Pediatrics

After more than 5 decades of trying, the drug industry is on the verge of providing effective immunizations against the respiratory syncytial virus (RSV), which has put an estimated 90,000 U.S. infants and small children in the hospital since the start of October.

But only one of the shots is designed to be given to babies, and a glitch in congressional language may make it difficult to allow children from low-income families to get it as readily as the well insured.

Since 1994, routine vaccination has been a childhood entitlement under the Vaccines for Children program, through which the federal government buys millions of vaccines and provides them free through pediatricians and clinics to children who are uninsured, underinsured, or on Medicaid – more than half of all American kids.

The 1993 law creating the program didn’t specifically include antibody shots, which were used only as rare emergency therapy at the time the bill was written.

But the first medication of its kind likely to be available to babies, called nirsevimab (it was approved in Europe in December, and Food and Drug Administration approval is expected in the summer of 2023), is not a vaccine but rather a monoclonal antibody that neutralizes RSV in the bloodstream.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices is certain to recommend giving the antibody to infants, said Kelly Moore, MD, president of the advocacy group Immunize.org. The CDC is currently assessing whether nirsevimab would be eligible for the Vaccines for Children program, agency spokesperson Kristen Nordlund told KHN.

Failing to do so would “consign thousands upon thousands of infants to hospitalization and serious illness for semantic reasons despite existence of an immunization that functionally performs just like a seasonal vaccine,” Dr. Moore said.

Officials from Sanofi, which is producing the nirsevimab injection along with AstraZeneca, declined to state a price but said the range would be similar to that of a pediatric vaccine course. The CDC pays about $650 for the most expensive routine vaccine, the four shots against pneumococcal infection. In other words, FDA approval would make nirsevimab a blockbuster drug worth billions annually if it’s given to a large share of the 3.7 million or so children born in the U.S. each year.

Pfizer and GlaxoSmithKline are making traditional vaccines against RSV and expect FDA approval later in 2023. Pfizer’s shot initially would be given to pregnant women – to shield their babies from the disease – while GSK’s would be given to the elderly.

Vaccines designed for infants are in the pipeline, but some experts are still nervous about them. A 1966 RSV vaccine trial failed spectacularly, killing two toddlers, and immunologists aren’t totally in agreement over the cause, said Barney Graham, MD, PhD, the retired National Institutes of Health scientist whose studies of the episode contributed to successful COVID-19 and RSV vaccines.

After 2 years of COVID lockdowns and masking slowed its transmission, RSV exploded across the United States in 2023, swamping pediatric intensive care units.

Sanofi and AstraZeneca hope to have nirsevimab approved by the FDA, recommended by the CDC, and deployed nationwide by fall to prevent future RSV epidemics.

Their product is designed to be provided before a baby’s first winter RSV season. In clinical trials, the antibodies provided up to 5 months of protection. Most children wouldn’t need a second dose because the virus is not a mortal danger to healthy kids over a year old, said Jon Heinrichs, a senior member of Sanofi’s vaccines division.

If the antibody treatment is not accepted for the Vaccines for Children program, that will limit access to the shot for the uninsured and those on Medicaid, the majority of whom represent racial or ethnic minorities, Dr. Moore said. The drugmakers would have to negotiate with each state’s Medicaid program to get it on their formularies.

Excluding the shot from Vaccines for Children “would only worsen existing health disparities,” said Sean O’Leary, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora, and chair of the infectious diseases committee of the American Academy of Pediatrics.

RSV affects babies of all social classes but tends to hit poor, crowded households hardest, said Dr. Graham. “Family history of asthma or allergy makes it worse,” he said, and premature babies are also at higher risk.

While 2%-3% of U.S. infants are hospitalized with RSV each year, only a few hundred don’t survive. But as many as 10,000 people 65 and older perish because of an infection every year, and a little-discussed legal change will make RSV and other vaccines more available to this group.

A section of the 2022 Inflation Reduction Act that went into effect Jan. 1 ends out-of-pocket payments for all vaccines by Medicare patients – including RSV vaccines, if they are licensed for this group.

Before, “if you hadn’t met your deductible, it could be very expensive,” said Leonard Friedland, MD, vice president for scientific affairs and public health in GSK’s vaccines division, which also makes shingles and combination tetanus-diphtheria-whooping cough boosters covered by the new law. “It’s a tremendously important advance.”

Of course, high levels of vaccine hesitancy are likely to blunt uptake of the shots regardless of who pays, said Jennifer Reich, a sociologist at the University of Colorado who studies vaccination attitudes.

New types of shots, like the Sanofi-AstraZeneca antibodies, often alarm parents, and Pfizer’s shot for pregnant women is likely to push fear buttons as well, she said.

Public health officials “don’t seem very savvy about how to get ahead” of claims that vaccines undermine fertility or otherwise harm people, said Ms. Reich.

On the other hand, this winter’s RSV epidemic will be persuasive to many parents, said Heidi Larson, leader of the Vaccine Confidence Project and a professor of anthropology at the London School of Hygiene and Tropical Medicine.

“It’s a scary thing to have your kid hospitalized with RSV,” she said.

While unfortunate, “the high number of children who died or were admitted to the ICU in the past season with RSV – in some ways that’s helpful,” said Laura Riley, MD, chair of obstetrics and gynecology at Weill Cornell Medicine, New York.

Specialists in her field haven’t really started talking about how to communicate with women about the vaccine, said Dr. Riley, who chairs the immunization group at the American College of Obstetricians and Gynecologists.

“Everyone’s been waiting to see if it gets approved,” she said. “The education has to start soon, but it’s hard to roll out education before you roll out the shot.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

After more than 5 decades of trying, the drug industry is on the verge of providing effective immunizations against the respiratory syncytial virus (RSV), which has put an estimated 90,000 U.S. infants and small children in the hospital since the start of October.

But only one of the shots is designed to be given to babies, and a glitch in congressional language may make it difficult to allow children from low-income families to get it as readily as the well insured.

Since 1994, routine vaccination has been a childhood entitlement under the Vaccines for Children program, through which the federal government buys millions of vaccines and provides them free through pediatricians and clinics to children who are uninsured, underinsured, or on Medicaid – more than half of all American kids.

The 1993 law creating the program didn’t specifically include antibody shots, which were used only as rare emergency therapy at the time the bill was written.

But the first medication of its kind likely to be available to babies, called nirsevimab (it was approved in Europe in December, and Food and Drug Administration approval is expected in the summer of 2023), is not a vaccine but rather a monoclonal antibody that neutralizes RSV in the bloodstream.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices is certain to recommend giving the antibody to infants, said Kelly Moore, MD, president of the advocacy group Immunize.org. The CDC is currently assessing whether nirsevimab would be eligible for the Vaccines for Children program, agency spokesperson Kristen Nordlund told KHN.

Failing to do so would “consign thousands upon thousands of infants to hospitalization and serious illness for semantic reasons despite existence of an immunization that functionally performs just like a seasonal vaccine,” Dr. Moore said.

Officials from Sanofi, which is producing the nirsevimab injection along with AstraZeneca, declined to state a price but said the range would be similar to that of a pediatric vaccine course. The CDC pays about $650 for the most expensive routine vaccine, the four shots against pneumococcal infection. In other words, FDA approval would make nirsevimab a blockbuster drug worth billions annually if it’s given to a large share of the 3.7 million or so children born in the U.S. each year.

Pfizer and GlaxoSmithKline are making traditional vaccines against RSV and expect FDA approval later in 2023. Pfizer’s shot initially would be given to pregnant women – to shield their babies from the disease – while GSK’s would be given to the elderly.

Vaccines designed for infants are in the pipeline, but some experts are still nervous about them. A 1966 RSV vaccine trial failed spectacularly, killing two toddlers, and immunologists aren’t totally in agreement over the cause, said Barney Graham, MD, PhD, the retired National Institutes of Health scientist whose studies of the episode contributed to successful COVID-19 and RSV vaccines.

After 2 years of COVID lockdowns and masking slowed its transmission, RSV exploded across the United States in 2023, swamping pediatric intensive care units.

Sanofi and AstraZeneca hope to have nirsevimab approved by the FDA, recommended by the CDC, and deployed nationwide by fall to prevent future RSV epidemics.

Their product is designed to be provided before a baby’s first winter RSV season. In clinical trials, the antibodies provided up to 5 months of protection. Most children wouldn’t need a second dose because the virus is not a mortal danger to healthy kids over a year old, said Jon Heinrichs, a senior member of Sanofi’s vaccines division.

If the antibody treatment is not accepted for the Vaccines for Children program, that will limit access to the shot for the uninsured and those on Medicaid, the majority of whom represent racial or ethnic minorities, Dr. Moore said. The drugmakers would have to negotiate with each state’s Medicaid program to get it on their formularies.

Excluding the shot from Vaccines for Children “would only worsen existing health disparities,” said Sean O’Leary, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora, and chair of the infectious diseases committee of the American Academy of Pediatrics.

RSV affects babies of all social classes but tends to hit poor, crowded households hardest, said Dr. Graham. “Family history of asthma or allergy makes it worse,” he said, and premature babies are also at higher risk.

While 2%-3% of U.S. infants are hospitalized with RSV each year, only a few hundred don’t survive. But as many as 10,000 people 65 and older perish because of an infection every year, and a little-discussed legal change will make RSV and other vaccines more available to this group.

A section of the 2022 Inflation Reduction Act that went into effect Jan. 1 ends out-of-pocket payments for all vaccines by Medicare patients – including RSV vaccines, if they are licensed for this group.

Before, “if you hadn’t met your deductible, it could be very expensive,” said Leonard Friedland, MD, vice president for scientific affairs and public health in GSK’s vaccines division, which also makes shingles and combination tetanus-diphtheria-whooping cough boosters covered by the new law. “It’s a tremendously important advance.”

Of course, high levels of vaccine hesitancy are likely to blunt uptake of the shots regardless of who pays, said Jennifer Reich, a sociologist at the University of Colorado who studies vaccination attitudes.

New types of shots, like the Sanofi-AstraZeneca antibodies, often alarm parents, and Pfizer’s shot for pregnant women is likely to push fear buttons as well, she said.

Public health officials “don’t seem very savvy about how to get ahead” of claims that vaccines undermine fertility or otherwise harm people, said Ms. Reich.

On the other hand, this winter’s RSV epidemic will be persuasive to many parents, said Heidi Larson, leader of the Vaccine Confidence Project and a professor of anthropology at the London School of Hygiene and Tropical Medicine.

“It’s a scary thing to have your kid hospitalized with RSV,” she said.

While unfortunate, “the high number of children who died or were admitted to the ICU in the past season with RSV – in some ways that’s helpful,” said Laura Riley, MD, chair of obstetrics and gynecology at Weill Cornell Medicine, New York.

Specialists in her field haven’t really started talking about how to communicate with women about the vaccine, said Dr. Riley, who chairs the immunization group at the American College of Obstetricians and Gynecologists.

“Everyone’s been waiting to see if it gets approved,” she said. “The education has to start soon, but it’s hard to roll out education before you roll out the shot.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

After more than 5 decades of trying, the drug industry is on the verge of providing effective immunizations against the respiratory syncytial virus (RSV), which has put an estimated 90,000 U.S. infants and small children in the hospital since the start of October.

But only one of the shots is designed to be given to babies, and a glitch in congressional language may make it difficult to allow children from low-income families to get it as readily as the well insured.

Since 1994, routine vaccination has been a childhood entitlement under the Vaccines for Children program, through which the federal government buys millions of vaccines and provides them free through pediatricians and clinics to children who are uninsured, underinsured, or on Medicaid – more than half of all American kids.

The 1993 law creating the program didn’t specifically include antibody shots, which were used only as rare emergency therapy at the time the bill was written.

But the first medication of its kind likely to be available to babies, called nirsevimab (it was approved in Europe in December, and Food and Drug Administration approval is expected in the summer of 2023), is not a vaccine but rather a monoclonal antibody that neutralizes RSV in the bloodstream.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices is certain to recommend giving the antibody to infants, said Kelly Moore, MD, president of the advocacy group Immunize.org. The CDC is currently assessing whether nirsevimab would be eligible for the Vaccines for Children program, agency spokesperson Kristen Nordlund told KHN.

Failing to do so would “consign thousands upon thousands of infants to hospitalization and serious illness for semantic reasons despite existence of an immunization that functionally performs just like a seasonal vaccine,” Dr. Moore said.

Officials from Sanofi, which is producing the nirsevimab injection along with AstraZeneca, declined to state a price but said the range would be similar to that of a pediatric vaccine course. The CDC pays about $650 for the most expensive routine vaccine, the four shots against pneumococcal infection. In other words, FDA approval would make nirsevimab a blockbuster drug worth billions annually if it’s given to a large share of the 3.7 million or so children born in the U.S. each year.

Pfizer and GlaxoSmithKline are making traditional vaccines against RSV and expect FDA approval later in 2023. Pfizer’s shot initially would be given to pregnant women – to shield their babies from the disease – while GSK’s would be given to the elderly.

Vaccines designed for infants are in the pipeline, but some experts are still nervous about them. A 1966 RSV vaccine trial failed spectacularly, killing two toddlers, and immunologists aren’t totally in agreement over the cause, said Barney Graham, MD, PhD, the retired National Institutes of Health scientist whose studies of the episode contributed to successful COVID-19 and RSV vaccines.

After 2 years of COVID lockdowns and masking slowed its transmission, RSV exploded across the United States in 2023, swamping pediatric intensive care units.

Sanofi and AstraZeneca hope to have nirsevimab approved by the FDA, recommended by the CDC, and deployed nationwide by fall to prevent future RSV epidemics.

Their product is designed to be provided before a baby’s first winter RSV season. In clinical trials, the antibodies provided up to 5 months of protection. Most children wouldn’t need a second dose because the virus is not a mortal danger to healthy kids over a year old, said Jon Heinrichs, a senior member of Sanofi’s vaccines division.

If the antibody treatment is not accepted for the Vaccines for Children program, that will limit access to the shot for the uninsured and those on Medicaid, the majority of whom represent racial or ethnic minorities, Dr. Moore said. The drugmakers would have to negotiate with each state’s Medicaid program to get it on their formularies.

Excluding the shot from Vaccines for Children “would only worsen existing health disparities,” said Sean O’Leary, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora, and chair of the infectious diseases committee of the American Academy of Pediatrics.

RSV affects babies of all social classes but tends to hit poor, crowded households hardest, said Dr. Graham. “Family history of asthma or allergy makes it worse,” he said, and premature babies are also at higher risk.

While 2%-3% of U.S. infants are hospitalized with RSV each year, only a few hundred don’t survive. But as many as 10,000 people 65 and older perish because of an infection every year, and a little-discussed legal change will make RSV and other vaccines more available to this group.

A section of the 2022 Inflation Reduction Act that went into effect Jan. 1 ends out-of-pocket payments for all vaccines by Medicare patients – including RSV vaccines, if they are licensed for this group.

Before, “if you hadn’t met your deductible, it could be very expensive,” said Leonard Friedland, MD, vice president for scientific affairs and public health in GSK’s vaccines division, which also makes shingles and combination tetanus-diphtheria-whooping cough boosters covered by the new law. “It’s a tremendously important advance.”

Of course, high levels of vaccine hesitancy are likely to blunt uptake of the shots regardless of who pays, said Jennifer Reich, a sociologist at the University of Colorado who studies vaccination attitudes.

New types of shots, like the Sanofi-AstraZeneca antibodies, often alarm parents, and Pfizer’s shot for pregnant women is likely to push fear buttons as well, she said.

Public health officials “don’t seem very savvy about how to get ahead” of claims that vaccines undermine fertility or otherwise harm people, said Ms. Reich.

On the other hand, this winter’s RSV epidemic will be persuasive to many parents, said Heidi Larson, leader of the Vaccine Confidence Project and a professor of anthropology at the London School of Hygiene and Tropical Medicine.

“It’s a scary thing to have your kid hospitalized with RSV,” she said.

While unfortunate, “the high number of children who died or were admitted to the ICU in the past season with RSV – in some ways that’s helpful,” said Laura Riley, MD, chair of obstetrics and gynecology at Weill Cornell Medicine, New York.

Specialists in her field haven’t really started talking about how to communicate with women about the vaccine, said Dr. Riley, who chairs the immunization group at the American College of Obstetricians and Gynecologists.

“Everyone’s been waiting to see if it gets approved,” she said. “The education has to start soon, but it’s hard to roll out education before you roll out the shot.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Isotretinoin was not associated with a 1-year risk of incident inflammatory bowel disease (IBD) in a large population-based cohort study that also found no significant association of oral tetracycline-class antibiotics with IBD – and a small but statistically significant association of acne itself with the inflammatory disorders that make up IBD.

For the study, senior author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, and his colleagues used data from the TriNetX global research platform, which mines patient-level electronic medical record data from dozens of health care organizations, mainly in the United States. The network includes over 106 million patients. They looked at four cohorts: Patients without acne; those with acne but no current or prior use of systemic medications; those with acne managed with isotretinoin (and no prior use of oral tetracycline-class antibiotics); and those with acne managed with oral tetracycline-class antibiotics (and no exposure to isotretinoin).

Ocskay Bence/Fotolia.com

For the acne cohorts, the investigators captured first encounters with a diagnosis of acne and first prescriptions of interest. And studywide, they used propensity score matching to balance cohorts for age, sex, race, ethnicity, and combined oral contraceptive use.

“These data should provide more reassurance to patients and prescribers that isotretinoin does not appear to result in a meaningfully increased risk of inflammatory bowel disease,” they wrote in the study, published online in the Journal of the American Academy of Dermatology.

“These are important findings as isotretinoin is a valuable treatment for acne that can result in a durable remission of disease activity, prevent acne scarring, and reduce our overreliance on oral antibiotics for acne,” they added.

Indeed, dermatologist Jonathan S. Weiss, MD, who was not involved in the research and was asked to comment on the study, said that the findings “are reassuring given the large numbers of patients evaluated and treated.” The smallest cohort – the isotretinoin group – had over 11,000 patients, and the other cohorts had over 100,000 patients each, he said in an interview.

“At this point, I’m not sure we need any other immediate information to feel comfortable using isotretinoin with respect to a potential to cause IBD, but it would be nice to see some longitudinal follow-up data for longer-term reassurance,” added Dr. Weiss, who practices in Snellville, Georgia, and is on the board of the directors of the American Acne and Rosacea Society.

 

The findings: Risk with acne

To assess the potential association between acne and IBD, the researchers identified more than 350,000 patients with acne managed without systemic medications, and propensity score matched them with patients who did not have acne. Altogether, their mean age was 22; 32.1% were male, and 59.6% were White.

Compared with the controls who did not have acne, they found a statistically significant association between acne and risk of incident IBD (odds ratio, 1.42; 95% confidence interval, 1.23-1.65) and an absolute risk difference of .04%. Separated into Crohn’s disease (CD) and ulcerative colitis (UC), ORs were 1.56 and 1.62, respectively.
 

Tetracyclines

To assess the association of oral tetracycline use and IBD, they compared more than 144,000 patients whose acne was managed with antibiotics with patients whose acne was managed without systemic medications. The patients had a mean age of 24.4; 34.7% were male, and 68.2% were White.

Compared with the patients who were not on systemic medications, there were no significant associations among those on oral tetracyclines, with an OR for incident IBD of 1 (95% CI, 0.82-1.22), an OR for incident CD of 1.09 (95% CI, 0.86-1.38), and an OR for UC of 0.78 (95% CI, 0.61-1.00).
 

Isotretinoin

To evaluate the association of isotretinoin and IBD, the researchers compared more than 11,000 patients treated with isotretinoin with two matched groups: patients with acne managed without systemic medications, and patients with acne managed with oral tetracyclines. The latter comparison was made to minimize potential confounding by acne severity. These patients had a mean age of 21.1; 49.5% were male, and 75.3% were White.

In the first comparison, compared with patients not treated with systemic medications, the OR for 1-year incidence of IBD among patients treated with isotretinoin was 1.29 (95% CI, 0.64-2.59), with an absolute risk difference of .036%. The ORs for CD and UC were 1.00 (95% CI, 0.45-2.23) and 1.27 (95% CI, .58-2.80), respectively.

And compared with the antibiotic-managed group, the OR for incident IBD among those on isotretinoin was 1.13 (95% CI, 0.57-2.21), with an absolute risk difference of .018%. The OR for CD was 1.00 (95% CI, 0.45-2.23). The OR for UC could not be accurately estimated because of an insufficient number of events in the tetracycline-treated group.
 

‘Challenging’ area of research

Researching acne treatments and the potential risk of IBD has been a methodologically “challenging topic to study” because of possible confounding and surveillance bias depending on study designs, Dr. Barbieri, director of the Brigham and Women’s Advanced Acne Therapeutics Clinic, said in an interview.

Studies that have identified a potential association between isotretinoin and IBD often have not adequately controlled for prior antibiotic exposure, for instance. And other studies, including a retrospective cohort study also published recently in JAAD using the same TriNetX database, have found 6-month isotretinoin-related risks of IBD but no increased risk at 1 year or more of follow-up – a finding that suggests a role of surveillance bias, Dr. Barbieri said.

The follow-up period of 1 year in their new study was chosen to minimize the risk of such bias. “Since patients on isotretinoin are seen more often, and since there are historical concerns about isotretinoin and IBD, patients on isotretinoin may be more likely to be screened earlier and thus could be diagnosed sooner than those not on [the medication],” he said.

He and his coauthors considered similar potential bias in designing the no-acne cohort, choosing patients who had routine primary care visits without abnormal findings in order to “reduce potential for bias due to frequency of interaction with the health care system,” they noted in their paper. (Patients had no prior encounters for acne and no history of acne treatments.)
 

Antibiotics, acne itself

Research on antibiotic use for acne and risk of IBD is scant, and the few studies that have been published show conflicting findings, Dr. Barbieri noted. In the meantime, studies and meta-analyses in the general medical literature – not involving acne – have identified an association between lifetime oral antibiotic exposure and IBD, he said.

While the results of the new study “are reassuring that oral tetracycline-class exposure for acne may not be associated with a significant absolute risk of inflammatory bowel disease, given the potential for antibiotic resistance and other antibiotic-associated complications, it remains important to be judicious” with their use in acne management, he and his coauthors wrote in the study.

The potential association between antibiotics for acne and IBD needs further study, preferably with longer follow-up duration, Dr. Barbieri said in the interview, but researchers are challenged by the lack of datasets with high-quality longitudinal data “beyond a few years of follow-up.”

The extent to which acne itself is associated with IBD is another area ripe for more research. Thus far, it seems that IBD and acne – and other chronic inflammatory skin diseases such as psoriasis – involve similar pathogenic pathways. “We know that in IBD Th17 and TNF immunologic pathways are important, so it’s not surprising that there may be associations,” he said.

In their paper, Dr. Barbieri and his coauthors emphasize, however, that the absolute risk difference between acne and IBD is small. It’s “unlikely that population level screening is warranted among patients with acne,” they wrote.

A second new study

The other study, also published recently in JAAD, used the same TriNetX research platform to identify approximately 77,000 patients with acne starting isotretinoin and matched them with patients starting oral antibiotics.

The investigators, Khalaf Kridin MD, PhD, and Ralf J. Ludwig, MD, of the Lübeck Institute of Experimental Dermatology, University of Lübeck (Germany), found that the lifetime risks (greater than 6 months) for patients on isotretinoin were not significantly elevated, compared with those on oral antibiotics for either CD (hazard ratio 1.05; 95% CI, 0.89-1.24, P = .583) or UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) They also looked at the risk of irritable bowel syndrome (IBS) and found a lower lifetime risk in the isotretinoin group.

In the short term, during the first 6 months after drug initiation, there was a significant, but slight increase in UC in the isotretinoin group. But this risk decreased to the level of the antibiotic group with longer follow up. “The absolute incidence rates [of IBD] and the risk difference of UC within the first 6 months are of limited clinical significance,” they wrote.

It may be, Dr. Weiss said in commenting on this study, “that isotretinoin unmasks an already-existing genetic tendency to UC early on in the course of treatment, but that it does not truly cause an increased incidence of any type of IBD.”

Both studies, said Dr. Barbieri, “add to an extensive body of literature that supports that isotretinoin is not associated with IBD.”

Dr. Barbieri had no disclosures for the study, for which Matthew T. Taylor served as first author. Coauthor Shawn Kwatra, MD, disclosed that he is an advisory board member/consultant for numerous pharmaceutical companies and has served as an investigator for several. Both are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The other authors had no disclosures. Dr. Kridin and Dr. Ludwig had no disclosures for their study. Dr. Weiss had no disclosures.

Isotretinoin was not associated with a 1-year risk of incident inflammatory bowel disease (IBD) in a large population-based cohort study that also found no significant association of oral tetracycline-class antibiotics with IBD – and a small but statistically significant association of acne itself with the inflammatory disorders that make up IBD.

For the study, senior author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, and his colleagues used data from the TriNetX global research platform, which mines patient-level electronic medical record data from dozens of health care organizations, mainly in the United States. The network includes over 106 million patients. They looked at four cohorts: Patients without acne; those with acne but no current or prior use of systemic medications; those with acne managed with isotretinoin (and no prior use of oral tetracycline-class antibiotics); and those with acne managed with oral tetracycline-class antibiotics (and no exposure to isotretinoin).

Ocskay Bence/Fotolia.com

For the acne cohorts, the investigators captured first encounters with a diagnosis of acne and first prescriptions of interest. And studywide, they used propensity score matching to balance cohorts for age, sex, race, ethnicity, and combined oral contraceptive use.

“These data should provide more reassurance to patients and prescribers that isotretinoin does not appear to result in a meaningfully increased risk of inflammatory bowel disease,” they wrote in the study, published online in the Journal of the American Academy of Dermatology.

“These are important findings as isotretinoin is a valuable treatment for acne that can result in a durable remission of disease activity, prevent acne scarring, and reduce our overreliance on oral antibiotics for acne,” they added.

Indeed, dermatologist Jonathan S. Weiss, MD, who was not involved in the research and was asked to comment on the study, said that the findings “are reassuring given the large numbers of patients evaluated and treated.” The smallest cohort – the isotretinoin group – had over 11,000 patients, and the other cohorts had over 100,000 patients each, he said in an interview.

“At this point, I’m not sure we need any other immediate information to feel comfortable using isotretinoin with respect to a potential to cause IBD, but it would be nice to see some longitudinal follow-up data for longer-term reassurance,” added Dr. Weiss, who practices in Snellville, Georgia, and is on the board of the directors of the American Acne and Rosacea Society.

 

The findings: Risk with acne

To assess the potential association between acne and IBD, the researchers identified more than 350,000 patients with acne managed without systemic medications, and propensity score matched them with patients who did not have acne. Altogether, their mean age was 22; 32.1% were male, and 59.6% were White.

Compared with the controls who did not have acne, they found a statistically significant association between acne and risk of incident IBD (odds ratio, 1.42; 95% confidence interval, 1.23-1.65) and an absolute risk difference of .04%. Separated into Crohn’s disease (CD) and ulcerative colitis (UC), ORs were 1.56 and 1.62, respectively.
 

Tetracyclines

To assess the association of oral tetracycline use and IBD, they compared more than 144,000 patients whose acne was managed with antibiotics with patients whose acne was managed without systemic medications. The patients had a mean age of 24.4; 34.7% were male, and 68.2% were White.

Compared with the patients who were not on systemic medications, there were no significant associations among those on oral tetracyclines, with an OR for incident IBD of 1 (95% CI, 0.82-1.22), an OR for incident CD of 1.09 (95% CI, 0.86-1.38), and an OR for UC of 0.78 (95% CI, 0.61-1.00).
 

Isotretinoin

To evaluate the association of isotretinoin and IBD, the researchers compared more than 11,000 patients treated with isotretinoin with two matched groups: patients with acne managed without systemic medications, and patients with acne managed with oral tetracyclines. The latter comparison was made to minimize potential confounding by acne severity. These patients had a mean age of 21.1; 49.5% were male, and 75.3% were White.

In the first comparison, compared with patients not treated with systemic medications, the OR for 1-year incidence of IBD among patients treated with isotretinoin was 1.29 (95% CI, 0.64-2.59), with an absolute risk difference of .036%. The ORs for CD and UC were 1.00 (95% CI, 0.45-2.23) and 1.27 (95% CI, .58-2.80), respectively.

And compared with the antibiotic-managed group, the OR for incident IBD among those on isotretinoin was 1.13 (95% CI, 0.57-2.21), with an absolute risk difference of .018%. The OR for CD was 1.00 (95% CI, 0.45-2.23). The OR for UC could not be accurately estimated because of an insufficient number of events in the tetracycline-treated group.
 

‘Challenging’ area of research

Researching acne treatments and the potential risk of IBD has been a methodologically “challenging topic to study” because of possible confounding and surveillance bias depending on study designs, Dr. Barbieri, director of the Brigham and Women’s Advanced Acne Therapeutics Clinic, said in an interview.

Studies that have identified a potential association between isotretinoin and IBD often have not adequately controlled for prior antibiotic exposure, for instance. And other studies, including a retrospective cohort study also published recently in JAAD using the same TriNetX database, have found 6-month isotretinoin-related risks of IBD but no increased risk at 1 year or more of follow-up – a finding that suggests a role of surveillance bias, Dr. Barbieri said.

The follow-up period of 1 year in their new study was chosen to minimize the risk of such bias. “Since patients on isotretinoin are seen more often, and since there are historical concerns about isotretinoin and IBD, patients on isotretinoin may be more likely to be screened earlier and thus could be diagnosed sooner than those not on [the medication],” he said.

He and his coauthors considered similar potential bias in designing the no-acne cohort, choosing patients who had routine primary care visits without abnormal findings in order to “reduce potential for bias due to frequency of interaction with the health care system,” they noted in their paper. (Patients had no prior encounters for acne and no history of acne treatments.)
 

Antibiotics, acne itself

Research on antibiotic use for acne and risk of IBD is scant, and the few studies that have been published show conflicting findings, Dr. Barbieri noted. In the meantime, studies and meta-analyses in the general medical literature – not involving acne – have identified an association between lifetime oral antibiotic exposure and IBD, he said.

While the results of the new study “are reassuring that oral tetracycline-class exposure for acne may not be associated with a significant absolute risk of inflammatory bowel disease, given the potential for antibiotic resistance and other antibiotic-associated complications, it remains important to be judicious” with their use in acne management, he and his coauthors wrote in the study.

The potential association between antibiotics for acne and IBD needs further study, preferably with longer follow-up duration, Dr. Barbieri said in the interview, but researchers are challenged by the lack of datasets with high-quality longitudinal data “beyond a few years of follow-up.”

The extent to which acne itself is associated with IBD is another area ripe for more research. Thus far, it seems that IBD and acne – and other chronic inflammatory skin diseases such as psoriasis – involve similar pathogenic pathways. “We know that in IBD Th17 and TNF immunologic pathways are important, so it’s not surprising that there may be associations,” he said.

In their paper, Dr. Barbieri and his coauthors emphasize, however, that the absolute risk difference between acne and IBD is small. It’s “unlikely that population level screening is warranted among patients with acne,” they wrote.

A second new study

The other study, also published recently in JAAD, used the same TriNetX research platform to identify approximately 77,000 patients with acne starting isotretinoin and matched them with patients starting oral antibiotics.

The investigators, Khalaf Kridin MD, PhD, and Ralf J. Ludwig, MD, of the Lübeck Institute of Experimental Dermatology, University of Lübeck (Germany), found that the lifetime risks (greater than 6 months) for patients on isotretinoin were not significantly elevated, compared with those on oral antibiotics for either CD (hazard ratio 1.05; 95% CI, 0.89-1.24, P = .583) or UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) They also looked at the risk of irritable bowel syndrome (IBS) and found a lower lifetime risk in the isotretinoin group.

In the short term, during the first 6 months after drug initiation, there was a significant, but slight increase in UC in the isotretinoin group. But this risk decreased to the level of the antibiotic group with longer follow up. “The absolute incidence rates [of IBD] and the risk difference of UC within the first 6 months are of limited clinical significance,” they wrote.

It may be, Dr. Weiss said in commenting on this study, “that isotretinoin unmasks an already-existing genetic tendency to UC early on in the course of treatment, but that it does not truly cause an increased incidence of any type of IBD.”

Both studies, said Dr. Barbieri, “add to an extensive body of literature that supports that isotretinoin is not associated with IBD.”

Dr. Barbieri had no disclosures for the study, for which Matthew T. Taylor served as first author. Coauthor Shawn Kwatra, MD, disclosed that he is an advisory board member/consultant for numerous pharmaceutical companies and has served as an investigator for several. Both are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The other authors had no disclosures. Dr. Kridin and Dr. Ludwig had no disclosures for their study. Dr. Weiss had no disclosures.

Isotretinoin was not associated with a 1-year risk of incident inflammatory bowel disease (IBD) in a large population-based cohort study that also found no significant association of oral tetracycline-class antibiotics with IBD – and a small but statistically significant association of acne itself with the inflammatory disorders that make up IBD.

For the study, senior author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, and his colleagues used data from the TriNetX global research platform, which mines patient-level electronic medical record data from dozens of health care organizations, mainly in the United States. The network includes over 106 million patients. They looked at four cohorts: Patients without acne; those with acne but no current or prior use of systemic medications; those with acne managed with isotretinoin (and no prior use of oral tetracycline-class antibiotics); and those with acne managed with oral tetracycline-class antibiotics (and no exposure to isotretinoin).

Ocskay Bence/Fotolia.com

For the acne cohorts, the investigators captured first encounters with a diagnosis of acne and first prescriptions of interest. And studywide, they used propensity score matching to balance cohorts for age, sex, race, ethnicity, and combined oral contraceptive use.

“These data should provide more reassurance to patients and prescribers that isotretinoin does not appear to result in a meaningfully increased risk of inflammatory bowel disease,” they wrote in the study, published online in the Journal of the American Academy of Dermatology.

“These are important findings as isotretinoin is a valuable treatment for acne that can result in a durable remission of disease activity, prevent acne scarring, and reduce our overreliance on oral antibiotics for acne,” they added.

Indeed, dermatologist Jonathan S. Weiss, MD, who was not involved in the research and was asked to comment on the study, said that the findings “are reassuring given the large numbers of patients evaluated and treated.” The smallest cohort – the isotretinoin group – had over 11,000 patients, and the other cohorts had over 100,000 patients each, he said in an interview.

“At this point, I’m not sure we need any other immediate information to feel comfortable using isotretinoin with respect to a potential to cause IBD, but it would be nice to see some longitudinal follow-up data for longer-term reassurance,” added Dr. Weiss, who practices in Snellville, Georgia, and is on the board of the directors of the American Acne and Rosacea Society.

 

The findings: Risk with acne

To assess the potential association between acne and IBD, the researchers identified more than 350,000 patients with acne managed without systemic medications, and propensity score matched them with patients who did not have acne. Altogether, their mean age was 22; 32.1% were male, and 59.6% were White.

Compared with the controls who did not have acne, they found a statistically significant association between acne and risk of incident IBD (odds ratio, 1.42; 95% confidence interval, 1.23-1.65) and an absolute risk difference of .04%. Separated into Crohn’s disease (CD) and ulcerative colitis (UC), ORs were 1.56 and 1.62, respectively.
 

Tetracyclines

To assess the association of oral tetracycline use and IBD, they compared more than 144,000 patients whose acne was managed with antibiotics with patients whose acne was managed without systemic medications. The patients had a mean age of 24.4; 34.7% were male, and 68.2% were White.

Compared with the patients who were not on systemic medications, there were no significant associations among those on oral tetracyclines, with an OR for incident IBD of 1 (95% CI, 0.82-1.22), an OR for incident CD of 1.09 (95% CI, 0.86-1.38), and an OR for UC of 0.78 (95% CI, 0.61-1.00).
 

Isotretinoin

To evaluate the association of isotretinoin and IBD, the researchers compared more than 11,000 patients treated with isotretinoin with two matched groups: patients with acne managed without systemic medications, and patients with acne managed with oral tetracyclines. The latter comparison was made to minimize potential confounding by acne severity. These patients had a mean age of 21.1; 49.5% were male, and 75.3% were White.

In the first comparison, compared with patients not treated with systemic medications, the OR for 1-year incidence of IBD among patients treated with isotretinoin was 1.29 (95% CI, 0.64-2.59), with an absolute risk difference of .036%. The ORs for CD and UC were 1.00 (95% CI, 0.45-2.23) and 1.27 (95% CI, .58-2.80), respectively.

And compared with the antibiotic-managed group, the OR for incident IBD among those on isotretinoin was 1.13 (95% CI, 0.57-2.21), with an absolute risk difference of .018%. The OR for CD was 1.00 (95% CI, 0.45-2.23). The OR for UC could not be accurately estimated because of an insufficient number of events in the tetracycline-treated group.
 

‘Challenging’ area of research

Researching acne treatments and the potential risk of IBD has been a methodologically “challenging topic to study” because of possible confounding and surveillance bias depending on study designs, Dr. Barbieri, director of the Brigham and Women’s Advanced Acne Therapeutics Clinic, said in an interview.

Studies that have identified a potential association between isotretinoin and IBD often have not adequately controlled for prior antibiotic exposure, for instance. And other studies, including a retrospective cohort study also published recently in JAAD using the same TriNetX database, have found 6-month isotretinoin-related risks of IBD but no increased risk at 1 year or more of follow-up – a finding that suggests a role of surveillance bias, Dr. Barbieri said.

The follow-up period of 1 year in their new study was chosen to minimize the risk of such bias. “Since patients on isotretinoin are seen more often, and since there are historical concerns about isotretinoin and IBD, patients on isotretinoin may be more likely to be screened earlier and thus could be diagnosed sooner than those not on [the medication],” he said.

He and his coauthors considered similar potential bias in designing the no-acne cohort, choosing patients who had routine primary care visits without abnormal findings in order to “reduce potential for bias due to frequency of interaction with the health care system,” they noted in their paper. (Patients had no prior encounters for acne and no history of acne treatments.)
 

Antibiotics, acne itself

Research on antibiotic use for acne and risk of IBD is scant, and the few studies that have been published show conflicting findings, Dr. Barbieri noted. In the meantime, studies and meta-analyses in the general medical literature – not involving acne – have identified an association between lifetime oral antibiotic exposure and IBD, he said.

While the results of the new study “are reassuring that oral tetracycline-class exposure for acne may not be associated with a significant absolute risk of inflammatory bowel disease, given the potential for antibiotic resistance and other antibiotic-associated complications, it remains important to be judicious” with their use in acne management, he and his coauthors wrote in the study.

The potential association between antibiotics for acne and IBD needs further study, preferably with longer follow-up duration, Dr. Barbieri said in the interview, but researchers are challenged by the lack of datasets with high-quality longitudinal data “beyond a few years of follow-up.”

The extent to which acne itself is associated with IBD is another area ripe for more research. Thus far, it seems that IBD and acne – and other chronic inflammatory skin diseases such as psoriasis – involve similar pathogenic pathways. “We know that in IBD Th17 and TNF immunologic pathways are important, so it’s not surprising that there may be associations,” he said.

In their paper, Dr. Barbieri and his coauthors emphasize, however, that the absolute risk difference between acne and IBD is small. It’s “unlikely that population level screening is warranted among patients with acne,” they wrote.

A second new study

The other study, also published recently in JAAD, used the same TriNetX research platform to identify approximately 77,000 patients with acne starting isotretinoin and matched them with patients starting oral antibiotics.

The investigators, Khalaf Kridin MD, PhD, and Ralf J. Ludwig, MD, of the Lübeck Institute of Experimental Dermatology, University of Lübeck (Germany), found that the lifetime risks (greater than 6 months) for patients on isotretinoin were not significantly elevated, compared with those on oral antibiotics for either CD (hazard ratio 1.05; 95% CI, 0.89-1.24, P = .583) or UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) They also looked at the risk of irritable bowel syndrome (IBS) and found a lower lifetime risk in the isotretinoin group.

In the short term, during the first 6 months after drug initiation, there was a significant, but slight increase in UC in the isotretinoin group. But this risk decreased to the level of the antibiotic group with longer follow up. “The absolute incidence rates [of IBD] and the risk difference of UC within the first 6 months are of limited clinical significance,” they wrote.

It may be, Dr. Weiss said in commenting on this study, “that isotretinoin unmasks an already-existing genetic tendency to UC early on in the course of treatment, but that it does not truly cause an increased incidence of any type of IBD.”

Both studies, said Dr. Barbieri, “add to an extensive body of literature that supports that isotretinoin is not associated with IBD.”

Dr. Barbieri had no disclosures for the study, for which Matthew T. Taylor served as first author. Coauthor Shawn Kwatra, MD, disclosed that he is an advisory board member/consultant for numerous pharmaceutical companies and has served as an investigator for several. Both are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The other authors had no disclosures. Dr. Kridin and Dr. Ludwig had no disclosures for their study. Dr. Weiss had no disclosures.

Pharmacies are running out of the antibiotics used to treat serious infections in children. This leaves parents and doctors frustrated and scared.

After weeks of overcrowded waiting rooms, extended office hours, and countless telephone calls during the viral respiratory surge, pediatricians are now facing a new challenge: an ever-growing list of medication shortages, including many of the most commonly used antibiotics.

These shortages primarily affect liquid formulations, so children – and the pediatricians’ offices and pharmacies serving them – are disproportionately impacted. Though there are multiple factors contributing, antibiotic overuse for viral infections during the surge has undoubtedly catalyzed the current crisis. It can be scary for parents to watch a child miserable with fever, which is why parents and pediatricians look for a quick fix in antibiotics, but unnecessary prescriptions that contribute to ongoing shortages should be avoided. We, as practicing pediatricians, think that this is a moment for reflection on when and why we use antibiotics during viral season. Though antibiotic overuse may have led us into this shortage, better antibiotic stewardship may just lead us out of it.

Since amoxicillin was approved for medical use in 1974, it has been one of the most commonly prescribed antibiotics in children. It is particularly well-suited for use in children because it treats common pediatric infections such as ear infections, strep throat, and pneumonia. These factors, along with its low cost and bubblegum flavor, make it no surprise that amoxicillin was consistently one of the top 25 medications prescribed in the United States between 2013 and 2019, with over 25 million prescriptions annually.

Amoxicillin remains the best first-line treatment option for the most common bacterial respiratory tract infections in children. With liquid formulations scarce, pediatricians, parents, and pharmacists are getting creative with crushed tablets or sprinkling capsules when possible.

However, without liquid amoxicillin readily available in our pediatric arsenal, we have recently had to turn to antibiotics with higher costs and more side effects. These broad-spectrum antibiotics target a more extensive range of bacteria and are rarely necessary for common pediatric infections. Further, their use risks increasing the already dire problem of antibiotic resistance, which causes more than 35,000 deaths in the United States each year. And perhaps most importantly, broader spectrum antibiotics aren’t better than amoxicillin for the treatment of respiratory tract infections; they are sometimes worse.

The urge to turn to antibiotics as a potential cure for childhood illnesses is an understandable one for parents and clinicians alike. A common refrain in pediatrician offices is, “Isn’t there anything we can give them?” as parents look for respite in a long viral season. As viruses continue to surge, it is helpful to remember that children will get 8 to 10 viral infections per year, with most of those occurring in the fall and winter. When parents report that their child is always sick, they aren’t far off.

Most of these infections will be cured by a child’s own immune system rather than our medications. For example, in children older than 2 years, studies have demonstrated that waiting about 2 days to start antibiotics after an ear infection is diagnosed is just as effective as starting the antibiotics right away. As tempting as it is to ask for antibiotics early, that prescription may only worsen the situation if it is a virus. Instead, pediatricians can offer parents support in treating their children at home with humidifiers, pain/fever relievers when appropriate, honey in children over 12 months, and hydration.

This drug shortage is a pivotal moment for parents and clinicians to reconsider how and when we use antibiotics during viral season. Though antibiotics may be one of the greatest inventions of the 20th century, it is how we use them now that will determine our health in the century to come.

Dr. Lockwood is Associate Professor, department of pediatrics, University of Pennsylvania, Philadelphia. Dr. Same is Assistant Professor, department of clinical pediatrics, at the University of Pennsylvania. Neither reported any conflicts of interest.

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

Pharmacies are running out of the antibiotics used to treat serious infections in children. This leaves parents and doctors frustrated and scared.

After weeks of overcrowded waiting rooms, extended office hours, and countless telephone calls during the viral respiratory surge, pediatricians are now facing a new challenge: an ever-growing list of medication shortages, including many of the most commonly used antibiotics.

These shortages primarily affect liquid formulations, so children – and the pediatricians’ offices and pharmacies serving them – are disproportionately impacted. Though there are multiple factors contributing, antibiotic overuse for viral infections during the surge has undoubtedly catalyzed the current crisis. It can be scary for parents to watch a child miserable with fever, which is why parents and pediatricians look for a quick fix in antibiotics, but unnecessary prescriptions that contribute to ongoing shortages should be avoided. We, as practicing pediatricians, think that this is a moment for reflection on when and why we use antibiotics during viral season. Though antibiotic overuse may have led us into this shortage, better antibiotic stewardship may just lead us out of it.

Since amoxicillin was approved for medical use in 1974, it has been one of the most commonly prescribed antibiotics in children. It is particularly well-suited for use in children because it treats common pediatric infections such as ear infections, strep throat, and pneumonia. These factors, along with its low cost and bubblegum flavor, make it no surprise that amoxicillin was consistently one of the top 25 medications prescribed in the United States between 2013 and 2019, with over 25 million prescriptions annually.

Amoxicillin remains the best first-line treatment option for the most common bacterial respiratory tract infections in children. With liquid formulations scarce, pediatricians, parents, and pharmacists are getting creative with crushed tablets or sprinkling capsules when possible.

However, without liquid amoxicillin readily available in our pediatric arsenal, we have recently had to turn to antibiotics with higher costs and more side effects. These broad-spectrum antibiotics target a more extensive range of bacteria and are rarely necessary for common pediatric infections. Further, their use risks increasing the already dire problem of antibiotic resistance, which causes more than 35,000 deaths in the United States each year. And perhaps most importantly, broader spectrum antibiotics aren’t better than amoxicillin for the treatment of respiratory tract infections; they are sometimes worse.

The urge to turn to antibiotics as a potential cure for childhood illnesses is an understandable one for parents and clinicians alike. A common refrain in pediatrician offices is, “Isn’t there anything we can give them?” as parents look for respite in a long viral season. As viruses continue to surge, it is helpful to remember that children will get 8 to 10 viral infections per year, with most of those occurring in the fall and winter. When parents report that their child is always sick, they aren’t far off.

Most of these infections will be cured by a child’s own immune system rather than our medications. For example, in children older than 2 years, studies have demonstrated that waiting about 2 days to start antibiotics after an ear infection is diagnosed is just as effective as starting the antibiotics right away. As tempting as it is to ask for antibiotics early, that prescription may only worsen the situation if it is a virus. Instead, pediatricians can offer parents support in treating their children at home with humidifiers, pain/fever relievers when appropriate, honey in children over 12 months, and hydration.

This drug shortage is a pivotal moment for parents and clinicians to reconsider how and when we use antibiotics during viral season. Though antibiotics may be one of the greatest inventions of the 20th century, it is how we use them now that will determine our health in the century to come.

Dr. Lockwood is Associate Professor, department of pediatrics, University of Pennsylvania, Philadelphia. Dr. Same is Assistant Professor, department of clinical pediatrics, at the University of Pennsylvania. Neither reported any conflicts of interest.

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

Pharmacies are running out of the antibiotics used to treat serious infections in children. This leaves parents and doctors frustrated and scared.

After weeks of overcrowded waiting rooms, extended office hours, and countless telephone calls during the viral respiratory surge, pediatricians are now facing a new challenge: an ever-growing list of medication shortages, including many of the most commonly used antibiotics.

These shortages primarily affect liquid formulations, so children – and the pediatricians’ offices and pharmacies serving them – are disproportionately impacted. Though there are multiple factors contributing, antibiotic overuse for viral infections during the surge has undoubtedly catalyzed the current crisis. It can be scary for parents to watch a child miserable with fever, which is why parents and pediatricians look for a quick fix in antibiotics, but unnecessary prescriptions that contribute to ongoing shortages should be avoided. We, as practicing pediatricians, think that this is a moment for reflection on when and why we use antibiotics during viral season. Though antibiotic overuse may have led us into this shortage, better antibiotic stewardship may just lead us out of it.

Since amoxicillin was approved for medical use in 1974, it has been one of the most commonly prescribed antibiotics in children. It is particularly well-suited for use in children because it treats common pediatric infections such as ear infections, strep throat, and pneumonia. These factors, along with its low cost and bubblegum flavor, make it no surprise that amoxicillin was consistently one of the top 25 medications prescribed in the United States between 2013 and 2019, with over 25 million prescriptions annually.

Amoxicillin remains the best first-line treatment option for the most common bacterial respiratory tract infections in children. With liquid formulations scarce, pediatricians, parents, and pharmacists are getting creative with crushed tablets or sprinkling capsules when possible.

However, without liquid amoxicillin readily available in our pediatric arsenal, we have recently had to turn to antibiotics with higher costs and more side effects. These broad-spectrum antibiotics target a more extensive range of bacteria and are rarely necessary for common pediatric infections. Further, their use risks increasing the already dire problem of antibiotic resistance, which causes more than 35,000 deaths in the United States each year. And perhaps most importantly, broader spectrum antibiotics aren’t better than amoxicillin for the treatment of respiratory tract infections; they are sometimes worse.

The urge to turn to antibiotics as a potential cure for childhood illnesses is an understandable one for parents and clinicians alike. A common refrain in pediatrician offices is, “Isn’t there anything we can give them?” as parents look for respite in a long viral season. As viruses continue to surge, it is helpful to remember that children will get 8 to 10 viral infections per year, with most of those occurring in the fall and winter. When parents report that their child is always sick, they aren’t far off.

Most of these infections will be cured by a child’s own immune system rather than our medications. For example, in children older than 2 years, studies have demonstrated that waiting about 2 days to start antibiotics after an ear infection is diagnosed is just as effective as starting the antibiotics right away. As tempting as it is to ask for antibiotics early, that prescription may only worsen the situation if it is a virus. Instead, pediatricians can offer parents support in treating their children at home with humidifiers, pain/fever relievers when appropriate, honey in children over 12 months, and hydration.

This drug shortage is a pivotal moment for parents and clinicians to reconsider how and when we use antibiotics during viral season. Though antibiotics may be one of the greatest inventions of the 20th century, it is how we use them now that will determine our health in the century to come.

Dr. Lockwood is Associate Professor, department of pediatrics, University of Pennsylvania, Philadelphia. Dr. Same is Assistant Professor, department of clinical pediatrics, at the University of Pennsylvania. Neither reported any conflicts of interest.

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

Two-thirds of children who underwent genetic testing in the pediatric intensive care unit showed a genetic variant, and a third of these children received changes in care as a result, according to a new study presented at the Society of Critical Care Medicine’s 2023 Critical Care Congress.

“We have had a lot of success using genome sequencing to help not only with diagnosis, but also changes in management,” lead author Katherine Rodriguez, MD, a pediatric critical care fellow physician at Rady Children’s Hospital, San Diego, told this news organization.

However, data on the use of rapid whole genome sequencing (rWGS) in the pediatric intensive care unit (PICU) are limited, and data from multiple institutions are lacking, Dr. Rodriguez said. In the current study, data from multiple hospitals allowed the researchers to examine differences in management across institutions, she said.

Dr. Rodriguez, with principal investigator Nicole Coufal, MD, also of Rady Children’s, and colleagues conducted the study at three children’s hospitals from March 2019 to July 2022. The study population included 80 children whose origin of illness was uncertain. The patients underwent rWGS testing in the PICU or cardiac ICU setting. The patients ranged in age from 0 to 17 years; 64% were younger than 1 year, (mean age, 2.8 years); 56% were male, and 59% were White.  

After rWGS testing, 65% of the children were positive for a genetic variant. The data prompted changes to care for 42% of these patients; 38% of the changes occurred during the patient’s PICU stay, including medication changes and procedures that were either avoided or completed.

The remaining 62% of the changes were subacute and affected management for the remainder of the child’s hospitalization and after discharge, Dr. Rodriguez explained in her presentation.

The average turnaround time for the testing was 10 days, which is important to an intensivist, who may have been hesitant to order tests because of the time involved, Dr. Rodriguez said. The current study shows that “we can get test results in a reasonable time to make meaningful changes in care,” she told this news organization.

Choosing which patients to test can be a challenge for clinicians, Dr. Rodriguez acknowledged. “We have gotten a sense of which patients are likely to have diagnostic or not diagnostic genomes, but it is also a gut feeling,” she said.

“If this child is your patient and you are concerned, if they seem sicker than expected, or have a concerning family history, then send the test,” she said. “It is becoming more affordable, and can come back quickly enough to guide treatment while the patient is still in the ICU.”

In the current study, the greatest diagnostic utility appeared in patients with cardiac symptoms, such as congenital heart disease, sudden cardiac arrest, or suspected channelopathy, Dr. Rodriguez said in her presentation.

Patients with suspected neurological disease had a 50% rate of molecular diagnosis. “Interestingly, 74% of patients with respiratory disease where an underlying genetic etiology was suspected received a molecular diagnosis,” although rWGS was not applied to general populations with RSV or other respiratory illnesses, she said.

In her presentation, Dr. Rodriguez shared examples of how genetic testing had a dramatic impact on patient survival. In one case, a 14-year-old girl presented in cardiac arrest and was found to have new-onset dilated cardiomyopathy. Whether the etiology was acquired or infectious and possibly reversible or genetic was unclear, she said.

“A diagnostic genome result within 48 hours indicated a genetic etiology,” she said. The patient was listed for heart transplant despite the incomplete infectious workup, and received a successful heart transplant 1 week after admission, Dr. Rodriguez said.

Guidelines for which PICU patients should undergo genetic testing do not yet exist, Dr. Rodriguez told this news organization. “We are trying to find some more meaningful parameters where we can say that a patient has a high pretest possibility of a genetic condition,” she said.

“Increasing availability of rWGS can significantly impact patient care and assist families in making difficult decisions during times of critical illness,” she said.

Insurance coverage and testing access are improving, said Dr. Rodriguez. Medicaid policies exist for neonates/infants in the ICU in several states, including Oregon, California, Michigan, Maryland, and Louisiana, she said. In some areas, hospitals may pay for testing for these children if insurance will not, she added.

Dr. Rodriguez and colleagues are continuing to enroll patients in a prospective study of the impact of rWGS, with the addition of a fourth study site and inclusion of family surveys. “We also will be looking at a secondary analysis of cost savings and benefits,” she said.

Ultimately, the current study should be empowering to physicians, “especially if they don’t have good access to geneticists,” Dr. Rodriguez said in an interview.

The study received no outside funding. Dr. Rodriguez reports no relevant financial relationships. 

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

Two-thirds of children who underwent genetic testing in the pediatric intensive care unit showed a genetic variant, and a third of these children received changes in care as a result, according to a new study presented at the Society of Critical Care Medicine’s 2023 Critical Care Congress.

“We have had a lot of success using genome sequencing to help not only with diagnosis, but also changes in management,” lead author Katherine Rodriguez, MD, a pediatric critical care fellow physician at Rady Children’s Hospital, San Diego, told this news organization.

However, data on the use of rapid whole genome sequencing (rWGS) in the pediatric intensive care unit (PICU) are limited, and data from multiple institutions are lacking, Dr. Rodriguez said. In the current study, data from multiple hospitals allowed the researchers to examine differences in management across institutions, she said.

Dr. Rodriguez, with principal investigator Nicole Coufal, MD, also of Rady Children’s, and colleagues conducted the study at three children’s hospitals from March 2019 to July 2022. The study population included 80 children whose origin of illness was uncertain. The patients underwent rWGS testing in the PICU or cardiac ICU setting. The patients ranged in age from 0 to 17 years; 64% were younger than 1 year, (mean age, 2.8 years); 56% were male, and 59% were White.  

After rWGS testing, 65% of the children were positive for a genetic variant. The data prompted changes to care for 42% of these patients; 38% of the changes occurred during the patient’s PICU stay, including medication changes and procedures that were either avoided or completed.

The remaining 62% of the changes were subacute and affected management for the remainder of the child’s hospitalization and after discharge, Dr. Rodriguez explained in her presentation.

The average turnaround time for the testing was 10 days, which is important to an intensivist, who may have been hesitant to order tests because of the time involved, Dr. Rodriguez said. The current study shows that “we can get test results in a reasonable time to make meaningful changes in care,” she told this news organization.

Choosing which patients to test can be a challenge for clinicians, Dr. Rodriguez acknowledged. “We have gotten a sense of which patients are likely to have diagnostic or not diagnostic genomes, but it is also a gut feeling,” she said.

“If this child is your patient and you are concerned, if they seem sicker than expected, or have a concerning family history, then send the test,” she said. “It is becoming more affordable, and can come back quickly enough to guide treatment while the patient is still in the ICU.”

In the current study, the greatest diagnostic utility appeared in patients with cardiac symptoms, such as congenital heart disease, sudden cardiac arrest, or suspected channelopathy, Dr. Rodriguez said in her presentation.

Patients with suspected neurological disease had a 50% rate of molecular diagnosis. “Interestingly, 74% of patients with respiratory disease where an underlying genetic etiology was suspected received a molecular diagnosis,” although rWGS was not applied to general populations with RSV or other respiratory illnesses, she said.

In her presentation, Dr. Rodriguez shared examples of how genetic testing had a dramatic impact on patient survival. In one case, a 14-year-old girl presented in cardiac arrest and was found to have new-onset dilated cardiomyopathy. Whether the etiology was acquired or infectious and possibly reversible or genetic was unclear, she said.

“A diagnostic genome result within 48 hours indicated a genetic etiology,” she said. The patient was listed for heart transplant despite the incomplete infectious workup, and received a successful heart transplant 1 week after admission, Dr. Rodriguez said.

Guidelines for which PICU patients should undergo genetic testing do not yet exist, Dr. Rodriguez told this news organization. “We are trying to find some more meaningful parameters where we can say that a patient has a high pretest possibility of a genetic condition,” she said.

“Increasing availability of rWGS can significantly impact patient care and assist families in making difficult decisions during times of critical illness,” she said.

Insurance coverage and testing access are improving, said Dr. Rodriguez. Medicaid policies exist for neonates/infants in the ICU in several states, including Oregon, California, Michigan, Maryland, and Louisiana, she said. In some areas, hospitals may pay for testing for these children if insurance will not, she added.

Dr. Rodriguez and colleagues are continuing to enroll patients in a prospective study of the impact of rWGS, with the addition of a fourth study site and inclusion of family surveys. “We also will be looking at a secondary analysis of cost savings and benefits,” she said.

Ultimately, the current study should be empowering to physicians, “especially if they don’t have good access to geneticists,” Dr. Rodriguez said in an interview.

The study received no outside funding. Dr. Rodriguez reports no relevant financial relationships. 

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

Two-thirds of children who underwent genetic testing in the pediatric intensive care unit showed a genetic variant, and a third of these children received changes in care as a result, according to a new study presented at the Society of Critical Care Medicine’s 2023 Critical Care Congress.

“We have had a lot of success using genome sequencing to help not only with diagnosis, but also changes in management,” lead author Katherine Rodriguez, MD, a pediatric critical care fellow physician at Rady Children’s Hospital, San Diego, told this news organization.

However, data on the use of rapid whole genome sequencing (rWGS) in the pediatric intensive care unit (PICU) are limited, and data from multiple institutions are lacking, Dr. Rodriguez said. In the current study, data from multiple hospitals allowed the researchers to examine differences in management across institutions, she said.

Dr. Rodriguez, with principal investigator Nicole Coufal, MD, also of Rady Children’s, and colleagues conducted the study at three children’s hospitals from March 2019 to July 2022. The study population included 80 children whose origin of illness was uncertain. The patients underwent rWGS testing in the PICU or cardiac ICU setting. The patients ranged in age from 0 to 17 years; 64% were younger than 1 year, (mean age, 2.8 years); 56% were male, and 59% were White.  

After rWGS testing, 65% of the children were positive for a genetic variant. The data prompted changes to care for 42% of these patients; 38% of the changes occurred during the patient’s PICU stay, including medication changes and procedures that were either avoided or completed.

The remaining 62% of the changes were subacute and affected management for the remainder of the child’s hospitalization and after discharge, Dr. Rodriguez explained in her presentation.

The average turnaround time for the testing was 10 days, which is important to an intensivist, who may have been hesitant to order tests because of the time involved, Dr. Rodriguez said. The current study shows that “we can get test results in a reasonable time to make meaningful changes in care,” she told this news organization.

Choosing which patients to test can be a challenge for clinicians, Dr. Rodriguez acknowledged. “We have gotten a sense of which patients are likely to have diagnostic or not diagnostic genomes, but it is also a gut feeling,” she said.

“If this child is your patient and you are concerned, if they seem sicker than expected, or have a concerning family history, then send the test,” she said. “It is becoming more affordable, and can come back quickly enough to guide treatment while the patient is still in the ICU.”

In the current study, the greatest diagnostic utility appeared in patients with cardiac symptoms, such as congenital heart disease, sudden cardiac arrest, or suspected channelopathy, Dr. Rodriguez said in her presentation.

Patients with suspected neurological disease had a 50% rate of molecular diagnosis. “Interestingly, 74% of patients with respiratory disease where an underlying genetic etiology was suspected received a molecular diagnosis,” although rWGS was not applied to general populations with RSV or other respiratory illnesses, she said.

In her presentation, Dr. Rodriguez shared examples of how genetic testing had a dramatic impact on patient survival. In one case, a 14-year-old girl presented in cardiac arrest and was found to have new-onset dilated cardiomyopathy. Whether the etiology was acquired or infectious and possibly reversible or genetic was unclear, she said.

“A diagnostic genome result within 48 hours indicated a genetic etiology,” she said. The patient was listed for heart transplant despite the incomplete infectious workup, and received a successful heart transplant 1 week after admission, Dr. Rodriguez said.

Guidelines for which PICU patients should undergo genetic testing do not yet exist, Dr. Rodriguez told this news organization. “We are trying to find some more meaningful parameters where we can say that a patient has a high pretest possibility of a genetic condition,” she said.

“Increasing availability of rWGS can significantly impact patient care and assist families in making difficult decisions during times of critical illness,” she said.

Insurance coverage and testing access are improving, said Dr. Rodriguez. Medicaid policies exist for neonates/infants in the ICU in several states, including Oregon, California, Michigan, Maryland, and Louisiana, she said. In some areas, hospitals may pay for testing for these children if insurance will not, she added.

Dr. Rodriguez and colleagues are continuing to enroll patients in a prospective study of the impact of rWGS, with the addition of a fourth study site and inclusion of family surveys. “We also will be looking at a secondary analysis of cost savings and benefits,” she said.

Ultimately, the current study should be empowering to physicians, “especially if they don’t have good access to geneticists,” Dr. Rodriguez said in an interview.

The study received no outside funding. Dr. Rodriguez reports no relevant financial relationships. 

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

Childhood stress can change the brain negatively, according to a new study that says Black children are affected more because they experience more poverty and adversity.

“The researchers analyzed MRI scans to identify small differences in the volume of certain brain structures, and said these could accumulate as children age and play a role in the later development of mental health problems,” STAT News reported. “The finding, part of an emerging research field looking at how racism and other social factors may affect the physical architecture of the brain, may help explain longstanding racial disparities in the prevalence of psychiatric disorders such as PTSD.”

The study was published in The American Journal of Psychiatry.

Brain development is affected by “disparities faced by certain groups of people,” even among children as young as 9 years old, said Nathaniel Harnett, an assistant professor of psychiatry at Harvard Medical School, Boston, and the study’s senior author. “If we’re going to treat the world as colorblind, we’re not going to create mental health solutions that are effective for all people.”

The study used evidence from the Adolescent Brain Cognitive Development Study, which the National Institutes of Health established in 2015 to study the brains and experiences of thousands of American children through early adulthood.

Brain scans revealed that Black children had less gray matter in 11 of 14 brain areas that were examined. Disparities in 8 of the 14 brain areas were affected by childhood adversity, particularly poverty.

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

Childhood stress can change the brain negatively, according to a new study that says Black children are affected more because they experience more poverty and adversity.

“The researchers analyzed MRI scans to identify small differences in the volume of certain brain structures, and said these could accumulate as children age and play a role in the later development of mental health problems,” STAT News reported. “The finding, part of an emerging research field looking at how racism and other social factors may affect the physical architecture of the brain, may help explain longstanding racial disparities in the prevalence of psychiatric disorders such as PTSD.”

The study was published in The American Journal of Psychiatry.

Brain development is affected by “disparities faced by certain groups of people,” even among children as young as 9 years old, said Nathaniel Harnett, an assistant professor of psychiatry at Harvard Medical School, Boston, and the study’s senior author. “If we’re going to treat the world as colorblind, we’re not going to create mental health solutions that are effective for all people.”

The study used evidence from the Adolescent Brain Cognitive Development Study, which the National Institutes of Health established in 2015 to study the brains and experiences of thousands of American children through early adulthood.

Brain scans revealed that Black children had less gray matter in 11 of 14 brain areas that were examined. Disparities in 8 of the 14 brain areas were affected by childhood adversity, particularly poverty.

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

Childhood stress can change the brain negatively, according to a new study that says Black children are affected more because they experience more poverty and adversity.

“The researchers analyzed MRI scans to identify small differences in the volume of certain brain structures, and said these could accumulate as children age and play a role in the later development of mental health problems,” STAT News reported. “The finding, part of an emerging research field looking at how racism and other social factors may affect the physical architecture of the brain, may help explain longstanding racial disparities in the prevalence of psychiatric disorders such as PTSD.”

The study was published in The American Journal of Psychiatry.

Brain development is affected by “disparities faced by certain groups of people,” even among children as young as 9 years old, said Nathaniel Harnett, an assistant professor of psychiatry at Harvard Medical School, Boston, and the study’s senior author. “If we’re going to treat the world as colorblind, we’re not going to create mental health solutions that are effective for all people.”

The study used evidence from the Adolescent Brain Cognitive Development Study, which the National Institutes of Health established in 2015 to study the brains and experiences of thousands of American children through early adulthood.

Brain scans revealed that Black children had less gray matter in 11 of 14 brain areas that were examined. Disparities in 8 of the 14 brain areas were affected by childhood adversity, particularly poverty.

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

People with untreatable dystrophic epidermolysis bullosa (DEB) may soon have access to an investigational gene therapy delivered in a topical gel that is currently under review by the Food and Drug Administration.

In a phase 3 study of patients with DEB, “we found that repeated topical application of B-VEC [beremagene geperpavec], an HSV-1–based gene therapy, resulted in a greater likelihood of complete wound healing than the topical application of placebo at up to 6 months,” the authors wrote. The study was published in The New England Journal of Medicine. “Longer and larger trials are warranted to determine the durability of effect and risks of this approach,” the authors noted.

“The results prove that B-VEC, the first topical in vivo gene therapy to reach late-stage development, can heal DEB,” senior author M. Peter Marinkovich, MD, associate professor of dermatology at Stanford University, Redwood City, Calif., said in an interview.

“In the past, DEB was a very specialized disease that only a handful of dermatologists would see but could not do much to treat,” he said. “With gene therapy, many more dermatologists who may not be familiar with DEB will be able to treat these patients in their offices.” It is expected that nurses will be able to administer the treatment to patients at home, he added.
 

Rare, life-threatening, genetic blistering disease

DEB, a rare disease that affects one to three persons per million in the United States, is caused by mutations in the COL7A1 gene that encodes the alpha-1 chain of collagen type VII (C7) protein. C7 forms the anchoring fibrils that attach the epidermis to the underlying dermal connective tissue.

COL71A mutations that lead to defective, decreased, or absent C7 can make the skin so fragile it tears with the slightest touch. This has led to patients being called “butterfly children.” Epithelial tissues blister and scar, causing esophageal and genitourinary strictures, adhesion of digits, malnutrition, anemia, infection, and bothersome itch and pain. Morbidity and mortality are high. The leading cause of death in adults is chronic wounds leading to aggressive squamous cell cancers.
 

The first therapy for DEB, under FDA review

B-VEC restores C7 protein by using an engineered replication-defective herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells to restore functional C7 protein fibrils that stabilize the skin structure.

On the basis of manufacturing information submitted to the FDA in December 2022, the agency extended the date for a decision on approval by 3 months, to May 19, 2023, according to a statement from Krystal Biotech, the developer of B-VEC and the sponsor of the NEJM study.

Dr. Marinkovich and his colleagues conducted the double-blind, randomized, controlled GEM-3 trial of B-VEC at three sites in the United States. The 31 study participants ranged in age from 1 to 44 years (median age, 16 years) and had genetically confirmed DEB (30 with the recessive form and 1 with the dominant form).

For each participant, a pair of wounds was chosen that were matched in size, region, and appearance. The wounds within each pair were randomly allocated to receive weekly applications of either B-VEC or placebo gel for 26 weeks.

The results of the study included the following:

• Complete healing at 6 months occurred in 67% of the wounds treated with B-VEC (including a wound in the patient with dominant DEB), vs. 22% of those who received placebo (95% confidence interval [CI], 24-68; P = .002).
• Complete healing at 3 months occurred in 71% of the wounds treated with B-VEC, vs. 20% of those who received placebo (95% CI, 29-73; P < .001).
• The mean change from baseline to week 22 in pain severity during wound-dressing changes for patients aged 6 years and older, as determined on the basis of a visual analogue scale, was –0.88 with B-VEC, vs. –0.71 with placebo (adjusted least-squares mean difference, –0.61; 95% CI, –1.10 to –0.13); similar mean changes were seen at weeks 24 and 26.
• Among all patients, 58% had at least one adverse event. Most adverse events were mild or moderate. The most common were pruritus, chills, and squamous cell carcinoma (SCC), which were reported in three patients each (SCC cases occurred at wound sites that had not been exposed to B-VEC or placebo). Serious adverse events, which were unrelated to the treatment, occurred in three patients: diarrhea, anemia, cellulitis, and a positive blood culture related to a hemodialysis catheter.

“With the ability to treat patients with topical gene therapy, dermatology is entering a new age of treatment possibilities,” Dr. Marinkovich said in the interview.

The researchers were surprised that the redosable in vivo gene therapy worked so well, he added. In vivo gene therapy has been plagued by the occurrence of immune reactions against the viral vectors used, Dr. Marinkovich explained. But because the herpes simplex virus has evolved to evade the immune system, his team could use the viral vector every week for 6 months without inflammatory reactions.

“The immune system’s inability to fight off or get rid of the herpes simplex vector makes it bad as a disease, but as a gene therapy vector, it provides a huge advantage,” he added.

Asked to comment on the results, Christen Ebens, MD, MPH, assistant professor in the department of pediatrics at the University of Minnesota, Minneapolis, whose clinical and research interests include EB, called the results exciting for patients, families, and doctors.

“Side effects were minimal, and importantly, use of the replication-incompetent HSV vector means that the payload gene does not integrate into the patient’s DNA,” Dr. Ebens, who was not involved in the study, said in an interview. “B-VEC is not a lifelong cure but potentially an effective maintenance therapy requiring repeated doses,” she added.

Although the researchers found no clinically important immune reactions to B-VEC, Dr. Ebens said she would like to see results from longer studies of the treatment. “We will want to see that patients do not produce neutralizing antibodies against B-VEC or its components, as such antibodies may yield the treatment ineffective or cause significant side effects.”

In an interview, Vanessa R. Holland, MD, associate clinical professor in the division of dermatology at UCLA Health, Burbank, Calif., who was not involved in the study, said that “topical replication-defective HSV-1 is a brilliant vector to deliver the depleted collagen.” She added that “such a vehicle may significantly alter management of these disorders and improve or extend lives by minimizing potentially fatal complications.”

Paras P. Vakharia, MD, PharmD, assistant professor of dermatology at Northwestern University, Chicago, who was not involved in the study, was surprised by the high percentage of healed wounds and wounds that remained healed over time.

B-VEC for treating other conditions

Dr. Marinkovich noted that an ongoing phase 1 clinical trial, also sponsored by Krystal Biotech, is using the HSV-1 vector to deliver a different biologic (KB105) to establish dose and safety in the treatment of ichthyosis. He added that he would like to explore the use of B-VEC to treat DEB at mucosal surfaces, including inside the mouth, the eye, and the esophagus.

Authors of two editorials that accompanied the study also referred to other conditions B-VEC might treat.

This study “highlights potential future investigations,” David V. Schaffer, PhD, professor of chemical and biomolecular engineering, bioengineering, and molecular and cell biology at the University of California, Berkeley, wrotes in one of the editorials.

Important considerations he mentioned include the likelihood of the treatment becoming lifelong; the inability of HSV to penetrate intact skin, making B-VEC unsuitable for preventing the development of new wounds; and the inability of this treatment to treat EB lesions along the digestive tract. “This important trial builds on and extends gene-therapy successes to new targets and vectors, an advance for patients,” he added.

In the second editorial, Aimee S. Payne, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia, raised the question of whether B-VEC’s clinical success for treating DEB can translate to other genetic diseases.

“Formulations for ophthalmic, oral-gastrointestinal, or respiratory delivery would be of great value to address the extracutaneous manifestations of epidermolysis bullosa and other genetic diseases,” she wrote.

Referring to an ongoing trial of a topical gene therapy for cystic fibrosis that is delivered by a nebulizer, Dr. Payne noted, “Ultimately, the completion of clinical trials such as this one will be required to determine whether HSV-1–mediated gene delivery can go more than skin deep.”

Earlier data and more details of the study were presented in a poster at the annual meeting of the Society for Pediatric Dermatology in July 2022.

Dr. Marinkovich has disclosed no relevant financial relationships. Several coauthors are employees of or have other financial relationships with Krystal Biotech, the study’s sponsor and the developer of beremagene geperpavec. Dr. Schaffer and Dr. Payne have financial relationships with the pharmaceutical industry. Dr. Ebens, Dr. Holland, and Dr. Vakharia have disclosed no relevant financial relationships.

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

People with untreatable dystrophic epidermolysis bullosa (DEB) may soon have access to an investigational gene therapy delivered in a topical gel that is currently under review by the Food and Drug Administration.

In a phase 3 study of patients with DEB, “we found that repeated topical application of B-VEC [beremagene geperpavec], an HSV-1–based gene therapy, resulted in a greater likelihood of complete wound healing than the topical application of placebo at up to 6 months,” the authors wrote. The study was published in The New England Journal of Medicine. “Longer and larger trials are warranted to determine the durability of effect and risks of this approach,” the authors noted.

“The results prove that B-VEC, the first topical in vivo gene therapy to reach late-stage development, can heal DEB,” senior author M. Peter Marinkovich, MD, associate professor of dermatology at Stanford University, Redwood City, Calif., said in an interview.

“In the past, DEB was a very specialized disease that only a handful of dermatologists would see but could not do much to treat,” he said. “With gene therapy, many more dermatologists who may not be familiar with DEB will be able to treat these patients in their offices.” It is expected that nurses will be able to administer the treatment to patients at home, he added.
 

Rare, life-threatening, genetic blistering disease

DEB, a rare disease that affects one to three persons per million in the United States, is caused by mutations in the COL7A1 gene that encodes the alpha-1 chain of collagen type VII (C7) protein. C7 forms the anchoring fibrils that attach the epidermis to the underlying dermal connective tissue.

COL71A mutations that lead to defective, decreased, or absent C7 can make the skin so fragile it tears with the slightest touch. This has led to patients being called “butterfly children.” Epithelial tissues blister and scar, causing esophageal and genitourinary strictures, adhesion of digits, malnutrition, anemia, infection, and bothersome itch and pain. Morbidity and mortality are high. The leading cause of death in adults is chronic wounds leading to aggressive squamous cell cancers.
 

The first therapy for DEB, under FDA review

B-VEC restores C7 protein by using an engineered replication-defective herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells to restore functional C7 protein fibrils that stabilize the skin structure.

On the basis of manufacturing information submitted to the FDA in December 2022, the agency extended the date for a decision on approval by 3 months, to May 19, 2023, according to a statement from Krystal Biotech, the developer of B-VEC and the sponsor of the NEJM study.

Dr. Marinkovich and his colleagues conducted the double-blind, randomized, controlled GEM-3 trial of B-VEC at three sites in the United States. The 31 study participants ranged in age from 1 to 44 years (median age, 16 years) and had genetically confirmed DEB (30 with the recessive form and 1 with the dominant form).

For each participant, a pair of wounds was chosen that were matched in size, region, and appearance. The wounds within each pair were randomly allocated to receive weekly applications of either B-VEC or placebo gel for 26 weeks.

The results of the study included the following:

• Complete healing at 6 months occurred in 67% of the wounds treated with B-VEC (including a wound in the patient with dominant DEB), vs. 22% of those who received placebo (95% confidence interval [CI], 24-68; P = .002).
• Complete healing at 3 months occurred in 71% of the wounds treated with B-VEC, vs. 20% of those who received placebo (95% CI, 29-73; P < .001).
• The mean change from baseline to week 22 in pain severity during wound-dressing changes for patients aged 6 years and older, as determined on the basis of a visual analogue scale, was –0.88 with B-VEC, vs. –0.71 with placebo (adjusted least-squares mean difference, –0.61; 95% CI, –1.10 to –0.13); similar mean changes were seen at weeks 24 and 26.
• Among all patients, 58% had at least one adverse event. Most adverse events were mild or moderate. The most common were pruritus, chills, and squamous cell carcinoma (SCC), which were reported in three patients each (SCC cases occurred at wound sites that had not been exposed to B-VEC or placebo). Serious adverse events, which were unrelated to the treatment, occurred in three patients: diarrhea, anemia, cellulitis, and a positive blood culture related to a hemodialysis catheter.

“With the ability to treat patients with topical gene therapy, dermatology is entering a new age of treatment possibilities,” Dr. Marinkovich said in the interview.

The researchers were surprised that the redosable in vivo gene therapy worked so well, he added. In vivo gene therapy has been plagued by the occurrence of immune reactions against the viral vectors used, Dr. Marinkovich explained. But because the herpes simplex virus has evolved to evade the immune system, his team could use the viral vector every week for 6 months without inflammatory reactions.

“The immune system’s inability to fight off or get rid of the herpes simplex vector makes it bad as a disease, but as a gene therapy vector, it provides a huge advantage,” he added.

Asked to comment on the results, Christen Ebens, MD, MPH, assistant professor in the department of pediatrics at the University of Minnesota, Minneapolis, whose clinical and research interests include EB, called the results exciting for patients, families, and doctors.

“Side effects were minimal, and importantly, use of the replication-incompetent HSV vector means that the payload gene does not integrate into the patient’s DNA,” Dr. Ebens, who was not involved in the study, said in an interview. “B-VEC is not a lifelong cure but potentially an effective maintenance therapy requiring repeated doses,” she added.

Although the researchers found no clinically important immune reactions to B-VEC, Dr. Ebens said she would like to see results from longer studies of the treatment. “We will want to see that patients do not produce neutralizing antibodies against B-VEC or its components, as such antibodies may yield the treatment ineffective or cause significant side effects.”

In an interview, Vanessa R. Holland, MD, associate clinical professor in the division of dermatology at UCLA Health, Burbank, Calif., who was not involved in the study, said that “topical replication-defective HSV-1 is a brilliant vector to deliver the depleted collagen.” She added that “such a vehicle may significantly alter management of these disorders and improve or extend lives by minimizing potentially fatal complications.”

Paras P. Vakharia, MD, PharmD, assistant professor of dermatology at Northwestern University, Chicago, who was not involved in the study, was surprised by the high percentage of healed wounds and wounds that remained healed over time.

B-VEC for treating other conditions

Dr. Marinkovich noted that an ongoing phase 1 clinical trial, also sponsored by Krystal Biotech, is using the HSV-1 vector to deliver a different biologic (KB105) to establish dose and safety in the treatment of ichthyosis. He added that he would like to explore the use of B-VEC to treat DEB at mucosal surfaces, including inside the mouth, the eye, and the esophagus.

Authors of two editorials that accompanied the study also referred to other conditions B-VEC might treat.

This study “highlights potential future investigations,” David V. Schaffer, PhD, professor of chemical and biomolecular engineering, bioengineering, and molecular and cell biology at the University of California, Berkeley, wrotes in one of the editorials.

Important considerations he mentioned include the likelihood of the treatment becoming lifelong; the inability of HSV to penetrate intact skin, making B-VEC unsuitable for preventing the development of new wounds; and the inability of this treatment to treat EB lesions along the digestive tract. “This important trial builds on and extends gene-therapy successes to new targets and vectors, an advance for patients,” he added.

In the second editorial, Aimee S. Payne, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia, raised the question of whether B-VEC’s clinical success for treating DEB can translate to other genetic diseases.

“Formulations for ophthalmic, oral-gastrointestinal, or respiratory delivery would be of great value to address the extracutaneous manifestations of epidermolysis bullosa and other genetic diseases,” she wrote.

Referring to an ongoing trial of a topical gene therapy for cystic fibrosis that is delivered by a nebulizer, Dr. Payne noted, “Ultimately, the completion of clinical trials such as this one will be required to determine whether HSV-1–mediated gene delivery can go more than skin deep.”

Earlier data and more details of the study were presented in a poster at the annual meeting of the Society for Pediatric Dermatology in July 2022.

Dr. Marinkovich has disclosed no relevant financial relationships. Several coauthors are employees of or have other financial relationships with Krystal Biotech, the study’s sponsor and the developer of beremagene geperpavec. Dr. Schaffer and Dr. Payne have financial relationships with the pharmaceutical industry. Dr. Ebens, Dr. Holland, and Dr. Vakharia have disclosed no relevant financial relationships.

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

People with untreatable dystrophic epidermolysis bullosa (DEB) may soon have access to an investigational gene therapy delivered in a topical gel that is currently under review by the Food and Drug Administration.

In a phase 3 study of patients with DEB, “we found that repeated topical application of B-VEC [beremagene geperpavec], an HSV-1–based gene therapy, resulted in a greater likelihood of complete wound healing than the topical application of placebo at up to 6 months,” the authors wrote. The study was published in The New England Journal of Medicine. “Longer and larger trials are warranted to determine the durability of effect and risks of this approach,” the authors noted.

“The results prove that B-VEC, the first topical in vivo gene therapy to reach late-stage development, can heal DEB,” senior author M. Peter Marinkovich, MD, associate professor of dermatology at Stanford University, Redwood City, Calif., said in an interview.

“In the past, DEB was a very specialized disease that only a handful of dermatologists would see but could not do much to treat,” he said. “With gene therapy, many more dermatologists who may not be familiar with DEB will be able to treat these patients in their offices.” It is expected that nurses will be able to administer the treatment to patients at home, he added.
 

Rare, life-threatening, genetic blistering disease

DEB, a rare disease that affects one to three persons per million in the United States, is caused by mutations in the COL7A1 gene that encodes the alpha-1 chain of collagen type VII (C7) protein. C7 forms the anchoring fibrils that attach the epidermis to the underlying dermal connective tissue.

COL71A mutations that lead to defective, decreased, or absent C7 can make the skin so fragile it tears with the slightest touch. This has led to patients being called “butterfly children.” Epithelial tissues blister and scar, causing esophageal and genitourinary strictures, adhesion of digits, malnutrition, anemia, infection, and bothersome itch and pain. Morbidity and mortality are high. The leading cause of death in adults is chronic wounds leading to aggressive squamous cell cancers.
 

The first therapy for DEB, under FDA review

B-VEC restores C7 protein by using an engineered replication-defective herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to skin cells to restore functional C7 protein fibrils that stabilize the skin structure.

On the basis of manufacturing information submitted to the FDA in December 2022, the agency extended the date for a decision on approval by 3 months, to May 19, 2023, according to a statement from Krystal Biotech, the developer of B-VEC and the sponsor of the NEJM study.

Dr. Marinkovich and his colleagues conducted the double-blind, randomized, controlled GEM-3 trial of B-VEC at three sites in the United States. The 31 study participants ranged in age from 1 to 44 years (median age, 16 years) and had genetically confirmed DEB (30 with the recessive form and 1 with the dominant form).

For each participant, a pair of wounds was chosen that were matched in size, region, and appearance. The wounds within each pair were randomly allocated to receive weekly applications of either B-VEC or placebo gel for 26 weeks.

The results of the study included the following:

• Complete healing at 6 months occurred in 67% of the wounds treated with B-VEC (including a wound in the patient with dominant DEB), vs. 22% of those who received placebo (95% confidence interval [CI], 24-68; P = .002).
• Complete healing at 3 months occurred in 71% of the wounds treated with B-VEC, vs. 20% of those who received placebo (95% CI, 29-73; P < .001).
• The mean change from baseline to week 22 in pain severity during wound-dressing changes for patients aged 6 years and older, as determined on the basis of a visual analogue scale, was –0.88 with B-VEC, vs. –0.71 with placebo (adjusted least-squares mean difference, –0.61; 95% CI, –1.10 to –0.13); similar mean changes were seen at weeks 24 and 26.
• Among all patients, 58% had at least one adverse event. Most adverse events were mild or moderate. The most common were pruritus, chills, and squamous cell carcinoma (SCC), which were reported in three patients each (SCC cases occurred at wound sites that had not been exposed to B-VEC or placebo). Serious adverse events, which were unrelated to the treatment, occurred in three patients: diarrhea, anemia, cellulitis, and a positive blood culture related to a hemodialysis catheter.

“With the ability to treat patients with topical gene therapy, dermatology is entering a new age of treatment possibilities,” Dr. Marinkovich said in the interview.

The researchers were surprised that the redosable in vivo gene therapy worked so well, he added. In vivo gene therapy has been plagued by the occurrence of immune reactions against the viral vectors used, Dr. Marinkovich explained. But because the herpes simplex virus has evolved to evade the immune system, his team could use the viral vector every week for 6 months without inflammatory reactions.

“The immune system’s inability to fight off or get rid of the herpes simplex vector makes it bad as a disease, but as a gene therapy vector, it provides a huge advantage,” he added.

Asked to comment on the results, Christen Ebens, MD, MPH, assistant professor in the department of pediatrics at the University of Minnesota, Minneapolis, whose clinical and research interests include EB, called the results exciting for patients, families, and doctors.

“Side effects were minimal, and importantly, use of the replication-incompetent HSV vector means that the payload gene does not integrate into the patient’s DNA,” Dr. Ebens, who was not involved in the study, said in an interview. “B-VEC is not a lifelong cure but potentially an effective maintenance therapy requiring repeated doses,” she added.

Although the researchers found no clinically important immune reactions to B-VEC, Dr. Ebens said she would like to see results from longer studies of the treatment. “We will want to see that patients do not produce neutralizing antibodies against B-VEC or its components, as such antibodies may yield the treatment ineffective or cause significant side effects.”

In an interview, Vanessa R. Holland, MD, associate clinical professor in the division of dermatology at UCLA Health, Burbank, Calif., who was not involved in the study, said that “topical replication-defective HSV-1 is a brilliant vector to deliver the depleted collagen.” She added that “such a vehicle may significantly alter management of these disorders and improve or extend lives by minimizing potentially fatal complications.”

Paras P. Vakharia, MD, PharmD, assistant professor of dermatology at Northwestern University, Chicago, who was not involved in the study, was surprised by the high percentage of healed wounds and wounds that remained healed over time.

B-VEC for treating other conditions

Dr. Marinkovich noted that an ongoing phase 1 clinical trial, also sponsored by Krystal Biotech, is using the HSV-1 vector to deliver a different biologic (KB105) to establish dose and safety in the treatment of ichthyosis. He added that he would like to explore the use of B-VEC to treat DEB at mucosal surfaces, including inside the mouth, the eye, and the esophagus.

Authors of two editorials that accompanied the study also referred to other conditions B-VEC might treat.

This study “highlights potential future investigations,” David V. Schaffer, PhD, professor of chemical and biomolecular engineering, bioengineering, and molecular and cell biology at the University of California, Berkeley, wrotes in one of the editorials.

Important considerations he mentioned include the likelihood of the treatment becoming lifelong; the inability of HSV to penetrate intact skin, making B-VEC unsuitable for preventing the development of new wounds; and the inability of this treatment to treat EB lesions along the digestive tract. “This important trial builds on and extends gene-therapy successes to new targets and vectors, an advance for patients,” he added.

In the second editorial, Aimee S. Payne, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia, raised the question of whether B-VEC’s clinical success for treating DEB can translate to other genetic diseases.

“Formulations for ophthalmic, oral-gastrointestinal, or respiratory delivery would be of great value to address the extracutaneous manifestations of epidermolysis bullosa and other genetic diseases,” she wrote.

Referring to an ongoing trial of a topical gene therapy for cystic fibrosis that is delivered by a nebulizer, Dr. Payne noted, “Ultimately, the completion of clinical trials such as this one will be required to determine whether HSV-1–mediated gene delivery can go more than skin deep.”

Earlier data and more details of the study were presented in a poster at the annual meeting of the Society for Pediatric Dermatology in July 2022.

Dr. Marinkovich has disclosed no relevant financial relationships. Several coauthors are employees of or have other financial relationships with Krystal Biotech, the study’s sponsor and the developer of beremagene geperpavec. Dr. Schaffer and Dr. Payne have financial relationships with the pharmaceutical industry. Dr. Ebens, Dr. Holland, and Dr. Vakharia have disclosed no relevant financial relationships.

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

It’s the end of an era. The Biden administration announced Jan. 30 that it will be ending the twin COVID-19 emergency declarations, marking a major change in the 3-year-old pandemic.

The orders spanned two presidencies. The Trump administration’s Health and Human Services Secretary Alex Azar issued a public health emergency in January 2020. Then-President Donald Trump declared the COVID-19 pandemic a national emergency 2 months later. Both emergency declarations – which remained in effect under President Joe Biden – are set to expire May 11. 

Read on for an overview of how the end of the public health emergency will trigger multiple federal policy changes. 
 

Changes that affect everyone

• There will be cost-sharing changes for COVID-19 vaccines, testing, and certain treatments. One hundred–percent coverage for COVID testing, including free at-home tests, will expire May 11. 
• Telemedicine cannot be used to prescribe controlled substances after May 11, 2023.
• Enhanced federal funding will be phased down through Dec. 31, 2023. This extends the time states must receive federally matched funds for COVID-related services and products, through the Consolidated Appropriations Act of 2023. Otherwise, this would have expired June 30, 2023.
• Emergency use authorizations for COVID-19 treatments and vaccinations will not be affected and/or end on May 11.

Changes that affect people with private health insurance

• Many will likely see higher costs for COVID-19 tests, as free testing expires and cost-sharing begins in the coming months.
• COVID-19 vaccinations and boosters will continue to be covered until the federal government’s vaccination supply is depleted. If that happens, you will need an in-network provider.
• You will still have access to COVID-19 treatments – but that could change when the federal supply dwindles.

Changes that affect Medicare recipients

• Medicare telehealth flexibilities will be extended through Dec. 31, 2024, regardless of public health emergency status. This means people can access telehealth services from anywhere, not just rural areas; can use a smartphone for telehealth; and can access telehealth in their homes. 
• Medicare cost-sharing for testing and treatments will expire May 11, except for oral antivirals. 

Changes that affect Medicaid/CHIP recipients

• Medicaid and Children’s Health Insurance Program (CHIP) recipients will continue to receive approved vaccinations free of charge, but testing and treatment without cost-sharing will expire during the third quarter of 2024.
• The Medicaid continuous enrollment provision will be separated from the public health emergency, and continuous enrollment will end March 31, 2023.

Changes that affect uninsured people

• The uninsured will no longer have access to 100% coverage for these products and services (free COVID-19 treatments, vaccines, and testing). 

Changes that affect health care providers

• There will be changes to how much providers get paid for diagnosing people with COVID-19, ending the enhanced Inpatient Prospective Payment System reimbursement rate, as of May 11, 2023.
• Health Insurance Portability and Accountability Act (HIPAA) potential penalty waivers will end. This allows providers to communicate with patients through telehealth on a smartphone, for example, without violating privacy laws and incurring penalties.

What the experts are saying 

This news organization asked several health experts for their thoughts on ending the emergency health declarations for COVID, and what effects this could have. Many expressed concerns about the timing of the ending, saying that the move could limit access to COVID-related treatments. Others said the move was inevitable but raised concerns about federal guidance related to the decision. 

Question: Do you agree with the timing of the end to the emergency order?

Answer: Robert Atmar, MD, professor of infectious diseases at Baylor College of Medicine in Houston: “A lead time to prepare and anticipate these consequences may ease the transition, compared to an abrupt declaration that ends the declaration.” 

Answer: Georges C. Benjamin, MD, executive director of the American Public Health Association: “I think it’s time to do so. It has to be done in a great, thoughtful, and organized way because we’ve attached so many different things to this public health emergency. It’s going to take time for the system to adapt. [Centers for Disease Control and Prevention] data collection most likely will continue. People are used to reporting now. The CDC needs to give guidance to the states so that we’re clear about what we’re reporting, what we’re not. If we did that abruptly, it would just be a mess.”

Answer: Bruce Farber, MD, chief public health and epidemiology officer at Northwell Health in Manhasset, N.Y.: “I would have hoped to see it delayed.”

Answer: Steven Newmark, JD, chief legal officer and director of policy at the Global Healthy Living Foundation: “While we understand that an emergency cannot last forever, we hope that expanded services such as free vaccination, promotion of widespread vaccination, increased use of pharmacists to administer vaccines, telehealth availability and reimbursement, flexibility in work-from-home opportunities, and more continues. Access to equitable health care should never backtrack or be reduced.”

Q: What will the end of free COVID vaccinations and free testing mean? 

A: Dr. Farber: “There will likely be a decrease in vaccinations and testing. The vaccination rates are very low to begin with, and this will likely lower it further.”

A: Dr. Atmar: “I think it will mean that fewer people will get tested and vaccinated,” which “could lead to increased transmission, although wastewater testing suggests that there is a lot of unrecognized infection already occurring.” 

A: Dr. Benjamin: “That is a big concern. It means that for people, particularly for people who are uninsured and underinsured, we’ve got to make sure they have access to those. There’s a lot of discussion and debate about what the cost of those tests and vaccines will be, and it looks like the companies are going to impose very steep, increasing costs.”

Q: How will this affect higher-risk populations, like people with weakened immune systems? 

A: Dr. Farber: “Without monoclonals [drugs to treat COVID] and free Paxlovid,” people with weakened immune systems “may be undertreated.”

A: Dr. Atmar: “The implications of ongoing widespread virus transmission are that immunocompromised individuals may be more likely to be exposed and infected and to suffer the consequences of such infection, including severe illness. However, to a certain degree, this may already be happening. We are still seeing about 500 deaths/day, primarily in persons at highest risk of severe disease.”

A: Dr. Benjamin:  “People who have good insurance, can afford to get immunized, and have good relations with practitioners probably will continue to be covered. But lower-income individuals and people who really can’t afford to get tested or get immunized would likely become underimmunized and more infected. 

“So even though the federal emergency declaration will go away, I’m hoping that the federal government will continue to encourage all of us to emphasize those populations at the highest risk – those with chronic disease and those who are immunocompromised.”

A: Mr. Newmark: “People who are immunocompromised by their chronic illness or the medicines they take to treat acute or chronic conditions remain at higher risk for COVID-19 and its serious complications. The administration needs to support continued development of effective treatments and updated vaccines to protect the individual and public health. We’re also concerned that increased health care services - such as vaccination or telehealth – may fall back to prepandemic levels while the burden of protection, such as masking, may fall to chronic disease patients alone, which adds to the burden of living with disease.”

Q: What effect will ending Medicaid expansion money have? 

A: Dr. Benjamin: Anywhere from 16 to 20 million people are going to lose in coverage. I’m hoping that states will look at their experience over these last 2 years or so and come to the decision that there were improvements in healthier populations.

Q: Will this have any effect on how the public perceives the pandemic? 

A: Dr. Farber: “It is likely to give the impression that COVID is gone, which clearly is not the case.”

A: Dr. Benjamin: “It’ll be another argument by some that the pandemic is over. People should think about this as kind of like a hurricane. A hurricane comes through and tragically tears up communities, and we have an emergency during that time. But then we have to go through a period of recovery. I’m hoping people will realize that even though the public health emergencies have gone away, that we still need to go through a period of transition ... and that means that they still need to protect themselves, get vaccinated, and wear a mask when appropriate.”

A: Dr. Atmar: “There needs to be messaging that while we are transitioning away from emergency management of COVID-19, it is still a significant public health concern.”

A version of this article originally appeared on WebMD.com.

It’s the end of an era. The Biden administration announced Jan. 30 that it will be ending the twin COVID-19 emergency declarations, marking a major change in the 3-year-old pandemic.

The orders spanned two presidencies. The Trump administration’s Health and Human Services Secretary Alex Azar issued a public health emergency in January 2020. Then-President Donald Trump declared the COVID-19 pandemic a national emergency 2 months later. Both emergency declarations – which remained in effect under President Joe Biden – are set to expire May 11. 

Read on for an overview of how the end of the public health emergency will trigger multiple federal policy changes. 
 

Changes that affect everyone

• There will be cost-sharing changes for COVID-19 vaccines, testing, and certain treatments. One hundred–percent coverage for COVID testing, including free at-home tests, will expire May 11. 
• Telemedicine cannot be used to prescribe controlled substances after May 11, 2023.
• Enhanced federal funding will be phased down through Dec. 31, 2023. This extends the time states must receive federally matched funds for COVID-related services and products, through the Consolidated Appropriations Act of 2023. Otherwise, this would have expired June 30, 2023.
• Emergency use authorizations for COVID-19 treatments and vaccinations will not be affected and/or end on May 11.

Changes that affect people with private health insurance

• Many will likely see higher costs for COVID-19 tests, as free testing expires and cost-sharing begins in the coming months.
• COVID-19 vaccinations and boosters will continue to be covered until the federal government’s vaccination supply is depleted. If that happens, you will need an in-network provider.
• You will still have access to COVID-19 treatments – but that could change when the federal supply dwindles.

Changes that affect Medicare recipients

• Medicare telehealth flexibilities will be extended through Dec. 31, 2024, regardless of public health emergency status. This means people can access telehealth services from anywhere, not just rural areas; can use a smartphone for telehealth; and can access telehealth in their homes. 
• Medicare cost-sharing for testing and treatments will expire May 11, except for oral antivirals. 

Changes that affect Medicaid/CHIP recipients

• Medicaid and Children’s Health Insurance Program (CHIP) recipients will continue to receive approved vaccinations free of charge, but testing and treatment without cost-sharing will expire during the third quarter of 2024.
• The Medicaid continuous enrollment provision will be separated from the public health emergency, and continuous enrollment will end March 31, 2023.

Changes that affect uninsured people

• The uninsured will no longer have access to 100% coverage for these products and services (free COVID-19 treatments, vaccines, and testing). 

Changes that affect health care providers

• There will be changes to how much providers get paid for diagnosing people with COVID-19, ending the enhanced Inpatient Prospective Payment System reimbursement rate, as of May 11, 2023.
• Health Insurance Portability and Accountability Act (HIPAA) potential penalty waivers will end. This allows providers to communicate with patients through telehealth on a smartphone, for example, without violating privacy laws and incurring penalties.

What the experts are saying 

This news organization asked several health experts for their thoughts on ending the emergency health declarations for COVID, and what effects this could have. Many expressed concerns about the timing of the ending, saying that the move could limit access to COVID-related treatments. Others said the move was inevitable but raised concerns about federal guidance related to the decision. 

Question: Do you agree with the timing of the end to the emergency order?

Answer: Robert Atmar, MD, professor of infectious diseases at Baylor College of Medicine in Houston: “A lead time to prepare and anticipate these consequences may ease the transition, compared to an abrupt declaration that ends the declaration.” 

Answer: Georges C. Benjamin, MD, executive director of the American Public Health Association: “I think it’s time to do so. It has to be done in a great, thoughtful, and organized way because we’ve attached so many different things to this public health emergency. It’s going to take time for the system to adapt. [Centers for Disease Control and Prevention] data collection most likely will continue. People are used to reporting now. The CDC needs to give guidance to the states so that we’re clear about what we’re reporting, what we’re not. If we did that abruptly, it would just be a mess.”

Answer: Bruce Farber, MD, chief public health and epidemiology officer at Northwell Health in Manhasset, N.Y.: “I would have hoped to see it delayed.”

Answer: Steven Newmark, JD, chief legal officer and director of policy at the Global Healthy Living Foundation: “While we understand that an emergency cannot last forever, we hope that expanded services such as free vaccination, promotion of widespread vaccination, increased use of pharmacists to administer vaccines, telehealth availability and reimbursement, flexibility in work-from-home opportunities, and more continues. Access to equitable health care should never backtrack or be reduced.”

Q: What will the end of free COVID vaccinations and free testing mean? 

A: Dr. Farber: “There will likely be a decrease in vaccinations and testing. The vaccination rates are very low to begin with, and this will likely lower it further.”

A: Dr. Atmar: “I think it will mean that fewer people will get tested and vaccinated,” which “could lead to increased transmission, although wastewater testing suggests that there is a lot of unrecognized infection already occurring.” 

A: Dr. Benjamin: “That is a big concern. It means that for people, particularly for people who are uninsured and underinsured, we’ve got to make sure they have access to those. There’s a lot of discussion and debate about what the cost of those tests and vaccines will be, and it looks like the companies are going to impose very steep, increasing costs.”

Q: How will this affect higher-risk populations, like people with weakened immune systems? 

A: Dr. Farber: “Without monoclonals [drugs to treat COVID] and free Paxlovid,” people with weakened immune systems “may be undertreated.”

A: Dr. Atmar: “The implications of ongoing widespread virus transmission are that immunocompromised individuals may be more likely to be exposed and infected and to suffer the consequences of such infection, including severe illness. However, to a certain degree, this may already be happening. We are still seeing about 500 deaths/day, primarily in persons at highest risk of severe disease.”

A: Dr. Benjamin:  “People who have good insurance, can afford to get immunized, and have good relations with practitioners probably will continue to be covered. But lower-income individuals and people who really can’t afford to get tested or get immunized would likely become underimmunized and more infected. 

“So even though the federal emergency declaration will go away, I’m hoping that the federal government will continue to encourage all of us to emphasize those populations at the highest risk – those with chronic disease and those who are immunocompromised.”

A: Mr. Newmark: “People who are immunocompromised by their chronic illness or the medicines they take to treat acute or chronic conditions remain at higher risk for COVID-19 and its serious complications. The administration needs to support continued development of effective treatments and updated vaccines to protect the individual and public health. We’re also concerned that increased health care services - such as vaccination or telehealth – may fall back to prepandemic levels while the burden of protection, such as masking, may fall to chronic disease patients alone, which adds to the burden of living with disease.”

Q: What effect will ending Medicaid expansion money have? 

A: Dr. Benjamin: Anywhere from 16 to 20 million people are going to lose in coverage. I’m hoping that states will look at their experience over these last 2 years or so and come to the decision that there were improvements in healthier populations.

Q: Will this have any effect on how the public perceives the pandemic? 

A: Dr. Farber: “It is likely to give the impression that COVID is gone, which clearly is not the case.”

A: Dr. Benjamin: “It’ll be another argument by some that the pandemic is over. People should think about this as kind of like a hurricane. A hurricane comes through and tragically tears up communities, and we have an emergency during that time. But then we have to go through a period of recovery. I’m hoping people will realize that even though the public health emergencies have gone away, that we still need to go through a period of transition ... and that means that they still need to protect themselves, get vaccinated, and wear a mask when appropriate.”

A: Dr. Atmar: “There needs to be messaging that while we are transitioning away from emergency management of COVID-19, it is still a significant public health concern.”

A version of this article originally appeared on WebMD.com.

It’s the end of an era. The Biden administration announced Jan. 30 that it will be ending the twin COVID-19 emergency declarations, marking a major change in the 3-year-old pandemic.

The orders spanned two presidencies. The Trump administration’s Health and Human Services Secretary Alex Azar issued a public health emergency in January 2020. Then-President Donald Trump declared the COVID-19 pandemic a national emergency 2 months later. Both emergency declarations – which remained in effect under President Joe Biden – are set to expire May 11. 

Read on for an overview of how the end of the public health emergency will trigger multiple federal policy changes. 
 

Changes that affect everyone

• There will be cost-sharing changes for COVID-19 vaccines, testing, and certain treatments. One hundred–percent coverage for COVID testing, including free at-home tests, will expire May 11. 
• Telemedicine cannot be used to prescribe controlled substances after May 11, 2023.
• Enhanced federal funding will be phased down through Dec. 31, 2023. This extends the time states must receive federally matched funds for COVID-related services and products, through the Consolidated Appropriations Act of 2023. Otherwise, this would have expired June 30, 2023.
• Emergency use authorizations for COVID-19 treatments and vaccinations will not be affected and/or end on May 11.

Changes that affect people with private health insurance

• Many will likely see higher costs for COVID-19 tests, as free testing expires and cost-sharing begins in the coming months.
• COVID-19 vaccinations and boosters will continue to be covered until the federal government’s vaccination supply is depleted. If that happens, you will need an in-network provider.
• You will still have access to COVID-19 treatments – but that could change when the federal supply dwindles.

Changes that affect Medicare recipients

• Medicare telehealth flexibilities will be extended through Dec. 31, 2024, regardless of public health emergency status. This means people can access telehealth services from anywhere, not just rural areas; can use a smartphone for telehealth; and can access telehealth in their homes. 
• Medicare cost-sharing for testing and treatments will expire May 11, except for oral antivirals. 

Changes that affect Medicaid/CHIP recipients

• Medicaid and Children’s Health Insurance Program (CHIP) recipients will continue to receive approved vaccinations free of charge, but testing and treatment without cost-sharing will expire during the third quarter of 2024.
• The Medicaid continuous enrollment provision will be separated from the public health emergency, and continuous enrollment will end March 31, 2023.

Changes that affect uninsured people

• The uninsured will no longer have access to 100% coverage for these products and services (free COVID-19 treatments, vaccines, and testing). 

Changes that affect health care providers

• There will be changes to how much providers get paid for diagnosing people with COVID-19, ending the enhanced Inpatient Prospective Payment System reimbursement rate, as of May 11, 2023.
• Health Insurance Portability and Accountability Act (HIPAA) potential penalty waivers will end. This allows providers to communicate with patients through telehealth on a smartphone, for example, without violating privacy laws and incurring penalties.

What the experts are saying 

This news organization asked several health experts for their thoughts on ending the emergency health declarations for COVID, and what effects this could have. Many expressed concerns about the timing of the ending, saying that the move could limit access to COVID-related treatments. Others said the move was inevitable but raised concerns about federal guidance related to the decision. 

Question: Do you agree with the timing of the end to the emergency order?

Answer: Robert Atmar, MD, professor of infectious diseases at Baylor College of Medicine in Houston: “A lead time to prepare and anticipate these consequences may ease the transition, compared to an abrupt declaration that ends the declaration.” 

Answer: Georges C. Benjamin, MD, executive director of the American Public Health Association: “I think it’s time to do so. It has to be done in a great, thoughtful, and organized way because we’ve attached so many different things to this public health emergency. It’s going to take time for the system to adapt. [Centers for Disease Control and Prevention] data collection most likely will continue. People are used to reporting now. The CDC needs to give guidance to the states so that we’re clear about what we’re reporting, what we’re not. If we did that abruptly, it would just be a mess.”

Answer: Bruce Farber, MD, chief public health and epidemiology officer at Northwell Health in Manhasset, N.Y.: “I would have hoped to see it delayed.”

Answer: Steven Newmark, JD, chief legal officer and director of policy at the Global Healthy Living Foundation: “While we understand that an emergency cannot last forever, we hope that expanded services such as free vaccination, promotion of widespread vaccination, increased use of pharmacists to administer vaccines, telehealth availability and reimbursement, flexibility in work-from-home opportunities, and more continues. Access to equitable health care should never backtrack or be reduced.”

Q: What will the end of free COVID vaccinations and free testing mean? 

A: Dr. Farber: “There will likely be a decrease in vaccinations and testing. The vaccination rates are very low to begin with, and this will likely lower it further.”

A: Dr. Atmar: “I think it will mean that fewer people will get tested and vaccinated,” which “could lead to increased transmission, although wastewater testing suggests that there is a lot of unrecognized infection already occurring.” 

A: Dr. Benjamin: “That is a big concern. It means that for people, particularly for people who are uninsured and underinsured, we’ve got to make sure they have access to those. There’s a lot of discussion and debate about what the cost of those tests and vaccines will be, and it looks like the companies are going to impose very steep, increasing costs.”

Q: How will this affect higher-risk populations, like people with weakened immune systems? 

A: Dr. Farber: “Without monoclonals [drugs to treat COVID] and free Paxlovid,” people with weakened immune systems “may be undertreated.”

A: Dr. Atmar: “The implications of ongoing widespread virus transmission are that immunocompromised individuals may be more likely to be exposed and infected and to suffer the consequences of such infection, including severe illness. However, to a certain degree, this may already be happening. We are still seeing about 500 deaths/day, primarily in persons at highest risk of severe disease.”

A: Dr. Benjamin:  “People who have good insurance, can afford to get immunized, and have good relations with practitioners probably will continue to be covered. But lower-income individuals and people who really can’t afford to get tested or get immunized would likely become underimmunized and more infected. 

“So even though the federal emergency declaration will go away, I’m hoping that the federal government will continue to encourage all of us to emphasize those populations at the highest risk – those with chronic disease and those who are immunocompromised.”

A: Mr. Newmark: “People who are immunocompromised by their chronic illness or the medicines they take to treat acute or chronic conditions remain at higher risk for COVID-19 and its serious complications. The administration needs to support continued development of effective treatments and updated vaccines to protect the individual and public health. We’re also concerned that increased health care services - such as vaccination or telehealth – may fall back to prepandemic levels while the burden of protection, such as masking, may fall to chronic disease patients alone, which adds to the burden of living with disease.”

Q: What effect will ending Medicaid expansion money have? 

A: Dr. Benjamin: Anywhere from 16 to 20 million people are going to lose in coverage. I’m hoping that states will look at their experience over these last 2 years or so and come to the decision that there were improvements in healthier populations.

Q: Will this have any effect on how the public perceives the pandemic? 

A: Dr. Farber: “It is likely to give the impression that COVID is gone, which clearly is not the case.”

A: Dr. Benjamin: “It’ll be another argument by some that the pandemic is over. People should think about this as kind of like a hurricane. A hurricane comes through and tragically tears up communities, and we have an emergency during that time. But then we have to go through a period of recovery. I’m hoping people will realize that even though the public health emergencies have gone away, that we still need to go through a period of transition ... and that means that they still need to protect themselves, get vaccinated, and wear a mask when appropriate.”

A: Dr. Atmar: “There needs to be messaging that while we are transitioning away from emergency management of COVID-19, it is still a significant public health concern.”

A version of this article originally appeared on WebMD.com.

People with autism are more likely to face diabetes, high cholesterol, and heart disease than those without the neurologic condition, according to a study published in JAMA Pediatrics. Researchers also found that children with autism are especially likely to develop diabetes compared with their peers, and are at greater risk of hypertension, too.

While the link between autism and risk for obesity and gastrointestinal ailments is well-established, the new findings suggest that clinicians who care for these patients – particularly children – should focus on cardiometabolic health more broadly.

“Clinicians who are treating kids with autism need to pay more attention to this,” said Chanaka N. Kahathuduwa, MD, PhD, MPhil, of the department of neurology at Texas Tech University Health Sciences Center, in Lubbock, and a coauthor of the new study.

A pediatrician may prescribe an atypical antipsychotic medication such as risperidone to regulate the behavior of an autistic child, Dr. Kahathuduwa said, which may increase their cholesterol levels. Although this or similar drugs may be necessary in some cases, Dr. Kahathuduwa advised that clinicians explore other treatment options first.
 

Mining data from previously published studies

For the new analysis, Dr. Kahathuduwa and his colleagues pooled the results of 34 previously published studies, which included medical records of more than 276,000 people with autism and close to 8 million people without the condition.

Study participants were an average age of 31 years, and 47% were female. Some studies reported age ranges that enabled the researchers to differentiate between children and adults.

People with autism were 64% more likely to develop type 1 diabetes, 146% more likely to experience type 2 diabetes, and 46% more likely to have heart disease, overall, the study found. Children with autism were almost twice as likely as their peers to develop diabetes (184%) and high blood pressure (154%).

The study found associations, not causation, and does not include detailed data about medication prescribing patterns. While it would be ideal to understand why autism is linked to cardiometabolic risk, to address the link most effectively, Dr. Kahathuduwa said the causes likely are multifactorial. Medication history and genetics each play a role in a way that is hard to untangle. Even so, Dr. Kahathuduwa said he hoped the findings prompt clinicians to reevaluate how they treat their patients with autism.

“This may be an eye opener,” he said.

An editorial accompanying the study noted that people with autism may die up to 30 years earlier than people without autism, in part because of the physical health problems surfaced in the new research. They also are more likely than others to attempt suicide.

Elizabeth M. Weir, PhD, of the Autism Research Centre at the University of Cambridge (England) and author of the editorial, argued that current health delivery models often fail autistic people by not taking their needs into account.

Dr. Weir told this news organization that making adjustments such as dimming the lights for a light-sensitive patient or allowing people with autism to bring an advocate to appointments could build rapport.

“I diagnose autism pretty much every day and I know families get so overwhelmed with all the recommendations that we give,” said Sonia Monteiro, MD, a developmental and behavioral pediatrician at Texas Children’s Hospital in Houston. Still, Dr. Monteiro said clinicians should help parents of children with autism address the potential long-term cardiovascular risks – but to do so by layering in the information rather than merely adding more bullet points to an already long presentation.

“We know this information now, but finding a way to share that with families without overwhelming them even more, I think is challenging,” Dr. Monteiro said. “But it’s not something we can ignore.”

Dr. Kahathuduwa, Dr. Weir, and Dr. Monteiro report no relevant financial relationships.

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

People with autism are more likely to face diabetes, high cholesterol, and heart disease than those without the neurologic condition, according to a study published in JAMA Pediatrics. Researchers also found that children with autism are especially likely to develop diabetes compared with their peers, and are at greater risk of hypertension, too.

While the link between autism and risk for obesity and gastrointestinal ailments is well-established, the new findings suggest that clinicians who care for these patients – particularly children – should focus on cardiometabolic health more broadly.

“Clinicians who are treating kids with autism need to pay more attention to this,” said Chanaka N. Kahathuduwa, MD, PhD, MPhil, of the department of neurology at Texas Tech University Health Sciences Center, in Lubbock, and a coauthor of the new study.

A pediatrician may prescribe an atypical antipsychotic medication such as risperidone to regulate the behavior of an autistic child, Dr. Kahathuduwa said, which may increase their cholesterol levels. Although this or similar drugs may be necessary in some cases, Dr. Kahathuduwa advised that clinicians explore other treatment options first.
 

Mining data from previously published studies

For the new analysis, Dr. Kahathuduwa and his colleagues pooled the results of 34 previously published studies, which included medical records of more than 276,000 people with autism and close to 8 million people without the condition.

Study participants were an average age of 31 years, and 47% were female. Some studies reported age ranges that enabled the researchers to differentiate between children and adults.

People with autism were 64% more likely to develop type 1 diabetes, 146% more likely to experience type 2 diabetes, and 46% more likely to have heart disease, overall, the study found. Children with autism were almost twice as likely as their peers to develop diabetes (184%) and high blood pressure (154%).

The study found associations, not causation, and does not include detailed data about medication prescribing patterns. While it would be ideal to understand why autism is linked to cardiometabolic risk, to address the link most effectively, Dr. Kahathuduwa said the causes likely are multifactorial. Medication history and genetics each play a role in a way that is hard to untangle. Even so, Dr. Kahathuduwa said he hoped the findings prompt clinicians to reevaluate how they treat their patients with autism.

“This may be an eye opener,” he said.

An editorial accompanying the study noted that people with autism may die up to 30 years earlier than people without autism, in part because of the physical health problems surfaced in the new research. They also are more likely than others to attempt suicide.

Elizabeth M. Weir, PhD, of the Autism Research Centre at the University of Cambridge (England) and author of the editorial, argued that current health delivery models often fail autistic people by not taking their needs into account.

Dr. Weir told this news organization that making adjustments such as dimming the lights for a light-sensitive patient or allowing people with autism to bring an advocate to appointments could build rapport.

“I diagnose autism pretty much every day and I know families get so overwhelmed with all the recommendations that we give,” said Sonia Monteiro, MD, a developmental and behavioral pediatrician at Texas Children’s Hospital in Houston. Still, Dr. Monteiro said clinicians should help parents of children with autism address the potential long-term cardiovascular risks – but to do so by layering in the information rather than merely adding more bullet points to an already long presentation.

“We know this information now, but finding a way to share that with families without overwhelming them even more, I think is challenging,” Dr. Monteiro said. “But it’s not something we can ignore.”

Dr. Kahathuduwa, Dr. Weir, and Dr. Monteiro report no relevant financial relationships.

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

People with autism are more likely to face diabetes, high cholesterol, and heart disease than those without the neurologic condition, according to a study published in JAMA Pediatrics. Researchers also found that children with autism are especially likely to develop diabetes compared with their peers, and are at greater risk of hypertension, too.

While the link between autism and risk for obesity and gastrointestinal ailments is well-established, the new findings suggest that clinicians who care for these patients – particularly children – should focus on cardiometabolic health more broadly.

“Clinicians who are treating kids with autism need to pay more attention to this,” said Chanaka N. Kahathuduwa, MD, PhD, MPhil, of the department of neurology at Texas Tech University Health Sciences Center, in Lubbock, and a coauthor of the new study.

A pediatrician may prescribe an atypical antipsychotic medication such as risperidone to regulate the behavior of an autistic child, Dr. Kahathuduwa said, which may increase their cholesterol levels. Although this or similar drugs may be necessary in some cases, Dr. Kahathuduwa advised that clinicians explore other treatment options first.
 

Mining data from previously published studies

For the new analysis, Dr. Kahathuduwa and his colleagues pooled the results of 34 previously published studies, which included medical records of more than 276,000 people with autism and close to 8 million people without the condition.

Study participants were an average age of 31 years, and 47% were female. Some studies reported age ranges that enabled the researchers to differentiate between children and adults.

People with autism were 64% more likely to develop type 1 diabetes, 146% more likely to experience type 2 diabetes, and 46% more likely to have heart disease, overall, the study found. Children with autism were almost twice as likely as their peers to develop diabetes (184%) and high blood pressure (154%).

The study found associations, not causation, and does not include detailed data about medication prescribing patterns. While it would be ideal to understand why autism is linked to cardiometabolic risk, to address the link most effectively, Dr. Kahathuduwa said the causes likely are multifactorial. Medication history and genetics each play a role in a way that is hard to untangle. Even so, Dr. Kahathuduwa said he hoped the findings prompt clinicians to reevaluate how they treat their patients with autism.

“This may be an eye opener,” he said.

An editorial accompanying the study noted that people with autism may die up to 30 years earlier than people without autism, in part because of the physical health problems surfaced in the new research. They also are more likely than others to attempt suicide.

Elizabeth M. Weir, PhD, of the Autism Research Centre at the University of Cambridge (England) and author of the editorial, argued that current health delivery models often fail autistic people by not taking their needs into account.

Dr. Weir told this news organization that making adjustments such as dimming the lights for a light-sensitive patient or allowing people with autism to bring an advocate to appointments could build rapport.

“I diagnose autism pretty much every day and I know families get so overwhelmed with all the recommendations that we give,” said Sonia Monteiro, MD, a developmental and behavioral pediatrician at Texas Children’s Hospital in Houston. Still, Dr. Monteiro said clinicians should help parents of children with autism address the potential long-term cardiovascular risks – but to do so by layering in the information rather than merely adding more bullet points to an already long presentation.

“We know this information now, but finding a way to share that with families without overwhelming them even more, I think is challenging,” Dr. Monteiro said. “But it’s not something we can ignore.”

Dr. Kahathuduwa, Dr. Weir, and Dr. Monteiro report no relevant financial relationships.

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

More than 2,800 counties in the United States lack a practicing pediatric ophthalmologist, limiting easy access to specialized eye care, a new study found.
 

The review of public, online pediatric ophthalmology directories found 1,056 pediatric ophthalmologists registered. The majority of these doctors practiced in densely populated areas, leaving many poor and rural residents across the United States without a nearby doctor to visit, and with the burden of spending time and money to get care for their children.

Travel for that care may be out of reach for some, according to Hannah Walsh, a medical student at the University of Miami, who led the study published in JAMA Ophthalmology.

Ms. Walsh’s research found that the median income of families living in a county without a pediatric ophthalmologist was nearly $17,000 lower than that for families with access to such specialists (95% confidence interval, −$18,544 to −$14,389; P < .001). These families were also less likely to own a car.

“We found that counties that didn’t have access to ophthalmic care for pediatrics were already disproportionately affected by lower socioeconomic status,” she said.

Children often receive routine vision screenings through their primary care clinician, but children who fail a routine screening may need to visit a pediatric ophthalmologist for a full eye examination, according to the American Academy of Ophthalmology.

Ms. Walsh and colleagues pulled data in March 2022 on the demographics of pediatric ophthalmologists from online directories hosted by the AAO and the American Association of Pediatric Ophthalmology and Strabismus. Ms. Walsh cautioned that the directories might include eye doctors who are no longer practicing, or there might be specialists who had not registered for the databases.

Yasmin Bradfield, MD, a pediatric ophthalmologist at the University of Wisconsin–Madison, noted that after the study published, pediatric ophthalmologists from Vermont and New Mexico notified study authors and AAPOS that they are practicing in the states.

Dr. Bradfield, a board member of AAPOS who also heads the organization’s recruitment task force, said the organization is aware of only one state – Wyoming – without a currently practicing pediatric ophthalmologist.

But based on the March 2022 data, Ms. Walsh and her colleagues found four states – New Mexico, North Dakota, South Dakota, and Vermont – did not have any pediatric ophthalmologists listed in directories for the organizations. Meanwhile, the country’s most populous states – California, New York, Florida, and Texas – had the most pediatric ophthalmologists.

For every million people, the study identified 7.7 pediatric ophthalmologists nationwide.

Julius T. Oatts, MD, the lead author of an accompanying editorial, said the findings are “valuable and sobering.” Even in San Francisco, where Dr. Oatts practices, most pediatric eye specialists have 6-month wait lists, he said.

Not fixing the shortage of children’s eye doctors could carry lifetime consequences, Dr. Oatts and his colleagues warned.

“Vision and eye health represent an important health barrier to learning in children,” Dr. Oatts and his colleagues wrote. “Lack of access to pediatric vision screening and care also contributes to the academic achievement gap and educational disparities.”

Dr. Bradfield said that disparities in pediatric ophthalmology care could leave some children at risk for losing their vision or never being able to see 20/20. Parents living in areas without a specialist may decide to instead visit an optometrist, but they are not trained to treat serious cases, such as strabismus, and only test and diagnose vision changes, according to AAPOS.

“If we don’t get to the kids in time, they can lose vision permanently, even if it’s something as simple as they just need glasses as a toddler,” Dr. Bradfield said.

Dr. Bradfield said AAPOS is recruiting new pediatric ophthalmologists by offering fellowships for medical students to attend the association’s annual conference and creating shadowing opportunities for students. The society also will release a survey of pediatric ophthalmology salaries to dispel rumors that the specialty does not have lucrative wages.

Ms. Walsh said she was interested in looking at disparities in pediatric ophthalmology care, in part, because she was surprised by how few of her classmates attending medical school were interested in the field of study.

“I hope it encourages ophthalmologists to consider pediatric ophthalmology, or to consider volunteering their time, or going to underserved areas to provide care to families that really are in need,” she said.

Coauthor Jayanth Sridhar, MD, reported receiving personal fees from Alcon, Apellis, Allergan, Dutch Ophthalmic Research Center, Genentech, OcuTerra Therapeutics, and Regeneron outside the submitted work. The other authors and the editorialists report no relevant financial relationships.

*This article was updated on 2/2/2023.

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

More than 2,800 counties in the United States lack a practicing pediatric ophthalmologist, limiting easy access to specialized eye care, a new study found.
 

The review of public, online pediatric ophthalmology directories found 1,056 pediatric ophthalmologists registered. The majority of these doctors practiced in densely populated areas, leaving many poor and rural residents across the United States without a nearby doctor to visit, and with the burden of spending time and money to get care for their children.

Travel for that care may be out of reach for some, according to Hannah Walsh, a medical student at the University of Miami, who led the study published in JAMA Ophthalmology.

Ms. Walsh’s research found that the median income of families living in a county without a pediatric ophthalmologist was nearly $17,000 lower than that for families with access to such specialists (95% confidence interval, −$18,544 to −$14,389; P < .001). These families were also less likely to own a car.

“We found that counties that didn’t have access to ophthalmic care for pediatrics were already disproportionately affected by lower socioeconomic status,” she said.

Children often receive routine vision screenings through their primary care clinician, but children who fail a routine screening may need to visit a pediatric ophthalmologist for a full eye examination, according to the American Academy of Ophthalmology.

Ms. Walsh and colleagues pulled data in March 2022 on the demographics of pediatric ophthalmologists from online directories hosted by the AAO and the American Association of Pediatric Ophthalmology and Strabismus. Ms. Walsh cautioned that the directories might include eye doctors who are no longer practicing, or there might be specialists who had not registered for the databases.

Yasmin Bradfield, MD, a pediatric ophthalmologist at the University of Wisconsin–Madison, noted that after the study published, pediatric ophthalmologists from Vermont and New Mexico notified study authors and AAPOS that they are practicing in the states.

Dr. Bradfield, a board member of AAPOS who also heads the organization’s recruitment task force, said the organization is aware of only one state – Wyoming – without a currently practicing pediatric ophthalmologist.

But based on the March 2022 data, Ms. Walsh and her colleagues found four states – New Mexico, North Dakota, South Dakota, and Vermont – did not have any pediatric ophthalmologists listed in directories for the organizations. Meanwhile, the country’s most populous states – California, New York, Florida, and Texas – had the most pediatric ophthalmologists.

For every million people, the study identified 7.7 pediatric ophthalmologists nationwide.

Julius T. Oatts, MD, the lead author of an accompanying editorial, said the findings are “valuable and sobering.” Even in San Francisco, where Dr. Oatts practices, most pediatric eye specialists have 6-month wait lists, he said.

Not fixing the shortage of children’s eye doctors could carry lifetime consequences, Dr. Oatts and his colleagues warned.

“Vision and eye health represent an important health barrier to learning in children,” Dr. Oatts and his colleagues wrote. “Lack of access to pediatric vision screening and care also contributes to the academic achievement gap and educational disparities.”

Dr. Bradfield said that disparities in pediatric ophthalmology care could leave some children at risk for losing their vision or never being able to see 20/20. Parents living in areas without a specialist may decide to instead visit an optometrist, but they are not trained to treat serious cases, such as strabismus, and only test and diagnose vision changes, according to AAPOS.

“If we don’t get to the kids in time, they can lose vision permanently, even if it’s something as simple as they just need glasses as a toddler,” Dr. Bradfield said.

Dr. Bradfield said AAPOS is recruiting new pediatric ophthalmologists by offering fellowships for medical students to attend the association’s annual conference and creating shadowing opportunities for students. The society also will release a survey of pediatric ophthalmology salaries to dispel rumors that the specialty does not have lucrative wages.

Ms. Walsh said she was interested in looking at disparities in pediatric ophthalmology care, in part, because she was surprised by how few of her classmates attending medical school were interested in the field of study.

“I hope it encourages ophthalmologists to consider pediatric ophthalmology, or to consider volunteering their time, or going to underserved areas to provide care to families that really are in need,” she said.

Coauthor Jayanth Sridhar, MD, reported receiving personal fees from Alcon, Apellis, Allergan, Dutch Ophthalmic Research Center, Genentech, OcuTerra Therapeutics, and Regeneron outside the submitted work. The other authors and the editorialists report no relevant financial relationships.

*This article was updated on 2/2/2023.

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

More than 2,800 counties in the United States lack a practicing pediatric ophthalmologist, limiting easy access to specialized eye care, a new study found.
 

The review of public, online pediatric ophthalmology directories found 1,056 pediatric ophthalmologists registered. The majority of these doctors practiced in densely populated areas, leaving many poor and rural residents across the United States without a nearby doctor to visit, and with the burden of spending time and money to get care for their children.

Travel for that care may be out of reach for some, according to Hannah Walsh, a medical student at the University of Miami, who led the study published in JAMA Ophthalmology.

Ms. Walsh’s research found that the median income of families living in a county without a pediatric ophthalmologist was nearly $17,000 lower than that for families with access to such specialists (95% confidence interval, −$18,544 to −$14,389; P < .001). These families were also less likely to own a car.

“We found that counties that didn’t have access to ophthalmic care for pediatrics were already disproportionately affected by lower socioeconomic status,” she said.

Children often receive routine vision screenings through their primary care clinician, but children who fail a routine screening may need to visit a pediatric ophthalmologist for a full eye examination, according to the American Academy of Ophthalmology.

Ms. Walsh and colleagues pulled data in March 2022 on the demographics of pediatric ophthalmologists from online directories hosted by the AAO and the American Association of Pediatric Ophthalmology and Strabismus. Ms. Walsh cautioned that the directories might include eye doctors who are no longer practicing, or there might be specialists who had not registered for the databases.

Yasmin Bradfield, MD, a pediatric ophthalmologist at the University of Wisconsin–Madison, noted that after the study published, pediatric ophthalmologists from Vermont and New Mexico notified study authors and AAPOS that they are practicing in the states.

Dr. Bradfield, a board member of AAPOS who also heads the organization’s recruitment task force, said the organization is aware of only one state – Wyoming – without a currently practicing pediatric ophthalmologist.

But based on the March 2022 data, Ms. Walsh and her colleagues found four states – New Mexico, North Dakota, South Dakota, and Vermont – did not have any pediatric ophthalmologists listed in directories for the organizations. Meanwhile, the country’s most populous states – California, New York, Florida, and Texas – had the most pediatric ophthalmologists.

For every million people, the study identified 7.7 pediatric ophthalmologists nationwide.

Julius T. Oatts, MD, the lead author of an accompanying editorial, said the findings are “valuable and sobering.” Even in San Francisco, where Dr. Oatts practices, most pediatric eye specialists have 6-month wait lists, he said.

Not fixing the shortage of children’s eye doctors could carry lifetime consequences, Dr. Oatts and his colleagues warned.

“Vision and eye health represent an important health barrier to learning in children,” Dr. Oatts and his colleagues wrote. “Lack of access to pediatric vision screening and care also contributes to the academic achievement gap and educational disparities.”

Dr. Bradfield said that disparities in pediatric ophthalmology care could leave some children at risk for losing their vision or never being able to see 20/20. Parents living in areas without a specialist may decide to instead visit an optometrist, but they are not trained to treat serious cases, such as strabismus, and only test and diagnose vision changes, according to AAPOS.

“If we don’t get to the kids in time, they can lose vision permanently, even if it’s something as simple as they just need glasses as a toddler,” Dr. Bradfield said.

Dr. Bradfield said AAPOS is recruiting new pediatric ophthalmologists by offering fellowships for medical students to attend the association’s annual conference and creating shadowing opportunities for students. The society also will release a survey of pediatric ophthalmology salaries to dispel rumors that the specialty does not have lucrative wages.

Ms. Walsh said she was interested in looking at disparities in pediatric ophthalmology care, in part, because she was surprised by how few of her classmates attending medical school were interested in the field of study.

“I hope it encourages ophthalmologists to consider pediatric ophthalmology, or to consider volunteering their time, or going to underserved areas to provide care to families that really are in need,” she said.

Coauthor Jayanth Sridhar, MD, reported receiving personal fees from Alcon, Apellis, Allergan, Dutch Ophthalmic Research Center, Genentech, OcuTerra Therapeutics, and Regeneron outside the submitted work. The other authors and the editorialists report no relevant financial relationships.

*This article was updated on 2/2/2023.

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

ORLANDO – Three weeks after a course of trimethoprim/sulfamethoxazole (Bactrim), a young female patient developed facial edema that involved “dusky erythematous papules” that were itchy. The eruption spread away from the head and her transaminase levels were “dramatic,” in the 700s, said Kalyani S. Marathe, MD, MPH, associate professor of dermatology and pediatrics at the University of Cincinnati.

Dr. Marathe, director of the division of dermatology at Cincinnati Children’s Hospital, reviewed this case in a presentation on pediatric dermatologic emergencies at the ODAC Dermatology, Aesthetic & Surgery Conference, pointing out potential pitfalls and important aspects that might require swift action.

The patient was diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS).

Facial involvement is common in pediatric cases of DRESS, but edema of the face is less common in children than adults, Dr. Marathe said.

Antiepileptic medications are the most common cause of DRESS, followed by antibiotics – most often, vancomycin and trimethoprim/sulfamethoxazole, she said. But sometimes the trigger is not clear, she noted, recalling a vexing case she once saw in which IV contrast was eventually identified as the cause.

When DRESS is suspected, she said, lab work should be done during the acute eruption and after resolution. This should include CBC, liver function tests, creatinine, and urinalysis, and human herpesvirus 6 (HHV-6) and thyroid testing.

Treatment typically includes supportive care, unless symptoms are systemic, or if there is impending liver failure, when steroids, cyclosporine, or IVIG can be used.

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): Mortality rates when these diseases overlap is 4%, Dr. Marathe said. Clues to diagnosing this other medication-induced condition include involvement of the palms and the soles of the feet; presence of the Nikolsky sign in which the top layers of the skin slip away from the lower layers when rubbed; mucosal involvement, which often precedes cutaneous involvement; and these symptoms occurring within the first 8 weeks of taking a medication, which are most commonly antibiotics and anti-epileptics.

Dr. Marathe underscored how important it is to get ophthalmology involved right away, because of the risk of vision loss. Amniotic membrane transfer to the eye at the time of diagnosis has been found to produce dramatically better outcomes, she said. The membrane has anti-inflammatory and antiscarring properties and can promote wound healing on the surface of the eye.

“I would recommend getting your ophthalmology team on board early because they have to advocate for these patients,” she said.

Corticosteroids and IVIG can improve ocular outcomes, but cyclosporine is associated with better mortality outcomes, she said. Emerging data on etanercept has also led to more use of that drug, she said.

Erythema multiforme (EM): unlike urticaria, multiforme EM can have mucosal involvement, Dr. Marathe said. Clinicians should look for three zones of color: A central duskiness, a rim of pallor, and a ring of erythema.

EM is triggered by a virus, which is usually herpes simplex virus (HSV). But she added that HSV is not always found. “So, there are certainly other triggers out there that we just haven’t identified,” she said.

If HSV is suspected, oral acyclovir is effective, she noted.

Other cases might not be as straightforward. Dr. Marathe said that during her fellowship, she saw a patient with EM that was controlled only by IVIG, so it was administered every 3 months. In that case, the trigger was never found.

Multisystem inflammatory syndrome in children (MIS-C): This syndrome can follow COVID-19 infection, and usually presents with 3-5 days of fever after COVID has resolved. It can include gastrointestinal, cardiorespiratory, and neurocognitive symptoms.

The skin presentation is mainly a morbilliform pattern, but clinicians might also see conjunctival involvement, mucosal involvement, and “COVID toes,” painful red or purple lesions on the toes.

Treatment is usually IVIG and systemic corticosteroids, with the treatment course depending on the severity.

MIS-C was initially thought to be Kawasaki’s disease, another autoinflammatory disorder, which is related but distinct, Dr. Marathe said.

Patients with MIS-C “are usually going to have COVID-positive antibodies,” she said. But since almost everybody may have COVID antibodies, “it’s not usually a helpful test for you now. But early on, that’s what we used as helpful indicator.”

Dr. Marathe reported no relevant financial relationships.

ORLANDO – Three weeks after a course of trimethoprim/sulfamethoxazole (Bactrim), a young female patient developed facial edema that involved “dusky erythematous papules” that were itchy. The eruption spread away from the head and her transaminase levels were “dramatic,” in the 700s, said Kalyani S. Marathe, MD, MPH, associate professor of dermatology and pediatrics at the University of Cincinnati.

Dr. Marathe, director of the division of dermatology at Cincinnati Children’s Hospital, reviewed this case in a presentation on pediatric dermatologic emergencies at the ODAC Dermatology, Aesthetic & Surgery Conference, pointing out potential pitfalls and important aspects that might require swift action.

The patient was diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS).

Facial involvement is common in pediatric cases of DRESS, but edema of the face is less common in children than adults, Dr. Marathe said.

Antiepileptic medications are the most common cause of DRESS, followed by antibiotics – most often, vancomycin and trimethoprim/sulfamethoxazole, she said. But sometimes the trigger is not clear, she noted, recalling a vexing case she once saw in which IV contrast was eventually identified as the cause.

When DRESS is suspected, she said, lab work should be done during the acute eruption and after resolution. This should include CBC, liver function tests, creatinine, and urinalysis, and human herpesvirus 6 (HHV-6) and thyroid testing.

Treatment typically includes supportive care, unless symptoms are systemic, or if there is impending liver failure, when steroids, cyclosporine, or IVIG can be used.

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): Mortality rates when these diseases overlap is 4%, Dr. Marathe said. Clues to diagnosing this other medication-induced condition include involvement of the palms and the soles of the feet; presence of the Nikolsky sign in which the top layers of the skin slip away from the lower layers when rubbed; mucosal involvement, which often precedes cutaneous involvement; and these symptoms occurring within the first 8 weeks of taking a medication, which are most commonly antibiotics and anti-epileptics.

Dr. Marathe underscored how important it is to get ophthalmology involved right away, because of the risk of vision loss. Amniotic membrane transfer to the eye at the time of diagnosis has been found to produce dramatically better outcomes, she said. The membrane has anti-inflammatory and antiscarring properties and can promote wound healing on the surface of the eye.

“I would recommend getting your ophthalmology team on board early because they have to advocate for these patients,” she said.

Corticosteroids and IVIG can improve ocular outcomes, but cyclosporine is associated with better mortality outcomes, she said. Emerging data on etanercept has also led to more use of that drug, she said.

Erythema multiforme (EM): unlike urticaria, multiforme EM can have mucosal involvement, Dr. Marathe said. Clinicians should look for three zones of color: A central duskiness, a rim of pallor, and a ring of erythema.

EM is triggered by a virus, which is usually herpes simplex virus (HSV). But she added that HSV is not always found. “So, there are certainly other triggers out there that we just haven’t identified,” she said.

If HSV is suspected, oral acyclovir is effective, she noted.

Other cases might not be as straightforward. Dr. Marathe said that during her fellowship, she saw a patient with EM that was controlled only by IVIG, so it was administered every 3 months. In that case, the trigger was never found.

Multisystem inflammatory syndrome in children (MIS-C): This syndrome can follow COVID-19 infection, and usually presents with 3-5 days of fever after COVID has resolved. It can include gastrointestinal, cardiorespiratory, and neurocognitive symptoms.

The skin presentation is mainly a morbilliform pattern, but clinicians might also see conjunctival involvement, mucosal involvement, and “COVID toes,” painful red or purple lesions on the toes.

Treatment is usually IVIG and systemic corticosteroids, with the treatment course depending on the severity.

MIS-C was initially thought to be Kawasaki’s disease, another autoinflammatory disorder, which is related but distinct, Dr. Marathe said.

Patients with MIS-C “are usually going to have COVID-positive antibodies,” she said. But since almost everybody may have COVID antibodies, “it’s not usually a helpful test for you now. But early on, that’s what we used as helpful indicator.”

Dr. Marathe reported no relevant financial relationships.

ORLANDO – Three weeks after a course of trimethoprim/sulfamethoxazole (Bactrim), a young female patient developed facial edema that involved “dusky erythematous papules” that were itchy. The eruption spread away from the head and her transaminase levels were “dramatic,” in the 700s, said Kalyani S. Marathe, MD, MPH, associate professor of dermatology and pediatrics at the University of Cincinnati.

Dr. Marathe, director of the division of dermatology at Cincinnati Children’s Hospital, reviewed this case in a presentation on pediatric dermatologic emergencies at the ODAC Dermatology, Aesthetic & Surgery Conference, pointing out potential pitfalls and important aspects that might require swift action.

The patient was diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS).

Facial involvement is common in pediatric cases of DRESS, but edema of the face is less common in children than adults, Dr. Marathe said.

Antiepileptic medications are the most common cause of DRESS, followed by antibiotics – most often, vancomycin and trimethoprim/sulfamethoxazole, she said. But sometimes the trigger is not clear, she noted, recalling a vexing case she once saw in which IV contrast was eventually identified as the cause.

When DRESS is suspected, she said, lab work should be done during the acute eruption and after resolution. This should include CBC, liver function tests, creatinine, and urinalysis, and human herpesvirus 6 (HHV-6) and thyroid testing.

Treatment typically includes supportive care, unless symptoms are systemic, or if there is impending liver failure, when steroids, cyclosporine, or IVIG can be used.

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): Mortality rates when these diseases overlap is 4%, Dr. Marathe said. Clues to diagnosing this other medication-induced condition include involvement of the palms and the soles of the feet; presence of the Nikolsky sign in which the top layers of the skin slip away from the lower layers when rubbed; mucosal involvement, which often precedes cutaneous involvement; and these symptoms occurring within the first 8 weeks of taking a medication, which are most commonly antibiotics and anti-epileptics.

Dr. Marathe underscored how important it is to get ophthalmology involved right away, because of the risk of vision loss. Amniotic membrane transfer to the eye at the time of diagnosis has been found to produce dramatically better outcomes, she said. The membrane has anti-inflammatory and antiscarring properties and can promote wound healing on the surface of the eye.

“I would recommend getting your ophthalmology team on board early because they have to advocate for these patients,” she said.

Corticosteroids and IVIG can improve ocular outcomes, but cyclosporine is associated with better mortality outcomes, she said. Emerging data on etanercept has also led to more use of that drug, she said.

Erythema multiforme (EM): unlike urticaria, multiforme EM can have mucosal involvement, Dr. Marathe said. Clinicians should look for three zones of color: A central duskiness, a rim of pallor, and a ring of erythema.

EM is triggered by a virus, which is usually herpes simplex virus (HSV). But she added that HSV is not always found. “So, there are certainly other triggers out there that we just haven’t identified,” she said.

If HSV is suspected, oral acyclovir is effective, she noted.

Other cases might not be as straightforward. Dr. Marathe said that during her fellowship, she saw a patient with EM that was controlled only by IVIG, so it was administered every 3 months. In that case, the trigger was never found.

Multisystem inflammatory syndrome in children (MIS-C): This syndrome can follow COVID-19 infection, and usually presents with 3-5 days of fever after COVID has resolved. It can include gastrointestinal, cardiorespiratory, and neurocognitive symptoms.

The skin presentation is mainly a morbilliform pattern, but clinicians might also see conjunctival involvement, mucosal involvement, and “COVID toes,” painful red or purple lesions on the toes.

Treatment is usually IVIG and systemic corticosteroids, with the treatment course depending on the severity.

MIS-C was initially thought to be Kawasaki’s disease, another autoinflammatory disorder, which is related but distinct, Dr. Marathe said.

Patients with MIS-C “are usually going to have COVID-positive antibodies,” she said. But since almost everybody may have COVID antibodies, “it’s not usually a helpful test for you now. But early on, that’s what we used as helpful indicator.”

Dr. Marathe reported no relevant financial relationships.