associated with improvements in sperm parameters, including one randomized controlled trial in which one group lost weight with liraglutide and the other with lifestyle modifications; both groups showed increases in the concentration and number of sperm.
One of the key questions requiring further research, then, is whether GLP-1 agents have direct effects on male fertility independent of a reduction in obesity. The randomized controlled trials comparing liraglutide and lifestyle modifications failed to find additional effects on semen in the men taking liraglutide; however, the study had only 56 participants, and results from liraglutide cannot be generalized to potential effects of semaglutide or tirzepatide, Dr. Sadeghi-Nejad said.
“Determining the relative contributions of weight loss versus direct drug actions on fertility outcomes remains challenging without robust data,” Dr. Ramasamy said. “While acknowledged that diet and physical activity positively impact fertility, confirming the synergistic role of GLP-1 receptor agonists requires evidence from well-designed randomized clinical trials.”
Rodent studies suggest that GLP-1 RAs may independently affect testicular function because GLP-1 receptors exist in Sertoli and Leydig cells of the testes. In one study, for example, obese mice who received the GLP-1 agonist exenatide for 8 weeks had “improved sperm motility, DNA integrity, and decreased expression of pro-inflammatory cytokines,” the authors of the review reported. But the precise mechanisms aren’t well understood.
“We know that there are GLP-1 receptors in the reproductive tract, but the extent of the downstream effect of stimulating those receptors, I don’t think we know well,” said John P. Lindsey II, MD, MEng, assistant professor of urology at University of California San Francisco Health.
Other hormonal effects of GLP-1 agonists, such as stimulating insulin production and better regulating blood glucose levels, are better understood, said Raevti Bole, MD, a urologist at Cleveland Clinic, in Ohio, but still other effects of the drugs may not yet be identified.
“I think the really big unknown is whether these types of drugs have effects that are not hormonal on male fertility and what those effects are, and how those affect sperm,” Dr. Bole said. “For example, we know that these drugs slow gastric emptying. Is it possible that slow gastric emptying affects some of the nutrients that you absorb, and that could affect fertility?” Similarly, she said, it’s not clear whether GLP-1 agonists would have any effects on the thyroid that could then affect fertility.
Effects on Offspring
Another open question about GLP-1 RAs and male fertility is their potential effects on the offspring, said Sriram Machineni, MBBS, associate professor of endocrinology at the Albert Einstein College of Medicine in New York City. The clinical trials involving the drugs for treating type 2 diabetes and obesity required both men and women to use contraception. If sperm contributing to a pregnancy are exposed to a GLP-1 agent, “we don’t know what the consequences could be,” Dr. Machineni said. “Just increasing the fertility of the man is not enough. We need to make sure it’s safe long-term for the fetus.”
Dr. Bole also pointed out the need for understanding potential effects in the fetus.
“We know that there are epigenetic changes that can happen to sperm that are influenced by the lifestyle and the physical health and environment of the parent,” Dr. Bole said. “So how could these drugs potentially affect those epigenetic changes that then potentially are passed on to the offspring? We don’t know that.”
An ideal source for that data would be a cohort registry of people who are taking the medication and then cause a pregnancy. “They have a registry for pregnant women,” Dr. Machineni said, “but we need something similar for men.”
Dr. Sadeghi-Nejad said that he and his coauthors are working on developing a registry for men who take GLP-1 RAs that would enable long-term tracking of multiple andrologic outcomes, including fertility and sexual dysfunction. Such a registry could theoretically be useful in tracking pregnancy and offspring outcomes as well.
Too Soon for Prescribing
Additional options for treating fertility in men with obesity would be welcome. Current treatments include the selective estrogen receptor modulator (SERM) clomiphene citrate and the aromatase inhibitor anastrozole. But these have their drawbacks, Dr. Sadeghi-Nejad pointed out; in the overweight population in particular, they “are not necessarily ideal,” he said.
“Although both are viable treatments for enhancing hormonal balance and semen parameters, clomiphene citrate has rare but documented side effects, including thromboembolism, gastrointestinal distress and occasional weight gain in men,” Dr. Sadeghi-Nejad and his colleagues wrote. “Furthermore, despite clomiphene citrate’s association with significant increases in sperm concentration, it is not universally effective, with a meta-analysis indicating a significant increase in sperm concentration in approximately 60% of men.”
For men who have obesity and oligospermia but normal levels of testosterone and estradiol, “conventional pharmaceutical approaches like clomiphene may not be suitable,” the authors wrote.
Still, GLP-1 RAs may have a role to play for this population.
“I think it is within the wheelhouse of a reproductive urologist to consider those types of medications,” Dr. Lindsey said. For example, for a patient who has overweight or obesity, “does it make sense to think about doing clomiphene therapy, which we often do for someone who has low testosterone, in conjunction [with a GLP-1 agonist]? Maybe there’s a kind of an additive effect of having both on board.”
Dr. Ramasamy similarly noted that GLP-1 agonists cannot replace SERMs but may work “synergistically” with them.
“Despite the established popularity of GLP-1 receptor agonists, there may be some reluctance among urologists and fertility specialists to prescribe them, with some others advocating for their use to enhance semen parameters,” Dr. Ramasamy said. “However, robust scientific evidence is still lacking, necessitating caution and a wait for more substantial data.”
Even if GLP-1 RAs prove to have therapeutic benefit for fertility, considerations such as availability and cost may affect prescribing.
“We do currently have safe and effective drugs that we use for male fertility, and those are generally nowhere near as expensive,” Dr. Bole said. “When we start talking about another drug that we can add, we have to think about the efficacy and the potential side effect but also, is this affordable for patients?”
Eventually, once more evidence become available, all of the urologists who spoke with this news organization said that they expect discussion about the possible therapeutic utility of GLP-1 agonists to make its way into clinical guidelines.
“Obesity is such a huge impediment for fertility in the modern environment,” Dr. Machineni said. “We will have to clarify the use of these agents, so I think this will be a part of the guidelines some point, but I think we need more information.”
The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the American Cancer Society. The review authors and other quoted physicians reported no disclosures. Dr. Machineni has consulted for Novo Nordisk and Lilly and has conducted clinical trials with semaglutide and tirzepatide for those companies.
A version of this article appeared on Medscape.com.
The explosion of interest in glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, has raised questions about what therapeutic effects this class of medication might have beyond their current indications for type 2 diabetes and obesity.
Recent clinical trials have recently identified benefits from GLP-1 agents for the heart, liver, and kidneys, but the current evidence base is murkier regarding how the drugs may affect male fertility.
For starters, overweight and obesity are strongly associated with male infertility in several overlapping ways. Obesity can disrupt hormones linked to fertility, increase the risk for defective sperm, adversely affect semen quality, and even make sexual intercourse more difficult due to obesity’s link to erectile dysfunction. As a result, GLP-1 RAs should at least in theory boost male fertility in men who take the drugs to lose weight.
But animal studies and a handful of small trials and observational data point to the potential for GLP-1 RAs to improve male fertility in other ways.
A recent narrative review on GLP-1 RAs and male reproductive health, published in the journal Medicina in December 2023, surveyed the potential of the drugs for male infertility and offered reason for optimism.
Hossein Sadeghi-Nejad, MD, director of urology at NYU Langone Health, New York, and a coauthor of the article, said that one reason he and his colleagues conducted their analysis was the known association between weight loss and an increase in testosterone.
“Most of the animal studies that are out there show that this class of drugs does affect testosterone levels,” Dr. Sadeghi-Nejad said; they wanted to better understand what other evidence showed about GLP-1 agonists and other fertility factors.
Link Between Obesity and Fertility
The recent paper first reviews the well-established link between obesity and poorer fertility outcomes.
“Certainly, obesity poses a significant societal problem with substantial impacts on both overall health and economic aspects,” senior author Ranjith Ramasamy, MD, associate professor of urology and director of the reproductive urology Fellowship program at the University of Miami’s Miller School of Medicine, told this news organization. “The escalating global obesity rates raise concerns, especially in the field of male infertility, where excessive body fat induces intrinsic hormonal changes leading to alterations, eventually, in semen parameters.”
The authors noted that obesity has been linked in the research to worse assisted reproductive technology (ART) outcomes and to subfecundity, taking more than 12 months to achieve pregnancy. They also referenced a systematic review that found men with obesity were more likely to have lower sperm counts and less viable sperm.
“From our standpoint, I think the key point was to raise awareness about the fact that obesity, because of the aromatization of testosterone to estradiol [from excess adipose tissue], will affect the hormonal axis and the availability of testosterone and, therefore, indirectly affects spermatogenesis,” Dr. Sadeghi-Nejad said.
Obesity is also linked to lower levels of inhibin B, which stimulates testosterone secretion in Sertoli cells, which, when combined with the proinflammatory state of obesity, “results in a less favorable environment for sperm production,” he said. Finally, the link between obesity and poorer sexual function further inhibits fertility potential, he added.
Until recently, the primary treatments for obesity in men experiencing fertility problems have been lifestyle modifications or surgical interventions. But the recent approval of GLP-1 RA drugs for obesity present an additional option depending on how these drugs affect other fertility parameters.
Direct or Indirect Effects?
Most of the available evidence on GLP-RAs and sperm parameters comes from preclinical research. One of the few clinical trials, published last year in the Journal of Clinical Medicine, investigated the effects of liraglutide in men with metabolic hypogonadism, a body mass index between (BMI) 30 and 40, and severe erectile dysfunction.
Among the 110 men enrolled in the study, only the 35 participants who said that they were not seeking fatherhood received liraglutide. After 4 months of treatment, these men had significantly improved semen concentration, motility, and morphology than did those wanting to conceive who received conventional fertility treatment. Erectile dysfunction was also more improved in the liraglutide group, according to the researchers.
Though this study demonstrated the potential for liraglutide to treat metabolic hypogonadism, the men in that group also had greater weight loss and BMI reduction than the other participants. The review cited several other studies — albeit small ones — in which weight loss was associated with improvements in sperm parameters, including one randomized controlled trial in which one group lost weight with liraglutide and the other with lifestyle modifications; both groups showed increases in the concentration and number of sperm.
One of the key questions requiring further research, then, is whether GLP-1 agents have direct effects on male fertility independent of a reduction in obesity. The randomized controlled trials comparing liraglutide and lifestyle modifications failed to find additional effects on semen in the men taking liraglutide; however, the study had only 56 participants, and results from liraglutide cannot be generalized to potential effects of semaglutide or tirzepatide, Dr. Sadeghi-Nejad said.
“Determining the relative contributions of weight loss versus direct drug actions on fertility outcomes remains challenging without robust data,” Dr. Ramasamy said. “While acknowledged that diet and physical activity positively impact fertility, confirming the synergistic role of GLP-1 receptor agonists requires evidence from well-designed randomized clinical trials.”
Rodent studies suggest that GLP-1 RAs may independently affect testicular function because GLP-1 receptors exist in Sertoli and Leydig cells of the testes. In one study, for example, obese mice who received the GLP-1 agonist exenatide for 8 weeks had “improved sperm motility, DNA integrity, and decreased expression of pro-inflammatory cytokines,” the authors of the review reported. But the precise mechanisms aren’t well understood.
“We know that there are GLP-1 receptors in the reproductive tract, but the extent of the downstream effect of stimulating those receptors, I don’t think we know well,” said John P. Lindsey II, MD, MEng, assistant professor of urology at University of California San Francisco Health.
Other hormonal effects of GLP-1 agonists, such as stimulating insulin production and better regulating blood glucose levels, are better understood, said Raevti Bole, MD, a urologist at Cleveland Clinic, in Ohio, but still other effects of the drugs may not yet be identified.
“I think the really big unknown is whether these types of drugs have effects that are not hormonal on male fertility and what those effects are, and how those affect sperm,” Dr. Bole said. “For example, we know that these drugs slow gastric emptying. Is it possible that slow gastric emptying affects some of the nutrients that you absorb, and that could affect fertility?” Similarly, she said, it’s not clear whether GLP-1 agonists would have any effects on the thyroid that could then affect fertility.
Effects on Offspring
Another open question about GLP-1 RAs and male fertility is their potential effects on the offspring, said Sriram Machineni, MBBS, associate professor of endocrinology at the Albert Einstein College of Medicine in New York City. The clinical trials involving the drugs for treating type 2 diabetes and obesity required both men and women to use contraception. If sperm contributing to a pregnancy are exposed to a GLP-1 agent, “we don’t know what the consequences could be,” Dr. Machineni said. “Just increasing the fertility of the man is not enough. We need to make sure it’s safe long-term for the fetus.”
Dr. Bole also pointed out the need for understanding potential effects in the fetus.
“We know that there are epigenetic changes that can happen to sperm that are influenced by the lifestyle and the physical health and environment of the parent,” Dr. Bole said. “So how could these drugs potentially affect those epigenetic changes that then potentially are passed on to the offspring? We don’t know that.”
An ideal source for that data would be a cohort registry of people who are taking the medication and then cause a pregnancy. “They have a registry for pregnant women,” Dr. Machineni said, “but we need something similar for men.”
Dr. Sadeghi-Nejad said that he and his coauthors are working on developing a registry for men who take GLP-1 RAs that would enable long-term tracking of multiple andrologic outcomes, including fertility and sexual dysfunction. Such a registry could theoretically be useful in tracking pregnancy and offspring outcomes as well.
Too Soon for Prescribing
Additional options for treating fertility in men with obesity would be welcome. Current treatments include the selective estrogen receptor modulator (SERM) clomiphene citrate and the aromatase inhibitor anastrozole. But these have their drawbacks, Dr. Sadeghi-Nejad pointed out; in the overweight population in particular, they “are not necessarily ideal,” he said.
“Although both are viable treatments for enhancing hormonal balance and semen parameters, clomiphene citrate has rare but documented side effects, including thromboembolism, gastrointestinal distress and occasional weight gain in men,” Dr. Sadeghi-Nejad and his colleagues wrote. “Furthermore, despite clomiphene citrate’s association with significant increases in sperm concentration, it is not universally effective, with a meta-analysis indicating a significant increase in sperm concentration in approximately 60% of men.”
For men who have obesity and oligospermia but normal levels of testosterone and estradiol, “conventional pharmaceutical approaches like clomiphene may not be suitable,” the authors wrote.
Still, GLP-1 RAs may have a role to play for this population.
“I think it is within the wheelhouse of a reproductive urologist to consider those types of medications,” Dr. Lindsey said. For example, for a patient who has overweight or obesity, “does it make sense to think about doing clomiphene therapy, which we often do for someone who has low testosterone, in conjunction [with a GLP-1 agonist]? Maybe there’s a kind of an additive effect of having both on board.”
Dr. Ramasamy similarly noted that GLP-1 agonists cannot replace SERMs but may work “synergistically” with them.
“Despite the established popularity of GLP-1 receptor agonists, there may be some reluctance among urologists and fertility specialists to prescribe them, with some others advocating for their use to enhance semen parameters,” Dr. Ramasamy said. “However, robust scientific evidence is still lacking, necessitating caution and a wait for more substantial data.”
Even if GLP-1 RAs prove to have therapeutic benefit for fertility, considerations such as availability and cost may affect prescribing.
“We do currently have safe and effective drugs that we use for male fertility, and those are generally nowhere near as expensive,” Dr. Bole said. “When we start talking about another drug that we can add, we have to think about the efficacy and the potential side effect but also, is this affordable for patients?”
Eventually, once more evidence become available, all of the urologists who spoke with this news organization said that they expect discussion about the possible therapeutic utility of GLP-1 agonists to make its way into clinical guidelines.
“Obesity is such a huge impediment for fertility in the modern environment,” Dr. Machineni said. “We will have to clarify the use of these agents, so I think this will be a part of the guidelines some point, but I think we need more information.”
The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the American Cancer Society. The review authors and other quoted physicians reported no disclosures. Dr. Machineni has consulted for Novo Nordisk and Lilly and has conducted clinical trials with semaglutide and tirzepatide for those companies.
A version of this article appeared on Medscape.com.
Autoimmune Disease Risk May Rise Following Cushing Disease Remission After Surgery
Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.
Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).
“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.
Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
Monitor Patients With Family History of Autoimmune Disease?
The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.
If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.
At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.
The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.
The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”
Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.
Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.
After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).
Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.
Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”
Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
Could Postoperative Adrenal Insufficiency Contribute to Risk?
Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.
“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”
Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).
“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.
At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.
Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
A version of this article appeared on Medscape.com.
Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.
Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).
“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.
Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
Monitor Patients With Family History of Autoimmune Disease?
The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.
If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.
At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.
The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.
The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”
Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.
Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.
After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).
Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.
Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”
Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
Could Postoperative Adrenal Insufficiency Contribute to Risk?
Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.
“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”
Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).
“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.
At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.
Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
A version of this article appeared on Medscape.com.
Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.
Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).
“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.
Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
Monitor Patients With Family History of Autoimmune Disease?
The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.
If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.
At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.
The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.
The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”
Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.
Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.
After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).
Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.
Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”
Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
Could Postoperative Adrenal Insufficiency Contribute to Risk?
Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.
“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”
Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).
“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.
At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.
Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
A version of this article appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Sepsis mortality greater in Black than White children despite similar interventions
WASHINGTON – , according to research presented at the annual meeting of the American Academy of Pediatrics.
The only other difference between Black and White pediatric patients was the length of hospital stay and the length of time in the ICU among those who died. In both cases, Black children who died spent more time in the hospital and in the ICU, reported Michael H. Stroud, MD, a pediatric critical care physician at the University of Arkansas for Medical Sciences in Little Rock, and his colleagues.
“Further investigations are needed to identify biases, conscious and unconscious, potential socioeconomic factors, and genetic predispositions leading to racial disparities in outcomes of children with pediatric sepsis, severe sepsis, and septic shock,” Dr Stroud and his colleagues said.
Nathan T. Chomilo, MD, adjunct assistant professor of pediatrics at the University of Minnesota, Minneapolis, who was not involved in the study but reviewed it, said the research “builds upon existing evidence that our health care system has work to do to meet its goal of treating patients equitably and provide everyone the opportunity for health.” He found the racial disparity in death particularly striking in 2023. “In the U.S., with all our wealth, knowledge, and resources, very few children should die from this, let alone there be such a stark gap,” Dr. Chomilo wrote.
Racial disparities persist
Dr. Stroud noted that many institutions currently use “automated, real-time, algorithm-based detection of sepsis, severe sepsis, and septic shock incorporated into the electronic medical record,” which leads to earlier recognition and resuscitation and overall better outcomes. Yet racial disparities in sepsis mortality rates persist, and he and his colleagues wanted to explore whether they remained even with these EMR-incorporated systems.
The researchers analyzed data from all patients at Arkansas Children’s Hospital who had sepsis, severe sepsis, or septic shock between January 2018 and April 2022. The hospital uses a best practice advisory (BPA) in the EMR whose activation leads to a bedside huddle and clinical interventions. For this study, the researchers defined a sepsis episode as either a BPA activation or an EMR diagnosis of sepsis, severe sepsis, or septic shock.
Among the 3,514 patients who had a sepsis episode during the study, 60.5% were White (n = 2,126) and 20.9% were Black (n = 736). Overall mortality was 1.65%, but that included 3.13% of Black children versus 1.27% of White children (odds ratio [OR] 2.51, P = .001). No significant differences in mortality were seen in gender or age.
Clinical interventions in the two groups were also similar: Total IV antibiotic days were 23.8 days for Black children and 21.6 days for White children (P = .38); total vasoactive infusion days were 2.2 for Black children and 2.6 for White (P = .18); and extracorporeal membrane oxygenation was necessary for 26.1% of Black children and 18.5% of White children (P = .52).
Length of hospitalization stay, however, was an average 4 days longer for Black children (16.7 days) versus White children (12.7 days) who died (P = .03). ICU stay for Black children who died was also an average 1.9 days longer (7.57 vs. 5.7 days; P = .01). There were no significant differences in the EMR between Black and White patients, however, in the percent who were over the threshold for antibiotic administration and the percent who received an IV fluid bolus.
Contributing factors
Dr. Chomilo said that most BPA systems require staff – including rooming and triage staff, nurses. and physicians – to enter vital signs, order labs, enter the results into the system, and enter other data used by the algorithm. “So even though the time from when those BPA warnings flagged to when clinical interventions were documented didn’t show a significant difference, there are numerous other points along a child’s illness that may be contributing to these numbers,” Dr. Chomilo said.
For example, he pointed out that differences in health insurance coverage could have influenced whether their parent or caregiver was able to bring them in early enough to be diagnosed since studies have revealed disparate access to regular care due to structural racism in the health care system. Studies have also shown disparate rates of patients being triaged or having to wait longer in emergency departments, he added.
“When the child was brought in, how were they triaged? How long did they wait before they had vitals taken? How long until they were seen by a clinician?” Dr. Chomilo said. “Was their care on the inpatient ward the same or different? What was the source of sepsis? Was it all infectious or other issues [since] cancer and autoimmune illnesses can also trigger a sepsis evaluation, for example? Overall, I suspect answers to several of these questions would reveal a disparity due to structural racism that contributed to the ultimate disparity in deaths.”
Other social determinants of health that could have played a role in the outcome disparities here might include the family’s access to transportation options, parental employment or child care options, and nutrition access since baseline nutritional status can be a factor in the outcomes of severe illnesses like sepsis.
”I don’t think this study provided enough information about the potential causative factors to come to any strong conclusions,” Dr. Chomilo said. But it’s important for clinicians to be aware of how biases in the health care system put Black, Indigenous and other communities at higher risk for worse clinical outcomes.
“I would reiterate that clinicians in the hospital can help improve outcomes by being aware of structural racism and structural inequity and how that may contribute to their patient’s risk of severe illness as the decide how to approach their treatment and engaging the patient’s family,” Dr. Chomilo said. “We cannot rely solely on universal tools that don’t take this into account when we are looking to improve clinical outcomes for everyone. Otherwise we will see these gaps persist.”
No external funding sources were noted. Dr. Stroud and Dr. Chomilo had no disclosures.
WASHINGTON – , according to research presented at the annual meeting of the American Academy of Pediatrics.
The only other difference between Black and White pediatric patients was the length of hospital stay and the length of time in the ICU among those who died. In both cases, Black children who died spent more time in the hospital and in the ICU, reported Michael H. Stroud, MD, a pediatric critical care physician at the University of Arkansas for Medical Sciences in Little Rock, and his colleagues.
“Further investigations are needed to identify biases, conscious and unconscious, potential socioeconomic factors, and genetic predispositions leading to racial disparities in outcomes of children with pediatric sepsis, severe sepsis, and septic shock,” Dr Stroud and his colleagues said.
Nathan T. Chomilo, MD, adjunct assistant professor of pediatrics at the University of Minnesota, Minneapolis, who was not involved in the study but reviewed it, said the research “builds upon existing evidence that our health care system has work to do to meet its goal of treating patients equitably and provide everyone the opportunity for health.” He found the racial disparity in death particularly striking in 2023. “In the U.S., with all our wealth, knowledge, and resources, very few children should die from this, let alone there be such a stark gap,” Dr. Chomilo wrote.
Racial disparities persist
Dr. Stroud noted that many institutions currently use “automated, real-time, algorithm-based detection of sepsis, severe sepsis, and septic shock incorporated into the electronic medical record,” which leads to earlier recognition and resuscitation and overall better outcomes. Yet racial disparities in sepsis mortality rates persist, and he and his colleagues wanted to explore whether they remained even with these EMR-incorporated systems.
The researchers analyzed data from all patients at Arkansas Children’s Hospital who had sepsis, severe sepsis, or septic shock between January 2018 and April 2022. The hospital uses a best practice advisory (BPA) in the EMR whose activation leads to a bedside huddle and clinical interventions. For this study, the researchers defined a sepsis episode as either a BPA activation or an EMR diagnosis of sepsis, severe sepsis, or septic shock.
Among the 3,514 patients who had a sepsis episode during the study, 60.5% were White (n = 2,126) and 20.9% were Black (n = 736). Overall mortality was 1.65%, but that included 3.13% of Black children versus 1.27% of White children (odds ratio [OR] 2.51, P = .001). No significant differences in mortality were seen in gender or age.
Clinical interventions in the two groups were also similar: Total IV antibiotic days were 23.8 days for Black children and 21.6 days for White children (P = .38); total vasoactive infusion days were 2.2 for Black children and 2.6 for White (P = .18); and extracorporeal membrane oxygenation was necessary for 26.1% of Black children and 18.5% of White children (P = .52).
Length of hospitalization stay, however, was an average 4 days longer for Black children (16.7 days) versus White children (12.7 days) who died (P = .03). ICU stay for Black children who died was also an average 1.9 days longer (7.57 vs. 5.7 days; P = .01). There were no significant differences in the EMR between Black and White patients, however, in the percent who were over the threshold for antibiotic administration and the percent who received an IV fluid bolus.
Contributing factors
Dr. Chomilo said that most BPA systems require staff – including rooming and triage staff, nurses. and physicians – to enter vital signs, order labs, enter the results into the system, and enter other data used by the algorithm. “So even though the time from when those BPA warnings flagged to when clinical interventions were documented didn’t show a significant difference, there are numerous other points along a child’s illness that may be contributing to these numbers,” Dr. Chomilo said.
For example, he pointed out that differences in health insurance coverage could have influenced whether their parent or caregiver was able to bring them in early enough to be diagnosed since studies have revealed disparate access to regular care due to structural racism in the health care system. Studies have also shown disparate rates of patients being triaged or having to wait longer in emergency departments, he added.
“When the child was brought in, how were they triaged? How long did they wait before they had vitals taken? How long until they were seen by a clinician?” Dr. Chomilo said. “Was their care on the inpatient ward the same or different? What was the source of sepsis? Was it all infectious or other issues [since] cancer and autoimmune illnesses can also trigger a sepsis evaluation, for example? Overall, I suspect answers to several of these questions would reveal a disparity due to structural racism that contributed to the ultimate disparity in deaths.”
Other social determinants of health that could have played a role in the outcome disparities here might include the family’s access to transportation options, parental employment or child care options, and nutrition access since baseline nutritional status can be a factor in the outcomes of severe illnesses like sepsis.
”I don’t think this study provided enough information about the potential causative factors to come to any strong conclusions,” Dr. Chomilo said. But it’s important for clinicians to be aware of how biases in the health care system put Black, Indigenous and other communities at higher risk for worse clinical outcomes.
“I would reiterate that clinicians in the hospital can help improve outcomes by being aware of structural racism and structural inequity and how that may contribute to their patient’s risk of severe illness as the decide how to approach their treatment and engaging the patient’s family,” Dr. Chomilo said. “We cannot rely solely on universal tools that don’t take this into account when we are looking to improve clinical outcomes for everyone. Otherwise we will see these gaps persist.”
No external funding sources were noted. Dr. Stroud and Dr. Chomilo had no disclosures.
WASHINGTON – , according to research presented at the annual meeting of the American Academy of Pediatrics.
The only other difference between Black and White pediatric patients was the length of hospital stay and the length of time in the ICU among those who died. In both cases, Black children who died spent more time in the hospital and in the ICU, reported Michael H. Stroud, MD, a pediatric critical care physician at the University of Arkansas for Medical Sciences in Little Rock, and his colleagues.
“Further investigations are needed to identify biases, conscious and unconscious, potential socioeconomic factors, and genetic predispositions leading to racial disparities in outcomes of children with pediatric sepsis, severe sepsis, and septic shock,” Dr Stroud and his colleagues said.
Nathan T. Chomilo, MD, adjunct assistant professor of pediatrics at the University of Minnesota, Minneapolis, who was not involved in the study but reviewed it, said the research “builds upon existing evidence that our health care system has work to do to meet its goal of treating patients equitably and provide everyone the opportunity for health.” He found the racial disparity in death particularly striking in 2023. “In the U.S., with all our wealth, knowledge, and resources, very few children should die from this, let alone there be such a stark gap,” Dr. Chomilo wrote.
Racial disparities persist
Dr. Stroud noted that many institutions currently use “automated, real-time, algorithm-based detection of sepsis, severe sepsis, and septic shock incorporated into the electronic medical record,” which leads to earlier recognition and resuscitation and overall better outcomes. Yet racial disparities in sepsis mortality rates persist, and he and his colleagues wanted to explore whether they remained even with these EMR-incorporated systems.
The researchers analyzed data from all patients at Arkansas Children’s Hospital who had sepsis, severe sepsis, or septic shock between January 2018 and April 2022. The hospital uses a best practice advisory (BPA) in the EMR whose activation leads to a bedside huddle and clinical interventions. For this study, the researchers defined a sepsis episode as either a BPA activation or an EMR diagnosis of sepsis, severe sepsis, or septic shock.
Among the 3,514 patients who had a sepsis episode during the study, 60.5% were White (n = 2,126) and 20.9% were Black (n = 736). Overall mortality was 1.65%, but that included 3.13% of Black children versus 1.27% of White children (odds ratio [OR] 2.51, P = .001). No significant differences in mortality were seen in gender or age.
Clinical interventions in the two groups were also similar: Total IV antibiotic days were 23.8 days for Black children and 21.6 days for White children (P = .38); total vasoactive infusion days were 2.2 for Black children and 2.6 for White (P = .18); and extracorporeal membrane oxygenation was necessary for 26.1% of Black children and 18.5% of White children (P = .52).
Length of hospitalization stay, however, was an average 4 days longer for Black children (16.7 days) versus White children (12.7 days) who died (P = .03). ICU stay for Black children who died was also an average 1.9 days longer (7.57 vs. 5.7 days; P = .01). There were no significant differences in the EMR between Black and White patients, however, in the percent who were over the threshold for antibiotic administration and the percent who received an IV fluid bolus.
Contributing factors
Dr. Chomilo said that most BPA systems require staff – including rooming and triage staff, nurses. and physicians – to enter vital signs, order labs, enter the results into the system, and enter other data used by the algorithm. “So even though the time from when those BPA warnings flagged to when clinical interventions were documented didn’t show a significant difference, there are numerous other points along a child’s illness that may be contributing to these numbers,” Dr. Chomilo said.
For example, he pointed out that differences in health insurance coverage could have influenced whether their parent or caregiver was able to bring them in early enough to be diagnosed since studies have revealed disparate access to regular care due to structural racism in the health care system. Studies have also shown disparate rates of patients being triaged or having to wait longer in emergency departments, he added.
“When the child was brought in, how were they triaged? How long did they wait before they had vitals taken? How long until they were seen by a clinician?” Dr. Chomilo said. “Was their care on the inpatient ward the same or different? What was the source of sepsis? Was it all infectious or other issues [since] cancer and autoimmune illnesses can also trigger a sepsis evaluation, for example? Overall, I suspect answers to several of these questions would reveal a disparity due to structural racism that contributed to the ultimate disparity in deaths.”
Other social determinants of health that could have played a role in the outcome disparities here might include the family’s access to transportation options, parental employment or child care options, and nutrition access since baseline nutritional status can be a factor in the outcomes of severe illnesses like sepsis.
”I don’t think this study provided enough information about the potential causative factors to come to any strong conclusions,” Dr. Chomilo said. But it’s important for clinicians to be aware of how biases in the health care system put Black, Indigenous and other communities at higher risk for worse clinical outcomes.
“I would reiterate that clinicians in the hospital can help improve outcomes by being aware of structural racism and structural inequity and how that may contribute to their patient’s risk of severe illness as the decide how to approach their treatment and engaging the patient’s family,” Dr. Chomilo said. “We cannot rely solely on universal tools that don’t take this into account when we are looking to improve clinical outcomes for everyone. Otherwise we will see these gaps persist.”
No external funding sources were noted. Dr. Stroud and Dr. Chomilo had no disclosures.
AT AAP 2023
Five times greater suicide risk for trans, gender-diverse teens in ED
WASHINGTON – , according to a study presented at the annual meeting of the American Academy of Pediatrics.
“The take-home message here is this study emphasizes the importance of universal screening to identify gender-diverse youth at risk,” Amanda Burnside, PhD, assistant professor of psychiatry and behavioral sciences at Ann and Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, told attendees. “We really need to develop robust strategies and systems to link better mental health services.”
Suicide rates in transgender and gender-diverse youth are exceptionally high among youth in the U.S., Dr. Burnside said during her presentation. For example, the 2022 LGBTQ health survey from the Trevor Project found that much higher percentages of transgender and gender nonconforming youth had considered suicide in the past year compared with cisgender youth, even within the LGBTQ umbrella. Among nearly 34,000 LGBTQ youth aged 13-24, nearly half of trans females (48%) and more than half of trans males (59%) had considered suicide, compared with 28% of cisgender males and 37% of cisgender females. The rate among nonbinary/genderqueer individuals was 53%, and it was 48% for those questioning their gender.
Current methods of identifying trans and gender-diverse (TGD) youth in the hospital, however, may not actually be capturing the entire population.
“In health care settings, research involving TGD individuals has historically been limited to specialized clinic populations or youth with gender-specific diagnostic codes documented in the electronic medical record,” an approach that “likely significantly underestimates the prevalence of TGD youth in health care settings.” While at least one study has attempted to bridge this gap by searching the EMR for keywords, that study only tried to identify trans youth and not other youth on the gender diversity spectrum, such as nonbinary youth or those questioning their gender identity. Dr. Burnside and her colleagues therefore designed a study that used keywords to identify both trans youth and other gender-diverse youth who visited the ED so they could assess the rate of positive suicide screens in this population.
Underestimating the population at risk?
The researchers conducted a retrospective cross-sectional study of EMR data for all ED visits during which the patient underwent suicide screening. For the period of November 2019 to August 2022, they collected data on the screening results and the patient’s gender identity, age, race/ethnicity, insurance status, chief complaint in the ED and child opportunity index, which assess a youth’s access to resources based on geography. The suicide screener used was the Ask Suicide–Screening Questions (ASQ) tool.
The keywords they looked for in the EMR to identify trans and gender-diverse youth included transgender, pronouns, agender, gender dysphoria, male-to-female, female-to-male, nonbinary, preferred name, and they/them (captured as a complete term, not as “they” and “them” separately).
“If a keyword was present, the surrounding text was extracted and reviewed by two members of our team,” Dr. Burnside explained in her presentation. “We categorized keywords into either indicative of gender-diverse identity or not, and if it wasn’t clear based on the text extracted, we would conduct a manual chart review,” though that only occurred in about 3% of cases, she added.
Among 15,413 ED encounters with a suicide screen, the researchers identified 1,126 of these keywords in the EMR, among which 91.2% were classified as referring to a gender-diverse patient. Nearly all of the words were at least 90% effective in identify a gender-diverse youth, Dr. Burnside said, and all of the 197 instances of “they/them” were classified as gender diverse.
The accuracy was a little lower for the two keywords that appeared most frequently: For “pronouns,” 86.3% of 306 instances were classified as gender diverse, and for “transgender,” 83.1% of 207 instances were classified as gender diverse. Since some providers ask all patients their pronouns, the presence of “pronouns” in the EMR alone did not necessarily indicate the patient was gender diverse, Dr. Burnside said. A common reason the term “transgender” occurred in the EMR of non–gender diverse patients is that the department’s list of crisis resources includes transgender hotlines.
After identifying all the keywords, the researchers determined how many of these occurred in unique ED encounters and removed those with incomplete screening. Overall, they found 565 encounters by 399 gender-diverse individuals who had a suicide screening, representing 4.6% of total visits. This percentage is slightly lower than recent population-based estimates of gender-diverse youth, the researchers noted.
This population ranged from 8 to 23 years old, and 43% were publicly insured. The chief complaint for most of the patients (77.5%) was a mental health one. They were predominantly White (43%) or Hispanic (35%), with 10% Black youth, 4% Asian youth, and 8% youth who were “other” or two or more races. About half (52%) lived in a neighborhood with a “low” or “very low” child opportunity index.
Within this population, 81% of the patients screened positive on the suicide screening, compared with 23% positive screens across all ED visits. One in ten (10%) gender-diverse youth had active suicidal ideation, compared with 3.4% of the rest of the ED patient population. The researchers calculated that gender-diverse youth had 5.35 times greater odds of screening positive than cisgender youth in the ED (95% confidence interval [CI] 8.7-15.92). Further, a quarter (25%) of the trans and gender-diverse youth who screened positive for suicide risk had come to the ED for a primary complaint unrelated to mental health.
“We had a kid who came in because he broke his arm who had active suicidal ideation,” study coauthor Jennifer A. Hoffmann, MD, assistant professor of pediatrics at the Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, mentioned after the presentation. That particular patient even had a suicide plan, but was identified as actively suicidal only because of the screening. In other cases, she said, a youth may come in with self-inflicted injuries, and while those are the primary complaint, they are linked with suicidal ideation.
Among the study’s limitations are that gender identity is not necessarily being systematically assessed during visits, misspellings might have missed some youth, and their search strategy has not yet been externally validated, though they plan to seek that.
“Overall, however, this study did demonstrate that keyword searching is a promising technique to identify and prioritize gender-diverse youth in health services research,” Dr. Burnside said. In addition to showing the feasibility of using a keyword search strategy for identifying gender-diverse youth, Dr. Burnside noted that 31% of the encounters were identified by just one of the keywords they used, “highlighting the importance of using a comprehensive list of keywords to identify gender-diverse youth.”
Uncovering valuable information
Jason Rafferty, MD, MPH, EdM, clinical assistant professor of pediatrics and of psychiatry and human behavior at Brown University, Providence, R.I., who attended the presentation, noted that the study provides information on a population that’s often difficult to get through traditional EMR research methods.
“A lot of medical record systems don’t have uniform ways of capturing [gender diversity], but what we know as providers is that kids are really struggling and that it’s not a surprise that we’re seeing these disparities with suicidality,” Dr. Rafferty said.
The study also provides more discrete estimates by age than what most other current research measures, which tends to be lifetime suicidality as opposed to suicidal thoughts or attempts within the past year, Dr. Rafferty added.
”What this shows is, for adolescents, the risk of suicide is something we need to be paying attention to. Because it’s not that it’s something that only happens in adults, this really dispels a lot of the misquoting of the data that’s out there.” That kind of information is valuable for determining resource allocation, he said. “A disparity like this really underlies the importance of mental health resources in this field,” he said.
Dr. Burnside, Dr. Hoffmann, and Dr. Rafferty had no disclosures, and no external funding sources were noted.
WASHINGTON – , according to a study presented at the annual meeting of the American Academy of Pediatrics.
“The take-home message here is this study emphasizes the importance of universal screening to identify gender-diverse youth at risk,” Amanda Burnside, PhD, assistant professor of psychiatry and behavioral sciences at Ann and Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, told attendees. “We really need to develop robust strategies and systems to link better mental health services.”
Suicide rates in transgender and gender-diverse youth are exceptionally high among youth in the U.S., Dr. Burnside said during her presentation. For example, the 2022 LGBTQ health survey from the Trevor Project found that much higher percentages of transgender and gender nonconforming youth had considered suicide in the past year compared with cisgender youth, even within the LGBTQ umbrella. Among nearly 34,000 LGBTQ youth aged 13-24, nearly half of trans females (48%) and more than half of trans males (59%) had considered suicide, compared with 28% of cisgender males and 37% of cisgender females. The rate among nonbinary/genderqueer individuals was 53%, and it was 48% for those questioning their gender.
Current methods of identifying trans and gender-diverse (TGD) youth in the hospital, however, may not actually be capturing the entire population.
“In health care settings, research involving TGD individuals has historically been limited to specialized clinic populations or youth with gender-specific diagnostic codes documented in the electronic medical record,” an approach that “likely significantly underestimates the prevalence of TGD youth in health care settings.” While at least one study has attempted to bridge this gap by searching the EMR for keywords, that study only tried to identify trans youth and not other youth on the gender diversity spectrum, such as nonbinary youth or those questioning their gender identity. Dr. Burnside and her colleagues therefore designed a study that used keywords to identify both trans youth and other gender-diverse youth who visited the ED so they could assess the rate of positive suicide screens in this population.
Underestimating the population at risk?
The researchers conducted a retrospective cross-sectional study of EMR data for all ED visits during which the patient underwent suicide screening. For the period of November 2019 to August 2022, they collected data on the screening results and the patient’s gender identity, age, race/ethnicity, insurance status, chief complaint in the ED and child opportunity index, which assess a youth’s access to resources based on geography. The suicide screener used was the Ask Suicide–Screening Questions (ASQ) tool.
The keywords they looked for in the EMR to identify trans and gender-diverse youth included transgender, pronouns, agender, gender dysphoria, male-to-female, female-to-male, nonbinary, preferred name, and they/them (captured as a complete term, not as “they” and “them” separately).
“If a keyword was present, the surrounding text was extracted and reviewed by two members of our team,” Dr. Burnside explained in her presentation. “We categorized keywords into either indicative of gender-diverse identity or not, and if it wasn’t clear based on the text extracted, we would conduct a manual chart review,” though that only occurred in about 3% of cases, she added.
Among 15,413 ED encounters with a suicide screen, the researchers identified 1,126 of these keywords in the EMR, among which 91.2% were classified as referring to a gender-diverse patient. Nearly all of the words were at least 90% effective in identify a gender-diverse youth, Dr. Burnside said, and all of the 197 instances of “they/them” were classified as gender diverse.
The accuracy was a little lower for the two keywords that appeared most frequently: For “pronouns,” 86.3% of 306 instances were classified as gender diverse, and for “transgender,” 83.1% of 207 instances were classified as gender diverse. Since some providers ask all patients their pronouns, the presence of “pronouns” in the EMR alone did not necessarily indicate the patient was gender diverse, Dr. Burnside said. A common reason the term “transgender” occurred in the EMR of non–gender diverse patients is that the department’s list of crisis resources includes transgender hotlines.
After identifying all the keywords, the researchers determined how many of these occurred in unique ED encounters and removed those with incomplete screening. Overall, they found 565 encounters by 399 gender-diverse individuals who had a suicide screening, representing 4.6% of total visits. This percentage is slightly lower than recent population-based estimates of gender-diverse youth, the researchers noted.
This population ranged from 8 to 23 years old, and 43% were publicly insured. The chief complaint for most of the patients (77.5%) was a mental health one. They were predominantly White (43%) or Hispanic (35%), with 10% Black youth, 4% Asian youth, and 8% youth who were “other” or two or more races. About half (52%) lived in a neighborhood with a “low” or “very low” child opportunity index.
Within this population, 81% of the patients screened positive on the suicide screening, compared with 23% positive screens across all ED visits. One in ten (10%) gender-diverse youth had active suicidal ideation, compared with 3.4% of the rest of the ED patient population. The researchers calculated that gender-diverse youth had 5.35 times greater odds of screening positive than cisgender youth in the ED (95% confidence interval [CI] 8.7-15.92). Further, a quarter (25%) of the trans and gender-diverse youth who screened positive for suicide risk had come to the ED for a primary complaint unrelated to mental health.
“We had a kid who came in because he broke his arm who had active suicidal ideation,” study coauthor Jennifer A. Hoffmann, MD, assistant professor of pediatrics at the Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, mentioned after the presentation. That particular patient even had a suicide plan, but was identified as actively suicidal only because of the screening. In other cases, she said, a youth may come in with self-inflicted injuries, and while those are the primary complaint, they are linked with suicidal ideation.
Among the study’s limitations are that gender identity is not necessarily being systematically assessed during visits, misspellings might have missed some youth, and their search strategy has not yet been externally validated, though they plan to seek that.
“Overall, however, this study did demonstrate that keyword searching is a promising technique to identify and prioritize gender-diverse youth in health services research,” Dr. Burnside said. In addition to showing the feasibility of using a keyword search strategy for identifying gender-diverse youth, Dr. Burnside noted that 31% of the encounters were identified by just one of the keywords they used, “highlighting the importance of using a comprehensive list of keywords to identify gender-diverse youth.”
Uncovering valuable information
Jason Rafferty, MD, MPH, EdM, clinical assistant professor of pediatrics and of psychiatry and human behavior at Brown University, Providence, R.I., who attended the presentation, noted that the study provides information on a population that’s often difficult to get through traditional EMR research methods.
“A lot of medical record systems don’t have uniform ways of capturing [gender diversity], but what we know as providers is that kids are really struggling and that it’s not a surprise that we’re seeing these disparities with suicidality,” Dr. Rafferty said.
The study also provides more discrete estimates by age than what most other current research measures, which tends to be lifetime suicidality as opposed to suicidal thoughts or attempts within the past year, Dr. Rafferty added.
”What this shows is, for adolescents, the risk of suicide is something we need to be paying attention to. Because it’s not that it’s something that only happens in adults, this really dispels a lot of the misquoting of the data that’s out there.” That kind of information is valuable for determining resource allocation, he said. “A disparity like this really underlies the importance of mental health resources in this field,” he said.
Dr. Burnside, Dr. Hoffmann, and Dr. Rafferty had no disclosures, and no external funding sources were noted.
WASHINGTON – , according to a study presented at the annual meeting of the American Academy of Pediatrics.
“The take-home message here is this study emphasizes the importance of universal screening to identify gender-diverse youth at risk,” Amanda Burnside, PhD, assistant professor of psychiatry and behavioral sciences at Ann and Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, told attendees. “We really need to develop robust strategies and systems to link better mental health services.”
Suicide rates in transgender and gender-diverse youth are exceptionally high among youth in the U.S., Dr. Burnside said during her presentation. For example, the 2022 LGBTQ health survey from the Trevor Project found that much higher percentages of transgender and gender nonconforming youth had considered suicide in the past year compared with cisgender youth, even within the LGBTQ umbrella. Among nearly 34,000 LGBTQ youth aged 13-24, nearly half of trans females (48%) and more than half of trans males (59%) had considered suicide, compared with 28% of cisgender males and 37% of cisgender females. The rate among nonbinary/genderqueer individuals was 53%, and it was 48% for those questioning their gender.
Current methods of identifying trans and gender-diverse (TGD) youth in the hospital, however, may not actually be capturing the entire population.
“In health care settings, research involving TGD individuals has historically been limited to specialized clinic populations or youth with gender-specific diagnostic codes documented in the electronic medical record,” an approach that “likely significantly underestimates the prevalence of TGD youth in health care settings.” While at least one study has attempted to bridge this gap by searching the EMR for keywords, that study only tried to identify trans youth and not other youth on the gender diversity spectrum, such as nonbinary youth or those questioning their gender identity. Dr. Burnside and her colleagues therefore designed a study that used keywords to identify both trans youth and other gender-diverse youth who visited the ED so they could assess the rate of positive suicide screens in this population.
Underestimating the population at risk?
The researchers conducted a retrospective cross-sectional study of EMR data for all ED visits during which the patient underwent suicide screening. For the period of November 2019 to August 2022, they collected data on the screening results and the patient’s gender identity, age, race/ethnicity, insurance status, chief complaint in the ED and child opportunity index, which assess a youth’s access to resources based on geography. The suicide screener used was the Ask Suicide–Screening Questions (ASQ) tool.
The keywords they looked for in the EMR to identify trans and gender-diverse youth included transgender, pronouns, agender, gender dysphoria, male-to-female, female-to-male, nonbinary, preferred name, and they/them (captured as a complete term, not as “they” and “them” separately).
“If a keyword was present, the surrounding text was extracted and reviewed by two members of our team,” Dr. Burnside explained in her presentation. “We categorized keywords into either indicative of gender-diverse identity or not, and if it wasn’t clear based on the text extracted, we would conduct a manual chart review,” though that only occurred in about 3% of cases, she added.
Among 15,413 ED encounters with a suicide screen, the researchers identified 1,126 of these keywords in the EMR, among which 91.2% were classified as referring to a gender-diverse patient. Nearly all of the words were at least 90% effective in identify a gender-diverse youth, Dr. Burnside said, and all of the 197 instances of “they/them” were classified as gender diverse.
The accuracy was a little lower for the two keywords that appeared most frequently: For “pronouns,” 86.3% of 306 instances were classified as gender diverse, and for “transgender,” 83.1% of 207 instances were classified as gender diverse. Since some providers ask all patients their pronouns, the presence of “pronouns” in the EMR alone did not necessarily indicate the patient was gender diverse, Dr. Burnside said. A common reason the term “transgender” occurred in the EMR of non–gender diverse patients is that the department’s list of crisis resources includes transgender hotlines.
After identifying all the keywords, the researchers determined how many of these occurred in unique ED encounters and removed those with incomplete screening. Overall, they found 565 encounters by 399 gender-diverse individuals who had a suicide screening, representing 4.6% of total visits. This percentage is slightly lower than recent population-based estimates of gender-diverse youth, the researchers noted.
This population ranged from 8 to 23 years old, and 43% were publicly insured. The chief complaint for most of the patients (77.5%) was a mental health one. They were predominantly White (43%) or Hispanic (35%), with 10% Black youth, 4% Asian youth, and 8% youth who were “other” or two or more races. About half (52%) lived in a neighborhood with a “low” or “very low” child opportunity index.
Within this population, 81% of the patients screened positive on the suicide screening, compared with 23% positive screens across all ED visits. One in ten (10%) gender-diverse youth had active suicidal ideation, compared with 3.4% of the rest of the ED patient population. The researchers calculated that gender-diverse youth had 5.35 times greater odds of screening positive than cisgender youth in the ED (95% confidence interval [CI] 8.7-15.92). Further, a quarter (25%) of the trans and gender-diverse youth who screened positive for suicide risk had come to the ED for a primary complaint unrelated to mental health.
“We had a kid who came in because he broke his arm who had active suicidal ideation,” study coauthor Jennifer A. Hoffmann, MD, assistant professor of pediatrics at the Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, mentioned after the presentation. That particular patient even had a suicide plan, but was identified as actively suicidal only because of the screening. In other cases, she said, a youth may come in with self-inflicted injuries, and while those are the primary complaint, they are linked with suicidal ideation.
Among the study’s limitations are that gender identity is not necessarily being systematically assessed during visits, misspellings might have missed some youth, and their search strategy has not yet been externally validated, though they plan to seek that.
“Overall, however, this study did demonstrate that keyword searching is a promising technique to identify and prioritize gender-diverse youth in health services research,” Dr. Burnside said. In addition to showing the feasibility of using a keyword search strategy for identifying gender-diverse youth, Dr. Burnside noted that 31% of the encounters were identified by just one of the keywords they used, “highlighting the importance of using a comprehensive list of keywords to identify gender-diverse youth.”
Uncovering valuable information
Jason Rafferty, MD, MPH, EdM, clinical assistant professor of pediatrics and of psychiatry and human behavior at Brown University, Providence, R.I., who attended the presentation, noted that the study provides information on a population that’s often difficult to get through traditional EMR research methods.
“A lot of medical record systems don’t have uniform ways of capturing [gender diversity], but what we know as providers is that kids are really struggling and that it’s not a surprise that we’re seeing these disparities with suicidality,” Dr. Rafferty said.
The study also provides more discrete estimates by age than what most other current research measures, which tends to be lifetime suicidality as opposed to suicidal thoughts or attempts within the past year, Dr. Rafferty added.
”What this shows is, for adolescents, the risk of suicide is something we need to be paying attention to. Because it’s not that it’s something that only happens in adults, this really dispels a lot of the misquoting of the data that’s out there.” That kind of information is valuable for determining resource allocation, he said. “A disparity like this really underlies the importance of mental health resources in this field,” he said.
Dr. Burnside, Dr. Hoffmann, and Dr. Rafferty had no disclosures, and no external funding sources were noted.
AT AAP 2023
Teens streaming on Twitch vulnerable to predators
WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.
A ‘clandestine, threatening digital environment’
the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”
Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”
To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.
The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.
Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.
”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
Open-minded parental guidance is warranted
Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.
“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”
Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.
Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”
“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.
David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.
“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.
“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”
An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.
For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
Useful advice
Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:
- Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
- Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
- Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”
Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.
WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.
A ‘clandestine, threatening digital environment’
the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”
Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”
To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.
The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.
Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.
”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
Open-minded parental guidance is warranted
Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.
“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”
Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.
Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”
“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.
David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.
“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.
“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”
An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.
For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
Useful advice
Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:
- Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
- Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
- Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”
Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.
WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.
A ‘clandestine, threatening digital environment’
the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”
Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”
To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.
The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.
Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.
”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
Open-minded parental guidance is warranted
Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.
“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”
Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.
Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”
“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.
David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.
“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.
“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”
An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.
For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
Useful advice
Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:
- Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
- Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
- Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”
Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.
AT AAP 2023
Teens have easy online access to Delta-8 cannabinoid products
WASHINGTON – , researchers reported at the 2023 annual meeting of the American Academy of Pediatrics. Most of the products identified came in bright, colorful, kid-friendly packaging and cost less than $10, the researchers found, and only 2 out of 45 sites had a third-party age verification requirement for purchases.
Delta-8 THC, also called D8, is a synthetically produced cannabinoid whose chemical structure and effects are nearly identical to traditional THC, the authors explained, and past research has found that D8 products, such as e-cigarettes, can contain toxic byproducts and contaminants.
”Since D8 is not traditional THC, minors may underestimate its strength and potential danger,” wrote lead author Abhijeet Grewal, BS, a research assistant at Cohen Children’s Medical Center, New York, and senior author Ruth Milanaik, DO, director of the Neonatal Neurodevelopmental Program at Cohen Children’s and a developmental/behavioral pediatrician at Northwell Health, also in New York. “Although traditional THC is a federally banned substance, D8 is legal on a federal level and less restricted on a state by state basis, making it easier for individuals to acquire D8.”
Easily accessible
During the first seven moments of 2021, 77% of reports of accidental exposure occurred in people under age 18, including some children who required ICU admission. The U.S. Food and Drug Administration also received 104 reports of adverse events from products containing D8 between December 2020-February 2022, and more than half of those required medical intervention.
To better understand how easy it is to access D8, the authors collected data on 45 websites they identified that sold D8. The researchers looked for age verification questions for accessing the site, third-party age certification, what kinds of products (edibles, smoke products, or tinctures) were sold, the price and dosage of the cheapest product, and examples of packaging, flavors, marketing claims, and warning statements at each site.
More than a third of the sites (36%) did not ask for customers’ age and almost none of the sites asked for proof: 96% of the sites lacked formal third-party age verification procedures. All but one of the sites sold D8 edibles, and most (82%) sold D8 vaping or smoking products. Only 42% sold tinctures, a mix of concentrated D8 with oil that’s orally consumed.
The cheapest product was priced under $5 on one-third of the sites and under $10 on another third of the sites. The cheapest product was between $10-20 on 16% of the sites while the remaining nine sites’ cheapest product was more than $20. In assessing only the cheapest D8 products on each site, nearly half (47%) contained 51 mg or more of D8, and 20% of the products didn’t report the dosage. Another 22% contained 41-50 mg of D8, and the remaining five products contained 20-40 mg.
Kid-friendly D8
More than half of the D8 products were sold in kid-friendly packaging – packages with bright, colorful designs and fonts that resemble candy or snack food, sometimes cartoon characters or fun items like dice on the packaging. Further, 24% of the websites did not include any warnings or other health information about D8.
“The low prices, high dosages available, and eye-popping packaging make these products extremely attractive to teens who are looking for a high,” the researchers concluded. They advised clinicians to talk with teen patients about the dangers of D8 and advocated for policymakers to more strictly regulate online distributors of D8 products, particularly in requiring age verification procedures and prohibiting kid-friendly packaging.
Megan Moreno, MD, MSEd, MPH, an adolescent medicine physician and researcher at the University of Wisconsin, Madison, School of Medicine and Public Health and UWHealthKids, was particularly struck by how eye-catching the packaging was. “The bright colors and font choices are really designed to attract adolescents,” commented Dr. Moreno, who was not involved in the study. But she was not surprised overall by the findings.
“Other studies have found that the cannabis industry leverages online tools and social media, alongside youth-friendly packaging, to attract youth to their products,” she said. “What is disappointing is that these companies do not use industry standard approaches, such as the alcohol industry, to age-gate their websites.”
It’s important for providers who care for adolescents to ask about substance use but to especially include questions about substances that teens might not think of as “drugs,” such as Delta 8, Dr. Moreno said.
“Prior research on other types of substance such as these has found that teens can think these are less dangerous versions of cannabis, so providing accurate information and asking about these products can prevent harm to kids,” Dr. Moreno said. Although this study focused on websites that sell D8 products, she said that “another important area of influence to consider is social media messaging around these products, which may drive traffic to the purchasing site.” It’s clear this industry is not going to self-regulate without policy changes, Dr. Moreno added, so she noted the importance of advocating for policy that regulates these sites.
Mr. Grewal, Dr. Milanaik and Dr. Moreno had no disclosures. No external funding sources were noted.
WASHINGTON – , researchers reported at the 2023 annual meeting of the American Academy of Pediatrics. Most of the products identified came in bright, colorful, kid-friendly packaging and cost less than $10, the researchers found, and only 2 out of 45 sites had a third-party age verification requirement for purchases.
Delta-8 THC, also called D8, is a synthetically produced cannabinoid whose chemical structure and effects are nearly identical to traditional THC, the authors explained, and past research has found that D8 products, such as e-cigarettes, can contain toxic byproducts and contaminants.
”Since D8 is not traditional THC, minors may underestimate its strength and potential danger,” wrote lead author Abhijeet Grewal, BS, a research assistant at Cohen Children’s Medical Center, New York, and senior author Ruth Milanaik, DO, director of the Neonatal Neurodevelopmental Program at Cohen Children’s and a developmental/behavioral pediatrician at Northwell Health, also in New York. “Although traditional THC is a federally banned substance, D8 is legal on a federal level and less restricted on a state by state basis, making it easier for individuals to acquire D8.”
Easily accessible
During the first seven moments of 2021, 77% of reports of accidental exposure occurred in people under age 18, including some children who required ICU admission. The U.S. Food and Drug Administration also received 104 reports of adverse events from products containing D8 between December 2020-February 2022, and more than half of those required medical intervention.
To better understand how easy it is to access D8, the authors collected data on 45 websites they identified that sold D8. The researchers looked for age verification questions for accessing the site, third-party age certification, what kinds of products (edibles, smoke products, or tinctures) were sold, the price and dosage of the cheapest product, and examples of packaging, flavors, marketing claims, and warning statements at each site.
More than a third of the sites (36%) did not ask for customers’ age and almost none of the sites asked for proof: 96% of the sites lacked formal third-party age verification procedures. All but one of the sites sold D8 edibles, and most (82%) sold D8 vaping or smoking products. Only 42% sold tinctures, a mix of concentrated D8 with oil that’s orally consumed.
The cheapest product was priced under $5 on one-third of the sites and under $10 on another third of the sites. The cheapest product was between $10-20 on 16% of the sites while the remaining nine sites’ cheapest product was more than $20. In assessing only the cheapest D8 products on each site, nearly half (47%) contained 51 mg or more of D8, and 20% of the products didn’t report the dosage. Another 22% contained 41-50 mg of D8, and the remaining five products contained 20-40 mg.
Kid-friendly D8
More than half of the D8 products were sold in kid-friendly packaging – packages with bright, colorful designs and fonts that resemble candy or snack food, sometimes cartoon characters or fun items like dice on the packaging. Further, 24% of the websites did not include any warnings or other health information about D8.
“The low prices, high dosages available, and eye-popping packaging make these products extremely attractive to teens who are looking for a high,” the researchers concluded. They advised clinicians to talk with teen patients about the dangers of D8 and advocated for policymakers to more strictly regulate online distributors of D8 products, particularly in requiring age verification procedures and prohibiting kid-friendly packaging.
Megan Moreno, MD, MSEd, MPH, an adolescent medicine physician and researcher at the University of Wisconsin, Madison, School of Medicine and Public Health and UWHealthKids, was particularly struck by how eye-catching the packaging was. “The bright colors and font choices are really designed to attract adolescents,” commented Dr. Moreno, who was not involved in the study. But she was not surprised overall by the findings.
“Other studies have found that the cannabis industry leverages online tools and social media, alongside youth-friendly packaging, to attract youth to their products,” she said. “What is disappointing is that these companies do not use industry standard approaches, such as the alcohol industry, to age-gate their websites.”
It’s important for providers who care for adolescents to ask about substance use but to especially include questions about substances that teens might not think of as “drugs,” such as Delta 8, Dr. Moreno said.
“Prior research on other types of substance such as these has found that teens can think these are less dangerous versions of cannabis, so providing accurate information and asking about these products can prevent harm to kids,” Dr. Moreno said. Although this study focused on websites that sell D8 products, she said that “another important area of influence to consider is social media messaging around these products, which may drive traffic to the purchasing site.” It’s clear this industry is not going to self-regulate without policy changes, Dr. Moreno added, so she noted the importance of advocating for policy that regulates these sites.
Mr. Grewal, Dr. Milanaik and Dr. Moreno had no disclosures. No external funding sources were noted.
WASHINGTON – , researchers reported at the 2023 annual meeting of the American Academy of Pediatrics. Most of the products identified came in bright, colorful, kid-friendly packaging and cost less than $10, the researchers found, and only 2 out of 45 sites had a third-party age verification requirement for purchases.
Delta-8 THC, also called D8, is a synthetically produced cannabinoid whose chemical structure and effects are nearly identical to traditional THC, the authors explained, and past research has found that D8 products, such as e-cigarettes, can contain toxic byproducts and contaminants.
”Since D8 is not traditional THC, minors may underestimate its strength and potential danger,” wrote lead author Abhijeet Grewal, BS, a research assistant at Cohen Children’s Medical Center, New York, and senior author Ruth Milanaik, DO, director of the Neonatal Neurodevelopmental Program at Cohen Children’s and a developmental/behavioral pediatrician at Northwell Health, also in New York. “Although traditional THC is a federally banned substance, D8 is legal on a federal level and less restricted on a state by state basis, making it easier for individuals to acquire D8.”
Easily accessible
During the first seven moments of 2021, 77% of reports of accidental exposure occurred in people under age 18, including some children who required ICU admission. The U.S. Food and Drug Administration also received 104 reports of adverse events from products containing D8 between December 2020-February 2022, and more than half of those required medical intervention.
To better understand how easy it is to access D8, the authors collected data on 45 websites they identified that sold D8. The researchers looked for age verification questions for accessing the site, third-party age certification, what kinds of products (edibles, smoke products, or tinctures) were sold, the price and dosage of the cheapest product, and examples of packaging, flavors, marketing claims, and warning statements at each site.
More than a third of the sites (36%) did not ask for customers’ age and almost none of the sites asked for proof: 96% of the sites lacked formal third-party age verification procedures. All but one of the sites sold D8 edibles, and most (82%) sold D8 vaping or smoking products. Only 42% sold tinctures, a mix of concentrated D8 with oil that’s orally consumed.
The cheapest product was priced under $5 on one-third of the sites and under $10 on another third of the sites. The cheapest product was between $10-20 on 16% of the sites while the remaining nine sites’ cheapest product was more than $20. In assessing only the cheapest D8 products on each site, nearly half (47%) contained 51 mg or more of D8, and 20% of the products didn’t report the dosage. Another 22% contained 41-50 mg of D8, and the remaining five products contained 20-40 mg.
Kid-friendly D8
More than half of the D8 products were sold in kid-friendly packaging – packages with bright, colorful designs and fonts that resemble candy or snack food, sometimes cartoon characters or fun items like dice on the packaging. Further, 24% of the websites did not include any warnings or other health information about D8.
“The low prices, high dosages available, and eye-popping packaging make these products extremely attractive to teens who are looking for a high,” the researchers concluded. They advised clinicians to talk with teen patients about the dangers of D8 and advocated for policymakers to more strictly regulate online distributors of D8 products, particularly in requiring age verification procedures and prohibiting kid-friendly packaging.
Megan Moreno, MD, MSEd, MPH, an adolescent medicine physician and researcher at the University of Wisconsin, Madison, School of Medicine and Public Health and UWHealthKids, was particularly struck by how eye-catching the packaging was. “The bright colors and font choices are really designed to attract adolescents,” commented Dr. Moreno, who was not involved in the study. But she was not surprised overall by the findings.
“Other studies have found that the cannabis industry leverages online tools and social media, alongside youth-friendly packaging, to attract youth to their products,” she said. “What is disappointing is that these companies do not use industry standard approaches, such as the alcohol industry, to age-gate their websites.”
It’s important for providers who care for adolescents to ask about substance use but to especially include questions about substances that teens might not think of as “drugs,” such as Delta 8, Dr. Moreno said.
“Prior research on other types of substance such as these has found that teens can think these are less dangerous versions of cannabis, so providing accurate information and asking about these products can prevent harm to kids,” Dr. Moreno said. Although this study focused on websites that sell D8 products, she said that “another important area of influence to consider is social media messaging around these products, which may drive traffic to the purchasing site.” It’s clear this industry is not going to self-regulate without policy changes, Dr. Moreno added, so she noted the importance of advocating for policy that regulates these sites.
Mr. Grewal, Dr. Milanaik and Dr. Moreno had no disclosures. No external funding sources were noted.
At AAP 2023
How clinicians can prepare for and defend against social media attacks
WASHINGTON – The entire video clip is just 15 seconds — 15 seconds that went viral and temporarily upended the entire life and disrupted the medical practice of Nicole Baldwin, MD, a pediatrician in Cincinnati, Ohio, in January 2020. At the annual meeting of the American Academy of Pediatrics, Dr. Baldwin told attendees how her pro-vaccine TikTok video led a horde of anti-vaccine activists to swarm her social media profiles across multiple platforms, leave one-star reviews with false stories about her medical practice on various doctor review sites, and personally threaten her.
The initial response to the video was positive, with 50,000 views in the first 24 hours after the video was posted and more than 1.5 million views the next day. But 2 days after the video was posted, an organized attack that originated on Facebook required Dr. Baldwin to enlist the help of 16 volunteers, working 24/7 for a week, to help ban and block more than 6,000 users on Facebook, Instagram, and TikTok. Just 4 days after she’d posted the video, Dr. Baldwin was reporting personal threats to the police and had begun contacting sites such as Yelp, Google, Healthgrades, Vitals, RateMDs, and WebMD so they could start removing false reviews about her practice.
Today, years after those 2 exhausting, intense weeks of attacks, Dr. Baldwin has found two silver linings in the experience: More people have found her profiles, allowing her to share evidence-based information with an even wider audience, and she can now help other physicians protect themselves and reduce the risk of similar attacks, or at least know how to respond to them if they occur. Dr. Baldwin shared a wealth of tips and resources during her lecture to help pediatricians prepare ahead for the possibility that they will be targeted next, whether the issue is vaccines or another topic.
Online risks and benefits
A Pew survey of U.S. adults in September 2020 found that 41% have personally experienced online harassment, including a quarter of Americans who have experienced severe harassment. More than half of respondents said online harassment and bullying is a major problem – and that was a poll of the entire population, not even just physicians and scientists.
“Now, these numbers would be higher,” Dr. Baldwin said. “A lot has changed in the past 3 years, and the landscape is very different.”
The pandemic contributed to those changes to the landscape, including an increase in harassment of doctors and researchers. A June 2023 study revealed that two-thirds of 359 respondents in an online survey reported harassment on social media, a substantial number even after accounting for selection bias in the individuals who chose to respond to the survey. Although most of the attacks (88%) resulted from the respondent’s advocacy online, nearly half the attacks (45%) were gender based, 27% were based on race/ethnicity, and 13% were based on sexual orientation.
While hateful comments are likely the most common type of online harassment, other types can involve sharing or tagging your profile, creating fake profiles to misrepresent you, fake reviews of your practice, harassing phone calls and hate mail at your office, and doxxing, in which someone online widely shares your personal address, phone number, email, or other contact information.
Despite the risks of all these forms of harassment, Dr. Baldwin emphasized the value of doctors having a social media presence given how much misinformation thrives online. For example, a recent report from the Kaiser Family Foundation revealed how many people weren’t sure whether certain health misinformation claims were true or false. Barely a third of people were sure that COVID-19 vaccines had not caused thousands of deaths in healthy people, and only 22% of people were sure that ivermectin is not an effective treatment for COVID.
“There is so much that we need to be doing and working in these spaces to put evidence-based content out there so that people are not finding all of this crap from everybody else,” Dr. Baldwin said. Having an online presence is particularly important given that the public still has high levels of trust in their doctors, she added.
“They trust their physician, and you may not be their physician online, but I will tell you from experience, when you build a community of followers, you become that trusted source of information for them, and it is so important,” Dr. Baldwin said. “There is room for everybody in this space, and we need all of you.”
Proactive steps for protection
Dr. Baldwin then went through the details of what people should do now to make things easier in the event of an attack later. “The best defense is a good offense,” Dr. Baldwin said, “so make sure all of your accounts are secure.”
She recommended the following steps:
- Use two-factor authentication for all of your logins.
- Use strong, unique passwords for all of your logins.
- Use strong privacy settings on all of your private social media profiles, such as making sure photos are not visible on your personal Facebook account.
- Claim your Google profile and Yelp business profile.
- Claim your doctor and/or business profile on all of the medical review sites where you have one, including Google, Healthgrades, Vitals, RateMDs, and WebMD.
For doctors who are attacked specifically because of pro-vaccine advocacy, Dr. Baldwin recommended contacting Shots Heard Round The World, a site that was created by a physician whose practice was attacked by anti-vaccine activists. The site also has a toolkit that anyone can download for tips on preparing ahead for possible attacks and what to do if you are attacked.
Dr. Baldwin then reviewed how to set up different social media profiles to automatically hide certain comments, including comments with words commonly used by online harassers and trolls:
- Sheep
- Sheeple
- Pharma
- Shill
- Die
- Psychopath
- Clown
- Various curse words
- The clown emoji
In Instagram, go to “Settings and privacy —> Hidden Words” for options on hiding offensive comments and messages and for managing custom words and phrases that should be automatically hidden.
On Facebook, go to “Professional dashboard —> Moderation Assist,” where you can add or edit criteria to automatically hide comments on your Facebook page. In addition to hiding comments with certain keywords, you can hide comments from new accounts, accounts without profile photos, or accounts with no friends or followers.
On TikTok, click the three-line menu icon in the upper right, and choose “Privacy —> Comments —> Filter keywords.”
On the platform formerly known as Twitter, go to “Settings and privacy —> Privacy and safety —> Mute and block —> Muted words.”
On YouTube, under “Manage your community & comments,” select “Learn about comment settings.”
Dr. Baldwin did not discourage doctors from posting about controversial topics, but she said it’s important to know what they are so that you can be prepared for the possibility that a post about one of these topics could lead to online harassment. These hot button topics include vaccines, firearm safety, gender-affirming care, reproductive choice, safe sleep/bedsharing, breastfeeding, and COVID masks.
If you do post on one of these and suspect it could result in harassment, Dr. Baldwin recommends turning on your notifications so you know when attacks begin, alerting your office and call center staff if you think they might receive calls, and, when possible, post your content at a time when you’re more likely to be able to monitor the post. She acknowledged that this last tip isn’t always relevant since attacks can take a few days to start or gain steam.
Defending yourself in an attack
Even after taking all these precautions, it’s not possible to altogether prevent an attack from happening, so Dr. Baldwin provided suggestions on what to do if one occurs, starting with taking a deep breath.
“If you are attacked, first of all, please remain calm, which is a lot easier said than done,” she said. “But know that this too shall pass. These things do come to an end.”
She advises you to get help if you need it, enlisting friends or colleagues to help with moderation and banning/blocking. If necessary, alert your employer to the attack, as attackers may contact your employer. Some people may opt to turn off comments on their post, but doing so “is a really personal decision,” she said. It’s okay to turn off comments if you don’t have the bandwidth or help to deal with them.
However, Dr. Baldwin said she never turns off comments because she wants to be able to ban and block people to reduce the likelihood of a future attack from them, and each comment brings the post higher in the algorithm so that more people are able to see the original content. “So sometimes these things are actually a blessing in disguise,” she said.
If you do have comments turned on, take screenshots of the most egregious or threatening ones and then report them and ban/block them. The screenshots are evidence since blocking will remove the comment.
“Take breaks when you need to,” she said. “Don’t stay up all night” since there are only going to be more in the morning, and if you’re using keywords to help hide many of these comments, that will hide them from your followers while you’re away. She also advised monitoring your online reviews at doctor/practice review sites so you know whether you’re receiving spurious reviews that need to be removed.
Dr. Baldwin also addressed how to handle trolls, the people online who intentionally antagonize others with inflammatory, irrelevant, offensive, or otherwise disruptive comments or content. The No. 1 rule is not to engage – “Don’t feed the trolls” – but Dr. Baldwin acknowledged that she can find that difficult sometimes. So she uses kindness or humor to defuse them or calls them out on their inaccurate information and then thanks them for their engagement. Don’t forget that you are in charge of your own page, so any complaints about “censorship” or infringing “free speech” aren’t relevant.
If the comments are growing out of control and you’re unable to manage them, multiple social media platforms have options for limited interactions or who can comment on your page.
On Instagram under “Settings and privacy,” check out “Limited interactions,” “Comments —> Allow comments from,” and “Tags and mentions” to see ways you can limit who is able to comment, tag or mention your account. If you need a complete break, you can turn off commenting by clicking the three dots in the upper right corner of the post, or make your account temporarily private under “Settings and privacy —> Account privacy.”
On Facebook, click the three dots in the upper right corner of posts to select “Who can comment on your post?” Also, under “Settings —> Privacy —> Your Activity,” you can adjust who sees your future posts. Again, if things are out of control, you can temporarily deactivate your page under “Settings —> Privacy —> Facebook Page information.”
On TikTok, click the three lines in the upper right corner of your profile and select “Privacy —> Comments” to adjust who can comment and to filter comments. Again, you can make your account private under “Settings and privacy —> Privacy —> Private account.”
On the platform formerly known as Twitter, click the three dots in the upper right corner of the tweet to change who can reply to the tweet. If you select “Only people you mentioned,” then no one can reply if you did not mention anyone. You can control tagging under “Settings and privacy —> Privacy and safety —> Audience and tagging.”
If you or your practice receive false reviews on review sites, report the reviews and alert the rating site when you can. In the meantime, lock down your private social media accounts and ensure that no photos of your family are publicly available.
Social media self-care
Dr. Baldwin acknowledged that experiencing a social media attack can be intense and even frightening, but it’s rare and outweighed by the “hundreds and hundreds and hundreds of positive comments all the time.” She also reminded attendees that being on social media doesn’t mean being there all the time.
“Over time, my use of social media has certainly changed. It ebbs and flows,” she said. “There are times when I have a lot of bandwidth and I’m posting a lot, and then I actually have had some struggles with my own mental health, with some anxiety and mild depression, so I took a break from social media for a while. When I came back, I posted about my mental health struggles, and you wouldn’t believe how many people were so appreciative of that.”
Accurate information from a trusted source
Ultimately, Dr. Baldwin sees her work online as an extension of her work educating patients.
“This is where our patients are. They are in your office for maybe 10-15 minutes maybe once a year, but they are on these platforms every single day for hours,” she said. “They need to see this information from medical professionals because there are random people out there that are telling them [misinformation].”
Elizabeth Murray, DO, MBA, an emergency medicine pediatrician at Golisano Children’s Hospital at the University of Rochester, agreed that there’s substantial value in doctors sharing accurate information online.
“Disinformation and misinformation is rampant, and at the end of the day, we know the facts,” Dr. Murray said. “We know what parents want to hear and what they want to learn about, so we need to share that information and get the facts out there.”
Dr. Murray found the session very helpful because there’s so much to learn across different social media platforms and it can feel overwhelming if you aren’t familiar with the tools.
“Social media is always going to be here. We need to learn to live with all of these platforms,” Dr. Murray said. “That’s a skill set. We need to learn the skills and teach our kids the skill set. You never really know what you might put out there that, in your mind is innocent or very science-based, that for whatever reason somebody might take issue with. You might as well be ready because we’re all about prevention in pediatrics.”
There were no funders for the presentation. Dr. Baldwin and Dr. Murray had no disclosures.
WASHINGTON – The entire video clip is just 15 seconds — 15 seconds that went viral and temporarily upended the entire life and disrupted the medical practice of Nicole Baldwin, MD, a pediatrician in Cincinnati, Ohio, in January 2020. At the annual meeting of the American Academy of Pediatrics, Dr. Baldwin told attendees how her pro-vaccine TikTok video led a horde of anti-vaccine activists to swarm her social media profiles across multiple platforms, leave one-star reviews with false stories about her medical practice on various doctor review sites, and personally threaten her.
The initial response to the video was positive, with 50,000 views in the first 24 hours after the video was posted and more than 1.5 million views the next day. But 2 days after the video was posted, an organized attack that originated on Facebook required Dr. Baldwin to enlist the help of 16 volunteers, working 24/7 for a week, to help ban and block more than 6,000 users on Facebook, Instagram, and TikTok. Just 4 days after she’d posted the video, Dr. Baldwin was reporting personal threats to the police and had begun contacting sites such as Yelp, Google, Healthgrades, Vitals, RateMDs, and WebMD so they could start removing false reviews about her practice.
Today, years after those 2 exhausting, intense weeks of attacks, Dr. Baldwin has found two silver linings in the experience: More people have found her profiles, allowing her to share evidence-based information with an even wider audience, and she can now help other physicians protect themselves and reduce the risk of similar attacks, or at least know how to respond to them if they occur. Dr. Baldwin shared a wealth of tips and resources during her lecture to help pediatricians prepare ahead for the possibility that they will be targeted next, whether the issue is vaccines or another topic.
Online risks and benefits
A Pew survey of U.S. adults in September 2020 found that 41% have personally experienced online harassment, including a quarter of Americans who have experienced severe harassment. More than half of respondents said online harassment and bullying is a major problem – and that was a poll of the entire population, not even just physicians and scientists.
“Now, these numbers would be higher,” Dr. Baldwin said. “A lot has changed in the past 3 years, and the landscape is very different.”
The pandemic contributed to those changes to the landscape, including an increase in harassment of doctors and researchers. A June 2023 study revealed that two-thirds of 359 respondents in an online survey reported harassment on social media, a substantial number even after accounting for selection bias in the individuals who chose to respond to the survey. Although most of the attacks (88%) resulted from the respondent’s advocacy online, nearly half the attacks (45%) were gender based, 27% were based on race/ethnicity, and 13% were based on sexual orientation.
While hateful comments are likely the most common type of online harassment, other types can involve sharing or tagging your profile, creating fake profiles to misrepresent you, fake reviews of your practice, harassing phone calls and hate mail at your office, and doxxing, in which someone online widely shares your personal address, phone number, email, or other contact information.
Despite the risks of all these forms of harassment, Dr. Baldwin emphasized the value of doctors having a social media presence given how much misinformation thrives online. For example, a recent report from the Kaiser Family Foundation revealed how many people weren’t sure whether certain health misinformation claims were true or false. Barely a third of people were sure that COVID-19 vaccines had not caused thousands of deaths in healthy people, and only 22% of people were sure that ivermectin is not an effective treatment for COVID.
“There is so much that we need to be doing and working in these spaces to put evidence-based content out there so that people are not finding all of this crap from everybody else,” Dr. Baldwin said. Having an online presence is particularly important given that the public still has high levels of trust in their doctors, she added.
“They trust their physician, and you may not be their physician online, but I will tell you from experience, when you build a community of followers, you become that trusted source of information for them, and it is so important,” Dr. Baldwin said. “There is room for everybody in this space, and we need all of you.”
Proactive steps for protection
Dr. Baldwin then went through the details of what people should do now to make things easier in the event of an attack later. “The best defense is a good offense,” Dr. Baldwin said, “so make sure all of your accounts are secure.”
She recommended the following steps:
- Use two-factor authentication for all of your logins.
- Use strong, unique passwords for all of your logins.
- Use strong privacy settings on all of your private social media profiles, such as making sure photos are not visible on your personal Facebook account.
- Claim your Google profile and Yelp business profile.
- Claim your doctor and/or business profile on all of the medical review sites where you have one, including Google, Healthgrades, Vitals, RateMDs, and WebMD.
For doctors who are attacked specifically because of pro-vaccine advocacy, Dr. Baldwin recommended contacting Shots Heard Round The World, a site that was created by a physician whose practice was attacked by anti-vaccine activists. The site also has a toolkit that anyone can download for tips on preparing ahead for possible attacks and what to do if you are attacked.
Dr. Baldwin then reviewed how to set up different social media profiles to automatically hide certain comments, including comments with words commonly used by online harassers and trolls:
- Sheep
- Sheeple
- Pharma
- Shill
- Die
- Psychopath
- Clown
- Various curse words
- The clown emoji
In Instagram, go to “Settings and privacy —> Hidden Words” for options on hiding offensive comments and messages and for managing custom words and phrases that should be automatically hidden.
On Facebook, go to “Professional dashboard —> Moderation Assist,” where you can add or edit criteria to automatically hide comments on your Facebook page. In addition to hiding comments with certain keywords, you can hide comments from new accounts, accounts without profile photos, or accounts with no friends or followers.
On TikTok, click the three-line menu icon in the upper right, and choose “Privacy —> Comments —> Filter keywords.”
On the platform formerly known as Twitter, go to “Settings and privacy —> Privacy and safety —> Mute and block —> Muted words.”
On YouTube, under “Manage your community & comments,” select “Learn about comment settings.”
Dr. Baldwin did not discourage doctors from posting about controversial topics, but she said it’s important to know what they are so that you can be prepared for the possibility that a post about one of these topics could lead to online harassment. These hot button topics include vaccines, firearm safety, gender-affirming care, reproductive choice, safe sleep/bedsharing, breastfeeding, and COVID masks.
If you do post on one of these and suspect it could result in harassment, Dr. Baldwin recommends turning on your notifications so you know when attacks begin, alerting your office and call center staff if you think they might receive calls, and, when possible, post your content at a time when you’re more likely to be able to monitor the post. She acknowledged that this last tip isn’t always relevant since attacks can take a few days to start or gain steam.
Defending yourself in an attack
Even after taking all these precautions, it’s not possible to altogether prevent an attack from happening, so Dr. Baldwin provided suggestions on what to do if one occurs, starting with taking a deep breath.
“If you are attacked, first of all, please remain calm, which is a lot easier said than done,” she said. “But know that this too shall pass. These things do come to an end.”
She advises you to get help if you need it, enlisting friends or colleagues to help with moderation and banning/blocking. If necessary, alert your employer to the attack, as attackers may contact your employer. Some people may opt to turn off comments on their post, but doing so “is a really personal decision,” she said. It’s okay to turn off comments if you don’t have the bandwidth or help to deal with them.
However, Dr. Baldwin said she never turns off comments because she wants to be able to ban and block people to reduce the likelihood of a future attack from them, and each comment brings the post higher in the algorithm so that more people are able to see the original content. “So sometimes these things are actually a blessing in disguise,” she said.
If you do have comments turned on, take screenshots of the most egregious or threatening ones and then report them and ban/block them. The screenshots are evidence since blocking will remove the comment.
“Take breaks when you need to,” she said. “Don’t stay up all night” since there are only going to be more in the morning, and if you’re using keywords to help hide many of these comments, that will hide them from your followers while you’re away. She also advised monitoring your online reviews at doctor/practice review sites so you know whether you’re receiving spurious reviews that need to be removed.
Dr. Baldwin also addressed how to handle trolls, the people online who intentionally antagonize others with inflammatory, irrelevant, offensive, or otherwise disruptive comments or content. The No. 1 rule is not to engage – “Don’t feed the trolls” – but Dr. Baldwin acknowledged that she can find that difficult sometimes. So she uses kindness or humor to defuse them or calls them out on their inaccurate information and then thanks them for their engagement. Don’t forget that you are in charge of your own page, so any complaints about “censorship” or infringing “free speech” aren’t relevant.
If the comments are growing out of control and you’re unable to manage them, multiple social media platforms have options for limited interactions or who can comment on your page.
On Instagram under “Settings and privacy,” check out “Limited interactions,” “Comments —> Allow comments from,” and “Tags and mentions” to see ways you can limit who is able to comment, tag or mention your account. If you need a complete break, you can turn off commenting by clicking the three dots in the upper right corner of the post, or make your account temporarily private under “Settings and privacy —> Account privacy.”
On Facebook, click the three dots in the upper right corner of posts to select “Who can comment on your post?” Also, under “Settings —> Privacy —> Your Activity,” you can adjust who sees your future posts. Again, if things are out of control, you can temporarily deactivate your page under “Settings —> Privacy —> Facebook Page information.”
On TikTok, click the three lines in the upper right corner of your profile and select “Privacy —> Comments” to adjust who can comment and to filter comments. Again, you can make your account private under “Settings and privacy —> Privacy —> Private account.”
On the platform formerly known as Twitter, click the three dots in the upper right corner of the tweet to change who can reply to the tweet. If you select “Only people you mentioned,” then no one can reply if you did not mention anyone. You can control tagging under “Settings and privacy —> Privacy and safety —> Audience and tagging.”
If you or your practice receive false reviews on review sites, report the reviews and alert the rating site when you can. In the meantime, lock down your private social media accounts and ensure that no photos of your family are publicly available.
Social media self-care
Dr. Baldwin acknowledged that experiencing a social media attack can be intense and even frightening, but it’s rare and outweighed by the “hundreds and hundreds and hundreds of positive comments all the time.” She also reminded attendees that being on social media doesn’t mean being there all the time.
“Over time, my use of social media has certainly changed. It ebbs and flows,” she said. “There are times when I have a lot of bandwidth and I’m posting a lot, and then I actually have had some struggles with my own mental health, with some anxiety and mild depression, so I took a break from social media for a while. When I came back, I posted about my mental health struggles, and you wouldn’t believe how many people were so appreciative of that.”
Accurate information from a trusted source
Ultimately, Dr. Baldwin sees her work online as an extension of her work educating patients.
“This is where our patients are. They are in your office for maybe 10-15 minutes maybe once a year, but they are on these platforms every single day for hours,” she said. “They need to see this information from medical professionals because there are random people out there that are telling them [misinformation].”
Elizabeth Murray, DO, MBA, an emergency medicine pediatrician at Golisano Children’s Hospital at the University of Rochester, agreed that there’s substantial value in doctors sharing accurate information online.
“Disinformation and misinformation is rampant, and at the end of the day, we know the facts,” Dr. Murray said. “We know what parents want to hear and what they want to learn about, so we need to share that information and get the facts out there.”
Dr. Murray found the session very helpful because there’s so much to learn across different social media platforms and it can feel overwhelming if you aren’t familiar with the tools.
“Social media is always going to be here. We need to learn to live with all of these platforms,” Dr. Murray said. “That’s a skill set. We need to learn the skills and teach our kids the skill set. You never really know what you might put out there that, in your mind is innocent or very science-based, that for whatever reason somebody might take issue with. You might as well be ready because we’re all about prevention in pediatrics.”
There were no funders for the presentation. Dr. Baldwin and Dr. Murray had no disclosures.
WASHINGTON – The entire video clip is just 15 seconds — 15 seconds that went viral and temporarily upended the entire life and disrupted the medical practice of Nicole Baldwin, MD, a pediatrician in Cincinnati, Ohio, in January 2020. At the annual meeting of the American Academy of Pediatrics, Dr. Baldwin told attendees how her pro-vaccine TikTok video led a horde of anti-vaccine activists to swarm her social media profiles across multiple platforms, leave one-star reviews with false stories about her medical practice on various doctor review sites, and personally threaten her.
The initial response to the video was positive, with 50,000 views in the first 24 hours after the video was posted and more than 1.5 million views the next day. But 2 days after the video was posted, an organized attack that originated on Facebook required Dr. Baldwin to enlist the help of 16 volunteers, working 24/7 for a week, to help ban and block more than 6,000 users on Facebook, Instagram, and TikTok. Just 4 days after she’d posted the video, Dr. Baldwin was reporting personal threats to the police and had begun contacting sites such as Yelp, Google, Healthgrades, Vitals, RateMDs, and WebMD so they could start removing false reviews about her practice.
Today, years after those 2 exhausting, intense weeks of attacks, Dr. Baldwin has found two silver linings in the experience: More people have found her profiles, allowing her to share evidence-based information with an even wider audience, and she can now help other physicians protect themselves and reduce the risk of similar attacks, or at least know how to respond to them if they occur. Dr. Baldwin shared a wealth of tips and resources during her lecture to help pediatricians prepare ahead for the possibility that they will be targeted next, whether the issue is vaccines or another topic.
Online risks and benefits
A Pew survey of U.S. adults in September 2020 found that 41% have personally experienced online harassment, including a quarter of Americans who have experienced severe harassment. More than half of respondents said online harassment and bullying is a major problem – and that was a poll of the entire population, not even just physicians and scientists.
“Now, these numbers would be higher,” Dr. Baldwin said. “A lot has changed in the past 3 years, and the landscape is very different.”
The pandemic contributed to those changes to the landscape, including an increase in harassment of doctors and researchers. A June 2023 study revealed that two-thirds of 359 respondents in an online survey reported harassment on social media, a substantial number even after accounting for selection bias in the individuals who chose to respond to the survey. Although most of the attacks (88%) resulted from the respondent’s advocacy online, nearly half the attacks (45%) were gender based, 27% were based on race/ethnicity, and 13% were based on sexual orientation.
While hateful comments are likely the most common type of online harassment, other types can involve sharing or tagging your profile, creating fake profiles to misrepresent you, fake reviews of your practice, harassing phone calls and hate mail at your office, and doxxing, in which someone online widely shares your personal address, phone number, email, or other contact information.
Despite the risks of all these forms of harassment, Dr. Baldwin emphasized the value of doctors having a social media presence given how much misinformation thrives online. For example, a recent report from the Kaiser Family Foundation revealed how many people weren’t sure whether certain health misinformation claims were true or false. Barely a third of people were sure that COVID-19 vaccines had not caused thousands of deaths in healthy people, and only 22% of people were sure that ivermectin is not an effective treatment for COVID.
“There is so much that we need to be doing and working in these spaces to put evidence-based content out there so that people are not finding all of this crap from everybody else,” Dr. Baldwin said. Having an online presence is particularly important given that the public still has high levels of trust in their doctors, she added.
“They trust their physician, and you may not be their physician online, but I will tell you from experience, when you build a community of followers, you become that trusted source of information for them, and it is so important,” Dr. Baldwin said. “There is room for everybody in this space, and we need all of you.”
Proactive steps for protection
Dr. Baldwin then went through the details of what people should do now to make things easier in the event of an attack later. “The best defense is a good offense,” Dr. Baldwin said, “so make sure all of your accounts are secure.”
She recommended the following steps:
- Use two-factor authentication for all of your logins.
- Use strong, unique passwords for all of your logins.
- Use strong privacy settings on all of your private social media profiles, such as making sure photos are not visible on your personal Facebook account.
- Claim your Google profile and Yelp business profile.
- Claim your doctor and/or business profile on all of the medical review sites where you have one, including Google, Healthgrades, Vitals, RateMDs, and WebMD.
For doctors who are attacked specifically because of pro-vaccine advocacy, Dr. Baldwin recommended contacting Shots Heard Round The World, a site that was created by a physician whose practice was attacked by anti-vaccine activists. The site also has a toolkit that anyone can download for tips on preparing ahead for possible attacks and what to do if you are attacked.
Dr. Baldwin then reviewed how to set up different social media profiles to automatically hide certain comments, including comments with words commonly used by online harassers and trolls:
- Sheep
- Sheeple
- Pharma
- Shill
- Die
- Psychopath
- Clown
- Various curse words
- The clown emoji
In Instagram, go to “Settings and privacy —> Hidden Words” for options on hiding offensive comments and messages and for managing custom words and phrases that should be automatically hidden.
On Facebook, go to “Professional dashboard —> Moderation Assist,” where you can add or edit criteria to automatically hide comments on your Facebook page. In addition to hiding comments with certain keywords, you can hide comments from new accounts, accounts without profile photos, or accounts with no friends or followers.
On TikTok, click the three-line menu icon in the upper right, and choose “Privacy —> Comments —> Filter keywords.”
On the platform formerly known as Twitter, go to “Settings and privacy —> Privacy and safety —> Mute and block —> Muted words.”
On YouTube, under “Manage your community & comments,” select “Learn about comment settings.”
Dr. Baldwin did not discourage doctors from posting about controversial topics, but she said it’s important to know what they are so that you can be prepared for the possibility that a post about one of these topics could lead to online harassment. These hot button topics include vaccines, firearm safety, gender-affirming care, reproductive choice, safe sleep/bedsharing, breastfeeding, and COVID masks.
If you do post on one of these and suspect it could result in harassment, Dr. Baldwin recommends turning on your notifications so you know when attacks begin, alerting your office and call center staff if you think they might receive calls, and, when possible, post your content at a time when you’re more likely to be able to monitor the post. She acknowledged that this last tip isn’t always relevant since attacks can take a few days to start or gain steam.
Defending yourself in an attack
Even after taking all these precautions, it’s not possible to altogether prevent an attack from happening, so Dr. Baldwin provided suggestions on what to do if one occurs, starting with taking a deep breath.
“If you are attacked, first of all, please remain calm, which is a lot easier said than done,” she said. “But know that this too shall pass. These things do come to an end.”
She advises you to get help if you need it, enlisting friends or colleagues to help with moderation and banning/blocking. If necessary, alert your employer to the attack, as attackers may contact your employer. Some people may opt to turn off comments on their post, but doing so “is a really personal decision,” she said. It’s okay to turn off comments if you don’t have the bandwidth or help to deal with them.
However, Dr. Baldwin said she never turns off comments because she wants to be able to ban and block people to reduce the likelihood of a future attack from them, and each comment brings the post higher in the algorithm so that more people are able to see the original content. “So sometimes these things are actually a blessing in disguise,” she said.
If you do have comments turned on, take screenshots of the most egregious or threatening ones and then report them and ban/block them. The screenshots are evidence since blocking will remove the comment.
“Take breaks when you need to,” she said. “Don’t stay up all night” since there are only going to be more in the morning, and if you’re using keywords to help hide many of these comments, that will hide them from your followers while you’re away. She also advised monitoring your online reviews at doctor/practice review sites so you know whether you’re receiving spurious reviews that need to be removed.
Dr. Baldwin also addressed how to handle trolls, the people online who intentionally antagonize others with inflammatory, irrelevant, offensive, or otherwise disruptive comments or content. The No. 1 rule is not to engage – “Don’t feed the trolls” – but Dr. Baldwin acknowledged that she can find that difficult sometimes. So she uses kindness or humor to defuse them or calls them out on their inaccurate information and then thanks them for their engagement. Don’t forget that you are in charge of your own page, so any complaints about “censorship” or infringing “free speech” aren’t relevant.
If the comments are growing out of control and you’re unable to manage them, multiple social media platforms have options for limited interactions or who can comment on your page.
On Instagram under “Settings and privacy,” check out “Limited interactions,” “Comments —> Allow comments from,” and “Tags and mentions” to see ways you can limit who is able to comment, tag or mention your account. If you need a complete break, you can turn off commenting by clicking the three dots in the upper right corner of the post, or make your account temporarily private under “Settings and privacy —> Account privacy.”
On Facebook, click the three dots in the upper right corner of posts to select “Who can comment on your post?” Also, under “Settings —> Privacy —> Your Activity,” you can adjust who sees your future posts. Again, if things are out of control, you can temporarily deactivate your page under “Settings —> Privacy —> Facebook Page information.”
On TikTok, click the three lines in the upper right corner of your profile and select “Privacy —> Comments” to adjust who can comment and to filter comments. Again, you can make your account private under “Settings and privacy —> Privacy —> Private account.”
On the platform formerly known as Twitter, click the three dots in the upper right corner of the tweet to change who can reply to the tweet. If you select “Only people you mentioned,” then no one can reply if you did not mention anyone. You can control tagging under “Settings and privacy —> Privacy and safety —> Audience and tagging.”
If you or your practice receive false reviews on review sites, report the reviews and alert the rating site when you can. In the meantime, lock down your private social media accounts and ensure that no photos of your family are publicly available.
Social media self-care
Dr. Baldwin acknowledged that experiencing a social media attack can be intense and even frightening, but it’s rare and outweighed by the “hundreds and hundreds and hundreds of positive comments all the time.” She also reminded attendees that being on social media doesn’t mean being there all the time.
“Over time, my use of social media has certainly changed. It ebbs and flows,” she said. “There are times when I have a lot of bandwidth and I’m posting a lot, and then I actually have had some struggles with my own mental health, with some anxiety and mild depression, so I took a break from social media for a while. When I came back, I posted about my mental health struggles, and you wouldn’t believe how many people were so appreciative of that.”
Accurate information from a trusted source
Ultimately, Dr. Baldwin sees her work online as an extension of her work educating patients.
“This is where our patients are. They are in your office for maybe 10-15 minutes maybe once a year, but they are on these platforms every single day for hours,” she said. “They need to see this information from medical professionals because there are random people out there that are telling them [misinformation].”
Elizabeth Murray, DO, MBA, an emergency medicine pediatrician at Golisano Children’s Hospital at the University of Rochester, agreed that there’s substantial value in doctors sharing accurate information online.
“Disinformation and misinformation is rampant, and at the end of the day, we know the facts,” Dr. Murray said. “We know what parents want to hear and what they want to learn about, so we need to share that information and get the facts out there.”
Dr. Murray found the session very helpful because there’s so much to learn across different social media platforms and it can feel overwhelming if you aren’t familiar with the tools.
“Social media is always going to be here. We need to learn to live with all of these platforms,” Dr. Murray said. “That’s a skill set. We need to learn the skills and teach our kids the skill set. You never really know what you might put out there that, in your mind is innocent or very science-based, that for whatever reason somebody might take issue with. You might as well be ready because we’re all about prevention in pediatrics.”
There were no funders for the presentation. Dr. Baldwin and Dr. Murray had no disclosures.
AT AAP 2023
Postmenopausal stress linked to mood, cognitive symptoms
PHILADELPHIA – , according to research presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
“This work suggests that markers of hypothalamic-pituitary-axis activation that capture total cortisol secretion over multiple months, [such as] hair cortisol, strongly correlate with cognitive performance on attention and working memory tasks, whereas measures of more acute cortisol, [such as] salivary cortisol, may be more strongly associated with depression symptom severity and verbal learning,” Christina Metcalf, PhD, an assistant professor of psychiatry in the Colorado Center for Women’s Behavioral Health and Wellness at the University of Colorado at Denver, Aurora, told attendees. “Given the associations with chronic stress, there’s a lot of potential here to increase our knowledge about how women are doing and managing stress and life stressors during this life transition,” she said.
The study involved collecting hair and saliva samples from 43 healthy women in late perimenopause or early postmenopause with an average age of 51. The participants were predominantly white and college educated. The hair sample was taken within 2 cm of the scalp, and the saliva samples were collected the day after the hair sample collection, at the start and end of a 30-minute rest period that took place between 2:00 and 3:00 p.m. local time.
All the participants had an intact uterus and at least one ovary. None of the participants were current smokers or had recent alcohol or drug dependence, and none had used hormones within the previous 6 months. The study also excluded women who were pregnant or breastfeeding, who had bleached hair or no hair, who were taking steroids, beta blockers or opioid medication, and who had recently taken NSAIDS.
Measuring hair cortisol more feasible
The study was conducted remotely, with participants using video conferencing to communicate with the study personnel and then completing study procedures at home, including 2 days of cognitive testing with the California Verbal Learning Test – Third Edition and the n-back and continuous performance tasks. The participants also completed the Center for Epidemiologic Studies Depression Scale (CES-D).
Participants with higher levels of hair cortisol and salivary cortisol also had more severe depression symptoms (P < .001). Hair cortisol was also significantly associated with attention and working memory: Women with higher levels had fewer correct answers on the 0-back and 1-back trials (P < .01) and made more mistakes on the 2-back trial (P < .001). They also scored with less specificity on the continuous performance tasks (P = .022).
Although no association existed between hair cortisol levels and verbal learning or verbal memory (P > .05), participants with higher hair cortisol did score worse on the immediate recall trials (P = .034). Salivary cortisol levels, on the other hand, showed no association with memory recall trials, attention or working memory (P > .05).
Measuring cortisol from hair samples is more feasible than using saliva samples and may offer valuable insights regarding hypothalamic-pituitary-axis activity “to consider alongside the cognitive and mental health of late peri-/early postmenopausal women,” Dr. Metcalf told attendees. The next step is to find out whether the hypothalamic-pituitary-axis axis is a modifiable biomarker that can be used to improve executive function.
The study was limited by its small population, its cross-sectional design, and the lack of covariates in the current analyses.
Monitor symptoms in midlife
Hadine Joffe, MD, MSc, a professor of psychiatry and executive director of the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said the study findings were not surprising given how common the complaints of stress and depressive symptoms are.
“Mood changes are linked with acute, immediate cortisol levels at the same point in time, and cognitive symptoms were linked to more chronically elevated cortisol levels,” Dr. Joffe said in an interview. “Women and their providers should monitor for these challenging brain symptoms in midlife as they affect performance and quality of life and are linked with changes in the HPA axis as stress biomarkers.”
Because the study is small and has a cross-sectional design, it’s not possible to determine the direction of the associations or to make any inferences about causation, Dr. Joffe said.
“We cannot make the conclusion that stress is adversely affecting mood and cognitive performance given the design limitations. It is possible that mood and cognitive issues contributed to these stress markers,” Dr. Joffe said.“However, it is known that the experience of stress is linked with vulnerability to mood and cognitive symptoms, and also that mood and cognitive symptoms induce significant stress.”
The research was funded by the Menopause Society, Colorado University, the Ludeman Family Center for Women’s Health Research, the National Institute of Mental Health, and the National Institute of Aging. Dr. Metcalf had no disclosures. Dr. Joffe has received grant support from Merck, Pfizer and Sage, and has been a consultant or advisor for Bayer, Merck and Hello Therapeutics.
PHILADELPHIA – , according to research presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
“This work suggests that markers of hypothalamic-pituitary-axis activation that capture total cortisol secretion over multiple months, [such as] hair cortisol, strongly correlate with cognitive performance on attention and working memory tasks, whereas measures of more acute cortisol, [such as] salivary cortisol, may be more strongly associated with depression symptom severity and verbal learning,” Christina Metcalf, PhD, an assistant professor of psychiatry in the Colorado Center for Women’s Behavioral Health and Wellness at the University of Colorado at Denver, Aurora, told attendees. “Given the associations with chronic stress, there’s a lot of potential here to increase our knowledge about how women are doing and managing stress and life stressors during this life transition,” she said.
The study involved collecting hair and saliva samples from 43 healthy women in late perimenopause or early postmenopause with an average age of 51. The participants were predominantly white and college educated. The hair sample was taken within 2 cm of the scalp, and the saliva samples were collected the day after the hair sample collection, at the start and end of a 30-minute rest period that took place between 2:00 and 3:00 p.m. local time.
All the participants had an intact uterus and at least one ovary. None of the participants were current smokers or had recent alcohol or drug dependence, and none had used hormones within the previous 6 months. The study also excluded women who were pregnant or breastfeeding, who had bleached hair or no hair, who were taking steroids, beta blockers or opioid medication, and who had recently taken NSAIDS.
Measuring hair cortisol more feasible
The study was conducted remotely, with participants using video conferencing to communicate with the study personnel and then completing study procedures at home, including 2 days of cognitive testing with the California Verbal Learning Test – Third Edition and the n-back and continuous performance tasks. The participants also completed the Center for Epidemiologic Studies Depression Scale (CES-D).
Participants with higher levels of hair cortisol and salivary cortisol also had more severe depression symptoms (P < .001). Hair cortisol was also significantly associated with attention and working memory: Women with higher levels had fewer correct answers on the 0-back and 1-back trials (P < .01) and made more mistakes on the 2-back trial (P < .001). They also scored with less specificity on the continuous performance tasks (P = .022).
Although no association existed between hair cortisol levels and verbal learning or verbal memory (P > .05), participants with higher hair cortisol did score worse on the immediate recall trials (P = .034). Salivary cortisol levels, on the other hand, showed no association with memory recall trials, attention or working memory (P > .05).
Measuring cortisol from hair samples is more feasible than using saliva samples and may offer valuable insights regarding hypothalamic-pituitary-axis activity “to consider alongside the cognitive and mental health of late peri-/early postmenopausal women,” Dr. Metcalf told attendees. The next step is to find out whether the hypothalamic-pituitary-axis axis is a modifiable biomarker that can be used to improve executive function.
The study was limited by its small population, its cross-sectional design, and the lack of covariates in the current analyses.
Monitor symptoms in midlife
Hadine Joffe, MD, MSc, a professor of psychiatry and executive director of the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said the study findings were not surprising given how common the complaints of stress and depressive symptoms are.
“Mood changes are linked with acute, immediate cortisol levels at the same point in time, and cognitive symptoms were linked to more chronically elevated cortisol levels,” Dr. Joffe said in an interview. “Women and their providers should monitor for these challenging brain symptoms in midlife as they affect performance and quality of life and are linked with changes in the HPA axis as stress biomarkers.”
Because the study is small and has a cross-sectional design, it’s not possible to determine the direction of the associations or to make any inferences about causation, Dr. Joffe said.
“We cannot make the conclusion that stress is adversely affecting mood and cognitive performance given the design limitations. It is possible that mood and cognitive issues contributed to these stress markers,” Dr. Joffe said.“However, it is known that the experience of stress is linked with vulnerability to mood and cognitive symptoms, and also that mood and cognitive symptoms induce significant stress.”
The research was funded by the Menopause Society, Colorado University, the Ludeman Family Center for Women’s Health Research, the National Institute of Mental Health, and the National Institute of Aging. Dr. Metcalf had no disclosures. Dr. Joffe has received grant support from Merck, Pfizer and Sage, and has been a consultant or advisor for Bayer, Merck and Hello Therapeutics.
PHILADELPHIA – , according to research presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).
“This work suggests that markers of hypothalamic-pituitary-axis activation that capture total cortisol secretion over multiple months, [such as] hair cortisol, strongly correlate with cognitive performance on attention and working memory tasks, whereas measures of more acute cortisol, [such as] salivary cortisol, may be more strongly associated with depression symptom severity and verbal learning,” Christina Metcalf, PhD, an assistant professor of psychiatry in the Colorado Center for Women’s Behavioral Health and Wellness at the University of Colorado at Denver, Aurora, told attendees. “Given the associations with chronic stress, there’s a lot of potential here to increase our knowledge about how women are doing and managing stress and life stressors during this life transition,” she said.
The study involved collecting hair and saliva samples from 43 healthy women in late perimenopause or early postmenopause with an average age of 51. The participants were predominantly white and college educated. The hair sample was taken within 2 cm of the scalp, and the saliva samples were collected the day after the hair sample collection, at the start and end of a 30-minute rest period that took place between 2:00 and 3:00 p.m. local time.
All the participants had an intact uterus and at least one ovary. None of the participants were current smokers or had recent alcohol or drug dependence, and none had used hormones within the previous 6 months. The study also excluded women who were pregnant or breastfeeding, who had bleached hair or no hair, who were taking steroids, beta blockers or opioid medication, and who had recently taken NSAIDS.
Measuring hair cortisol more feasible
The study was conducted remotely, with participants using video conferencing to communicate with the study personnel and then completing study procedures at home, including 2 days of cognitive testing with the California Verbal Learning Test – Third Edition and the n-back and continuous performance tasks. The participants also completed the Center for Epidemiologic Studies Depression Scale (CES-D).
Participants with higher levels of hair cortisol and salivary cortisol also had more severe depression symptoms (P < .001). Hair cortisol was also significantly associated with attention and working memory: Women with higher levels had fewer correct answers on the 0-back and 1-back trials (P < .01) and made more mistakes on the 2-back trial (P < .001). They also scored with less specificity on the continuous performance tasks (P = .022).
Although no association existed between hair cortisol levels and verbal learning or verbal memory (P > .05), participants with higher hair cortisol did score worse on the immediate recall trials (P = .034). Salivary cortisol levels, on the other hand, showed no association with memory recall trials, attention or working memory (P > .05).
Measuring cortisol from hair samples is more feasible than using saliva samples and may offer valuable insights regarding hypothalamic-pituitary-axis activity “to consider alongside the cognitive and mental health of late peri-/early postmenopausal women,” Dr. Metcalf told attendees. The next step is to find out whether the hypothalamic-pituitary-axis axis is a modifiable biomarker that can be used to improve executive function.
The study was limited by its small population, its cross-sectional design, and the lack of covariates in the current analyses.
Monitor symptoms in midlife
Hadine Joffe, MD, MSc, a professor of psychiatry and executive director of the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said the study findings were not surprising given how common the complaints of stress and depressive symptoms are.
“Mood changes are linked with acute, immediate cortisol levels at the same point in time, and cognitive symptoms were linked to more chronically elevated cortisol levels,” Dr. Joffe said in an interview. “Women and their providers should monitor for these challenging brain symptoms in midlife as they affect performance and quality of life and are linked with changes in the HPA axis as stress biomarkers.”
Because the study is small and has a cross-sectional design, it’s not possible to determine the direction of the associations or to make any inferences about causation, Dr. Joffe said.
“We cannot make the conclusion that stress is adversely affecting mood and cognitive performance given the design limitations. It is possible that mood and cognitive issues contributed to these stress markers,” Dr. Joffe said.“However, it is known that the experience of stress is linked with vulnerability to mood and cognitive symptoms, and also that mood and cognitive symptoms induce significant stress.”
The research was funded by the Menopause Society, Colorado University, the Ludeman Family Center for Women’s Health Research, the National Institute of Mental Health, and the National Institute of Aging. Dr. Metcalf had no disclosures. Dr. Joffe has received grant support from Merck, Pfizer and Sage, and has been a consultant or advisor for Bayer, Merck and Hello Therapeutics.
AT NAMS 2023