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Does exposure to cell phone Wi-Fi spell trouble for sperm?
A small new study suggests – but doesn’t prove – that exposure to Wi-Fi signals from cell phones in pants pockets could disrupt male fertility. Researchers found that sperm placed next to an in-use iPhone on the Wi-Fi setting over 6 hours had less motility (50% vs. 38%, P = .024) and viability (60% vs. 47%, P = .003) than those set to 4G and 5G.
The findings, presented at the American Society for Reproductive Medicine’s 2022 meeting, don’t confirm that cell phones are harmful, lead author Kevin Y. Chu, MD, a Los Angeles urologist, said in an interview. “We cannot draw conclusions from this study, as the study population was too small. What we did observe was that Wi-Fi, which was previously less studied, may have had an impact on sperm. We did not see an effect on sperm quality by the 4G or 5G wireless spectrum.”
According to Dr. Chu, dozens of studies have examined the possible effect of cell phone exposure on sperm quality. “In human survey studies, there was no association of use and decline of sperm quality,” he said. “In human sperm in vitro studies, there was a decline of sperm motility and viability. And in animal studies, there was decline of sperm motility and viability.”
The new study is a pilot “to see if it is feasible to do a large-scale project” to analyze any possible effects from radiofrequency-electromagnetic radiation (RF-EMR) transmitted by cell phones, he said.
According to the study, cell phones emit radiation when they “transmit data for social media, web browsing, and music/podcast streaming,” and the rise of Bluetooth earbuds “presumably prolonged the amount of time the cell phone resides in the trouser pockets of men. This places the cell phone and its respective RF-EMR near the testicles for prolonged [periods].”
Researchers obtained semen samples from 27 men aged 25-35 who were fertile with normal sperm. Then they placed the samples on top of a current-generation iPhone that was set to talk mode via WhatsApp and transmitted/received signals via Wi-Fi, 4G, or 5G.
The researchers found no difference in sperm quality between control samples and those exposed to 4G or 5G (n = 9), but Wi-Fi (n = 18) seemed to have an effect. “We also tested conditions with the phone in a cover, as well as separating it by about 6 inches [from the sperm samples]. We found that both did dampen the effect of what we were seeing in comparison to direct exposure,” Dr. Chu said. “It appears that heat that is emanated from the device contributes to this effect.”
Dr. Chu cautioned that the study examined only ejaculated sperm, and “does not replicate real life where there is scrotal wall protection [and] pants material.”
For now, he said, there’s not enough evidence to allow clinicians to provide guidance to patients about possible links between cell phone exposure and male fertility. None of the study authors have changed their own use of cell phones as a result of the findings, he added.
Moving forward, he said, “continued research on exposure effects is needed and the current association should be considered cautiously as hypothesis generating.”
In an interview, University of Utah urologist James Hotaling, MD, who’s familiar with the study findings but didn’t take part in the research, said the authors “have done a good job looking at this issue,” but with acknowledged limitations.
The study size is very small, he said, “making generalizability difficult.” And “while the results, particularly on the Wi-Fi part, are interesting, they must be validated.”
In the big picture, he said, “the decline in sperm counts over the last 40 years is multifactorial so it cannot all be attributed to this. Finally, to really make the claim that Wi-Fi impacted fertility, you would need to have a much larger study and, ideally, look at pregnancy rates in couples trying to conceive.”
Overall, he said, the scientific community is “still skeptical” about a link between cell phone use and a decline in male fertility.
The study authors and Dr. Hotaling have no relevant disclosures.
A small new study suggests – but doesn’t prove – that exposure to Wi-Fi signals from cell phones in pants pockets could disrupt male fertility. Researchers found that sperm placed next to an in-use iPhone on the Wi-Fi setting over 6 hours had less motility (50% vs. 38%, P = .024) and viability (60% vs. 47%, P = .003) than those set to 4G and 5G.
The findings, presented at the American Society for Reproductive Medicine’s 2022 meeting, don’t confirm that cell phones are harmful, lead author Kevin Y. Chu, MD, a Los Angeles urologist, said in an interview. “We cannot draw conclusions from this study, as the study population was too small. What we did observe was that Wi-Fi, which was previously less studied, may have had an impact on sperm. We did not see an effect on sperm quality by the 4G or 5G wireless spectrum.”
According to Dr. Chu, dozens of studies have examined the possible effect of cell phone exposure on sperm quality. “In human survey studies, there was no association of use and decline of sperm quality,” he said. “In human sperm in vitro studies, there was a decline of sperm motility and viability. And in animal studies, there was decline of sperm motility and viability.”
The new study is a pilot “to see if it is feasible to do a large-scale project” to analyze any possible effects from radiofrequency-electromagnetic radiation (RF-EMR) transmitted by cell phones, he said.
According to the study, cell phones emit radiation when they “transmit data for social media, web browsing, and music/podcast streaming,” and the rise of Bluetooth earbuds “presumably prolonged the amount of time the cell phone resides in the trouser pockets of men. This places the cell phone and its respective RF-EMR near the testicles for prolonged [periods].”
Researchers obtained semen samples from 27 men aged 25-35 who were fertile with normal sperm. Then they placed the samples on top of a current-generation iPhone that was set to talk mode via WhatsApp and transmitted/received signals via Wi-Fi, 4G, or 5G.
The researchers found no difference in sperm quality between control samples and those exposed to 4G or 5G (n = 9), but Wi-Fi (n = 18) seemed to have an effect. “We also tested conditions with the phone in a cover, as well as separating it by about 6 inches [from the sperm samples]. We found that both did dampen the effect of what we were seeing in comparison to direct exposure,” Dr. Chu said. “It appears that heat that is emanated from the device contributes to this effect.”
Dr. Chu cautioned that the study examined only ejaculated sperm, and “does not replicate real life where there is scrotal wall protection [and] pants material.”
For now, he said, there’s not enough evidence to allow clinicians to provide guidance to patients about possible links between cell phone exposure and male fertility. None of the study authors have changed their own use of cell phones as a result of the findings, he added.
Moving forward, he said, “continued research on exposure effects is needed and the current association should be considered cautiously as hypothesis generating.”
In an interview, University of Utah urologist James Hotaling, MD, who’s familiar with the study findings but didn’t take part in the research, said the authors “have done a good job looking at this issue,” but with acknowledged limitations.
The study size is very small, he said, “making generalizability difficult.” And “while the results, particularly on the Wi-Fi part, are interesting, they must be validated.”
In the big picture, he said, “the decline in sperm counts over the last 40 years is multifactorial so it cannot all be attributed to this. Finally, to really make the claim that Wi-Fi impacted fertility, you would need to have a much larger study and, ideally, look at pregnancy rates in couples trying to conceive.”
Overall, he said, the scientific community is “still skeptical” about a link between cell phone use and a decline in male fertility.
The study authors and Dr. Hotaling have no relevant disclosures.
A small new study suggests – but doesn’t prove – that exposure to Wi-Fi signals from cell phones in pants pockets could disrupt male fertility. Researchers found that sperm placed next to an in-use iPhone on the Wi-Fi setting over 6 hours had less motility (50% vs. 38%, P = .024) and viability (60% vs. 47%, P = .003) than those set to 4G and 5G.
The findings, presented at the American Society for Reproductive Medicine’s 2022 meeting, don’t confirm that cell phones are harmful, lead author Kevin Y. Chu, MD, a Los Angeles urologist, said in an interview. “We cannot draw conclusions from this study, as the study population was too small. What we did observe was that Wi-Fi, which was previously less studied, may have had an impact on sperm. We did not see an effect on sperm quality by the 4G or 5G wireless spectrum.”
According to Dr. Chu, dozens of studies have examined the possible effect of cell phone exposure on sperm quality. “In human survey studies, there was no association of use and decline of sperm quality,” he said. “In human sperm in vitro studies, there was a decline of sperm motility and viability. And in animal studies, there was decline of sperm motility and viability.”
The new study is a pilot “to see if it is feasible to do a large-scale project” to analyze any possible effects from radiofrequency-electromagnetic radiation (RF-EMR) transmitted by cell phones, he said.
According to the study, cell phones emit radiation when they “transmit data for social media, web browsing, and music/podcast streaming,” and the rise of Bluetooth earbuds “presumably prolonged the amount of time the cell phone resides in the trouser pockets of men. This places the cell phone and its respective RF-EMR near the testicles for prolonged [periods].”
Researchers obtained semen samples from 27 men aged 25-35 who were fertile with normal sperm. Then they placed the samples on top of a current-generation iPhone that was set to talk mode via WhatsApp and transmitted/received signals via Wi-Fi, 4G, or 5G.
The researchers found no difference in sperm quality between control samples and those exposed to 4G or 5G (n = 9), but Wi-Fi (n = 18) seemed to have an effect. “We also tested conditions with the phone in a cover, as well as separating it by about 6 inches [from the sperm samples]. We found that both did dampen the effect of what we were seeing in comparison to direct exposure,” Dr. Chu said. “It appears that heat that is emanated from the device contributes to this effect.”
Dr. Chu cautioned that the study examined only ejaculated sperm, and “does not replicate real life where there is scrotal wall protection [and] pants material.”
For now, he said, there’s not enough evidence to allow clinicians to provide guidance to patients about possible links between cell phone exposure and male fertility. None of the study authors have changed their own use of cell phones as a result of the findings, he added.
Moving forward, he said, “continued research on exposure effects is needed and the current association should be considered cautiously as hypothesis generating.”
In an interview, University of Utah urologist James Hotaling, MD, who’s familiar with the study findings but didn’t take part in the research, said the authors “have done a good job looking at this issue,” but with acknowledged limitations.
The study size is very small, he said, “making generalizability difficult.” And “while the results, particularly on the Wi-Fi part, are interesting, they must be validated.”
In the big picture, he said, “the decline in sperm counts over the last 40 years is multifactorial so it cannot all be attributed to this. Finally, to really make the claim that Wi-Fi impacted fertility, you would need to have a much larger study and, ideally, look at pregnancy rates in couples trying to conceive.”
Overall, he said, the scientific community is “still skeptical” about a link between cell phone use and a decline in male fertility.
The study authors and Dr. Hotaling have no relevant disclosures.
BY RANDY DOTINGA FROM ASRM 2022
Stopping levothyroxine in subclinical hypothyroidism safe, feasible
MONTREAL – Patients who discontinue levothyroxine for subclinical hypothyroidism may gravitate towards becoming mildly hypothyroid again, but they importantly show no differences in terms of symptoms and quality of life – and sometimes show even improvement – compared with those who continue treatment, new research shows.
“Our results show feasibility of patient enrollment and safety of discontinuing levothyroxine in patients with subclinical hypothyroidism,” said first author Spyridoula Maraka, MD, when presenting the findings at the American Thyroid Association annual meeting.
With evidence showing widespread overtreatment with levothyroxine for a variety of reasons, “a discontinuation study like this is important to understand the true need for life-long thyroxine therapy,” commented James V. Hennessey, MD, director of clinical endocrinology at Beth Israel Deaconess Medical Center, Boston.
Recommendations against levothyroxine for subclinical hypothyroidism
Subclinical hypothyroidism is commonly over-diagnosed, and treatment with thyroid hormone replacement, levothyroxine, has been shown to provide little, if any, benefit in terms of quality of life or relief of thyroid-related symptoms for these patients.
The treatment is meanwhile associated with burdens including cost and lifestyle adjustments, and one guideline panel recently issued a strong recommendation against routine levothyroxine use in most adults with subclinical hypothyroidism.
Nevertheless, levothyroxine treatment has soared in popularity and become one of the most commonly prescribed drugs in the United States.
With research lacking on one key solution of discontinuation of the therapy, Dr. Maraka, who is part of the Division of Endocrinology and Metabolism at the University of Arkansas for Medical Sciences, Little Rock, and colleagues conducted a double-blind, placebo-controlled trial at the Central Arkansas Veterans Healthcare System. In total, 50 patients treated for subclinical hypothyroidism were randomized 1:1 to continue receiving levothyroxine (25-75 mcg daily) or to discontinue treatment and receive a placebo instead, with a planned 6-month follow-up.
In the current interim analysis, Dr. Maraka reported results for the first 40 patients, including 20 randomized to levothyroxine and 20 to discontinuation.
There were no significant differences between the discontinuation and levothyroxine groups at baseline, which were of a similar age (66.2 vs. 70.8 years) and gender (75% women vs. 85% men).
The groups had similar baseline thyroid-stimulating hormone (TSH) levels (3.0 vs. 2.6 mIU/L), free T4 (both 0.9 ng/dL), thyroid peroxidase antibody positivity (17% vs. 11%), and similar clinical symptoms. All patients had at least one elevated TSH reading prior to starting levothyroxine.
With a follow-up of 6-8 weeks, 36.8% of patients in the discontinuation group had subclinical hypothyroidism, compared with 10% of patients who remained on levothyroxine (P = .0648), TSH levels were 5.5 versus 2.7 mIU/L (P = .001) and free T4 levels were 0.8 versus 0.9 ng/dL (P = .011).
No differences in symptoms, quality of life between groups
Importantly, there were no significant differences between the discontinuation versus levothyroxine groups in terms of symptoms, and even some improvements with discontinuation, including Thyroid-Specific Quality of Life Patient-Reported Outcome (ThyPRO)-Hypothyroid Symptoms score (4.6 reduction vs. 2.2 increase), tiredness (2.6 reduction vs. 1.1 increase), and EuroQoL 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life score, for which there were no differences between groups.
There were no reports of overt hypothyroidism; hyperthyroidism; cardiovascular events including atrial fibrillation, stroke, or heart failure; osteoporotic fractures; or deaths.
One patient in the discontinuation group had a TSH level of 11 mIU/L at 6-8 weeks and switched to open-label levothyroxine 75 mcg daily. Another patient in the discontinuation group switched to open-label levothyroxine 75 mcg daily at 10 weeks due to fatigue; however, the patient was diagnosed with metastatic colon cancer 1 month later.
The finding that only about a third of patients who discontinued levothyroxine developed subclinical hypothyroidism was lower than expected, Dr. Maraka noted.
“This was ... unexpected ... for us,” she said. “We were expecting a larger number of patients to develop hypothyroidism, but to our surprise, that was not the case.”
“But what is more important is that there was no difference in the quality of life measures,” she added. “If anything, the placebo group was a little better, though the [differences] were not statistically significant.”
Dr. Maraka also noted that in further research and a final 6-month analysis, the authors will look at factors associated with developing subclinical hypothyroidism after treatment discontinuation, among other issues.
Discontinuation of levothyroxine is manageable
The results are encouraging, as they provide assurance that discontinuation of levothyroxine is manageable.
“This research will pave the way for initiatives to promote levothyroxine deprescription and implementation of evidence-based care for patients with subclinical hypothyroidism,” she said.
In further comments, Dr. Hennessey noted that the dilemma of having patients on levothyroxine who may not be benefitting from treatment is “significant,” with patients sometimes reluctant to discontinue treatment due to concerns of developing hypothyroidism-associated symptoms such as brain fog and weight gain.
He noted, however, that “many with mildly elevated TSH actually go on to normalize with time, so they are not really hypothyroid, [and] if we remove thyroxine from people with normal thyroid function, they will remain normal.”
Dr. Maraka has reported no relevant financial relationships. Dr. Hennessey has reported consulting for pharmaceutical companies to design clinical studies for thyroid medications.
A version of this article first appeared on Medscape.com.
MONTREAL – Patients who discontinue levothyroxine for subclinical hypothyroidism may gravitate towards becoming mildly hypothyroid again, but they importantly show no differences in terms of symptoms and quality of life – and sometimes show even improvement – compared with those who continue treatment, new research shows.
“Our results show feasibility of patient enrollment and safety of discontinuing levothyroxine in patients with subclinical hypothyroidism,” said first author Spyridoula Maraka, MD, when presenting the findings at the American Thyroid Association annual meeting.
With evidence showing widespread overtreatment with levothyroxine for a variety of reasons, “a discontinuation study like this is important to understand the true need for life-long thyroxine therapy,” commented James V. Hennessey, MD, director of clinical endocrinology at Beth Israel Deaconess Medical Center, Boston.
Recommendations against levothyroxine for subclinical hypothyroidism
Subclinical hypothyroidism is commonly over-diagnosed, and treatment with thyroid hormone replacement, levothyroxine, has been shown to provide little, if any, benefit in terms of quality of life or relief of thyroid-related symptoms for these patients.
The treatment is meanwhile associated with burdens including cost and lifestyle adjustments, and one guideline panel recently issued a strong recommendation against routine levothyroxine use in most adults with subclinical hypothyroidism.
Nevertheless, levothyroxine treatment has soared in popularity and become one of the most commonly prescribed drugs in the United States.
With research lacking on one key solution of discontinuation of the therapy, Dr. Maraka, who is part of the Division of Endocrinology and Metabolism at the University of Arkansas for Medical Sciences, Little Rock, and colleagues conducted a double-blind, placebo-controlled trial at the Central Arkansas Veterans Healthcare System. In total, 50 patients treated for subclinical hypothyroidism were randomized 1:1 to continue receiving levothyroxine (25-75 mcg daily) or to discontinue treatment and receive a placebo instead, with a planned 6-month follow-up.
In the current interim analysis, Dr. Maraka reported results for the first 40 patients, including 20 randomized to levothyroxine and 20 to discontinuation.
There were no significant differences between the discontinuation and levothyroxine groups at baseline, which were of a similar age (66.2 vs. 70.8 years) and gender (75% women vs. 85% men).
The groups had similar baseline thyroid-stimulating hormone (TSH) levels (3.0 vs. 2.6 mIU/L), free T4 (both 0.9 ng/dL), thyroid peroxidase antibody positivity (17% vs. 11%), and similar clinical symptoms. All patients had at least one elevated TSH reading prior to starting levothyroxine.
With a follow-up of 6-8 weeks, 36.8% of patients in the discontinuation group had subclinical hypothyroidism, compared with 10% of patients who remained on levothyroxine (P = .0648), TSH levels were 5.5 versus 2.7 mIU/L (P = .001) and free T4 levels were 0.8 versus 0.9 ng/dL (P = .011).
No differences in symptoms, quality of life between groups
Importantly, there were no significant differences between the discontinuation versus levothyroxine groups in terms of symptoms, and even some improvements with discontinuation, including Thyroid-Specific Quality of Life Patient-Reported Outcome (ThyPRO)-Hypothyroid Symptoms score (4.6 reduction vs. 2.2 increase), tiredness (2.6 reduction vs. 1.1 increase), and EuroQoL 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life score, for which there were no differences between groups.
There were no reports of overt hypothyroidism; hyperthyroidism; cardiovascular events including atrial fibrillation, stroke, or heart failure; osteoporotic fractures; or deaths.
One patient in the discontinuation group had a TSH level of 11 mIU/L at 6-8 weeks and switched to open-label levothyroxine 75 mcg daily. Another patient in the discontinuation group switched to open-label levothyroxine 75 mcg daily at 10 weeks due to fatigue; however, the patient was diagnosed with metastatic colon cancer 1 month later.
The finding that only about a third of patients who discontinued levothyroxine developed subclinical hypothyroidism was lower than expected, Dr. Maraka noted.
“This was ... unexpected ... for us,” she said. “We were expecting a larger number of patients to develop hypothyroidism, but to our surprise, that was not the case.”
“But what is more important is that there was no difference in the quality of life measures,” she added. “If anything, the placebo group was a little better, though the [differences] were not statistically significant.”
Dr. Maraka also noted that in further research and a final 6-month analysis, the authors will look at factors associated with developing subclinical hypothyroidism after treatment discontinuation, among other issues.
Discontinuation of levothyroxine is manageable
The results are encouraging, as they provide assurance that discontinuation of levothyroxine is manageable.
“This research will pave the way for initiatives to promote levothyroxine deprescription and implementation of evidence-based care for patients with subclinical hypothyroidism,” she said.
In further comments, Dr. Hennessey noted that the dilemma of having patients on levothyroxine who may not be benefitting from treatment is “significant,” with patients sometimes reluctant to discontinue treatment due to concerns of developing hypothyroidism-associated symptoms such as brain fog and weight gain.
He noted, however, that “many with mildly elevated TSH actually go on to normalize with time, so they are not really hypothyroid, [and] if we remove thyroxine from people with normal thyroid function, they will remain normal.”
Dr. Maraka has reported no relevant financial relationships. Dr. Hennessey has reported consulting for pharmaceutical companies to design clinical studies for thyroid medications.
A version of this article first appeared on Medscape.com.
MONTREAL – Patients who discontinue levothyroxine for subclinical hypothyroidism may gravitate towards becoming mildly hypothyroid again, but they importantly show no differences in terms of symptoms and quality of life – and sometimes show even improvement – compared with those who continue treatment, new research shows.
“Our results show feasibility of patient enrollment and safety of discontinuing levothyroxine in patients with subclinical hypothyroidism,” said first author Spyridoula Maraka, MD, when presenting the findings at the American Thyroid Association annual meeting.
With evidence showing widespread overtreatment with levothyroxine for a variety of reasons, “a discontinuation study like this is important to understand the true need for life-long thyroxine therapy,” commented James V. Hennessey, MD, director of clinical endocrinology at Beth Israel Deaconess Medical Center, Boston.
Recommendations against levothyroxine for subclinical hypothyroidism
Subclinical hypothyroidism is commonly over-diagnosed, and treatment with thyroid hormone replacement, levothyroxine, has been shown to provide little, if any, benefit in terms of quality of life or relief of thyroid-related symptoms for these patients.
The treatment is meanwhile associated with burdens including cost and lifestyle adjustments, and one guideline panel recently issued a strong recommendation against routine levothyroxine use in most adults with subclinical hypothyroidism.
Nevertheless, levothyroxine treatment has soared in popularity and become one of the most commonly prescribed drugs in the United States.
With research lacking on one key solution of discontinuation of the therapy, Dr. Maraka, who is part of the Division of Endocrinology and Metabolism at the University of Arkansas for Medical Sciences, Little Rock, and colleagues conducted a double-blind, placebo-controlled trial at the Central Arkansas Veterans Healthcare System. In total, 50 patients treated for subclinical hypothyroidism were randomized 1:1 to continue receiving levothyroxine (25-75 mcg daily) or to discontinue treatment and receive a placebo instead, with a planned 6-month follow-up.
In the current interim analysis, Dr. Maraka reported results for the first 40 patients, including 20 randomized to levothyroxine and 20 to discontinuation.
There were no significant differences between the discontinuation and levothyroxine groups at baseline, which were of a similar age (66.2 vs. 70.8 years) and gender (75% women vs. 85% men).
The groups had similar baseline thyroid-stimulating hormone (TSH) levels (3.0 vs. 2.6 mIU/L), free T4 (both 0.9 ng/dL), thyroid peroxidase antibody positivity (17% vs. 11%), and similar clinical symptoms. All patients had at least one elevated TSH reading prior to starting levothyroxine.
With a follow-up of 6-8 weeks, 36.8% of patients in the discontinuation group had subclinical hypothyroidism, compared with 10% of patients who remained on levothyroxine (P = .0648), TSH levels were 5.5 versus 2.7 mIU/L (P = .001) and free T4 levels were 0.8 versus 0.9 ng/dL (P = .011).
No differences in symptoms, quality of life between groups
Importantly, there were no significant differences between the discontinuation versus levothyroxine groups in terms of symptoms, and even some improvements with discontinuation, including Thyroid-Specific Quality of Life Patient-Reported Outcome (ThyPRO)-Hypothyroid Symptoms score (4.6 reduction vs. 2.2 increase), tiredness (2.6 reduction vs. 1.1 increase), and EuroQoL 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life score, for which there were no differences between groups.
There were no reports of overt hypothyroidism; hyperthyroidism; cardiovascular events including atrial fibrillation, stroke, or heart failure; osteoporotic fractures; or deaths.
One patient in the discontinuation group had a TSH level of 11 mIU/L at 6-8 weeks and switched to open-label levothyroxine 75 mcg daily. Another patient in the discontinuation group switched to open-label levothyroxine 75 mcg daily at 10 weeks due to fatigue; however, the patient was diagnosed with metastatic colon cancer 1 month later.
The finding that only about a third of patients who discontinued levothyroxine developed subclinical hypothyroidism was lower than expected, Dr. Maraka noted.
“This was ... unexpected ... for us,” she said. “We were expecting a larger number of patients to develop hypothyroidism, but to our surprise, that was not the case.”
“But what is more important is that there was no difference in the quality of life measures,” she added. “If anything, the placebo group was a little better, though the [differences] were not statistically significant.”
Dr. Maraka also noted that in further research and a final 6-month analysis, the authors will look at factors associated with developing subclinical hypothyroidism after treatment discontinuation, among other issues.
Discontinuation of levothyroxine is manageable
The results are encouraging, as they provide assurance that discontinuation of levothyroxine is manageable.
“This research will pave the way for initiatives to promote levothyroxine deprescription and implementation of evidence-based care for patients with subclinical hypothyroidism,” she said.
In further comments, Dr. Hennessey noted that the dilemma of having patients on levothyroxine who may not be benefitting from treatment is “significant,” with patients sometimes reluctant to discontinue treatment due to concerns of developing hypothyroidism-associated symptoms such as brain fog and weight gain.
He noted, however, that “many with mildly elevated TSH actually go on to normalize with time, so they are not really hypothyroid, [and] if we remove thyroxine from people with normal thyroid function, they will remain normal.”
Dr. Maraka has reported no relevant financial relationships. Dr. Hennessey has reported consulting for pharmaceutical companies to design clinical studies for thyroid medications.
A version of this article first appeared on Medscape.com.
AT ATA 2022
Criminal profiles of medical murderers
Today’s health care professionals run the very real risk of being sued. This is especially true when a patient dies unexpectedly. But many times, doctors find that they’re defending themselves against very serious charges, such as murder and attempted murder.
In Mexico, a physician can be wrongfully accused of such crimes, as was Azucena Calvillo, MD, last year in Durango. The case drew much media attention, and the accusations were so implausible and ridiculous that the charges were dropped and the case was dismissed.
There are instances in which the authorities create a circuslike atmosphere by making farcical and false accusations against healthcare professionals. Still, there are medical murderers – and these killers are among the most difficult to identify. As John E. Douglas put it, “Medical murderers (physicians, nurses, elder care workers) can have a long list of victims, longer than other kinds of serial killers.” Ted Bundy, one of the most written-about serial killers, confessed to 30 murders. The cases discussed below involve from 60 to 200.
Mr. Douglas was a special agent with the United States Federal Bureau of Investigation. He is the author of Mindhunter, a nonfiction crime book in which he recounts the early days of the FBI’s Behavioral Science Unit and how he and his colleagues began to study the criminal profiles of serial killers. The book has been adapted into a Netflix TV series of the same name.
He is also one of the authors of Crime Classification Manual: A Standard System for Investigating and Classifying Violent Crime. In this book, there are descriptions of criminal profiles of medical murderers.
According to the authors, Each type is associated with a different motive. In the former, the murderers believe that they’re alleviating the patient’s suffering; in the latter, the murderers create a medical emergency so that they can play the hero in what they know will be an unsuccessful attempt to save the patient’s life.
Pseudo-mercy homicide
An example of pseudo-mercy homicide is the infamous case of Harold Shipman, MD, who was convicted of killing 15 people, although an investigation found that more than 200 persons, and possibly as many as 250, died at his hands. In Prescription for Murder: The True Story of Dr. Harold Frederick Shipman, biographer Brian Whittle writes that the general practitioner is England’s (if not the world’s) most prolific serial killer. Dr. Shipman is the only physician in that country’s history to have been convicted of killing his patients.
His modus operandi? Injecting morphine. Most of his victims were elderly women. And though unconfirmed, his youngest victim may have been only 4 years old. It was the death of 81-year-old Kathleen Grundy that led to the physician’s arrest. Her family became extremely suspicious when they learned that her will named Dr. Shipman as the beneficiary of her entire estate.
He always denied being involved in the murders, for which authorities have yet to determine a motive. The speculation is that he enjoyed watching people die. Almost none of the cases attributed to Dr. Shipman involved a critically ill individual with a life-threatening condition. Therefore, his acts were not real acts of mercy. He would make a house call to carry out a routine visit. Once in the patient’s home, he would inject a lethal dose of morphine. Sometimes, relatives and physicians alike would be struck by the strange turn of events.
In 2004, Dr. Shipman committed suicide in prison. His case led to numerous changes to British law with respect to the use of controlled substances, the issuance of death certificates, and the procedure for reporting healthcare staff suspected of engaging in illegal activities. Biographer Whittle concluded, “It is very unlikely that the world will ever see another physician as unrelentingly wicked as Dr. Shipman.”
Pseudo-hero homicide
The pseudo-hero creates serious situations, generally by administering drugs, and then tries to save the patient. Mr. Douglas presents a terrifying case study: Genene Jones, a nurse known as the “Angel of Death.”
Many of Ms. Jones’ colleagues considered her an excellent nurse, an expert at handling unexpected emergencies. If a child died while she was on duty, she would sometimes accompany their body to the morgue. She would even sing children’s songs to their lifeless body. When people started to question the number of deaths that were occurring during her shifts, the staff stood up for Ms. Jones, saying that it was because she took on the most serious cases.
Ms. Jones was found out when a vial of succinylcholine went missing. After it was located, a physician, who had been suspicious of the nurse, noticed that there were two puncture holes in the stopper. None of the staff could offer any explanation. A few days before this event, that same physician had left a healthy 15-month-old girl in Jones’ care. Within a few minutes, the child was showing signs of paralysis and started to have seizures. It appears that Ms. Jones had used succinylcholine to make it appear that the children were sick or were experiencing some sort of emergency so that she could then attempt to save them, and they could die in her arms.
This case highlights the need for mortality review committees and for proper statistical analysis to discern trends in deaths and complications among patients. Genene Jones was convicted of killing the 15-month-old girl and was sentenced to 99 years in prison. Authorities suspect that the nurse was responsible for the deaths of up to 60 children.
A new criminal profile?
Through the podcast and subsequent TV series Dr. Death, many people have come to know of a more recent medical murderer: Christopher Duntsch, MD, PhD. The Texas neurosurgeon killed at least two patients, and his actions left several others with adverse outcomes and serious injuries.
These acts occurred during surgical procedures. Witnesses said that the deaths and injuries were the result of unprecedented, egregious negligence, as though the operations had been performed by someone who had never been trained in the specialty. This is something that resonates very strongly for those who are aware of what’s going on in Mexico, where it’s well known that many physicians who lack specialty training perform operations (mainly cosmetic surgery). No doubt cases such as Dr. Duntsch’s are more frequent in Mexico.
What makes the situation in the United States involving Christopher Duntsch so astonishing is that it resulted from a perfect storm of a physician whom some colleagues described as a “sociopath” and legal loopholes in the country’s healthcare system. Apparently, during his residency, Dr. Duntsch never developed the skills necessary to perform operations. He spent more time carrying out research and engaging in other activities than in participating in the operating room. This is a case that calls into question the way specialists are trained, as it seems that what matters is not how much time they’re spending inside the hospital but what they’re doing and learning there.
Dr. Duntsch’s license was suspended and then permanently revoked. He is currently serving a life sentence. Through the podcast or the TV series, one comes to realize that it’s not easy to catch medical murderers. They are among the most difficult to identify – serial killers who commit numerous homicides before they are captured. Reading about the case of Christopher Duntsch, one might ask, What’s his criminal profile: pseudo-hero? Pseudo-mercy? It is hard to say. Maybe his is a different kind of profile – one that will open a new chapter in the books on medical murderers.
Dr. Sarmiento studied medicine and did his residency in anatomic pathology, internal medicine, and clinical hematology. He went on to study at Central University City Campus Law School, National Autonomous University of Mexico. He now runs a law firm that, among other things, advises physicians on matters of civil liability, administrative processes, and the legal implications of practicing medicine.
This article was translated from the Medscape Spanish edition.
Today’s health care professionals run the very real risk of being sued. This is especially true when a patient dies unexpectedly. But many times, doctors find that they’re defending themselves against very serious charges, such as murder and attempted murder.
In Mexico, a physician can be wrongfully accused of such crimes, as was Azucena Calvillo, MD, last year in Durango. The case drew much media attention, and the accusations were so implausible and ridiculous that the charges were dropped and the case was dismissed.
There are instances in which the authorities create a circuslike atmosphere by making farcical and false accusations against healthcare professionals. Still, there are medical murderers – and these killers are among the most difficult to identify. As John E. Douglas put it, “Medical murderers (physicians, nurses, elder care workers) can have a long list of victims, longer than other kinds of serial killers.” Ted Bundy, one of the most written-about serial killers, confessed to 30 murders. The cases discussed below involve from 60 to 200.
Mr. Douglas was a special agent with the United States Federal Bureau of Investigation. He is the author of Mindhunter, a nonfiction crime book in which he recounts the early days of the FBI’s Behavioral Science Unit and how he and his colleagues began to study the criminal profiles of serial killers. The book has been adapted into a Netflix TV series of the same name.
He is also one of the authors of Crime Classification Manual: A Standard System for Investigating and Classifying Violent Crime. In this book, there are descriptions of criminal profiles of medical murderers.
According to the authors, Each type is associated with a different motive. In the former, the murderers believe that they’re alleviating the patient’s suffering; in the latter, the murderers create a medical emergency so that they can play the hero in what they know will be an unsuccessful attempt to save the patient’s life.
Pseudo-mercy homicide
An example of pseudo-mercy homicide is the infamous case of Harold Shipman, MD, who was convicted of killing 15 people, although an investigation found that more than 200 persons, and possibly as many as 250, died at his hands. In Prescription for Murder: The True Story of Dr. Harold Frederick Shipman, biographer Brian Whittle writes that the general practitioner is England’s (if not the world’s) most prolific serial killer. Dr. Shipman is the only physician in that country’s history to have been convicted of killing his patients.
His modus operandi? Injecting morphine. Most of his victims were elderly women. And though unconfirmed, his youngest victim may have been only 4 years old. It was the death of 81-year-old Kathleen Grundy that led to the physician’s arrest. Her family became extremely suspicious when they learned that her will named Dr. Shipman as the beneficiary of her entire estate.
He always denied being involved in the murders, for which authorities have yet to determine a motive. The speculation is that he enjoyed watching people die. Almost none of the cases attributed to Dr. Shipman involved a critically ill individual with a life-threatening condition. Therefore, his acts were not real acts of mercy. He would make a house call to carry out a routine visit. Once in the patient’s home, he would inject a lethal dose of morphine. Sometimes, relatives and physicians alike would be struck by the strange turn of events.
In 2004, Dr. Shipman committed suicide in prison. His case led to numerous changes to British law with respect to the use of controlled substances, the issuance of death certificates, and the procedure for reporting healthcare staff suspected of engaging in illegal activities. Biographer Whittle concluded, “It is very unlikely that the world will ever see another physician as unrelentingly wicked as Dr. Shipman.”
Pseudo-hero homicide
The pseudo-hero creates serious situations, generally by administering drugs, and then tries to save the patient. Mr. Douglas presents a terrifying case study: Genene Jones, a nurse known as the “Angel of Death.”
Many of Ms. Jones’ colleagues considered her an excellent nurse, an expert at handling unexpected emergencies. If a child died while she was on duty, she would sometimes accompany their body to the morgue. She would even sing children’s songs to their lifeless body. When people started to question the number of deaths that were occurring during her shifts, the staff stood up for Ms. Jones, saying that it was because she took on the most serious cases.
Ms. Jones was found out when a vial of succinylcholine went missing. After it was located, a physician, who had been suspicious of the nurse, noticed that there were two puncture holes in the stopper. None of the staff could offer any explanation. A few days before this event, that same physician had left a healthy 15-month-old girl in Jones’ care. Within a few minutes, the child was showing signs of paralysis and started to have seizures. It appears that Ms. Jones had used succinylcholine to make it appear that the children were sick or were experiencing some sort of emergency so that she could then attempt to save them, and they could die in her arms.
This case highlights the need for mortality review committees and for proper statistical analysis to discern trends in deaths and complications among patients. Genene Jones was convicted of killing the 15-month-old girl and was sentenced to 99 years in prison. Authorities suspect that the nurse was responsible for the deaths of up to 60 children.
A new criminal profile?
Through the podcast and subsequent TV series Dr. Death, many people have come to know of a more recent medical murderer: Christopher Duntsch, MD, PhD. The Texas neurosurgeon killed at least two patients, and his actions left several others with adverse outcomes and serious injuries.
These acts occurred during surgical procedures. Witnesses said that the deaths and injuries were the result of unprecedented, egregious negligence, as though the operations had been performed by someone who had never been trained in the specialty. This is something that resonates very strongly for those who are aware of what’s going on in Mexico, where it’s well known that many physicians who lack specialty training perform operations (mainly cosmetic surgery). No doubt cases such as Dr. Duntsch’s are more frequent in Mexico.
What makes the situation in the United States involving Christopher Duntsch so astonishing is that it resulted from a perfect storm of a physician whom some colleagues described as a “sociopath” and legal loopholes in the country’s healthcare system. Apparently, during his residency, Dr. Duntsch never developed the skills necessary to perform operations. He spent more time carrying out research and engaging in other activities than in participating in the operating room. This is a case that calls into question the way specialists are trained, as it seems that what matters is not how much time they’re spending inside the hospital but what they’re doing and learning there.
Dr. Duntsch’s license was suspended and then permanently revoked. He is currently serving a life sentence. Through the podcast or the TV series, one comes to realize that it’s not easy to catch medical murderers. They are among the most difficult to identify – serial killers who commit numerous homicides before they are captured. Reading about the case of Christopher Duntsch, one might ask, What’s his criminal profile: pseudo-hero? Pseudo-mercy? It is hard to say. Maybe his is a different kind of profile – one that will open a new chapter in the books on medical murderers.
Dr. Sarmiento studied medicine and did his residency in anatomic pathology, internal medicine, and clinical hematology. He went on to study at Central University City Campus Law School, National Autonomous University of Mexico. He now runs a law firm that, among other things, advises physicians on matters of civil liability, administrative processes, and the legal implications of practicing medicine.
This article was translated from the Medscape Spanish edition.
Today’s health care professionals run the very real risk of being sued. This is especially true when a patient dies unexpectedly. But many times, doctors find that they’re defending themselves against very serious charges, such as murder and attempted murder.
In Mexico, a physician can be wrongfully accused of such crimes, as was Azucena Calvillo, MD, last year in Durango. The case drew much media attention, and the accusations were so implausible and ridiculous that the charges were dropped and the case was dismissed.
There are instances in which the authorities create a circuslike atmosphere by making farcical and false accusations against healthcare professionals. Still, there are medical murderers – and these killers are among the most difficult to identify. As John E. Douglas put it, “Medical murderers (physicians, nurses, elder care workers) can have a long list of victims, longer than other kinds of serial killers.” Ted Bundy, one of the most written-about serial killers, confessed to 30 murders. The cases discussed below involve from 60 to 200.
Mr. Douglas was a special agent with the United States Federal Bureau of Investigation. He is the author of Mindhunter, a nonfiction crime book in which he recounts the early days of the FBI’s Behavioral Science Unit and how he and his colleagues began to study the criminal profiles of serial killers. The book has been adapted into a Netflix TV series of the same name.
He is also one of the authors of Crime Classification Manual: A Standard System for Investigating and Classifying Violent Crime. In this book, there are descriptions of criminal profiles of medical murderers.
According to the authors, Each type is associated with a different motive. In the former, the murderers believe that they’re alleviating the patient’s suffering; in the latter, the murderers create a medical emergency so that they can play the hero in what they know will be an unsuccessful attempt to save the patient’s life.
Pseudo-mercy homicide
An example of pseudo-mercy homicide is the infamous case of Harold Shipman, MD, who was convicted of killing 15 people, although an investigation found that more than 200 persons, and possibly as many as 250, died at his hands. In Prescription for Murder: The True Story of Dr. Harold Frederick Shipman, biographer Brian Whittle writes that the general practitioner is England’s (if not the world’s) most prolific serial killer. Dr. Shipman is the only physician in that country’s history to have been convicted of killing his patients.
His modus operandi? Injecting morphine. Most of his victims were elderly women. And though unconfirmed, his youngest victim may have been only 4 years old. It was the death of 81-year-old Kathleen Grundy that led to the physician’s arrest. Her family became extremely suspicious when they learned that her will named Dr. Shipman as the beneficiary of her entire estate.
He always denied being involved in the murders, for which authorities have yet to determine a motive. The speculation is that he enjoyed watching people die. Almost none of the cases attributed to Dr. Shipman involved a critically ill individual with a life-threatening condition. Therefore, his acts were not real acts of mercy. He would make a house call to carry out a routine visit. Once in the patient’s home, he would inject a lethal dose of morphine. Sometimes, relatives and physicians alike would be struck by the strange turn of events.
In 2004, Dr. Shipman committed suicide in prison. His case led to numerous changes to British law with respect to the use of controlled substances, the issuance of death certificates, and the procedure for reporting healthcare staff suspected of engaging in illegal activities. Biographer Whittle concluded, “It is very unlikely that the world will ever see another physician as unrelentingly wicked as Dr. Shipman.”
Pseudo-hero homicide
The pseudo-hero creates serious situations, generally by administering drugs, and then tries to save the patient. Mr. Douglas presents a terrifying case study: Genene Jones, a nurse known as the “Angel of Death.”
Many of Ms. Jones’ colleagues considered her an excellent nurse, an expert at handling unexpected emergencies. If a child died while she was on duty, she would sometimes accompany their body to the morgue. She would even sing children’s songs to their lifeless body. When people started to question the number of deaths that were occurring during her shifts, the staff stood up for Ms. Jones, saying that it was because she took on the most serious cases.
Ms. Jones was found out when a vial of succinylcholine went missing. After it was located, a physician, who had been suspicious of the nurse, noticed that there were two puncture holes in the stopper. None of the staff could offer any explanation. A few days before this event, that same physician had left a healthy 15-month-old girl in Jones’ care. Within a few minutes, the child was showing signs of paralysis and started to have seizures. It appears that Ms. Jones had used succinylcholine to make it appear that the children were sick or were experiencing some sort of emergency so that she could then attempt to save them, and they could die in her arms.
This case highlights the need for mortality review committees and for proper statistical analysis to discern trends in deaths and complications among patients. Genene Jones was convicted of killing the 15-month-old girl and was sentenced to 99 years in prison. Authorities suspect that the nurse was responsible for the deaths of up to 60 children.
A new criminal profile?
Through the podcast and subsequent TV series Dr. Death, many people have come to know of a more recent medical murderer: Christopher Duntsch, MD, PhD. The Texas neurosurgeon killed at least two patients, and his actions left several others with adverse outcomes and serious injuries.
These acts occurred during surgical procedures. Witnesses said that the deaths and injuries were the result of unprecedented, egregious negligence, as though the operations had been performed by someone who had never been trained in the specialty. This is something that resonates very strongly for those who are aware of what’s going on in Mexico, where it’s well known that many physicians who lack specialty training perform operations (mainly cosmetic surgery). No doubt cases such as Dr. Duntsch’s are more frequent in Mexico.
What makes the situation in the United States involving Christopher Duntsch so astonishing is that it resulted from a perfect storm of a physician whom some colleagues described as a “sociopath” and legal loopholes in the country’s healthcare system. Apparently, during his residency, Dr. Duntsch never developed the skills necessary to perform operations. He spent more time carrying out research and engaging in other activities than in participating in the operating room. This is a case that calls into question the way specialists are trained, as it seems that what matters is not how much time they’re spending inside the hospital but what they’re doing and learning there.
Dr. Duntsch’s license was suspended and then permanently revoked. He is currently serving a life sentence. Through the podcast or the TV series, one comes to realize that it’s not easy to catch medical murderers. They are among the most difficult to identify – serial killers who commit numerous homicides before they are captured. Reading about the case of Christopher Duntsch, one might ask, What’s his criminal profile: pseudo-hero? Pseudo-mercy? It is hard to say. Maybe his is a different kind of profile – one that will open a new chapter in the books on medical murderers.
Dr. Sarmiento studied medicine and did his residency in anatomic pathology, internal medicine, and clinical hematology. He went on to study at Central University City Campus Law School, National Autonomous University of Mexico. He now runs a law firm that, among other things, advises physicians on matters of civil liability, administrative processes, and the legal implications of practicing medicine.
This article was translated from the Medscape Spanish edition.
A gender primer for psychiatrists
Psychiatrists have a long tradition of supporting LGBTQAI+ (lesbian, gay, bisexual, transgender, queer/questioning, asexual, intersex, and others) persons. In professional and public settings, we are educators, role models, and advocates for self-expression and personal empowerment. By better educating ourselves on the topic of gender and its variations, we can become champions of gender-affirming care.
Sex vs gender
A person’s sex is assigned at birth based on their physiological characteristics, including their genitalia and chromosome composition. Male, female, and intersex are a few recognized sexes. Gender or gender identity describe one’s innermost perception of self as a man, a woman, a variation of both, or neither, that may not always be visible to others. When sex and gender identity align, this is known as cisgender.1
Gender identity
Gender identity is best described as a spectrum rather than a binary. Terms that fall under a gender binary include man, woman, trans man, and trans woman. A nonbinary gender identity is one outside the traditional binary of men or women. Being transgender simply means having a gender identity different than the sex assigned at birth. This includes persons whose gender identities cross the gender spectrum, such as trans men or trans women, and those who fall anywhere outside or in between genders. In this way, nonbinary persons are transgender.1
The nonbinary spectrum
The term nonbinary encompasses many gender-nonconforming identities, such as agender, bigender, demigender, genderfluid, genderqueer, intergender, or pangender. Agender people have little connection to gender. Bigender individuals identify as 2 separate genders. Demigender persons feel a partial connection to a gender. Genderfluid individuals have a gender experience that is fluid and can change over time. Genderqueer people have a gender identity that falls in between or outside the binary. Intergender people have a gender identity between genders or identify as a combination of genders. Pangender people identify with a combination of genders. Note that patients may use some of these terms interchangeably or ascribe to them different meanings.2 As the language around gender continues to evolve, psychiatrists should ask patients from a place of nonjudgmental curiosity what gender terms they use, how they define them, and what their gender means to them.
Gender expression and transitioning
Transitioning is what a transgender person does to align their gender identity and expression.3 Gender expression is the external manifestation of gender, including names, pronouns, clothing, haircuts, behaviors, voice, body characteristics, and more.1 Transgender individuals can transition using a combination of social (name, pronouns, dress), legal (changing sex on legal documents, name change), or medical (surgeries, hormone therapies, puberty blockade) means. Transitions often help ease gender dysphoria, which is the clinically significant distress a person experiences when their sex assigned at birth does not align with their gender identity.3 Note that not all transgender persons choose to change their gender expression, and not all transgender individuals experience gender dysphoria. In this case, the proper medical term is gender incongruence, which is simply when someone’s gender identity does not align with their sex assigned at birth.4
Names and pronouns
For many transgender persons, names and pronouns are an important part of their gender transition and expression.2 Most of us have gotten into the habit of assuming pronouns because of socially established gender roles. This assumes that a person’s physical appearance matches their gender identity, which is not always the case.1 To be more affirming, psychiatrists and other health care professionals should try to break the habit of assuming pronouns. Often, an easy way to learn someone’s pronouns is to introduce yourself with yours. For example, “I am Dr. Agapoff. I use they/them/theirs pronouns. It is nice to meet you.” This creates a safe and open space for the other person to share their gender identity if they choose.
Why it’s important
One does not have to be a gender specialist to deliver gender-affirming care. As psychiatrists, having a basic understanding of the differences between sex, gender identity, and gender expression can help us build rapport and support our patients who are transgender. Based on the many kinds of gender identity and expression, judging someone’s gender based solely upon physical appearance is misguided at best and harmful at worst. Even people who are cisgender have many kinds of gender expression. For this reason, psychiatrists should approach gender with the same openness and curiosity as sexual orientation or other important considerations of emotional and physical health. Gender-informed care starts with us.
1. LGBTQIA Resource Center Glossary. UC Davis LGBTQIA Resource Center. Accessed July 19, 2022. https://lgbtqia.ucdavis.edu/educated/glossary
2. Richards C, Bouman WP, Seal L, et al. Non-binary or genderqueer genders. Int Rev Psychiatry. 2016;28(1):95-102. doi:10.3109/09540261.2015.1106446
3. Understanding transitions. TransFamilies.Org. Accessed June 1, 2022. https://transfamilies.org/understanding-transitions/
4. Claahsen-van der Grinten H, Verhaak C, Steensma T, et al. Gender incongruence and gender dysphoria in childhood and adolescence—current insights in diagnostics, management, and follow-up. Eur J Pediatr. 2021;180(5):1349-1357.
Psychiatrists have a long tradition of supporting LGBTQAI+ (lesbian, gay, bisexual, transgender, queer/questioning, asexual, intersex, and others) persons. In professional and public settings, we are educators, role models, and advocates for self-expression and personal empowerment. By better educating ourselves on the topic of gender and its variations, we can become champions of gender-affirming care.
Sex vs gender
A person’s sex is assigned at birth based on their physiological characteristics, including their genitalia and chromosome composition. Male, female, and intersex are a few recognized sexes. Gender or gender identity describe one’s innermost perception of self as a man, a woman, a variation of both, or neither, that may not always be visible to others. When sex and gender identity align, this is known as cisgender.1
Gender identity
Gender identity is best described as a spectrum rather than a binary. Terms that fall under a gender binary include man, woman, trans man, and trans woman. A nonbinary gender identity is one outside the traditional binary of men or women. Being transgender simply means having a gender identity different than the sex assigned at birth. This includes persons whose gender identities cross the gender spectrum, such as trans men or trans women, and those who fall anywhere outside or in between genders. In this way, nonbinary persons are transgender.1
The nonbinary spectrum
The term nonbinary encompasses many gender-nonconforming identities, such as agender, bigender, demigender, genderfluid, genderqueer, intergender, or pangender. Agender people have little connection to gender. Bigender individuals identify as 2 separate genders. Demigender persons feel a partial connection to a gender. Genderfluid individuals have a gender experience that is fluid and can change over time. Genderqueer people have a gender identity that falls in between or outside the binary. Intergender people have a gender identity between genders or identify as a combination of genders. Pangender people identify with a combination of genders. Note that patients may use some of these terms interchangeably or ascribe to them different meanings.2 As the language around gender continues to evolve, psychiatrists should ask patients from a place of nonjudgmental curiosity what gender terms they use, how they define them, and what their gender means to them.
Gender expression and transitioning
Transitioning is what a transgender person does to align their gender identity and expression.3 Gender expression is the external manifestation of gender, including names, pronouns, clothing, haircuts, behaviors, voice, body characteristics, and more.1 Transgender individuals can transition using a combination of social (name, pronouns, dress), legal (changing sex on legal documents, name change), or medical (surgeries, hormone therapies, puberty blockade) means. Transitions often help ease gender dysphoria, which is the clinically significant distress a person experiences when their sex assigned at birth does not align with their gender identity.3 Note that not all transgender persons choose to change their gender expression, and not all transgender individuals experience gender dysphoria. In this case, the proper medical term is gender incongruence, which is simply when someone’s gender identity does not align with their sex assigned at birth.4
Names and pronouns
For many transgender persons, names and pronouns are an important part of their gender transition and expression.2 Most of us have gotten into the habit of assuming pronouns because of socially established gender roles. This assumes that a person’s physical appearance matches their gender identity, which is not always the case.1 To be more affirming, psychiatrists and other health care professionals should try to break the habit of assuming pronouns. Often, an easy way to learn someone’s pronouns is to introduce yourself with yours. For example, “I am Dr. Agapoff. I use they/them/theirs pronouns. It is nice to meet you.” This creates a safe and open space for the other person to share their gender identity if they choose.
Why it’s important
One does not have to be a gender specialist to deliver gender-affirming care. As psychiatrists, having a basic understanding of the differences between sex, gender identity, and gender expression can help us build rapport and support our patients who are transgender. Based on the many kinds of gender identity and expression, judging someone’s gender based solely upon physical appearance is misguided at best and harmful at worst. Even people who are cisgender have many kinds of gender expression. For this reason, psychiatrists should approach gender with the same openness and curiosity as sexual orientation or other important considerations of emotional and physical health. Gender-informed care starts with us.
Psychiatrists have a long tradition of supporting LGBTQAI+ (lesbian, gay, bisexual, transgender, queer/questioning, asexual, intersex, and others) persons. In professional and public settings, we are educators, role models, and advocates for self-expression and personal empowerment. By better educating ourselves on the topic of gender and its variations, we can become champions of gender-affirming care.
Sex vs gender
A person’s sex is assigned at birth based on their physiological characteristics, including their genitalia and chromosome composition. Male, female, and intersex are a few recognized sexes. Gender or gender identity describe one’s innermost perception of self as a man, a woman, a variation of both, or neither, that may not always be visible to others. When sex and gender identity align, this is known as cisgender.1
Gender identity
Gender identity is best described as a spectrum rather than a binary. Terms that fall under a gender binary include man, woman, trans man, and trans woman. A nonbinary gender identity is one outside the traditional binary of men or women. Being transgender simply means having a gender identity different than the sex assigned at birth. This includes persons whose gender identities cross the gender spectrum, such as trans men or trans women, and those who fall anywhere outside or in between genders. In this way, nonbinary persons are transgender.1
The nonbinary spectrum
The term nonbinary encompasses many gender-nonconforming identities, such as agender, bigender, demigender, genderfluid, genderqueer, intergender, or pangender. Agender people have little connection to gender. Bigender individuals identify as 2 separate genders. Demigender persons feel a partial connection to a gender. Genderfluid individuals have a gender experience that is fluid and can change over time. Genderqueer people have a gender identity that falls in between or outside the binary. Intergender people have a gender identity between genders or identify as a combination of genders. Pangender people identify with a combination of genders. Note that patients may use some of these terms interchangeably or ascribe to them different meanings.2 As the language around gender continues to evolve, psychiatrists should ask patients from a place of nonjudgmental curiosity what gender terms they use, how they define them, and what their gender means to them.
Gender expression and transitioning
Transitioning is what a transgender person does to align their gender identity and expression.3 Gender expression is the external manifestation of gender, including names, pronouns, clothing, haircuts, behaviors, voice, body characteristics, and more.1 Transgender individuals can transition using a combination of social (name, pronouns, dress), legal (changing sex on legal documents, name change), or medical (surgeries, hormone therapies, puberty blockade) means. Transitions often help ease gender dysphoria, which is the clinically significant distress a person experiences when their sex assigned at birth does not align with their gender identity.3 Note that not all transgender persons choose to change their gender expression, and not all transgender individuals experience gender dysphoria. In this case, the proper medical term is gender incongruence, which is simply when someone’s gender identity does not align with their sex assigned at birth.4
Names and pronouns
For many transgender persons, names and pronouns are an important part of their gender transition and expression.2 Most of us have gotten into the habit of assuming pronouns because of socially established gender roles. This assumes that a person’s physical appearance matches their gender identity, which is not always the case.1 To be more affirming, psychiatrists and other health care professionals should try to break the habit of assuming pronouns. Often, an easy way to learn someone’s pronouns is to introduce yourself with yours. For example, “I am Dr. Agapoff. I use they/them/theirs pronouns. It is nice to meet you.” This creates a safe and open space for the other person to share their gender identity if they choose.
Why it’s important
One does not have to be a gender specialist to deliver gender-affirming care. As psychiatrists, having a basic understanding of the differences between sex, gender identity, and gender expression can help us build rapport and support our patients who are transgender. Based on the many kinds of gender identity and expression, judging someone’s gender based solely upon physical appearance is misguided at best and harmful at worst. Even people who are cisgender have many kinds of gender expression. For this reason, psychiatrists should approach gender with the same openness and curiosity as sexual orientation or other important considerations of emotional and physical health. Gender-informed care starts with us.
1. LGBTQIA Resource Center Glossary. UC Davis LGBTQIA Resource Center. Accessed July 19, 2022. https://lgbtqia.ucdavis.edu/educated/glossary
2. Richards C, Bouman WP, Seal L, et al. Non-binary or genderqueer genders. Int Rev Psychiatry. 2016;28(1):95-102. doi:10.3109/09540261.2015.1106446
3. Understanding transitions. TransFamilies.Org. Accessed June 1, 2022. https://transfamilies.org/understanding-transitions/
4. Claahsen-van der Grinten H, Verhaak C, Steensma T, et al. Gender incongruence and gender dysphoria in childhood and adolescence—current insights in diagnostics, management, and follow-up. Eur J Pediatr. 2021;180(5):1349-1357.
1. LGBTQIA Resource Center Glossary. UC Davis LGBTQIA Resource Center. Accessed July 19, 2022. https://lgbtqia.ucdavis.edu/educated/glossary
2. Richards C, Bouman WP, Seal L, et al. Non-binary or genderqueer genders. Int Rev Psychiatry. 2016;28(1):95-102. doi:10.3109/09540261.2015.1106446
3. Understanding transitions. TransFamilies.Org. Accessed June 1, 2022. https://transfamilies.org/understanding-transitions/
4. Claahsen-van der Grinten H, Verhaak C, Steensma T, et al. Gender incongruence and gender dysphoria in childhood and adolescence—current insights in diagnostics, management, and follow-up. Eur J Pediatr. 2021;180(5):1349-1357.
Healthy diet, less news helped prevent anxiety, depression during COVID
VIENNA –
Results from a longitudinal Spanish survey study of more than 1,000 adults showed that being outside, relaxing, participating in physical activities, and drinking plenty of water were also beneficial. However, social contact with friends and relatives, following a routine, and pursuing hobbies had no significant impact.
“This was a little surprising,” lead author Joaquim Radua, MD, PhD, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, said in a release.
“Like many people, we had assumed that personal contact would play a bigger part in avoiding anxiety and depression during stressful times,” he added.
However, Dr. Radua said that because the study was conducted during the COVID-19 pandemic, “people who socialized may also have been anxious about getting infected.”
Consequently, “it may be that this specific behavior cannot be extrapolated to other times, when there is no pandemic,” he said.
The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
Correlational versus longitudinal studies
Dr. Radua emphasized that individuals “should socialize,” of course.
“We think it’s important that people continue to follow what works for them and that if you enjoy seeing friends or following a hobby, you continue to do so,” he said.
“Our work was centered on COVID, but we now need to see if these factors apply to other stressful circumstances. These simple behaviors may prevent anxiety and depression, and prevention is better than cure,” he added.
The researchers note that, in “times of uncertainty” such as the COVID-19 pandemic, many individuals experience increases in both anxiety and depressive symptoms.
Although a range of behaviors are recommended to help people cope, the investigators add that some of the recommendations are based on correlational studies.
Indeed, the researchers previously identified a correlation between following a healthy/balanced diet, among other measures, and lower anxiety and depressive symptoms during the pandemic.
However, it is unclear from cross-sectional studies whether the behavior alters the symptoms, in which case the behavior could be considered “helpful,” or conversely whether the symptoms alter an individual’s behavior, in which case the behaviors “may be useless,” the investigators note.
The investigative team therefore set out to provide more robust evidence for making recommendations and conducted a prospective longitudinal study.
They recruited 1,049 adults online via social networks, matching them to the regional, age and sex, and urbanicity distribution of the overall Spanish population.
Every 2 weeks for 12 months, the researchers administered the General Anxiety Disorder (GAD)-7, the Patient Health Questionnaire (PHQ)-9, and a two-item ecological momentary assessment to minimize recall bias, among other measures. They also asked about 10 self-report coping behaviors.
Significant coping behaviors
The study was completed by 942 individuals, indicating a retention of 90%.
Among both completers and non-completers there was an over-representation of individuals aged 18-34 years and women, compared with the general population, and fewer participants aged at least 65 years.
Pre-recruitment, the mean baseline GAD-7 score among completers was 7.4, falling to around 5.5 at the time of the first questionnaire. Scores on the PHQ-9 were 7.6 and 5.6, respectively.
Performing population-weighted autoregressive moving average models to analyze the relationship between the current frequency of the coping behaviors and future changes in anxiety and depressive symptoms, the investigators found that the greatest effect was from following a healthy, balanced diet, with an impact size of 0.95.
This was followed by avoiding too much stressful news (impact size, 0.91), staying outdoors or looking outside (0.40), doing relaxing activities (0.33), participating in physical exercise (0.32), and drinking water to hydrate (0.25).
Overall, these coping behaviors were associated with a significant reduction in anxiety and depressive symptoms (all, P < .001).
On the other hand, there was no impact on future symptoms from socializing with friends and relatives, whether or not they lived in the same household. There was also no effect from following a routine, pursuing hobbies, or performing home tasks.
The researchers note that similar results were obtained when excluding participants with hazardous alcohol consumption, defined as a score on the Alcohol Use Disorders Identification Test of 8 or higher.
However, they point out that despite its prospective design and large cohort, the study was not interventional. Therefore, they “cannot rule out the possibility that decreasing the frequency of a behavior is an early sign of some mechanism that later leads to increased anxiety and depression symptoms.”
Nevertheless, they believe that possibility “seems unlikely.”
Reflective of a unique time?
Commenting on the findings, Catherine Harmer, PhD, director of the Psychopharmacology and Emotional Research Lab, department of psychiatry, University of Oxford (England), said in the release this was an “interesting study” that “provides some important insights as to which behaviors may protect our mental health during times of significant stress.”
She said the finding that social contact was not beneficial was “surprising” but may reflect the fact that, during the pandemic, it was “stressful even to have those social contacts, even if we managed to meet a friend outside.”
The results of the study may therefore be “reflective of the unique experience” of the COVID-19 pandemic, said Dr. Harmer, who was not involved with the research.
“I wouldn’t think that reading too much news would generally be something that has a negative impact on depression and anxiety, but I think it was very much at the time,” she said.
With the pandemic overwhelming one country after another, “the more you read about it, the more frightening it was,” she added, noting that it is “easy to forget how frightened we were at the beginning.”
Dr. Harmer noted that “it would be interesting” if the study was repeated and the same factors came out – or if they were unique to that time.
This would be “useful to know, as these times may come again. And the more information we have to cope with a pandemic, the better,” she concluded.
The research was supported by the AXA Research Fund via an AXA Award granted to Dr. Radua from the call for projects “mitigating risk in the wake of the COVID-19 pandemic.” The investigators and Dr. Harmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VIENNA –
Results from a longitudinal Spanish survey study of more than 1,000 adults showed that being outside, relaxing, participating in physical activities, and drinking plenty of water were also beneficial. However, social contact with friends and relatives, following a routine, and pursuing hobbies had no significant impact.
“This was a little surprising,” lead author Joaquim Radua, MD, PhD, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, said in a release.
“Like many people, we had assumed that personal contact would play a bigger part in avoiding anxiety and depression during stressful times,” he added.
However, Dr. Radua said that because the study was conducted during the COVID-19 pandemic, “people who socialized may also have been anxious about getting infected.”
Consequently, “it may be that this specific behavior cannot be extrapolated to other times, when there is no pandemic,” he said.
The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
Correlational versus longitudinal studies
Dr. Radua emphasized that individuals “should socialize,” of course.
“We think it’s important that people continue to follow what works for them and that if you enjoy seeing friends or following a hobby, you continue to do so,” he said.
“Our work was centered on COVID, but we now need to see if these factors apply to other stressful circumstances. These simple behaviors may prevent anxiety and depression, and prevention is better than cure,” he added.
The researchers note that, in “times of uncertainty” such as the COVID-19 pandemic, many individuals experience increases in both anxiety and depressive symptoms.
Although a range of behaviors are recommended to help people cope, the investigators add that some of the recommendations are based on correlational studies.
Indeed, the researchers previously identified a correlation between following a healthy/balanced diet, among other measures, and lower anxiety and depressive symptoms during the pandemic.
However, it is unclear from cross-sectional studies whether the behavior alters the symptoms, in which case the behavior could be considered “helpful,” or conversely whether the symptoms alter an individual’s behavior, in which case the behaviors “may be useless,” the investigators note.
The investigative team therefore set out to provide more robust evidence for making recommendations and conducted a prospective longitudinal study.
They recruited 1,049 adults online via social networks, matching them to the regional, age and sex, and urbanicity distribution of the overall Spanish population.
Every 2 weeks for 12 months, the researchers administered the General Anxiety Disorder (GAD)-7, the Patient Health Questionnaire (PHQ)-9, and a two-item ecological momentary assessment to minimize recall bias, among other measures. They also asked about 10 self-report coping behaviors.
Significant coping behaviors
The study was completed by 942 individuals, indicating a retention of 90%.
Among both completers and non-completers there was an over-representation of individuals aged 18-34 years and women, compared with the general population, and fewer participants aged at least 65 years.
Pre-recruitment, the mean baseline GAD-7 score among completers was 7.4, falling to around 5.5 at the time of the first questionnaire. Scores on the PHQ-9 were 7.6 and 5.6, respectively.
Performing population-weighted autoregressive moving average models to analyze the relationship between the current frequency of the coping behaviors and future changes in anxiety and depressive symptoms, the investigators found that the greatest effect was from following a healthy, balanced diet, with an impact size of 0.95.
This was followed by avoiding too much stressful news (impact size, 0.91), staying outdoors or looking outside (0.40), doing relaxing activities (0.33), participating in physical exercise (0.32), and drinking water to hydrate (0.25).
Overall, these coping behaviors were associated with a significant reduction in anxiety and depressive symptoms (all, P < .001).
On the other hand, there was no impact on future symptoms from socializing with friends and relatives, whether or not they lived in the same household. There was also no effect from following a routine, pursuing hobbies, or performing home tasks.
The researchers note that similar results were obtained when excluding participants with hazardous alcohol consumption, defined as a score on the Alcohol Use Disorders Identification Test of 8 or higher.
However, they point out that despite its prospective design and large cohort, the study was not interventional. Therefore, they “cannot rule out the possibility that decreasing the frequency of a behavior is an early sign of some mechanism that later leads to increased anxiety and depression symptoms.”
Nevertheless, they believe that possibility “seems unlikely.”
Reflective of a unique time?
Commenting on the findings, Catherine Harmer, PhD, director of the Psychopharmacology and Emotional Research Lab, department of psychiatry, University of Oxford (England), said in the release this was an “interesting study” that “provides some important insights as to which behaviors may protect our mental health during times of significant stress.”
She said the finding that social contact was not beneficial was “surprising” but may reflect the fact that, during the pandemic, it was “stressful even to have those social contacts, even if we managed to meet a friend outside.”
The results of the study may therefore be “reflective of the unique experience” of the COVID-19 pandemic, said Dr. Harmer, who was not involved with the research.
“I wouldn’t think that reading too much news would generally be something that has a negative impact on depression and anxiety, but I think it was very much at the time,” she said.
With the pandemic overwhelming one country after another, “the more you read about it, the more frightening it was,” she added, noting that it is “easy to forget how frightened we were at the beginning.”
Dr. Harmer noted that “it would be interesting” if the study was repeated and the same factors came out – or if they were unique to that time.
This would be “useful to know, as these times may come again. And the more information we have to cope with a pandemic, the better,” she concluded.
The research was supported by the AXA Research Fund via an AXA Award granted to Dr. Radua from the call for projects “mitigating risk in the wake of the COVID-19 pandemic.” The investigators and Dr. Harmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VIENNA –
Results from a longitudinal Spanish survey study of more than 1,000 adults showed that being outside, relaxing, participating in physical activities, and drinking plenty of water were also beneficial. However, social contact with friends and relatives, following a routine, and pursuing hobbies had no significant impact.
“This was a little surprising,” lead author Joaquim Radua, MD, PhD, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, said in a release.
“Like many people, we had assumed that personal contact would play a bigger part in avoiding anxiety and depression during stressful times,” he added.
However, Dr. Radua said that because the study was conducted during the COVID-19 pandemic, “people who socialized may also have been anxious about getting infected.”
Consequently, “it may be that this specific behavior cannot be extrapolated to other times, when there is no pandemic,” he said.
The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
Correlational versus longitudinal studies
Dr. Radua emphasized that individuals “should socialize,” of course.
“We think it’s important that people continue to follow what works for them and that if you enjoy seeing friends or following a hobby, you continue to do so,” he said.
“Our work was centered on COVID, but we now need to see if these factors apply to other stressful circumstances. These simple behaviors may prevent anxiety and depression, and prevention is better than cure,” he added.
The researchers note that, in “times of uncertainty” such as the COVID-19 pandemic, many individuals experience increases in both anxiety and depressive symptoms.
Although a range of behaviors are recommended to help people cope, the investigators add that some of the recommendations are based on correlational studies.
Indeed, the researchers previously identified a correlation between following a healthy/balanced diet, among other measures, and lower anxiety and depressive symptoms during the pandemic.
However, it is unclear from cross-sectional studies whether the behavior alters the symptoms, in which case the behavior could be considered “helpful,” or conversely whether the symptoms alter an individual’s behavior, in which case the behaviors “may be useless,” the investigators note.
The investigative team therefore set out to provide more robust evidence for making recommendations and conducted a prospective longitudinal study.
They recruited 1,049 adults online via social networks, matching them to the regional, age and sex, and urbanicity distribution of the overall Spanish population.
Every 2 weeks for 12 months, the researchers administered the General Anxiety Disorder (GAD)-7, the Patient Health Questionnaire (PHQ)-9, and a two-item ecological momentary assessment to minimize recall bias, among other measures. They also asked about 10 self-report coping behaviors.
Significant coping behaviors
The study was completed by 942 individuals, indicating a retention of 90%.
Among both completers and non-completers there was an over-representation of individuals aged 18-34 years and women, compared with the general population, and fewer participants aged at least 65 years.
Pre-recruitment, the mean baseline GAD-7 score among completers was 7.4, falling to around 5.5 at the time of the first questionnaire. Scores on the PHQ-9 were 7.6 and 5.6, respectively.
Performing population-weighted autoregressive moving average models to analyze the relationship between the current frequency of the coping behaviors and future changes in anxiety and depressive symptoms, the investigators found that the greatest effect was from following a healthy, balanced diet, with an impact size of 0.95.
This was followed by avoiding too much stressful news (impact size, 0.91), staying outdoors or looking outside (0.40), doing relaxing activities (0.33), participating in physical exercise (0.32), and drinking water to hydrate (0.25).
Overall, these coping behaviors were associated with a significant reduction in anxiety and depressive symptoms (all, P < .001).
On the other hand, there was no impact on future symptoms from socializing with friends and relatives, whether or not they lived in the same household. There was also no effect from following a routine, pursuing hobbies, or performing home tasks.
The researchers note that similar results were obtained when excluding participants with hazardous alcohol consumption, defined as a score on the Alcohol Use Disorders Identification Test of 8 or higher.
However, they point out that despite its prospective design and large cohort, the study was not interventional. Therefore, they “cannot rule out the possibility that decreasing the frequency of a behavior is an early sign of some mechanism that later leads to increased anxiety and depression symptoms.”
Nevertheless, they believe that possibility “seems unlikely.”
Reflective of a unique time?
Commenting on the findings, Catherine Harmer, PhD, director of the Psychopharmacology and Emotional Research Lab, department of psychiatry, University of Oxford (England), said in the release this was an “interesting study” that “provides some important insights as to which behaviors may protect our mental health during times of significant stress.”
She said the finding that social contact was not beneficial was “surprising” but may reflect the fact that, during the pandemic, it was “stressful even to have those social contacts, even if we managed to meet a friend outside.”
The results of the study may therefore be “reflective of the unique experience” of the COVID-19 pandemic, said Dr. Harmer, who was not involved with the research.
“I wouldn’t think that reading too much news would generally be something that has a negative impact on depression and anxiety, but I think it was very much at the time,” she said.
With the pandemic overwhelming one country after another, “the more you read about it, the more frightening it was,” she added, noting that it is “easy to forget how frightened we were at the beginning.”
Dr. Harmer noted that “it would be interesting” if the study was repeated and the same factors came out – or if they were unique to that time.
This would be “useful to know, as these times may come again. And the more information we have to cope with a pandemic, the better,” she concluded.
The research was supported by the AXA Research Fund via an AXA Award granted to Dr. Radua from the call for projects “mitigating risk in the wake of the COVID-19 pandemic.” The investigators and Dr. Harmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ECNP 2022
Myocarditis after COVID vax rare and mild in teens
New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.
The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.
Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.
The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).
The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.
In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.
Eight cases occurred after the second vaccine dose. All nine cases were mild.
Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.
Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.
Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.
Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.
At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.
This research had no specific funding. Five authors have received research grants from Pfizer.
A version of this article first appeared on Medscape.com.
New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.
The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.
Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.
The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).
The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.
In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.
Eight cases occurred after the second vaccine dose. All nine cases were mild.
Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.
Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.
Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.
Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.
At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.
This research had no specific funding. Five authors have received research grants from Pfizer.
A version of this article first appeared on Medscape.com.
New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.
The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.
Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.
The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).
The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.
In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.
Eight cases occurred after the second vaccine dose. All nine cases were mild.
Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.
Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.
Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.
Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.
At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.
This research had no specific funding. Five authors have received research grants from Pfizer.
A version of this article first appeared on Medscape.com.
Immediate skin-to-skin contact after cesarean section improves outcomes for parent, newborn
Birth parents are typically separated from their newborns following a cesarean section. However, a recent study published in the journal Nursing Open suggests immediate skin-to-skin contact may accelerate uterine contractions, reduce maternal blood loss, reduce newborn crying, improve patient satisfaction and comfort, and increase the rate of breastfeeding.
“[O]ur study contributes to scientific knowledge with key information to reduce maternal morbidity and mortality rates in mothers who have undergone scheduled cesarean sections,” José Miguel Pérez-Jiménez, MD, of the faculty of nursing, physiotherapy, and podiatry at Hospital Universitario Virgen Macarena, University of Sevilla, Spain, and colleagues wrote in their study. It promotes greater stability in the mothers by reducing the risk of postpartum hemorrhage, making it better to not separate mother and child in the first hours after this surgery, he said.
Dr. Pérez-Jiménez and colleagues evaluated 83 women who underwent a scheduled cesarean section in an unblinded, randomized controlled trial. The women were randomized to receive skin-to-skin contact in the operating room that continued in the postpartum unit, or the normal protocol after cesarean section that consisted of having the mother transferred to the postanesthesia recovery room while the newborn was sent to a maternity room with a parent or companion. Researchers assessed variables such as plasma hemoglobin, uterine contractions, breastfeeding, and postoperative pain, as well as subjective measures such as maternal satisfaction, comfort, previous cesarean section experience, and newborn crying.
Women who received usual care following cesarean section were more likely to have uterine contractions at the umbilical level compared with the skin-to-skin contact group (70% vs. 3%; P ≤ .0001), while the skin-to-skin group was more likely to have uterine contractions at the infraumbilical level (92.5% vs. 22.5%; P ≤ .0001). There was a statistically significant decrease in predischarge hemoglobin in the control group compared with the skin-to-skin group (10.522 vs. 11.075 g/dL; P ≤ .017); the level of hemoglobin reduction favored the skin-to-skin group (1.01 vs. 2.265 g/dL; P ≤ .0001). Women in the skin-to-skin group were more likely to report mild pain on a 10-point visual analog scale (VAS) after being transferred to the recovery room (1.48 vs. 6.23 points; P ≤ .0001) and being transferred to a maternity room or room in the postpartum unit (0.60 vs. 5.23 points; P ≤ .0001). Breastfeeding at birth was significantly higher among patients with immediate skin-to-skin contact compared with the control group (92.5% vs. 32.5%; P ≤ .0001), and continued at 1 month after birth (92.5% vs. 12.5%; P ≤ .0001). Newborns of mothers in the skin-to-skin group were significantly less likely to cry compared with newborns in the control group (90% vs. 55%; P ≤ .001).
When asked to rate their satisfaction on a 10-point Likert scale, women in the skin-to-skin contact group rated their experience significantly higher than did the control group (9.98 vs. 6.5; P ≤ .0001), and all women who had previously had a cesarean section in the skin-to-skin group (30%) rated their experience at 10 points compared with their previous cesarean section without skin-to-skin contact.
Implementing skin-to-skin contact after cesarean section
Betsy M. Collins, MD, MPH, assistant professor of obstetrics and gynecology at Emory University, Atlanta, said in an interview that while some of the findings were largely unsurprising and “confirmed a lot of the things that we already know about skin-to-skin [contact],” one major finding was the “stark difference” in the percentage of new birth parents who started breastfeeding after skin-to-skin contact and were still breastfeeding at 1 month postpartum compared with birth parents in the control group. She was not involved with the study and noted that the results complement recommendations from the World Health Organization on starting breastfeeding within the first hour after birth and continuing breastfeeding through the first 6 months of life.
“That was likely one of the greatest take-home points from the study ... that early skin-to-skin really promoted initiation of breastfeeding,” Dr. Collins said.
Two reasons why skin-to-skin contact after cesarean section isn’t regularly provided is that it can be difficult for personnel and safety reasons to have an extra nurse to continue monitoring the health of the newborn in the operating room, and there is a lack of culture supporting of skin-to-skin contact in the OR, Dr. Collins explained.
“Just like anything else, if it’s built into your standard operating procedure, then you have everything set up in place to do that initial assessment of the infant and then get the baby skin-to-skin as quickly as possible,” she said. If it’s your standard operating procedure to not provide skin-to-skin contact, she said, then there is a little bit more inertia to overcome to start providing it as a standard procedure.
At her center, Dr. Collins said skin-to-skin contact is initiated as soon as possible after birth, even in the operating room. The steps to implementing that policy involved getting the anesthesiology department on board with supporting the policy in the OR and training the circulating nursing staff to ensure a that nurse is available to monitor the newborn.
“I think the most important thing to know is that it’s absolutely doable and that you just have to have a champion just like any other quality initiative,” she said. One of the best ways to do that is to have the patients themselves request it, she noted, compared with its being requested by a physician or nurse.
“I think some patients are disappointed when they have to undergo cesarean delivery or feel like they’re missing out if they can’t have a vaginal delivery,” Dr. Collins said. Immediate skin-to-skin contact is “very good for not only physiology, as we read about in this paper – all the things they said about the benefits of skin-to-skin [contact] are true – but it’s really good for mental health. That bonding begins right away.”
As a birth parent, being separated from your newborn for several hours after a cesarean section, on the other hand, can be “pretty devastating,” Dr. Collins said.
“I think this is something that, once it becomes a standard of care, it will be expected that most hospitals should be doing this,” she said.
The authors and Dr. Collins report no relevant conflicts of interest.
Birth parents are typically separated from their newborns following a cesarean section. However, a recent study published in the journal Nursing Open suggests immediate skin-to-skin contact may accelerate uterine contractions, reduce maternal blood loss, reduce newborn crying, improve patient satisfaction and comfort, and increase the rate of breastfeeding.
“[O]ur study contributes to scientific knowledge with key information to reduce maternal morbidity and mortality rates in mothers who have undergone scheduled cesarean sections,” José Miguel Pérez-Jiménez, MD, of the faculty of nursing, physiotherapy, and podiatry at Hospital Universitario Virgen Macarena, University of Sevilla, Spain, and colleagues wrote in their study. It promotes greater stability in the mothers by reducing the risk of postpartum hemorrhage, making it better to not separate mother and child in the first hours after this surgery, he said.
Dr. Pérez-Jiménez and colleagues evaluated 83 women who underwent a scheduled cesarean section in an unblinded, randomized controlled trial. The women were randomized to receive skin-to-skin contact in the operating room that continued in the postpartum unit, or the normal protocol after cesarean section that consisted of having the mother transferred to the postanesthesia recovery room while the newborn was sent to a maternity room with a parent or companion. Researchers assessed variables such as plasma hemoglobin, uterine contractions, breastfeeding, and postoperative pain, as well as subjective measures such as maternal satisfaction, comfort, previous cesarean section experience, and newborn crying.
Women who received usual care following cesarean section were more likely to have uterine contractions at the umbilical level compared with the skin-to-skin contact group (70% vs. 3%; P ≤ .0001), while the skin-to-skin group was more likely to have uterine contractions at the infraumbilical level (92.5% vs. 22.5%; P ≤ .0001). There was a statistically significant decrease in predischarge hemoglobin in the control group compared with the skin-to-skin group (10.522 vs. 11.075 g/dL; P ≤ .017); the level of hemoglobin reduction favored the skin-to-skin group (1.01 vs. 2.265 g/dL; P ≤ .0001). Women in the skin-to-skin group were more likely to report mild pain on a 10-point visual analog scale (VAS) after being transferred to the recovery room (1.48 vs. 6.23 points; P ≤ .0001) and being transferred to a maternity room or room in the postpartum unit (0.60 vs. 5.23 points; P ≤ .0001). Breastfeeding at birth was significantly higher among patients with immediate skin-to-skin contact compared with the control group (92.5% vs. 32.5%; P ≤ .0001), and continued at 1 month after birth (92.5% vs. 12.5%; P ≤ .0001). Newborns of mothers in the skin-to-skin group were significantly less likely to cry compared with newborns in the control group (90% vs. 55%; P ≤ .001).
When asked to rate their satisfaction on a 10-point Likert scale, women in the skin-to-skin contact group rated their experience significantly higher than did the control group (9.98 vs. 6.5; P ≤ .0001), and all women who had previously had a cesarean section in the skin-to-skin group (30%) rated their experience at 10 points compared with their previous cesarean section without skin-to-skin contact.
Implementing skin-to-skin contact after cesarean section
Betsy M. Collins, MD, MPH, assistant professor of obstetrics and gynecology at Emory University, Atlanta, said in an interview that while some of the findings were largely unsurprising and “confirmed a lot of the things that we already know about skin-to-skin [contact],” one major finding was the “stark difference” in the percentage of new birth parents who started breastfeeding after skin-to-skin contact and were still breastfeeding at 1 month postpartum compared with birth parents in the control group. She was not involved with the study and noted that the results complement recommendations from the World Health Organization on starting breastfeeding within the first hour after birth and continuing breastfeeding through the first 6 months of life.
“That was likely one of the greatest take-home points from the study ... that early skin-to-skin really promoted initiation of breastfeeding,” Dr. Collins said.
Two reasons why skin-to-skin contact after cesarean section isn’t regularly provided is that it can be difficult for personnel and safety reasons to have an extra nurse to continue monitoring the health of the newborn in the operating room, and there is a lack of culture supporting of skin-to-skin contact in the OR, Dr. Collins explained.
“Just like anything else, if it’s built into your standard operating procedure, then you have everything set up in place to do that initial assessment of the infant and then get the baby skin-to-skin as quickly as possible,” she said. If it’s your standard operating procedure to not provide skin-to-skin contact, she said, then there is a little bit more inertia to overcome to start providing it as a standard procedure.
At her center, Dr. Collins said skin-to-skin contact is initiated as soon as possible after birth, even in the operating room. The steps to implementing that policy involved getting the anesthesiology department on board with supporting the policy in the OR and training the circulating nursing staff to ensure a that nurse is available to monitor the newborn.
“I think the most important thing to know is that it’s absolutely doable and that you just have to have a champion just like any other quality initiative,” she said. One of the best ways to do that is to have the patients themselves request it, she noted, compared with its being requested by a physician or nurse.
“I think some patients are disappointed when they have to undergo cesarean delivery or feel like they’re missing out if they can’t have a vaginal delivery,” Dr. Collins said. Immediate skin-to-skin contact is “very good for not only physiology, as we read about in this paper – all the things they said about the benefits of skin-to-skin [contact] are true – but it’s really good for mental health. That bonding begins right away.”
As a birth parent, being separated from your newborn for several hours after a cesarean section, on the other hand, can be “pretty devastating,” Dr. Collins said.
“I think this is something that, once it becomes a standard of care, it will be expected that most hospitals should be doing this,” she said.
The authors and Dr. Collins report no relevant conflicts of interest.
Birth parents are typically separated from their newborns following a cesarean section. However, a recent study published in the journal Nursing Open suggests immediate skin-to-skin contact may accelerate uterine contractions, reduce maternal blood loss, reduce newborn crying, improve patient satisfaction and comfort, and increase the rate of breastfeeding.
“[O]ur study contributes to scientific knowledge with key information to reduce maternal morbidity and mortality rates in mothers who have undergone scheduled cesarean sections,” José Miguel Pérez-Jiménez, MD, of the faculty of nursing, physiotherapy, and podiatry at Hospital Universitario Virgen Macarena, University of Sevilla, Spain, and colleagues wrote in their study. It promotes greater stability in the mothers by reducing the risk of postpartum hemorrhage, making it better to not separate mother and child in the first hours after this surgery, he said.
Dr. Pérez-Jiménez and colleagues evaluated 83 women who underwent a scheduled cesarean section in an unblinded, randomized controlled trial. The women were randomized to receive skin-to-skin contact in the operating room that continued in the postpartum unit, or the normal protocol after cesarean section that consisted of having the mother transferred to the postanesthesia recovery room while the newborn was sent to a maternity room with a parent or companion. Researchers assessed variables such as plasma hemoglobin, uterine contractions, breastfeeding, and postoperative pain, as well as subjective measures such as maternal satisfaction, comfort, previous cesarean section experience, and newborn crying.
Women who received usual care following cesarean section were more likely to have uterine contractions at the umbilical level compared with the skin-to-skin contact group (70% vs. 3%; P ≤ .0001), while the skin-to-skin group was more likely to have uterine contractions at the infraumbilical level (92.5% vs. 22.5%; P ≤ .0001). There was a statistically significant decrease in predischarge hemoglobin in the control group compared with the skin-to-skin group (10.522 vs. 11.075 g/dL; P ≤ .017); the level of hemoglobin reduction favored the skin-to-skin group (1.01 vs. 2.265 g/dL; P ≤ .0001). Women in the skin-to-skin group were more likely to report mild pain on a 10-point visual analog scale (VAS) after being transferred to the recovery room (1.48 vs. 6.23 points; P ≤ .0001) and being transferred to a maternity room or room in the postpartum unit (0.60 vs. 5.23 points; P ≤ .0001). Breastfeeding at birth was significantly higher among patients with immediate skin-to-skin contact compared with the control group (92.5% vs. 32.5%; P ≤ .0001), and continued at 1 month after birth (92.5% vs. 12.5%; P ≤ .0001). Newborns of mothers in the skin-to-skin group were significantly less likely to cry compared with newborns in the control group (90% vs. 55%; P ≤ .001).
When asked to rate their satisfaction on a 10-point Likert scale, women in the skin-to-skin contact group rated their experience significantly higher than did the control group (9.98 vs. 6.5; P ≤ .0001), and all women who had previously had a cesarean section in the skin-to-skin group (30%) rated their experience at 10 points compared with their previous cesarean section without skin-to-skin contact.
Implementing skin-to-skin contact after cesarean section
Betsy M. Collins, MD, MPH, assistant professor of obstetrics and gynecology at Emory University, Atlanta, said in an interview that while some of the findings were largely unsurprising and “confirmed a lot of the things that we already know about skin-to-skin [contact],” one major finding was the “stark difference” in the percentage of new birth parents who started breastfeeding after skin-to-skin contact and were still breastfeeding at 1 month postpartum compared with birth parents in the control group. She was not involved with the study and noted that the results complement recommendations from the World Health Organization on starting breastfeeding within the first hour after birth and continuing breastfeeding through the first 6 months of life.
“That was likely one of the greatest take-home points from the study ... that early skin-to-skin really promoted initiation of breastfeeding,” Dr. Collins said.
Two reasons why skin-to-skin contact after cesarean section isn’t regularly provided is that it can be difficult for personnel and safety reasons to have an extra nurse to continue monitoring the health of the newborn in the operating room, and there is a lack of culture supporting of skin-to-skin contact in the OR, Dr. Collins explained.
“Just like anything else, if it’s built into your standard operating procedure, then you have everything set up in place to do that initial assessment of the infant and then get the baby skin-to-skin as quickly as possible,” she said. If it’s your standard operating procedure to not provide skin-to-skin contact, she said, then there is a little bit more inertia to overcome to start providing it as a standard procedure.
At her center, Dr. Collins said skin-to-skin contact is initiated as soon as possible after birth, even in the operating room. The steps to implementing that policy involved getting the anesthesiology department on board with supporting the policy in the OR and training the circulating nursing staff to ensure a that nurse is available to monitor the newborn.
“I think the most important thing to know is that it’s absolutely doable and that you just have to have a champion just like any other quality initiative,” she said. One of the best ways to do that is to have the patients themselves request it, she noted, compared with its being requested by a physician or nurse.
“I think some patients are disappointed when they have to undergo cesarean delivery or feel like they’re missing out if they can’t have a vaginal delivery,” Dr. Collins said. Immediate skin-to-skin contact is “very good for not only physiology, as we read about in this paper – all the things they said about the benefits of skin-to-skin [contact] are true – but it’s really good for mental health. That bonding begins right away.”
As a birth parent, being separated from your newborn for several hours after a cesarean section, on the other hand, can be “pretty devastating,” Dr. Collins said.
“I think this is something that, once it becomes a standard of care, it will be expected that most hospitals should be doing this,” she said.
The authors and Dr. Collins report no relevant conflicts of interest.
FROM NURSING OPEN
Goodbye ‘diabetes insipidus’, hello ‘AVP-D’ and ‘AVP-R’
An international group representing leading endocrinology associations has recommended that the name “diabetes insipidus” – which in some cases has led to harm – be changed to eliminate confusion with “diabetes mellitus” and to reflect the former condition’s pathophysiology.
The new proposed names are arginine vasopressin deficiency (AVP-D) for central (also called “cranial”) etiologies and arginine vasopressin resistance (AVP-R) for nephrogenic (kidney) etiologies.
“What we’re proposing is to rename the disease according to the pathophysiology that defines it,” statement co-author Joseph G. Verbalis, MD, professor of medicine and chief of endocrinology and metabolism at Georgetown University Medical Center, Washington, told this news organization.
The statement advises that henceforth the new names be used in manuscripts and the medical literature while keeping the old names in parentheses during a transition period, as in “AVP-deficiency (cranial diabetes insipidus)” and “AVP-resistance (nephrogenic diabetes insipidus).”
The condition formerly known as diabetes insipidus is relatively rare, occurring in about 1 person per 10-15,000 population. It is caused by either deficient production or resistance in the kidney to the hormone AVP, normally produced by the hypothalamus and stored in the pituitary gland. AVP, also called antidiuretic hormone, regulates the body’s water level and urine production by the kidney.
Both etiologies lead to extreme thirst and excessive production of urine. Common causes of the deficiency include head trauma or brain tumor, while resistance in the kidney is often congenital. It is currently treated with a synthetic form of AVP called desmopressin and fluid replacement.
What’s in a name?
The proposal to change the name by the Working Group for Renaming Diabetes Insipidus is endorsed by The Endocrine Society, European Society of Endocrinology, Pituitary Society, Society for Endocrinology, European Society for Paediatric Endocrinology, Endocrine Society of Australia, Brazilian Endocrine Society, and Japanese Endocrine Society and is under review by several other societies. It was published as a position statement in several of those society’s journals, with more to follow.
Historically, the word “diabetes,” a Greek word meaning “siphon,” was used in the 1st and 2nd century BC to describe excess flow of urine. The Latin word “mellitus” or “honey” was added in the late 17th century to describe the sweetness of the urine in the dysglycemic condition.
A century later, the Latin word “insipidus,” meaning insipid or tasteless, was coined to distinguish between the two types of polyuria, the position statement details.
In the late 19th to early 20th century, the vasopressor and antidiuretic actions of posterior pituitary extracts were discovered and used to treat people with both the central and nephrogenic etiologies, which were also recognized around that time, yet the name “diabetes insipidus” has persisted.
“From a historical perspective, the name is perfectly appropriate. At the time it was identified, and it was realized that it was different from diabetes mellitus, that was a perfectly appropriate terminology based on what was known in the late 19th century – but not now. It has persisted through the years simply because in medicine there’s a lot of inertia for change ... It’s just always been called that. If there’s not a compelling reason to change a name, generally there’s no move to change it,” Dr. Verbalis observed.
‘Dramatic cases of patient mismanagement’ due to name confusion
Unfortunately, the urgency for the change arose from tragedy. In 2009, a 22-year-old man was admitted to the orthopedics department of a London teaching hospital for a hip replacement. Despite his known panhypopituitarism and diabetes insipidus, the nurses continually checked his blood glucose but didn’t give him desmopressin or sufficient fluids. Laboratory testing showed normal glucose, but his serum sodium was 149 mmol/L. The morning after his operation, he had a fatal cardiac arrest with a serum sodium of 169 mmol/L.
“The nurses thought he had diabetes mellitus ... So that was death due to failure to recognize that diabetes insipidus is not diabetes mellitus,” Dr. Verbalis said. “If he had been admitted to endocrinology, this wouldn’t have happened. But he was admitted to orthopedics. Non-endocrinologists are not so aware of diabetes insipidus, because it is a rare disease.”
In 2016, National Health Service England issued a patient safety alert about the “risk of severe harm or death when desmopressin is omitted or delayed in patients with cranial diabetes insipidus,” citing at least four incidents within the prior 7 years where omission of desmopressin had resulted in severe dehydration and death, with another 76 cases of omission or delay that were acted on before the patients became critically ill.
Further impetus for the name change came from the results of an anonymous web-based survey of 1,034 adult and pediatric patients with central diabetes insipidus conducted between August 2021 and February 2022. Overall, 80% reported encountering situations in which their condition had been confused with diabetes mellitus by health care professionals, and 85% supported renaming the disease.
There was some divergence in opinion as to what the new name(s) should be, but clear agreement that the term “diabetes” should not be part of it.
“We’ve only become recently aware that there are dramatic cases of patient mismanagement due to the confusion caused by the word ‘diabetes.’ We think patients should have a voice. If a legitimate patient survey says over 80% think this name should be changed, then I think we as endocrinologists need to pay attention to that,” Dr. Verbalis said.
But while endocrinologists are the ones who see these patients the most often, Dr. Verbalis said a main aim of the position statement “is really to change the mindset of non-endocrinologist doctors and nurses and other health care professionals that this is not diabetes mellitus. It’s a totally different disease. And if we give it a totally different name, then I think they will better recognize that.”
As to how long Dr. Verbalis thinks it will take for the new names to catch on, he pointed out that it’s taken about a decade for the rheumatology field to fully adopt the name “granulomatosis with polyangiitis” as a replacement for “Wegener’s granulomatosis” after the eponymous physician’s Nazi ties were revealed.
“So we’re not anticipating that this is going to change terminology tomorrow. It’s a long process. We just wanted to get the process started,” he said.
Dr. Verbalis has reported consulting for Otsuka.
A version of this article first appeared on Medscape.com.
An international group representing leading endocrinology associations has recommended that the name “diabetes insipidus” – which in some cases has led to harm – be changed to eliminate confusion with “diabetes mellitus” and to reflect the former condition’s pathophysiology.
The new proposed names are arginine vasopressin deficiency (AVP-D) for central (also called “cranial”) etiologies and arginine vasopressin resistance (AVP-R) for nephrogenic (kidney) etiologies.
“What we’re proposing is to rename the disease according to the pathophysiology that defines it,” statement co-author Joseph G. Verbalis, MD, professor of medicine and chief of endocrinology and metabolism at Georgetown University Medical Center, Washington, told this news organization.
The statement advises that henceforth the new names be used in manuscripts and the medical literature while keeping the old names in parentheses during a transition period, as in “AVP-deficiency (cranial diabetes insipidus)” and “AVP-resistance (nephrogenic diabetes insipidus).”
The condition formerly known as diabetes insipidus is relatively rare, occurring in about 1 person per 10-15,000 population. It is caused by either deficient production or resistance in the kidney to the hormone AVP, normally produced by the hypothalamus and stored in the pituitary gland. AVP, also called antidiuretic hormone, regulates the body’s water level and urine production by the kidney.
Both etiologies lead to extreme thirst and excessive production of urine. Common causes of the deficiency include head trauma or brain tumor, while resistance in the kidney is often congenital. It is currently treated with a synthetic form of AVP called desmopressin and fluid replacement.
What’s in a name?
The proposal to change the name by the Working Group for Renaming Diabetes Insipidus is endorsed by The Endocrine Society, European Society of Endocrinology, Pituitary Society, Society for Endocrinology, European Society for Paediatric Endocrinology, Endocrine Society of Australia, Brazilian Endocrine Society, and Japanese Endocrine Society and is under review by several other societies. It was published as a position statement in several of those society’s journals, with more to follow.
Historically, the word “diabetes,” a Greek word meaning “siphon,” was used in the 1st and 2nd century BC to describe excess flow of urine. The Latin word “mellitus” or “honey” was added in the late 17th century to describe the sweetness of the urine in the dysglycemic condition.
A century later, the Latin word “insipidus,” meaning insipid or tasteless, was coined to distinguish between the two types of polyuria, the position statement details.
In the late 19th to early 20th century, the vasopressor and antidiuretic actions of posterior pituitary extracts were discovered and used to treat people with both the central and nephrogenic etiologies, which were also recognized around that time, yet the name “diabetes insipidus” has persisted.
“From a historical perspective, the name is perfectly appropriate. At the time it was identified, and it was realized that it was different from diabetes mellitus, that was a perfectly appropriate terminology based on what was known in the late 19th century – but not now. It has persisted through the years simply because in medicine there’s a lot of inertia for change ... It’s just always been called that. If there’s not a compelling reason to change a name, generally there’s no move to change it,” Dr. Verbalis observed.
‘Dramatic cases of patient mismanagement’ due to name confusion
Unfortunately, the urgency for the change arose from tragedy. In 2009, a 22-year-old man was admitted to the orthopedics department of a London teaching hospital for a hip replacement. Despite his known panhypopituitarism and diabetes insipidus, the nurses continually checked his blood glucose but didn’t give him desmopressin or sufficient fluids. Laboratory testing showed normal glucose, but his serum sodium was 149 mmol/L. The morning after his operation, he had a fatal cardiac arrest with a serum sodium of 169 mmol/L.
“The nurses thought he had diabetes mellitus ... So that was death due to failure to recognize that diabetes insipidus is not diabetes mellitus,” Dr. Verbalis said. “If he had been admitted to endocrinology, this wouldn’t have happened. But he was admitted to orthopedics. Non-endocrinologists are not so aware of diabetes insipidus, because it is a rare disease.”
In 2016, National Health Service England issued a patient safety alert about the “risk of severe harm or death when desmopressin is omitted or delayed in patients with cranial diabetes insipidus,” citing at least four incidents within the prior 7 years where omission of desmopressin had resulted in severe dehydration and death, with another 76 cases of omission or delay that were acted on before the patients became critically ill.
Further impetus for the name change came from the results of an anonymous web-based survey of 1,034 adult and pediatric patients with central diabetes insipidus conducted between August 2021 and February 2022. Overall, 80% reported encountering situations in which their condition had been confused with diabetes mellitus by health care professionals, and 85% supported renaming the disease.
There was some divergence in opinion as to what the new name(s) should be, but clear agreement that the term “diabetes” should not be part of it.
“We’ve only become recently aware that there are dramatic cases of patient mismanagement due to the confusion caused by the word ‘diabetes.’ We think patients should have a voice. If a legitimate patient survey says over 80% think this name should be changed, then I think we as endocrinologists need to pay attention to that,” Dr. Verbalis said.
But while endocrinologists are the ones who see these patients the most often, Dr. Verbalis said a main aim of the position statement “is really to change the mindset of non-endocrinologist doctors and nurses and other health care professionals that this is not diabetes mellitus. It’s a totally different disease. And if we give it a totally different name, then I think they will better recognize that.”
As to how long Dr. Verbalis thinks it will take for the new names to catch on, he pointed out that it’s taken about a decade for the rheumatology field to fully adopt the name “granulomatosis with polyangiitis” as a replacement for “Wegener’s granulomatosis” after the eponymous physician’s Nazi ties were revealed.
“So we’re not anticipating that this is going to change terminology tomorrow. It’s a long process. We just wanted to get the process started,” he said.
Dr. Verbalis has reported consulting for Otsuka.
A version of this article first appeared on Medscape.com.
An international group representing leading endocrinology associations has recommended that the name “diabetes insipidus” – which in some cases has led to harm – be changed to eliminate confusion with “diabetes mellitus” and to reflect the former condition’s pathophysiology.
The new proposed names are arginine vasopressin deficiency (AVP-D) for central (also called “cranial”) etiologies and arginine vasopressin resistance (AVP-R) for nephrogenic (kidney) etiologies.
“What we’re proposing is to rename the disease according to the pathophysiology that defines it,” statement co-author Joseph G. Verbalis, MD, professor of medicine and chief of endocrinology and metabolism at Georgetown University Medical Center, Washington, told this news organization.
The statement advises that henceforth the new names be used in manuscripts and the medical literature while keeping the old names in parentheses during a transition period, as in “AVP-deficiency (cranial diabetes insipidus)” and “AVP-resistance (nephrogenic diabetes insipidus).”
The condition formerly known as diabetes insipidus is relatively rare, occurring in about 1 person per 10-15,000 population. It is caused by either deficient production or resistance in the kidney to the hormone AVP, normally produced by the hypothalamus and stored in the pituitary gland. AVP, also called antidiuretic hormone, regulates the body’s water level and urine production by the kidney.
Both etiologies lead to extreme thirst and excessive production of urine. Common causes of the deficiency include head trauma or brain tumor, while resistance in the kidney is often congenital. It is currently treated with a synthetic form of AVP called desmopressin and fluid replacement.
What’s in a name?
The proposal to change the name by the Working Group for Renaming Diabetes Insipidus is endorsed by The Endocrine Society, European Society of Endocrinology, Pituitary Society, Society for Endocrinology, European Society for Paediatric Endocrinology, Endocrine Society of Australia, Brazilian Endocrine Society, and Japanese Endocrine Society and is under review by several other societies. It was published as a position statement in several of those society’s journals, with more to follow.
Historically, the word “diabetes,” a Greek word meaning “siphon,” was used in the 1st and 2nd century BC to describe excess flow of urine. The Latin word “mellitus” or “honey” was added in the late 17th century to describe the sweetness of the urine in the dysglycemic condition.
A century later, the Latin word “insipidus,” meaning insipid or tasteless, was coined to distinguish between the two types of polyuria, the position statement details.
In the late 19th to early 20th century, the vasopressor and antidiuretic actions of posterior pituitary extracts were discovered and used to treat people with both the central and nephrogenic etiologies, which were also recognized around that time, yet the name “diabetes insipidus” has persisted.
“From a historical perspective, the name is perfectly appropriate. At the time it was identified, and it was realized that it was different from diabetes mellitus, that was a perfectly appropriate terminology based on what was known in the late 19th century – but not now. It has persisted through the years simply because in medicine there’s a lot of inertia for change ... It’s just always been called that. If there’s not a compelling reason to change a name, generally there’s no move to change it,” Dr. Verbalis observed.
‘Dramatic cases of patient mismanagement’ due to name confusion
Unfortunately, the urgency for the change arose from tragedy. In 2009, a 22-year-old man was admitted to the orthopedics department of a London teaching hospital for a hip replacement. Despite his known panhypopituitarism and diabetes insipidus, the nurses continually checked his blood glucose but didn’t give him desmopressin or sufficient fluids. Laboratory testing showed normal glucose, but his serum sodium was 149 mmol/L. The morning after his operation, he had a fatal cardiac arrest with a serum sodium of 169 mmol/L.
“The nurses thought he had diabetes mellitus ... So that was death due to failure to recognize that diabetes insipidus is not diabetes mellitus,” Dr. Verbalis said. “If he had been admitted to endocrinology, this wouldn’t have happened. But he was admitted to orthopedics. Non-endocrinologists are not so aware of diabetes insipidus, because it is a rare disease.”
In 2016, National Health Service England issued a patient safety alert about the “risk of severe harm or death when desmopressin is omitted or delayed in patients with cranial diabetes insipidus,” citing at least four incidents within the prior 7 years where omission of desmopressin had resulted in severe dehydration and death, with another 76 cases of omission or delay that were acted on before the patients became critically ill.
Further impetus for the name change came from the results of an anonymous web-based survey of 1,034 adult and pediatric patients with central diabetes insipidus conducted between August 2021 and February 2022. Overall, 80% reported encountering situations in which their condition had been confused with diabetes mellitus by health care professionals, and 85% supported renaming the disease.
There was some divergence in opinion as to what the new name(s) should be, but clear agreement that the term “diabetes” should not be part of it.
“We’ve only become recently aware that there are dramatic cases of patient mismanagement due to the confusion caused by the word ‘diabetes.’ We think patients should have a voice. If a legitimate patient survey says over 80% think this name should be changed, then I think we as endocrinologists need to pay attention to that,” Dr. Verbalis said.
But while endocrinologists are the ones who see these patients the most often, Dr. Verbalis said a main aim of the position statement “is really to change the mindset of non-endocrinologist doctors and nurses and other health care professionals that this is not diabetes mellitus. It’s a totally different disease. And if we give it a totally different name, then I think they will better recognize that.”
As to how long Dr. Verbalis thinks it will take for the new names to catch on, he pointed out that it’s taken about a decade for the rheumatology field to fully adopt the name “granulomatosis with polyangiitis” as a replacement for “Wegener’s granulomatosis” after the eponymous physician’s Nazi ties were revealed.
“So we’re not anticipating that this is going to change terminology tomorrow. It’s a long process. We just wanted to get the process started,” he said.
Dr. Verbalis has reported consulting for Otsuka.
A version of this article first appeared on Medscape.com.
Two-year dupilumab data: Continued response for moderate to severe pediatric asthma
NASHVILLE, TENN. – For children with uncontrolled asthma on standard therapies and meeting criteria of a type 2 (T2) inflammatory phenotype, a prospective 1-year extension from a phase 3 trial supports the biologic dupilumab as a potential treatment standard, according to the investigator who presented the findings at the annual meeting of the American College of Chest Physicians (CHEST).
said Leonard B. Bacharier, MD, section chief, division of pediatric allergy, immunology, and pulmonary medicine, Vanderbilt University Medical Center, Nashville, Tenn.
By T2 inflammatory phenotype, Dr. Bacharier specified that key features include an eosinophil count of at least 150 cells/mL and a FENO level of at least 20 ppb. If children meet these and inadequate standard-therapy response criteria, Dr. Bacharier thinks the extension data support dupilumab as a routine therapy despite the cost.
“As a pediatrician, I think it is really important that children with asthma finish their childhood with the best bone health and the lowest risk of other steroid-associated adverse events,” Dr. Bacharier said.
Over the course of the 1-year extension, called EXCURSION, there was no evidence of diminished efficacy nor of any new safety signal. In other words, patients have remained well controlled for 2 years with a well-tolerated therapy. Dr. Bacharier pointed out, however, that one of the most compelling reasons to consider this as a potential standard was the very low rates at which patients required a course of steroids.
At the end of 1 year in the extension trial, called VOYAGE, the unadjusted annualized total number of steroid courses per patient was 0.414 in the dupilumab group vs. 0.816 in the placebo group. At the end of EXCURSION, following an additional year of therapy, the rate was 0.152.
“This means that fewer than 2 patients out of 10 required prednisone in the previous year,” Dr. Bacharier said.
The EXCURSION extension study did not capture data on steroid-related adverse events, but Dr. Bacharier said that these data are reassuring for both acute and long-term risks of steroid exposure.
“We know that the adverse effects associated with oral steroids are related to cumulative exposure. The more you receive, the greater the risk of adverse effects,” he said.
In patients who were randomly assigned to placebo in the VOYAGE trial and then switched to dupilumab in the EXCURSION extension, steroid exposure was also very low, but whether evaluated as annualized total courses (0.152 vs. 0.181) or by proportion of patients with any steroid intake (10.5% vs. 13.2%), there was a numerical advantage for starting and remaining on dupilumab over the 2-year follow-up.
In VOYAGE, which was published last year in the New England Journal of Medicine, 408 children from ages 6 to 11 years were randomly assigned in a 2:1 ratio to dupilumab or matching placebo. For children weighing less than 30 kg, the dose was 200 mg. For those who weighed less, the dose was 100 mg. Both doses were administered every 2 weeks.
As previously reported, the study met the primary endpoint of annualized rate of severe asthma exacerbations, which was 0.31 in the dupilumab group vs. 0.75 in the placebo group, a relative reduction of 59.3% (P < .001). Dupilumab was also superior on several secondary endpoints, including measures of lung function and asthma control.
The EXCURSION extension study enrolled 365 of the patients who participated in VOYAGE. This included 125 of the 135 randomly assigned to placebo and 240 of the 273 randomly assigned to dupilumab. Those initially randomly assigned to placebo were transitioned to dupilumab. The same weight-based dosing was employed.
At baseline, the children enrolled in VOYAGE had an annualized rate of 2.560 severe exacerbations. At the end of VOYAGE, this rate was 0.330. At the end of EXCURSION after 2 years on dupilumab, the rate was 0.118. In the group switched from placebo to dupilumab, the rate was 0.124.
During EXCURSION, treatment-emergent adverse events occurred in 2.5% of those who remained on dupilumab and 0.8% of those switched from placebo to dupilumab. Three patients (1.3%) permanently discontinued therapy because of a treatment-related event. The most common adverse events involved upper respiratory complaints, such as nasopharyngitis, pharyngitis, upper respiratory tract infections, and rhinitis influenza, but all were reported in fewer than 10% of patients. Other reported side effects, such as injection-site reactions and diarrhea, occurred in 5% or fewer of patients.
“Over the 2 years, dupilumab was well tolerated, and there was evidence of an increased risk of adverse events for longer exposure,” Dr. Bacharier reported.
It is for this reason that Dr. Bacharier concluded that children with repeated exacerbations requiring steroids despite standard therapies should be considered for dupilumab if they also meet criteria for the T2 inflammatory phenotype. This last point is important.
“In children with low levels of eosinophil and low phenol, we are not seeing these kinds of response,” Dr. Bacharier said. Rather, in the absence of eosinophilia, “there is probably no difference between dupilumab and placebo.”
An important steroid-sparing effect is “suggested” by the data, but Sally E. Wenzel, MD, director of the University of Pittsburgh Asthma and Environmental Lung Health Institute in Pittsburgh, characterized the idea that dupilumab is emerging to be a standard in uncontrolled asthma in children with the T2 phenotype as “a bit premature.”
She challenged the conclusion that the EXCURSION data associated dupilumab with a reduction in annualized steroid courses over time. While the number was lower after 2 years of treatment than after 1, Dr. Wenzel pointed out that all patients were on dupilumab in the second year, “so we don’t know what really happens without treatment.” She said there are other potential explanations, including the possibility that aging children have less active disease.
More importantly, Dr. Wenzel said in an interview that she would also hesitate to urge biologics in every child who meets the criteria that Dr. Bacharier outlined.
“The most important concern is that we do not know how long one should continue the dupilumab and if the long-term treatment adversely or positively affects a growing immune system,” she said.
There is reason to be concerned that blockage of an entire immune pathway with a biologic could adversely affect autoimmunity as well as susceptibility to cancer, according to Dr. Wenzel. She hopes this does not prove to be the case, but she encouraged prudence until there are more data to judge.
While extension data for dupilumab “sound good,” she thinks moving toward any type of standard of care with biologics in children “has to be done with caution and constant evaluation and reevaluation.”
Dr. Bacharier disclosed relationships with AstraZeneca, GlaxoSmithKline, Regeneron and Sanofi. The two latter companies collaborated on the development and marketing of dupilumab. Dr. Wenzel disclosed relationships with AstraZeneca, GlaxoSmithKline, Knopp Pharmaceuticals, Pieris, and Sanofi-Regeneron.
A version of this article first appeared on Medscape.com.
NASHVILLE, TENN. – For children with uncontrolled asthma on standard therapies and meeting criteria of a type 2 (T2) inflammatory phenotype, a prospective 1-year extension from a phase 3 trial supports the biologic dupilumab as a potential treatment standard, according to the investigator who presented the findings at the annual meeting of the American College of Chest Physicians (CHEST).
said Leonard B. Bacharier, MD, section chief, division of pediatric allergy, immunology, and pulmonary medicine, Vanderbilt University Medical Center, Nashville, Tenn.
By T2 inflammatory phenotype, Dr. Bacharier specified that key features include an eosinophil count of at least 150 cells/mL and a FENO level of at least 20 ppb. If children meet these and inadequate standard-therapy response criteria, Dr. Bacharier thinks the extension data support dupilumab as a routine therapy despite the cost.
“As a pediatrician, I think it is really important that children with asthma finish their childhood with the best bone health and the lowest risk of other steroid-associated adverse events,” Dr. Bacharier said.
Over the course of the 1-year extension, called EXCURSION, there was no evidence of diminished efficacy nor of any new safety signal. In other words, patients have remained well controlled for 2 years with a well-tolerated therapy. Dr. Bacharier pointed out, however, that one of the most compelling reasons to consider this as a potential standard was the very low rates at which patients required a course of steroids.
At the end of 1 year in the extension trial, called VOYAGE, the unadjusted annualized total number of steroid courses per patient was 0.414 in the dupilumab group vs. 0.816 in the placebo group. At the end of EXCURSION, following an additional year of therapy, the rate was 0.152.
“This means that fewer than 2 patients out of 10 required prednisone in the previous year,” Dr. Bacharier said.
The EXCURSION extension study did not capture data on steroid-related adverse events, but Dr. Bacharier said that these data are reassuring for both acute and long-term risks of steroid exposure.
“We know that the adverse effects associated with oral steroids are related to cumulative exposure. The more you receive, the greater the risk of adverse effects,” he said.
In patients who were randomly assigned to placebo in the VOYAGE trial and then switched to dupilumab in the EXCURSION extension, steroid exposure was also very low, but whether evaluated as annualized total courses (0.152 vs. 0.181) or by proportion of patients with any steroid intake (10.5% vs. 13.2%), there was a numerical advantage for starting and remaining on dupilumab over the 2-year follow-up.
In VOYAGE, which was published last year in the New England Journal of Medicine, 408 children from ages 6 to 11 years were randomly assigned in a 2:1 ratio to dupilumab or matching placebo. For children weighing less than 30 kg, the dose was 200 mg. For those who weighed less, the dose was 100 mg. Both doses were administered every 2 weeks.
As previously reported, the study met the primary endpoint of annualized rate of severe asthma exacerbations, which was 0.31 in the dupilumab group vs. 0.75 in the placebo group, a relative reduction of 59.3% (P < .001). Dupilumab was also superior on several secondary endpoints, including measures of lung function and asthma control.
The EXCURSION extension study enrolled 365 of the patients who participated in VOYAGE. This included 125 of the 135 randomly assigned to placebo and 240 of the 273 randomly assigned to dupilumab. Those initially randomly assigned to placebo were transitioned to dupilumab. The same weight-based dosing was employed.
At baseline, the children enrolled in VOYAGE had an annualized rate of 2.560 severe exacerbations. At the end of VOYAGE, this rate was 0.330. At the end of EXCURSION after 2 years on dupilumab, the rate was 0.118. In the group switched from placebo to dupilumab, the rate was 0.124.
During EXCURSION, treatment-emergent adverse events occurred in 2.5% of those who remained on dupilumab and 0.8% of those switched from placebo to dupilumab. Three patients (1.3%) permanently discontinued therapy because of a treatment-related event. The most common adverse events involved upper respiratory complaints, such as nasopharyngitis, pharyngitis, upper respiratory tract infections, and rhinitis influenza, but all were reported in fewer than 10% of patients. Other reported side effects, such as injection-site reactions and diarrhea, occurred in 5% or fewer of patients.
“Over the 2 years, dupilumab was well tolerated, and there was evidence of an increased risk of adverse events for longer exposure,” Dr. Bacharier reported.
It is for this reason that Dr. Bacharier concluded that children with repeated exacerbations requiring steroids despite standard therapies should be considered for dupilumab if they also meet criteria for the T2 inflammatory phenotype. This last point is important.
“In children with low levels of eosinophil and low phenol, we are not seeing these kinds of response,” Dr. Bacharier said. Rather, in the absence of eosinophilia, “there is probably no difference between dupilumab and placebo.”
An important steroid-sparing effect is “suggested” by the data, but Sally E. Wenzel, MD, director of the University of Pittsburgh Asthma and Environmental Lung Health Institute in Pittsburgh, characterized the idea that dupilumab is emerging to be a standard in uncontrolled asthma in children with the T2 phenotype as “a bit premature.”
She challenged the conclusion that the EXCURSION data associated dupilumab with a reduction in annualized steroid courses over time. While the number was lower after 2 years of treatment than after 1, Dr. Wenzel pointed out that all patients were on dupilumab in the second year, “so we don’t know what really happens without treatment.” She said there are other potential explanations, including the possibility that aging children have less active disease.
More importantly, Dr. Wenzel said in an interview that she would also hesitate to urge biologics in every child who meets the criteria that Dr. Bacharier outlined.
“The most important concern is that we do not know how long one should continue the dupilumab and if the long-term treatment adversely or positively affects a growing immune system,” she said.
There is reason to be concerned that blockage of an entire immune pathway with a biologic could adversely affect autoimmunity as well as susceptibility to cancer, according to Dr. Wenzel. She hopes this does not prove to be the case, but she encouraged prudence until there are more data to judge.
While extension data for dupilumab “sound good,” she thinks moving toward any type of standard of care with biologics in children “has to be done with caution and constant evaluation and reevaluation.”
Dr. Bacharier disclosed relationships with AstraZeneca, GlaxoSmithKline, Regeneron and Sanofi. The two latter companies collaborated on the development and marketing of dupilumab. Dr. Wenzel disclosed relationships with AstraZeneca, GlaxoSmithKline, Knopp Pharmaceuticals, Pieris, and Sanofi-Regeneron.
A version of this article first appeared on Medscape.com.
NASHVILLE, TENN. – For children with uncontrolled asthma on standard therapies and meeting criteria of a type 2 (T2) inflammatory phenotype, a prospective 1-year extension from a phase 3 trial supports the biologic dupilumab as a potential treatment standard, according to the investigator who presented the findings at the annual meeting of the American College of Chest Physicians (CHEST).
said Leonard B. Bacharier, MD, section chief, division of pediatric allergy, immunology, and pulmonary medicine, Vanderbilt University Medical Center, Nashville, Tenn.
By T2 inflammatory phenotype, Dr. Bacharier specified that key features include an eosinophil count of at least 150 cells/mL and a FENO level of at least 20 ppb. If children meet these and inadequate standard-therapy response criteria, Dr. Bacharier thinks the extension data support dupilumab as a routine therapy despite the cost.
“As a pediatrician, I think it is really important that children with asthma finish their childhood with the best bone health and the lowest risk of other steroid-associated adverse events,” Dr. Bacharier said.
Over the course of the 1-year extension, called EXCURSION, there was no evidence of diminished efficacy nor of any new safety signal. In other words, patients have remained well controlled for 2 years with a well-tolerated therapy. Dr. Bacharier pointed out, however, that one of the most compelling reasons to consider this as a potential standard was the very low rates at which patients required a course of steroids.
At the end of 1 year in the extension trial, called VOYAGE, the unadjusted annualized total number of steroid courses per patient was 0.414 in the dupilumab group vs. 0.816 in the placebo group. At the end of EXCURSION, following an additional year of therapy, the rate was 0.152.
“This means that fewer than 2 patients out of 10 required prednisone in the previous year,” Dr. Bacharier said.
The EXCURSION extension study did not capture data on steroid-related adverse events, but Dr. Bacharier said that these data are reassuring for both acute and long-term risks of steroid exposure.
“We know that the adverse effects associated with oral steroids are related to cumulative exposure. The more you receive, the greater the risk of adverse effects,” he said.
In patients who were randomly assigned to placebo in the VOYAGE trial and then switched to dupilumab in the EXCURSION extension, steroid exposure was also very low, but whether evaluated as annualized total courses (0.152 vs. 0.181) or by proportion of patients with any steroid intake (10.5% vs. 13.2%), there was a numerical advantage for starting and remaining on dupilumab over the 2-year follow-up.
In VOYAGE, which was published last year in the New England Journal of Medicine, 408 children from ages 6 to 11 years were randomly assigned in a 2:1 ratio to dupilumab or matching placebo. For children weighing less than 30 kg, the dose was 200 mg. For those who weighed less, the dose was 100 mg. Both doses were administered every 2 weeks.
As previously reported, the study met the primary endpoint of annualized rate of severe asthma exacerbations, which was 0.31 in the dupilumab group vs. 0.75 in the placebo group, a relative reduction of 59.3% (P < .001). Dupilumab was also superior on several secondary endpoints, including measures of lung function and asthma control.
The EXCURSION extension study enrolled 365 of the patients who participated in VOYAGE. This included 125 of the 135 randomly assigned to placebo and 240 of the 273 randomly assigned to dupilumab. Those initially randomly assigned to placebo were transitioned to dupilumab. The same weight-based dosing was employed.
At baseline, the children enrolled in VOYAGE had an annualized rate of 2.560 severe exacerbations. At the end of VOYAGE, this rate was 0.330. At the end of EXCURSION after 2 years on dupilumab, the rate was 0.118. In the group switched from placebo to dupilumab, the rate was 0.124.
During EXCURSION, treatment-emergent adverse events occurred in 2.5% of those who remained on dupilumab and 0.8% of those switched from placebo to dupilumab. Three patients (1.3%) permanently discontinued therapy because of a treatment-related event. The most common adverse events involved upper respiratory complaints, such as nasopharyngitis, pharyngitis, upper respiratory tract infections, and rhinitis influenza, but all were reported in fewer than 10% of patients. Other reported side effects, such as injection-site reactions and diarrhea, occurred in 5% or fewer of patients.
“Over the 2 years, dupilumab was well tolerated, and there was evidence of an increased risk of adverse events for longer exposure,” Dr. Bacharier reported.
It is for this reason that Dr. Bacharier concluded that children with repeated exacerbations requiring steroids despite standard therapies should be considered for dupilumab if they also meet criteria for the T2 inflammatory phenotype. This last point is important.
“In children with low levels of eosinophil and low phenol, we are not seeing these kinds of response,” Dr. Bacharier said. Rather, in the absence of eosinophilia, “there is probably no difference between dupilumab and placebo.”
An important steroid-sparing effect is “suggested” by the data, but Sally E. Wenzel, MD, director of the University of Pittsburgh Asthma and Environmental Lung Health Institute in Pittsburgh, characterized the idea that dupilumab is emerging to be a standard in uncontrolled asthma in children with the T2 phenotype as “a bit premature.”
She challenged the conclusion that the EXCURSION data associated dupilumab with a reduction in annualized steroid courses over time. While the number was lower after 2 years of treatment than after 1, Dr. Wenzel pointed out that all patients were on dupilumab in the second year, “so we don’t know what really happens without treatment.” She said there are other potential explanations, including the possibility that aging children have less active disease.
More importantly, Dr. Wenzel said in an interview that she would also hesitate to urge biologics in every child who meets the criteria that Dr. Bacharier outlined.
“The most important concern is that we do not know how long one should continue the dupilumab and if the long-term treatment adversely or positively affects a growing immune system,” she said.
There is reason to be concerned that blockage of an entire immune pathway with a biologic could adversely affect autoimmunity as well as susceptibility to cancer, according to Dr. Wenzel. She hopes this does not prove to be the case, but she encouraged prudence until there are more data to judge.
While extension data for dupilumab “sound good,” she thinks moving toward any type of standard of care with biologics in children “has to be done with caution and constant evaluation and reevaluation.”
Dr. Bacharier disclosed relationships with AstraZeneca, GlaxoSmithKline, Regeneron and Sanofi. The two latter companies collaborated on the development and marketing of dupilumab. Dr. Wenzel disclosed relationships with AstraZeneca, GlaxoSmithKline, Knopp Pharmaceuticals, Pieris, and Sanofi-Regeneron.
A version of this article first appeared on Medscape.com.
AT CHEST 2022
Life expectancy 6.3 years shorter for Black MSM with HIV
WASHINGTON –
Lead author Katherine Rich, MPH, a student at Harvard Medical School, Boston, presented the data during an annual scientific meeting on infectious diseases.
“Substantial disparities in care exist between Black and White MSM here in the United States,” she said. “The 2030 goals of the EHE [Ending the HIV Epidemic in the U.S. initiative] won’t be met until HIV-related disparities are reduced.”
Using modeling, the team was able to measure both the gaps and the potential of interventions to address those gaps.
- The team found that improving engagement in care had the largest benefit in narrowing the gap. Improving engagement and retention in care, they write, would result in a gain of 1.4 life-years for Black MSM and 1 year for White MSM.
- Annual testing would add 0.6 life-years for Black MSM and 0.3 life-years for White MSM, compared with standard care.
- In simulating viral suppression, the model-predicted gain would be 1.1 years for Black MSM and 0.3 for White.
Furthermore, a combination of annual testing, 95% engagement in care, and 95% virologic suppression would add 3.4 years for Black MSM (more than double the increase in life-years for any one intervention) and 1.6 years for their White counterparts, the research suggests.
The researchers projected life expectancy from age 15 to be 52.2 years for Black MSM (or 67.2 years old) and 58.5 years from age 15 for White MSM (or 73.5 years old), a difference of 6.3 years.
Kathleen McManus, MD, assistant professor of medicine in infectious diseases and international health at the University of Virginia, Charlottesville, said in an interview that the projected gap in years of life should be a call to action. Dr. McManus was not involved with the study.
Life expectancy gap ‘alarming’
“It is alarming that with current usual HIV care Black MSM with HIV have 6.3 fewer years of life expectancy than White MSM,” she said. “Black MSM having lower retention in care and a lower rate of viral suppression than White MSM demonstrates that there is a problem with our current health care delivery to Black MSM.”
With qualitative, community-engaged research, she said, “we need to ask the Black MSM community what care innovations they need – and then we need clinics and organizations to make the identified changes.”
Researchers used the validated CEPAC (Cost-Effectiveness of Preventing AIDS Complications) microsimulation HIV model to project life expectancy. Using data from the United States Centers for Disease Control and Prevention, they estimated the average age at HIV infection to be 26.8 years for Black MSM and 35 years for White MSM.
They estimated the proportion of time that MSM with diagnosed HIV are retained in care to be 75.2% for Black MSM and 80.6% for White MSM. They calculated the proportion who achieve virologic suppression to be 82% for Black MSM and 91.2% for White MSM.
Senior author Emily P. Hyle, MD, associate professor of medicine at Harvard and infectious diseases physician at Massachusetts General Hospital, both in Boston, said in a press conference before the presentation that strategies to narrow the gap will look different by region.
“Our study highlights that if you can find effective interventions, the effect can be incredibly large. These are very large differences in life-years and life expectancies,” she said.
Ms. Rich gave an example of promising interventions by pointing to work by study coauthor Aima Ahonkhai, MD, MPH, assistant professor of medicine at Vanderbilt University, Nashville, Tenn., who has received federal funding to pursue research on whether preventive care outreach in barbershops can improve prevention for Black men with HIV.
Ms. Rich noted that the modeling has limitations in that it focused on health outcomes and did not simulate transmissions. Results also reflect national data and not local HIV care continuums, which, she acknowledged, differ substantially.
Dr. McManus and the study authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON –
Lead author Katherine Rich, MPH, a student at Harvard Medical School, Boston, presented the data during an annual scientific meeting on infectious diseases.
“Substantial disparities in care exist between Black and White MSM here in the United States,” she said. “The 2030 goals of the EHE [Ending the HIV Epidemic in the U.S. initiative] won’t be met until HIV-related disparities are reduced.”
Using modeling, the team was able to measure both the gaps and the potential of interventions to address those gaps.
- The team found that improving engagement in care had the largest benefit in narrowing the gap. Improving engagement and retention in care, they write, would result in a gain of 1.4 life-years for Black MSM and 1 year for White MSM.
- Annual testing would add 0.6 life-years for Black MSM and 0.3 life-years for White MSM, compared with standard care.
- In simulating viral suppression, the model-predicted gain would be 1.1 years for Black MSM and 0.3 for White.
Furthermore, a combination of annual testing, 95% engagement in care, and 95% virologic suppression would add 3.4 years for Black MSM (more than double the increase in life-years for any one intervention) and 1.6 years for their White counterparts, the research suggests.
The researchers projected life expectancy from age 15 to be 52.2 years for Black MSM (or 67.2 years old) and 58.5 years from age 15 for White MSM (or 73.5 years old), a difference of 6.3 years.
Kathleen McManus, MD, assistant professor of medicine in infectious diseases and international health at the University of Virginia, Charlottesville, said in an interview that the projected gap in years of life should be a call to action. Dr. McManus was not involved with the study.
Life expectancy gap ‘alarming’
“It is alarming that with current usual HIV care Black MSM with HIV have 6.3 fewer years of life expectancy than White MSM,” she said. “Black MSM having lower retention in care and a lower rate of viral suppression than White MSM demonstrates that there is a problem with our current health care delivery to Black MSM.”
With qualitative, community-engaged research, she said, “we need to ask the Black MSM community what care innovations they need – and then we need clinics and organizations to make the identified changes.”
Researchers used the validated CEPAC (Cost-Effectiveness of Preventing AIDS Complications) microsimulation HIV model to project life expectancy. Using data from the United States Centers for Disease Control and Prevention, they estimated the average age at HIV infection to be 26.8 years for Black MSM and 35 years for White MSM.
They estimated the proportion of time that MSM with diagnosed HIV are retained in care to be 75.2% for Black MSM and 80.6% for White MSM. They calculated the proportion who achieve virologic suppression to be 82% for Black MSM and 91.2% for White MSM.
Senior author Emily P. Hyle, MD, associate professor of medicine at Harvard and infectious diseases physician at Massachusetts General Hospital, both in Boston, said in a press conference before the presentation that strategies to narrow the gap will look different by region.
“Our study highlights that if you can find effective interventions, the effect can be incredibly large. These are very large differences in life-years and life expectancies,” she said.
Ms. Rich gave an example of promising interventions by pointing to work by study coauthor Aima Ahonkhai, MD, MPH, assistant professor of medicine at Vanderbilt University, Nashville, Tenn., who has received federal funding to pursue research on whether preventive care outreach in barbershops can improve prevention for Black men with HIV.
Ms. Rich noted that the modeling has limitations in that it focused on health outcomes and did not simulate transmissions. Results also reflect national data and not local HIV care continuums, which, she acknowledged, differ substantially.
Dr. McManus and the study authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON –
Lead author Katherine Rich, MPH, a student at Harvard Medical School, Boston, presented the data during an annual scientific meeting on infectious diseases.
“Substantial disparities in care exist between Black and White MSM here in the United States,” she said. “The 2030 goals of the EHE [Ending the HIV Epidemic in the U.S. initiative] won’t be met until HIV-related disparities are reduced.”
Using modeling, the team was able to measure both the gaps and the potential of interventions to address those gaps.
- The team found that improving engagement in care had the largest benefit in narrowing the gap. Improving engagement and retention in care, they write, would result in a gain of 1.4 life-years for Black MSM and 1 year for White MSM.
- Annual testing would add 0.6 life-years for Black MSM and 0.3 life-years for White MSM, compared with standard care.
- In simulating viral suppression, the model-predicted gain would be 1.1 years for Black MSM and 0.3 for White.
Furthermore, a combination of annual testing, 95% engagement in care, and 95% virologic suppression would add 3.4 years for Black MSM (more than double the increase in life-years for any one intervention) and 1.6 years for their White counterparts, the research suggests.
The researchers projected life expectancy from age 15 to be 52.2 years for Black MSM (or 67.2 years old) and 58.5 years from age 15 for White MSM (or 73.5 years old), a difference of 6.3 years.
Kathleen McManus, MD, assistant professor of medicine in infectious diseases and international health at the University of Virginia, Charlottesville, said in an interview that the projected gap in years of life should be a call to action. Dr. McManus was not involved with the study.
Life expectancy gap ‘alarming’
“It is alarming that with current usual HIV care Black MSM with HIV have 6.3 fewer years of life expectancy than White MSM,” she said. “Black MSM having lower retention in care and a lower rate of viral suppression than White MSM demonstrates that there is a problem with our current health care delivery to Black MSM.”
With qualitative, community-engaged research, she said, “we need to ask the Black MSM community what care innovations they need – and then we need clinics and organizations to make the identified changes.”
Researchers used the validated CEPAC (Cost-Effectiveness of Preventing AIDS Complications) microsimulation HIV model to project life expectancy. Using data from the United States Centers for Disease Control and Prevention, they estimated the average age at HIV infection to be 26.8 years for Black MSM and 35 years for White MSM.
They estimated the proportion of time that MSM with diagnosed HIV are retained in care to be 75.2% for Black MSM and 80.6% for White MSM. They calculated the proportion who achieve virologic suppression to be 82% for Black MSM and 91.2% for White MSM.
Senior author Emily P. Hyle, MD, associate professor of medicine at Harvard and infectious diseases physician at Massachusetts General Hospital, both in Boston, said in a press conference before the presentation that strategies to narrow the gap will look different by region.
“Our study highlights that if you can find effective interventions, the effect can be incredibly large. These are very large differences in life-years and life expectancies,” she said.
Ms. Rich gave an example of promising interventions by pointing to work by study coauthor Aima Ahonkhai, MD, MPH, assistant professor of medicine at Vanderbilt University, Nashville, Tenn., who has received federal funding to pursue research on whether preventive care outreach in barbershops can improve prevention for Black men with HIV.
Ms. Rich noted that the modeling has limitations in that it focused on health outcomes and did not simulate transmissions. Results also reflect national data and not local HIV care continuums, which, she acknowledged, differ substantially.
Dr. McManus and the study authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT IDWEEK 2022