Pediatric News

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

I would like to briefly discuss a very interesting paper that appeared in Nature:“Megastudy Shows That Reminders Boost Vaccination but Adding Free Rides Does Not.” 

Obviously, the paper has a provocative title. This is really an excellent example of what one might call implementation research, or quite frankly, what might work and what might not work in terms of having a very pragmatic goal. In this case, it was how do we get people to receive vaccinations. 

This specific study looked at individuals who were scheduled to receive or were candidates to receive COVID-19 booster vaccinations. The question came up: If you gave them free rides to the location — this is obviously a high-risk population — would that increase the vaccination rate vs the other item that they were looking at here, which was potentially texting them to remind them?

The study very importantly and relevantly demonstrated, quite nicely, that offering free rides did not make a difference, but sending texts to remind them increased the 30-day vaccination rate in this population by 21%. 

Again, it was a very pragmatic question that the trial addressed, and one might use this information in the future to increase the vaccination rate of a population where it is critical to do so. This type of research, which involves looking at very pragmatic questions and answering what is the optimal and most cost-effective way of doing it, should be encouraged. 

I encourage you to look at this paper if you’re interested in this topic.

Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed ties with GlaxoSmithKline and AstraZeneca.

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

This transcript has been edited for clarity. 

I would like to briefly discuss a very interesting paper that appeared in Nature:“Megastudy Shows That Reminders Boost Vaccination but Adding Free Rides Does Not.” 

Obviously, the paper has a provocative title. This is really an excellent example of what one might call implementation research, or quite frankly, what might work and what might not work in terms of having a very pragmatic goal. In this case, it was how do we get people to receive vaccinations. 

This specific study looked at individuals who were scheduled to receive or were candidates to receive COVID-19 booster vaccinations. The question came up: If you gave them free rides to the location — this is obviously a high-risk population — would that increase the vaccination rate vs the other item that they were looking at here, which was potentially texting them to remind them?

The study very importantly and relevantly demonstrated, quite nicely, that offering free rides did not make a difference, but sending texts to remind them increased the 30-day vaccination rate in this population by 21%. 

Again, it was a very pragmatic question that the trial addressed, and one might use this information in the future to increase the vaccination rate of a population where it is critical to do so. This type of research, which involves looking at very pragmatic questions and answering what is the optimal and most cost-effective way of doing it, should be encouraged. 

I encourage you to look at this paper if you’re interested in this topic.

Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed ties with GlaxoSmithKline and AstraZeneca.

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

This transcript has been edited for clarity. 

I would like to briefly discuss a very interesting paper that appeared in Nature:“Megastudy Shows That Reminders Boost Vaccination but Adding Free Rides Does Not.” 

Obviously, the paper has a provocative title. This is really an excellent example of what one might call implementation research, or quite frankly, what might work and what might not work in terms of having a very pragmatic goal. In this case, it was how do we get people to receive vaccinations. 

This specific study looked at individuals who were scheduled to receive or were candidates to receive COVID-19 booster vaccinations. The question came up: If you gave them free rides to the location — this is obviously a high-risk population — would that increase the vaccination rate vs the other item that they were looking at here, which was potentially texting them to remind them?

The study very importantly and relevantly demonstrated, quite nicely, that offering free rides did not make a difference, but sending texts to remind them increased the 30-day vaccination rate in this population by 21%. 

Again, it was a very pragmatic question that the trial addressed, and one might use this information in the future to increase the vaccination rate of a population where it is critical to do so. This type of research, which involves looking at very pragmatic questions and answering what is the optimal and most cost-effective way of doing it, should be encouraged. 

I encourage you to look at this paper if you’re interested in this topic.

Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed ties with GlaxoSmithKline and AstraZeneca.

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

The pediatrician’s first patient of the day was an 8-year-old boy, accompanied by both of his parents. It was the boy’s third visit in just over a week for fever and left-sided neck swelling, and the family was understandably anxious for answers.

“The antibiotics don’t seem to be working,” the mother explained. “He still has fever every day, as high as 104, and his neck looks just as swollen.”

A quick review of the chart revealed the boy’s initial diagnosis had been bacterial lymphadenitis, for which amoxicillin-clavulanate had been prescribed. Three days later, given lack of clinical improvement, therapy was transitioned to clindamycin. On examination, the boy was febrile and ill-appearing with a 3-cm by 5-cm tender, non-fluctuant swelling over the left sternocleidomastoid muscle. 

 

The pediatrician ran through a quick mental checklist of diagnostic possibilities for his patient’s continued symptoms. Staphylococcal lymphadenitis still seemed possible. Could the boy be infected with methicillin-resistant Staphylococcus aureus that was also clindamycin resistant? Alternately, perhaps the problem was “source control” and the boy had developed an occult neck abscess that needed to be drained. An ultrasound could help sort that out. Finally, the pediatrician considered less common bacterial causes of lymph node swelling and fever. He placed Bartonella henselae, the cause of cat scratch disease, near the top of his list. “I’ve never seen it,” he told the parents, “But we could also consider tularemia.”

Tularemia is a rare zoonotic infection caused by Francisella tularenis. On average, 200 cases of tularemia are reported in the United States each year, and the incidence of disease is increasing, according to a surveillance report released by the Centers for Disease Control and Prevention in December 2023.¹

Between 2011 and 2022, 2462 tularemia cases were reported in the United States. That translated to an average annual incidence of 0.064 per 100,000 population, an increase of 56% compared with 2001-2010. Forty-seven states reported at least one case of tularemia, although half of all reported cases came from four states — Arkansas (18%), Kansas (11%), Missouri (11%), and Oklahoma (10%). The incidence of tularemia was highest in children ages 5-9 years old, older men, and American Indian or Alaska Natives individuals. Although cases occurred year-round, 78% had symptom onset May through September. 

In the United States, most human cases of tularemia have been arthropod borne, transmitted by the bite of an infected tick or deer fly. Infection also can be spread through contact with infected animals or animal tissue, particularly rabbits, hares, muskrats, prairie dogs, and other rodents, including hamsters. Outbreaks of tularemia have occurred among pet store hamsters, and at least one child in the United States developed tularemia after being bitten by a pet hamster.

Tularemia is almost always associated with fever but other clinical manifestations vary by the type of exposure. Ulceroglandular disease occurs after a tick or deer fly bite or after handling an infected animal. An ulcer develops at the site where the bacteria entered the body, along with enlargement of regional lymph nodes. Less commonly, lymph node swelling can occur without the development of an ulcer. If the bacteria enter through the eye, symptoms include conjunctivitis and swelling of pre-auricular lymph nodes. Eating or drinking contaminated food or water is associated with sore throat, mouth ulcers, tonsillitis, and swelling of lymph glands in the neck. Pneumonic tularemia, the most serious form of the disease, typically happens after inhaling bacteria-containing dust or aerosols and is associated with cough, chest pain, and difficulty breathing. Pneumonic tularemia can develop if other forms of tularemia are untreated, and the bacteria spread to the lung.

Back in the exam room, the pediatrician carefully re-examined the boy’s scalp. A 1-cm poorly healing ulcer on the left occiput added support for the diagnosis of ulceroglandular tularemia, the most common form of the disease in children. Serologic testing ultimately confirmed the diagnosis and the boy’s symptoms resolved with treatment.

Gentamicin administered intravenously or intramuscularly is the drug of choice for the treatment of tularemia in children. Ciprofloxacin is considered an alternative but is not approved by the U.S. Food and Drug Administration for this indication.

The pediatrician reported the case of tularemia to his local health department. Tularemia is a nationally notifiable disease in the United States; state health departments report to the CDC through the National Notifiable Diseases Surveillance System. In turn, public health authorities shared information to prevent tularemia. Steps to prevent tick and deer fly bites include the use of an Environmental Protection Agency–registered insect repellent. Individuals who hunt, trap, or skin animals are encouraged to wear gloves when handling animals —especially rabbits, muskrats, and prairie dogs — and cook game meat thoroughly. Tularemia can be inadvertently aerosolized if an infected animal or carcass is run over with a tractor or lawnmower. Checking for carcasses before mowing may reduce the risk.

 

Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta and Gilead. Email her at pdnews@mdedge.com. (Also kristina.bryant@louisville.edu.) 

Reference

1. Rich SN et al. Tularemia—United States, 2011-2022. MMWR Morb Mortal Wkly Rep 2025;73:1152–1156. doi: 

The pediatrician’s first patient of the day was an 8-year-old boy, accompanied by both of his parents. It was the boy’s third visit in just over a week for fever and left-sided neck swelling, and the family was understandably anxious for answers.

“The antibiotics don’t seem to be working,” the mother explained. “He still has fever every day, as high as 104, and his neck looks just as swollen.”

A quick review of the chart revealed the boy’s initial diagnosis had been bacterial lymphadenitis, for which amoxicillin-clavulanate had been prescribed. Three days later, given lack of clinical improvement, therapy was transitioned to clindamycin. On examination, the boy was febrile and ill-appearing with a 3-cm by 5-cm tender, non-fluctuant swelling over the left sternocleidomastoid muscle. 

 

The pediatrician ran through a quick mental checklist of diagnostic possibilities for his patient’s continued symptoms. Staphylococcal lymphadenitis still seemed possible. Could the boy be infected with methicillin-resistant Staphylococcus aureus that was also clindamycin resistant? Alternately, perhaps the problem was “source control” and the boy had developed an occult neck abscess that needed to be drained. An ultrasound could help sort that out. Finally, the pediatrician considered less common bacterial causes of lymph node swelling and fever. He placed Bartonella henselae, the cause of cat scratch disease, near the top of his list. “I’ve never seen it,” he told the parents, “But we could also consider tularemia.”

Tularemia is a rare zoonotic infection caused by Francisella tularenis. On average, 200 cases of tularemia are reported in the United States each year, and the incidence of disease is increasing, according to a surveillance report released by the Centers for Disease Control and Prevention in December 2023.¹

Between 2011 and 2022, 2462 tularemia cases were reported in the United States. That translated to an average annual incidence of 0.064 per 100,000 population, an increase of 56% compared with 2001-2010. Forty-seven states reported at least one case of tularemia, although half of all reported cases came from four states — Arkansas (18%), Kansas (11%), Missouri (11%), and Oklahoma (10%). The incidence of tularemia was highest in children ages 5-9 years old, older men, and American Indian or Alaska Natives individuals. Although cases occurred year-round, 78% had symptom onset May through September. 

In the United States, most human cases of tularemia have been arthropod borne, transmitted by the bite of an infected tick or deer fly. Infection also can be spread through contact with infected animals or animal tissue, particularly rabbits, hares, muskrats, prairie dogs, and other rodents, including hamsters. Outbreaks of tularemia have occurred among pet store hamsters, and at least one child in the United States developed tularemia after being bitten by a pet hamster.

Tularemia is almost always associated with fever but other clinical manifestations vary by the type of exposure. Ulceroglandular disease occurs after a tick or deer fly bite or after handling an infected animal. An ulcer develops at the site where the bacteria entered the body, along with enlargement of regional lymph nodes. Less commonly, lymph node swelling can occur without the development of an ulcer. If the bacteria enter through the eye, symptoms include conjunctivitis and swelling of pre-auricular lymph nodes. Eating or drinking contaminated food or water is associated with sore throat, mouth ulcers, tonsillitis, and swelling of lymph glands in the neck. Pneumonic tularemia, the most serious form of the disease, typically happens after inhaling bacteria-containing dust or aerosols and is associated with cough, chest pain, and difficulty breathing. Pneumonic tularemia can develop if other forms of tularemia are untreated, and the bacteria spread to the lung.

Back in the exam room, the pediatrician carefully re-examined the boy’s scalp. A 1-cm poorly healing ulcer on the left occiput added support for the diagnosis of ulceroglandular tularemia, the most common form of the disease in children. Serologic testing ultimately confirmed the diagnosis and the boy’s symptoms resolved with treatment.

Gentamicin administered intravenously or intramuscularly is the drug of choice for the treatment of tularemia in children. Ciprofloxacin is considered an alternative but is not approved by the U.S. Food and Drug Administration for this indication.

The pediatrician reported the case of tularemia to his local health department. Tularemia is a nationally notifiable disease in the United States; state health departments report to the CDC through the National Notifiable Diseases Surveillance System. In turn, public health authorities shared information to prevent tularemia. Steps to prevent tick and deer fly bites include the use of an Environmental Protection Agency–registered insect repellent. Individuals who hunt, trap, or skin animals are encouraged to wear gloves when handling animals —especially rabbits, muskrats, and prairie dogs — and cook game meat thoroughly. Tularemia can be inadvertently aerosolized if an infected animal or carcass is run over with a tractor or lawnmower. Checking for carcasses before mowing may reduce the risk.

 

Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta and Gilead. Email her at pdnews@mdedge.com. (Also kristina.bryant@louisville.edu.) 

Reference

1. Rich SN et al. Tularemia—United States, 2011-2022. MMWR Morb Mortal Wkly Rep 2025;73:1152–1156. doi: 

The pediatrician’s first patient of the day was an 8-year-old boy, accompanied by both of his parents. It was the boy’s third visit in just over a week for fever and left-sided neck swelling, and the family was understandably anxious for answers.

“The antibiotics don’t seem to be working,” the mother explained. “He still has fever every day, as high as 104, and his neck looks just as swollen.”

A quick review of the chart revealed the boy’s initial diagnosis had been bacterial lymphadenitis, for which amoxicillin-clavulanate had been prescribed. Three days later, given lack of clinical improvement, therapy was transitioned to clindamycin. On examination, the boy was febrile and ill-appearing with a 3-cm by 5-cm tender, non-fluctuant swelling over the left sternocleidomastoid muscle. 

 

The pediatrician ran through a quick mental checklist of diagnostic possibilities for his patient’s continued symptoms. Staphylococcal lymphadenitis still seemed possible. Could the boy be infected with methicillin-resistant Staphylococcus aureus that was also clindamycin resistant? Alternately, perhaps the problem was “source control” and the boy had developed an occult neck abscess that needed to be drained. An ultrasound could help sort that out. Finally, the pediatrician considered less common bacterial causes of lymph node swelling and fever. He placed Bartonella henselae, the cause of cat scratch disease, near the top of his list. “I’ve never seen it,” he told the parents, “But we could also consider tularemia.”

Tularemia is a rare zoonotic infection caused by Francisella tularenis. On average, 200 cases of tularemia are reported in the United States each year, and the incidence of disease is increasing, according to a surveillance report released by the Centers for Disease Control and Prevention in December 2023.¹

Between 2011 and 2022, 2462 tularemia cases were reported in the United States. That translated to an average annual incidence of 0.064 per 100,000 population, an increase of 56% compared with 2001-2010. Forty-seven states reported at least one case of tularemia, although half of all reported cases came from four states — Arkansas (18%), Kansas (11%), Missouri (11%), and Oklahoma (10%). The incidence of tularemia was highest in children ages 5-9 years old, older men, and American Indian or Alaska Natives individuals. Although cases occurred year-round, 78% had symptom onset May through September. 

In the United States, most human cases of tularemia have been arthropod borne, transmitted by the bite of an infected tick or deer fly. Infection also can be spread through contact with infected animals or animal tissue, particularly rabbits, hares, muskrats, prairie dogs, and other rodents, including hamsters. Outbreaks of tularemia have occurred among pet store hamsters, and at least one child in the United States developed tularemia after being bitten by a pet hamster.

Tularemia is almost always associated with fever but other clinical manifestations vary by the type of exposure. Ulceroglandular disease occurs after a tick or deer fly bite or after handling an infected animal. An ulcer develops at the site where the bacteria entered the body, along with enlargement of regional lymph nodes. Less commonly, lymph node swelling can occur without the development of an ulcer. If the bacteria enter through the eye, symptoms include conjunctivitis and swelling of pre-auricular lymph nodes. Eating or drinking contaminated food or water is associated with sore throat, mouth ulcers, tonsillitis, and swelling of lymph glands in the neck. Pneumonic tularemia, the most serious form of the disease, typically happens after inhaling bacteria-containing dust or aerosols and is associated with cough, chest pain, and difficulty breathing. Pneumonic tularemia can develop if other forms of tularemia are untreated, and the bacteria spread to the lung.

Back in the exam room, the pediatrician carefully re-examined the boy’s scalp. A 1-cm poorly healing ulcer on the left occiput added support for the diagnosis of ulceroglandular tularemia, the most common form of the disease in children. Serologic testing ultimately confirmed the diagnosis and the boy’s symptoms resolved with treatment.

Gentamicin administered intravenously or intramuscularly is the drug of choice for the treatment of tularemia in children. Ciprofloxacin is considered an alternative but is not approved by the U.S. Food and Drug Administration for this indication.

The pediatrician reported the case of tularemia to his local health department. Tularemia is a nationally notifiable disease in the United States; state health departments report to the CDC through the National Notifiable Diseases Surveillance System. In turn, public health authorities shared information to prevent tularemia. Steps to prevent tick and deer fly bites include the use of an Environmental Protection Agency–registered insect repellent. Individuals who hunt, trap, or skin animals are encouraged to wear gloves when handling animals —especially rabbits, muskrats, and prairie dogs — and cook game meat thoroughly. Tularemia can be inadvertently aerosolized if an infected animal or carcass is run over with a tractor or lawnmower. Checking for carcasses before mowing may reduce the risk.

 

Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta and Gilead. Email her at pdnews@mdedge.com. (Also kristina.bryant@louisville.edu.) 

Reference

1. Rich SN et al. Tularemia—United States, 2011-2022. MMWR Morb Mortal Wkly Rep 2025;73:1152–1156. doi: 

Results published from a systematic review and meta-analysis find an inverse association and a dose-response link between fluoride exposure and children’s IQ scores.

Kyla W. Taylor, PhD, with the Division of Translational Toxicology at the National Institutes of Health, Morrisville, North Carolina, led the multicountry study published online in JAMA Pediatrics.

Two accompanying editorials offer two very different perspectives on how to interpret the researchers’ conclusions.
 

Study Results

The authors noted that, of the 74 studies included in the review (64 cross-sectional and 10 cohort studies), most (45) were conducted in China. Other countries included were Canada (3), Denmark (1), India (12), Iran (4), Mexico (4), New Zealand (1), Pakistan (2), Spain (1), and Taiwan (1). “Fifty-two studies were rated high risk of bias, and 22 were rated low risk of bias,” the authors stated.

Researchers found that 64 of the 74 studies reported inverse associations between fluoride exposure measures and children’s IQ scores. Their analysis of 59 studies with group-level measures of fluoride in drinking water, dental fluorosis, or other measures of fluoride exposure showed an inverse relationship between fluoride exposure and IQ (pooled standardized mean difference [SMD], −0.45; 95% CI, −0.57 to −0.33; P < .001). Of those 59 studies, encompassing 20,932 children, 47 had high risk for bias and 12 had low risk for bias.

In 31 studies that reported fluoride measurements in drinking water, a dose-response relationship was found between exposed and reference groups (SMD, –0.15; 95% CI, –0.20 to –0.11; P < .001). That relationship remained inverse when exposed groups were limited to less than 4 mg fluoride/L and less than 2 mg/L. However, the association was not seen at less than 1.5 mg/L.

In 20 studies reporting fluoride measured in urine, there was an inverse dose-response association (SMD, –0.15; 95% CI, –0.23 to –0.07; P < .001). Those inverse relationships held at levels less than 4 mg/L, less than 2 mg/L, and less than 1.5 mg/L fluoride in urine.

For perspective, in the United States, the US Public Health Service in 2015 lowered the recommended concentration of fluoride in drinking water from a range of 0.7-1.2 mg/L to 0.7 mg/L to reduce the risk for dental fluorosis while keeping its protective effect against dental caries. 

When Taylor’s team analyzed 13 studies with individual-level measures, they found an IQ score decrease of 1.63 points (95% CI, –2.33 to –0.93; P < .001) per 1-mg/L increase in urinary fluoride. Among studies with a low risk for bias, they observed an IQ score decrease of 1.14 points (95% CI, –1.68 to –0.61; P < .001). The inverse relationship remained when stratified by factors including risk for bias, sex, age, country, outcome assessment type, exposure timing (prenatal or postnatal), and exposure matrix (urinary fluoride, intake and water fluoride), the authors wrote.

The authors conclude both that inverse relationships and a dose-response association between fluoride measured in urine and drinking water and children’s IQs were found across the literature examined but also that “there were limited data and uncertainty in the dose-response association between fluoride exposure and children’s IQ when fluoride exposure was estimated by drinking water alone at concentrations less than 1.5 mg/L.”

The authors point out that, “To our knowledge, no studies of fluoride exposure and children’s IQ have been performed in the United States and no nationally representative urinary fluoride levels are available, hindering application of these findings to the US population.”
 

Editorial: Time to Reassess Systemic Fluoride

Bruce P. Lanphear, MD, MPH, with Simon Fraser University, Vancouver, British Columbia, Canada, is the lead author on an editorial that suggests these data point to the need to reassess systemic fluoride exposure.

“Their study is the largest and includes the most rigorous series of meta-analyses of fluoride ever conducted,” Lanphear and colleagues wrote. “It is time for health organizations and regulatory bodies to reassess the risks and benefits of fluoride, particularly for pregnant women and infants.”

Lanphear’s team says distinguishing between water fluoride and urinary fluoride levels is important in these results “because regulatory and public health agencies must consider total fluoride intake when assessing risks.”

Taylor and colleagues’ finding that there was no statistically significant association between water fluoride les than 1.5 mg/L and children’s IQ scores in the dose-response meta-analysis doesn’t mean fluoride is not a potential risk for lower IQ scores in fluoridated communities, they wrote. “Water fluoride concentration does not capture the amount of water ingested or other sources of ingested fluoride. In contrast, urinary fluoride is a biological measure of total fluoride exposure, including the dynamic interface between bone fluoride stores and blood fluoride.”
 

Editorial: Be Cautious About the Conclusions

Steven M. Levy, DDS, MPH, cites “major areas of concern” in the meta-analysis in his editorial.

He points to the large majority of studies in the meta-analysis that were at “high risk of bias” (47 high risk vs 12 that were low risk). He also cited information from a further look at the low-risk-of-bias studies included in the supplement.

“The studies with lower risk of bias showed a negligible effect (standardized mean difference [SMD], −0.19; 95% CI, −0.35 to −0.04) with very high heterogeneity (I2 = 87%), and a majority of publications (8 of 12) did not show a negative association between fluoride and childhood IQ,” Levy wrote. 

“Taylor et al do not adequately justify selection or omission of studies or explain or justify the calculated individual effect sizes presented in the main analysis. Also, readers are not told which studies with lower risk of bias are included in the subanalyses for water fluoride levels less than 1.5 mg/L, less than 2.0 mg/L, and less than 4.0 mg/L; therefore, readers cannot independently consider important differences across these studies.”

Levy also states that the magnitudes of the possible IQ differences are unfairly inflated. For the United Staes and most of the world, he points out, the recommended community water fluoridation level is 0.7 mg/L. Therefore, the difference between a community with low fluoride levels (about 0.2 mg/L) and one with optimal levels is about 0.5 mg/L. 

“However, Taylor and colleagues use a difference of 1.0 mg/L in their calculations, artificially doubling the estimated impact on IQ,” Levy wrote.

The meta-analysis should not affect public policy on adding fluoride to community water systems “and the widespread use of fluoride for caries prevention should continue,” Levy concluded.
 

Concerns About Quality of Studies Included

Charlotte Lewis, MD, MPH, associate professor of pediatrics at the University of Washington School of Medicine and part of Seattle Children’s Multidisciplinary Infant Nutrition and Feeding Team, Seattle, who was not involved in the meta-analysis or editorials, said that systemic fluoridation should not change based on these results, citing what she said are problems with methodology.

“There are many concerns about the quality of studies included in this meta-analysis,” Lewis said. “Although the authors claim to have separated out low-bias studies, it is important to note that many of these same studies have substantial methodological flaws.”

She said studies deemed low-bias and included in the meta-analysis “relied on multiple examiners for cognitive testing without consideration for inter-rater variation or reliability measures.” She added that “a number of the studies failed to account for maternal IQ scores, breastfeeding, lead exposure, or other factors that could affect cognitive development, further contributing to biased conclusions.”

Importantly, she said, many of the studies, including one by Rivka Green and colleagues published in JAMA Pediatrics, relied on maternal spot urinary fluoride to assess fetal exposure to fluoride. “This is not a valid way to assess fetal exposure to fluoride and including such studies in this meta-analysis has led to inappropriate conclusions because they are based on studies using a flawed exposure measure.” 

She pointed to recent longitudinal, population-based studies, including one by Jayant V Kumar and colleagues that have found no adverse impact on IQ, or other cognitive tests, of drinking water with low levels of fluoride present, comparable to US community water fluoridation standards. 

“Relative to the small convenience-sample, cross-sectional studies included in this meta-analysis, longitudinal, population-based studies are considered significantly more reliable for establishing cause and effect,” she said.
 

Fluoride Levels Different Globally

Lewis said in some parts of the world fluoride is present in the environment in much higher levels than in fluoridated water in the United States.

“There are known adverse health effects of high fluoride ingestion in these endemic regions found primarily in China, India, and Iran. This points to the importance of dose response. What is beneficial at low levels can be toxic at high levels and that appears to be the case, not surprisingly, for fluoride as well. However, at 0.7 ppm, the level of fluoride in community water fluoridation, we experience fluoride’s beneficial effects when we regularly drink optimally fluoridated water.”

“Water fluoridation is an important public health approach available and beneficial to all, even those unable to afford or access dental care,” she said. “Water fluoridation diminishes oral health disparities, and its removal threatens to worsen disparities and increased suffering from dental disease. I remain confident in the benefits and safety of community water fluoridation.”

Taylor and colleagues reported no relevant financial relationships. Lanphear reported grants from the National Institute of Environmental Health Sciences and the Canadian Institute for Health Research and having served as a nonretained and unpaid expert witness in a federal fluoride suit against the US EPA. Levy reported past grants from the National Institute of Dental and Craniofacial Research related to fluoride, dental caries, dental fluorosis, and bone development. He reported small grant funding from the Centers for Disease Control and Prevention related to fluoride, dental caries, and fluorosis. He consults for the Centers for Disease Control and Prevention and the National Institute of Dental and Craniofacial Research and serves on the National Fluoride Advisory Committee for the American Dental Association.

A version of this article appeared on Medscape.com.

Results published from a systematic review and meta-analysis find an inverse association and a dose-response link between fluoride exposure and children’s IQ scores.

Kyla W. Taylor, PhD, with the Division of Translational Toxicology at the National Institutes of Health, Morrisville, North Carolina, led the multicountry study published online in JAMA Pediatrics.

Two accompanying editorials offer two very different perspectives on how to interpret the researchers’ conclusions.
 

Study Results

The authors noted that, of the 74 studies included in the review (64 cross-sectional and 10 cohort studies), most (45) were conducted in China. Other countries included were Canada (3), Denmark (1), India (12), Iran (4), Mexico (4), New Zealand (1), Pakistan (2), Spain (1), and Taiwan (1). “Fifty-two studies were rated high risk of bias, and 22 were rated low risk of bias,” the authors stated.

Researchers found that 64 of the 74 studies reported inverse associations between fluoride exposure measures and children’s IQ scores. Their analysis of 59 studies with group-level measures of fluoride in drinking water, dental fluorosis, or other measures of fluoride exposure showed an inverse relationship between fluoride exposure and IQ (pooled standardized mean difference [SMD], −0.45; 95% CI, −0.57 to −0.33; P < .001). Of those 59 studies, encompassing 20,932 children, 47 had high risk for bias and 12 had low risk for bias.

In 31 studies that reported fluoride measurements in drinking water, a dose-response relationship was found between exposed and reference groups (SMD, –0.15; 95% CI, –0.20 to –0.11; P < .001). That relationship remained inverse when exposed groups were limited to less than 4 mg fluoride/L and less than 2 mg/L. However, the association was not seen at less than 1.5 mg/L.

In 20 studies reporting fluoride measured in urine, there was an inverse dose-response association (SMD, –0.15; 95% CI, –0.23 to –0.07; P < .001). Those inverse relationships held at levels less than 4 mg/L, less than 2 mg/L, and less than 1.5 mg/L fluoride in urine.

For perspective, in the United States, the US Public Health Service in 2015 lowered the recommended concentration of fluoride in drinking water from a range of 0.7-1.2 mg/L to 0.7 mg/L to reduce the risk for dental fluorosis while keeping its protective effect against dental caries. 

When Taylor’s team analyzed 13 studies with individual-level measures, they found an IQ score decrease of 1.63 points (95% CI, –2.33 to –0.93; P < .001) per 1-mg/L increase in urinary fluoride. Among studies with a low risk for bias, they observed an IQ score decrease of 1.14 points (95% CI, –1.68 to –0.61; P < .001). The inverse relationship remained when stratified by factors including risk for bias, sex, age, country, outcome assessment type, exposure timing (prenatal or postnatal), and exposure matrix (urinary fluoride, intake and water fluoride), the authors wrote.

The authors conclude both that inverse relationships and a dose-response association between fluoride measured in urine and drinking water and children’s IQs were found across the literature examined but also that “there were limited data and uncertainty in the dose-response association between fluoride exposure and children’s IQ when fluoride exposure was estimated by drinking water alone at concentrations less than 1.5 mg/L.”

The authors point out that, “To our knowledge, no studies of fluoride exposure and children’s IQ have been performed in the United States and no nationally representative urinary fluoride levels are available, hindering application of these findings to the US population.”
 

Editorial: Time to Reassess Systemic Fluoride

Bruce P. Lanphear, MD, MPH, with Simon Fraser University, Vancouver, British Columbia, Canada, is the lead author on an editorial that suggests these data point to the need to reassess systemic fluoride exposure.

“Their study is the largest and includes the most rigorous series of meta-analyses of fluoride ever conducted,” Lanphear and colleagues wrote. “It is time for health organizations and regulatory bodies to reassess the risks and benefits of fluoride, particularly for pregnant women and infants.”

Lanphear’s team says distinguishing between water fluoride and urinary fluoride levels is important in these results “because regulatory and public health agencies must consider total fluoride intake when assessing risks.”

Taylor and colleagues’ finding that there was no statistically significant association between water fluoride les than 1.5 mg/L and children’s IQ scores in the dose-response meta-analysis doesn’t mean fluoride is not a potential risk for lower IQ scores in fluoridated communities, they wrote. “Water fluoride concentration does not capture the amount of water ingested or other sources of ingested fluoride. In contrast, urinary fluoride is a biological measure of total fluoride exposure, including the dynamic interface between bone fluoride stores and blood fluoride.”
 

Editorial: Be Cautious About the Conclusions

Steven M. Levy, DDS, MPH, cites “major areas of concern” in the meta-analysis in his editorial.

He points to the large majority of studies in the meta-analysis that were at “high risk of bias” (47 high risk vs 12 that were low risk). He also cited information from a further look at the low-risk-of-bias studies included in the supplement.

“The studies with lower risk of bias showed a negligible effect (standardized mean difference [SMD], −0.19; 95% CI, −0.35 to −0.04) with very high heterogeneity (I2 = 87%), and a majority of publications (8 of 12) did not show a negative association between fluoride and childhood IQ,” Levy wrote. 

“Taylor et al do not adequately justify selection or omission of studies or explain or justify the calculated individual effect sizes presented in the main analysis. Also, readers are not told which studies with lower risk of bias are included in the subanalyses for water fluoride levels less than 1.5 mg/L, less than 2.0 mg/L, and less than 4.0 mg/L; therefore, readers cannot independently consider important differences across these studies.”

Levy also states that the magnitudes of the possible IQ differences are unfairly inflated. For the United Staes and most of the world, he points out, the recommended community water fluoridation level is 0.7 mg/L. Therefore, the difference between a community with low fluoride levels (about 0.2 mg/L) and one with optimal levels is about 0.5 mg/L. 

“However, Taylor and colleagues use a difference of 1.0 mg/L in their calculations, artificially doubling the estimated impact on IQ,” Levy wrote.

The meta-analysis should not affect public policy on adding fluoride to community water systems “and the widespread use of fluoride for caries prevention should continue,” Levy concluded.
 

Concerns About Quality of Studies Included

Charlotte Lewis, MD, MPH, associate professor of pediatrics at the University of Washington School of Medicine and part of Seattle Children’s Multidisciplinary Infant Nutrition and Feeding Team, Seattle, who was not involved in the meta-analysis or editorials, said that systemic fluoridation should not change based on these results, citing what she said are problems with methodology.

“There are many concerns about the quality of studies included in this meta-analysis,” Lewis said. “Although the authors claim to have separated out low-bias studies, it is important to note that many of these same studies have substantial methodological flaws.”

She said studies deemed low-bias and included in the meta-analysis “relied on multiple examiners for cognitive testing without consideration for inter-rater variation or reliability measures.” She added that “a number of the studies failed to account for maternal IQ scores, breastfeeding, lead exposure, or other factors that could affect cognitive development, further contributing to biased conclusions.”

Importantly, she said, many of the studies, including one by Rivka Green and colleagues published in JAMA Pediatrics, relied on maternal spot urinary fluoride to assess fetal exposure to fluoride. “This is not a valid way to assess fetal exposure to fluoride and including such studies in this meta-analysis has led to inappropriate conclusions because they are based on studies using a flawed exposure measure.” 

She pointed to recent longitudinal, population-based studies, including one by Jayant V Kumar and colleagues that have found no adverse impact on IQ, or other cognitive tests, of drinking water with low levels of fluoride present, comparable to US community water fluoridation standards. 

“Relative to the small convenience-sample, cross-sectional studies included in this meta-analysis, longitudinal, population-based studies are considered significantly more reliable for establishing cause and effect,” she said.
 

Fluoride Levels Different Globally

Lewis said in some parts of the world fluoride is present in the environment in much higher levels than in fluoridated water in the United States.

“There are known adverse health effects of high fluoride ingestion in these endemic regions found primarily in China, India, and Iran. This points to the importance of dose response. What is beneficial at low levels can be toxic at high levels and that appears to be the case, not surprisingly, for fluoride as well. However, at 0.7 ppm, the level of fluoride in community water fluoridation, we experience fluoride’s beneficial effects when we regularly drink optimally fluoridated water.”

“Water fluoridation is an important public health approach available and beneficial to all, even those unable to afford or access dental care,” she said. “Water fluoridation diminishes oral health disparities, and its removal threatens to worsen disparities and increased suffering from dental disease. I remain confident in the benefits and safety of community water fluoridation.”

Taylor and colleagues reported no relevant financial relationships. Lanphear reported grants from the National Institute of Environmental Health Sciences and the Canadian Institute for Health Research and having served as a nonretained and unpaid expert witness in a federal fluoride suit against the US EPA. Levy reported past grants from the National Institute of Dental and Craniofacial Research related to fluoride, dental caries, dental fluorosis, and bone development. He reported small grant funding from the Centers for Disease Control and Prevention related to fluoride, dental caries, and fluorosis. He consults for the Centers for Disease Control and Prevention and the National Institute of Dental and Craniofacial Research and serves on the National Fluoride Advisory Committee for the American Dental Association.

A version of this article appeared on Medscape.com.

Results published from a systematic review and meta-analysis find an inverse association and a dose-response link between fluoride exposure and children’s IQ scores.

Kyla W. Taylor, PhD, with the Division of Translational Toxicology at the National Institutes of Health, Morrisville, North Carolina, led the multicountry study published online in JAMA Pediatrics.

Two accompanying editorials offer two very different perspectives on how to interpret the researchers’ conclusions.
 

Study Results

The authors noted that, of the 74 studies included in the review (64 cross-sectional and 10 cohort studies), most (45) were conducted in China. Other countries included were Canada (3), Denmark (1), India (12), Iran (4), Mexico (4), New Zealand (1), Pakistan (2), Spain (1), and Taiwan (1). “Fifty-two studies were rated high risk of bias, and 22 were rated low risk of bias,” the authors stated.

Researchers found that 64 of the 74 studies reported inverse associations between fluoride exposure measures and children’s IQ scores. Their analysis of 59 studies with group-level measures of fluoride in drinking water, dental fluorosis, or other measures of fluoride exposure showed an inverse relationship between fluoride exposure and IQ (pooled standardized mean difference [SMD], −0.45; 95% CI, −0.57 to −0.33; P < .001). Of those 59 studies, encompassing 20,932 children, 47 had high risk for bias and 12 had low risk for bias.

In 31 studies that reported fluoride measurements in drinking water, a dose-response relationship was found between exposed and reference groups (SMD, –0.15; 95% CI, –0.20 to –0.11; P < .001). That relationship remained inverse when exposed groups were limited to less than 4 mg fluoride/L and less than 2 mg/L. However, the association was not seen at less than 1.5 mg/L.

In 20 studies reporting fluoride measured in urine, there was an inverse dose-response association (SMD, –0.15; 95% CI, –0.23 to –0.07; P < .001). Those inverse relationships held at levels less than 4 mg/L, less than 2 mg/L, and less than 1.5 mg/L fluoride in urine.

For perspective, in the United States, the US Public Health Service in 2015 lowered the recommended concentration of fluoride in drinking water from a range of 0.7-1.2 mg/L to 0.7 mg/L to reduce the risk for dental fluorosis while keeping its protective effect against dental caries. 

When Taylor’s team analyzed 13 studies with individual-level measures, they found an IQ score decrease of 1.63 points (95% CI, –2.33 to –0.93; P < .001) per 1-mg/L increase in urinary fluoride. Among studies with a low risk for bias, they observed an IQ score decrease of 1.14 points (95% CI, –1.68 to –0.61; P < .001). The inverse relationship remained when stratified by factors including risk for bias, sex, age, country, outcome assessment type, exposure timing (prenatal or postnatal), and exposure matrix (urinary fluoride, intake and water fluoride), the authors wrote.

The authors conclude both that inverse relationships and a dose-response association between fluoride measured in urine and drinking water and children’s IQs were found across the literature examined but also that “there were limited data and uncertainty in the dose-response association between fluoride exposure and children’s IQ when fluoride exposure was estimated by drinking water alone at concentrations less than 1.5 mg/L.”

The authors point out that, “To our knowledge, no studies of fluoride exposure and children’s IQ have been performed in the United States and no nationally representative urinary fluoride levels are available, hindering application of these findings to the US population.”
 

Editorial: Time to Reassess Systemic Fluoride

Bruce P. Lanphear, MD, MPH, with Simon Fraser University, Vancouver, British Columbia, Canada, is the lead author on an editorial that suggests these data point to the need to reassess systemic fluoride exposure.

“Their study is the largest and includes the most rigorous series of meta-analyses of fluoride ever conducted,” Lanphear and colleagues wrote. “It is time for health organizations and regulatory bodies to reassess the risks and benefits of fluoride, particularly for pregnant women and infants.”

Lanphear’s team says distinguishing between water fluoride and urinary fluoride levels is important in these results “because regulatory and public health agencies must consider total fluoride intake when assessing risks.”

Taylor and colleagues’ finding that there was no statistically significant association between water fluoride les than 1.5 mg/L and children’s IQ scores in the dose-response meta-analysis doesn’t mean fluoride is not a potential risk for lower IQ scores in fluoridated communities, they wrote. “Water fluoride concentration does not capture the amount of water ingested or other sources of ingested fluoride. In contrast, urinary fluoride is a biological measure of total fluoride exposure, including the dynamic interface between bone fluoride stores and blood fluoride.”
 

Editorial: Be Cautious About the Conclusions

Steven M. Levy, DDS, MPH, cites “major areas of concern” in the meta-analysis in his editorial.

He points to the large majority of studies in the meta-analysis that were at “high risk of bias” (47 high risk vs 12 that were low risk). He also cited information from a further look at the low-risk-of-bias studies included in the supplement.

“The studies with lower risk of bias showed a negligible effect (standardized mean difference [SMD], −0.19; 95% CI, −0.35 to −0.04) with very high heterogeneity (I2 = 87%), and a majority of publications (8 of 12) did not show a negative association between fluoride and childhood IQ,” Levy wrote. 

“Taylor et al do not adequately justify selection or omission of studies or explain or justify the calculated individual effect sizes presented in the main analysis. Also, readers are not told which studies with lower risk of bias are included in the subanalyses for water fluoride levels less than 1.5 mg/L, less than 2.0 mg/L, and less than 4.0 mg/L; therefore, readers cannot independently consider important differences across these studies.”

Levy also states that the magnitudes of the possible IQ differences are unfairly inflated. For the United Staes and most of the world, he points out, the recommended community water fluoridation level is 0.7 mg/L. Therefore, the difference between a community with low fluoride levels (about 0.2 mg/L) and one with optimal levels is about 0.5 mg/L. 

“However, Taylor and colleagues use a difference of 1.0 mg/L in their calculations, artificially doubling the estimated impact on IQ,” Levy wrote.

The meta-analysis should not affect public policy on adding fluoride to community water systems “and the widespread use of fluoride for caries prevention should continue,” Levy concluded.
 

Concerns About Quality of Studies Included

Charlotte Lewis, MD, MPH, associate professor of pediatrics at the University of Washington School of Medicine and part of Seattle Children’s Multidisciplinary Infant Nutrition and Feeding Team, Seattle, who was not involved in the meta-analysis or editorials, said that systemic fluoridation should not change based on these results, citing what she said are problems with methodology.

“There are many concerns about the quality of studies included in this meta-analysis,” Lewis said. “Although the authors claim to have separated out low-bias studies, it is important to note that many of these same studies have substantial methodological flaws.”

She said studies deemed low-bias and included in the meta-analysis “relied on multiple examiners for cognitive testing without consideration for inter-rater variation or reliability measures.” She added that “a number of the studies failed to account for maternal IQ scores, breastfeeding, lead exposure, or other factors that could affect cognitive development, further contributing to biased conclusions.”

Importantly, she said, many of the studies, including one by Rivka Green and colleagues published in JAMA Pediatrics, relied on maternal spot urinary fluoride to assess fetal exposure to fluoride. “This is not a valid way to assess fetal exposure to fluoride and including such studies in this meta-analysis has led to inappropriate conclusions because they are based on studies using a flawed exposure measure.” 

She pointed to recent longitudinal, population-based studies, including one by Jayant V Kumar and colleagues that have found no adverse impact on IQ, or other cognitive tests, of drinking water with low levels of fluoride present, comparable to US community water fluoridation standards. 

“Relative to the small convenience-sample, cross-sectional studies included in this meta-analysis, longitudinal, population-based studies are considered significantly more reliable for establishing cause and effect,” she said.
 

Fluoride Levels Different Globally

Lewis said in some parts of the world fluoride is present in the environment in much higher levels than in fluoridated water in the United States.

“There are known adverse health effects of high fluoride ingestion in these endemic regions found primarily in China, India, and Iran. This points to the importance of dose response. What is beneficial at low levels can be toxic at high levels and that appears to be the case, not surprisingly, for fluoride as well. However, at 0.7 ppm, the level of fluoride in community water fluoridation, we experience fluoride’s beneficial effects when we regularly drink optimally fluoridated water.”

“Water fluoridation is an important public health approach available and beneficial to all, even those unable to afford or access dental care,” she said. “Water fluoridation diminishes oral health disparities, and its removal threatens to worsen disparities and increased suffering from dental disease. I remain confident in the benefits and safety of community water fluoridation.”

Taylor and colleagues reported no relevant financial relationships. Lanphear reported grants from the National Institute of Environmental Health Sciences and the Canadian Institute for Health Research and having served as a nonretained and unpaid expert witness in a federal fluoride suit against the US EPA. Levy reported past grants from the National Institute of Dental and Craniofacial Research related to fluoride, dental caries, dental fluorosis, and bone development. He reported small grant funding from the Centers for Disease Control and Prevention related to fluoride, dental caries, and fluorosis. He consults for the Centers for Disease Control and Prevention and the National Institute of Dental and Craniofacial Research and serves on the National Fluoride Advisory Committee for the American Dental Association.

A version of this article appeared on Medscape.com.

Current management of children and adolescents with long COVID was the focus of various presentations at the 3rd Long COVID Congress in Berlin in November 2024. The congress aimed to facilitate in-depth discussions on recent research projects, diagnostic procedures, and therapeutic approaches to enhance care for long COVID patients. This year, the focus was on research into long COVID in children and adolescents and how to improve their care.

Uta Behrends, MD, head of the Munich Chronic Fatigue Center, Center for Pediatric and Adolescent Medicine at the Technical University of Munich, Germany, and Nicole Toepfner, MD, a pediatrician at the University Hospital in Dresden, Germany, provided an initial overview.

Prevalence Data Are Limited

Data on the incidence and prevalence of the condition in children and adolescents are limited because most studies have primarily examined adults. A 2022 Swiss study estimated that it affects between 2% and 3.5% of children and adolescents who contract COVID-19. A recent study published in JAMA involving 5367 children and adolescents found that 20% of children aged 6-11 years and 14% of adolescents met the researchers’ criteria for long COVID.

Impaired Mental Health

Initial data from the latest wave of the population-based longitudinal COPSY (Corona and Psyche) study showed that compared with their peer group children and adolescents diagnosed with long COVID exhibit significantly higher rates of psychological issues and depressive symptoms. Although no significant differences were found in anxiety levels, study leader Ulrike Ravens-Sieberer, PhD, from the University Medical Center Hamburg-Eppendorf, Germany, told the congress that those with long COVID do also report more frequent somatic or psychological health complaints and lower health-related quality of life than peers.

Addressing Data Gaps

Another study due to launch in January 2025 and run through to 2028 is the COVYOUTH data study, which aims to better understand the nature, frequency, and risk factors of COVID-related sequelae in children and adolescents.

Study centers include Ruhr University Bochum, University Hospital Cologne, the Paul-Ehrlich-Institut, and University Medical Center Hamburg-Eppendorf. Using routine data from statutory health insurance and newly developed case definitions, researchers aim to investigate:

• Psychological stress caused by COVID-19 measures 
• Post-COVID syndrome and myocarditis 
• Adverse effects of COVID-19 vaccinations 

Specialized Diagnostics and Care

The Post-COVID Kids Bavaria project offers specialized diagnostics and care for children and adolescents, including a day clinic, telemedical follow-ups, and an inpatient pain therapy module providing age-appropriate care as close to patients’ homes as possible.

MOVE-COVID is a model project for patient-focused research on long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involving university pediatric hospitals in Freiburg, Heidelberg, Tübingen, and Ulm. It also aims to establish a care network across the state of Baden-Württemberg, including the establishment of long COVID outpatient clinics at social pediatric centers in the network hospitals, as well as enhanced telemedical support and standardized diagnostic and treatment protocols. “MOVE-COVID has successfully consolidated competencies and capacities in patient care, health services research, and patient-focused studies across multiple centers,” Behrends said.

Chronic Pain and Fatigue

Post-COVID syndromes in children and adolescents may feature profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance and overlap with conditions such as ME/CFS. According to the German patient association Fatigatio, Berlin, research and studies for these conditions in children remain limited compared with those in adults. However, the US Centers for Disease Control estimates that around 2% of ME/CFS patients are children or adolescents, with the majority being teenagers.

Two inpatient treatment concepts, SHARK and TIGER, developed by Lea Höfel, PhD, head of the Centre for Pain Therapy for Young People and the Psychological Service at the Children’s Hospital in Garmisch-Partenkirchen, address chronic pain, fatigue, and ME/CFS in young people. These programs integrate structured breaks and flexible access to multiple therapists as needed. The TIGER program focuses on those with post-exertional malaise, while the SHARK program is designed for adolescents without this symptom. Both programs last 4.5-5 weeks and emphasize symptom reduction, education, and energy management.

Preliminary Results

SHARK included 30 participants (7 men; average age, 16 years), of whom 12 had a history of SARS-CoV-2 infection. TIGER involved 100 participants (24 men; average age, 16.7 years), of whom 32 had a SARS-CoV-2 infection as a triggering event. Other triggers included Epstein-Barr virus and other infections.

Preliminary findings from the projects indicate that optimized management with outpatient and follow-up care can yield positive, sometimes lasting effects. No significant differences between SARS-CoV-2 and other triggers emerged, but pain proved more manageable in the SHARK group than in the TIGER group, suggesting they may involve different pathological mechanisms.

Hope for Improved Outcomes

“It’s important to move away from the idea that nothing can be done,” Behrends said. This is a common attitude with children and adolescents displaying these types of symptoms, but it’s simply not true. “Even in pediatrics, we have numerous therapeutic options that may offer relief, from medication to psychosocial interventions,” she concluded.

This story was translated from Medscape’s German edition using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Current management of children and adolescents with long COVID was the focus of various presentations at the 3rd Long COVID Congress in Berlin in November 2024. The congress aimed to facilitate in-depth discussions on recent research projects, diagnostic procedures, and therapeutic approaches to enhance care for long COVID patients. This year, the focus was on research into long COVID in children and adolescents and how to improve their care.

Uta Behrends, MD, head of the Munich Chronic Fatigue Center, Center for Pediatric and Adolescent Medicine at the Technical University of Munich, Germany, and Nicole Toepfner, MD, a pediatrician at the University Hospital in Dresden, Germany, provided an initial overview.

Prevalence Data Are Limited

Data on the incidence and prevalence of the condition in children and adolescents are limited because most studies have primarily examined adults. A 2022 Swiss study estimated that it affects between 2% and 3.5% of children and adolescents who contract COVID-19. A recent study published in JAMA involving 5367 children and adolescents found that 20% of children aged 6-11 years and 14% of adolescents met the researchers’ criteria for long COVID.

Impaired Mental Health

Initial data from the latest wave of the population-based longitudinal COPSY (Corona and Psyche) study showed that compared with their peer group children and adolescents diagnosed with long COVID exhibit significantly higher rates of psychological issues and depressive symptoms. Although no significant differences were found in anxiety levels, study leader Ulrike Ravens-Sieberer, PhD, from the University Medical Center Hamburg-Eppendorf, Germany, told the congress that those with long COVID do also report more frequent somatic or psychological health complaints and lower health-related quality of life than peers.

Addressing Data Gaps

Another study due to launch in January 2025 and run through to 2028 is the COVYOUTH data study, which aims to better understand the nature, frequency, and risk factors of COVID-related sequelae in children and adolescents.

Study centers include Ruhr University Bochum, University Hospital Cologne, the Paul-Ehrlich-Institut, and University Medical Center Hamburg-Eppendorf. Using routine data from statutory health insurance and newly developed case definitions, researchers aim to investigate:

• Psychological stress caused by COVID-19 measures 
• Post-COVID syndrome and myocarditis 
• Adverse effects of COVID-19 vaccinations 

Specialized Diagnostics and Care

The Post-COVID Kids Bavaria project offers specialized diagnostics and care for children and adolescents, including a day clinic, telemedical follow-ups, and an inpatient pain therapy module providing age-appropriate care as close to patients’ homes as possible.

MOVE-COVID is a model project for patient-focused research on long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involving university pediatric hospitals in Freiburg, Heidelberg, Tübingen, and Ulm. It also aims to establish a care network across the state of Baden-Württemberg, including the establishment of long COVID outpatient clinics at social pediatric centers in the network hospitals, as well as enhanced telemedical support and standardized diagnostic and treatment protocols. “MOVE-COVID has successfully consolidated competencies and capacities in patient care, health services research, and patient-focused studies across multiple centers,” Behrends said.

Chronic Pain and Fatigue

Post-COVID syndromes in children and adolescents may feature profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance and overlap with conditions such as ME/CFS. According to the German patient association Fatigatio, Berlin, research and studies for these conditions in children remain limited compared with those in adults. However, the US Centers for Disease Control estimates that around 2% of ME/CFS patients are children or adolescents, with the majority being teenagers.

Two inpatient treatment concepts, SHARK and TIGER, developed by Lea Höfel, PhD, head of the Centre for Pain Therapy for Young People and the Psychological Service at the Children’s Hospital in Garmisch-Partenkirchen, address chronic pain, fatigue, and ME/CFS in young people. These programs integrate structured breaks and flexible access to multiple therapists as needed. The TIGER program focuses on those with post-exertional malaise, while the SHARK program is designed for adolescents without this symptom. Both programs last 4.5-5 weeks and emphasize symptom reduction, education, and energy management.

Preliminary Results

SHARK included 30 participants (7 men; average age, 16 years), of whom 12 had a history of SARS-CoV-2 infection. TIGER involved 100 participants (24 men; average age, 16.7 years), of whom 32 had a SARS-CoV-2 infection as a triggering event. Other triggers included Epstein-Barr virus and other infections.

Preliminary findings from the projects indicate that optimized management with outpatient and follow-up care can yield positive, sometimes lasting effects. No significant differences between SARS-CoV-2 and other triggers emerged, but pain proved more manageable in the SHARK group than in the TIGER group, suggesting they may involve different pathological mechanisms.

Hope for Improved Outcomes

“It’s important to move away from the idea that nothing can be done,” Behrends said. This is a common attitude with children and adolescents displaying these types of symptoms, but it’s simply not true. “Even in pediatrics, we have numerous therapeutic options that may offer relief, from medication to psychosocial interventions,” she concluded.

This story was translated from Medscape’s German edition using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Current management of children and adolescents with long COVID was the focus of various presentations at the 3rd Long COVID Congress in Berlin in November 2024. The congress aimed to facilitate in-depth discussions on recent research projects, diagnostic procedures, and therapeutic approaches to enhance care for long COVID patients. This year, the focus was on research into long COVID in children and adolescents and how to improve their care.

Uta Behrends, MD, head of the Munich Chronic Fatigue Center, Center for Pediatric and Adolescent Medicine at the Technical University of Munich, Germany, and Nicole Toepfner, MD, a pediatrician at the University Hospital in Dresden, Germany, provided an initial overview.

Prevalence Data Are Limited

Data on the incidence and prevalence of the condition in children and adolescents are limited because most studies have primarily examined adults. A 2022 Swiss study estimated that it affects between 2% and 3.5% of children and adolescents who contract COVID-19. A recent study published in JAMA involving 5367 children and adolescents found that 20% of children aged 6-11 years and 14% of adolescents met the researchers’ criteria for long COVID.

Impaired Mental Health

Initial data from the latest wave of the population-based longitudinal COPSY (Corona and Psyche) study showed that compared with their peer group children and adolescents diagnosed with long COVID exhibit significantly higher rates of psychological issues and depressive symptoms. Although no significant differences were found in anxiety levels, study leader Ulrike Ravens-Sieberer, PhD, from the University Medical Center Hamburg-Eppendorf, Germany, told the congress that those with long COVID do also report more frequent somatic or psychological health complaints and lower health-related quality of life than peers.

Addressing Data Gaps

Another study due to launch in January 2025 and run through to 2028 is the COVYOUTH data study, which aims to better understand the nature, frequency, and risk factors of COVID-related sequelae in children and adolescents.

Study centers include Ruhr University Bochum, University Hospital Cologne, the Paul-Ehrlich-Institut, and University Medical Center Hamburg-Eppendorf. Using routine data from statutory health insurance and newly developed case definitions, researchers aim to investigate:

• Psychological stress caused by COVID-19 measures 
• Post-COVID syndrome and myocarditis 
• Adverse effects of COVID-19 vaccinations 

Specialized Diagnostics and Care

The Post-COVID Kids Bavaria project offers specialized diagnostics and care for children and adolescents, including a day clinic, telemedical follow-ups, and an inpatient pain therapy module providing age-appropriate care as close to patients’ homes as possible.

MOVE-COVID is a model project for patient-focused research on long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involving university pediatric hospitals in Freiburg, Heidelberg, Tübingen, and Ulm. It also aims to establish a care network across the state of Baden-Württemberg, including the establishment of long COVID outpatient clinics at social pediatric centers in the network hospitals, as well as enhanced telemedical support and standardized diagnostic and treatment protocols. “MOVE-COVID has successfully consolidated competencies and capacities in patient care, health services research, and patient-focused studies across multiple centers,” Behrends said.

Chronic Pain and Fatigue

Post-COVID syndromes in children and adolescents may feature profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance and overlap with conditions such as ME/CFS. According to the German patient association Fatigatio, Berlin, research and studies for these conditions in children remain limited compared with those in adults. However, the US Centers for Disease Control estimates that around 2% of ME/CFS patients are children or adolescents, with the majority being teenagers.

Two inpatient treatment concepts, SHARK and TIGER, developed by Lea Höfel, PhD, head of the Centre for Pain Therapy for Young People and the Psychological Service at the Children’s Hospital in Garmisch-Partenkirchen, address chronic pain, fatigue, and ME/CFS in young people. These programs integrate structured breaks and flexible access to multiple therapists as needed. The TIGER program focuses on those with post-exertional malaise, while the SHARK program is designed for adolescents without this symptom. Both programs last 4.5-5 weeks and emphasize symptom reduction, education, and energy management.

Preliminary Results

SHARK included 30 participants (7 men; average age, 16 years), of whom 12 had a history of SARS-CoV-2 infection. TIGER involved 100 participants (24 men; average age, 16.7 years), of whom 32 had a SARS-CoV-2 infection as a triggering event. Other triggers included Epstein-Barr virus and other infections.

Preliminary findings from the projects indicate that optimized management with outpatient and follow-up care can yield positive, sometimes lasting effects. No significant differences between SARS-CoV-2 and other triggers emerged, but pain proved more manageable in the SHARK group than in the TIGER group, suggesting they may involve different pathological mechanisms.

Hope for Improved Outcomes

“It’s important to move away from the idea that nothing can be done,” Behrends said. This is a common attitude with children and adolescents displaying these types of symptoms, but it’s simply not true. “Even in pediatrics, we have numerous therapeutic options that may offer relief, from medication to psychosocial interventions,” she concluded.

This story was translated from Medscape’s German edition using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

In the second half of the school year, you may find that there is a surge of families coming to appointments with concerns about school performance, wondering if their child has ADHD. We expect you are very familiar with this condition, both diagnosing and treating it. So this month we will offer “mythbusters” for ADHD: Responding to common misperceptions about ADHD with a summary of what the research has demonstrated as emerging facts, what is clearly fiction and what falls into the gray space between.

Demographics

A CDC survey of parents from 2022 indicates that 11.4% of children aged 3-17 have ever been diagnosed with ADHD in the United States. This is more than double the ADHD global prevalence of 5%, suggesting that there is overdiagnosis of this condition in this country. Boys are almost twice as likely to be diagnosed (14.5%) as girls (8%), and White children were more likely to be diagnosed than were Black and Hispanic children. The prevalence of ADHD diagnosis decreases as family income increases, and the condition is more frequently diagnosed in 12- to 17-year-olds than in children 11 and younger. The great majority of youth with an ADHD diagnosis (78%) have at least one co-occurring psychiatric condition. Of the children diagnosed with ADHD, slightly over half receive medication treatment (53.6%) whereas nearly a third (30.1%) receive no ADHD-specific treatment.

The Multimodal Treatment of ADHD Study (MTA), a large (600 children, aged 7-9 years), multicenter, longitudinal study of treatment outcomes for medication as well as behavioral and combination therapies demonstrated in every site that medication alone and combination therapy were significantly superior to intensive behavioral treatment alone and to routine community care in the reduction of ADHD symptoms. Of note, problems commonly associated with ADHD (parent-child conflict, anxiety symptoms, poor academic performance, and limited social skills) improved only with the combination treatment. This suggests that while core ADHD symptoms require medication, associated problems will also require behavioral treatment.

The American Academy of Pediatrics has a useful resource guide (healthychildren.org) highlighting the possible symptoms of inattention, hyperactivity, and impulsivity that should be investigated when considering this diagnosis. It is a clinical diagnosis, but screening instruments (such as the Vanderbilt) can be very helpful to identifying symptoms that should be present in more than one setting (home and school). While a child with ADHD can appear calm and focused when receiving direct one-to-one attention (as during a pediatrician’s appointment), symptoms may flourish in less structured or supervised settings. Sometimes parents are keen reporters of a child’s behaviors, but some loving (and exhausted) parents may overreact to a normal degree of inattention or disobedience. This can be especially true when a parent has a more detail-oriented temperament than the child, or with younger children and first-time parents. It is important to consider ADHD when you hear about social difficulties as well as academic ones, where there is a family history of ADHD or when a child is more impulsive, hyperactive, or inattentive than you would expect given their age and developmental stage. Confirm your clinical exam with teacher and parent reports. If the reports don’t line up or there are persistent learning problems in school, consider neuropsychological testing to root out a learning disability.

 

Myth 1: “ADHD never starts in adolescence; you can’t diagnose it after elementary school.”

Diagnostic criteria used to require that symptoms were present before the age of 7 (DSM 3). But current criteria allow for diagnosis before 12 years of age or after. While the consensus is that ADHD is present in childhood, its symptoms are often not apparent. This is because normal development in much younger children is marked by higher levels of activity, distractibility, and impulsivity. Also, children with inattentive-type ADHD may not be apparent to adults if they are performing adequately in school. These youth often do not present for assessment until the challenges of a busy course load make their inattention and consequent inefficiency apparent, in high school or even college. Certainly, when a teenager presents complaining of trouble performing at school, it is critical to rule out an overburdened schedule, anxiety or mood disorder, poor sleep habits or sleep disorder, and substance use disorders, all of which are more common in adolescence. But inattentive-type ADHD that was previously missed is also a possibility worth investigating.

Myth 2: “Most children outgrow ADHD; it’s best to find natural solutions and wait it out.”

Early epidemiological studies suggested that as many as 30% of ADHD cases remitted by adulthood, but more recent data has adjusted that number down substantially, closer to 9%. Interestingly, it appears that 10% of patients will experience sustained symptoms, 9% will experience recovery (sustained remission without treatment), and a large majority will have a remitting and relapsing course into adulthood.¹

This emerging evidence suggests that ADHD is almost always a lifelong condition. Untreated, it can threaten healthy development (including social skills and self-esteem) and day-to-day function (academic, social and athletic performance and even vulnerability to accidents) in ways that can be profound. The MTA Study has powerfully demonstrated the efficacy of pharmacological treatment and of specific behavioral treatments for ADHD and associated problems.

 

Myth 3: “You should exhaust natural cures first before trying medications.”

There has been a large amount of research into a variety of “natural” treatments for ADHD: special diets, supplements, increased exercise, and interventions like neurofeedback. While high-dose omega 3 fatty acid supplementation has demonstrated mild improvement in ADHD symptoms, no “natural” treatment has come close to the efficacy of stimulant medications. Interventions such as neurofeedback are expensive and time-consuming without any demonstrated efficacy. That said, improving a child’s routines around sleep, nutrition, and regular exercise are broadly useful strategies to improve any child’s (or adult’s) energy, impulse control, attention, motivation, and capacity to manage adversity and stress. Start any treatment by addressing sleep and exercise, including moderating time spent on screens, to support healthy function. But only medication will achieve symptom remission if your patient has underlying ADHD.

Myth 4: “All medications are equally effective in ADHD.”

It is well-established that stimulants are more effective than non-stimulants in the treatment of ADHD symptoms, with an effect size that is almost double that of non-stimulants.²

Amphetamine-based medications are slightly more effective than methylphenidate-based medications, but they are also generally less well-tolerated. Individual patients commonly have a better response to one class than the other, but you will need a trial to determine which one. It is reasonable to start a patient with an extended formulation of one class, based on your assessment of their vulnerability to side effects or a family history of medication response. Non-stimulants are of use when stimulants are not tolerated (ie, use of atomoxetine with patients who have comorbid anxiety), or to target specific symptoms, such as guanfacine or clonidine for hyperactivity.

 

Myth 5: “You can’t treat ADHD in substance abusing teens, stimulant medications are addictive.”

ADHD itself (not medications) increases the risk for addiction; those with ADHD are almost twice as likely to develop a substance use disorder, with highest risk for marijuana, alcohol, and nicotine abuse.³

This may be a function of limited impulse control or increased sensitivity in the ADHD brain to a drug’s addictive potential. Importantly, there is growing evidence that youth whose ADHD is treated pharmacologically are at lower risk for addiction than their peers with untreated ADHD.⁴

Those youth who have both ADHD and addiction are more likely to stay engaged in treatment for addiction when their ADHD is effectively treated, and there are medication formulations (lisdexamfetamine) that are safe in addiction (cannot be absorbed nasally or intravenously). It is important for you to talk about the heightened vulnerability to addiction with your ADHD patients and their parents, and the value of effective treatment in preventing this complication.

 

Myth 6: “ADHD is usually behavioral. Help parents to set rules, expectations, and limits instead of medicating the problem.”

Bad parenting does not cause ADHD. ADHD is marked by difficulties with impulse control, hyperactivity, and sustaining attention with matters that are not intrinsically engaging. “Behavioral issues” are patterns of behavior children learn to seek rewards or avoid negative consequences. Youth with ADHD can develop behavioral problems, but these are usually driven by negative feedback about their activity level, forgetfulness, or impulse control, which they are not able to change. This can lead to frustration and irritability, poor self-esteem, and even hopelessness — in parents and children both!

While parents are not the source of ADHD symptoms, there is a great deal of parent education and support that can be powerfully effective for these families. Parents benefit from learning strategies that can help their children to shift their attention, plan ahead, and manage frustration, especially for times when their children are unmedicated (vacations and bedtime). It is worth noting that ADHD is among the most heritable of youth psychiatric illnesses, so it is not uncommon for a parent of a child with ADHD to have similar symptoms. If the parents’ ADHD is untreated, they may be more impulsive themselves. They may also be extra sensitive to the qualities they dislike in themselves, inadvertently adding to their children’s sense of shame. ADHD is very treatable, and those with it can learn executive function skills and organizational strategies that can equip them to manage residual symptoms. Parents will benefit from strategies to understand their children and to help them learn adaptive skills in a realistic way. Your discussions with parents could help the families in your practice make adjustments that can translate into big differences in their child’s healthiest development.

Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Sibley MH et al. MTA Cooperative Group. Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD. Am J Psychiatry. 2022 Feb;179(2):142-151. doi: 10.1176/appi.ajp.2021.21010032.

2. Cortese S et al. Comparative Efficacy and Tolerability of Medications for Attention-Deficit Hyperactivity Disorder in Children, Adolescents, and Adults: A Systematic Review and Network Meta-Analysis. Lancet Psychiatry. 2018 Sep;5(9):727-738. doi: 10.1016/S2215-0366(18)30269-4.

3. Lee SS et al. Prospective Association of Childhood Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use and Abuse/Dependence: A Meta-Analytic Review. Clin Psychol Rev. 2011 Apr;31(3):328-41. doi: 10.1016/j.cpr.2011.01.006. 

4. Chorniy A, Kitashima L. Sex, Drugs, and ADHD: The Effects of ADHD Pharmacological Treatment on Teens’ Risky Behaviors. Labour Economics. 2016;43:87-105. doi.org/10.1016/j.labeco.2016.06.014.

In the second half of the school year, you may find that there is a surge of families coming to appointments with concerns about school performance, wondering if their child has ADHD. We expect you are very familiar with this condition, both diagnosing and treating it. So this month we will offer “mythbusters” for ADHD: Responding to common misperceptions about ADHD with a summary of what the research has demonstrated as emerging facts, what is clearly fiction and what falls into the gray space between.

Demographics

A CDC survey of parents from 2022 indicates that 11.4% of children aged 3-17 have ever been diagnosed with ADHD in the United States. This is more than double the ADHD global prevalence of 5%, suggesting that there is overdiagnosis of this condition in this country. Boys are almost twice as likely to be diagnosed (14.5%) as girls (8%), and White children were more likely to be diagnosed than were Black and Hispanic children. The prevalence of ADHD diagnosis decreases as family income increases, and the condition is more frequently diagnosed in 12- to 17-year-olds than in children 11 and younger. The great majority of youth with an ADHD diagnosis (78%) have at least one co-occurring psychiatric condition. Of the children diagnosed with ADHD, slightly over half receive medication treatment (53.6%) whereas nearly a third (30.1%) receive no ADHD-specific treatment.

The Multimodal Treatment of ADHD Study (MTA), a large (600 children, aged 7-9 years), multicenter, longitudinal study of treatment outcomes for medication as well as behavioral and combination therapies demonstrated in every site that medication alone and combination therapy were significantly superior to intensive behavioral treatment alone and to routine community care in the reduction of ADHD symptoms. Of note, problems commonly associated with ADHD (parent-child conflict, anxiety symptoms, poor academic performance, and limited social skills) improved only with the combination treatment. This suggests that while core ADHD symptoms require medication, associated problems will also require behavioral treatment.

The American Academy of Pediatrics has a useful resource guide (healthychildren.org) highlighting the possible symptoms of inattention, hyperactivity, and impulsivity that should be investigated when considering this diagnosis. It is a clinical diagnosis, but screening instruments (such as the Vanderbilt) can be very helpful to identifying symptoms that should be present in more than one setting (home and school). While a child with ADHD can appear calm and focused when receiving direct one-to-one attention (as during a pediatrician’s appointment), symptoms may flourish in less structured or supervised settings. Sometimes parents are keen reporters of a child’s behaviors, but some loving (and exhausted) parents may overreact to a normal degree of inattention or disobedience. This can be especially true when a parent has a more detail-oriented temperament than the child, or with younger children and first-time parents. It is important to consider ADHD when you hear about social difficulties as well as academic ones, where there is a family history of ADHD or when a child is more impulsive, hyperactive, or inattentive than you would expect given their age and developmental stage. Confirm your clinical exam with teacher and parent reports. If the reports don’t line up or there are persistent learning problems in school, consider neuropsychological testing to root out a learning disability.

 

Myth 1: “ADHD never starts in adolescence; you can’t diagnose it after elementary school.”

Diagnostic criteria used to require that symptoms were present before the age of 7 (DSM 3). But current criteria allow for diagnosis before 12 years of age or after. While the consensus is that ADHD is present in childhood, its symptoms are often not apparent. This is because normal development in much younger children is marked by higher levels of activity, distractibility, and impulsivity. Also, children with inattentive-type ADHD may not be apparent to adults if they are performing adequately in school. These youth often do not present for assessment until the challenges of a busy course load make their inattention and consequent inefficiency apparent, in high school or even college. Certainly, when a teenager presents complaining of trouble performing at school, it is critical to rule out an overburdened schedule, anxiety or mood disorder, poor sleep habits or sleep disorder, and substance use disorders, all of which are more common in adolescence. But inattentive-type ADHD that was previously missed is also a possibility worth investigating.

Myth 2: “Most children outgrow ADHD; it’s best to find natural solutions and wait it out.”

Early epidemiological studies suggested that as many as 30% of ADHD cases remitted by adulthood, but more recent data has adjusted that number down substantially, closer to 9%. Interestingly, it appears that 10% of patients will experience sustained symptoms, 9% will experience recovery (sustained remission without treatment), and a large majority will have a remitting and relapsing course into adulthood.¹

This emerging evidence suggests that ADHD is almost always a lifelong condition. Untreated, it can threaten healthy development (including social skills and self-esteem) and day-to-day function (academic, social and athletic performance and even vulnerability to accidents) in ways that can be profound. The MTA Study has powerfully demonstrated the efficacy of pharmacological treatment and of specific behavioral treatments for ADHD and associated problems.

 

Myth 3: “You should exhaust natural cures first before trying medications.”

There has been a large amount of research into a variety of “natural” treatments for ADHD: special diets, supplements, increased exercise, and interventions like neurofeedback. While high-dose omega 3 fatty acid supplementation has demonstrated mild improvement in ADHD symptoms, no “natural” treatment has come close to the efficacy of stimulant medications. Interventions such as neurofeedback are expensive and time-consuming without any demonstrated efficacy. That said, improving a child’s routines around sleep, nutrition, and regular exercise are broadly useful strategies to improve any child’s (or adult’s) energy, impulse control, attention, motivation, and capacity to manage adversity and stress. Start any treatment by addressing sleep and exercise, including moderating time spent on screens, to support healthy function. But only medication will achieve symptom remission if your patient has underlying ADHD.

Myth 4: “All medications are equally effective in ADHD.”

It is well-established that stimulants are more effective than non-stimulants in the treatment of ADHD symptoms, with an effect size that is almost double that of non-stimulants.²

Amphetamine-based medications are slightly more effective than methylphenidate-based medications, but they are also generally less well-tolerated. Individual patients commonly have a better response to one class than the other, but you will need a trial to determine which one. It is reasonable to start a patient with an extended formulation of one class, based on your assessment of their vulnerability to side effects or a family history of medication response. Non-stimulants are of use when stimulants are not tolerated (ie, use of atomoxetine with patients who have comorbid anxiety), or to target specific symptoms, such as guanfacine or clonidine for hyperactivity.

 

Myth 5: “You can’t treat ADHD in substance abusing teens, stimulant medications are addictive.”

ADHD itself (not medications) increases the risk for addiction; those with ADHD are almost twice as likely to develop a substance use disorder, with highest risk for marijuana, alcohol, and nicotine abuse.³

This may be a function of limited impulse control or increased sensitivity in the ADHD brain to a drug’s addictive potential. Importantly, there is growing evidence that youth whose ADHD is treated pharmacologically are at lower risk for addiction than their peers with untreated ADHD.⁴

Those youth who have both ADHD and addiction are more likely to stay engaged in treatment for addiction when their ADHD is effectively treated, and there are medication formulations (lisdexamfetamine) that are safe in addiction (cannot be absorbed nasally or intravenously). It is important for you to talk about the heightened vulnerability to addiction with your ADHD patients and their parents, and the value of effective treatment in preventing this complication.

 

Myth 6: “ADHD is usually behavioral. Help parents to set rules, expectations, and limits instead of medicating the problem.”

Bad parenting does not cause ADHD. ADHD is marked by difficulties with impulse control, hyperactivity, and sustaining attention with matters that are not intrinsically engaging. “Behavioral issues” are patterns of behavior children learn to seek rewards or avoid negative consequences. Youth with ADHD can develop behavioral problems, but these are usually driven by negative feedback about their activity level, forgetfulness, or impulse control, which they are not able to change. This can lead to frustration and irritability, poor self-esteem, and even hopelessness — in parents and children both!

While parents are not the source of ADHD symptoms, there is a great deal of parent education and support that can be powerfully effective for these families. Parents benefit from learning strategies that can help their children to shift their attention, plan ahead, and manage frustration, especially for times when their children are unmedicated (vacations and bedtime). It is worth noting that ADHD is among the most heritable of youth psychiatric illnesses, so it is not uncommon for a parent of a child with ADHD to have similar symptoms. If the parents’ ADHD is untreated, they may be more impulsive themselves. They may also be extra sensitive to the qualities they dislike in themselves, inadvertently adding to their children’s sense of shame. ADHD is very treatable, and those with it can learn executive function skills and organizational strategies that can equip them to manage residual symptoms. Parents will benefit from strategies to understand their children and to help them learn adaptive skills in a realistic way. Your discussions with parents could help the families in your practice make adjustments that can translate into big differences in their child’s healthiest development.

Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Sibley MH et al. MTA Cooperative Group. Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD. Am J Psychiatry. 2022 Feb;179(2):142-151. doi: 10.1176/appi.ajp.2021.21010032.

2. Cortese S et al. Comparative Efficacy and Tolerability of Medications for Attention-Deficit Hyperactivity Disorder in Children, Adolescents, and Adults: A Systematic Review and Network Meta-Analysis. Lancet Psychiatry. 2018 Sep;5(9):727-738. doi: 10.1016/S2215-0366(18)30269-4.

3. Lee SS et al. Prospective Association of Childhood Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use and Abuse/Dependence: A Meta-Analytic Review. Clin Psychol Rev. 2011 Apr;31(3):328-41. doi: 10.1016/j.cpr.2011.01.006. 

4. Chorniy A, Kitashima L. Sex, Drugs, and ADHD: The Effects of ADHD Pharmacological Treatment on Teens’ Risky Behaviors. Labour Economics. 2016;43:87-105. doi.org/10.1016/j.labeco.2016.06.014.

In the second half of the school year, you may find that there is a surge of families coming to appointments with concerns about school performance, wondering if their child has ADHD. We expect you are very familiar with this condition, both diagnosing and treating it. So this month we will offer “mythbusters” for ADHD: Responding to common misperceptions about ADHD with a summary of what the research has demonstrated as emerging facts, what is clearly fiction and what falls into the gray space between.

Demographics

A CDC survey of parents from 2022 indicates that 11.4% of children aged 3-17 have ever been diagnosed with ADHD in the United States. This is more than double the ADHD global prevalence of 5%, suggesting that there is overdiagnosis of this condition in this country. Boys are almost twice as likely to be diagnosed (14.5%) as girls (8%), and White children were more likely to be diagnosed than were Black and Hispanic children. The prevalence of ADHD diagnosis decreases as family income increases, and the condition is more frequently diagnosed in 12- to 17-year-olds than in children 11 and younger. The great majority of youth with an ADHD diagnosis (78%) have at least one co-occurring psychiatric condition. Of the children diagnosed with ADHD, slightly over half receive medication treatment (53.6%) whereas nearly a third (30.1%) receive no ADHD-specific treatment.

The Multimodal Treatment of ADHD Study (MTA), a large (600 children, aged 7-9 years), multicenter, longitudinal study of treatment outcomes for medication as well as behavioral and combination therapies demonstrated in every site that medication alone and combination therapy were significantly superior to intensive behavioral treatment alone and to routine community care in the reduction of ADHD symptoms. Of note, problems commonly associated with ADHD (parent-child conflict, anxiety symptoms, poor academic performance, and limited social skills) improved only with the combination treatment. This suggests that while core ADHD symptoms require medication, associated problems will also require behavioral treatment.

The American Academy of Pediatrics has a useful resource guide (healthychildren.org) highlighting the possible symptoms of inattention, hyperactivity, and impulsivity that should be investigated when considering this diagnosis. It is a clinical diagnosis, but screening instruments (such as the Vanderbilt) can be very helpful to identifying symptoms that should be present in more than one setting (home and school). While a child with ADHD can appear calm and focused when receiving direct one-to-one attention (as during a pediatrician’s appointment), symptoms may flourish in less structured or supervised settings. Sometimes parents are keen reporters of a child’s behaviors, but some loving (and exhausted) parents may overreact to a normal degree of inattention or disobedience. This can be especially true when a parent has a more detail-oriented temperament than the child, or with younger children and first-time parents. It is important to consider ADHD when you hear about social difficulties as well as academic ones, where there is a family history of ADHD or when a child is more impulsive, hyperactive, or inattentive than you would expect given their age and developmental stage. Confirm your clinical exam with teacher and parent reports. If the reports don’t line up or there are persistent learning problems in school, consider neuropsychological testing to root out a learning disability.

 

Myth 1: “ADHD never starts in adolescence; you can’t diagnose it after elementary school.”

Diagnostic criteria used to require that symptoms were present before the age of 7 (DSM 3). But current criteria allow for diagnosis before 12 years of age or after. While the consensus is that ADHD is present in childhood, its symptoms are often not apparent. This is because normal development in much younger children is marked by higher levels of activity, distractibility, and impulsivity. Also, children with inattentive-type ADHD may not be apparent to adults if they are performing adequately in school. These youth often do not present for assessment until the challenges of a busy course load make their inattention and consequent inefficiency apparent, in high school or even college. Certainly, when a teenager presents complaining of trouble performing at school, it is critical to rule out an overburdened schedule, anxiety or mood disorder, poor sleep habits or sleep disorder, and substance use disorders, all of which are more common in adolescence. But inattentive-type ADHD that was previously missed is also a possibility worth investigating.

Myth 2: “Most children outgrow ADHD; it’s best to find natural solutions and wait it out.”

Early epidemiological studies suggested that as many as 30% of ADHD cases remitted by adulthood, but more recent data has adjusted that number down substantially, closer to 9%. Interestingly, it appears that 10% of patients will experience sustained symptoms, 9% will experience recovery (sustained remission without treatment), and a large majority will have a remitting and relapsing course into adulthood.¹

This emerging evidence suggests that ADHD is almost always a lifelong condition. Untreated, it can threaten healthy development (including social skills and self-esteem) and day-to-day function (academic, social and athletic performance and even vulnerability to accidents) in ways that can be profound. The MTA Study has powerfully demonstrated the efficacy of pharmacological treatment and of specific behavioral treatments for ADHD and associated problems.

 

Myth 3: “You should exhaust natural cures first before trying medications.”

There has been a large amount of research into a variety of “natural” treatments for ADHD: special diets, supplements, increased exercise, and interventions like neurofeedback. While high-dose omega 3 fatty acid supplementation has demonstrated mild improvement in ADHD symptoms, no “natural” treatment has come close to the efficacy of stimulant medications. Interventions such as neurofeedback are expensive and time-consuming without any demonstrated efficacy. That said, improving a child’s routines around sleep, nutrition, and regular exercise are broadly useful strategies to improve any child’s (or adult’s) energy, impulse control, attention, motivation, and capacity to manage adversity and stress. Start any treatment by addressing sleep and exercise, including moderating time spent on screens, to support healthy function. But only medication will achieve symptom remission if your patient has underlying ADHD.

Myth 4: “All medications are equally effective in ADHD.”

It is well-established that stimulants are more effective than non-stimulants in the treatment of ADHD symptoms, with an effect size that is almost double that of non-stimulants.²

Amphetamine-based medications are slightly more effective than methylphenidate-based medications, but they are also generally less well-tolerated. Individual patients commonly have a better response to one class than the other, but you will need a trial to determine which one. It is reasonable to start a patient with an extended formulation of one class, based on your assessment of their vulnerability to side effects or a family history of medication response. Non-stimulants are of use when stimulants are not tolerated (ie, use of atomoxetine with patients who have comorbid anxiety), or to target specific symptoms, such as guanfacine or clonidine for hyperactivity.

 

Myth 5: “You can’t treat ADHD in substance abusing teens, stimulant medications are addictive.”

ADHD itself (not medications) increases the risk for addiction; those with ADHD are almost twice as likely to develop a substance use disorder, with highest risk for marijuana, alcohol, and nicotine abuse.³

This may be a function of limited impulse control or increased sensitivity in the ADHD brain to a drug’s addictive potential. Importantly, there is growing evidence that youth whose ADHD is treated pharmacologically are at lower risk for addiction than their peers with untreated ADHD.⁴

Those youth who have both ADHD and addiction are more likely to stay engaged in treatment for addiction when their ADHD is effectively treated, and there are medication formulations (lisdexamfetamine) that are safe in addiction (cannot be absorbed nasally or intravenously). It is important for you to talk about the heightened vulnerability to addiction with your ADHD patients and their parents, and the value of effective treatment in preventing this complication.

 

Myth 6: “ADHD is usually behavioral. Help parents to set rules, expectations, and limits instead of medicating the problem.”

Bad parenting does not cause ADHD. ADHD is marked by difficulties with impulse control, hyperactivity, and sustaining attention with matters that are not intrinsically engaging. “Behavioral issues” are patterns of behavior children learn to seek rewards or avoid negative consequences. Youth with ADHD can develop behavioral problems, but these are usually driven by negative feedback about their activity level, forgetfulness, or impulse control, which they are not able to change. This can lead to frustration and irritability, poor self-esteem, and even hopelessness — in parents and children both!

While parents are not the source of ADHD symptoms, there is a great deal of parent education and support that can be powerfully effective for these families. Parents benefit from learning strategies that can help their children to shift their attention, plan ahead, and manage frustration, especially for times when their children are unmedicated (vacations and bedtime). It is worth noting that ADHD is among the most heritable of youth psychiatric illnesses, so it is not uncommon for a parent of a child with ADHD to have similar symptoms. If the parents’ ADHD is untreated, they may be more impulsive themselves. They may also be extra sensitive to the qualities they dislike in themselves, inadvertently adding to their children’s sense of shame. ADHD is very treatable, and those with it can learn executive function skills and organizational strategies that can equip them to manage residual symptoms. Parents will benefit from strategies to understand their children and to help them learn adaptive skills in a realistic way. Your discussions with parents could help the families in your practice make adjustments that can translate into big differences in their child’s healthiest development.

Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Sibley MH et al. MTA Cooperative Group. Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD. Am J Psychiatry. 2022 Feb;179(2):142-151. doi: 10.1176/appi.ajp.2021.21010032.

2. Cortese S et al. Comparative Efficacy and Tolerability of Medications for Attention-Deficit Hyperactivity Disorder in Children, Adolescents, and Adults: A Systematic Review and Network Meta-Analysis. Lancet Psychiatry. 2018 Sep;5(9):727-738. doi: 10.1016/S2215-0366(18)30269-4.

3. Lee SS et al. Prospective Association of Childhood Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use and Abuse/Dependence: A Meta-Analytic Review. Clin Psychol Rev. 2011 Apr;31(3):328-41. doi: 10.1016/j.cpr.2011.01.006. 

4. Chorniy A, Kitashima L. Sex, Drugs, and ADHD: The Effects of ADHD Pharmacological Treatment on Teens’ Risky Behaviors. Labour Economics. 2016;43:87-105. doi.org/10.1016/j.labeco.2016.06.014.

TOPLINE:

Children with congenital cataract in one eye are more likely to achieve nearly normal vision when their caregivers maintain consistent daily patching schedules in the first year after surgery, particularly in the morning or at regular times every day.

METHODOLOGY:

• Researchers conducted a post hoc analysis of the Infant Aphakia Treatment Study to examine the association between the reported consistency in patching during the first year after unilateral cataract surgery and visual acuity.
• They included data from 101 children whose caregivers completed 7-day patching diaries at 2 months after surgery or at age 13 months.
• The treatment protocol required caregivers to have their child wear a patch over the fellow eye for 1 hour daily from the second week after cataract surgery until age 8 months, followed by patching for 50% of waking hours until age 5 years.
• Consistent patching was defined as daily patching with an average start time before 9 AM or an interquartile range of the first application time of 60 minutes or less.
• Visual acuity in the treated eye was the primary outcome, assessed at ages 54 + 1 months and 10.5 years; participants with a visual acuity of 20/40 or better were said to have near-normal vision.

TAKEAWAY:

• Children whose caregivers reported consistent patching patterns demonstrated better average visual acuity at age 54 months than those whose caregivers reported inconsistent patching patterns (mean difference in logMAR visual acuity, 0.55; 95% CI, 0.22-0.87); the results were promising for children aged 10.5 years, as well.
• Data from the diary completed at age 13 months showed children whose caregivers reported patching before 9 AM or around the same time daily were more likely to achieve near-normal vision at age 54 + 1 months and 10.5 years (relative risk, 3.55; 95% CI, 1.61-7.80, and 2.31; 95% CI, 1.12-4.78, respectively) than those whose caregivers did not report such behavior.
• Children whose caregivers reported consistent vs inconsistent patching patterns achieved more average daily hours of patching both during the first year (4.82 h vs 3.50 h) and between ages 12 and 48 months (4.96 h vs 3.03 h).

IN PRACTICE:

“This information can be used by healthcare providers to motivate caregivers to develop consistent patching habits. Further, providers can present caregivers with simple advice: Apply the patch every day either first thing in the morning or about the same time every day,” the authors of the study wrote.

SOURCE:

The study was led by Carolyn Drews-Botsch, PhD, MPH, of the Department of Global and Community Health at George Mason University, in Fairfax, Virginia. It was published online in Ophthalmology.

LIMITATIONS:

The diaries covered only 14 days of the first year following surgery, which may not have fully represented patching patterns during other periods. The researchers noted that establishing a routine for patching was particularly challenging for infants aged less than 5 months at the time of the first diary completion as these infants may not yet have established regular sleep and feeding routines. Parents who participated in this trial may have differed from those in routine practice, potentially affecting the generalizability of the findings to general clinical populations.

DISCLOSURES:

This study was supported by the following grants: 1 R21 EY032152, 2 UG1 EY031287, 5 U10 EY013287, 5 UG1 EY02553, and 7 UG1 EY013272. The authors declared having no conflicts of interest.

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:

Children with congenital cataract in one eye are more likely to achieve nearly normal vision when their caregivers maintain consistent daily patching schedules in the first year after surgery, particularly in the morning or at regular times every day.

METHODOLOGY:

• Researchers conducted a post hoc analysis of the Infant Aphakia Treatment Study to examine the association between the reported consistency in patching during the first year after unilateral cataract surgery and visual acuity.
• They included data from 101 children whose caregivers completed 7-day patching diaries at 2 months after surgery or at age 13 months.
• The treatment protocol required caregivers to have their child wear a patch over the fellow eye for 1 hour daily from the second week after cataract surgery until age 8 months, followed by patching for 50% of waking hours until age 5 years.
• Consistent patching was defined as daily patching with an average start time before 9 AM or an interquartile range of the first application time of 60 minutes or less.
• Visual acuity in the treated eye was the primary outcome, assessed at ages 54 + 1 months and 10.5 years; participants with a visual acuity of 20/40 or better were said to have near-normal vision.

TAKEAWAY:

• Children whose caregivers reported consistent patching patterns demonstrated better average visual acuity at age 54 months than those whose caregivers reported inconsistent patching patterns (mean difference in logMAR visual acuity, 0.55; 95% CI, 0.22-0.87); the results were promising for children aged 10.5 years, as well.
• Data from the diary completed at age 13 months showed children whose caregivers reported patching before 9 AM or around the same time daily were more likely to achieve near-normal vision at age 54 + 1 months and 10.5 years (relative risk, 3.55; 95% CI, 1.61-7.80, and 2.31; 95% CI, 1.12-4.78, respectively) than those whose caregivers did not report such behavior.
• Children whose caregivers reported consistent vs inconsistent patching patterns achieved more average daily hours of patching both during the first year (4.82 h vs 3.50 h) and between ages 12 and 48 months (4.96 h vs 3.03 h).

IN PRACTICE:

“This information can be used by healthcare providers to motivate caregivers to develop consistent patching habits. Further, providers can present caregivers with simple advice: Apply the patch every day either first thing in the morning or about the same time every day,” the authors of the study wrote.

SOURCE:

The study was led by Carolyn Drews-Botsch, PhD, MPH, of the Department of Global and Community Health at George Mason University, in Fairfax, Virginia. It was published online in Ophthalmology.

LIMITATIONS:

The diaries covered only 14 days of the first year following surgery, which may not have fully represented patching patterns during other periods. The researchers noted that establishing a routine for patching was particularly challenging for infants aged less than 5 months at the time of the first diary completion as these infants may not yet have established regular sleep and feeding routines. Parents who participated in this trial may have differed from those in routine practice, potentially affecting the generalizability of the findings to general clinical populations.

DISCLOSURES:

This study was supported by the following grants: 1 R21 EY032152, 2 UG1 EY031287, 5 U10 EY013287, 5 UG1 EY02553, and 7 UG1 EY013272. The authors declared having no conflicts of interest.

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:

Children with congenital cataract in one eye are more likely to achieve nearly normal vision when their caregivers maintain consistent daily patching schedules in the first year after surgery, particularly in the morning or at regular times every day.

METHODOLOGY:

• Researchers conducted a post hoc analysis of the Infant Aphakia Treatment Study to examine the association between the reported consistency in patching during the first year after unilateral cataract surgery and visual acuity.
• They included data from 101 children whose caregivers completed 7-day patching diaries at 2 months after surgery or at age 13 months.
• The treatment protocol required caregivers to have their child wear a patch over the fellow eye for 1 hour daily from the second week after cataract surgery until age 8 months, followed by patching for 50% of waking hours until age 5 years.
• Consistent patching was defined as daily patching with an average start time before 9 AM or an interquartile range of the first application time of 60 minutes or less.
• Visual acuity in the treated eye was the primary outcome, assessed at ages 54 + 1 months and 10.5 years; participants with a visual acuity of 20/40 or better were said to have near-normal vision.

TAKEAWAY:

• Children whose caregivers reported consistent patching patterns demonstrated better average visual acuity at age 54 months than those whose caregivers reported inconsistent patching patterns (mean difference in logMAR visual acuity, 0.55; 95% CI, 0.22-0.87); the results were promising for children aged 10.5 years, as well.
• Data from the diary completed at age 13 months showed children whose caregivers reported patching before 9 AM or around the same time daily were more likely to achieve near-normal vision at age 54 + 1 months and 10.5 years (relative risk, 3.55; 95% CI, 1.61-7.80, and 2.31; 95% CI, 1.12-4.78, respectively) than those whose caregivers did not report such behavior.
• Children whose caregivers reported consistent vs inconsistent patching patterns achieved more average daily hours of patching both during the first year (4.82 h vs 3.50 h) and between ages 12 and 48 months (4.96 h vs 3.03 h).

IN PRACTICE:

“This information can be used by healthcare providers to motivate caregivers to develop consistent patching habits. Further, providers can present caregivers with simple advice: Apply the patch every day either first thing in the morning or about the same time every day,” the authors of the study wrote.

SOURCE:

The study was led by Carolyn Drews-Botsch, PhD, MPH, of the Department of Global and Community Health at George Mason University, in Fairfax, Virginia. It was published online in Ophthalmology.

LIMITATIONS:

The diaries covered only 14 days of the first year following surgery, which may not have fully represented patching patterns during other periods. The researchers noted that establishing a routine for patching was particularly challenging for infants aged less than 5 months at the time of the first diary completion as these infants may not yet have established regular sleep and feeding routines. Parents who participated in this trial may have differed from those in routine practice, potentially affecting the generalizability of the findings to general clinical populations.

DISCLOSURES:

This study was supported by the following grants: 1 R21 EY032152, 2 UG1 EY031287, 5 U10 EY013287, 5 UG1 EY02553, and 7 UG1 EY013272. The authors declared having no conflicts of interest.

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.

Almost 70 years after the discovery of the respiratory syncytial virus (RSV), vaccines and preventive treatments are giving babies a chance to beat the potentially deadly childhood infection.

As doctors turn to monoclonal antibody therapies and governments plan vaccination programs, clinical researchers are asking whether these measures will reduce the spread of the virus. Will fewer babies die from RSV, and fewer children develop permanent wheezing?

Recent studies offer clues.

Fabio Midulla, an associate professor of pediatrics at Sapienza University of Rome in Rome, Italy, said that the pharmaceutical industry is poised to push governments to use vaccines and monoclonal antibodies for even more children. “Such a push might work,” he said at the European Respiratory Society (ERS) 2024 Congress, “given that several studies have already demonstrated that their use can improve outcomes for children who do become infected and reduce societal costs by reducing hospitalizations.”

But Mariëlle WH Pijnenburg, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands, said at the Congress that greater rollout would require governments to force industry to lower prices. If treatments remain beyond the reach of lower-income countries — where the burden of RSV is the greatest — the death toll from this common childhood infection will remain stubbornly high, and the prospect of global elimination will remain forever out of reach, she said.

New Tools in the Fight Against RSV

Nirsevimab, a long-acting monoclonal antibody given to newborns to prevent severe infection, was approved by the European Medicines Agency (EMA) in October 2022 and the US Food and Drug Administration (FDA) in July 2023. And Abrysvo, a vaccine given to older adults and pregnant women to stop them from passing the virus to babies from birth through 6 months of age, was approved by the FDA and the EMA in 2023.

RSV is responsible for over 33 million lung infections in children younger than 5 years annually, with more than 4 million hospitalizations and nearly 200,000 deaths. According to the Centers for Disease Control and Prevention, every year, 2.1 million children younger than 5 years old visit a healthcare provider because of an RSV infection and between 58,000 and 80,000 children younger than 5 years old are hospitalized in the United States. The burden of severe RSV disease is also high among adults, with an estimated 123,000-193,000 hospitalizations, 24,400-34,900 ICU admissions, and 4680-8620 in-hospital deaths occurring annually among US adults.

While the virus affects all age groups, it is particularly severe in infants, swelling their airways and causing them to struggle for breath. Infection in infancy can lead to later complications, such as the development of wheezing, a condition that causes breathlessness and a feeling of tightening in the chest, and possibly also asthma.

Studies have shown that children and preterm infants infected with RSV who were given monoclonal antibodies experienced less post-infection wheezing, suggesting that RSV prophylaxis could prevent the development of wheezing bronchitis.

A study conducted in Galicia, Spain, showed that only 0.3% of infants who received prophylaxis with Nirsevimab were hospitalized for RSV-related lower respiratory tract infections. “This is very promising,” Yvonne Maldonado, MD, professor of pediatrics and epidemiology and population health at Stanford University in Stanford, California, told Medscape Medical News. “But this virus is ubiquitous. It’s found everywhere. It comes around every winter season. And immunity is not long-lasting.”

Older children who are not receiving monoclonal antibodies still experience RSV-related hospitalizations, suggesting the virus continues to circulate at high enough levels in the community. “The vaccine and monoclonal antibodies can reduce the risk of hospitalization and more severe disease in young kids, but they won’t eliminate the virus,” Maldonado said. “Right now, the goal is to prevent serious infection, not to prevent the spread of the virus completely.”

Expanding Access to RSV Prevention in Low-Income Countries

Currently, the RSV vaccine and monoclonal antibodies are only given in the United States, Europe, United Kingdom, and Canada to newborns, children at risk for severe disease, and pregnant women. However, Midulla said that pharmaceutical companies are pushing to broaden the rollout to a broader population within these countries. Yet, he said, over 99% of RSV infection–related deaths occur in the Global South.

No pharmaceutical company has sought approval in low-income countries such as those in Africa. “Unless they see there being a market in a country, they’re not going to go through the onerous process of getting [a vaccine] licensed,” Shabir Madhi, dean of the faculty of health sciences and a professor of vaccinology at the University of the Witwatersrand, Johannesburg, South Africa, told Medscape Medical News.

He highlighted that almost 50% of RSV-related deaths occur in African children younger than 5 years, despite these children comprising just one fifth of the global under-5 population. The high burden of RSV mortality in the Global South is mainly due to poor access to healthcare and supportive treatments, such as supplemental oxygen, which can help children recover from severe RSV infection.

Companies are unlikely to pursue regulatory approval and licensing in low- and middle-income countries until GAVI, the global vaccine alliance, commits to procuring and funding the vaccines for these regions. GAVI’s decision would provide the necessary market incentive for manufacturers to seek approval.

Madhi suggested that GAVI’s decision on RSV vaccine procurement is imminent, likely early next year, following the World Health Organization’s Strategic Advisory Group of Experts on Immunization recommendation to vaccinate all pregnant women with the RSV vaccine, regardless of whether they are in high-income or low-income countries.

Nevertheless, even if vaccines become available, many African countries may still struggle to afford them. Madhi said that these countries would likely depend on GAVI and organizations like UNICEF to procure the vaccines at affordable prices. “The unfortunate reality is that many countries — especially in Africa — still wouldn’t be able to afford it, even if the vaccine cost as little as $5,” said Madhi. “But that’s where they would have the greatest impact.”

Midulla, Pijnenburg reported no relevant financial relationships. Madhi’s research unit, the Vaccines and Infectious Disease Analytics Unit, was involved in the clinical trials for the Pfizer RSV vaccine, the GSK RSV vaccine (which was terminated), as well as the MEDLEY trial of palivizumab. All funding for these studies went to his institution, the University of the Witwatersrand. Maldonado was Stanford principal investigator for the Pfizer RSV vaccine.
 

A version of this article appeared on Medscape.com.

Almost 70 years after the discovery of the respiratory syncytial virus (RSV), vaccines and preventive treatments are giving babies a chance to beat the potentially deadly childhood infection.

As doctors turn to monoclonal antibody therapies and governments plan vaccination programs, clinical researchers are asking whether these measures will reduce the spread of the virus. Will fewer babies die from RSV, and fewer children develop permanent wheezing?

Recent studies offer clues.

Fabio Midulla, an associate professor of pediatrics at Sapienza University of Rome in Rome, Italy, said that the pharmaceutical industry is poised to push governments to use vaccines and monoclonal antibodies for even more children. “Such a push might work,” he said at the European Respiratory Society (ERS) 2024 Congress, “given that several studies have already demonstrated that their use can improve outcomes for children who do become infected and reduce societal costs by reducing hospitalizations.”

But Mariëlle WH Pijnenburg, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands, said at the Congress that greater rollout would require governments to force industry to lower prices. If treatments remain beyond the reach of lower-income countries — where the burden of RSV is the greatest — the death toll from this common childhood infection will remain stubbornly high, and the prospect of global elimination will remain forever out of reach, she said.

New Tools in the Fight Against RSV

Nirsevimab, a long-acting monoclonal antibody given to newborns to prevent severe infection, was approved by the European Medicines Agency (EMA) in October 2022 and the US Food and Drug Administration (FDA) in July 2023. And Abrysvo, a vaccine given to older adults and pregnant women to stop them from passing the virus to babies from birth through 6 months of age, was approved by the FDA and the EMA in 2023.

RSV is responsible for over 33 million lung infections in children younger than 5 years annually, with more than 4 million hospitalizations and nearly 200,000 deaths. According to the Centers for Disease Control and Prevention, every year, 2.1 million children younger than 5 years old visit a healthcare provider because of an RSV infection and between 58,000 and 80,000 children younger than 5 years old are hospitalized in the United States. The burden of severe RSV disease is also high among adults, with an estimated 123,000-193,000 hospitalizations, 24,400-34,900 ICU admissions, and 4680-8620 in-hospital deaths occurring annually among US adults.

While the virus affects all age groups, it is particularly severe in infants, swelling their airways and causing them to struggle for breath. Infection in infancy can lead to later complications, such as the development of wheezing, a condition that causes breathlessness and a feeling of tightening in the chest, and possibly also asthma.

Studies have shown that children and preterm infants infected with RSV who were given monoclonal antibodies experienced less post-infection wheezing, suggesting that RSV prophylaxis could prevent the development of wheezing bronchitis.

A study conducted in Galicia, Spain, showed that only 0.3% of infants who received prophylaxis with Nirsevimab were hospitalized for RSV-related lower respiratory tract infections. “This is very promising,” Yvonne Maldonado, MD, professor of pediatrics and epidemiology and population health at Stanford University in Stanford, California, told Medscape Medical News. “But this virus is ubiquitous. It’s found everywhere. It comes around every winter season. And immunity is not long-lasting.”

Older children who are not receiving monoclonal antibodies still experience RSV-related hospitalizations, suggesting the virus continues to circulate at high enough levels in the community. “The vaccine and monoclonal antibodies can reduce the risk of hospitalization and more severe disease in young kids, but they won’t eliminate the virus,” Maldonado said. “Right now, the goal is to prevent serious infection, not to prevent the spread of the virus completely.”

Expanding Access to RSV Prevention in Low-Income Countries

Currently, the RSV vaccine and monoclonal antibodies are only given in the United States, Europe, United Kingdom, and Canada to newborns, children at risk for severe disease, and pregnant women. However, Midulla said that pharmaceutical companies are pushing to broaden the rollout to a broader population within these countries. Yet, he said, over 99% of RSV infection–related deaths occur in the Global South.

No pharmaceutical company has sought approval in low-income countries such as those in Africa. “Unless they see there being a market in a country, they’re not going to go through the onerous process of getting [a vaccine] licensed,” Shabir Madhi, dean of the faculty of health sciences and a professor of vaccinology at the University of the Witwatersrand, Johannesburg, South Africa, told Medscape Medical News.

He highlighted that almost 50% of RSV-related deaths occur in African children younger than 5 years, despite these children comprising just one fifth of the global under-5 population. The high burden of RSV mortality in the Global South is mainly due to poor access to healthcare and supportive treatments, such as supplemental oxygen, which can help children recover from severe RSV infection.

Companies are unlikely to pursue regulatory approval and licensing in low- and middle-income countries until GAVI, the global vaccine alliance, commits to procuring and funding the vaccines for these regions. GAVI’s decision would provide the necessary market incentive for manufacturers to seek approval.

Madhi suggested that GAVI’s decision on RSV vaccine procurement is imminent, likely early next year, following the World Health Organization’s Strategic Advisory Group of Experts on Immunization recommendation to vaccinate all pregnant women with the RSV vaccine, regardless of whether they are in high-income or low-income countries.

Nevertheless, even if vaccines become available, many African countries may still struggle to afford them. Madhi said that these countries would likely depend on GAVI and organizations like UNICEF to procure the vaccines at affordable prices. “The unfortunate reality is that many countries — especially in Africa — still wouldn’t be able to afford it, even if the vaccine cost as little as $5,” said Madhi. “But that’s where they would have the greatest impact.”

Midulla, Pijnenburg reported no relevant financial relationships. Madhi’s research unit, the Vaccines and Infectious Disease Analytics Unit, was involved in the clinical trials for the Pfizer RSV vaccine, the GSK RSV vaccine (which was terminated), as well as the MEDLEY trial of palivizumab. All funding for these studies went to his institution, the University of the Witwatersrand. Maldonado was Stanford principal investigator for the Pfizer RSV vaccine.
 

A version of this article appeared on Medscape.com.

Almost 70 years after the discovery of the respiratory syncytial virus (RSV), vaccines and preventive treatments are giving babies a chance to beat the potentially deadly childhood infection.

As doctors turn to monoclonal antibody therapies and governments plan vaccination programs, clinical researchers are asking whether these measures will reduce the spread of the virus. Will fewer babies die from RSV, and fewer children develop permanent wheezing?

Recent studies offer clues.

Fabio Midulla, an associate professor of pediatrics at Sapienza University of Rome in Rome, Italy, said that the pharmaceutical industry is poised to push governments to use vaccines and monoclonal antibodies for even more children. “Such a push might work,” he said at the European Respiratory Society (ERS) 2024 Congress, “given that several studies have already demonstrated that their use can improve outcomes for children who do become infected and reduce societal costs by reducing hospitalizations.”

But Mariëlle WH Pijnenburg, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands, said at the Congress that greater rollout would require governments to force industry to lower prices. If treatments remain beyond the reach of lower-income countries — where the burden of RSV is the greatest — the death toll from this common childhood infection will remain stubbornly high, and the prospect of global elimination will remain forever out of reach, she said.

New Tools in the Fight Against RSV

Nirsevimab, a long-acting monoclonal antibody given to newborns to prevent severe infection, was approved by the European Medicines Agency (EMA) in October 2022 and the US Food and Drug Administration (FDA) in July 2023. And Abrysvo, a vaccine given to older adults and pregnant women to stop them from passing the virus to babies from birth through 6 months of age, was approved by the FDA and the EMA in 2023.

RSV is responsible for over 33 million lung infections in children younger than 5 years annually, with more than 4 million hospitalizations and nearly 200,000 deaths. According to the Centers for Disease Control and Prevention, every year, 2.1 million children younger than 5 years old visit a healthcare provider because of an RSV infection and between 58,000 and 80,000 children younger than 5 years old are hospitalized in the United States. The burden of severe RSV disease is also high among adults, with an estimated 123,000-193,000 hospitalizations, 24,400-34,900 ICU admissions, and 4680-8620 in-hospital deaths occurring annually among US adults.

While the virus affects all age groups, it is particularly severe in infants, swelling their airways and causing them to struggle for breath. Infection in infancy can lead to later complications, such as the development of wheezing, a condition that causes breathlessness and a feeling of tightening in the chest, and possibly also asthma.

Studies have shown that children and preterm infants infected with RSV who were given monoclonal antibodies experienced less post-infection wheezing, suggesting that RSV prophylaxis could prevent the development of wheezing bronchitis.

A study conducted in Galicia, Spain, showed that only 0.3% of infants who received prophylaxis with Nirsevimab were hospitalized for RSV-related lower respiratory tract infections. “This is very promising,” Yvonne Maldonado, MD, professor of pediatrics and epidemiology and population health at Stanford University in Stanford, California, told Medscape Medical News. “But this virus is ubiquitous. It’s found everywhere. It comes around every winter season. And immunity is not long-lasting.”

Older children who are not receiving monoclonal antibodies still experience RSV-related hospitalizations, suggesting the virus continues to circulate at high enough levels in the community. “The vaccine and monoclonal antibodies can reduce the risk of hospitalization and more severe disease in young kids, but they won’t eliminate the virus,” Maldonado said. “Right now, the goal is to prevent serious infection, not to prevent the spread of the virus completely.”

Expanding Access to RSV Prevention in Low-Income Countries

Currently, the RSV vaccine and monoclonal antibodies are only given in the United States, Europe, United Kingdom, and Canada to newborns, children at risk for severe disease, and pregnant women. However, Midulla said that pharmaceutical companies are pushing to broaden the rollout to a broader population within these countries. Yet, he said, over 99% of RSV infection–related deaths occur in the Global South.

No pharmaceutical company has sought approval in low-income countries such as those in Africa. “Unless they see there being a market in a country, they’re not going to go through the onerous process of getting [a vaccine] licensed,” Shabir Madhi, dean of the faculty of health sciences and a professor of vaccinology at the University of the Witwatersrand, Johannesburg, South Africa, told Medscape Medical News.

He highlighted that almost 50% of RSV-related deaths occur in African children younger than 5 years, despite these children comprising just one fifth of the global under-5 population. The high burden of RSV mortality in the Global South is mainly due to poor access to healthcare and supportive treatments, such as supplemental oxygen, which can help children recover from severe RSV infection.

Companies are unlikely to pursue regulatory approval and licensing in low- and middle-income countries until GAVI, the global vaccine alliance, commits to procuring and funding the vaccines for these regions. GAVI’s decision would provide the necessary market incentive for manufacturers to seek approval.

Madhi suggested that GAVI’s decision on RSV vaccine procurement is imminent, likely early next year, following the World Health Organization’s Strategic Advisory Group of Experts on Immunization recommendation to vaccinate all pregnant women with the RSV vaccine, regardless of whether they are in high-income or low-income countries.

Nevertheless, even if vaccines become available, many African countries may still struggle to afford them. Madhi said that these countries would likely depend on GAVI and organizations like UNICEF to procure the vaccines at affordable prices. “The unfortunate reality is that many countries — especially in Africa — still wouldn’t be able to afford it, even if the vaccine cost as little as $5,” said Madhi. “But that’s where they would have the greatest impact.”

Midulla, Pijnenburg reported no relevant financial relationships. Madhi’s research unit, the Vaccines and Infectious Disease Analytics Unit, was involved in the clinical trials for the Pfizer RSV vaccine, the GSK RSV vaccine (which was terminated), as well as the MEDLEY trial of palivizumab. All funding for these studies went to his institution, the University of the Witwatersrand. Maldonado was Stanford principal investigator for the Pfizer RSV vaccine.
 

A version of this article appeared on Medscape.com.