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AAP Updates Guidance on Vaccine Communication and Hesitancy
The measles outbreak in Florida, occurring just as health officials announced an official end to Philadelphia’s measles outbreak and rising global cases, has cast attention once again on concerns about vaccine hesitancy. In the midst of Florida’s surgeon general avoiding measles vaccination recommendations for parents, the American Academy of Pediatrics has updated its clinical guidance on vaccine communication.
“Disruption to routine pediatric vaccination during the COVID-19 pandemic has left many children vulnerable to vaccine-preventable diseases and more locations susceptible to outbreaks in the United States and around the world,” Sean T. O’Leary, MD, MPH, a pediatric infectious diseases specialist and associate professor of pediatrics at the University of Colorado in Aurora, and his colleagues, wrote in the new report, published in the March issue of Pediatrics. “Geographic clustering of vaccine refusal further increases the risk of communicable disease outbreaks in certain communities even when vaccination rates at a state or national level remain high overall.”
The authors note that disease resurgence may bolster vaccine uptake, with media coverage of recent outbreaks linked to more pro-vaccine discussions and attitudes among parents. But the evidence on that remains inconclusive, and the authors point out the slow uptake in COVID-19 vaccination as parents navigate ongoing spread of both the disease and vaccine misinformation.
Conflicting Evidence on Postpandemic Attitudes
It remains unclear how parent attitudes toward vaccines have shifted, if at all, since the pandemic. A study published in Pediatrics from October 2023, which Dr. O’Leary also coauthored, analyzed data from an online survey of Colorado mothers between 2018 and 2021 and found no significant difference in vaccine hesitancy during the pandemic compared with pre-pandemic.
Among 3,553 respondents, 1 in 5 (20.4%) were vaccine hesitant overall. Though parents were twice as likely to feel uncertain in trusting vaccine information after the COVID-19 vaccines were authorized (adjusted odds ratio [aOR] 2.14), they were half as likely to be unsure about hesitancy toward childhood vaccines (aOR 0.48).
Another study in Pediatrics from October 2023 found that common concerns about COVID-19 vaccines among parents included infertility, long-term effects from the vaccines, and effects on preexisting medical conditions. But even then, participants in focus groups “expressed that they would listen to their doctor for information about COVID-19 vaccines,” wrote Aubree Honcoop, MPS, of the University of Nebraska Medical Center in Omaha, and her colleagues.
“I think what we’re seeing, very importantly, is that physicians seem to be the source people rely on,” said Walter Orenstein, MD, professor of medicine and associate director of the Emory Vaccine Center at Emory University in Atlanta. “But we need to give the physicians time and incentives to spend time with families,” such as a billing code for vaccine counseling, he said.
Dr. Orenstein was surprised to see the results from Colorado, but he noted they were from a small survey in a single state. He pointed to other findings, such as those from the University of Pennsylvania’s Annenberg Public Policy Center in November 2023, that found lower confidence overall among Americans toward vaccines.
Paul Offit, MD, director of the Vaccine Education Center and an attending infectious disease physician at Children’s Hospital of Philadelphia, where the city’s measles outbreak began, is similarly skeptical about the Colorado study’s findings that parent vaccine attitudes have changed little since the pandemic. At the AAP’s annual conference in October 2023, Dr. Offit asked pediatricians about their experiences while he signed books.
“I would ask, ‘So what’s it like out there? Are we winning or losing?’ ” he said. “I would say, to a person, everyone said they felt things were much worse now than they ever have been before.”
Clinical Guidance
The new report reviews previously published evidence on the spectrum of parental vaccine acceptance — from supporters and “go along to get along” parents to cautious acceptors and fence sitters to vaccine refusers — and the determinants that contribute to hesitancy. They also noted the social inequities that have played a role in vaccine uptake disparities.
“Distrust of health systems based on historic and ongoing discrimination and inequitable access to care are intertwined challenges that contribute to racial and ethnic disparities in vaccine uptake,” the authors wrote. “Although there has been progress in reducing racial, ethnic, and socioeconomic disparities in childhood vaccination coverage, the COVID-19 pandemic made clear how much work is yet to be done.”
The report also reviewed the societal, individual, payer and pediatric practice costs of vaccine refusal. The 1-year cost to taxpayers from the measles outbreak in New York City in 2018-2019, for example, was $8.4 million, excluding vaccination programs.
The report provides background information to equip pediatricians for conversations with parents about vaccines. Since safety is the top concern for vaccine hesitancy among parents, the authors advised pediatricians to be familiar with the process of vaccine testing, emergency use authorization, licensure, approval, recommendations, and safety monitoring, including the Vaccine Safety Datalink, the Vaccine Adverse Event Reporting System (VAERS), the FDA’s Biologics Effectiveness and Safety (BEST) system, and the CDC’s Clinical Immunization Safety Assessment Project (CISA).
“Because vaccines are generally given to healthy individuals to prevent disease, they are held to a higher safety standard than other medications,” the authors wrote before providing a summary of the process for physicians to reference. The report also includes information on vaccine ingredients and a chart of common misconceptions about vaccines with the corresponding facts.
Overcoming Hesitancy
Evidence-based strategies for increasing childhood vaccine uptake begin with a strong vaccine recommendation using a presumptive rather than participatory approach, the authors wrote. “A presumptive format is one in which the clinician asserts a position regarding vaccines using a closed-ended statement, such as ‘Sara is due for several vaccines today’ or ‘Well, we have to do some shots,’ ” the authors wrote. “This strategy is in contrast to a participatory format, in which an open-ended question is used to more explicitly invite the parent to voice an opinion, such as ‘How do you feel about vaccines today?’ ” The presumptive format and a strong recommendation are both associated with greater uptake, evidence shows.
For parents who express hesitancy, the authors provide a summary of additional evidence-based communication strategies, starting with motivational interviewing. Two other strategies they highlight include using language to re-emphasize the importance of adhering to the CDC recommended schedule — “He really needs these shots” — and bundling discussion of all recommended vaccines for a visit at once.
“Finally, clinicians can emphasize their own experiences when discussing the need for vaccination, including personal experience with vaccine-preventable diseases and the fact that they and their families are vaccinated because of their confidence in the safety and efficacy of the vaccines,” the authors wrote.
For families who refuse or delay vaccines, the authors reviewed the “ethical arguments both in favor of and against dismissal policies,” noting that nearly all pediatricians who report dismissing families who refuse vaccination are in private practice, since large systems are often unable to dismiss patients. They also point out that fewer pediatricians dismiss families for spreading out vaccines than outright refusing all vaccines.
”Dismissal of child patients of vaccine-refusing parents can be a difficult decision arrived at after considering multiple factors and documented attempts to counsel vaccine-refusing families,” they wrote. “However, if repeated attempts to help understand and address parental values and vaccine concerns fails to engender trust, move parents toward vaccine acceptance, or strengthen the therapeutic alliance, dismissal can be an acceptable option.”
Finally, the authors reminded pediatricians “that vaccine-hesitant parents are a heterogeneous group and that specific parental vaccine concerns need to be individually identified and addressed.” Working with families to discuss their questions and concerns is an opportunity to “build rapport and trust with a family,” they wrote, ”and, ultimately, protect their children from the scourge of vaccine-preventable diseases.”
The focus groups study was funded by the National Institutes of Health, and the authors reported having no disclosures. The Colorado attitudes study used no external funding, and the authors reported no disclosures. The new clinical report used no external funding, and the authors reported no disclosures. Dr. Orenstein is an uncompensated member of the Moderna Scientific Advisory Board. Dr. Offit codeveloped a licensed rotavirus vaccine, but he does not receive any royalties or own a patent for that.
The measles outbreak in Florida, occurring just as health officials announced an official end to Philadelphia’s measles outbreak and rising global cases, has cast attention once again on concerns about vaccine hesitancy. In the midst of Florida’s surgeon general avoiding measles vaccination recommendations for parents, the American Academy of Pediatrics has updated its clinical guidance on vaccine communication.
“Disruption to routine pediatric vaccination during the COVID-19 pandemic has left many children vulnerable to vaccine-preventable diseases and more locations susceptible to outbreaks in the United States and around the world,” Sean T. O’Leary, MD, MPH, a pediatric infectious diseases specialist and associate professor of pediatrics at the University of Colorado in Aurora, and his colleagues, wrote in the new report, published in the March issue of Pediatrics. “Geographic clustering of vaccine refusal further increases the risk of communicable disease outbreaks in certain communities even when vaccination rates at a state or national level remain high overall.”
The authors note that disease resurgence may bolster vaccine uptake, with media coverage of recent outbreaks linked to more pro-vaccine discussions and attitudes among parents. But the evidence on that remains inconclusive, and the authors point out the slow uptake in COVID-19 vaccination as parents navigate ongoing spread of both the disease and vaccine misinformation.
Conflicting Evidence on Postpandemic Attitudes
It remains unclear how parent attitudes toward vaccines have shifted, if at all, since the pandemic. A study published in Pediatrics from October 2023, which Dr. O’Leary also coauthored, analyzed data from an online survey of Colorado mothers between 2018 and 2021 and found no significant difference in vaccine hesitancy during the pandemic compared with pre-pandemic.
Among 3,553 respondents, 1 in 5 (20.4%) were vaccine hesitant overall. Though parents were twice as likely to feel uncertain in trusting vaccine information after the COVID-19 vaccines were authorized (adjusted odds ratio [aOR] 2.14), they were half as likely to be unsure about hesitancy toward childhood vaccines (aOR 0.48).
Another study in Pediatrics from October 2023 found that common concerns about COVID-19 vaccines among parents included infertility, long-term effects from the vaccines, and effects on preexisting medical conditions. But even then, participants in focus groups “expressed that they would listen to their doctor for information about COVID-19 vaccines,” wrote Aubree Honcoop, MPS, of the University of Nebraska Medical Center in Omaha, and her colleagues.
“I think what we’re seeing, very importantly, is that physicians seem to be the source people rely on,” said Walter Orenstein, MD, professor of medicine and associate director of the Emory Vaccine Center at Emory University in Atlanta. “But we need to give the physicians time and incentives to spend time with families,” such as a billing code for vaccine counseling, he said.
Dr. Orenstein was surprised to see the results from Colorado, but he noted they were from a small survey in a single state. He pointed to other findings, such as those from the University of Pennsylvania’s Annenberg Public Policy Center in November 2023, that found lower confidence overall among Americans toward vaccines.
Paul Offit, MD, director of the Vaccine Education Center and an attending infectious disease physician at Children’s Hospital of Philadelphia, where the city’s measles outbreak began, is similarly skeptical about the Colorado study’s findings that parent vaccine attitudes have changed little since the pandemic. At the AAP’s annual conference in October 2023, Dr. Offit asked pediatricians about their experiences while he signed books.
“I would ask, ‘So what’s it like out there? Are we winning or losing?’ ” he said. “I would say, to a person, everyone said they felt things were much worse now than they ever have been before.”
Clinical Guidance
The new report reviews previously published evidence on the spectrum of parental vaccine acceptance — from supporters and “go along to get along” parents to cautious acceptors and fence sitters to vaccine refusers — and the determinants that contribute to hesitancy. They also noted the social inequities that have played a role in vaccine uptake disparities.
“Distrust of health systems based on historic and ongoing discrimination and inequitable access to care are intertwined challenges that contribute to racial and ethnic disparities in vaccine uptake,” the authors wrote. “Although there has been progress in reducing racial, ethnic, and socioeconomic disparities in childhood vaccination coverage, the COVID-19 pandemic made clear how much work is yet to be done.”
The report also reviewed the societal, individual, payer and pediatric practice costs of vaccine refusal. The 1-year cost to taxpayers from the measles outbreak in New York City in 2018-2019, for example, was $8.4 million, excluding vaccination programs.
The report provides background information to equip pediatricians for conversations with parents about vaccines. Since safety is the top concern for vaccine hesitancy among parents, the authors advised pediatricians to be familiar with the process of vaccine testing, emergency use authorization, licensure, approval, recommendations, and safety monitoring, including the Vaccine Safety Datalink, the Vaccine Adverse Event Reporting System (VAERS), the FDA’s Biologics Effectiveness and Safety (BEST) system, and the CDC’s Clinical Immunization Safety Assessment Project (CISA).
“Because vaccines are generally given to healthy individuals to prevent disease, they are held to a higher safety standard than other medications,” the authors wrote before providing a summary of the process for physicians to reference. The report also includes information on vaccine ingredients and a chart of common misconceptions about vaccines with the corresponding facts.
Overcoming Hesitancy
Evidence-based strategies for increasing childhood vaccine uptake begin with a strong vaccine recommendation using a presumptive rather than participatory approach, the authors wrote. “A presumptive format is one in which the clinician asserts a position regarding vaccines using a closed-ended statement, such as ‘Sara is due for several vaccines today’ or ‘Well, we have to do some shots,’ ” the authors wrote. “This strategy is in contrast to a participatory format, in which an open-ended question is used to more explicitly invite the parent to voice an opinion, such as ‘How do you feel about vaccines today?’ ” The presumptive format and a strong recommendation are both associated with greater uptake, evidence shows.
For parents who express hesitancy, the authors provide a summary of additional evidence-based communication strategies, starting with motivational interviewing. Two other strategies they highlight include using language to re-emphasize the importance of adhering to the CDC recommended schedule — “He really needs these shots” — and bundling discussion of all recommended vaccines for a visit at once.
“Finally, clinicians can emphasize their own experiences when discussing the need for vaccination, including personal experience with vaccine-preventable diseases and the fact that they and their families are vaccinated because of their confidence in the safety and efficacy of the vaccines,” the authors wrote.
For families who refuse or delay vaccines, the authors reviewed the “ethical arguments both in favor of and against dismissal policies,” noting that nearly all pediatricians who report dismissing families who refuse vaccination are in private practice, since large systems are often unable to dismiss patients. They also point out that fewer pediatricians dismiss families for spreading out vaccines than outright refusing all vaccines.
”Dismissal of child patients of vaccine-refusing parents can be a difficult decision arrived at after considering multiple factors and documented attempts to counsel vaccine-refusing families,” they wrote. “However, if repeated attempts to help understand and address parental values and vaccine concerns fails to engender trust, move parents toward vaccine acceptance, or strengthen the therapeutic alliance, dismissal can be an acceptable option.”
Finally, the authors reminded pediatricians “that vaccine-hesitant parents are a heterogeneous group and that specific parental vaccine concerns need to be individually identified and addressed.” Working with families to discuss their questions and concerns is an opportunity to “build rapport and trust with a family,” they wrote, ”and, ultimately, protect their children from the scourge of vaccine-preventable diseases.”
The focus groups study was funded by the National Institutes of Health, and the authors reported having no disclosures. The Colorado attitudes study used no external funding, and the authors reported no disclosures. The new clinical report used no external funding, and the authors reported no disclosures. Dr. Orenstein is an uncompensated member of the Moderna Scientific Advisory Board. Dr. Offit codeveloped a licensed rotavirus vaccine, but he does not receive any royalties or own a patent for that.
The measles outbreak in Florida, occurring just as health officials announced an official end to Philadelphia’s measles outbreak and rising global cases, has cast attention once again on concerns about vaccine hesitancy. In the midst of Florida’s surgeon general avoiding measles vaccination recommendations for parents, the American Academy of Pediatrics has updated its clinical guidance on vaccine communication.
“Disruption to routine pediatric vaccination during the COVID-19 pandemic has left many children vulnerable to vaccine-preventable diseases and more locations susceptible to outbreaks in the United States and around the world,” Sean T. O’Leary, MD, MPH, a pediatric infectious diseases specialist and associate professor of pediatrics at the University of Colorado in Aurora, and his colleagues, wrote in the new report, published in the March issue of Pediatrics. “Geographic clustering of vaccine refusal further increases the risk of communicable disease outbreaks in certain communities even when vaccination rates at a state or national level remain high overall.”
The authors note that disease resurgence may bolster vaccine uptake, with media coverage of recent outbreaks linked to more pro-vaccine discussions and attitudes among parents. But the evidence on that remains inconclusive, and the authors point out the slow uptake in COVID-19 vaccination as parents navigate ongoing spread of both the disease and vaccine misinformation.
Conflicting Evidence on Postpandemic Attitudes
It remains unclear how parent attitudes toward vaccines have shifted, if at all, since the pandemic. A study published in Pediatrics from October 2023, which Dr. O’Leary also coauthored, analyzed data from an online survey of Colorado mothers between 2018 and 2021 and found no significant difference in vaccine hesitancy during the pandemic compared with pre-pandemic.
Among 3,553 respondents, 1 in 5 (20.4%) were vaccine hesitant overall. Though parents were twice as likely to feel uncertain in trusting vaccine information after the COVID-19 vaccines were authorized (adjusted odds ratio [aOR] 2.14), they were half as likely to be unsure about hesitancy toward childhood vaccines (aOR 0.48).
Another study in Pediatrics from October 2023 found that common concerns about COVID-19 vaccines among parents included infertility, long-term effects from the vaccines, and effects on preexisting medical conditions. But even then, participants in focus groups “expressed that they would listen to their doctor for information about COVID-19 vaccines,” wrote Aubree Honcoop, MPS, of the University of Nebraska Medical Center in Omaha, and her colleagues.
“I think what we’re seeing, very importantly, is that physicians seem to be the source people rely on,” said Walter Orenstein, MD, professor of medicine and associate director of the Emory Vaccine Center at Emory University in Atlanta. “But we need to give the physicians time and incentives to spend time with families,” such as a billing code for vaccine counseling, he said.
Dr. Orenstein was surprised to see the results from Colorado, but he noted they were from a small survey in a single state. He pointed to other findings, such as those from the University of Pennsylvania’s Annenberg Public Policy Center in November 2023, that found lower confidence overall among Americans toward vaccines.
Paul Offit, MD, director of the Vaccine Education Center and an attending infectious disease physician at Children’s Hospital of Philadelphia, where the city’s measles outbreak began, is similarly skeptical about the Colorado study’s findings that parent vaccine attitudes have changed little since the pandemic. At the AAP’s annual conference in October 2023, Dr. Offit asked pediatricians about their experiences while he signed books.
“I would ask, ‘So what’s it like out there? Are we winning or losing?’ ” he said. “I would say, to a person, everyone said they felt things were much worse now than they ever have been before.”
Clinical Guidance
The new report reviews previously published evidence on the spectrum of parental vaccine acceptance — from supporters and “go along to get along” parents to cautious acceptors and fence sitters to vaccine refusers — and the determinants that contribute to hesitancy. They also noted the social inequities that have played a role in vaccine uptake disparities.
“Distrust of health systems based on historic and ongoing discrimination and inequitable access to care are intertwined challenges that contribute to racial and ethnic disparities in vaccine uptake,” the authors wrote. “Although there has been progress in reducing racial, ethnic, and socioeconomic disparities in childhood vaccination coverage, the COVID-19 pandemic made clear how much work is yet to be done.”
The report also reviewed the societal, individual, payer and pediatric practice costs of vaccine refusal. The 1-year cost to taxpayers from the measles outbreak in New York City in 2018-2019, for example, was $8.4 million, excluding vaccination programs.
The report provides background information to equip pediatricians for conversations with parents about vaccines. Since safety is the top concern for vaccine hesitancy among parents, the authors advised pediatricians to be familiar with the process of vaccine testing, emergency use authorization, licensure, approval, recommendations, and safety monitoring, including the Vaccine Safety Datalink, the Vaccine Adverse Event Reporting System (VAERS), the FDA’s Biologics Effectiveness and Safety (BEST) system, and the CDC’s Clinical Immunization Safety Assessment Project (CISA).
“Because vaccines are generally given to healthy individuals to prevent disease, they are held to a higher safety standard than other medications,” the authors wrote before providing a summary of the process for physicians to reference. The report also includes information on vaccine ingredients and a chart of common misconceptions about vaccines with the corresponding facts.
Overcoming Hesitancy
Evidence-based strategies for increasing childhood vaccine uptake begin with a strong vaccine recommendation using a presumptive rather than participatory approach, the authors wrote. “A presumptive format is one in which the clinician asserts a position regarding vaccines using a closed-ended statement, such as ‘Sara is due for several vaccines today’ or ‘Well, we have to do some shots,’ ” the authors wrote. “This strategy is in contrast to a participatory format, in which an open-ended question is used to more explicitly invite the parent to voice an opinion, such as ‘How do you feel about vaccines today?’ ” The presumptive format and a strong recommendation are both associated with greater uptake, evidence shows.
For parents who express hesitancy, the authors provide a summary of additional evidence-based communication strategies, starting with motivational interviewing. Two other strategies they highlight include using language to re-emphasize the importance of adhering to the CDC recommended schedule — “He really needs these shots” — and bundling discussion of all recommended vaccines for a visit at once.
“Finally, clinicians can emphasize their own experiences when discussing the need for vaccination, including personal experience with vaccine-preventable diseases and the fact that they and their families are vaccinated because of their confidence in the safety and efficacy of the vaccines,” the authors wrote.
For families who refuse or delay vaccines, the authors reviewed the “ethical arguments both in favor of and against dismissal policies,” noting that nearly all pediatricians who report dismissing families who refuse vaccination are in private practice, since large systems are often unable to dismiss patients. They also point out that fewer pediatricians dismiss families for spreading out vaccines than outright refusing all vaccines.
”Dismissal of child patients of vaccine-refusing parents can be a difficult decision arrived at after considering multiple factors and documented attempts to counsel vaccine-refusing families,” they wrote. “However, if repeated attempts to help understand and address parental values and vaccine concerns fails to engender trust, move parents toward vaccine acceptance, or strengthen the therapeutic alliance, dismissal can be an acceptable option.”
Finally, the authors reminded pediatricians “that vaccine-hesitant parents are a heterogeneous group and that specific parental vaccine concerns need to be individually identified and addressed.” Working with families to discuss their questions and concerns is an opportunity to “build rapport and trust with a family,” they wrote, ”and, ultimately, protect their children from the scourge of vaccine-preventable diseases.”
The focus groups study was funded by the National Institutes of Health, and the authors reported having no disclosures. The Colorado attitudes study used no external funding, and the authors reported no disclosures. The new clinical report used no external funding, and the authors reported no disclosures. Dr. Orenstein is an uncompensated member of the Moderna Scientific Advisory Board. Dr. Offit codeveloped a licensed rotavirus vaccine, but he does not receive any royalties or own a patent for that.
FROM PEDIATRICS
Bigfoot, Bermuda Triangle, ‘No Lido With Epi’?
“Fingers, toes, ears, and nose are places where epinephrine never goes,” Thomas Ehlers, DPM, wrote in Podiatry Today. “That is an adage I heard during podiatry school, my clerkships, and from various attendings throughout my training.”
But as Dr. Ehlers added, epinephrine gets a bad rap. The catchy admonition “has been proven a myth time and time again.”
So Although medical trainees across multiple disciplines are taught to fear the practice, citing the potential for gangrene, its reputation for harm is not supported by the evidence.
Lack of Feeling Doesn’t Care About Your Facts
The debate surfaced anew in response to a recent column by Kenny Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency, in Lancaster, Pennsylvania, about the rather pedestrian topic of why he no longer performs surgery to correct ingrown toenails. Dr. Lin’s admission that he used to do the procedure with a combination of epinephrine and lidocaine turned into a major focus of the comments — many of them harshly critical of the practice:
“Epinephrine is not an appropriate drug to use for podiatry or use in any peripheral area. Gangrene?” one commenter posted.
“Leave epi out of lidocaine to fingers, toes, nose, and ear lobes,” another wrote.
“No lido with epi, whether or not it is contraindicated, because: If there’s any adverse outcome, a lawyer will find plenty of references saying it was contraindicated,” a reader chimed in.
Other commenters disagreed, with one saying, “Please, folks, don’t show that you trained 50 years ago and haven’t changed practice since…”
For Dr. Lin, the response was surprising given what he believes to be the lack of evidence supporting the purported dangers.
“When I think about this, it’s something that was taught to me during residency — that they should not be used on certain areas,” Dr. Lin said. “But since then, studies have been published looking at thousands of cases of people using epinephrine with lidocaine and haven’t found any cases of necrosis.”
Many doctors, like Dr. Lin, say they were cautioned against this in their training. Others don’t remember exactly where they’ve heard it but recognize the idea has a nebulous hold on practice.
Combining epinephrine with lidocaine helps make the numbing last longer, stops bleeding, and reduces the use of lidocaine required, all of which improve the chances of an effective and comfortable intervention for the patient, Dr. Lin said. The approach also reduces the use of tourniquets, which come with their own risks including nerve injury.
However, in areas with limited circulation, this vasoconstrictive effect may be more pronounced, potentially leading to complications for patients with complicating factors.
Clinicians who regularly use the combination of epinephrine and lidocaine for surgery do concede that it can pose certain hazards and considerations in areas without robust blood flow.
But the literature largely points to its safety.
In 2001, California-based plastic and reconstructive surgeon Keith Denkler, MD, published a deep dive on the topic starting in the 19th century, including a review of Index Medicus from 1880 to 1966, a computer review of the National Library of Medicine database from 1966 to 2000, and major textbooks from 1900 to 2000.
He found a total of 48 cases of digital gangrene — but most involved the use of cocaine or procaine. Of the 48 cases, 21 involved the use of epinephrine, and 17 used an unknown concentration based on manual dilution.
“Multiple other concurrent conditions (hot soaks, tight tourniquets, and infection) existed in these case reports, making it difficult to determine the exact cause of the tissue insult,” Dr. Denkler wrote.
In a 2010 retrospective review in the Journal of the American Society of Plastic Surgeons, authors examined 1111 cases involving digital and hand surgery. Of the 611 patients who received injections of 1% lidocaine with epinephrine, none experienced digital necrosis.
Another review from 2003 touted the combination’s safety, in hopes to “help dispel the myth that epinephrine has no place in podiatric anesthesia.” But authors noted limitations of use, including “known sensitivity, thyrotoxicosis, and use of either tricyclic antidepressants or monoamine oxidase inhibitors.”
James Christina, DPM, executive director and CEO of the American Podiatric Medical Association, echoed that sentiment. He said he regularly used the combination to correct bunions, hammer toes, and ingrown toenails over his 20 years of practicing but acknowledged the technique is not appropriate for all such patients.
“There’s always been caution when using epinephrine with local anesthetic,” Dr. Christina told this news organization. “You need a healthy patient with normal circulation and no other complications; someone without vascular compromise.”
Marie Hanna, MD, MEHP, chief of regional anesthesia and acute pain management at Johns Hopkins University, Baltimore, counts herself among the cautious. Citing Principles of Office Anesthesia: Part I. Infiltrative Anesthesia, Dr. Hanna said epinephrine should never be used in digital and penile blocks or in skin flaps with marginal viability.
“It is perfectly fine in certain areas, like the wrist or the arm,” Dr. Hanna said. “But specifically for use in end organs like nose, fingers, ears, toes — all of these with tenuous blood supply — it is not good practice.”
The divide among doctors comes down to theoretical concern, rather than empirical basis, said Rebecca Johnson, MD, chair of the American Society of Anesthesiologists committee on Regional Anesthesia and Acute Pain Medicine and a faculty member at Mayo Clinic, in Rochester, Minnesota.
“It’s just one of those myths we have in practice,” she said.
And legally, Dr. Johnson noted, the mere existence of a myth can be enough of a deterrent for medical practitioners: “Like anything, when you’re trying to do the right thing, if a complication would occur for another reason, you’d want to make sure a jury of your peers didn’t bring up that myth.”
The sources in this story reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
“Fingers, toes, ears, and nose are places where epinephrine never goes,” Thomas Ehlers, DPM, wrote in Podiatry Today. “That is an adage I heard during podiatry school, my clerkships, and from various attendings throughout my training.”
But as Dr. Ehlers added, epinephrine gets a bad rap. The catchy admonition “has been proven a myth time and time again.”
So Although medical trainees across multiple disciplines are taught to fear the practice, citing the potential for gangrene, its reputation for harm is not supported by the evidence.
Lack of Feeling Doesn’t Care About Your Facts
The debate surfaced anew in response to a recent column by Kenny Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency, in Lancaster, Pennsylvania, about the rather pedestrian topic of why he no longer performs surgery to correct ingrown toenails. Dr. Lin’s admission that he used to do the procedure with a combination of epinephrine and lidocaine turned into a major focus of the comments — many of them harshly critical of the practice:
“Epinephrine is not an appropriate drug to use for podiatry or use in any peripheral area. Gangrene?” one commenter posted.
“Leave epi out of lidocaine to fingers, toes, nose, and ear lobes,” another wrote.
“No lido with epi, whether or not it is contraindicated, because: If there’s any adverse outcome, a lawyer will find plenty of references saying it was contraindicated,” a reader chimed in.
Other commenters disagreed, with one saying, “Please, folks, don’t show that you trained 50 years ago and haven’t changed practice since…”
For Dr. Lin, the response was surprising given what he believes to be the lack of evidence supporting the purported dangers.
“When I think about this, it’s something that was taught to me during residency — that they should not be used on certain areas,” Dr. Lin said. “But since then, studies have been published looking at thousands of cases of people using epinephrine with lidocaine and haven’t found any cases of necrosis.”
Many doctors, like Dr. Lin, say they were cautioned against this in their training. Others don’t remember exactly where they’ve heard it but recognize the idea has a nebulous hold on practice.
Combining epinephrine with lidocaine helps make the numbing last longer, stops bleeding, and reduces the use of lidocaine required, all of which improve the chances of an effective and comfortable intervention for the patient, Dr. Lin said. The approach also reduces the use of tourniquets, which come with their own risks including nerve injury.
However, in areas with limited circulation, this vasoconstrictive effect may be more pronounced, potentially leading to complications for patients with complicating factors.
Clinicians who regularly use the combination of epinephrine and lidocaine for surgery do concede that it can pose certain hazards and considerations in areas without robust blood flow.
But the literature largely points to its safety.
In 2001, California-based plastic and reconstructive surgeon Keith Denkler, MD, published a deep dive on the topic starting in the 19th century, including a review of Index Medicus from 1880 to 1966, a computer review of the National Library of Medicine database from 1966 to 2000, and major textbooks from 1900 to 2000.
He found a total of 48 cases of digital gangrene — but most involved the use of cocaine or procaine. Of the 48 cases, 21 involved the use of epinephrine, and 17 used an unknown concentration based on manual dilution.
“Multiple other concurrent conditions (hot soaks, tight tourniquets, and infection) existed in these case reports, making it difficult to determine the exact cause of the tissue insult,” Dr. Denkler wrote.
In a 2010 retrospective review in the Journal of the American Society of Plastic Surgeons, authors examined 1111 cases involving digital and hand surgery. Of the 611 patients who received injections of 1% lidocaine with epinephrine, none experienced digital necrosis.
Another review from 2003 touted the combination’s safety, in hopes to “help dispel the myth that epinephrine has no place in podiatric anesthesia.” But authors noted limitations of use, including “known sensitivity, thyrotoxicosis, and use of either tricyclic antidepressants or monoamine oxidase inhibitors.”
James Christina, DPM, executive director and CEO of the American Podiatric Medical Association, echoed that sentiment. He said he regularly used the combination to correct bunions, hammer toes, and ingrown toenails over his 20 years of practicing but acknowledged the technique is not appropriate for all such patients.
“There’s always been caution when using epinephrine with local anesthetic,” Dr. Christina told this news organization. “You need a healthy patient with normal circulation and no other complications; someone without vascular compromise.”
Marie Hanna, MD, MEHP, chief of regional anesthesia and acute pain management at Johns Hopkins University, Baltimore, counts herself among the cautious. Citing Principles of Office Anesthesia: Part I. Infiltrative Anesthesia, Dr. Hanna said epinephrine should never be used in digital and penile blocks or in skin flaps with marginal viability.
“It is perfectly fine in certain areas, like the wrist or the arm,” Dr. Hanna said. “But specifically for use in end organs like nose, fingers, ears, toes — all of these with tenuous blood supply — it is not good practice.”
The divide among doctors comes down to theoretical concern, rather than empirical basis, said Rebecca Johnson, MD, chair of the American Society of Anesthesiologists committee on Regional Anesthesia and Acute Pain Medicine and a faculty member at Mayo Clinic, in Rochester, Minnesota.
“It’s just one of those myths we have in practice,” she said.
And legally, Dr. Johnson noted, the mere existence of a myth can be enough of a deterrent for medical practitioners: “Like anything, when you’re trying to do the right thing, if a complication would occur for another reason, you’d want to make sure a jury of your peers didn’t bring up that myth.”
The sources in this story reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
“Fingers, toes, ears, and nose are places where epinephrine never goes,” Thomas Ehlers, DPM, wrote in Podiatry Today. “That is an adage I heard during podiatry school, my clerkships, and from various attendings throughout my training.”
But as Dr. Ehlers added, epinephrine gets a bad rap. The catchy admonition “has been proven a myth time and time again.”
So Although medical trainees across multiple disciplines are taught to fear the practice, citing the potential for gangrene, its reputation for harm is not supported by the evidence.
Lack of Feeling Doesn’t Care About Your Facts
The debate surfaced anew in response to a recent column by Kenny Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency, in Lancaster, Pennsylvania, about the rather pedestrian topic of why he no longer performs surgery to correct ingrown toenails. Dr. Lin’s admission that he used to do the procedure with a combination of epinephrine and lidocaine turned into a major focus of the comments — many of them harshly critical of the practice:
“Epinephrine is not an appropriate drug to use for podiatry or use in any peripheral area. Gangrene?” one commenter posted.
“Leave epi out of lidocaine to fingers, toes, nose, and ear lobes,” another wrote.
“No lido with epi, whether or not it is contraindicated, because: If there’s any adverse outcome, a lawyer will find plenty of references saying it was contraindicated,” a reader chimed in.
Other commenters disagreed, with one saying, “Please, folks, don’t show that you trained 50 years ago and haven’t changed practice since…”
For Dr. Lin, the response was surprising given what he believes to be the lack of evidence supporting the purported dangers.
“When I think about this, it’s something that was taught to me during residency — that they should not be used on certain areas,” Dr. Lin said. “But since then, studies have been published looking at thousands of cases of people using epinephrine with lidocaine and haven’t found any cases of necrosis.”
Many doctors, like Dr. Lin, say they were cautioned against this in their training. Others don’t remember exactly where they’ve heard it but recognize the idea has a nebulous hold on practice.
Combining epinephrine with lidocaine helps make the numbing last longer, stops bleeding, and reduces the use of lidocaine required, all of which improve the chances of an effective and comfortable intervention for the patient, Dr. Lin said. The approach also reduces the use of tourniquets, which come with their own risks including nerve injury.
However, in areas with limited circulation, this vasoconstrictive effect may be more pronounced, potentially leading to complications for patients with complicating factors.
Clinicians who regularly use the combination of epinephrine and lidocaine for surgery do concede that it can pose certain hazards and considerations in areas without robust blood flow.
But the literature largely points to its safety.
In 2001, California-based plastic and reconstructive surgeon Keith Denkler, MD, published a deep dive on the topic starting in the 19th century, including a review of Index Medicus from 1880 to 1966, a computer review of the National Library of Medicine database from 1966 to 2000, and major textbooks from 1900 to 2000.
He found a total of 48 cases of digital gangrene — but most involved the use of cocaine or procaine. Of the 48 cases, 21 involved the use of epinephrine, and 17 used an unknown concentration based on manual dilution.
“Multiple other concurrent conditions (hot soaks, tight tourniquets, and infection) existed in these case reports, making it difficult to determine the exact cause of the tissue insult,” Dr. Denkler wrote.
In a 2010 retrospective review in the Journal of the American Society of Plastic Surgeons, authors examined 1111 cases involving digital and hand surgery. Of the 611 patients who received injections of 1% lidocaine with epinephrine, none experienced digital necrosis.
Another review from 2003 touted the combination’s safety, in hopes to “help dispel the myth that epinephrine has no place in podiatric anesthesia.” But authors noted limitations of use, including “known sensitivity, thyrotoxicosis, and use of either tricyclic antidepressants or monoamine oxidase inhibitors.”
James Christina, DPM, executive director and CEO of the American Podiatric Medical Association, echoed that sentiment. He said he regularly used the combination to correct bunions, hammer toes, and ingrown toenails over his 20 years of practicing but acknowledged the technique is not appropriate for all such patients.
“There’s always been caution when using epinephrine with local anesthetic,” Dr. Christina told this news organization. “You need a healthy patient with normal circulation and no other complications; someone without vascular compromise.”
Marie Hanna, MD, MEHP, chief of regional anesthesia and acute pain management at Johns Hopkins University, Baltimore, counts herself among the cautious. Citing Principles of Office Anesthesia: Part I. Infiltrative Anesthesia, Dr. Hanna said epinephrine should never be used in digital and penile blocks or in skin flaps with marginal viability.
“It is perfectly fine in certain areas, like the wrist or the arm,” Dr. Hanna said. “But specifically for use in end organs like nose, fingers, ears, toes — all of these with tenuous blood supply — it is not good practice.”
The divide among doctors comes down to theoretical concern, rather than empirical basis, said Rebecca Johnson, MD, chair of the American Society of Anesthesiologists committee on Regional Anesthesia and Acute Pain Medicine and a faculty member at Mayo Clinic, in Rochester, Minnesota.
“It’s just one of those myths we have in practice,” she said.
And legally, Dr. Johnson noted, the mere existence of a myth can be enough of a deterrent for medical practitioners: “Like anything, when you’re trying to do the right thing, if a complication would occur for another reason, you’d want to make sure a jury of your peers didn’t bring up that myth.”
The sources in this story reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
Thyroid Disorders and Gynecologic Cancers: Is There a Link?
TOPLINE:
METHODOLOGY:
- Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
- This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
- Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
- The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.
TAKEAWAY:
- Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
- The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
- The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
- A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.
IN PRACTICE:
The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.
SOURCE:
This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.
LIMITATIONS:
The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.
DISCLOSURES:
This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
- This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
- Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
- The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.
TAKEAWAY:
- Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
- The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
- The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
- A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.
IN PRACTICE:
The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.
SOURCE:
This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.
LIMITATIONS:
The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.
DISCLOSURES:
This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
- This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
- Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
- The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.
TAKEAWAY:
- Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
- The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
- The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
- A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.
IN PRACTICE:
The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.
SOURCE:
This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.
LIMITATIONS:
The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.
DISCLOSURES:
This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.
A version of this article appeared on Medscape.com.
Oral Herpes Tied to Double Dementia Risk in Older Adults
TOPLINE:
A history of herpes simplex virus (HSV) is associated with a more than doubling of the risk for dementia in older people, results of a prospective epidemiological study showed.
METHODOLOGY:
- The study included 1002 dementia-free 70-year-olds from the Prospective Investigation of Vasculature in Uppsala Seniors cohort who were assessed at baseline and at age 75 and 80 years and followed through medical records at age 85 years.
- Researchers collected and analyzed blood samples to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels and apolipoprotein epsilon 4 (APOE 4) status of participants.
- Investigators collected information on anti-herpesvirus drug treatment and reviewed dementia diagnoses obtained from medical records to classify as established or probable dementia or Alzheimer’s disease (AD).
TAKEAWAY:
- 82% of participants were anti-HSV IgG carriers, of which 6% had received drug treatment for herpes virus, and 7% of participants developed all-cause dementia and 4% AD during the median 15-year follow up.
- In HSV and HSV-1 subsamples, treatment for herpes virus was not significantly associated with lower risks for AD (HR, 1.46, P = .532 and HR, 1.64; P = .419, respectively) or dementia (HR 1.70; P = .222 and HR, 1.60; P = .320, respectively).
- There was no significant interaction between anti-HSV IgG seroprevalence and APOE 4 with regard to dementia risk, likely due to underpowering, and there were no associations between anti-CMV IgG positivity or anti-HSV IgM positivity and AD or dementia.
IN PRACTICE:
“What’s special about this particular study is that the participants are roughly the same age, which makes the results even more reliable since age differences, which are otherwise linked to the development of dementia, cannot confuse the results,” lead author Erika Vestin, a medical student in the Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Sweden, said in a press release. Findings may drive dementia research further towards treating the illness at an early stage using common anti-herpes virus drugs, Ms. Vestin added.
SOURCE:
The study, with Ms. Vestin as lead author, was published online on February 14, 2024, in the Journal of Alzheimer’s Disease.
LIMITATIONS:
The study underrepresented people with diabetes, heart failure, and stroke and lacked information on treatment compliance, dosage, and length and number of prescriptions, which prevented analysis of dose dependency. Since dementia data collection relied on medical records, dementia cases may be underreported. Some cases of AD could have been misclassified as vascular dementia or other dementia.
DISCLOSURES:
The study was supported by the Gun and Bertil Stohne’s Foundation, Swedish Dementia Association, Swedish Society of Medicine, Märta Lundqvist Foundation, Thureus Foundation, Region Uppsala, Gamla Tjänarinnor Foundation, and Swedish Brain Foundation. The authors had no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
A history of herpes simplex virus (HSV) is associated with a more than doubling of the risk for dementia in older people, results of a prospective epidemiological study showed.
METHODOLOGY:
- The study included 1002 dementia-free 70-year-olds from the Prospective Investigation of Vasculature in Uppsala Seniors cohort who were assessed at baseline and at age 75 and 80 years and followed through medical records at age 85 years.
- Researchers collected and analyzed blood samples to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels and apolipoprotein epsilon 4 (APOE 4) status of participants.
- Investigators collected information on anti-herpesvirus drug treatment and reviewed dementia diagnoses obtained from medical records to classify as established or probable dementia or Alzheimer’s disease (AD).
TAKEAWAY:
- 82% of participants were anti-HSV IgG carriers, of which 6% had received drug treatment for herpes virus, and 7% of participants developed all-cause dementia and 4% AD during the median 15-year follow up.
- In HSV and HSV-1 subsamples, treatment for herpes virus was not significantly associated with lower risks for AD (HR, 1.46, P = .532 and HR, 1.64; P = .419, respectively) or dementia (HR 1.70; P = .222 and HR, 1.60; P = .320, respectively).
- There was no significant interaction between anti-HSV IgG seroprevalence and APOE 4 with regard to dementia risk, likely due to underpowering, and there were no associations between anti-CMV IgG positivity or anti-HSV IgM positivity and AD or dementia.
IN PRACTICE:
“What’s special about this particular study is that the participants are roughly the same age, which makes the results even more reliable since age differences, which are otherwise linked to the development of dementia, cannot confuse the results,” lead author Erika Vestin, a medical student in the Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Sweden, said in a press release. Findings may drive dementia research further towards treating the illness at an early stage using common anti-herpes virus drugs, Ms. Vestin added.
SOURCE:
The study, with Ms. Vestin as lead author, was published online on February 14, 2024, in the Journal of Alzheimer’s Disease.
LIMITATIONS:
The study underrepresented people with diabetes, heart failure, and stroke and lacked information on treatment compliance, dosage, and length and number of prescriptions, which prevented analysis of dose dependency. Since dementia data collection relied on medical records, dementia cases may be underreported. Some cases of AD could have been misclassified as vascular dementia or other dementia.
DISCLOSURES:
The study was supported by the Gun and Bertil Stohne’s Foundation, Swedish Dementia Association, Swedish Society of Medicine, Märta Lundqvist Foundation, Thureus Foundation, Region Uppsala, Gamla Tjänarinnor Foundation, and Swedish Brain Foundation. The authors had no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
A history of herpes simplex virus (HSV) is associated with a more than doubling of the risk for dementia in older people, results of a prospective epidemiological study showed.
METHODOLOGY:
- The study included 1002 dementia-free 70-year-olds from the Prospective Investigation of Vasculature in Uppsala Seniors cohort who were assessed at baseline and at age 75 and 80 years and followed through medical records at age 85 years.
- Researchers collected and analyzed blood samples to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels and apolipoprotein epsilon 4 (APOE 4) status of participants.
- Investigators collected information on anti-herpesvirus drug treatment and reviewed dementia diagnoses obtained from medical records to classify as established or probable dementia or Alzheimer’s disease (AD).
TAKEAWAY:
- 82% of participants were anti-HSV IgG carriers, of which 6% had received drug treatment for herpes virus, and 7% of participants developed all-cause dementia and 4% AD during the median 15-year follow up.
- In HSV and HSV-1 subsamples, treatment for herpes virus was not significantly associated with lower risks for AD (HR, 1.46, P = .532 and HR, 1.64; P = .419, respectively) or dementia (HR 1.70; P = .222 and HR, 1.60; P = .320, respectively).
- There was no significant interaction between anti-HSV IgG seroprevalence and APOE 4 with regard to dementia risk, likely due to underpowering, and there were no associations between anti-CMV IgG positivity or anti-HSV IgM positivity and AD or dementia.
IN PRACTICE:
“What’s special about this particular study is that the participants are roughly the same age, which makes the results even more reliable since age differences, which are otherwise linked to the development of dementia, cannot confuse the results,” lead author Erika Vestin, a medical student in the Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Sweden, said in a press release. Findings may drive dementia research further towards treating the illness at an early stage using common anti-herpes virus drugs, Ms. Vestin added.
SOURCE:
The study, with Ms. Vestin as lead author, was published online on February 14, 2024, in the Journal of Alzheimer’s Disease.
LIMITATIONS:
The study underrepresented people with diabetes, heart failure, and stroke and lacked information on treatment compliance, dosage, and length and number of prescriptions, which prevented analysis of dose dependency. Since dementia data collection relied on medical records, dementia cases may be underreported. Some cases of AD could have been misclassified as vascular dementia or other dementia.
DISCLOSURES:
The study was supported by the Gun and Bertil Stohne’s Foundation, Swedish Dementia Association, Swedish Society of Medicine, Märta Lundqvist Foundation, Thureus Foundation, Region Uppsala, Gamla Tjänarinnor Foundation, and Swedish Brain Foundation. The authors had no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Do Kids With an October Birthday Have Protection From Flu?
TOPLINE:
A new study shows young children with October birthdays may have better protection against flu.
METHODOLOGY:
- Researchers analyzed data from the MarketScan Research Database between 2011 and 2018.
- They focused on 819,223 children aged 2-5 years who were vaccinated against influenza between August 1 and January 31 and whose birthdays fell during that window.
TAKEAWAY:
- Children born in October had the lowest rate of influenza diagnosis, with an average diagnosis rate of 2.7%, whereas those born in August had a diagnosis rate of 3%.
- Compared with children born in August, the adjusted odds ratio for influenza diagnosis in children born in October was 0.88 (95% CI, 0.85-0.92).
IN PRACTICE:
“The findings support current recommendations that children be vaccinated in October preceding a typical influenza season,” the authors of the study wrote.
SOURCE:
Anupam B. Jena, MD, PhD, with Harvard Medical School and Massachusetts General Hospital in Boston, Massachusetts, was the corresponding author on the study. The research was published online in BMJ .
LIMITATIONS:
The availability of the influenza vaccine and the peak of seasonal flu infections vary by year and region.
DISCLOSURES:
Researchers disclosed consulting fees from pharmaceutical and healthcare companies unrelated to the study.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
A new study shows young children with October birthdays may have better protection against flu.
METHODOLOGY:
- Researchers analyzed data from the MarketScan Research Database between 2011 and 2018.
- They focused on 819,223 children aged 2-5 years who were vaccinated against influenza between August 1 and January 31 and whose birthdays fell during that window.
TAKEAWAY:
- Children born in October had the lowest rate of influenza diagnosis, with an average diagnosis rate of 2.7%, whereas those born in August had a diagnosis rate of 3%.
- Compared with children born in August, the adjusted odds ratio for influenza diagnosis in children born in October was 0.88 (95% CI, 0.85-0.92).
IN PRACTICE:
“The findings support current recommendations that children be vaccinated in October preceding a typical influenza season,” the authors of the study wrote.
SOURCE:
Anupam B. Jena, MD, PhD, with Harvard Medical School and Massachusetts General Hospital in Boston, Massachusetts, was the corresponding author on the study. The research was published online in BMJ .
LIMITATIONS:
The availability of the influenza vaccine and the peak of seasonal flu infections vary by year and region.
DISCLOSURES:
Researchers disclosed consulting fees from pharmaceutical and healthcare companies unrelated to the study.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
A new study shows young children with October birthdays may have better protection against flu.
METHODOLOGY:
- Researchers analyzed data from the MarketScan Research Database between 2011 and 2018.
- They focused on 819,223 children aged 2-5 years who were vaccinated against influenza between August 1 and January 31 and whose birthdays fell during that window.
TAKEAWAY:
- Children born in October had the lowest rate of influenza diagnosis, with an average diagnosis rate of 2.7%, whereas those born in August had a diagnosis rate of 3%.
- Compared with children born in August, the adjusted odds ratio for influenza diagnosis in children born in October was 0.88 (95% CI, 0.85-0.92).
IN PRACTICE:
“The findings support current recommendations that children be vaccinated in October preceding a typical influenza season,” the authors of the study wrote.
SOURCE:
Anupam B. Jena, MD, PhD, with Harvard Medical School and Massachusetts General Hospital in Boston, Massachusetts, was the corresponding author on the study. The research was published online in BMJ .
LIMITATIONS:
The availability of the influenza vaccine and the peak of seasonal flu infections vary by year and region.
DISCLOSURES:
Researchers disclosed consulting fees from pharmaceutical and healthcare companies unrelated to the study.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
FDA Removes Harmful Chemicals From Food Packaging
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
B-ALL: CAR-T Outperforms Novel Therapies
“This is the first time there is a real-world comparison of CAR-T cell therapy versus other treatments in the era of other novel therapies such as inotuzumab or tyrosine kinase inhibitors (TKIs),” said first author Alexandros Rampotas, MD, of the University College London Hospital NHS Foundation Trust. “The study was looking retrospectively at patients treated in the UK, but the results should be applicable to most countries where similar treatments are available.”
Dr. Rampotas presented the research at the 6th European CAR T-cell Meeting jointly sponsored by the Society for Blood and Marrow Transplantation and the European Hematology Association.
Outcomes when patients with B-ALL relapse after allo-HCT treatment are generally very poor, and while the advent of CAR T-cell therapy has provided significant improvements, additional novel targeted therapies have also joined the field to further improve outcomes.
With no prior studies directly comparing outcomes between the various treatment options in a real-world setting, Dr. Rampotas and colleagues conducted a retrospective analysis of posttransplant relapsed B-ALL cases at six major transplant centers in the United Kingdom between 2010 and 2022.
Of 93 patients with sufficient data for the analysis, 17 had been treated with CAR T-cell therapy: 4 with UCART19, 1 with CD22 CAR T-cell, and 12 with the CD19-directed CAR T-cell products tisagenlecleucel (Kymriah) or obecabtagene autoleucel (obe-cel).
Among the remaining 75 patients who received non-CAR T-cell therapies, 24 received TKIs, 11 received blinatumumab, 12 received inotuzumab, 10 received intensive chemotherapy, 3 received intensive chemotherapy and TKI therapy, 14 received palliative/supportive regimens and 1 had a second allo-HCT following relapse from the first.
The median time from relapse to treatment was 2.8 months in the CAR T-cell therapy group, and 0.32 months for those receiving non-CAR T-cell therapies.
“The 2.8-month time-to-treat is quite expected as CAR T-cells can take a while to manufacture and be infused,” Dr. Rampotas noted. “This also comes with the bias that the patients who did receive them were likely fitter and could wait for that long.”
Patients receiving CAR T-cell therapy were also younger (median age 26 versus 47 in the non-CAR T-cell group) but the CAR T-cell group had higher risk disease and had a median of 2 prior lines of therapy versus 1 in the non-CAR T-cell group.
With a median follow-up of 24.8 months, patients receiving CAR T-cell therapy had significantly better rates of overall survival (OS), with 31 months compared with the non-CAR T-cell therapy OS of just 6.4 months (P = .0147).
The patients treated with CAR T-cell therapy also had improved progression-free survival (PFS) over the non-CAR T-cell patients (16.7 vs 3.7 months; P = .0001).
The superior outcomes in the CAR T-cell group remained consistent after exclusion of patients who received palliative approaches.
“In the realm of numerous innovative therapies for B-ALL, CAR Ts have now, for the first time, exhibited superior outcomes over alternative approaches in posttransplant relapsed B-ALL in the real world,” the authors reported. “The clear superior PFS and OS should encourage the use of more CAR T-cell therapies for this challenging cohort, while further improvements are imperative to enhance outcomes.”
In the meantime, “patients who relapse post transplant with B-ALL should be referred for CAR-T cell therapy as it is a superior treatment to other available options,” Dr. Rampotas said.
Dr. Rampotas discloses receiving conference fees from Gilead.
“This is the first time there is a real-world comparison of CAR-T cell therapy versus other treatments in the era of other novel therapies such as inotuzumab or tyrosine kinase inhibitors (TKIs),” said first author Alexandros Rampotas, MD, of the University College London Hospital NHS Foundation Trust. “The study was looking retrospectively at patients treated in the UK, but the results should be applicable to most countries where similar treatments are available.”
Dr. Rampotas presented the research at the 6th European CAR T-cell Meeting jointly sponsored by the Society for Blood and Marrow Transplantation and the European Hematology Association.
Outcomes when patients with B-ALL relapse after allo-HCT treatment are generally very poor, and while the advent of CAR T-cell therapy has provided significant improvements, additional novel targeted therapies have also joined the field to further improve outcomes.
With no prior studies directly comparing outcomes between the various treatment options in a real-world setting, Dr. Rampotas and colleagues conducted a retrospective analysis of posttransplant relapsed B-ALL cases at six major transplant centers in the United Kingdom between 2010 and 2022.
Of 93 patients with sufficient data for the analysis, 17 had been treated with CAR T-cell therapy: 4 with UCART19, 1 with CD22 CAR T-cell, and 12 with the CD19-directed CAR T-cell products tisagenlecleucel (Kymriah) or obecabtagene autoleucel (obe-cel).
Among the remaining 75 patients who received non-CAR T-cell therapies, 24 received TKIs, 11 received blinatumumab, 12 received inotuzumab, 10 received intensive chemotherapy, 3 received intensive chemotherapy and TKI therapy, 14 received palliative/supportive regimens and 1 had a second allo-HCT following relapse from the first.
The median time from relapse to treatment was 2.8 months in the CAR T-cell therapy group, and 0.32 months for those receiving non-CAR T-cell therapies.
“The 2.8-month time-to-treat is quite expected as CAR T-cells can take a while to manufacture and be infused,” Dr. Rampotas noted. “This also comes with the bias that the patients who did receive them were likely fitter and could wait for that long.”
Patients receiving CAR T-cell therapy were also younger (median age 26 versus 47 in the non-CAR T-cell group) but the CAR T-cell group had higher risk disease and had a median of 2 prior lines of therapy versus 1 in the non-CAR T-cell group.
With a median follow-up of 24.8 months, patients receiving CAR T-cell therapy had significantly better rates of overall survival (OS), with 31 months compared with the non-CAR T-cell therapy OS of just 6.4 months (P = .0147).
The patients treated with CAR T-cell therapy also had improved progression-free survival (PFS) over the non-CAR T-cell patients (16.7 vs 3.7 months; P = .0001).
The superior outcomes in the CAR T-cell group remained consistent after exclusion of patients who received palliative approaches.
“In the realm of numerous innovative therapies for B-ALL, CAR Ts have now, for the first time, exhibited superior outcomes over alternative approaches in posttransplant relapsed B-ALL in the real world,” the authors reported. “The clear superior PFS and OS should encourage the use of more CAR T-cell therapies for this challenging cohort, while further improvements are imperative to enhance outcomes.”
In the meantime, “patients who relapse post transplant with B-ALL should be referred for CAR-T cell therapy as it is a superior treatment to other available options,” Dr. Rampotas said.
Dr. Rampotas discloses receiving conference fees from Gilead.
“This is the first time there is a real-world comparison of CAR-T cell therapy versus other treatments in the era of other novel therapies such as inotuzumab or tyrosine kinase inhibitors (TKIs),” said first author Alexandros Rampotas, MD, of the University College London Hospital NHS Foundation Trust. “The study was looking retrospectively at patients treated in the UK, but the results should be applicable to most countries where similar treatments are available.”
Dr. Rampotas presented the research at the 6th European CAR T-cell Meeting jointly sponsored by the Society for Blood and Marrow Transplantation and the European Hematology Association.
Outcomes when patients with B-ALL relapse after allo-HCT treatment are generally very poor, and while the advent of CAR T-cell therapy has provided significant improvements, additional novel targeted therapies have also joined the field to further improve outcomes.
With no prior studies directly comparing outcomes between the various treatment options in a real-world setting, Dr. Rampotas and colleagues conducted a retrospective analysis of posttransplant relapsed B-ALL cases at six major transplant centers in the United Kingdom between 2010 and 2022.
Of 93 patients with sufficient data for the analysis, 17 had been treated with CAR T-cell therapy: 4 with UCART19, 1 with CD22 CAR T-cell, and 12 with the CD19-directed CAR T-cell products tisagenlecleucel (Kymriah) or obecabtagene autoleucel (obe-cel).
Among the remaining 75 patients who received non-CAR T-cell therapies, 24 received TKIs, 11 received blinatumumab, 12 received inotuzumab, 10 received intensive chemotherapy, 3 received intensive chemotherapy and TKI therapy, 14 received palliative/supportive regimens and 1 had a second allo-HCT following relapse from the first.
The median time from relapse to treatment was 2.8 months in the CAR T-cell therapy group, and 0.32 months for those receiving non-CAR T-cell therapies.
“The 2.8-month time-to-treat is quite expected as CAR T-cells can take a while to manufacture and be infused,” Dr. Rampotas noted. “This also comes with the bias that the patients who did receive them were likely fitter and could wait for that long.”
Patients receiving CAR T-cell therapy were also younger (median age 26 versus 47 in the non-CAR T-cell group) but the CAR T-cell group had higher risk disease and had a median of 2 prior lines of therapy versus 1 in the non-CAR T-cell group.
With a median follow-up of 24.8 months, patients receiving CAR T-cell therapy had significantly better rates of overall survival (OS), with 31 months compared with the non-CAR T-cell therapy OS of just 6.4 months (P = .0147).
The patients treated with CAR T-cell therapy also had improved progression-free survival (PFS) over the non-CAR T-cell patients (16.7 vs 3.7 months; P = .0001).
The superior outcomes in the CAR T-cell group remained consistent after exclusion of patients who received palliative approaches.
“In the realm of numerous innovative therapies for B-ALL, CAR Ts have now, for the first time, exhibited superior outcomes over alternative approaches in posttransplant relapsed B-ALL in the real world,” the authors reported. “The clear superior PFS and OS should encourage the use of more CAR T-cell therapies for this challenging cohort, while further improvements are imperative to enhance outcomes.”
In the meantime, “patients who relapse post transplant with B-ALL should be referred for CAR-T cell therapy as it is a superior treatment to other available options,” Dr. Rampotas said.
Dr. Rampotas discloses receiving conference fees from Gilead.
FROM THE 6TH EUROPEAN CAR T-CELL MEETING
Unexpectedly Helpful Effects of Drugs Used For Other Reasons
A 73-year-old man with hypertension is evaluated for right great toe pain. A tap of the toe reveals uric acid crystals. He has a history of hypertension and hyperlipidemia. His current medications are hydrochlorothiazide, amlodipine, and atorvastatin.
Which blood pressure medication would you recommend to replace his hydrochlorothiazide?
A. Furosemide
B. Chlorthalidone
C. Lisinopril
D. Losartan
E. Irbesartan
Losartan
Diuretics should be avoided if possible in a patient with gout, as they increase uric acid levels. Of the other three options, losartan offers the added benefit of lowering uric acid levels. Losartan has uricosuric effects — a property that is unique to losartan of the angiotensin receptor blockers (ARBs) that have been studied.1,2 The uric acid lowering appears to be a probenecid-like effect.
Losartan has also been evaluated to see whether using it in combination with a thiazide diuretic can reduce the rise in uric acid that occurs with thiazides. Matsumura and colleagues looked at data from the COMFORT trial, focusing on the effect of combining losartan with hydrochlorothiazide on uric acid levels.3 They looked at a group of 118 patients on an ARB other than losartan plus a diuretic, who were then randomly assigned to losartan 50 mg/hydrochlorothiazide 12.5 mg or continuation of another ARB plus a diuretic. Blood pressure control was the same between groups, but the patients who received the losartan combination had lower uric acid levels (P = .01).
Ferreira and colleagues looked at the difference in uric acid lowering between high-dose (150 mg/day) vs low-dose losartan (50 mg/day).4 Compared with low-dose, high-dose losartan reduced serum uric acid by 0.27 (0.34 to 0.21) mg/dL, P < .001.
SGLT2 inhibitors
SGLT2 inhibitors also lower uric acid. Suijik and colleagues conducted an analysis of two randomized trials of SGLT2 inhibitors (empagliflozin and dapagliflozin), and concluded that SGLT2 inhibitors induce uric acid excretion, which is strongly linked to urinary glucose excretion.5
Metformin
Metformin is used as a firstline drug for the treatment of diabetes. It also has evidence for decreasing colonic polyps. Cho and colleagues looked at over 12,000 patients with diabetes over a 12-year period; 3775 underwent colonoscopies.6 They compared frequency of polyps in patients who were using metformin with those who were not treated with metformin. The polyp detection rate was lower in the metformin group than in the no metformin group (39.4% vs. 62.4%, P < .01).
Higurashi and colleagues performed a double-blind, placebo-controlled trial of metformin in nondiabetic patients for the prevention of colon polyps.7 The dose of metformin used in this study was very low (250 mg/day). There were significantly fewer adenomas in the metformin group (22 of 71 patients) than in the placebo group (32 of 62) (relative risk, 0.60; 95% confidence interval, 0.39-0.92, P = .016).
Thiazide diuretics
Thiazide diuretics have long been used to help prevent kidney stones in addition to treating hypertension. They decrease urinary calcium excretion, which may reduce kidney stones. Could this reduction in calcium excretion be good for bones?
Xiao and colleagues did a meta-analysis of 11 prospective studies involving 2,193,160 participants.8 Thiazide diuretic users had a significant 14% reduction in the risk of all fractures (RR, 0.86; 95% CI, 0.80-0.93; P = .009) and an 18% reduction in the risk of hip fracture (RR, 0.82; 95% CI, 0.80-0.93; P = .009). Kruse and colleagues found that long duration and continuity of thiazide exposure seemed to be important to obtain this protective effect on fracture risk.9
Pearls:
- Losartan, but not other ARBs, lowers uric acid levels and may be helpful in managing hypertension in gout patients; higher doses lower uric acid more.
- Metformin use appears to decrease colon polyp formation.
- Thiazide diuretics may reduce fracture risk while patients are taking them.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Würzner G et al. Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout. J Hypertens. 2001 Oct;19(10):1855-60.
2. Puig JG et al. Effect of eprosartan and losartan on uric acid metabolism in patients with essential hypertension. J Hypertens. 1999 Jul;17(7):1033-9.
3. Matsumura K et al. Effect of losartan on serum uric acid in hypertension treated with a diuretic: The COMFORT study. Clin Exp Hypertens. 2015;37(3):192-6.
4. Ferreira JP et al. High- versus low-dose losartan and uric acid: An analysis from HEAAL. J Cardiol. 2023 Jul;82(1):57-61.
5. Suijk DLS et al. SGLT2 inhibition and uric acid excretion in patients with type 2 diabetes and normal kidney function. Soc Nephrol. 2022 May;17(5):663-71.
6. Youn Hee Cho et al. Does metformin affect the incidence of colonic polyps and adenomas in patients with type 2 diabetes mellitus? Intestinal Res. 2014 Apr;12(2):139-45.
7. Higurashi T et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: A multicentre double-blind, placebo-controlled, randomised phase 3 trial. Lancet Oncol. 2016;17:475-83.
8. Xiao X et al. Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies. Osteoporos Int. 2018 Jul;29(7):1515-24.
9. Kruse C et al. Continuous and long-term treatment is more important than dosage for the protective effect of thiazide use on bone metabolism and fracture risk. J Intern Med. 2016 Jan;279(1):110-22.
A 73-year-old man with hypertension is evaluated for right great toe pain. A tap of the toe reveals uric acid crystals. He has a history of hypertension and hyperlipidemia. His current medications are hydrochlorothiazide, amlodipine, and atorvastatin.
Which blood pressure medication would you recommend to replace his hydrochlorothiazide?
A. Furosemide
B. Chlorthalidone
C. Lisinopril
D. Losartan
E. Irbesartan
Losartan
Diuretics should be avoided if possible in a patient with gout, as they increase uric acid levels. Of the other three options, losartan offers the added benefit of lowering uric acid levels. Losartan has uricosuric effects — a property that is unique to losartan of the angiotensin receptor blockers (ARBs) that have been studied.1,2 The uric acid lowering appears to be a probenecid-like effect.
Losartan has also been evaluated to see whether using it in combination with a thiazide diuretic can reduce the rise in uric acid that occurs with thiazides. Matsumura and colleagues looked at data from the COMFORT trial, focusing on the effect of combining losartan with hydrochlorothiazide on uric acid levels.3 They looked at a group of 118 patients on an ARB other than losartan plus a diuretic, who were then randomly assigned to losartan 50 mg/hydrochlorothiazide 12.5 mg or continuation of another ARB plus a diuretic. Blood pressure control was the same between groups, but the patients who received the losartan combination had lower uric acid levels (P = .01).
Ferreira and colleagues looked at the difference in uric acid lowering between high-dose (150 mg/day) vs low-dose losartan (50 mg/day).4 Compared with low-dose, high-dose losartan reduced serum uric acid by 0.27 (0.34 to 0.21) mg/dL, P < .001.
SGLT2 inhibitors
SGLT2 inhibitors also lower uric acid. Suijik and colleagues conducted an analysis of two randomized trials of SGLT2 inhibitors (empagliflozin and dapagliflozin), and concluded that SGLT2 inhibitors induce uric acid excretion, which is strongly linked to urinary glucose excretion.5
Metformin
Metformin is used as a firstline drug for the treatment of diabetes. It also has evidence for decreasing colonic polyps. Cho and colleagues looked at over 12,000 patients with diabetes over a 12-year period; 3775 underwent colonoscopies.6 They compared frequency of polyps in patients who were using metformin with those who were not treated with metformin. The polyp detection rate was lower in the metformin group than in the no metformin group (39.4% vs. 62.4%, P < .01).
Higurashi and colleagues performed a double-blind, placebo-controlled trial of metformin in nondiabetic patients for the prevention of colon polyps.7 The dose of metformin used in this study was very low (250 mg/day). There were significantly fewer adenomas in the metformin group (22 of 71 patients) than in the placebo group (32 of 62) (relative risk, 0.60; 95% confidence interval, 0.39-0.92, P = .016).
Thiazide diuretics
Thiazide diuretics have long been used to help prevent kidney stones in addition to treating hypertension. They decrease urinary calcium excretion, which may reduce kidney stones. Could this reduction in calcium excretion be good for bones?
Xiao and colleagues did a meta-analysis of 11 prospective studies involving 2,193,160 participants.8 Thiazide diuretic users had a significant 14% reduction in the risk of all fractures (RR, 0.86; 95% CI, 0.80-0.93; P = .009) and an 18% reduction in the risk of hip fracture (RR, 0.82; 95% CI, 0.80-0.93; P = .009). Kruse and colleagues found that long duration and continuity of thiazide exposure seemed to be important to obtain this protective effect on fracture risk.9
Pearls:
- Losartan, but not other ARBs, lowers uric acid levels and may be helpful in managing hypertension in gout patients; higher doses lower uric acid more.
- Metformin use appears to decrease colon polyp formation.
- Thiazide diuretics may reduce fracture risk while patients are taking them.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Würzner G et al. Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout. J Hypertens. 2001 Oct;19(10):1855-60.
2. Puig JG et al. Effect of eprosartan and losartan on uric acid metabolism in patients with essential hypertension. J Hypertens. 1999 Jul;17(7):1033-9.
3. Matsumura K et al. Effect of losartan on serum uric acid in hypertension treated with a diuretic: The COMFORT study. Clin Exp Hypertens. 2015;37(3):192-6.
4. Ferreira JP et al. High- versus low-dose losartan and uric acid: An analysis from HEAAL. J Cardiol. 2023 Jul;82(1):57-61.
5. Suijk DLS et al. SGLT2 inhibition and uric acid excretion in patients with type 2 diabetes and normal kidney function. Soc Nephrol. 2022 May;17(5):663-71.
6. Youn Hee Cho et al. Does metformin affect the incidence of colonic polyps and adenomas in patients with type 2 diabetes mellitus? Intestinal Res. 2014 Apr;12(2):139-45.
7. Higurashi T et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: A multicentre double-blind, placebo-controlled, randomised phase 3 trial. Lancet Oncol. 2016;17:475-83.
8. Xiao X et al. Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies. Osteoporos Int. 2018 Jul;29(7):1515-24.
9. Kruse C et al. Continuous and long-term treatment is more important than dosage for the protective effect of thiazide use on bone metabolism and fracture risk. J Intern Med. 2016 Jan;279(1):110-22.
A 73-year-old man with hypertension is evaluated for right great toe pain. A tap of the toe reveals uric acid crystals. He has a history of hypertension and hyperlipidemia. His current medications are hydrochlorothiazide, amlodipine, and atorvastatin.
Which blood pressure medication would you recommend to replace his hydrochlorothiazide?
A. Furosemide
B. Chlorthalidone
C. Lisinopril
D. Losartan
E. Irbesartan
Losartan
Diuretics should be avoided if possible in a patient with gout, as they increase uric acid levels. Of the other three options, losartan offers the added benefit of lowering uric acid levels. Losartan has uricosuric effects — a property that is unique to losartan of the angiotensin receptor blockers (ARBs) that have been studied.1,2 The uric acid lowering appears to be a probenecid-like effect.
Losartan has also been evaluated to see whether using it in combination with a thiazide diuretic can reduce the rise in uric acid that occurs with thiazides. Matsumura and colleagues looked at data from the COMFORT trial, focusing on the effect of combining losartan with hydrochlorothiazide on uric acid levels.3 They looked at a group of 118 patients on an ARB other than losartan plus a diuretic, who were then randomly assigned to losartan 50 mg/hydrochlorothiazide 12.5 mg or continuation of another ARB plus a diuretic. Blood pressure control was the same between groups, but the patients who received the losartan combination had lower uric acid levels (P = .01).
Ferreira and colleagues looked at the difference in uric acid lowering between high-dose (150 mg/day) vs low-dose losartan (50 mg/day).4 Compared with low-dose, high-dose losartan reduced serum uric acid by 0.27 (0.34 to 0.21) mg/dL, P < .001.
SGLT2 inhibitors
SGLT2 inhibitors also lower uric acid. Suijik and colleagues conducted an analysis of two randomized trials of SGLT2 inhibitors (empagliflozin and dapagliflozin), and concluded that SGLT2 inhibitors induce uric acid excretion, which is strongly linked to urinary glucose excretion.5
Metformin
Metformin is used as a firstline drug for the treatment of diabetes. It also has evidence for decreasing colonic polyps. Cho and colleagues looked at over 12,000 patients with diabetes over a 12-year period; 3775 underwent colonoscopies.6 They compared frequency of polyps in patients who were using metformin with those who were not treated with metformin. The polyp detection rate was lower in the metformin group than in the no metformin group (39.4% vs. 62.4%, P < .01).
Higurashi and colleagues performed a double-blind, placebo-controlled trial of metformin in nondiabetic patients for the prevention of colon polyps.7 The dose of metformin used in this study was very low (250 mg/day). There were significantly fewer adenomas in the metformin group (22 of 71 patients) than in the placebo group (32 of 62) (relative risk, 0.60; 95% confidence interval, 0.39-0.92, P = .016).
Thiazide diuretics
Thiazide diuretics have long been used to help prevent kidney stones in addition to treating hypertension. They decrease urinary calcium excretion, which may reduce kidney stones. Could this reduction in calcium excretion be good for bones?
Xiao and colleagues did a meta-analysis of 11 prospective studies involving 2,193,160 participants.8 Thiazide diuretic users had a significant 14% reduction in the risk of all fractures (RR, 0.86; 95% CI, 0.80-0.93; P = .009) and an 18% reduction in the risk of hip fracture (RR, 0.82; 95% CI, 0.80-0.93; P = .009). Kruse and colleagues found that long duration and continuity of thiazide exposure seemed to be important to obtain this protective effect on fracture risk.9
Pearls:
- Losartan, but not other ARBs, lowers uric acid levels and may be helpful in managing hypertension in gout patients; higher doses lower uric acid more.
- Metformin use appears to decrease colon polyp formation.
- Thiazide diuretics may reduce fracture risk while patients are taking them.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Würzner G et al. Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout. J Hypertens. 2001 Oct;19(10):1855-60.
2. Puig JG et al. Effect of eprosartan and losartan on uric acid metabolism in patients with essential hypertension. J Hypertens. 1999 Jul;17(7):1033-9.
3. Matsumura K et al. Effect of losartan on serum uric acid in hypertension treated with a diuretic: The COMFORT study. Clin Exp Hypertens. 2015;37(3):192-6.
4. Ferreira JP et al. High- versus low-dose losartan and uric acid: An analysis from HEAAL. J Cardiol. 2023 Jul;82(1):57-61.
5. Suijk DLS et al. SGLT2 inhibition and uric acid excretion in patients with type 2 diabetes and normal kidney function. Soc Nephrol. 2022 May;17(5):663-71.
6. Youn Hee Cho et al. Does metformin affect the incidence of colonic polyps and adenomas in patients with type 2 diabetes mellitus? Intestinal Res. 2014 Apr;12(2):139-45.
7. Higurashi T et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: A multicentre double-blind, placebo-controlled, randomised phase 3 trial. Lancet Oncol. 2016;17:475-83.
8. Xiao X et al. Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies. Osteoporos Int. 2018 Jul;29(7):1515-24.
9. Kruse C et al. Continuous and long-term treatment is more important than dosage for the protective effect of thiazide use on bone metabolism and fracture risk. J Intern Med. 2016 Jan;279(1):110-22.
Ebola Vaccine Saves Lives Even After Exposure
The Ervebo vaccine not only reduces the risk for Ebola infection but also halves mortality rates. This is the result of a study published in The Lancet Infectious Diseases.
Rebecca Coulborn, an epidemiologist at Epicentre in Paris, France, and colleagues analyzed data collected during the 10th Ebola epidemic in the Democratic Republic of the Congo. Their analysis revealed that among the 2279 patients with confirmed Ebola who were admitted to an Ebola health facility between July 27, 2018, and April 27, 2020, the mortality risk was 56% for unvaccinated patients. In vaccinated patients, however, it was only 25%. The reduced mortality applied to all patients, regardless of age and gender.
The study was funded by Doctors Without Borders. For data collection, Epicentre, the epidemiological division of Doctors Without Borders, collaborated with the Institut National de Recherche Biomédicale and the Ministry of Health of the Democratic Republic of the Congo.
The study authors focused on the Ervebo vaccine, which is approved for use against Zaire ebolavirus in the European Union, the United States, and some African countries, among others. It is the only Ebola vaccine currently recommended for use during an epidemic. It is administered intramuscularly as a single dose and is approved for adults aged 18 years and older.
The vaccine is primarily recommended for ring vaccination of individuals at a high risk for infection during an epidemic. In studies, the vaccine has been used for ring vaccinations among contacts of diagnosed cases since the end of the Ebola outbreak in West Africa in 2014 and 2015 and since 2018 in the Democratic Republic of the Congo.
The preliminary estimated vaccine effectiveness 10 days after vaccination is 97.5%-100%. The duration of protection is unknown. Individuals who became ill despite vaccination typically experienced a milder course of illness.
Although people should be vaccinated as early as possible during Ebola outbreaks, the results of the Epicentre study showed that the vaccine still protects against the risk for infection even when administered after exposure to the virus.
Furthermore, Dr. Coulborn and her team found no antagonistic effect between vaccination and Ebola treatment in their analysis. “Vaccination following exposure to a person infected with Ebola still provides significant protection against death, even if administered shortly before the onset of symptoms,” said study author Dr. Coulborn in a press release from Doctors Without Borders.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
The Ervebo vaccine not only reduces the risk for Ebola infection but also halves mortality rates. This is the result of a study published in The Lancet Infectious Diseases.
Rebecca Coulborn, an epidemiologist at Epicentre in Paris, France, and colleagues analyzed data collected during the 10th Ebola epidemic in the Democratic Republic of the Congo. Their analysis revealed that among the 2279 patients with confirmed Ebola who were admitted to an Ebola health facility between July 27, 2018, and April 27, 2020, the mortality risk was 56% for unvaccinated patients. In vaccinated patients, however, it was only 25%. The reduced mortality applied to all patients, regardless of age and gender.
The study was funded by Doctors Without Borders. For data collection, Epicentre, the epidemiological division of Doctors Without Borders, collaborated with the Institut National de Recherche Biomédicale and the Ministry of Health of the Democratic Republic of the Congo.
The study authors focused on the Ervebo vaccine, which is approved for use against Zaire ebolavirus in the European Union, the United States, and some African countries, among others. It is the only Ebola vaccine currently recommended for use during an epidemic. It is administered intramuscularly as a single dose and is approved for adults aged 18 years and older.
The vaccine is primarily recommended for ring vaccination of individuals at a high risk for infection during an epidemic. In studies, the vaccine has been used for ring vaccinations among contacts of diagnosed cases since the end of the Ebola outbreak in West Africa in 2014 and 2015 and since 2018 in the Democratic Republic of the Congo.
The preliminary estimated vaccine effectiveness 10 days after vaccination is 97.5%-100%. The duration of protection is unknown. Individuals who became ill despite vaccination typically experienced a milder course of illness.
Although people should be vaccinated as early as possible during Ebola outbreaks, the results of the Epicentre study showed that the vaccine still protects against the risk for infection even when administered after exposure to the virus.
Furthermore, Dr. Coulborn and her team found no antagonistic effect between vaccination and Ebola treatment in their analysis. “Vaccination following exposure to a person infected with Ebola still provides significant protection against death, even if administered shortly before the onset of symptoms,” said study author Dr. Coulborn in a press release from Doctors Without Borders.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
The Ervebo vaccine not only reduces the risk for Ebola infection but also halves mortality rates. This is the result of a study published in The Lancet Infectious Diseases.
Rebecca Coulborn, an epidemiologist at Epicentre in Paris, France, and colleagues analyzed data collected during the 10th Ebola epidemic in the Democratic Republic of the Congo. Their analysis revealed that among the 2279 patients with confirmed Ebola who were admitted to an Ebola health facility between July 27, 2018, and April 27, 2020, the mortality risk was 56% for unvaccinated patients. In vaccinated patients, however, it was only 25%. The reduced mortality applied to all patients, regardless of age and gender.
The study was funded by Doctors Without Borders. For data collection, Epicentre, the epidemiological division of Doctors Without Borders, collaborated with the Institut National de Recherche Biomédicale and the Ministry of Health of the Democratic Republic of the Congo.
The study authors focused on the Ervebo vaccine, which is approved for use against Zaire ebolavirus in the European Union, the United States, and some African countries, among others. It is the only Ebola vaccine currently recommended for use during an epidemic. It is administered intramuscularly as a single dose and is approved for adults aged 18 years and older.
The vaccine is primarily recommended for ring vaccination of individuals at a high risk for infection during an epidemic. In studies, the vaccine has been used for ring vaccinations among contacts of diagnosed cases since the end of the Ebola outbreak in West Africa in 2014 and 2015 and since 2018 in the Democratic Republic of the Congo.
The preliminary estimated vaccine effectiveness 10 days after vaccination is 97.5%-100%. The duration of protection is unknown. Individuals who became ill despite vaccination typically experienced a milder course of illness.
Although people should be vaccinated as early as possible during Ebola outbreaks, the results of the Epicentre study showed that the vaccine still protects against the risk for infection even when administered after exposure to the virus.
Furthermore, Dr. Coulborn and her team found no antagonistic effect between vaccination and Ebola treatment in their analysis. “Vaccination following exposure to a person infected with Ebola still provides significant protection against death, even if administered shortly before the onset of symptoms,” said study author Dr. Coulborn in a press release from Doctors Without Borders.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
FROM THE LANCET INFECTIOUS DISEASES
Biological Sex Differences: Key to Understanding Long COVID?
Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.
After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”
Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.
What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.
“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.
Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.
Emerging ‘Menstrual Science’ Could Be Key
There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.
Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.
Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.
Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.
How Gender and Long COVID Intertwine
The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).
It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.
Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.
Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.
Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.
Sex-Specific Symptoms and Marginalized Communities
Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.
In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.
However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.
For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.
The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”
Where It All Leads
The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.
“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.
This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.
“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.
“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.
A version of this article appeared on Medscape.com.
Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.
After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”
Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.
What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.
“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.
Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.
Emerging ‘Menstrual Science’ Could Be Key
There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.
Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.
Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.
Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.
How Gender and Long COVID Intertwine
The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).
It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.
Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.
Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.
Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.
Sex-Specific Symptoms and Marginalized Communities
Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.
In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.
However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.
For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.
The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”
Where It All Leads
The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.
“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.
This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.
“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.
“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.
A version of this article appeared on Medscape.com.
Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.
After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”
Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.
What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.
“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.
Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.
Emerging ‘Menstrual Science’ Could Be Key
There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.
Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.
Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.
Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.
How Gender and Long COVID Intertwine
The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).
It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.
Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.
Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.
Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.
Sex-Specific Symptoms and Marginalized Communities
Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.
In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.
However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.
For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.
The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”
Where It All Leads
The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.
“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.
This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.
“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.
“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.
A version of this article appeared on Medscape.com.