Pediatric News

The European Centre for Disease Prevention and Control (ECDC) has issued a warning to travelers in areas in South and Central America and the Caribbean affected by a current outbreak of Oropouche virus (OROV) disease. The ECDC said that there had been more than 8000 cases reported in these areas since January, with 19 imported cases reported in Europe for the first time in June and July. Of these, 12 were in Spain, five were in Italy, and two were in Germany. 

The ECDC’s Threat Assessment Brief of Aug. 9 said that one of those affected had traveled to Brazil and the other 18 to Cuba; however, outbreaks have also been reported this year in Bolivia, Colombia, and Peru. Though the overall risk for infection to European travelers to OROV-epidemic countries was assessed as moderate, it was higher in the more affected municipalities of the northern states of Brazil and/or the Amazon region, and/or if personal protection measures are not taken.

An editorial published Aug. 8 in The Lancet Infectious Diseases described OROV as a “mysterious threat,” which there is limited knowledge about despite some half a million cases recorded since it was first detected in Trinidad and Tobago in 1955. 

OROV is transmitted primarily through bites from infected midges (Culicoides paraensis). However, some mosquitoes species can also spread the virus, which causes symptoms very similar to other arbovirus diseases from the same regions, such as dengue, chikungunya, and Zika virus infection. 

Most cases are mild, but meningitis and encephalitis can occur as well as possible fetal death and deformities after infection in pregnancy. Last month, the first fatal cases were reported in two young Brazilian women who, concerningly, had no comorbidities.

This news organization asked Jan Felix Drexler, MD, of the Institute of Virology at Charité – Universitätsmedizin in Berlin, Germany, who has studied the emergence of Oropouche fever in Latin America, what clinicians should know about OROV disease.

What are the main symptoms of OROV disease for which clinicians should be alert?

The main symptoms are not different from other arboviral infections, ie, fever, maybe joint and muscle pain, maybe rash. The problem is that we do not know how often severe disease may occur because we do not know whether the severe cases that have been postulated, including death in apparently healthy people and congenital infection, are due to increased testing; an altered virus; or an altered, more intense circulation (so that many more infections simply lead to rare severe cases appearing). Be alert and ask for testing in your patients. 

What is the differential diagnosis if a recent traveler to affected regions presents with symptoms? Are there any clues to suggest whether the disease is Oropouche as opposed to Zika, etc.?

The main message is: Do not assume a particular infection based on clinical symptoms. If your patient is returning from or living in an endemic area, consider OROV disease in the differential diagnosis.

What personal protective measures should clinicians advise travelers in affected areas to take? Do these differ from normal mosquito precautions?

Repellents are extremely important as usual. However, there are differences. Mosquito nets’ hole sizes need to be smaller than those used against the vectors of malaria or dengue; in other words, they need to have a higher mesh. The problem is that nets with high mesh are complicated in very hot and humid conditions because they also limit ventilation. Travelers should discuss with local suppliers about the best trade-off.

The risk for midge bites is likely highest at dawn and dusk in still and humid conditions. So on the one hand, one could recommend avoiding those areas and being outside during those times of the day. On the other hand, specific recommendations cannot be made robustly because we cannot exclude other invertebrate vectors at current knowledge. Some studies have implicated that mosquitoes may also transmit the virus. If that holds true, then we are back to reducing any bite.

Should pregnant women be advised to avoid travel to affected regions?

Not immediately, but caution must be taken. We simply do not have sufficient data to gauge the risk for potential congenital infection. Much more epidemiologic data and controlled infection experiments will be required to make evidence-based recommendations.

All the cases reported in Europe so far were imported from Cuba and Brazil. Is there any risk for local transmission, eg, via midges/mosquitoes that might hitch a ride on an aircraft, as in cases of airport malaria?

Not immediately, but it cannot be excluded. We know very little about the infection intensity in the vectors. Controlled infection experiments, including robustness of vectors against commonly used insecticides in airplanes, need to be done.

What is the risk for an animal reservoir emerging in Europe?

We do not know, but there is also no reason for ringing the alarm bells. Controlled infection experiments and surveillance will be required.

Is treatment purely supportive or are there any specific agents worth trying in case of severe symptoms/neurologic involvement?

No specific treatment can be recommended as is. However, severe dengue illustrates the relevance of supportive treatment, which is hugely effective in reducing mortality.

The Lancet paper states: “Several laboratory tests have been developed but robust commercial tests are hardly available.” How likely is it that laboratories in Europe will have the capability to test for the Oropouche organism? 

European laboratory networks have already taken action, and testing is now available at least in the major and reference laboratories. If a clinician asks for OROV testing, they will probably get a robust answer in a reasonable timespan. Of course, that can be improved once we have more cases and more laboratories will be equipped for testing.

Is there anything else you think clinicians should be aware of?

The most important is to think beyond the textbooks we know from medical school. Things change rapidly in a connected world under altered climate conditions.

Dr. Drexler has no conflicts of interest to declare.
 

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

The European Centre for Disease Prevention and Control (ECDC) has issued a warning to travelers in areas in South and Central America and the Caribbean affected by a current outbreak of Oropouche virus (OROV) disease. The ECDC said that there had been more than 8000 cases reported in these areas since January, with 19 imported cases reported in Europe for the first time in June and July. Of these, 12 were in Spain, five were in Italy, and two were in Germany. 

The ECDC’s Threat Assessment Brief of Aug. 9 said that one of those affected had traveled to Brazil and the other 18 to Cuba; however, outbreaks have also been reported this year in Bolivia, Colombia, and Peru. Though the overall risk for infection to European travelers to OROV-epidemic countries was assessed as moderate, it was higher in the more affected municipalities of the northern states of Brazil and/or the Amazon region, and/or if personal protection measures are not taken.

An editorial published Aug. 8 in The Lancet Infectious Diseases described OROV as a “mysterious threat,” which there is limited knowledge about despite some half a million cases recorded since it was first detected in Trinidad and Tobago in 1955. 

OROV is transmitted primarily through bites from infected midges (Culicoides paraensis). However, some mosquitoes species can also spread the virus, which causes symptoms very similar to other arbovirus diseases from the same regions, such as dengue, chikungunya, and Zika virus infection. 

Most cases are mild, but meningitis and encephalitis can occur as well as possible fetal death and deformities after infection in pregnancy. Last month, the first fatal cases were reported in two young Brazilian women who, concerningly, had no comorbidities.

This news organization asked Jan Felix Drexler, MD, of the Institute of Virology at Charité – Universitätsmedizin in Berlin, Germany, who has studied the emergence of Oropouche fever in Latin America, what clinicians should know about OROV disease.

What are the main symptoms of OROV disease for which clinicians should be alert?

The main symptoms are not different from other arboviral infections, ie, fever, maybe joint and muscle pain, maybe rash. The problem is that we do not know how often severe disease may occur because we do not know whether the severe cases that have been postulated, including death in apparently healthy people and congenital infection, are due to increased testing; an altered virus; or an altered, more intense circulation (so that many more infections simply lead to rare severe cases appearing). Be alert and ask for testing in your patients. 

What is the differential diagnosis if a recent traveler to affected regions presents with symptoms? Are there any clues to suggest whether the disease is Oropouche as opposed to Zika, etc.?

The main message is: Do not assume a particular infection based on clinical symptoms. If your patient is returning from or living in an endemic area, consider OROV disease in the differential diagnosis.

What personal protective measures should clinicians advise travelers in affected areas to take? Do these differ from normal mosquito precautions?

Repellents are extremely important as usual. However, there are differences. Mosquito nets’ hole sizes need to be smaller than those used against the vectors of malaria or dengue; in other words, they need to have a higher mesh. The problem is that nets with high mesh are complicated in very hot and humid conditions because they also limit ventilation. Travelers should discuss with local suppliers about the best trade-off.

The risk for midge bites is likely highest at dawn and dusk in still and humid conditions. So on the one hand, one could recommend avoiding those areas and being outside during those times of the day. On the other hand, specific recommendations cannot be made robustly because we cannot exclude other invertebrate vectors at current knowledge. Some studies have implicated that mosquitoes may also transmit the virus. If that holds true, then we are back to reducing any bite.

Should pregnant women be advised to avoid travel to affected regions?

Not immediately, but caution must be taken. We simply do not have sufficient data to gauge the risk for potential congenital infection. Much more epidemiologic data and controlled infection experiments will be required to make evidence-based recommendations.

All the cases reported in Europe so far were imported from Cuba and Brazil. Is there any risk for local transmission, eg, via midges/mosquitoes that might hitch a ride on an aircraft, as in cases of airport malaria?

Not immediately, but it cannot be excluded. We know very little about the infection intensity in the vectors. Controlled infection experiments, including robustness of vectors against commonly used insecticides in airplanes, need to be done.

What is the risk for an animal reservoir emerging in Europe?

We do not know, but there is also no reason for ringing the alarm bells. Controlled infection experiments and surveillance will be required.

Is treatment purely supportive or are there any specific agents worth trying in case of severe symptoms/neurologic involvement?

No specific treatment can be recommended as is. However, severe dengue illustrates the relevance of supportive treatment, which is hugely effective in reducing mortality.

The Lancet paper states: “Several laboratory tests have been developed but robust commercial tests are hardly available.” How likely is it that laboratories in Europe will have the capability to test for the Oropouche organism? 

European laboratory networks have already taken action, and testing is now available at least in the major and reference laboratories. If a clinician asks for OROV testing, they will probably get a robust answer in a reasonable timespan. Of course, that can be improved once we have more cases and more laboratories will be equipped for testing.

Is there anything else you think clinicians should be aware of?

The most important is to think beyond the textbooks we know from medical school. Things change rapidly in a connected world under altered climate conditions.

Dr. Drexler has no conflicts of interest to declare.
 

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

The European Centre for Disease Prevention and Control (ECDC) has issued a warning to travelers in areas in South and Central America and the Caribbean affected by a current outbreak of Oropouche virus (OROV) disease. The ECDC said that there had been more than 8000 cases reported in these areas since January, with 19 imported cases reported in Europe for the first time in June and July. Of these, 12 were in Spain, five were in Italy, and two were in Germany. 

The ECDC’s Threat Assessment Brief of Aug. 9 said that one of those affected had traveled to Brazil and the other 18 to Cuba; however, outbreaks have also been reported this year in Bolivia, Colombia, and Peru. Though the overall risk for infection to European travelers to OROV-epidemic countries was assessed as moderate, it was higher in the more affected municipalities of the northern states of Brazil and/or the Amazon region, and/or if personal protection measures are not taken.

An editorial published Aug. 8 in The Lancet Infectious Diseases described OROV as a “mysterious threat,” which there is limited knowledge about despite some half a million cases recorded since it was first detected in Trinidad and Tobago in 1955. 

OROV is transmitted primarily through bites from infected midges (Culicoides paraensis). However, some mosquitoes species can also spread the virus, which causes symptoms very similar to other arbovirus diseases from the same regions, such as dengue, chikungunya, and Zika virus infection. 

Most cases are mild, but meningitis and encephalitis can occur as well as possible fetal death and deformities after infection in pregnancy. Last month, the first fatal cases were reported in two young Brazilian women who, concerningly, had no comorbidities.

This news organization asked Jan Felix Drexler, MD, of the Institute of Virology at Charité – Universitätsmedizin in Berlin, Germany, who has studied the emergence of Oropouche fever in Latin America, what clinicians should know about OROV disease.

What are the main symptoms of OROV disease for which clinicians should be alert?

The main symptoms are not different from other arboviral infections, ie, fever, maybe joint and muscle pain, maybe rash. The problem is that we do not know how often severe disease may occur because we do not know whether the severe cases that have been postulated, including death in apparently healthy people and congenital infection, are due to increased testing; an altered virus; or an altered, more intense circulation (so that many more infections simply lead to rare severe cases appearing). Be alert and ask for testing in your patients. 

What is the differential diagnosis if a recent traveler to affected regions presents with symptoms? Are there any clues to suggest whether the disease is Oropouche as opposed to Zika, etc.?

The main message is: Do not assume a particular infection based on clinical symptoms. If your patient is returning from or living in an endemic area, consider OROV disease in the differential diagnosis.

What personal protective measures should clinicians advise travelers in affected areas to take? Do these differ from normal mosquito precautions?

Repellents are extremely important as usual. However, there are differences. Mosquito nets’ hole sizes need to be smaller than those used against the vectors of malaria or dengue; in other words, they need to have a higher mesh. The problem is that nets with high mesh are complicated in very hot and humid conditions because they also limit ventilation. Travelers should discuss with local suppliers about the best trade-off.

The risk for midge bites is likely highest at dawn and dusk in still and humid conditions. So on the one hand, one could recommend avoiding those areas and being outside during those times of the day. On the other hand, specific recommendations cannot be made robustly because we cannot exclude other invertebrate vectors at current knowledge. Some studies have implicated that mosquitoes may also transmit the virus. If that holds true, then we are back to reducing any bite.

Should pregnant women be advised to avoid travel to affected regions?

Not immediately, but caution must be taken. We simply do not have sufficient data to gauge the risk for potential congenital infection. Much more epidemiologic data and controlled infection experiments will be required to make evidence-based recommendations.

All the cases reported in Europe so far were imported from Cuba and Brazil. Is there any risk for local transmission, eg, via midges/mosquitoes that might hitch a ride on an aircraft, as in cases of airport malaria?

Not immediately, but it cannot be excluded. We know very little about the infection intensity in the vectors. Controlled infection experiments, including robustness of vectors against commonly used insecticides in airplanes, need to be done.

What is the risk for an animal reservoir emerging in Europe?

We do not know, but there is also no reason for ringing the alarm bells. Controlled infection experiments and surveillance will be required.

Is treatment purely supportive or are there any specific agents worth trying in case of severe symptoms/neurologic involvement?

No specific treatment can be recommended as is. However, severe dengue illustrates the relevance of supportive treatment, which is hugely effective in reducing mortality.

The Lancet paper states: “Several laboratory tests have been developed but robust commercial tests are hardly available.” How likely is it that laboratories in Europe will have the capability to test for the Oropouche organism? 

European laboratory networks have already taken action, and testing is now available at least in the major and reference laboratories. If a clinician asks for OROV testing, they will probably get a robust answer in a reasonable timespan. Of course, that can be improved once we have more cases and more laboratories will be equipped for testing.

Is there anything else you think clinicians should be aware of?

The most important is to think beyond the textbooks we know from medical school. Things change rapidly in a connected world under altered climate conditions.

Dr. Drexler has no conflicts of interest to declare.
 

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

The Heritage Foundation sponsored and developed Project 2025 for the explicit, stated purpose of building a conservative victory through policy, personnel, and training with a 180-day game plan after a sympathetic new President of the United States takes office. To date, Project 2025 has not been formally endorsed by any presidential campaign.

More than 100 conservative organizations are said to be participating. More than 400 conservative scholars and experts have collaborated in authorship of the mandate’s 40 chapters. Chapter 14 of the “Mandate for Leadership” is an exhaustive proposed overhaul of the Department of Health and Human Services (HHS), one of the major existing arms of the executive branch of the US government. 

The mandate’s sweeping recommendations, if implemented, would impact the lives of all Americans and all healthcare workers, as outlined in the following excerpts. 
 

Healthcare-Related Excerpts From Project 2025

• “From the moment of conception, every human being possesses inherent dignity and worth, and our humanity does not depend on our age, stage of development, race, or abilities. The Secretary must ensure that all HHS programs and activities are rooted in a deep respect for innocent human life from day one until natural death: Abortion and euthanasia are not health care.”
• “Unfortunately, family policies and programs under President Biden’s HHS are fraught with agenda items focusing on ‘LGBTQ+ equity,’ subsidizing single motherhood, disincentivizing work, and penalizing marriage. These policies should be repealed and replaced by policies that support the formation of stable, married, nuclear families.”
• “The next Administration should guard against the regulatory capture of our public health agencies by pharmaceutical companies, insurers, hospital conglomerates, and related economic interests that these agencies are meant to regulate. We must erect robust firewalls to mitigate these obvious financial conflicts of interest.”
• “All National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration regulators should be entirely free from private biopharmaceutical funding. In this realm, ‘public–private partnerships’ is a euphemism for agency capture, a thin veneer for corporatism. Funding for agencies and individual government researchers must come directly from the government with robust congressional oversight.”
• “The CDC [Centers for Disease Control and Prevention] operates several programs related to vaccine safety including the Vaccine Adverse Event Reporting System (VAERS); Vaccine Safety Datalink (VSD); and Clinical Immunization Safety Assessment (CISA) Project. Those functions and their associated funding should be transferred to the FDA [Food and Drug Administration], which is responsible for post-market surveillance and evaluation of all other drugs and biological products.”
• “Because liberal states have now become sanctuaries for abortion tourism, HHS should use every available tool, including the cutting of funds, to ensure that every state reports exactly how many abortions take place within its borders, at what gestational age of the child, for what reason, the mother’s state of residence, and by what method. It should also ensure that statistics are separated by category: spontaneous miscarriage; treatments that incidentally result in the death of a child (such as chemotherapy); stillbirths; and induced abortion. In addition, CDC should require monitoring and reporting for complications due to abortion and every instance of children being born alive after an abortion.”
• “The CDC should immediately end its collection of data on gender identity, which legitimizes the unscientific notion that men can become women (and vice versa) and encourages the phenomenon of ever-multiplying subjective identities.”
• “A test developed by a lab in accordance with the protocols developed by another lab (non-commercial sharing) currently constitutes a ‘new’ laboratory-developed test because the lab in which it will be used is different from the initial developing lab. To encourage interlaboratory collaboration and discourage duplicative test creation (and associated regulatory and logistical burdens), the FDA should introduce mechanisms through which laboratory-developed tests can easily be shared with other laboratories without the current regulatory burdens.”
• “[FDA should] Reverse its approval of chemical abortion drugs because the politicized approval process was illegal from the start. The FDA failed to abide by its legal obligations to protect the health, safety, and welfare of girls and women.”
• “[FDA should] Stop promoting or approving mail-order abortions in violation of long-standing federal laws that prohibit the mailing and interstate carriage of abortion drugs.”
• “[HHS should] Promptly restore the ethics advisory committee to oversee abortion-derived fetal tissue research, and Congress should prohibit such research altogether.”
• “[HHS should] End intramural research projects using tissue from aborted children within the NIH, which should end its human embryonic stem cell registry.”
• “Under Francis Collins, NIH became so focused on the #MeToo movement that it refused to sponsor scientific conferences unless there were a certain number of women panelists, which violates federal civil rights law against sex discrimination. This quota practice should be ended, and the NIH Office of Equity, Diversity, and Inclusion, which pushes such unlawful actions, should be abolished.”
• “Make Medicare Advantage [MA] the default enrollment option.”
• “[Legislation reforming legacy (non-MA) Medicare should] Repeal harmful health policies enacted under the Obama and Biden Administrations such as the Medicare Shared Savings Program and Inflation Reduction Act.”
• “…the next Administration should] Add work requirements and match Medicaid benefits to beneficiary needs. Because Medicaid serves a broad and diverse group of individuals, it should be flexible enough to accommodate different designs for different groups.”
• “The No Surprises Act should scrap the dispute resolution process in favor of a truth-in-advertising approach that will protect consumers and free doctors, insurers, and arbiters from confused and conflicting standards for resolving disputes that the disputing parties can best resolve themselves.”
• “Prohibit abortion travel funding. Providing funding for abortions increases the number of abortions and violates the conscience and religious freedom rights of Americans who object to subsidizing the taking of life.”
• “Prohibit Planned Parenthood from receiving Medicaid funds. During the 2020–2021 reporting period, Planned Parenthood performed more than 383,000 abortions.”
• “Protect faith-based grant recipients from religious liberty violations and maintain a biblically based, social science–reinforced definition of marriage and family. Social science reports that assess the objective outcomes for children raised in homes aside from a heterosexual, intact marriage are clear.”
• “Allocate funding to strategy programs promoting father involvement or terminate parental rights quickly.”
• “Eliminate the Head Start program.”
• “Support palliative care. Physician-assisted suicide (PAS) is legal in 10 states and the District of Columbia. Legalizing PAS is a grave mistake that endangers the weak and vulnerable, corrupts the practice of medicine and the doctor–patient relationship, compromises the family and intergenerational commitments, and betrays human dignity and equality before the law.”
• “Eliminate men’s preventive services from the women’s preventive services mandate. In December 2021, HRSA [Health Resources and Services Administration] updated its women’s preventive services guidelines to include male condoms.”
• “Prioritize funding for home-based childcare, not universal day care.”
• “ The Office of the Secretary should eliminate the HHS Reproductive Healthcare Access Task Force and install a pro-life task force to ensure that all of the department’s divisions seek to use their authority to promote the life and health of women and their unborn children.”
• “The ASH [Assistant Secretary for Health] and SG [Surgeon General] positions should be combined into one four-star position with the rank, responsibilities, and authority of the ASH retained but with the title of Surgeon General.”
• “OCR [Office for Civil Rights] should withdraw its Health Insurance Portability and Accountability Act (HIPAA) guidance on abortion.”

Dr. Lundberg is Editor in Chief, Cancer Commons, and has disclosed no relevant financial relationships.

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

The Heritage Foundation sponsored and developed Project 2025 for the explicit, stated purpose of building a conservative victory through policy, personnel, and training with a 180-day game plan after a sympathetic new President of the United States takes office. To date, Project 2025 has not been formally endorsed by any presidential campaign.

More than 100 conservative organizations are said to be participating. More than 400 conservative scholars and experts have collaborated in authorship of the mandate’s 40 chapters. Chapter 14 of the “Mandate for Leadership” is an exhaustive proposed overhaul of the Department of Health and Human Services (HHS), one of the major existing arms of the executive branch of the US government. 

The mandate’s sweeping recommendations, if implemented, would impact the lives of all Americans and all healthcare workers, as outlined in the following excerpts. 
 

Healthcare-Related Excerpts From Project 2025

• “From the moment of conception, every human being possesses inherent dignity and worth, and our humanity does not depend on our age, stage of development, race, or abilities. The Secretary must ensure that all HHS programs and activities are rooted in a deep respect for innocent human life from day one until natural death: Abortion and euthanasia are not health care.”
• “Unfortunately, family policies and programs under President Biden’s HHS are fraught with agenda items focusing on ‘LGBTQ+ equity,’ subsidizing single motherhood, disincentivizing work, and penalizing marriage. These policies should be repealed and replaced by policies that support the formation of stable, married, nuclear families.”
• “The next Administration should guard against the regulatory capture of our public health agencies by pharmaceutical companies, insurers, hospital conglomerates, and related economic interests that these agencies are meant to regulate. We must erect robust firewalls to mitigate these obvious financial conflicts of interest.”
• “All National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration regulators should be entirely free from private biopharmaceutical funding. In this realm, ‘public–private partnerships’ is a euphemism for agency capture, a thin veneer for corporatism. Funding for agencies and individual government researchers must come directly from the government with robust congressional oversight.”
• “The CDC [Centers for Disease Control and Prevention] operates several programs related to vaccine safety including the Vaccine Adverse Event Reporting System (VAERS); Vaccine Safety Datalink (VSD); and Clinical Immunization Safety Assessment (CISA) Project. Those functions and their associated funding should be transferred to the FDA [Food and Drug Administration], which is responsible for post-market surveillance and evaluation of all other drugs and biological products.”
• “Because liberal states have now become sanctuaries for abortion tourism, HHS should use every available tool, including the cutting of funds, to ensure that every state reports exactly how many abortions take place within its borders, at what gestational age of the child, for what reason, the mother’s state of residence, and by what method. It should also ensure that statistics are separated by category: spontaneous miscarriage; treatments that incidentally result in the death of a child (such as chemotherapy); stillbirths; and induced abortion. In addition, CDC should require monitoring and reporting for complications due to abortion and every instance of children being born alive after an abortion.”
• “The CDC should immediately end its collection of data on gender identity, which legitimizes the unscientific notion that men can become women (and vice versa) and encourages the phenomenon of ever-multiplying subjective identities.”
• “A test developed by a lab in accordance with the protocols developed by another lab (non-commercial sharing) currently constitutes a ‘new’ laboratory-developed test because the lab in which it will be used is different from the initial developing lab. To encourage interlaboratory collaboration and discourage duplicative test creation (and associated regulatory and logistical burdens), the FDA should introduce mechanisms through which laboratory-developed tests can easily be shared with other laboratories without the current regulatory burdens.”
• “[FDA should] Reverse its approval of chemical abortion drugs because the politicized approval process was illegal from the start. The FDA failed to abide by its legal obligations to protect the health, safety, and welfare of girls and women.”
• “[FDA should] Stop promoting or approving mail-order abortions in violation of long-standing federal laws that prohibit the mailing and interstate carriage of abortion drugs.”
• “[HHS should] Promptly restore the ethics advisory committee to oversee abortion-derived fetal tissue research, and Congress should prohibit such research altogether.”
• “[HHS should] End intramural research projects using tissue from aborted children within the NIH, which should end its human embryonic stem cell registry.”
• “Under Francis Collins, NIH became so focused on the #MeToo movement that it refused to sponsor scientific conferences unless there were a certain number of women panelists, which violates federal civil rights law against sex discrimination. This quota practice should be ended, and the NIH Office of Equity, Diversity, and Inclusion, which pushes such unlawful actions, should be abolished.”
• “Make Medicare Advantage [MA] the default enrollment option.”
• “[Legislation reforming legacy (non-MA) Medicare should] Repeal harmful health policies enacted under the Obama and Biden Administrations such as the Medicare Shared Savings Program and Inflation Reduction Act.”
• “…the next Administration should] Add work requirements and match Medicaid benefits to beneficiary needs. Because Medicaid serves a broad and diverse group of individuals, it should be flexible enough to accommodate different designs for different groups.”
• “The No Surprises Act should scrap the dispute resolution process in favor of a truth-in-advertising approach that will protect consumers and free doctors, insurers, and arbiters from confused and conflicting standards for resolving disputes that the disputing parties can best resolve themselves.”
• “Prohibit abortion travel funding. Providing funding for abortions increases the number of abortions and violates the conscience and religious freedom rights of Americans who object to subsidizing the taking of life.”
• “Prohibit Planned Parenthood from receiving Medicaid funds. During the 2020–2021 reporting period, Planned Parenthood performed more than 383,000 abortions.”
• “Protect faith-based grant recipients from religious liberty violations and maintain a biblically based, social science–reinforced definition of marriage and family. Social science reports that assess the objective outcomes for children raised in homes aside from a heterosexual, intact marriage are clear.”
• “Allocate funding to strategy programs promoting father involvement or terminate parental rights quickly.”
• “Eliminate the Head Start program.”
• “Support palliative care. Physician-assisted suicide (PAS) is legal in 10 states and the District of Columbia. Legalizing PAS is a grave mistake that endangers the weak and vulnerable, corrupts the practice of medicine and the doctor–patient relationship, compromises the family and intergenerational commitments, and betrays human dignity and equality before the law.”
• “Eliminate men’s preventive services from the women’s preventive services mandate. In December 2021, HRSA [Health Resources and Services Administration] updated its women’s preventive services guidelines to include male condoms.”
• “Prioritize funding for home-based childcare, not universal day care.”
• “ The Office of the Secretary should eliminate the HHS Reproductive Healthcare Access Task Force and install a pro-life task force to ensure that all of the department’s divisions seek to use their authority to promote the life and health of women and their unborn children.”
• “The ASH [Assistant Secretary for Health] and SG [Surgeon General] positions should be combined into one four-star position with the rank, responsibilities, and authority of the ASH retained but with the title of Surgeon General.”
• “OCR [Office for Civil Rights] should withdraw its Health Insurance Portability and Accountability Act (HIPAA) guidance on abortion.”

Dr. Lundberg is Editor in Chief, Cancer Commons, and has disclosed no relevant financial relationships.

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

The Heritage Foundation sponsored and developed Project 2025 for the explicit, stated purpose of building a conservative victory through policy, personnel, and training with a 180-day game plan after a sympathetic new President of the United States takes office. To date, Project 2025 has not been formally endorsed by any presidential campaign.

More than 100 conservative organizations are said to be participating. More than 400 conservative scholars and experts have collaborated in authorship of the mandate’s 40 chapters. Chapter 14 of the “Mandate for Leadership” is an exhaustive proposed overhaul of the Department of Health and Human Services (HHS), one of the major existing arms of the executive branch of the US government. 

The mandate’s sweeping recommendations, if implemented, would impact the lives of all Americans and all healthcare workers, as outlined in the following excerpts. 
 

Healthcare-Related Excerpts From Project 2025

• “From the moment of conception, every human being possesses inherent dignity and worth, and our humanity does not depend on our age, stage of development, race, or abilities. The Secretary must ensure that all HHS programs and activities are rooted in a deep respect for innocent human life from day one until natural death: Abortion and euthanasia are not health care.”
• “Unfortunately, family policies and programs under President Biden’s HHS are fraught with agenda items focusing on ‘LGBTQ+ equity,’ subsidizing single motherhood, disincentivizing work, and penalizing marriage. These policies should be repealed and replaced by policies that support the formation of stable, married, nuclear families.”
• “The next Administration should guard against the regulatory capture of our public health agencies by pharmaceutical companies, insurers, hospital conglomerates, and related economic interests that these agencies are meant to regulate. We must erect robust firewalls to mitigate these obvious financial conflicts of interest.”
• “All National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration regulators should be entirely free from private biopharmaceutical funding. In this realm, ‘public–private partnerships’ is a euphemism for agency capture, a thin veneer for corporatism. Funding for agencies and individual government researchers must come directly from the government with robust congressional oversight.”
• “The CDC [Centers for Disease Control and Prevention] operates several programs related to vaccine safety including the Vaccine Adverse Event Reporting System (VAERS); Vaccine Safety Datalink (VSD); and Clinical Immunization Safety Assessment (CISA) Project. Those functions and their associated funding should be transferred to the FDA [Food and Drug Administration], which is responsible for post-market surveillance and evaluation of all other drugs and biological products.”
• “Because liberal states have now become sanctuaries for abortion tourism, HHS should use every available tool, including the cutting of funds, to ensure that every state reports exactly how many abortions take place within its borders, at what gestational age of the child, for what reason, the mother’s state of residence, and by what method. It should also ensure that statistics are separated by category: spontaneous miscarriage; treatments that incidentally result in the death of a child (such as chemotherapy); stillbirths; and induced abortion. In addition, CDC should require monitoring and reporting for complications due to abortion and every instance of children being born alive after an abortion.”
• “The CDC should immediately end its collection of data on gender identity, which legitimizes the unscientific notion that men can become women (and vice versa) and encourages the phenomenon of ever-multiplying subjective identities.”
• “A test developed by a lab in accordance with the protocols developed by another lab (non-commercial sharing) currently constitutes a ‘new’ laboratory-developed test because the lab in which it will be used is different from the initial developing lab. To encourage interlaboratory collaboration and discourage duplicative test creation (and associated regulatory and logistical burdens), the FDA should introduce mechanisms through which laboratory-developed tests can easily be shared with other laboratories without the current regulatory burdens.”
• “[FDA should] Reverse its approval of chemical abortion drugs because the politicized approval process was illegal from the start. The FDA failed to abide by its legal obligations to protect the health, safety, and welfare of girls and women.”
• “[FDA should] Stop promoting or approving mail-order abortions in violation of long-standing federal laws that prohibit the mailing and interstate carriage of abortion drugs.”
• “[HHS should] Promptly restore the ethics advisory committee to oversee abortion-derived fetal tissue research, and Congress should prohibit such research altogether.”
• “[HHS should] End intramural research projects using tissue from aborted children within the NIH, which should end its human embryonic stem cell registry.”
• “Under Francis Collins, NIH became so focused on the #MeToo movement that it refused to sponsor scientific conferences unless there were a certain number of women panelists, which violates federal civil rights law against sex discrimination. This quota practice should be ended, and the NIH Office of Equity, Diversity, and Inclusion, which pushes such unlawful actions, should be abolished.”
• “Make Medicare Advantage [MA] the default enrollment option.”
• “[Legislation reforming legacy (non-MA) Medicare should] Repeal harmful health policies enacted under the Obama and Biden Administrations such as the Medicare Shared Savings Program and Inflation Reduction Act.”
• “…the next Administration should] Add work requirements and match Medicaid benefits to beneficiary needs. Because Medicaid serves a broad and diverse group of individuals, it should be flexible enough to accommodate different designs for different groups.”
• “The No Surprises Act should scrap the dispute resolution process in favor of a truth-in-advertising approach that will protect consumers and free doctors, insurers, and arbiters from confused and conflicting standards for resolving disputes that the disputing parties can best resolve themselves.”
• “Prohibit abortion travel funding. Providing funding for abortions increases the number of abortions and violates the conscience and religious freedom rights of Americans who object to subsidizing the taking of life.”
• “Prohibit Planned Parenthood from receiving Medicaid funds. During the 2020–2021 reporting period, Planned Parenthood performed more than 383,000 abortions.”
• “Protect faith-based grant recipients from religious liberty violations and maintain a biblically based, social science–reinforced definition of marriage and family. Social science reports that assess the objective outcomes for children raised in homes aside from a heterosexual, intact marriage are clear.”
• “Allocate funding to strategy programs promoting father involvement or terminate parental rights quickly.”
• “Eliminate the Head Start program.”
• “Support palliative care. Physician-assisted suicide (PAS) is legal in 10 states and the District of Columbia. Legalizing PAS is a grave mistake that endangers the weak and vulnerable, corrupts the practice of medicine and the doctor–patient relationship, compromises the family and intergenerational commitments, and betrays human dignity and equality before the law.”
• “Eliminate men’s preventive services from the women’s preventive services mandate. In December 2021, HRSA [Health Resources and Services Administration] updated its women’s preventive services guidelines to include male condoms.”
• “Prioritize funding for home-based childcare, not universal day care.”
• “ The Office of the Secretary should eliminate the HHS Reproductive Healthcare Access Task Force and install a pro-life task force to ensure that all of the department’s divisions seek to use their authority to promote the life and health of women and their unborn children.”
• “The ASH [Assistant Secretary for Health] and SG [Surgeon General] positions should be combined into one four-star position with the rank, responsibilities, and authority of the ASH retained but with the title of Surgeon General.”
• “OCR [Office for Civil Rights] should withdraw its Health Insurance Portability and Accountability Act (HIPAA) guidance on abortion.”

Dr. Lundberg is Editor in Chief, Cancer Commons, and has disclosed no relevant financial relationships.

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

Higher prenatal exposure to the chemical bisphenol A (BPA) is associated with a greater risk for autism spectrum disorder (ASD) in men, potentially via the disruption of a key enzyme in the developing brain.

BPA is a potent endocrine disruptor found in polycarbonate plastics and epoxy resins and has been banned by the Food and Drug Administration for use in baby bottles, sippy cups, and infant formula packaging.

“Exposure to BPA has already been shown in some studies to be associated with subsequent autism in offspring,” lead researcher Anne-Louise Ponsonby, PhD, The Florey Institute, Heidelberg, Australia, said in a statement.

“Our work is important because it demonstrates one of the biological mechanisms potentially involved. BPA can disrupt hormone-controlled male fetal brain development in several ways, including silencing a key enzyme, aromatase, that controls neurohormones and is especially important in fetal male brain development. This appears to be part of the autism puzzle,” she said.

Brain aromatase, encoded by CYP19A1, converts neural androgens to neural estrogens and has been implicated in ASD. Postmortem analyses of men with ASD also show markedly reduced aromatase activity.

The findings were published online in Nature Communications.
 

New Biological Mechanism

For the study, the researchers analyzed data from the Barwon Infant Study in 1067 infants in Australia. At age 7-11 years, 43 children had a confirmed ASD diagnosis, and 249 infants with Child Behavior Checklist (CBCL) data at age 2 years had an autism spectrum problem score above the median.

The researchers developed a CYP19A1 genetic score for aromatase activity based on five single nucleotide polymorphisms associated with lower estrogen levels. Among 595 children with prenatal BPA and CBCL, those with three or more variants were classified as “low aromatase activity” and the remaining were classified as “high.”

In regression analyses, boys with low aromatase activity and high prenatal BPA exposure (top quartile > 2.18 µg/L) were 3.5 times more likely to have autism symptoms at age 2 years (odds ratio [OR], 3.56; 95% CI, 1.13-11.22).

The odds of a confirmed ASD diagnosis were six times higher at age 9 years only in men with low aromatase activity (OR, 6.24; 95% CI, 1.02-38.26).

The researchers also found that higher BPA levels predicted higher methylation in cord blood across the CYP19A1 brain promoter PI.f region (P = .009).

To replicate the findings, data were used from the Columbia Centre for Children’s Health Study–Mothers and Newborns cohort in the United States. Once again, the BPA level was associated with hypermethylation of the aromatase brain promoter PI.f (P = .0089).

In both cohorts, there was evidence that the effect of increased BPA on brain-derived neurotrophic factor hypermethylation was mediated partly through higher aromatase gene methylation (P = .001). 

To validate the findings, the researchers examined human neuroblastoma SH-SY5Y cell lines and found aromatase protein levels were more than halved in the presence of BPA 50 µg/L (P = .01).

Additionally, mouse studies showed that male mice exposed to BPA 50 µg/L mid-gestation and male aromatase knockout mice — but not female mice — had social behavior deficits, such as interacting with a strange mouse, as well as structural and functional brain changes.

“We found that BPA suppresses the aromatase enzyme and is associated with anatomical, neurologic, and behavioral changes in the male mice that may be consistent with autism spectrum disorder,” Wah Chin Boon, PhD, co–lead researcher and research fellow, also with The Florey Institute, said in a statement.

“This is the first time a biological pathway has been identified that might help explain the connection between autism and BPA,” she said.

“In this study, not only were the levels of BPA higher than most people would be exposed to, but in at least one of the experiments the mice were injected with BPA directly, whereas humans would be exposed via food and drink,” observed Oliver Jones, PhD, MSc, professor of chemistry, RMIT University, Melbourne, Australia. “If you ingest the food, it undergoes metabolism before it gets to the bloodstream, which reduces the effective dose.”

Dr. Jones said further studies with larger numbers of participants measuring BPA throughout pregnancy and other chemicals the mother and child were exposed to are needed to be sure of any such link. “Just because there is a possible mechanism in place does not automatically mean that it is activated,” he said.

Dr. Ponsonby pointed out that BPA and other endocrine-disrupting chemicals are “almost impossible for individuals to avoid” and can enter the body through plastic food and drink packaging, home renovation fumes, and sources such as cosmetics.
 

Fatty Acid Helpful? 

Building on earlier observations that 10-hydroxy-2-decenoic acid (10HDA) may have estrogenic modulating activities, the researchers conducted additional studies suggesting that 10HDA may be effective as a competitive ligand that could counteract the effects of BPA on estrogen signaling within cells.

Further, among 3-week-old mice pups prenatally exposed to BPA, daily injections of 10HDA for 3 weeks showed striking and significant improvements in social interaction. Stopping 10HDA resulted in a deficit in social interaction that was again ameliorated by subsequent 10HDA treatment.

“10-hydroxy-2-decenoic acid shows early indications of potential in activating opposing biological pathways to improve autism-like characteristics when administered to animals that have been prenatally exposed to BPA,” Dr. Boon said. “It warrants further studies to see whether this potential treatment could be realized in humans.”

Reached for comment, Dr. Jones said “the human studies are not strong at all,” in large part because BPA levels were tested only once at 36 weeks in the BIS cohort.

“I would argue that if BPA is in the urine, it has been excreted and is no longer in the bloodstream, thus not able to affect the child,” he said. “I’d also argue that a single measurement at 36 weeks cannot give you any idea of the mother’s exposure to BPA over the rest of the pregnancy or what the child was exposed to after birth.”

The study was funded by the Minderoo Foundation, the National Health and Medical Research Council of Australia, the Australian Research Council, and numerous other sponsors. Dr. Boon is a coinventor on “Methods of treating neurodevelopmental diseases and disorders” and is a board member of Meizon Innovation Holdings. Dr. Ponsonby is a scientific adviser to Meizon Innovation Holdings. The remaining authors declared no competing interests.

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

Higher prenatal exposure to the chemical bisphenol A (BPA) is associated with a greater risk for autism spectrum disorder (ASD) in men, potentially via the disruption of a key enzyme in the developing brain.

BPA is a potent endocrine disruptor found in polycarbonate plastics and epoxy resins and has been banned by the Food and Drug Administration for use in baby bottles, sippy cups, and infant formula packaging.

“Exposure to BPA has already been shown in some studies to be associated with subsequent autism in offspring,” lead researcher Anne-Louise Ponsonby, PhD, The Florey Institute, Heidelberg, Australia, said in a statement.

“Our work is important because it demonstrates one of the biological mechanisms potentially involved. BPA can disrupt hormone-controlled male fetal brain development in several ways, including silencing a key enzyme, aromatase, that controls neurohormones and is especially important in fetal male brain development. This appears to be part of the autism puzzle,” she said.

Brain aromatase, encoded by CYP19A1, converts neural androgens to neural estrogens and has been implicated in ASD. Postmortem analyses of men with ASD also show markedly reduced aromatase activity.

The findings were published online in Nature Communications.
 

New Biological Mechanism

For the study, the researchers analyzed data from the Barwon Infant Study in 1067 infants in Australia. At age 7-11 years, 43 children had a confirmed ASD diagnosis, and 249 infants with Child Behavior Checklist (CBCL) data at age 2 years had an autism spectrum problem score above the median.

The researchers developed a CYP19A1 genetic score for aromatase activity based on five single nucleotide polymorphisms associated with lower estrogen levels. Among 595 children with prenatal BPA and CBCL, those with three or more variants were classified as “low aromatase activity” and the remaining were classified as “high.”

In regression analyses, boys with low aromatase activity and high prenatal BPA exposure (top quartile > 2.18 µg/L) were 3.5 times more likely to have autism symptoms at age 2 years (odds ratio [OR], 3.56; 95% CI, 1.13-11.22).

The odds of a confirmed ASD diagnosis were six times higher at age 9 years only in men with low aromatase activity (OR, 6.24; 95% CI, 1.02-38.26).

The researchers also found that higher BPA levels predicted higher methylation in cord blood across the CYP19A1 brain promoter PI.f region (P = .009).

To replicate the findings, data were used from the Columbia Centre for Children’s Health Study–Mothers and Newborns cohort in the United States. Once again, the BPA level was associated with hypermethylation of the aromatase brain promoter PI.f (P = .0089).

In both cohorts, there was evidence that the effect of increased BPA on brain-derived neurotrophic factor hypermethylation was mediated partly through higher aromatase gene methylation (P = .001). 

To validate the findings, the researchers examined human neuroblastoma SH-SY5Y cell lines and found aromatase protein levels were more than halved in the presence of BPA 50 µg/L (P = .01).

Additionally, mouse studies showed that male mice exposed to BPA 50 µg/L mid-gestation and male aromatase knockout mice — but not female mice — had social behavior deficits, such as interacting with a strange mouse, as well as structural and functional brain changes.

“We found that BPA suppresses the aromatase enzyme and is associated with anatomical, neurologic, and behavioral changes in the male mice that may be consistent with autism spectrum disorder,” Wah Chin Boon, PhD, co–lead researcher and research fellow, also with The Florey Institute, said in a statement.

“This is the first time a biological pathway has been identified that might help explain the connection between autism and BPA,” she said.

“In this study, not only were the levels of BPA higher than most people would be exposed to, but in at least one of the experiments the mice were injected with BPA directly, whereas humans would be exposed via food and drink,” observed Oliver Jones, PhD, MSc, professor of chemistry, RMIT University, Melbourne, Australia. “If you ingest the food, it undergoes metabolism before it gets to the bloodstream, which reduces the effective dose.”

Dr. Jones said further studies with larger numbers of participants measuring BPA throughout pregnancy and other chemicals the mother and child were exposed to are needed to be sure of any such link. “Just because there is a possible mechanism in place does not automatically mean that it is activated,” he said.

Dr. Ponsonby pointed out that BPA and other endocrine-disrupting chemicals are “almost impossible for individuals to avoid” and can enter the body through plastic food and drink packaging, home renovation fumes, and sources such as cosmetics.
 

Fatty Acid Helpful? 

Building on earlier observations that 10-hydroxy-2-decenoic acid (10HDA) may have estrogenic modulating activities, the researchers conducted additional studies suggesting that 10HDA may be effective as a competitive ligand that could counteract the effects of BPA on estrogen signaling within cells.

Further, among 3-week-old mice pups prenatally exposed to BPA, daily injections of 10HDA for 3 weeks showed striking and significant improvements in social interaction. Stopping 10HDA resulted in a deficit in social interaction that was again ameliorated by subsequent 10HDA treatment.

“10-hydroxy-2-decenoic acid shows early indications of potential in activating opposing biological pathways to improve autism-like characteristics when administered to animals that have been prenatally exposed to BPA,” Dr. Boon said. “It warrants further studies to see whether this potential treatment could be realized in humans.”

Reached for comment, Dr. Jones said “the human studies are not strong at all,” in large part because BPA levels were tested only once at 36 weeks in the BIS cohort.

“I would argue that if BPA is in the urine, it has been excreted and is no longer in the bloodstream, thus not able to affect the child,” he said. “I’d also argue that a single measurement at 36 weeks cannot give you any idea of the mother’s exposure to BPA over the rest of the pregnancy or what the child was exposed to after birth.”

The study was funded by the Minderoo Foundation, the National Health and Medical Research Council of Australia, the Australian Research Council, and numerous other sponsors. Dr. Boon is a coinventor on “Methods of treating neurodevelopmental diseases and disorders” and is a board member of Meizon Innovation Holdings. Dr. Ponsonby is a scientific adviser to Meizon Innovation Holdings. The remaining authors declared no competing interests.

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

Higher prenatal exposure to the chemical bisphenol A (BPA) is associated with a greater risk for autism spectrum disorder (ASD) in men, potentially via the disruption of a key enzyme in the developing brain.

BPA is a potent endocrine disruptor found in polycarbonate plastics and epoxy resins and has been banned by the Food and Drug Administration for use in baby bottles, sippy cups, and infant formula packaging.

“Exposure to BPA has already been shown in some studies to be associated with subsequent autism in offspring,” lead researcher Anne-Louise Ponsonby, PhD, The Florey Institute, Heidelberg, Australia, said in a statement.

“Our work is important because it demonstrates one of the biological mechanisms potentially involved. BPA can disrupt hormone-controlled male fetal brain development in several ways, including silencing a key enzyme, aromatase, that controls neurohormones and is especially important in fetal male brain development. This appears to be part of the autism puzzle,” she said.

Brain aromatase, encoded by CYP19A1, converts neural androgens to neural estrogens and has been implicated in ASD. Postmortem analyses of men with ASD also show markedly reduced aromatase activity.

The findings were published online in Nature Communications.
 

New Biological Mechanism

For the study, the researchers analyzed data from the Barwon Infant Study in 1067 infants in Australia. At age 7-11 years, 43 children had a confirmed ASD diagnosis, and 249 infants with Child Behavior Checklist (CBCL) data at age 2 years had an autism spectrum problem score above the median.

The researchers developed a CYP19A1 genetic score for aromatase activity based on five single nucleotide polymorphisms associated with lower estrogen levels. Among 595 children with prenatal BPA and CBCL, those with three or more variants were classified as “low aromatase activity” and the remaining were classified as “high.”

In regression analyses, boys with low aromatase activity and high prenatal BPA exposure (top quartile > 2.18 µg/L) were 3.5 times more likely to have autism symptoms at age 2 years (odds ratio [OR], 3.56; 95% CI, 1.13-11.22).

The odds of a confirmed ASD diagnosis were six times higher at age 9 years only in men with low aromatase activity (OR, 6.24; 95% CI, 1.02-38.26).

The researchers also found that higher BPA levels predicted higher methylation in cord blood across the CYP19A1 brain promoter PI.f region (P = .009).

To replicate the findings, data were used from the Columbia Centre for Children’s Health Study–Mothers and Newborns cohort in the United States. Once again, the BPA level was associated with hypermethylation of the aromatase brain promoter PI.f (P = .0089).

In both cohorts, there was evidence that the effect of increased BPA on brain-derived neurotrophic factor hypermethylation was mediated partly through higher aromatase gene methylation (P = .001). 

To validate the findings, the researchers examined human neuroblastoma SH-SY5Y cell lines and found aromatase protein levels were more than halved in the presence of BPA 50 µg/L (P = .01).

Additionally, mouse studies showed that male mice exposed to BPA 50 µg/L mid-gestation and male aromatase knockout mice — but not female mice — had social behavior deficits, such as interacting with a strange mouse, as well as structural and functional brain changes.

“We found that BPA suppresses the aromatase enzyme and is associated with anatomical, neurologic, and behavioral changes in the male mice that may be consistent with autism spectrum disorder,” Wah Chin Boon, PhD, co–lead researcher and research fellow, also with The Florey Institute, said in a statement.

“This is the first time a biological pathway has been identified that might help explain the connection between autism and BPA,” she said.

“In this study, not only were the levels of BPA higher than most people would be exposed to, but in at least one of the experiments the mice were injected with BPA directly, whereas humans would be exposed via food and drink,” observed Oliver Jones, PhD, MSc, professor of chemistry, RMIT University, Melbourne, Australia. “If you ingest the food, it undergoes metabolism before it gets to the bloodstream, which reduces the effective dose.”

Dr. Jones said further studies with larger numbers of participants measuring BPA throughout pregnancy and other chemicals the mother and child were exposed to are needed to be sure of any such link. “Just because there is a possible mechanism in place does not automatically mean that it is activated,” he said.

Dr. Ponsonby pointed out that BPA and other endocrine-disrupting chemicals are “almost impossible for individuals to avoid” and can enter the body through plastic food and drink packaging, home renovation fumes, and sources such as cosmetics.
 

Fatty Acid Helpful? 

Building on earlier observations that 10-hydroxy-2-decenoic acid (10HDA) may have estrogenic modulating activities, the researchers conducted additional studies suggesting that 10HDA may be effective as a competitive ligand that could counteract the effects of BPA on estrogen signaling within cells.

Further, among 3-week-old mice pups prenatally exposed to BPA, daily injections of 10HDA for 3 weeks showed striking and significant improvements in social interaction. Stopping 10HDA resulted in a deficit in social interaction that was again ameliorated by subsequent 10HDA treatment.

“10-hydroxy-2-decenoic acid shows early indications of potential in activating opposing biological pathways to improve autism-like characteristics when administered to animals that have been prenatally exposed to BPA,” Dr. Boon said. “It warrants further studies to see whether this potential treatment could be realized in humans.”

Reached for comment, Dr. Jones said “the human studies are not strong at all,” in large part because BPA levels were tested only once at 36 weeks in the BIS cohort.

“I would argue that if BPA is in the urine, it has been excreted and is no longer in the bloodstream, thus not able to affect the child,” he said. “I’d also argue that a single measurement at 36 weeks cannot give you any idea of the mother’s exposure to BPA over the rest of the pregnancy or what the child was exposed to after birth.”

The study was funded by the Minderoo Foundation, the National Health and Medical Research Council of Australia, the Australian Research Council, and numerous other sponsors. Dr. Boon is a coinventor on “Methods of treating neurodevelopmental diseases and disorders” and is a board member of Meizon Innovation Holdings. Dr. Ponsonby is a scientific adviser to Meizon Innovation Holdings. The remaining authors declared no competing interests.

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

Only one third of pediatric patients were correctly triaged at emergency departments (EDs) in a northern California health care system, according to a multicenter retrospective study published in JAMA Pediatrics. Researchers also identified gender, age, race, ethnicity, and comorbidity disparities in those who were undertriaged.

The researchers found that only 34.1% of visits were correctly triaged while 58.5% were overtriaged and 7.4% were undertriaged. The findings were based on analysis of more than 1 million pediatric emergency visits over a 5-year period that used the Emergency Severity Index (ESI) version 4 for triage.

“The ESI had poor sensitivity in identifying a critically ill pediatric patient, and undertriage occurred in 1 in 14 children,” wrote Dana R. Sax, MD, a senior emergency physician at The Permanente Medical Group in northern California, and her colleagues.

Disparities in Emergency Care

The results underscore the need for more work to address disparities in emergency care, wrote Warren D. Frankenberger, PhD, RN, a nurse scientist at Children’s Hospital of Philadelphia, and two colleagues in an accompanying editorial.

“Decisions in triage can have significant downstream effects on subsequent care during the ED visit,” they wrote in their editorial. “Given that the triage process in most instances is fully executed by nurses, nurse researchers are in a key position to evaluate these and other covariates to influence further improvements in triage.” They suggested that use of clinical decision support tools and artificial intelligence (AI) may improve the triage process, albeit with the caveat that AI often relies on models with pre-existing historical bias that may perpetuate structural inequalities.
 

Study Methodology

The researchers analyzed 1,016,816 pediatric visits at 21 emergency departments in Kaiser Permanente Northern California between January 2016 and December 2020. The patients were an average 7 years old, and 47% were female. The researchers excluded visits that lacked ESI data or had incomplete ED time variables as well as those with patients who left against medical advice, were not seen, or were transferred from another ED.

The study relied on novel definitions of ESI undertriage and overtriage developed through a modified Delphi process by a team of four emergency physicians, one pediatric emergency physician, two emergency nurses, and one pediatric ICU physician. The definition involved comparing ESI levels to the clinical outcomes and resource use.

Resources included laboratory analysis, electrocardiography, radiography, CT, MRI, diagnostic ultrasonography (not point of care), angiography, IV fluids, and IV, intramuscular, or nebulized medications. Resources did not include “oral medications, tetanus immunizations, point-of-care testing, history and physical examination, saline or heparin lock, prescription refills, simple wound care, crutches, splints, and slings.”

Level 1 events were those requiring time-sensitive, critical intervention, including high-risk sepsis. Level 2 events included most level 1 events that occurred after the first hour (except operating room admission or hospital transfer) as well as respiratory therapy, toxicology consult, lumbar puncture, suicidality as chief concern, at least 2 doses of albuterol or continuous albuterol nebulization, a skeletal survey x-ray order, and medical social work consult with an ED length of stay of at least 2 hours. Level 3 events included IV mediation order, any CT order, OR admission or hospital transfer after one hour, or any pediatric hospitalist consult.
 

Analyzing the ED Visits

Overtriaged cases were ESI level 1 or 2 cases in which fewer than 2 resources were used; level 3 cases where fewer than 2 resources were used and no level 1 or 2 events occurred; and level 4 cases where no resources were used.

Undertriaged cases were defined as the following:

• ESI level 5 cases where any resource was used and any level 1, 2, or 3 events occurred.
• Level 4 cases where more than 1 resource was used and any level 1, 2, or 3 events occurred.
• Level 3 cases where any level 1 event occurred, more than one level 2 event occurred, or any level 2 event occurred and more than one additional ED resource type was used.
• Level 2 cases where any level 1 event occurred.

About half the visits (51%) were assigned ESI 3, which was the category with the highest proportion of mistriage. After adjusting for study facility and triage vital signs, the researchers found that children age 6 and older were more likely to be undertriaged than those younger than 6, particularly those age 15 and older (relative risk [RR], 1.36).

Undertriage was also modestly more likely with male patients (female patients’ RR, 0.93), patients with comorbidities (RR, 1.11-1.2), patients who arrived by ambulance (RR, 1.04), and patients who were Asian (RR, 1.10), Black (RR, 1.05), or Hispanic (RR, 1.04). Undertriage became gradually less likely with each additional year in the study period, with an RR of 0.89 in 2019 and 2020.

Among the study’s limitations were use of ESI version 4, instead of the currently used 5, and the omission of common procedures from the outcome definition that “may systematically bias the analysis toward overtriage,” the editorial noted. The authors also did not include pain as a variable in the analysis, which can often indicate patient acuity.

Further, this study was unable to include covariates identified in other research that may influence clinical decision-making, such as “the presenting illness or injury, children with complex medical needs, and language proficiency,” Dr. Frankenberger and colleagues wrote. “Furthermore, environmental stressors, such as ED volume and crowding, can influence how a nurse prioritizes care and may increase bias in decision-making and/or increase practice variability.”

The study was funded by the Kaiser Permanente Northern California (KPNC) Community Health program. One author had consulting payments from CSL Behring and Abbott Point-of-Care, and six of the authors have received grant funding from the KPNC Community Health program. The editorial authors reported no conflicts of interest.

Only one third of pediatric patients were correctly triaged at emergency departments (EDs) in a northern California health care system, according to a multicenter retrospective study published in JAMA Pediatrics. Researchers also identified gender, age, race, ethnicity, and comorbidity disparities in those who were undertriaged.

The researchers found that only 34.1% of visits were correctly triaged while 58.5% were overtriaged and 7.4% were undertriaged. The findings were based on analysis of more than 1 million pediatric emergency visits over a 5-year period that used the Emergency Severity Index (ESI) version 4 for triage.

“The ESI had poor sensitivity in identifying a critically ill pediatric patient, and undertriage occurred in 1 in 14 children,” wrote Dana R. Sax, MD, a senior emergency physician at The Permanente Medical Group in northern California, and her colleagues.

Disparities in Emergency Care

The results underscore the need for more work to address disparities in emergency care, wrote Warren D. Frankenberger, PhD, RN, a nurse scientist at Children’s Hospital of Philadelphia, and two colleagues in an accompanying editorial.

“Decisions in triage can have significant downstream effects on subsequent care during the ED visit,” they wrote in their editorial. “Given that the triage process in most instances is fully executed by nurses, nurse researchers are in a key position to evaluate these and other covariates to influence further improvements in triage.” They suggested that use of clinical decision support tools and artificial intelligence (AI) may improve the triage process, albeit with the caveat that AI often relies on models with pre-existing historical bias that may perpetuate structural inequalities.
 

Study Methodology

The researchers analyzed 1,016,816 pediatric visits at 21 emergency departments in Kaiser Permanente Northern California between January 2016 and December 2020. The patients were an average 7 years old, and 47% were female. The researchers excluded visits that lacked ESI data or had incomplete ED time variables as well as those with patients who left against medical advice, were not seen, or were transferred from another ED.

The study relied on novel definitions of ESI undertriage and overtriage developed through a modified Delphi process by a team of four emergency physicians, one pediatric emergency physician, two emergency nurses, and one pediatric ICU physician. The definition involved comparing ESI levels to the clinical outcomes and resource use.

Resources included laboratory analysis, electrocardiography, radiography, CT, MRI, diagnostic ultrasonography (not point of care), angiography, IV fluids, and IV, intramuscular, or nebulized medications. Resources did not include “oral medications, tetanus immunizations, point-of-care testing, history and physical examination, saline or heparin lock, prescription refills, simple wound care, crutches, splints, and slings.”

Level 1 events were those requiring time-sensitive, critical intervention, including high-risk sepsis. Level 2 events included most level 1 events that occurred after the first hour (except operating room admission or hospital transfer) as well as respiratory therapy, toxicology consult, lumbar puncture, suicidality as chief concern, at least 2 doses of albuterol or continuous albuterol nebulization, a skeletal survey x-ray order, and medical social work consult with an ED length of stay of at least 2 hours. Level 3 events included IV mediation order, any CT order, OR admission or hospital transfer after one hour, or any pediatric hospitalist consult.
 

Analyzing the ED Visits

Overtriaged cases were ESI level 1 or 2 cases in which fewer than 2 resources were used; level 3 cases where fewer than 2 resources were used and no level 1 or 2 events occurred; and level 4 cases where no resources were used.

Undertriaged cases were defined as the following:

• ESI level 5 cases where any resource was used and any level 1, 2, or 3 events occurred.
• Level 4 cases where more than 1 resource was used and any level 1, 2, or 3 events occurred.
• Level 3 cases where any level 1 event occurred, more than one level 2 event occurred, or any level 2 event occurred and more than one additional ED resource type was used.
• Level 2 cases where any level 1 event occurred.

About half the visits (51%) were assigned ESI 3, which was the category with the highest proportion of mistriage. After adjusting for study facility and triage vital signs, the researchers found that children age 6 and older were more likely to be undertriaged than those younger than 6, particularly those age 15 and older (relative risk [RR], 1.36).

Undertriage was also modestly more likely with male patients (female patients’ RR, 0.93), patients with comorbidities (RR, 1.11-1.2), patients who arrived by ambulance (RR, 1.04), and patients who were Asian (RR, 1.10), Black (RR, 1.05), or Hispanic (RR, 1.04). Undertriage became gradually less likely with each additional year in the study period, with an RR of 0.89 in 2019 and 2020.

Among the study’s limitations were use of ESI version 4, instead of the currently used 5, and the omission of common procedures from the outcome definition that “may systematically bias the analysis toward overtriage,” the editorial noted. The authors also did not include pain as a variable in the analysis, which can often indicate patient acuity.

Further, this study was unable to include covariates identified in other research that may influence clinical decision-making, such as “the presenting illness or injury, children with complex medical needs, and language proficiency,” Dr. Frankenberger and colleagues wrote. “Furthermore, environmental stressors, such as ED volume and crowding, can influence how a nurse prioritizes care and may increase bias in decision-making and/or increase practice variability.”

The study was funded by the Kaiser Permanente Northern California (KPNC) Community Health program. One author had consulting payments from CSL Behring and Abbott Point-of-Care, and six of the authors have received grant funding from the KPNC Community Health program. The editorial authors reported no conflicts of interest.

Only one third of pediatric patients were correctly triaged at emergency departments (EDs) in a northern California health care system, according to a multicenter retrospective study published in JAMA Pediatrics. Researchers also identified gender, age, race, ethnicity, and comorbidity disparities in those who were undertriaged.

The researchers found that only 34.1% of visits were correctly triaged while 58.5% were overtriaged and 7.4% were undertriaged. The findings were based on analysis of more than 1 million pediatric emergency visits over a 5-year period that used the Emergency Severity Index (ESI) version 4 for triage.

“The ESI had poor sensitivity in identifying a critically ill pediatric patient, and undertriage occurred in 1 in 14 children,” wrote Dana R. Sax, MD, a senior emergency physician at The Permanente Medical Group in northern California, and her colleagues.

Disparities in Emergency Care

The results underscore the need for more work to address disparities in emergency care, wrote Warren D. Frankenberger, PhD, RN, a nurse scientist at Children’s Hospital of Philadelphia, and two colleagues in an accompanying editorial.

“Decisions in triage can have significant downstream effects on subsequent care during the ED visit,” they wrote in their editorial. “Given that the triage process in most instances is fully executed by nurses, nurse researchers are in a key position to evaluate these and other covariates to influence further improvements in triage.” They suggested that use of clinical decision support tools and artificial intelligence (AI) may improve the triage process, albeit with the caveat that AI often relies on models with pre-existing historical bias that may perpetuate structural inequalities.
 

Study Methodology

The researchers analyzed 1,016,816 pediatric visits at 21 emergency departments in Kaiser Permanente Northern California between January 2016 and December 2020. The patients were an average 7 years old, and 47% were female. The researchers excluded visits that lacked ESI data or had incomplete ED time variables as well as those with patients who left against medical advice, were not seen, or were transferred from another ED.

The study relied on novel definitions of ESI undertriage and overtriage developed through a modified Delphi process by a team of four emergency physicians, one pediatric emergency physician, two emergency nurses, and one pediatric ICU physician. The definition involved comparing ESI levels to the clinical outcomes and resource use.

Resources included laboratory analysis, electrocardiography, radiography, CT, MRI, diagnostic ultrasonography (not point of care), angiography, IV fluids, and IV, intramuscular, or nebulized medications. Resources did not include “oral medications, tetanus immunizations, point-of-care testing, history and physical examination, saline or heparin lock, prescription refills, simple wound care, crutches, splints, and slings.”

Level 1 events were those requiring time-sensitive, critical intervention, including high-risk sepsis. Level 2 events included most level 1 events that occurred after the first hour (except operating room admission or hospital transfer) as well as respiratory therapy, toxicology consult, lumbar puncture, suicidality as chief concern, at least 2 doses of albuterol or continuous albuterol nebulization, a skeletal survey x-ray order, and medical social work consult with an ED length of stay of at least 2 hours. Level 3 events included IV mediation order, any CT order, OR admission or hospital transfer after one hour, or any pediatric hospitalist consult.
 

Analyzing the ED Visits

Overtriaged cases were ESI level 1 or 2 cases in which fewer than 2 resources were used; level 3 cases where fewer than 2 resources were used and no level 1 or 2 events occurred; and level 4 cases where no resources were used.

Undertriaged cases were defined as the following:

• ESI level 5 cases where any resource was used and any level 1, 2, or 3 events occurred.
• Level 4 cases where more than 1 resource was used and any level 1, 2, or 3 events occurred.
• Level 3 cases where any level 1 event occurred, more than one level 2 event occurred, or any level 2 event occurred and more than one additional ED resource type was used.
• Level 2 cases where any level 1 event occurred.

About half the visits (51%) were assigned ESI 3, which was the category with the highest proportion of mistriage. After adjusting for study facility and triage vital signs, the researchers found that children age 6 and older were more likely to be undertriaged than those younger than 6, particularly those age 15 and older (relative risk [RR], 1.36).

Undertriage was also modestly more likely with male patients (female patients’ RR, 0.93), patients with comorbidities (RR, 1.11-1.2), patients who arrived by ambulance (RR, 1.04), and patients who were Asian (RR, 1.10), Black (RR, 1.05), or Hispanic (RR, 1.04). Undertriage became gradually less likely with each additional year in the study period, with an RR of 0.89 in 2019 and 2020.

Among the study’s limitations were use of ESI version 4, instead of the currently used 5, and the omission of common procedures from the outcome definition that “may systematically bias the analysis toward overtriage,” the editorial noted. The authors also did not include pain as a variable in the analysis, which can often indicate patient acuity.

Further, this study was unable to include covariates identified in other research that may influence clinical decision-making, such as “the presenting illness or injury, children with complex medical needs, and language proficiency,” Dr. Frankenberger and colleagues wrote. “Furthermore, environmental stressors, such as ED volume and crowding, can influence how a nurse prioritizes care and may increase bias in decision-making and/or increase practice variability.”

The study was funded by the Kaiser Permanente Northern California (KPNC) Community Health program. One author had consulting payments from CSL Behring and Abbott Point-of-Care, and six of the authors have received grant funding from the KPNC Community Health program. The editorial authors reported no conflicts of interest.

Bicycles have been woven into my life since I first straddled a hand-me-down with a fan belt drive when I was 3. At age 12 my friend Ricky and I took a 250 mile–plus 2-night adventure on our 3-speed “English” style bikes. We still marvel that our parents let us do it when neither cell phones nor GPS existed.

I have always bike commuted to work, including the years when that involved a perilous navigation into Boston from the suburbs. In our mid-50s my wife and I biked from Washington state back here to Maine with another couple unsupported. We continue to do at least one self-guided cycle tour out of the country each year.

Not surprisingly, I keep a close eye on what’s happening in the bicycle market. For decades the trends have shifted back and forth between sleek road models and beefier off-roaders. There have been boom years here and there for the dealers and manufacturers, but nothing like what the bike industry is experiencing now with the arrival of e-bikes on the market. Driven primarily by electrification, micromobility ridership (which includes conventional bikes and scooters) has grown more than 50-fold over the last 10 years. Projections suggest the market’s value will be $300 billion by 2030.

It doesn’t take an MBA with a major in marketing to understand the broad appeal of electrification. Most adults have ridden a bicycle as children, but several decades of gap years has left many of them with a level of fitness that makes pedaling against the wind or up any incline difficult and unappealing. An e-bike can put even the least fitness conscious back in the saddle and open the options for outdoor recreation they haven’t dreamed of since childhood.

In large part the people flocking to e-bikes are retiree’s who thought they were “over the hill.” They are having so much fun they don’t care if the Lycra-clad “serious” cyclists notice the battery bulge in the frame on their e-bikes. Another group of e-bike adopters are motivated by the “greenness” of a fossil-fuel–free electric powered transportation which, with minimal compromise, can be used as they would a car around town and for longer commutes than they would have considered on a purely pedal-powered bicycle.

Unfortunately, there is a growing group of younger e-bike riders who are motivated and uninhibited by the potential that the power boost of a small electric motor can provide. And here is where the ugliness begins to intrude on what was otherwise a beautiful and expanding landscape. With the increase in e-bike popularity, there has been an understandable increase in injuries in all age groups. However, it is the young who are, not surprisingly, drawn to the speed, and with any vehicle – motorized or conventional – as speed increases so does the frequency and seriousness of accidents.

The term e-bike covers a broad range of vehicles, from those designated class 1, which require pedaling and are limited to 20 miles per hour, to class 3, which may have a throttle and unmodified can hit 28 mph. Class 2 bikes have a throttle that will allow the rider to reach 20 mph without pedaling. Modifying any class of e-bike can substantially increase its speed, but this is more common in classes 2 and 3. As an example, some very fast micromobiles are considered unclassified e-bikes and avoid being labeled motorcycles simply because they have pedals.

One has to give some credit to the e-bike industry for eventually adopting this classification system. But, we must give the rest of us, including parents and public safety officials, a failing grade for doing a poor job of translating these scores into enforceable regulations to protect both riders and pedestrians from serious injury.

On the governmental side only a little more than half of US states have used the three category classification to craft their regulations. Many jurisdictions have failed to differentiate between streets, sidewalks, and trails. Regulations vary from state to state, and many states leave it up to local communities. From my experience chairing our town’s Bicycle and Pedestrian Advisory Committee, I can tell you that even “progressive” communities are struggling to decide who can ride what where. The result has been that people of all ages, but mostly adolescents, are traveling on busy streets and sidewalks at speeds that put themselves and pedestrians at risk.

On the parental side of the problem are families that have either allowed or enabled their children to ride class 2 and 3 e-bikes without proper safety equipment or consideration for the safety of the rest of the community. Currently, this is not much of a problem here in Maine thanks to the weather and the high price of e-bikes. However, I frequently visit an affluent community in the San Francisco Bay Area, where it is not uncommon to see middle school children speeding along well in excess of 20 mph.

Unfortunately this is another example, like television and cell phone, in which our society has been unable to keep up with technology by molding the behavior of our children and/or creating enforceable rules that allow us to reap the benefits of new discoveries while minimizing the collateral damage that can accompany them.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Bicycles have been woven into my life since I first straddled a hand-me-down with a fan belt drive when I was 3. At age 12 my friend Ricky and I took a 250 mile–plus 2-night adventure on our 3-speed “English” style bikes. We still marvel that our parents let us do it when neither cell phones nor GPS existed.

I have always bike commuted to work, including the years when that involved a perilous navigation into Boston from the suburbs. In our mid-50s my wife and I biked from Washington state back here to Maine with another couple unsupported. We continue to do at least one self-guided cycle tour out of the country each year.

Not surprisingly, I keep a close eye on what’s happening in the bicycle market. For decades the trends have shifted back and forth between sleek road models and beefier off-roaders. There have been boom years here and there for the dealers and manufacturers, but nothing like what the bike industry is experiencing now with the arrival of e-bikes on the market. Driven primarily by electrification, micromobility ridership (which includes conventional bikes and scooters) has grown more than 50-fold over the last 10 years. Projections suggest the market’s value will be $300 billion by 2030.

It doesn’t take an MBA with a major in marketing to understand the broad appeal of electrification. Most adults have ridden a bicycle as children, but several decades of gap years has left many of them with a level of fitness that makes pedaling against the wind or up any incline difficult and unappealing. An e-bike can put even the least fitness conscious back in the saddle and open the options for outdoor recreation they haven’t dreamed of since childhood.

In large part the people flocking to e-bikes are retiree’s who thought they were “over the hill.” They are having so much fun they don’t care if the Lycra-clad “serious” cyclists notice the battery bulge in the frame on their e-bikes. Another group of e-bike adopters are motivated by the “greenness” of a fossil-fuel–free electric powered transportation which, with minimal compromise, can be used as they would a car around town and for longer commutes than they would have considered on a purely pedal-powered bicycle.

Unfortunately, there is a growing group of younger e-bike riders who are motivated and uninhibited by the potential that the power boost of a small electric motor can provide. And here is where the ugliness begins to intrude on what was otherwise a beautiful and expanding landscape. With the increase in e-bike popularity, there has been an understandable increase in injuries in all age groups. However, it is the young who are, not surprisingly, drawn to the speed, and with any vehicle – motorized or conventional – as speed increases so does the frequency and seriousness of accidents.

The term e-bike covers a broad range of vehicles, from those designated class 1, which require pedaling and are limited to 20 miles per hour, to class 3, which may have a throttle and unmodified can hit 28 mph. Class 2 bikes have a throttle that will allow the rider to reach 20 mph without pedaling. Modifying any class of e-bike can substantially increase its speed, but this is more common in classes 2 and 3. As an example, some very fast micromobiles are considered unclassified e-bikes and avoid being labeled motorcycles simply because they have pedals.

One has to give some credit to the e-bike industry for eventually adopting this classification system. But, we must give the rest of us, including parents and public safety officials, a failing grade for doing a poor job of translating these scores into enforceable regulations to protect both riders and pedestrians from serious injury.

On the governmental side only a little more than half of US states have used the three category classification to craft their regulations. Many jurisdictions have failed to differentiate between streets, sidewalks, and trails. Regulations vary from state to state, and many states leave it up to local communities. From my experience chairing our town’s Bicycle and Pedestrian Advisory Committee, I can tell you that even “progressive” communities are struggling to decide who can ride what where. The result has been that people of all ages, but mostly adolescents, are traveling on busy streets and sidewalks at speeds that put themselves and pedestrians at risk.

On the parental side of the problem are families that have either allowed or enabled their children to ride class 2 and 3 e-bikes without proper safety equipment or consideration for the safety of the rest of the community. Currently, this is not much of a problem here in Maine thanks to the weather and the high price of e-bikes. However, I frequently visit an affluent community in the San Francisco Bay Area, where it is not uncommon to see middle school children speeding along well in excess of 20 mph.

Unfortunately this is another example, like television and cell phone, in which our society has been unable to keep up with technology by molding the behavior of our children and/or creating enforceable rules that allow us to reap the benefits of new discoveries while minimizing the collateral damage that can accompany them.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Bicycles have been woven into my life since I first straddled a hand-me-down with a fan belt drive when I was 3. At age 12 my friend Ricky and I took a 250 mile–plus 2-night adventure on our 3-speed “English” style bikes. We still marvel that our parents let us do it when neither cell phones nor GPS existed.

I have always bike commuted to work, including the years when that involved a perilous navigation into Boston from the suburbs. In our mid-50s my wife and I biked from Washington state back here to Maine with another couple unsupported. We continue to do at least one self-guided cycle tour out of the country each year.

Not surprisingly, I keep a close eye on what’s happening in the bicycle market. For decades the trends have shifted back and forth between sleek road models and beefier off-roaders. There have been boom years here and there for the dealers and manufacturers, but nothing like what the bike industry is experiencing now with the arrival of e-bikes on the market. Driven primarily by electrification, micromobility ridership (which includes conventional bikes and scooters) has grown more than 50-fold over the last 10 years. Projections suggest the market’s value will be $300 billion by 2030.

It doesn’t take an MBA with a major in marketing to understand the broad appeal of electrification. Most adults have ridden a bicycle as children, but several decades of gap years has left many of them with a level of fitness that makes pedaling against the wind or up any incline difficult and unappealing. An e-bike can put even the least fitness conscious back in the saddle and open the options for outdoor recreation they haven’t dreamed of since childhood.

In large part the people flocking to e-bikes are retiree’s who thought they were “over the hill.” They are having so much fun they don’t care if the Lycra-clad “serious” cyclists notice the battery bulge in the frame on their e-bikes. Another group of e-bike adopters are motivated by the “greenness” of a fossil-fuel–free electric powered transportation which, with minimal compromise, can be used as they would a car around town and for longer commutes than they would have considered on a purely pedal-powered bicycle.

Unfortunately, there is a growing group of younger e-bike riders who are motivated and uninhibited by the potential that the power boost of a small electric motor can provide. And here is where the ugliness begins to intrude on what was otherwise a beautiful and expanding landscape. With the increase in e-bike popularity, there has been an understandable increase in injuries in all age groups. However, it is the young who are, not surprisingly, drawn to the speed, and with any vehicle – motorized or conventional – as speed increases so does the frequency and seriousness of accidents.

The term e-bike covers a broad range of vehicles, from those designated class 1, which require pedaling and are limited to 20 miles per hour, to class 3, which may have a throttle and unmodified can hit 28 mph. Class 2 bikes have a throttle that will allow the rider to reach 20 mph without pedaling. Modifying any class of e-bike can substantially increase its speed, but this is more common in classes 2 and 3. As an example, some very fast micromobiles are considered unclassified e-bikes and avoid being labeled motorcycles simply because they have pedals.

One has to give some credit to the e-bike industry for eventually adopting this classification system. But, we must give the rest of us, including parents and public safety officials, a failing grade for doing a poor job of translating these scores into enforceable regulations to protect both riders and pedestrians from serious injury.

On the governmental side only a little more than half of US states have used the three category classification to craft their regulations. Many jurisdictions have failed to differentiate between streets, sidewalks, and trails. Regulations vary from state to state, and many states leave it up to local communities. From my experience chairing our town’s Bicycle and Pedestrian Advisory Committee, I can tell you that even “progressive” communities are struggling to decide who can ride what where. The result has been that people of all ages, but mostly adolescents, are traveling on busy streets and sidewalks at speeds that put themselves and pedestrians at risk.

On the parental side of the problem are families that have either allowed or enabled their children to ride class 2 and 3 e-bikes without proper safety equipment or consideration for the safety of the rest of the community. Currently, this is not much of a problem here in Maine thanks to the weather and the high price of e-bikes. However, I frequently visit an affluent community in the San Francisco Bay Area, where it is not uncommon to see middle school children speeding along well in excess of 20 mph.

Unfortunately this is another example, like television and cell phone, in which our society has been unable to keep up with technology by molding the behavior of our children and/or creating enforceable rules that allow us to reap the benefits of new discoveries while minimizing the collateral damage that can accompany them.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Many, many years ago there was a Thanksgiving when as I was just beginning to earn a reputation in my wife’s family. There were no place cards on the table and the usual hovering and jockeying seats was well underway. From behind me I heard one of my young nieces pipe up: “I want to sit next to Doctor I-don’t-know.”

After a few words of negotiation we were all settled in our places and ready to enjoy our meal. It took only a few seconds of introspection for me to grasp how I had received that moniker, which some physicians might consider disrespectful.

I was the only physician within several generations of that family and, as such, my in-laws thought it only appropriate to ask me medical questions. They courteously seemed to avoid personal questions about their own health and were particularly careful not to roll up their sleeves or unbutton their shirts to show me a lesion or a recently acquired surgical scar. No, my wife’s family members were curious. They wanted answers to deeper questions, the hard science so to speak. “How does aspirin work?” was a typical and painful example. Maybe pharmacologists today have better answers but 40 years ago I’m not so sure; I certainly didn’t know back then and would reply, “I don’t know.” Probably for the third or fourth time that day.

Usually I genuinely didn’t know the answer. However, sometimes my answer was going to be so different from the beliefs and biases of my inquisitor that, in the interest of expediency, “I don’t know” seemed the most appropriate response.

If you were reading Letters from Maine 25 years ago, that scenario might sound familiar. I have chosen to pull it out of the archives as a jumping-off point for a consideration of the unfortunate example some of us set when the COVID pandemic threw a tsunami of unknowns at us. Too many physician-“experts” were afraid to say, “I don’t know.” Instead, and maybe because, they themselves were afraid that the patients couldn’t handle the truth that none of us in the profession knew the correct answers. When so many initial pronouncements proved incorrect, it was too late to undo the damage that had been done to the community’s trust in the rest of us.

It turns out that my in-laws were not the only folks who thought of me as Doctor I-don’t-know. One of the perks of remaining in the same community after one retires is that encounters with former patients and their parents happen frequently. On more than one occasion a parent has thanked me for admitting my ignorance. Some have even claimed that my candid approach was what they remembered most fondly. And, that quality increased their trust when I finally provided an answer.

There is an art to delivering “I don’t know.” Thirty years ago I would excuse myself and tell the family I was going to my office to pull a book off the shelf or call a previous mentor. Now one only needs to ask Dr. Google. No need to leave the room. If appropriate, the provider can swing the computer screen so that the patient can share in the search for the answer.

That strategy only works when the provider merely needs to update or expand his/her knowledge. However, there are those difficult situations when no one could know the answer given the current parameters of the patient’s situation. More lab work might be needed. It may be too early in the trajectory of the patient’s illness for the illnesses signs and symptoms to declare themselves.

In these situations “I don’t know” must be followed by a “but.” It is what comes after that “but” and how it is delivered that can convert the provider’s admission of ignorance into a demonstration of his or her character. Is he/she a caring person trying to understand the patient’s concerns? Willing to enter into a cooperative relationship as together they search for the cause and hopefully for a cure for the patient’s currently mysterious illness?

I recently read about a physician who is encouraging medical educators to incorporate more discussions of “humility” and its role in patient care into the medical school and postgraduate training curricula. He feels, as do I, that if more physicians learned to say “I don’t know” early in their careers, the quality of care we are delivering as a profession will improve, as will the trust bestowed by our patients.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Many, many years ago there was a Thanksgiving when as I was just beginning to earn a reputation in my wife’s family. There were no place cards on the table and the usual hovering and jockeying seats was well underway. From behind me I heard one of my young nieces pipe up: “I want to sit next to Doctor I-don’t-know.”

After a few words of negotiation we were all settled in our places and ready to enjoy our meal. It took only a few seconds of introspection for me to grasp how I had received that moniker, which some physicians might consider disrespectful.

I was the only physician within several generations of that family and, as such, my in-laws thought it only appropriate to ask me medical questions. They courteously seemed to avoid personal questions about their own health and were particularly careful not to roll up their sleeves or unbutton their shirts to show me a lesion or a recently acquired surgical scar. No, my wife’s family members were curious. They wanted answers to deeper questions, the hard science so to speak. “How does aspirin work?” was a typical and painful example. Maybe pharmacologists today have better answers but 40 years ago I’m not so sure; I certainly didn’t know back then and would reply, “I don’t know.” Probably for the third or fourth time that day.

Usually I genuinely didn’t know the answer. However, sometimes my answer was going to be so different from the beliefs and biases of my inquisitor that, in the interest of expediency, “I don’t know” seemed the most appropriate response.

If you were reading Letters from Maine 25 years ago, that scenario might sound familiar. I have chosen to pull it out of the archives as a jumping-off point for a consideration of the unfortunate example some of us set when the COVID pandemic threw a tsunami of unknowns at us. Too many physician-“experts” were afraid to say, “I don’t know.” Instead, and maybe because, they themselves were afraid that the patients couldn’t handle the truth that none of us in the profession knew the correct answers. When so many initial pronouncements proved incorrect, it was too late to undo the damage that had been done to the community’s trust in the rest of us.

It turns out that my in-laws were not the only folks who thought of me as Doctor I-don’t-know. One of the perks of remaining in the same community after one retires is that encounters with former patients and their parents happen frequently. On more than one occasion a parent has thanked me for admitting my ignorance. Some have even claimed that my candid approach was what they remembered most fondly. And, that quality increased their trust when I finally provided an answer.

There is an art to delivering “I don’t know.” Thirty years ago I would excuse myself and tell the family I was going to my office to pull a book off the shelf or call a previous mentor. Now one only needs to ask Dr. Google. No need to leave the room. If appropriate, the provider can swing the computer screen so that the patient can share in the search for the answer.

That strategy only works when the provider merely needs to update or expand his/her knowledge. However, there are those difficult situations when no one could know the answer given the current parameters of the patient’s situation. More lab work might be needed. It may be too early in the trajectory of the patient’s illness for the illnesses signs and symptoms to declare themselves.

In these situations “I don’t know” must be followed by a “but.” It is what comes after that “but” and how it is delivered that can convert the provider’s admission of ignorance into a demonstration of his or her character. Is he/she a caring person trying to understand the patient’s concerns? Willing to enter into a cooperative relationship as together they search for the cause and hopefully for a cure for the patient’s currently mysterious illness?

I recently read about a physician who is encouraging medical educators to incorporate more discussions of “humility” and its role in patient care into the medical school and postgraduate training curricula. He feels, as do I, that if more physicians learned to say “I don’t know” early in their careers, the quality of care we are delivering as a profession will improve, as will the trust bestowed by our patients.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Many, many years ago there was a Thanksgiving when as I was just beginning to earn a reputation in my wife’s family. There were no place cards on the table and the usual hovering and jockeying seats was well underway. From behind me I heard one of my young nieces pipe up: “I want to sit next to Doctor I-don’t-know.”

After a few words of negotiation we were all settled in our places and ready to enjoy our meal. It took only a few seconds of introspection for me to grasp how I had received that moniker, which some physicians might consider disrespectful.

I was the only physician within several generations of that family and, as such, my in-laws thought it only appropriate to ask me medical questions. They courteously seemed to avoid personal questions about their own health and were particularly careful not to roll up their sleeves or unbutton their shirts to show me a lesion or a recently acquired surgical scar. No, my wife’s family members were curious. They wanted answers to deeper questions, the hard science so to speak. “How does aspirin work?” was a typical and painful example. Maybe pharmacologists today have better answers but 40 years ago I’m not so sure; I certainly didn’t know back then and would reply, “I don’t know.” Probably for the third or fourth time that day.

Usually I genuinely didn’t know the answer. However, sometimes my answer was going to be so different from the beliefs and biases of my inquisitor that, in the interest of expediency, “I don’t know” seemed the most appropriate response.

If you were reading Letters from Maine 25 years ago, that scenario might sound familiar. I have chosen to pull it out of the archives as a jumping-off point for a consideration of the unfortunate example some of us set when the COVID pandemic threw a tsunami of unknowns at us. Too many physician-“experts” were afraid to say, “I don’t know.” Instead, and maybe because, they themselves were afraid that the patients couldn’t handle the truth that none of us in the profession knew the correct answers. When so many initial pronouncements proved incorrect, it was too late to undo the damage that had been done to the community’s trust in the rest of us.

It turns out that my in-laws were not the only folks who thought of me as Doctor I-don’t-know. One of the perks of remaining in the same community after one retires is that encounters with former patients and their parents happen frequently. On more than one occasion a parent has thanked me for admitting my ignorance. Some have even claimed that my candid approach was what they remembered most fondly. And, that quality increased their trust when I finally provided an answer.

There is an art to delivering “I don’t know.” Thirty years ago I would excuse myself and tell the family I was going to my office to pull a book off the shelf or call a previous mentor. Now one only needs to ask Dr. Google. No need to leave the room. If appropriate, the provider can swing the computer screen so that the patient can share in the search for the answer.

That strategy only works when the provider merely needs to update or expand his/her knowledge. However, there are those difficult situations when no one could know the answer given the current parameters of the patient’s situation. More lab work might be needed. It may be too early in the trajectory of the patient’s illness for the illnesses signs and symptoms to declare themselves.

In these situations “I don’t know” must be followed by a “but.” It is what comes after that “but” and how it is delivered that can convert the provider’s admission of ignorance into a demonstration of his or her character. Is he/she a caring person trying to understand the patient’s concerns? Willing to enter into a cooperative relationship as together they search for the cause and hopefully for a cure for the patient’s currently mysterious illness?

I recently read about a physician who is encouraging medical educators to incorporate more discussions of “humility” and its role in patient care into the medical school and postgraduate training curricula. He feels, as do I, that if more physicians learned to say “I don’t know” early in their careers, the quality of care we are delivering as a profession will improve, as will the trust bestowed by our patients.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

TOPLINE:

Uptake of infliximab biosimilars rose slowly across private insurance, Medicaid, and Medicare when two were available in the United States during 2016-2020 but increased significantly through 2022 after the third biosimilar became available in July 2020. However, prescriptions in Medicare still lagged behind those in private insurance and Medicaid.

METHODOLOGY:

• Researchers analyzed electronic health records from over 1100 US rheumatologists who participated in a national registry, the Rheumatology Informatics System for Effectiveness (RISE), for all infliximab administrations (bio-originator or biosimilar) to patients older than 18 years from April 2016 to September 2022.
• They conducted an interrupted time series to account for autocorrelation and model the effect of each infliximab biosimilar release (infliximab-dyyb in November 2016, infliximab-abda in July 2017, and infliximab-axxq in July 2020) on uptake across Medicare, Medicaid, and private insurers.

TAKEAWAY:

• The researchers identified 659,988 infliximab administrations for 37,560 unique patients, with 52% on Medicare, 4.8% on Medicaid, and 43% on private insurance.
• Biosimilar uptake rose slowly with average annual increases < 5% from 2016 to June 2020 (Medicare, 3.2%; Medicaid, 5.2%; private insurance, 1.8%).
• After the third biosimilar release in July 2020, the average annual increase reached 13% for Medicaid and 16.4% for private insurance but remained low for Medicare (5.6%).
• By September 2022, biosimilar uptake was higher for Medicaid (43.8%) and private insurance (38.5%) than for Medicare (24%).

IN PRACTICE:

“Our results suggest policymakers may need to do more to allow biosimilars to get a foothold in the market by incentivizing the development and entry of multiple biosimilars, address anticompetitive pricing strategies, and may need to amend Medicare policy to [incentivize] uptake in order to ensure a competitive and sustainable biosimilar market that gradually reduces total drug expenditures and out-of-pocket costs over time,” wrote the authors of the study.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco. It was published online on July 30, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

First, while the biosimilar introductions are likely catalysts for many changes in the market, some changes in slopes may also be attributable to the natural growth of the market over time. Second, this study may neither be generalizable to academic medical centers, which are underrepresented in RISE, nor be generalizable to infliximab prescriptions from other specialties. Third, uptake among privately insured patients changed shortly after November-December 2020, raising the possibility that the delay reflected negotiations between insurance companies and relevant entities regarding formulary coverage.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author disclosed receiving consulting fees from Pfizer, AstraZeneca, and Bristol-Myers Squibb and grant funding from AstraZeneca, the Bristol-Myers Squibb Foundation, and Aurinia.

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 first appeared on Medscape.com.

TOPLINE:

Uptake of infliximab biosimilars rose slowly across private insurance, Medicaid, and Medicare when two were available in the United States during 2016-2020 but increased significantly through 2022 after the third biosimilar became available in July 2020. However, prescriptions in Medicare still lagged behind those in private insurance and Medicaid.

METHODOLOGY:

• Researchers analyzed electronic health records from over 1100 US rheumatologists who participated in a national registry, the Rheumatology Informatics System for Effectiveness (RISE), for all infliximab administrations (bio-originator or biosimilar) to patients older than 18 years from April 2016 to September 2022.
• They conducted an interrupted time series to account for autocorrelation and model the effect of each infliximab biosimilar release (infliximab-dyyb in November 2016, infliximab-abda in July 2017, and infliximab-axxq in July 2020) on uptake across Medicare, Medicaid, and private insurers.

TAKEAWAY:

• The researchers identified 659,988 infliximab administrations for 37,560 unique patients, with 52% on Medicare, 4.8% on Medicaid, and 43% on private insurance.
• Biosimilar uptake rose slowly with average annual increases < 5% from 2016 to June 2020 (Medicare, 3.2%; Medicaid, 5.2%; private insurance, 1.8%).
• After the third biosimilar release in July 2020, the average annual increase reached 13% for Medicaid and 16.4% for private insurance but remained low for Medicare (5.6%).
• By September 2022, biosimilar uptake was higher for Medicaid (43.8%) and private insurance (38.5%) than for Medicare (24%).

IN PRACTICE:

“Our results suggest policymakers may need to do more to allow biosimilars to get a foothold in the market by incentivizing the development and entry of multiple biosimilars, address anticompetitive pricing strategies, and may need to amend Medicare policy to [incentivize] uptake in order to ensure a competitive and sustainable biosimilar market that gradually reduces total drug expenditures and out-of-pocket costs over time,” wrote the authors of the study.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco. It was published online on July 30, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

First, while the biosimilar introductions are likely catalysts for many changes in the market, some changes in slopes may also be attributable to the natural growth of the market over time. Second, this study may neither be generalizable to academic medical centers, which are underrepresented in RISE, nor be generalizable to infliximab prescriptions from other specialties. Third, uptake among privately insured patients changed shortly after November-December 2020, raising the possibility that the delay reflected negotiations between insurance companies and relevant entities regarding formulary coverage.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author disclosed receiving consulting fees from Pfizer, AstraZeneca, and Bristol-Myers Squibb and grant funding from AstraZeneca, the Bristol-Myers Squibb Foundation, and Aurinia.

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 first appeared on Medscape.com.

TOPLINE:

Uptake of infliximab biosimilars rose slowly across private insurance, Medicaid, and Medicare when two were available in the United States during 2016-2020 but increased significantly through 2022 after the third biosimilar became available in July 2020. However, prescriptions in Medicare still lagged behind those in private insurance and Medicaid.

METHODOLOGY:

• Researchers analyzed electronic health records from over 1100 US rheumatologists who participated in a national registry, the Rheumatology Informatics System for Effectiveness (RISE), for all infliximab administrations (bio-originator or biosimilar) to patients older than 18 years from April 2016 to September 2022.
• They conducted an interrupted time series to account for autocorrelation and model the effect of each infliximab biosimilar release (infliximab-dyyb in November 2016, infliximab-abda in July 2017, and infliximab-axxq in July 2020) on uptake across Medicare, Medicaid, and private insurers.

TAKEAWAY:

• The researchers identified 659,988 infliximab administrations for 37,560 unique patients, with 52% on Medicare, 4.8% on Medicaid, and 43% on private insurance.
• Biosimilar uptake rose slowly with average annual increases < 5% from 2016 to June 2020 (Medicare, 3.2%; Medicaid, 5.2%; private insurance, 1.8%).
• After the third biosimilar release in July 2020, the average annual increase reached 13% for Medicaid and 16.4% for private insurance but remained low for Medicare (5.6%).
• By September 2022, biosimilar uptake was higher for Medicaid (43.8%) and private insurance (38.5%) than for Medicare (24%).

IN PRACTICE:

“Our results suggest policymakers may need to do more to allow biosimilars to get a foothold in the market by incentivizing the development and entry of multiple biosimilars, address anticompetitive pricing strategies, and may need to amend Medicare policy to [incentivize] uptake in order to ensure a competitive and sustainable biosimilar market that gradually reduces total drug expenditures and out-of-pocket costs over time,” wrote the authors of the study.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco. It was published online on July 30, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

First, while the biosimilar introductions are likely catalysts for many changes in the market, some changes in slopes may also be attributable to the natural growth of the market over time. Second, this study may neither be generalizable to academic medical centers, which are underrepresented in RISE, nor be generalizable to infliximab prescriptions from other specialties. Third, uptake among privately insured patients changed shortly after November-December 2020, raising the possibility that the delay reflected negotiations between insurance companies and relevant entities regarding formulary coverage.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author disclosed receiving consulting fees from Pfizer, AstraZeneca, and Bristol-Myers Squibb and grant funding from AstraZeneca, the Bristol-Myers Squibb Foundation, and Aurinia.

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 first appeared on Medscape.com.

TOPLINE:

Nemolizumab, an interleukin 31 receptor antagonist, was well tolerated and significantly improved inflammation and pruritus in patients with moderate to severe atopic dermatitis (AD).

METHODOLOGY:

• The researchers conducted two 48-week randomized, double-blind, placebo-controlled phase 3 trials, ARCADIA 1 (n = 941; 47% women) and ARCADIA 2 (n = 787; 52% women), involving patients aged 12 and older with moderate to severe AD.
• Participants were randomly assigned in a 2:1 ratio to receive either 30 mg nemolizumab (with a 60-mg loading dose) or placebo, along with background topical corticosteroids with or without topical calcineurin inhibitors. The mean age range was 33.3-35.2 years.
• The coprimary endpoints were Investigator’s Global Assessment (IGA) success (score of 0 or 1 with at least a two-point improvement from baseline) and at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16.

TAKEAWAY:

• At week 16, significantly more patients receiving nemolizumab vs placebo achieved IGA success in both the ARCADIA 1 (36% vs 25%; P = .0003) and ARCADIA 2 (38% vs 26%; P = .0006) trials.
• EASI-75 response rates were also significantly higher in the nemolizumab group than in the placebo group in both trials: ARCADIA 1 (44% vs 29%; P < .0001) and 2 (42% vs 30%; P = .0006).
• Significant improvements in pruritus were observed as early as week 1, with a greater proportion of participants in the nemolizumab vs placebo group achieving at least a four-point reduction in the Peak Pruritus Numerical Rating Scale score in both trials.
• Rates of adverse events were similar between the nemolizumab and placebo groups, with severe treatment-emergent adverse events occurring in 2%-4% of patients.

IN PRACTICE:

“Nemolizumab showed statistically and clinically significant improvements in inflammation and pruritus in adults and adolescents with moderate to severe atopic dermatitis and a rapid effect in reducing pruritus, as one of the primary complaints of patients. As such, nemolizumab might offer a valuable extension of the therapeutic armament if approved,” the authors concluded.

SOURCE:

The study was led by Jonathan Silverberg, MD, PhD, from the Department of Dermatology, George Washington University, Washington, DC. It was published online in The Lancet.

LIMITATIONS:

The study’s limitations included the absence of longer-term safety data. Additionally, the predominantly White population of the trials may limit the generalizability of the findings to other racial and ethnic groups. The use of concomitant topical therapy might have influenced the placebo response.

DISCLOSURES:

This study was funded by Galderma. Dr. Silverberg received honoraria from pharmaceutical companies, including Galderma, and his institution also received grants from Galderma, Incyte, and Pfizer. Four authors were employees of Galderma. Other authors also declared having ties with pharmaceutical companies, including Galderma, outside this work.

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 first appeared on Medscape.com.

TOPLINE:

Nemolizumab, an interleukin 31 receptor antagonist, was well tolerated and significantly improved inflammation and pruritus in patients with moderate to severe atopic dermatitis (AD).

METHODOLOGY:

• The researchers conducted two 48-week randomized, double-blind, placebo-controlled phase 3 trials, ARCADIA 1 (n = 941; 47% women) and ARCADIA 2 (n = 787; 52% women), involving patients aged 12 and older with moderate to severe AD.
• Participants were randomly assigned in a 2:1 ratio to receive either 30 mg nemolizumab (with a 60-mg loading dose) or placebo, along with background topical corticosteroids with or without topical calcineurin inhibitors. The mean age range was 33.3-35.2 years.
• The coprimary endpoints were Investigator’s Global Assessment (IGA) success (score of 0 or 1 with at least a two-point improvement from baseline) and at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16.

TAKEAWAY:

• At week 16, significantly more patients receiving nemolizumab vs placebo achieved IGA success in both the ARCADIA 1 (36% vs 25%; P = .0003) and ARCADIA 2 (38% vs 26%; P = .0006) trials.
• EASI-75 response rates were also significantly higher in the nemolizumab group than in the placebo group in both trials: ARCADIA 1 (44% vs 29%; P < .0001) and 2 (42% vs 30%; P = .0006).
• Significant improvements in pruritus were observed as early as week 1, with a greater proportion of participants in the nemolizumab vs placebo group achieving at least a four-point reduction in the Peak Pruritus Numerical Rating Scale score in both trials.
• Rates of adverse events were similar between the nemolizumab and placebo groups, with severe treatment-emergent adverse events occurring in 2%-4% of patients.

IN PRACTICE:

“Nemolizumab showed statistically and clinically significant improvements in inflammation and pruritus in adults and adolescents with moderate to severe atopic dermatitis and a rapid effect in reducing pruritus, as one of the primary complaints of patients. As such, nemolizumab might offer a valuable extension of the therapeutic armament if approved,” the authors concluded.

SOURCE:

The study was led by Jonathan Silverberg, MD, PhD, from the Department of Dermatology, George Washington University, Washington, DC. It was published online in The Lancet.

LIMITATIONS:

The study’s limitations included the absence of longer-term safety data. Additionally, the predominantly White population of the trials may limit the generalizability of the findings to other racial and ethnic groups. The use of concomitant topical therapy might have influenced the placebo response.

DISCLOSURES:

This study was funded by Galderma. Dr. Silverberg received honoraria from pharmaceutical companies, including Galderma, and his institution also received grants from Galderma, Incyte, and Pfizer. Four authors were employees of Galderma. Other authors also declared having ties with pharmaceutical companies, including Galderma, outside this work.

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 first appeared on Medscape.com.

TOPLINE:

Nemolizumab, an interleukin 31 receptor antagonist, was well tolerated and significantly improved inflammation and pruritus in patients with moderate to severe atopic dermatitis (AD).

METHODOLOGY:

• The researchers conducted two 48-week randomized, double-blind, placebo-controlled phase 3 trials, ARCADIA 1 (n = 941; 47% women) and ARCADIA 2 (n = 787; 52% women), involving patients aged 12 and older with moderate to severe AD.
• Participants were randomly assigned in a 2:1 ratio to receive either 30 mg nemolizumab (with a 60-mg loading dose) or placebo, along with background topical corticosteroids with or without topical calcineurin inhibitors. The mean age range was 33.3-35.2 years.
• The coprimary endpoints were Investigator’s Global Assessment (IGA) success (score of 0 or 1 with at least a two-point improvement from baseline) and at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16.

TAKEAWAY:

• At week 16, significantly more patients receiving nemolizumab vs placebo achieved IGA success in both the ARCADIA 1 (36% vs 25%; P = .0003) and ARCADIA 2 (38% vs 26%; P = .0006) trials.
• EASI-75 response rates were also significantly higher in the nemolizumab group than in the placebo group in both trials: ARCADIA 1 (44% vs 29%; P < .0001) and 2 (42% vs 30%; P = .0006).
• Significant improvements in pruritus were observed as early as week 1, with a greater proportion of participants in the nemolizumab vs placebo group achieving at least a four-point reduction in the Peak Pruritus Numerical Rating Scale score in both trials.
• Rates of adverse events were similar between the nemolizumab and placebo groups, with severe treatment-emergent adverse events occurring in 2%-4% of patients.

IN PRACTICE:

“Nemolizumab showed statistically and clinically significant improvements in inflammation and pruritus in adults and adolescents with moderate to severe atopic dermatitis and a rapid effect in reducing pruritus, as one of the primary complaints of patients. As such, nemolizumab might offer a valuable extension of the therapeutic armament if approved,” the authors concluded.

SOURCE:

The study was led by Jonathan Silverberg, MD, PhD, from the Department of Dermatology, George Washington University, Washington, DC. It was published online in The Lancet.

LIMITATIONS:

The study’s limitations included the absence of longer-term safety data. Additionally, the predominantly White population of the trials may limit the generalizability of the findings to other racial and ethnic groups. The use of concomitant topical therapy might have influenced the placebo response.

DISCLOSURES:

This study was funded by Galderma. Dr. Silverberg received honoraria from pharmaceutical companies, including Galderma, and his institution also received grants from Galderma, Incyte, and Pfizer. Four authors were employees of Galderma. Other authors also declared having ties with pharmaceutical companies, including Galderma, outside this work.

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 first appeared on Medscape.com.

TORONTO — When it comes to using artificial intelligence (AI) in your practice, pediatric dermatologist Albert Yan, MD, professor of pediatrics and dermatology at the University of Pennsylvania, Philadelphia, suggests that dermatologists “just jump in” and become familiar with the various AI models.

He reminds doctors that many of their colleagues and patients and their families are already using these systems, “and you don’t want to be left behind.”

In an interview following his presentation on AI at the annual meeting of the Society for Pediatric Dermatology (SPD), Dr. Yan discussed his tips for using AI.
 

Changing Fast 

From the outset, most generative AI systems have been very good at processing language — for example, generating letters of medical necessity and summarizing disease processes into lay terms. But now they’re becoming “truly multimodal,” said Dr. Yan. “You can enter images; you could have it process audio; you can even start to have it refine video.”

To get started, he recommends signing up for a free account with ChatGPT, Gemini, Perplexity, Claude, and/or Microsoft Copilot. “To make the best choice, you have to try them out yourself because they each have their own kind of flavor and strengths and weaknesses,” said Dr. Yan.

Personally, he finds that ChatGPT is the most versatile, Gemini perhaps a little better in terms of image generation, and Perplexity probably the best at references because it was designed as an online library.

Once you figure out which platforms you prefer, consider signing up for a premium subscription, which is typically month to month and can be canceled at any time, Dr. Yan said. “This will allow you to get the most out of the AI model.”

As these AI systems are based on large language models, they are excellent at text, Dr. Yan noted. He suggests asking one to generate a letter or patient instruction sheet. “If you have a premium model, give it a PDF to summarize an article or take a photo of something that you want its opinion on.”

Privacy Critical

Always pay attention to privacy issues and avoid entering any private health information that would violate the Health Insurance Portability and Accountability Act (HIPAA), he said.

“We have to be very careful about how we interact with AI,” said Dr. Yan. “We can’t be posting private patient health information into these systems, no matter how useful these systems are.” Many academic institutions are creating “walled gardens” — private areas of AI access that don’t allow patient information to “leak out,” he said. “These AI models may have HIPAA protections in place and come with specific guidelines of use.”

The AI “scribe,” which helps with electronic health record documentation, is one of the most useful tools for clinicians, he said. He referred to a recent study showing that an AI scribe saved users an average of 1 hour at the keyboard every day, and a small patient survey showing 71% reported that it led to spending more time with their physician.

When entering requests into a prompt line with an AI system, Dr. Yan stressed that these prompts need to be clear and concise. For a complicated calculation or multistep problem, try adding the words “let’s do this step by step,” he said. “This is a technique invoking a ‘chain of thought’ that allows the system to enhance its accuracy when solving problems.”

If the response is not satisfactory, try being more detailed in the request, he advised, and consider giving the system examples of what you’re looking for and telling it what you don’t want in the output.

“For instance, if you’re asking for a differential diagnosis of rashes that affect the hands and feet, you can stipulate that you only want rashes that are vesicular or that arise in neonates, so you can get a more focused answer,” said Dr. Yan.

If there are “long-winded verbose” responses, add the phrase “be concise,” and it will shorten the response by about 50%, he added.
 

AI Hallucinations

Dr. Yan broached an issue that occasionally comes up, AI hallucinations, which refer to inaccurate or misleading responses on the basis of incomplete training or intrinsic biases within the model. He pointed to the case of a doctor discussing issues related to a patient’s hands, feet, and mouth, which the AI-generated model summarized as “the patient being diagnosed with hand, foot, and mouth disease.”

Another example he provided was a request to generate a letter of medical necessity for using ustekinumab (Stelara) for treating hidradenitis suppurative in a child that included references for its effectiveness and safety in children. The AI system generated “false references that sounded like they should be real because the authors are often people who have written in that field or on that subject,” said Dr. Yan.

When pressed, the system did acknowledge the references were hypothetical but were meant to illustrate the types of studies that would typically support the use of this drug in pediatric patients with HS. “ It’s well meaning, in the sense that it’s trying to help you achieve your goals using this training system,” said Dr. Yan.

“If you’re skeptical about a response, double-check the answer with a Google search or run the response through another AI [tool] asking it to check if the response is accurate,” he added.

While AI systems won’t replace the clinician, they are continuing to improve and becoming more sophisticated. Dr. Yan advises keeping up with emerging developments and engaging and adapting the most appropriate AI tool for an individual clinician’s work.

Asked to comment on the presentation at the SPD meeting, Sheilagh Maguiness, MD, director of the Division of Pediatric Dermatology at the University of Minnesota, Minneapolis, who, like other doctors, is increasingly testing AI, said she foresees a time when AI scribes fully replace humans for completing tasks during patient interactions.

“The hope is that if the AI scribes get good enough, we can just open our phone, have them translate the interaction, and create the notes for us.”

While she likes the idea of using ChatGPT to help with tasks like letters of recommendation for medications, Dr. Yan’s comments reiterated the importance of “checking and double-checking ChatGPT because it’s not correct all the time.” She particularly welcomed the advice “that we can just go back and ask it again to clarify, and that may improve its answers.”

Dr. Yan’s disclosures included an investment portfolio that includes companies working in the AI space, including Google, Apple, Nvidia, Amazon, Microsoft, and Arm. Dr. Maguiness had no relevant disclosures.

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

TORONTO — When it comes to using artificial intelligence (AI) in your practice, pediatric dermatologist Albert Yan, MD, professor of pediatrics and dermatology at the University of Pennsylvania, Philadelphia, suggests that dermatologists “just jump in” and become familiar with the various AI models.

He reminds doctors that many of their colleagues and patients and their families are already using these systems, “and you don’t want to be left behind.”

In an interview following his presentation on AI at the annual meeting of the Society for Pediatric Dermatology (SPD), Dr. Yan discussed his tips for using AI.
 

Changing Fast 

From the outset, most generative AI systems have been very good at processing language — for example, generating letters of medical necessity and summarizing disease processes into lay terms. But now they’re becoming “truly multimodal,” said Dr. Yan. “You can enter images; you could have it process audio; you can even start to have it refine video.”

To get started, he recommends signing up for a free account with ChatGPT, Gemini, Perplexity, Claude, and/or Microsoft Copilot. “To make the best choice, you have to try them out yourself because they each have their own kind of flavor and strengths and weaknesses,” said Dr. Yan.

Personally, he finds that ChatGPT is the most versatile, Gemini perhaps a little better in terms of image generation, and Perplexity probably the best at references because it was designed as an online library.

Once you figure out which platforms you prefer, consider signing up for a premium subscription, which is typically month to month and can be canceled at any time, Dr. Yan said. “This will allow you to get the most out of the AI model.”

As these AI systems are based on large language models, they are excellent at text, Dr. Yan noted. He suggests asking one to generate a letter or patient instruction sheet. “If you have a premium model, give it a PDF to summarize an article or take a photo of something that you want its opinion on.”

Privacy Critical

Always pay attention to privacy issues and avoid entering any private health information that would violate the Health Insurance Portability and Accountability Act (HIPAA), he said.

“We have to be very careful about how we interact with AI,” said Dr. Yan. “We can’t be posting private patient health information into these systems, no matter how useful these systems are.” Many academic institutions are creating “walled gardens” — private areas of AI access that don’t allow patient information to “leak out,” he said. “These AI models may have HIPAA protections in place and come with specific guidelines of use.”

The AI “scribe,” which helps with electronic health record documentation, is one of the most useful tools for clinicians, he said. He referred to a recent study showing that an AI scribe saved users an average of 1 hour at the keyboard every day, and a small patient survey showing 71% reported that it led to spending more time with their physician.

When entering requests into a prompt line with an AI system, Dr. Yan stressed that these prompts need to be clear and concise. For a complicated calculation or multistep problem, try adding the words “let’s do this step by step,” he said. “This is a technique invoking a ‘chain of thought’ that allows the system to enhance its accuracy when solving problems.”

If the response is not satisfactory, try being more detailed in the request, he advised, and consider giving the system examples of what you’re looking for and telling it what you don’t want in the output.

“For instance, if you’re asking for a differential diagnosis of rashes that affect the hands and feet, you can stipulate that you only want rashes that are vesicular or that arise in neonates, so you can get a more focused answer,” said Dr. Yan.

If there are “long-winded verbose” responses, add the phrase “be concise,” and it will shorten the response by about 50%, he added.
 

AI Hallucinations

Dr. Yan broached an issue that occasionally comes up, AI hallucinations, which refer to inaccurate or misleading responses on the basis of incomplete training or intrinsic biases within the model. He pointed to the case of a doctor discussing issues related to a patient’s hands, feet, and mouth, which the AI-generated model summarized as “the patient being diagnosed with hand, foot, and mouth disease.”

Another example he provided was a request to generate a letter of medical necessity for using ustekinumab (Stelara) for treating hidradenitis suppurative in a child that included references for its effectiveness and safety in children. The AI system generated “false references that sounded like they should be real because the authors are often people who have written in that field or on that subject,” said Dr. Yan.

When pressed, the system did acknowledge the references were hypothetical but were meant to illustrate the types of studies that would typically support the use of this drug in pediatric patients with HS. “ It’s well meaning, in the sense that it’s trying to help you achieve your goals using this training system,” said Dr. Yan.

“If you’re skeptical about a response, double-check the answer with a Google search or run the response through another AI [tool] asking it to check if the response is accurate,” he added.

While AI systems won’t replace the clinician, they are continuing to improve and becoming more sophisticated. Dr. Yan advises keeping up with emerging developments and engaging and adapting the most appropriate AI tool for an individual clinician’s work.

Asked to comment on the presentation at the SPD meeting, Sheilagh Maguiness, MD, director of the Division of Pediatric Dermatology at the University of Minnesota, Minneapolis, who, like other doctors, is increasingly testing AI, said she foresees a time when AI scribes fully replace humans for completing tasks during patient interactions.

“The hope is that if the AI scribes get good enough, we can just open our phone, have them translate the interaction, and create the notes for us.”

While she likes the idea of using ChatGPT to help with tasks like letters of recommendation for medications, Dr. Yan’s comments reiterated the importance of “checking and double-checking ChatGPT because it’s not correct all the time.” She particularly welcomed the advice “that we can just go back and ask it again to clarify, and that may improve its answers.”

Dr. Yan’s disclosures included an investment portfolio that includes companies working in the AI space, including Google, Apple, Nvidia, Amazon, Microsoft, and Arm. Dr. Maguiness had no relevant disclosures.

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

TORONTO — When it comes to using artificial intelligence (AI) in your practice, pediatric dermatologist Albert Yan, MD, professor of pediatrics and dermatology at the University of Pennsylvania, Philadelphia, suggests that dermatologists “just jump in” and become familiar with the various AI models.

He reminds doctors that many of their colleagues and patients and their families are already using these systems, “and you don’t want to be left behind.”

In an interview following his presentation on AI at the annual meeting of the Society for Pediatric Dermatology (SPD), Dr. Yan discussed his tips for using AI.
 

Changing Fast 

From the outset, most generative AI systems have been very good at processing language — for example, generating letters of medical necessity and summarizing disease processes into lay terms. But now they’re becoming “truly multimodal,” said Dr. Yan. “You can enter images; you could have it process audio; you can even start to have it refine video.”

To get started, he recommends signing up for a free account with ChatGPT, Gemini, Perplexity, Claude, and/or Microsoft Copilot. “To make the best choice, you have to try them out yourself because they each have their own kind of flavor and strengths and weaknesses,” said Dr. Yan.

Personally, he finds that ChatGPT is the most versatile, Gemini perhaps a little better in terms of image generation, and Perplexity probably the best at references because it was designed as an online library.

Once you figure out which platforms you prefer, consider signing up for a premium subscription, which is typically month to month and can be canceled at any time, Dr. Yan said. “This will allow you to get the most out of the AI model.”

As these AI systems are based on large language models, they are excellent at text, Dr. Yan noted. He suggests asking one to generate a letter or patient instruction sheet. “If you have a premium model, give it a PDF to summarize an article or take a photo of something that you want its opinion on.”

Privacy Critical

Always pay attention to privacy issues and avoid entering any private health information that would violate the Health Insurance Portability and Accountability Act (HIPAA), he said.

“We have to be very careful about how we interact with AI,” said Dr. Yan. “We can’t be posting private patient health information into these systems, no matter how useful these systems are.” Many academic institutions are creating “walled gardens” — private areas of AI access that don’t allow patient information to “leak out,” he said. “These AI models may have HIPAA protections in place and come with specific guidelines of use.”

The AI “scribe,” which helps with electronic health record documentation, is one of the most useful tools for clinicians, he said. He referred to a recent study showing that an AI scribe saved users an average of 1 hour at the keyboard every day, and a small patient survey showing 71% reported that it led to spending more time with their physician.

When entering requests into a prompt line with an AI system, Dr. Yan stressed that these prompts need to be clear and concise. For a complicated calculation or multistep problem, try adding the words “let’s do this step by step,” he said. “This is a technique invoking a ‘chain of thought’ that allows the system to enhance its accuracy when solving problems.”

If the response is not satisfactory, try being more detailed in the request, he advised, and consider giving the system examples of what you’re looking for and telling it what you don’t want in the output.

“For instance, if you’re asking for a differential diagnosis of rashes that affect the hands and feet, you can stipulate that you only want rashes that are vesicular or that arise in neonates, so you can get a more focused answer,” said Dr. Yan.

If there are “long-winded verbose” responses, add the phrase “be concise,” and it will shorten the response by about 50%, he added.
 

AI Hallucinations

Dr. Yan broached an issue that occasionally comes up, AI hallucinations, which refer to inaccurate or misleading responses on the basis of incomplete training or intrinsic biases within the model. He pointed to the case of a doctor discussing issues related to a patient’s hands, feet, and mouth, which the AI-generated model summarized as “the patient being diagnosed with hand, foot, and mouth disease.”

Another example he provided was a request to generate a letter of medical necessity for using ustekinumab (Stelara) for treating hidradenitis suppurative in a child that included references for its effectiveness and safety in children. The AI system generated “false references that sounded like they should be real because the authors are often people who have written in that field or on that subject,” said Dr. Yan.

When pressed, the system did acknowledge the references were hypothetical but were meant to illustrate the types of studies that would typically support the use of this drug in pediatric patients with HS. “ It’s well meaning, in the sense that it’s trying to help you achieve your goals using this training system,” said Dr. Yan.

“If you’re skeptical about a response, double-check the answer with a Google search or run the response through another AI [tool] asking it to check if the response is accurate,” he added.

While AI systems won’t replace the clinician, they are continuing to improve and becoming more sophisticated. Dr. Yan advises keeping up with emerging developments and engaging and adapting the most appropriate AI tool for an individual clinician’s work.

Asked to comment on the presentation at the SPD meeting, Sheilagh Maguiness, MD, director of the Division of Pediatric Dermatology at the University of Minnesota, Minneapolis, who, like other doctors, is increasingly testing AI, said she foresees a time when AI scribes fully replace humans for completing tasks during patient interactions.

“The hope is that if the AI scribes get good enough, we can just open our phone, have them translate the interaction, and create the notes for us.”

While she likes the idea of using ChatGPT to help with tasks like letters of recommendation for medications, Dr. Yan’s comments reiterated the importance of “checking and double-checking ChatGPT because it’s not correct all the time.” She particularly welcomed the advice “that we can just go back and ask it again to clarify, and that may improve its answers.”

Dr. Yan’s disclosures included an investment portfolio that includes companies working in the AI space, including Google, Apple, Nvidia, Amazon, Microsoft, and Arm. Dr. Maguiness had no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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