MDedge Pediatrics

Sleeping with a light on can play havoc with insulin levels and consequently impair the response to glucose, a 2-night sleep-lab study of 20 people indicates.

“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.

And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.

The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.

Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”

“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.

That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
 

How light during sleep may affect insulin, melatonin, heart rate

Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.

In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.

Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).

However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.

The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.

Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.

The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”

The dim light condition was less than 3 lux, which is dimmer than a night light.

When participants were awake, the room lighting was 240 lux.

Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m².

The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.  

They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.

Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.

Participants slept for a similar time, around 7 hours, in both conditions.

Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.

In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.

The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.

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

Sleeping with a light on can play havoc with insulin levels and consequently impair the response to glucose, a 2-night sleep-lab study of 20 people indicates.

“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.

And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.

The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.

Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”

“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.

That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
 

How light during sleep may affect insulin, melatonin, heart rate

Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.

In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.

Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).

However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.

The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.

Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.

The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”

The dim light condition was less than 3 lux, which is dimmer than a night light.

When participants were awake, the room lighting was 240 lux.

Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m².

The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.  

They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.

Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.

Participants slept for a similar time, around 7 hours, in both conditions.

Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.

In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.

The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.

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

Sleeping with a light on can play havoc with insulin levels and consequently impair the response to glucose, a 2-night sleep-lab study of 20 people indicates.

“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.

And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.

The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.

Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”

“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.

That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
 

How light during sleep may affect insulin, melatonin, heart rate

Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.

In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.

Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).

However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.

The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.

Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.

The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”

The dim light condition was less than 3 lux, which is dimmer than a night light.

When participants were awake, the room lighting was 240 lux.

Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m².

The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.  

They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.

Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.

Participants slept for a similar time, around 7 hours, in both conditions.

Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.

In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.

The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.

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

Treatment of systemic juvenile idiopathic arthritis (sJIA) should emphasize early use of conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs), compared with the previous reliance on NSAIDs and glucocorticoids, according to new guidelines from the American College of Rheumatology. The recently published 2021 guidelines focus on therapeutic approaches for oligoarthritis, temporomandibular joint (TMJ) arthritis, and sJIA.

“Systemic JIA should be treated early with biologics to rapidly bring disease under control and to avoid long-term use of glucocorticoids,” Karen Onel, MD, chief of the division of pediatric rheumatology at Weill Cornell Medicine, New York, and lead author of the guidelines, told this news organization. “Unfortunately, biologics can and are frequently denied for first-line use. For this reason, the guidelines are critically important as they demonstrate that first-line use of biologics are standard of care for the treatment of sJIA.”

The new publication is the second part of the ACR’s process to update JIA guidelines that began in 2017 and complements the release in 2019 of guidelines on the management of nonsystemic polyarthritis, sacroiliitis, and enthesitis, as well as a separate guidance on JIA-associated uveitis. The new guidelines include a second publication focused on nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Both sets of guidelines grew out of a 15-member panel that included young adults with JIA and caregivers of children with JIA, and which required at least 70% agreement on recommendations.

“Though the scope of the two guidelines differed, one thing they had in common is the recognition of the importance of shared decision-making with the patient/caregiver,” Dr. Onel said. “Not every decision will be appropriate for every patient, which is why it was so instrumental to receive input from both patients and caregivers when creating these recommendations.”
 

Oligoarticular and TMJ arthritis

Oligoarticular and TMJ arthritis have similar recommendations, beginning with NSAIDs conditionally recommended and intra-articular glucocorticoids (IAGCs) strongly recommended as part of initial therapy. For oligoarticular arthritis, the guidelines specifically include a strong recommendation of triamcinolone hexacetonide as the preferred agent; no preferred agent is recommended for TMJ arthritis.

“The one thing that the panel was unanimous about was the use of triamcinolone hexacetonide for intra-articular steroid injections in oligoarticular kids,” Susan Shenoi, MBBS, MS, an associate professor and clinical director of pediatric rheumatology at Seattle Children’s Hospital and Research Center, said in an interview. “Triamcinolone hexacetonide has not been available recently, and through advocacy efforts, there is now a pathway to get that medication,” added Dr. Shenoi, a coauthor on the guidelines.

Dr. Onel said that “triamcinolone hexacetonide has been shown to be superior to alternative injectable glucocorticoids in achieving and maintaining remission in children with JIA,” but its unavailability meant physicians had to consider less effective, more potent, or more costly alternatives.” To address the shortage, “the FDA allowed the importation of one particular formulation of triamcinolone hexacetonide [Hexatrione 2%] specifically for joint injections in patients with JIA.”

The guidelines conditionally recommend against oral glucocorticoids for initial therapy for both oligoarticular and TMJ arthritis. In fact, throughout the guidelines it’s clear that the authors emphasize using steroids as little as possible, Dr. Shenoi said.

“Steroids are great anti-inflammatories, but in kids we worry about the long-term effects on growth and metabolism, and now we have many more DMARDs available,” Dr. Shenoi said.

The guidelines strongly recommend conventional synthetic DMARDs for patients with either of these diseases who cannot tolerate or do not respond to NSAIDs or IAGCs, with methotrexate conditionally recommended over leflunomide (Arava) for TMJ and over leflunomide, sulfasalazine (Azulfidine, Sulfazine), and hydroxychloroquine, respectively, for oligoarticular arthritis.

“NSAIDs remain widely used despite evidence supporting early use of DMARDs,” Dr. Onel said. “NSAIDs are readily available and familiar; however, they will not prevent disease progression. These guidelines should encourage short courses of NSAIDs only.”

If patients do not respond to or cannot tolerate NSAIDs, IAGCs, and at least one conventional DMARD, the guidelines strongly recommend a biologic DMARD for oligoarticular arthritis and conditionally recommend one for TMJ arthritis, without any preferences to the specific agent.

The guidelines also advise using validated disease activity measures to guide treatment decisions.

“The most important thing when you’re looking at these patients is to determine, do they have active disease or not?” Dr. Shenoi said. “If they have active disease, then you really want to step up therapy.” Using the relatively new concept of treat-to-target, Dr. Shenoi added that a crucial part of shared decision-making with the family is identifying the most appropriate target for that family “and then really trying hard to achieve that target.”

The guidelines also list risk factors for poor outcome that can be used to guide treatment decisions.

“Specific involvement of key joints, such as TMJ, wrist, sacroiliac, hip, and ankle, and other features were considered reasonable justification for early escalation of therapy,” Dr. Onel said. Other features included presence of erosive disease or enthesitis, delay in diagnosis, elevated levels of inflammation markers, and symmetric disease. “Moving quickly may be needed for a patient who is rapidly worsening, while moving slower may be appropriate for somebody who has improved substantially, but not fully.”

Systemic JIA with and without macrophage activation syndrome

For systemic JIA without macrophage activation syndrome (MAS), the guidelines similarly advise against oral glucocorticoids as initial monotherapy while conditionally recommending NSAIDs for initial monotherapy. Where the guidelines differ most from those for oligoarticular and TMJ arthritis is in progression of DMARD use, with a strong recommendation against conventional synthetic DMARDs as an initial monotherapy and interleukin-1 and IL-6 inhibitors conditionally recommended for initial monotherapy.

For patients who don’t adequately respond to NSAIDs or glucocorticoids, IL-1 and IL-6 inhibitors are strongly recommended over a single or combination of conventional DMARDs. Residual arthritis or an incomplete response to IL-1 or IL-6 inhibitors should lead next to biologic or conventional DMARDs instead of long-term glucocorticoids.

For patients with MAS, the guidelines conditionally recommend IL-1 and IL-6 inhibitors over calcineurin inhibitor monotherapy to reach inactive disease and MAS resolution, with glucocorticoids conditionally recommended in initial treatment. Again, however, for patients with incomplete responses to IL-1 or IL-6 inhibitors or with residual arthritis, the guidelines advise biologic or conventional DMARDs over long-term glucocorticoids.

In patients with sJIA with or without a history of MAS who have inactive disease, practitioners should taper and discontinue glucocorticoids (a strong recommendation). A conditional recommendation for tapering and discontinuing biologic DMARDs follows attainment of inactive disease.

Beyond pharmacology

Although many of the nonpharmacologic recommendations did not have strong evidence based on assessment with Grading of Recommendations Assessment, Development, and Evaluation methodology, consensus was more often the case than not, Dr. Onel said, such as with vaccination.

“There was strong support for the use of immunizations in children with JIA and specific guidance for children with JIA receiving immunosuppression, not on immunosuppression, and children who are underimmunized or unimmunized,” she said. “Although the supportive evidence was very low as per GRADE, panel members were strongly in favor [of immunizations], given risk of infection for immunosuppressed children as well as the preponderance of evidence in similar disease states, such as IBD [inflammatory bowel disease].”

An area with less consensus was whether to check antibody titers for vaccine-preventable childhood infections before beginning immunosuppressive medication, but more panelists opposed the practice than supported it, Dr. Onel said.

“Some panelists felt that the information might be useful for risk management in case of an outbreak or exposure,” she said. “Most believed that screening a fully immunized child was of low benefit and might delay treatment and incur unnecessary cost.”

The process of developing the documents also reveals where the biggest gaps are in research. 

“One of the things that we should strive for in the future is really to do more systematic studies so we have better quality of evidence going forward,” Dr. Shenoi said. Overall, however, the guidelines also reveal the progress made in treatment of JIA.

“We now know some of the key cytokines that are involved in the disease pathogenesis, and we have effective therapies for some of these pathways,” Dr. Shenoi said. “We used to use a lot more toxic medication for systemic JIA, and in past decades, these patients used to be on steroids forever. Now we have targeted therapies, and we have some patients who don’t ever need steroids because people are moving toward targeted therapies and having good results. That’s a huge step forward in the field.”

The research was funded by the ACR. Dr. Shenoi has been a consultant for Pfizer. Dr. Onel disclosed no relevant financial relationships.

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

Treatment of systemic juvenile idiopathic arthritis (sJIA) should emphasize early use of conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs), compared with the previous reliance on NSAIDs and glucocorticoids, according to new guidelines from the American College of Rheumatology. The recently published 2021 guidelines focus on therapeutic approaches for oligoarthritis, temporomandibular joint (TMJ) arthritis, and sJIA.

“Systemic JIA should be treated early with biologics to rapidly bring disease under control and to avoid long-term use of glucocorticoids,” Karen Onel, MD, chief of the division of pediatric rheumatology at Weill Cornell Medicine, New York, and lead author of the guidelines, told this news organization. “Unfortunately, biologics can and are frequently denied for first-line use. For this reason, the guidelines are critically important as they demonstrate that first-line use of biologics are standard of care for the treatment of sJIA.”

The new publication is the second part of the ACR’s process to update JIA guidelines that began in 2017 and complements the release in 2019 of guidelines on the management of nonsystemic polyarthritis, sacroiliitis, and enthesitis, as well as a separate guidance on JIA-associated uveitis. The new guidelines include a second publication focused on nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Both sets of guidelines grew out of a 15-member panel that included young adults with JIA and caregivers of children with JIA, and which required at least 70% agreement on recommendations.

“Though the scope of the two guidelines differed, one thing they had in common is the recognition of the importance of shared decision-making with the patient/caregiver,” Dr. Onel said. “Not every decision will be appropriate for every patient, which is why it was so instrumental to receive input from both patients and caregivers when creating these recommendations.”
 

Oligoarticular and TMJ arthritis

Oligoarticular and TMJ arthritis have similar recommendations, beginning with NSAIDs conditionally recommended and intra-articular glucocorticoids (IAGCs) strongly recommended as part of initial therapy. For oligoarticular arthritis, the guidelines specifically include a strong recommendation of triamcinolone hexacetonide as the preferred agent; no preferred agent is recommended for TMJ arthritis.

“The one thing that the panel was unanimous about was the use of triamcinolone hexacetonide for intra-articular steroid injections in oligoarticular kids,” Susan Shenoi, MBBS, MS, an associate professor and clinical director of pediatric rheumatology at Seattle Children’s Hospital and Research Center, said in an interview. “Triamcinolone hexacetonide has not been available recently, and through advocacy efforts, there is now a pathway to get that medication,” added Dr. Shenoi, a coauthor on the guidelines.

Dr. Onel said that “triamcinolone hexacetonide has been shown to be superior to alternative injectable glucocorticoids in achieving and maintaining remission in children with JIA,” but its unavailability meant physicians had to consider less effective, more potent, or more costly alternatives.” To address the shortage, “the FDA allowed the importation of one particular formulation of triamcinolone hexacetonide [Hexatrione 2%] specifically for joint injections in patients with JIA.”

The guidelines conditionally recommend against oral glucocorticoids for initial therapy for both oligoarticular and TMJ arthritis. In fact, throughout the guidelines it’s clear that the authors emphasize using steroids as little as possible, Dr. Shenoi said.

“Steroids are great anti-inflammatories, but in kids we worry about the long-term effects on growth and metabolism, and now we have many more DMARDs available,” Dr. Shenoi said.

The guidelines strongly recommend conventional synthetic DMARDs for patients with either of these diseases who cannot tolerate or do not respond to NSAIDs or IAGCs, with methotrexate conditionally recommended over leflunomide (Arava) for TMJ and over leflunomide, sulfasalazine (Azulfidine, Sulfazine), and hydroxychloroquine, respectively, for oligoarticular arthritis.

“NSAIDs remain widely used despite evidence supporting early use of DMARDs,” Dr. Onel said. “NSAIDs are readily available and familiar; however, they will not prevent disease progression. These guidelines should encourage short courses of NSAIDs only.”

If patients do not respond to or cannot tolerate NSAIDs, IAGCs, and at least one conventional DMARD, the guidelines strongly recommend a biologic DMARD for oligoarticular arthritis and conditionally recommend one for TMJ arthritis, without any preferences to the specific agent.

The guidelines also advise using validated disease activity measures to guide treatment decisions.

“The most important thing when you’re looking at these patients is to determine, do they have active disease or not?” Dr. Shenoi said. “If they have active disease, then you really want to step up therapy.” Using the relatively new concept of treat-to-target, Dr. Shenoi added that a crucial part of shared decision-making with the family is identifying the most appropriate target for that family “and then really trying hard to achieve that target.”

The guidelines also list risk factors for poor outcome that can be used to guide treatment decisions.

“Specific involvement of key joints, such as TMJ, wrist, sacroiliac, hip, and ankle, and other features were considered reasonable justification for early escalation of therapy,” Dr. Onel said. Other features included presence of erosive disease or enthesitis, delay in diagnosis, elevated levels of inflammation markers, and symmetric disease. “Moving quickly may be needed for a patient who is rapidly worsening, while moving slower may be appropriate for somebody who has improved substantially, but not fully.”

Systemic JIA with and without macrophage activation syndrome

For systemic JIA without macrophage activation syndrome (MAS), the guidelines similarly advise against oral glucocorticoids as initial monotherapy while conditionally recommending NSAIDs for initial monotherapy. Where the guidelines differ most from those for oligoarticular and TMJ arthritis is in progression of DMARD use, with a strong recommendation against conventional synthetic DMARDs as an initial monotherapy and interleukin-1 and IL-6 inhibitors conditionally recommended for initial monotherapy.

For patients who don’t adequately respond to NSAIDs or glucocorticoids, IL-1 and IL-6 inhibitors are strongly recommended over a single or combination of conventional DMARDs. Residual arthritis or an incomplete response to IL-1 or IL-6 inhibitors should lead next to biologic or conventional DMARDs instead of long-term glucocorticoids.

For patients with MAS, the guidelines conditionally recommend IL-1 and IL-6 inhibitors over calcineurin inhibitor monotherapy to reach inactive disease and MAS resolution, with glucocorticoids conditionally recommended in initial treatment. Again, however, for patients with incomplete responses to IL-1 or IL-6 inhibitors or with residual arthritis, the guidelines advise biologic or conventional DMARDs over long-term glucocorticoids.

In patients with sJIA with or without a history of MAS who have inactive disease, practitioners should taper and discontinue glucocorticoids (a strong recommendation). A conditional recommendation for tapering and discontinuing biologic DMARDs follows attainment of inactive disease.

Beyond pharmacology

Although many of the nonpharmacologic recommendations did not have strong evidence based on assessment with Grading of Recommendations Assessment, Development, and Evaluation methodology, consensus was more often the case than not, Dr. Onel said, such as with vaccination.

“There was strong support for the use of immunizations in children with JIA and specific guidance for children with JIA receiving immunosuppression, not on immunosuppression, and children who are underimmunized or unimmunized,” she said. “Although the supportive evidence was very low as per GRADE, panel members were strongly in favor [of immunizations], given risk of infection for immunosuppressed children as well as the preponderance of evidence in similar disease states, such as IBD [inflammatory bowel disease].”

An area with less consensus was whether to check antibody titers for vaccine-preventable childhood infections before beginning immunosuppressive medication, but more panelists opposed the practice than supported it, Dr. Onel said.

“Some panelists felt that the information might be useful for risk management in case of an outbreak or exposure,” she said. “Most believed that screening a fully immunized child was of low benefit and might delay treatment and incur unnecessary cost.”

The process of developing the documents also reveals where the biggest gaps are in research. 

“One of the things that we should strive for in the future is really to do more systematic studies so we have better quality of evidence going forward,” Dr. Shenoi said. Overall, however, the guidelines also reveal the progress made in treatment of JIA.

“We now know some of the key cytokines that are involved in the disease pathogenesis, and we have effective therapies for some of these pathways,” Dr. Shenoi said. “We used to use a lot more toxic medication for systemic JIA, and in past decades, these patients used to be on steroids forever. Now we have targeted therapies, and we have some patients who don’t ever need steroids because people are moving toward targeted therapies and having good results. That’s a huge step forward in the field.”

The research was funded by the ACR. Dr. Shenoi has been a consultant for Pfizer. Dr. Onel disclosed no relevant financial relationships.

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

Treatment of systemic juvenile idiopathic arthritis (sJIA) should emphasize early use of conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs), compared with the previous reliance on NSAIDs and glucocorticoids, according to new guidelines from the American College of Rheumatology. The recently published 2021 guidelines focus on therapeutic approaches for oligoarthritis, temporomandibular joint (TMJ) arthritis, and sJIA.

“Systemic JIA should be treated early with biologics to rapidly bring disease under control and to avoid long-term use of glucocorticoids,” Karen Onel, MD, chief of the division of pediatric rheumatology at Weill Cornell Medicine, New York, and lead author of the guidelines, told this news organization. “Unfortunately, biologics can and are frequently denied for first-line use. For this reason, the guidelines are critically important as they demonstrate that first-line use of biologics are standard of care for the treatment of sJIA.”

The new publication is the second part of the ACR’s process to update JIA guidelines that began in 2017 and complements the release in 2019 of guidelines on the management of nonsystemic polyarthritis, sacroiliitis, and enthesitis, as well as a separate guidance on JIA-associated uveitis. The new guidelines include a second publication focused on nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Both sets of guidelines grew out of a 15-member panel that included young adults with JIA and caregivers of children with JIA, and which required at least 70% agreement on recommendations.

“Though the scope of the two guidelines differed, one thing they had in common is the recognition of the importance of shared decision-making with the patient/caregiver,” Dr. Onel said. “Not every decision will be appropriate for every patient, which is why it was so instrumental to receive input from both patients and caregivers when creating these recommendations.”
 

Oligoarticular and TMJ arthritis

Oligoarticular and TMJ arthritis have similar recommendations, beginning with NSAIDs conditionally recommended and intra-articular glucocorticoids (IAGCs) strongly recommended as part of initial therapy. For oligoarticular arthritis, the guidelines specifically include a strong recommendation of triamcinolone hexacetonide as the preferred agent; no preferred agent is recommended for TMJ arthritis.

“The one thing that the panel was unanimous about was the use of triamcinolone hexacetonide for intra-articular steroid injections in oligoarticular kids,” Susan Shenoi, MBBS, MS, an associate professor and clinical director of pediatric rheumatology at Seattle Children’s Hospital and Research Center, said in an interview. “Triamcinolone hexacetonide has not been available recently, and through advocacy efforts, there is now a pathway to get that medication,” added Dr. Shenoi, a coauthor on the guidelines.

Dr. Onel said that “triamcinolone hexacetonide has been shown to be superior to alternative injectable glucocorticoids in achieving and maintaining remission in children with JIA,” but its unavailability meant physicians had to consider less effective, more potent, or more costly alternatives.” To address the shortage, “the FDA allowed the importation of one particular formulation of triamcinolone hexacetonide [Hexatrione 2%] specifically for joint injections in patients with JIA.”

The guidelines conditionally recommend against oral glucocorticoids for initial therapy for both oligoarticular and TMJ arthritis. In fact, throughout the guidelines it’s clear that the authors emphasize using steroids as little as possible, Dr. Shenoi said.

“Steroids are great anti-inflammatories, but in kids we worry about the long-term effects on growth and metabolism, and now we have many more DMARDs available,” Dr. Shenoi said.

The guidelines strongly recommend conventional synthetic DMARDs for patients with either of these diseases who cannot tolerate or do not respond to NSAIDs or IAGCs, with methotrexate conditionally recommended over leflunomide (Arava) for TMJ and over leflunomide, sulfasalazine (Azulfidine, Sulfazine), and hydroxychloroquine, respectively, for oligoarticular arthritis.

“NSAIDs remain widely used despite evidence supporting early use of DMARDs,” Dr. Onel said. “NSAIDs are readily available and familiar; however, they will not prevent disease progression. These guidelines should encourage short courses of NSAIDs only.”

If patients do not respond to or cannot tolerate NSAIDs, IAGCs, and at least one conventional DMARD, the guidelines strongly recommend a biologic DMARD for oligoarticular arthritis and conditionally recommend one for TMJ arthritis, without any preferences to the specific agent.

The guidelines also advise using validated disease activity measures to guide treatment decisions.

“The most important thing when you’re looking at these patients is to determine, do they have active disease or not?” Dr. Shenoi said. “If they have active disease, then you really want to step up therapy.” Using the relatively new concept of treat-to-target, Dr. Shenoi added that a crucial part of shared decision-making with the family is identifying the most appropriate target for that family “and then really trying hard to achieve that target.”

The guidelines also list risk factors for poor outcome that can be used to guide treatment decisions.

“Specific involvement of key joints, such as TMJ, wrist, sacroiliac, hip, and ankle, and other features were considered reasonable justification for early escalation of therapy,” Dr. Onel said. Other features included presence of erosive disease or enthesitis, delay in diagnosis, elevated levels of inflammation markers, and symmetric disease. “Moving quickly may be needed for a patient who is rapidly worsening, while moving slower may be appropriate for somebody who has improved substantially, but not fully.”

Systemic JIA with and without macrophage activation syndrome

For systemic JIA without macrophage activation syndrome (MAS), the guidelines similarly advise against oral glucocorticoids as initial monotherapy while conditionally recommending NSAIDs for initial monotherapy. Where the guidelines differ most from those for oligoarticular and TMJ arthritis is in progression of DMARD use, with a strong recommendation against conventional synthetic DMARDs as an initial monotherapy and interleukin-1 and IL-6 inhibitors conditionally recommended for initial monotherapy.

For patients who don’t adequately respond to NSAIDs or glucocorticoids, IL-1 and IL-6 inhibitors are strongly recommended over a single or combination of conventional DMARDs. Residual arthritis or an incomplete response to IL-1 or IL-6 inhibitors should lead next to biologic or conventional DMARDs instead of long-term glucocorticoids.

For patients with MAS, the guidelines conditionally recommend IL-1 and IL-6 inhibitors over calcineurin inhibitor monotherapy to reach inactive disease and MAS resolution, with glucocorticoids conditionally recommended in initial treatment. Again, however, for patients with incomplete responses to IL-1 or IL-6 inhibitors or with residual arthritis, the guidelines advise biologic or conventional DMARDs over long-term glucocorticoids.

In patients with sJIA with or without a history of MAS who have inactive disease, practitioners should taper and discontinue glucocorticoids (a strong recommendation). A conditional recommendation for tapering and discontinuing biologic DMARDs follows attainment of inactive disease.

Beyond pharmacology

Although many of the nonpharmacologic recommendations did not have strong evidence based on assessment with Grading of Recommendations Assessment, Development, and Evaluation methodology, consensus was more often the case than not, Dr. Onel said, such as with vaccination.

“There was strong support for the use of immunizations in children with JIA and specific guidance for children with JIA receiving immunosuppression, not on immunosuppression, and children who are underimmunized or unimmunized,” she said. “Although the supportive evidence was very low as per GRADE, panel members were strongly in favor [of immunizations], given risk of infection for immunosuppressed children as well as the preponderance of evidence in similar disease states, such as IBD [inflammatory bowel disease].”

An area with less consensus was whether to check antibody titers for vaccine-preventable childhood infections before beginning immunosuppressive medication, but more panelists opposed the practice than supported it, Dr. Onel said.

“Some panelists felt that the information might be useful for risk management in case of an outbreak or exposure,” she said. “Most believed that screening a fully immunized child was of low benefit and might delay treatment and incur unnecessary cost.”

The process of developing the documents also reveals where the biggest gaps are in research. 

“One of the things that we should strive for in the future is really to do more systematic studies so we have better quality of evidence going forward,” Dr. Shenoi said. Overall, however, the guidelines also reveal the progress made in treatment of JIA.

“We now know some of the key cytokines that are involved in the disease pathogenesis, and we have effective therapies for some of these pathways,” Dr. Shenoi said. “We used to use a lot more toxic medication for systemic JIA, and in past decades, these patients used to be on steroids forever. Now we have targeted therapies, and we have some patients who don’t ever need steroids because people are moving toward targeted therapies and having good results. That’s a huge step forward in the field.”

The research was funded by the ACR. Dr. Shenoi has been a consultant for Pfizer. Dr. Onel disclosed no relevant financial relationships.

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

Chernobyl. Fukushima. Three Mile Island.

The world knows these names all too well because of accidents there: complete or partial meltdowns of nuclear reactors that released massive amounts of cancer-causing radiation into the air, soil, and water.

The Santa Susana Field Lab is far less well-known, but no less infamous for what took place at this former rocket engine and nuclear energy test site just 28 miles northwest of downtown Los Angeles.

In July 1959, an accident involving one of 10 experimental nuclear reactors at the SSFL site released a cloud of harmful radiation and toxic chemicals over the surrounding area, including Simi Valley, San Gabriel Valley, Chatsworth, and Canoga Park. The small reactor had no containment vessel.

This accident resulted in a release of radioactive iodine estimated to be as much as 250 times that of the partial meltdown that would occur 2 decades later at Three Mile Island, a much larger commercial reactor that had a containment vessel.

Six decades later, hundreds of potentially carcinogenic chemicals remain in the surrounding environment. And local children are being diagnosed with rare cancers at a rate that far outpaces what experts would predict.
 

Decades-long cover-up

In 1959, the public knew nothing about what happened at the site.

According to John Pace, then an employee at SSFL, the accident was covered up. Mr. Pace recounted the cover-up in the documentary “In the Dark of the Valley,” which first aired in November 2021 on MSNBC.

In fact, the accident at SSFL remained under wraps for 2 decades, according to Daniel Hirsch, former director of the Program on Environmental and Nuclear Policy at the University of California, Santa Cruz, and now president of Committee to Bridge the Gap, a nuclear policy nongovernmental organization.

“Students working with me while I was teaching at UCLA in 1979 uncovered these Atomic Energy Commission reports from Atomics International,” he said in an interview. “We had to order the documents from the annex to the UCLA Engineering Library. They were stored offsite, and it took a few days, and when we got them, we opened them up, and there were these fold-out photographs of the fuel [rods]. As we folded out the photographs further, we saw one photo with an arrow labeled ‘longitudinal cracks,’ and then other arrows showing other kinds of cracks, and then another arrow labeled ‘melted blob.’ ”

Mr. Hirsch and his students found that other accidents had occurred at SSFL, including a fuel fabrication system that leached plutonium, fires in a “hot” lab where irradiated nuclear fuel from around the United States was handled, and open-air burn pits where radioactive and toxic chemical wastes were illegally torched.

According to the Committee to Bridge the Gap, when the 2,800-acre SSFL site was being developed under the name Rocketdyne by aircraft maker North American Aviation, the area was sparsely populated, with nearly as many grazing animals as people in its hills and valleys.

North American Aviation later became part of Rockwell International, which in turn sold its aerospace and defense business units to the Boeing Company in 1996. Boeing, now in charge of the site and the cleanup efforts, is doing everything in its power to shirk or diminish its responsibility, Mr. Hirsch and other critics say.
 

Parents against SSFL

Today, more than 150,000 people live within 5 miles of SSFL, and more than half a million live within 10 miles.

Melissa Bumstead is one of those residents. She and her family live 3.7 miles from the Santa Susana site. When her toddler Grace was diagnosed with a rare form of leukemia in 2014, doctors told Ms. Bumstead there were no known links between her daughter’s cancer and environmental contamination.

But during Grace’s treatment at Children’s Hospital Los Angeles, her mother began meeting other parents who lived near her and had children facing equally rare cancers.

Lauren Hammersley, whose daughter Hazel was diagnosed with a rare brain tumor called neuroblastoma at age 2, lived about 10 miles from Ms. Bumstead on the other side of a mountain and just over 4 miles from SSFL.

On her street alone, Ms. Bumstead discovered three cases of pediatric cancer, including two children in adjacent homes who had the same rare brain tumor as Hazel Hammersley.

As Ms. Bumstead told Los Angeles National Public Radio station KCRW in 2021, “I started to panic because I knew that childhood cancer is extremely rare. There’s only 15,000 new cases every year out of 72 million children in America. So, the chance of knowing your neighbors, especially at an internationally renowned hospital like Children’s Hospital Los Angeles – we knew something wasn’t right.”

After a relapse of her tumor, Hazel died in 2018, a few months after her seventh birthday.
 

Cancer clusters

Hoping to understand why their kids were getting so sick, Ms. Bumstead and the other parents formed a Facebook group. They plotted their homes on Google Maps and found that they all lived within roughly 10 miles of one another. It would take another year for them to realize that the SSFL site was at the center of the circle.

Once they realized that being close to SSFL could be their common thread, Ms. Bumstead and parents in her group began to gradually piece together the story, linking unusual or unexplained illnesses in their families to potential radiation or toxic chemical exposures from the lab.

“What really convinced me that this was absolutely a problem was when I learned about the epidemiological study by Dr. Hal Morgenstern that found that residents living within 2 miles of the Santa Susana Field Lab actually had a 60% higher cancer incidence rate and that over 1,500 workers have been diagnosed with cancer just from the Santa Susana Field Lab,” she told KCRW.

In 2015, Ms. Bumstead and other parents formed Parents Against Santa Susana Field Lab to hold SSFL site owner Boeing accountable for radiologic and toxic contamination and to ensure that Boeing cleans the site and surrounding areas. The group “seeks to reduce, to the greatest extent possible, the number of local families who have to hear the words, ‘Your child has cancer.’ ”
 

No longer quite so rare

Dr. Morgenstern, now retired from the University of Michigan, declined to be interviewed for this article. But as he and colleagues reported to the Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry in 2007, there were strong signs of a link between contamination of the site and cancer.

The researchers compared cancer rates of adults living within 2 miles and 2-5 miles from SSFL with those of adults living more than 5 miles away, in Ventura and Los Angeles counties. They found that from 1988 through 1995, residents living within 2 miles of SSFL had a 60% higher rate of cancers than the control group. These included cancers of the thyroid, oral and nasal cavities, pharynx, larynx, esophagus, and bladder, as well as blood cancers such as leukemia, lymphoma, and multiple myeloma.

In separate studies, the investigators found higher rates of certain cancers among workers at SSFL who were exposed to radiation and to hydrazine, a chemical in rocket fuel.

In an interview, Dr. Saro Armenian, a pediatric hematologist-oncologist who was not involved in the studies, said the 60% increase in cancer incidence, which translated into a 1.6-fold increase in risk, merits more investigation.

“In epidemiologic studies, a 1.6-fold risk is actually a pretty strong signal because typically, most signals that you get are somewhere around 1.1- to 1.2-fold increased risk,” noted Dr. Armenian, a specialist in pediatric cancer survivorship and outcomes at City of Hope National Medical Center in Duarte, Calif.

However, Dr. Thomas Mack, former director of the Los Angeles County Cancer Surveillance Program, contends that there is insufficient evidence to support a direct link between the 1959 reactor accident and recent incident cancers. Dr. Mack is currently a professor of preventive medicine and pathology at the University of Southern California in Los Angeles.

“I have evaluated concerns about local excesses of cancer at least 100 times, usually from county residents, but for a while I represented the CDC and the California cancer registry,” Dr. Mack said, in response to an emailed request for comment.

“So far I have seen no evidence of carcinogenic radionucleotides or chemical carcinogens from Santa Susana found in any meaningful amount in any nearby community, but if someone has such evidence that would constitute evidence, that needs a response,” Dr. Mack added.
 

Boeing and California

Boeing has said problems at SSFL were not responsible for the high cancer rates among children in the community.

In April 2007, in a statement opposing a bill before the California State Legislature that would compel Boeing to pay for SSFL site cleanup, the company said that “in contrast to the accusations made against The Boeing Company that falsely claim increased cancer rates in the communities surrounding SSFL, a recent study conducted by the University of Michigan School of Public Health just concluded the opposite.”

Yet as Dr. Morgenstern wrote in 2007 to California state Sen. Joe Simitian, then chair of the Committee on Environmental Quality: “For the period 1996 through 2002, we found that the incidence rate of thyroid cancer was more than 60% greater among residents living within 2 miles of SSFL than for residents living more than 5 miles from SSFL. The magnitude and consistency of the thyroid finding for both periods is especially provocative because of evidence from other studies linking thyroid cancer with environmental exposures originating at SSFL and found in the surrounding communities.”

Boeing chose to ignore the results and instead focused on the methods used in the study, where the authors acknowledged that they measured distance from the site rather than environmental exposures and thus could not conclusively link excess cancer rates to exposures arising from SSFL.

But Dr. Morgenstern emphasized the conclusion of the report: “Despite the methodologic limitations of this study, the findings suggest there may be elevated incidence rates of certain cancers near SSFL that have been linked in previous studies with hazardous substances used at Rocketdyne, some of which have been observed or projected to exist offsite.”
 

Failure to come clean

In 2008, a law that set standards for cleanup of the site was passed. But the law was overturned in 2014 after a legal challenge by Boeing.

That left in place a 2007 order of consent between Boeing, NASA, the U.S. Department of Energy, and the California Department of Toxic Substances Control (DTSC) that required cleanup of SSFL to a much less stringent standard.

As of last year, Boeing and DTSC had begun confidential, nonbinding agreements regarding the 2007 order of consent, according to Parents Against SSFL.

Among the contaminants lingering at the site are radioactive particles, chemical compounds, heavy metals, and polluted water.

“In fact, over 300 contaminants of concern have been found at the site, and they are refusing to clean it,” Mr. Hirsch said. “This company releases large amounts of carcinogens, and perhaps significant numbers of people get sick with cancer, and the company doesn’t go to prison. They get more federal contracts.”

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

April 20, 2022 – Editor’s note: This article has been updated to include an interview with Dr. Thomas Mack, former director of the Los Angeles County Cancer Surveillance Program, who contends that there is insufficient evidence to support a direct link between the 1959 reactor accident and recent incident cancers.

Chernobyl. Fukushima. Three Mile Island.

The world knows these names all too well because of accidents there: complete or partial meltdowns of nuclear reactors that released massive amounts of cancer-causing radiation into the air, soil, and water.

The Santa Susana Field Lab is far less well-known, but no less infamous for what took place at this former rocket engine and nuclear energy test site just 28 miles northwest of downtown Los Angeles.

In July 1959, an accident involving one of 10 experimental nuclear reactors at the SSFL site released a cloud of harmful radiation and toxic chemicals over the surrounding area, including Simi Valley, San Gabriel Valley, Chatsworth, and Canoga Park. The small reactor had no containment vessel.

This accident resulted in a release of radioactive iodine estimated to be as much as 250 times that of the partial meltdown that would occur 2 decades later at Three Mile Island, a much larger commercial reactor that had a containment vessel.

Six decades later, hundreds of potentially carcinogenic chemicals remain in the surrounding environment. And local children are being diagnosed with rare cancers at a rate that far outpaces what experts would predict.
 

Decades-long cover-up

In 1959, the public knew nothing about what happened at the site.

According to John Pace, then an employee at SSFL, the accident was covered up. Mr. Pace recounted the cover-up in the documentary “In the Dark of the Valley,” which first aired in November 2021 on MSNBC.

In fact, the accident at SSFL remained under wraps for 2 decades, according to Daniel Hirsch, former director of the Program on Environmental and Nuclear Policy at the University of California, Santa Cruz, and now president of Committee to Bridge the Gap, a nuclear policy nongovernmental organization.

“Students working with me while I was teaching at UCLA in 1979 uncovered these Atomic Energy Commission reports from Atomics International,” he said in an interview. “We had to order the documents from the annex to the UCLA Engineering Library. They were stored offsite, and it took a few days, and when we got them, we opened them up, and there were these fold-out photographs of the fuel [rods]. As we folded out the photographs further, we saw one photo with an arrow labeled ‘longitudinal cracks,’ and then other arrows showing other kinds of cracks, and then another arrow labeled ‘melted blob.’ ”

Mr. Hirsch and his students found that other accidents had occurred at SSFL, including a fuel fabrication system that leached plutonium, fires in a “hot” lab where irradiated nuclear fuel from around the United States was handled, and open-air burn pits where radioactive and toxic chemical wastes were illegally torched.

According to the Committee to Bridge the Gap, when the 2,800-acre SSFL site was being developed under the name Rocketdyne by aircraft maker North American Aviation, the area was sparsely populated, with nearly as many grazing animals as people in its hills and valleys.

North American Aviation later became part of Rockwell International, which in turn sold its aerospace and defense business units to the Boeing Company in 1996. Boeing, now in charge of the site and the cleanup efforts, is doing everything in its power to shirk or diminish its responsibility, Mr. Hirsch and other critics say.
 

Parents against SSFL

Today, more than 150,000 people live within 5 miles of SSFL, and more than half a million live within 10 miles.

Melissa Bumstead is one of those residents. She and her family live 3.7 miles from the Santa Susana site. When her toddler Grace was diagnosed with a rare form of leukemia in 2014, doctors told Ms. Bumstead there were no known links between her daughter’s cancer and environmental contamination.

But during Grace’s treatment at Children’s Hospital Los Angeles, her mother began meeting other parents who lived near her and had children facing equally rare cancers.

Lauren Hammersley, whose daughter Hazel was diagnosed with a rare brain tumor called neuroblastoma at age 2, lived about 10 miles from Ms. Bumstead on the other side of a mountain and just over 4 miles from SSFL.

On her street alone, Ms. Bumstead discovered three cases of pediatric cancer, including two children in adjacent homes who had the same rare brain tumor as Hazel Hammersley.

As Ms. Bumstead told Los Angeles National Public Radio station KCRW in 2021, “I started to panic because I knew that childhood cancer is extremely rare. There’s only 15,000 new cases every year out of 72 million children in America. So, the chance of knowing your neighbors, especially at an internationally renowned hospital like Children’s Hospital Los Angeles – we knew something wasn’t right.”

After a relapse of her tumor, Hazel died in 2018, a few months after her seventh birthday.
 

Cancer clusters

Hoping to understand why their kids were getting so sick, Ms. Bumstead and the other parents formed a Facebook group. They plotted their homes on Google Maps and found that they all lived within roughly 10 miles of one another. It would take another year for them to realize that the SSFL site was at the center of the circle.

Once they realized that being close to SSFL could be their common thread, Ms. Bumstead and parents in her group began to gradually piece together the story, linking unusual or unexplained illnesses in their families to potential radiation or toxic chemical exposures from the lab.

“What really convinced me that this was absolutely a problem was when I learned about the epidemiological study by Dr. Hal Morgenstern that found that residents living within 2 miles of the Santa Susana Field Lab actually had a 60% higher cancer incidence rate and that over 1,500 workers have been diagnosed with cancer just from the Santa Susana Field Lab,” she told KCRW.

In 2015, Ms. Bumstead and other parents formed Parents Against Santa Susana Field Lab to hold SSFL site owner Boeing accountable for radiologic and toxic contamination and to ensure that Boeing cleans the site and surrounding areas. The group “seeks to reduce, to the greatest extent possible, the number of local families who have to hear the words, ‘Your child has cancer.’ ”
 

No longer quite so rare

Dr. Morgenstern, now retired from the University of Michigan, declined to be interviewed for this article. But as he and colleagues reported to the Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry in 2007, there were strong signs of a link between contamination of the site and cancer.

The researchers compared cancer rates of adults living within 2 miles and 2-5 miles from SSFL with those of adults living more than 5 miles away, in Ventura and Los Angeles counties. They found that from 1988 through 1995, residents living within 2 miles of SSFL had a 60% higher rate of cancers than the control group. These included cancers of the thyroid, oral and nasal cavities, pharynx, larynx, esophagus, and bladder, as well as blood cancers such as leukemia, lymphoma, and multiple myeloma.

In separate studies, the investigators found higher rates of certain cancers among workers at SSFL who were exposed to radiation and to hydrazine, a chemical in rocket fuel.

In an interview, Dr. Saro Armenian, a pediatric hematologist-oncologist who was not involved in the studies, said the 60% increase in cancer incidence, which translated into a 1.6-fold increase in risk, merits more investigation.

“In epidemiologic studies, a 1.6-fold risk is actually a pretty strong signal because typically, most signals that you get are somewhere around 1.1- to 1.2-fold increased risk,” noted Dr. Armenian, a specialist in pediatric cancer survivorship and outcomes at City of Hope National Medical Center in Duarte, Calif.

However, Dr. Thomas Mack, former director of the Los Angeles County Cancer Surveillance Program, contends that there is insufficient evidence to support a direct link between the 1959 reactor accident and recent incident cancers. Dr. Mack is currently a professor of preventive medicine and pathology at the University of Southern California in Los Angeles.

“I have evaluated concerns about local excesses of cancer at least 100 times, usually from county residents, but for a while I represented the CDC and the California cancer registry,” Dr. Mack said, in response to an emailed request for comment.

“So far I have seen no evidence of carcinogenic radionucleotides or chemical carcinogens from Santa Susana found in any meaningful amount in any nearby community, but if someone has such evidence that would constitute evidence, that needs a response,” Dr. Mack added.
 

Boeing and California

Boeing has said problems at SSFL were not responsible for the high cancer rates among children in the community.

In April 2007, in a statement opposing a bill before the California State Legislature that would compel Boeing to pay for SSFL site cleanup, the company said that “in contrast to the accusations made against The Boeing Company that falsely claim increased cancer rates in the communities surrounding SSFL, a recent study conducted by the University of Michigan School of Public Health just concluded the opposite.”

Yet as Dr. Morgenstern wrote in 2007 to California state Sen. Joe Simitian, then chair of the Committee on Environmental Quality: “For the period 1996 through 2002, we found that the incidence rate of thyroid cancer was more than 60% greater among residents living within 2 miles of SSFL than for residents living more than 5 miles from SSFL. The magnitude and consistency of the thyroid finding for both periods is especially provocative because of evidence from other studies linking thyroid cancer with environmental exposures originating at SSFL and found in the surrounding communities.”

Boeing chose to ignore the results and instead focused on the methods used in the study, where the authors acknowledged that they measured distance from the site rather than environmental exposures and thus could not conclusively link excess cancer rates to exposures arising from SSFL.

But Dr. Morgenstern emphasized the conclusion of the report: “Despite the methodologic limitations of this study, the findings suggest there may be elevated incidence rates of certain cancers near SSFL that have been linked in previous studies with hazardous substances used at Rocketdyne, some of which have been observed or projected to exist offsite.”
 

Failure to come clean

In 2008, a law that set standards for cleanup of the site was passed. But the law was overturned in 2014 after a legal challenge by Boeing.

That left in place a 2007 order of consent between Boeing, NASA, the U.S. Department of Energy, and the California Department of Toxic Substances Control (DTSC) that required cleanup of SSFL to a much less stringent standard.

As of last year, Boeing and DTSC had begun confidential, nonbinding agreements regarding the 2007 order of consent, according to Parents Against SSFL.

Among the contaminants lingering at the site are radioactive particles, chemical compounds, heavy metals, and polluted water.

“In fact, over 300 contaminants of concern have been found at the site, and they are refusing to clean it,” Mr. Hirsch said. “This company releases large amounts of carcinogens, and perhaps significant numbers of people get sick with cancer, and the company doesn’t go to prison. They get more federal contracts.”

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

April 20, 2022 – Editor’s note: This article has been updated to include an interview with Dr. Thomas Mack, former director of the Los Angeles County Cancer Surveillance Program, who contends that there is insufficient evidence to support a direct link between the 1959 reactor accident and recent incident cancers.

Chernobyl. Fukushima. Three Mile Island.

The world knows these names all too well because of accidents there: complete or partial meltdowns of nuclear reactors that released massive amounts of cancer-causing radiation into the air, soil, and water.

The Santa Susana Field Lab is far less well-known, but no less infamous for what took place at this former rocket engine and nuclear energy test site just 28 miles northwest of downtown Los Angeles.

In July 1959, an accident involving one of 10 experimental nuclear reactors at the SSFL site released a cloud of harmful radiation and toxic chemicals over the surrounding area, including Simi Valley, San Gabriel Valley, Chatsworth, and Canoga Park. The small reactor had no containment vessel.

This accident resulted in a release of radioactive iodine estimated to be as much as 250 times that of the partial meltdown that would occur 2 decades later at Three Mile Island, a much larger commercial reactor that had a containment vessel.

Six decades later, hundreds of potentially carcinogenic chemicals remain in the surrounding environment. And local children are being diagnosed with rare cancers at a rate that far outpaces what experts would predict.
 

Decades-long cover-up

In 1959, the public knew nothing about what happened at the site.

According to John Pace, then an employee at SSFL, the accident was covered up. Mr. Pace recounted the cover-up in the documentary “In the Dark of the Valley,” which first aired in November 2021 on MSNBC.

In fact, the accident at SSFL remained under wraps for 2 decades, according to Daniel Hirsch, former director of the Program on Environmental and Nuclear Policy at the University of California, Santa Cruz, and now president of Committee to Bridge the Gap, a nuclear policy nongovernmental organization.

“Students working with me while I was teaching at UCLA in 1979 uncovered these Atomic Energy Commission reports from Atomics International,” he said in an interview. “We had to order the documents from the annex to the UCLA Engineering Library. They were stored offsite, and it took a few days, and when we got them, we opened them up, and there were these fold-out photographs of the fuel [rods]. As we folded out the photographs further, we saw one photo with an arrow labeled ‘longitudinal cracks,’ and then other arrows showing other kinds of cracks, and then another arrow labeled ‘melted blob.’ ”

Mr. Hirsch and his students found that other accidents had occurred at SSFL, including a fuel fabrication system that leached plutonium, fires in a “hot” lab where irradiated nuclear fuel from around the United States was handled, and open-air burn pits where radioactive and toxic chemical wastes were illegally torched.

According to the Committee to Bridge the Gap, when the 2,800-acre SSFL site was being developed under the name Rocketdyne by aircraft maker North American Aviation, the area was sparsely populated, with nearly as many grazing animals as people in its hills and valleys.

North American Aviation later became part of Rockwell International, which in turn sold its aerospace and defense business units to the Boeing Company in 1996. Boeing, now in charge of the site and the cleanup efforts, is doing everything in its power to shirk or diminish its responsibility, Mr. Hirsch and other critics say.
 

Parents against SSFL

Today, more than 150,000 people live within 5 miles of SSFL, and more than half a million live within 10 miles.

Melissa Bumstead is one of those residents. She and her family live 3.7 miles from the Santa Susana site. When her toddler Grace was diagnosed with a rare form of leukemia in 2014, doctors told Ms. Bumstead there were no known links between her daughter’s cancer and environmental contamination.

But during Grace’s treatment at Children’s Hospital Los Angeles, her mother began meeting other parents who lived near her and had children facing equally rare cancers.

Lauren Hammersley, whose daughter Hazel was diagnosed with a rare brain tumor called neuroblastoma at age 2, lived about 10 miles from Ms. Bumstead on the other side of a mountain and just over 4 miles from SSFL.

On her street alone, Ms. Bumstead discovered three cases of pediatric cancer, including two children in adjacent homes who had the same rare brain tumor as Hazel Hammersley.

As Ms. Bumstead told Los Angeles National Public Radio station KCRW in 2021, “I started to panic because I knew that childhood cancer is extremely rare. There’s only 15,000 new cases every year out of 72 million children in America. So, the chance of knowing your neighbors, especially at an internationally renowned hospital like Children’s Hospital Los Angeles – we knew something wasn’t right.”

After a relapse of her tumor, Hazel died in 2018, a few months after her seventh birthday.
 

Cancer clusters

Hoping to understand why their kids were getting so sick, Ms. Bumstead and the other parents formed a Facebook group. They plotted their homes on Google Maps and found that they all lived within roughly 10 miles of one another. It would take another year for them to realize that the SSFL site was at the center of the circle.

Once they realized that being close to SSFL could be their common thread, Ms. Bumstead and parents in her group began to gradually piece together the story, linking unusual or unexplained illnesses in their families to potential radiation or toxic chemical exposures from the lab.

“What really convinced me that this was absolutely a problem was when I learned about the epidemiological study by Dr. Hal Morgenstern that found that residents living within 2 miles of the Santa Susana Field Lab actually had a 60% higher cancer incidence rate and that over 1,500 workers have been diagnosed with cancer just from the Santa Susana Field Lab,” she told KCRW.

In 2015, Ms. Bumstead and other parents formed Parents Against Santa Susana Field Lab to hold SSFL site owner Boeing accountable for radiologic and toxic contamination and to ensure that Boeing cleans the site and surrounding areas. The group “seeks to reduce, to the greatest extent possible, the number of local families who have to hear the words, ‘Your child has cancer.’ ”
 

No longer quite so rare

Dr. Morgenstern, now retired from the University of Michigan, declined to be interviewed for this article. But as he and colleagues reported to the Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry in 2007, there were strong signs of a link between contamination of the site and cancer.

The researchers compared cancer rates of adults living within 2 miles and 2-5 miles from SSFL with those of adults living more than 5 miles away, in Ventura and Los Angeles counties. They found that from 1988 through 1995, residents living within 2 miles of SSFL had a 60% higher rate of cancers than the control group. These included cancers of the thyroid, oral and nasal cavities, pharynx, larynx, esophagus, and bladder, as well as blood cancers such as leukemia, lymphoma, and multiple myeloma.

In separate studies, the investigators found higher rates of certain cancers among workers at SSFL who were exposed to radiation and to hydrazine, a chemical in rocket fuel.

In an interview, Dr. Saro Armenian, a pediatric hematologist-oncologist who was not involved in the studies, said the 60% increase in cancer incidence, which translated into a 1.6-fold increase in risk, merits more investigation.

“In epidemiologic studies, a 1.6-fold risk is actually a pretty strong signal because typically, most signals that you get are somewhere around 1.1- to 1.2-fold increased risk,” noted Dr. Armenian, a specialist in pediatric cancer survivorship and outcomes at City of Hope National Medical Center in Duarte, Calif.

However, Dr. Thomas Mack, former director of the Los Angeles County Cancer Surveillance Program, contends that there is insufficient evidence to support a direct link between the 1959 reactor accident and recent incident cancers. Dr. Mack is currently a professor of preventive medicine and pathology at the University of Southern California in Los Angeles.

“I have evaluated concerns about local excesses of cancer at least 100 times, usually from county residents, but for a while I represented the CDC and the California cancer registry,” Dr. Mack said, in response to an emailed request for comment.

“So far I have seen no evidence of carcinogenic radionucleotides or chemical carcinogens from Santa Susana found in any meaningful amount in any nearby community, but if someone has such evidence that would constitute evidence, that needs a response,” Dr. Mack added.
 

Boeing and California

Boeing has said problems at SSFL were not responsible for the high cancer rates among children in the community.

In April 2007, in a statement opposing a bill before the California State Legislature that would compel Boeing to pay for SSFL site cleanup, the company said that “in contrast to the accusations made against The Boeing Company that falsely claim increased cancer rates in the communities surrounding SSFL, a recent study conducted by the University of Michigan School of Public Health just concluded the opposite.”

Yet as Dr. Morgenstern wrote in 2007 to California state Sen. Joe Simitian, then chair of the Committee on Environmental Quality: “For the period 1996 through 2002, we found that the incidence rate of thyroid cancer was more than 60% greater among residents living within 2 miles of SSFL than for residents living more than 5 miles from SSFL. The magnitude and consistency of the thyroid finding for both periods is especially provocative because of evidence from other studies linking thyroid cancer with environmental exposures originating at SSFL and found in the surrounding communities.”

Boeing chose to ignore the results and instead focused on the methods used in the study, where the authors acknowledged that they measured distance from the site rather than environmental exposures and thus could not conclusively link excess cancer rates to exposures arising from SSFL.

But Dr. Morgenstern emphasized the conclusion of the report: “Despite the methodologic limitations of this study, the findings suggest there may be elevated incidence rates of certain cancers near SSFL that have been linked in previous studies with hazardous substances used at Rocketdyne, some of which have been observed or projected to exist offsite.”
 

Failure to come clean

In 2008, a law that set standards for cleanup of the site was passed. But the law was overturned in 2014 after a legal challenge by Boeing.

That left in place a 2007 order of consent between Boeing, NASA, the U.S. Department of Energy, and the California Department of Toxic Substances Control (DTSC) that required cleanup of SSFL to a much less stringent standard.

As of last year, Boeing and DTSC had begun confidential, nonbinding agreements regarding the 2007 order of consent, according to Parents Against SSFL.

Among the contaminants lingering at the site are radioactive particles, chemical compounds, heavy metals, and polluted water.

“In fact, over 300 contaminants of concern have been found at the site, and they are refusing to clean it,” Mr. Hirsch said. “This company releases large amounts of carcinogens, and perhaps significant numbers of people get sick with cancer, and the company doesn’t go to prison. They get more federal contracts.”

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

April 20, 2022 – Editor’s note: This article has been updated to include an interview with Dr. Thomas Mack, former director of the Los Angeles County Cancer Surveillance Program, who contends that there is insufficient evidence to support a direct link between the 1959 reactor accident and recent incident cancers.

It’s now known that tinnitus may be an unexpected side effect of SARS-CoV-2 vaccination, and there is an urgent need to understand the precise mechanisms and best treatment for vaccine-associated tinnitus, researchers say.

As of mid-September 2021, 12,247 cases of tinnitus, or ringing in the ears, following COVID-19 vaccination had been reported to the Vaccine Adverse Event Reporting System of the U.S. Centers for Disease Control and Prevention.

“Despite several cases of tinnitus being reported following SARS-CoV-2 vaccination, the precise pathophysiology is still not clear,” write Syed Hassan Ahmed, 3rd-year MBBS student, Dow University of Health Sciences, Karachi, Pakistan, and coauthors.

The researchers review what is known and unknown about SARS-CoV-2 vaccine-associated tinnitus in an article published online Feb. 11 in Annals of Medicine and Surgery.
 

Molecular mimicry?

The researchers say cross-reactivity between anti-spike SARS-CoV-2 antibodies and otologic antigens is one possibility, based on the mechanisms behind other COVID-19 vaccine–induced disorders and the phenomenon of molecular mimicry.

“The heptapeptide resemblance between coronavirus spike glycoprotein and numerous human proteins further supports molecular mimicry as a potential mechanism behind such vaccine-induced disorders,” they write.

Anti-spike antibodies may react with antigens anywhere along the auditory pathway and fuel an inflammatory reaction, they point out.

“Therefore, understanding the phenomenon of cross-reactivity and molecular mimicry may be helpful in postulating potential treatment behind not only tinnitus but also the rare events of vaccination associated hearing loss and other otologic manifestations,” the authors say.

Genetic predispositions and associated conditions may also play a significant role in determining whether an individual develops vaccine-induced tinnitus.

Stress and anxiety following COVID vaccination may also play a role, inasmuch as anxiety-related adverse events following vaccination have been reported. Vaccine-related anxiety as a potential cause of tinnitus developing after vaccination needs to be explored, they write.
 

Jury out on best management

How best to manage COVID vaccine-associated tinnitus also remains unclear, but it starts with a well-established diagnosis, the authors say.

A well-focused and detailed history and examination are essential, with particular emphasis placed on preexisting health conditions, specifically, autoimmune diseases, such as Hashimoto thyroiditis; otologic conditions, such as sensorineural hearing loss; glaucoma; and psychological well-being. According to the review, patients often present with a history of one or more of these disorders.

“However, any such association has not yet been established and requires further investigation to be concluded as potential risk factors for vaccine-induced tinnitus,” they caution.

Routine cranial nerve examination, otoscopy, Weber test, and Rinne test, which are used for tinnitus diagnosis in general, may be helpful for confirmation of vaccine-associated tinnitus.

Owing to the significant association between tinnitus and hearing impairment, audiology should also performed, the authors say.

Although treatments for non–vaccine-induced tinnitus vary significantly, corticosteroids are the top treatment choice for SARS-CoV-2 vaccine-induced tinnitus reported in the literature.

Trials of other drug and nondrug interventions that may uniquely help with vaccine-associated tinnitus are urgently needed, the authors say.

Summing up, the reviewers say, “Although the incidence of COVID-19 vaccine-associated tinnitus is rare, there is an overwhelming need to discern the precise pathophysiology and clinical management as a better understanding of adverse events may help in encountering vaccine hesitancy and hence fostering the COVID-19 global vaccination program.

“Despite the incidence of adverse events, the benefits of the SARS-CoV-2 vaccine in reducing hospitalization and deaths continue to outweigh the rare ramifications,” they conclude.

The research had no specific funding. The authors have disclosed no relevant financial relationships.

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

It’s now known that tinnitus may be an unexpected side effect of SARS-CoV-2 vaccination, and there is an urgent need to understand the precise mechanisms and best treatment for vaccine-associated tinnitus, researchers say.

As of mid-September 2021, 12,247 cases of tinnitus, or ringing in the ears, following COVID-19 vaccination had been reported to the Vaccine Adverse Event Reporting System of the U.S. Centers for Disease Control and Prevention.

“Despite several cases of tinnitus being reported following SARS-CoV-2 vaccination, the precise pathophysiology is still not clear,” write Syed Hassan Ahmed, 3rd-year MBBS student, Dow University of Health Sciences, Karachi, Pakistan, and coauthors.

The researchers review what is known and unknown about SARS-CoV-2 vaccine-associated tinnitus in an article published online Feb. 11 in Annals of Medicine and Surgery.
 

Molecular mimicry?

The researchers say cross-reactivity between anti-spike SARS-CoV-2 antibodies and otologic antigens is one possibility, based on the mechanisms behind other COVID-19 vaccine–induced disorders and the phenomenon of molecular mimicry.

“The heptapeptide resemblance between coronavirus spike glycoprotein and numerous human proteins further supports molecular mimicry as a potential mechanism behind such vaccine-induced disorders,” they write.

Anti-spike antibodies may react with antigens anywhere along the auditory pathway and fuel an inflammatory reaction, they point out.

“Therefore, understanding the phenomenon of cross-reactivity and molecular mimicry may be helpful in postulating potential treatment behind not only tinnitus but also the rare events of vaccination associated hearing loss and other otologic manifestations,” the authors say.

Genetic predispositions and associated conditions may also play a significant role in determining whether an individual develops vaccine-induced tinnitus.

Stress and anxiety following COVID vaccination may also play a role, inasmuch as anxiety-related adverse events following vaccination have been reported. Vaccine-related anxiety as a potential cause of tinnitus developing after vaccination needs to be explored, they write.
 

Jury out on best management

How best to manage COVID vaccine-associated tinnitus also remains unclear, but it starts with a well-established diagnosis, the authors say.

A well-focused and detailed history and examination are essential, with particular emphasis placed on preexisting health conditions, specifically, autoimmune diseases, such as Hashimoto thyroiditis; otologic conditions, such as sensorineural hearing loss; glaucoma; and psychological well-being. According to the review, patients often present with a history of one or more of these disorders.

“However, any such association has not yet been established and requires further investigation to be concluded as potential risk factors for vaccine-induced tinnitus,” they caution.

Routine cranial nerve examination, otoscopy, Weber test, and Rinne test, which are used for tinnitus diagnosis in general, may be helpful for confirmation of vaccine-associated tinnitus.

Owing to the significant association between tinnitus and hearing impairment, audiology should also performed, the authors say.

Although treatments for non–vaccine-induced tinnitus vary significantly, corticosteroids are the top treatment choice for SARS-CoV-2 vaccine-induced tinnitus reported in the literature.

Trials of other drug and nondrug interventions that may uniquely help with vaccine-associated tinnitus are urgently needed, the authors say.

Summing up, the reviewers say, “Although the incidence of COVID-19 vaccine-associated tinnitus is rare, there is an overwhelming need to discern the precise pathophysiology and clinical management as a better understanding of adverse events may help in encountering vaccine hesitancy and hence fostering the COVID-19 global vaccination program.

“Despite the incidence of adverse events, the benefits of the SARS-CoV-2 vaccine in reducing hospitalization and deaths continue to outweigh the rare ramifications,” they conclude.

The research had no specific funding. The authors have disclosed no relevant financial relationships.

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

It’s now known that tinnitus may be an unexpected side effect of SARS-CoV-2 vaccination, and there is an urgent need to understand the precise mechanisms and best treatment for vaccine-associated tinnitus, researchers say.

As of mid-September 2021, 12,247 cases of tinnitus, or ringing in the ears, following COVID-19 vaccination had been reported to the Vaccine Adverse Event Reporting System of the U.S. Centers for Disease Control and Prevention.

“Despite several cases of tinnitus being reported following SARS-CoV-2 vaccination, the precise pathophysiology is still not clear,” write Syed Hassan Ahmed, 3rd-year MBBS student, Dow University of Health Sciences, Karachi, Pakistan, and coauthors.

The researchers review what is known and unknown about SARS-CoV-2 vaccine-associated tinnitus in an article published online Feb. 11 in Annals of Medicine and Surgery.
 

Molecular mimicry?

The researchers say cross-reactivity between anti-spike SARS-CoV-2 antibodies and otologic antigens is one possibility, based on the mechanisms behind other COVID-19 vaccine–induced disorders and the phenomenon of molecular mimicry.

“The heptapeptide resemblance between coronavirus spike glycoprotein and numerous human proteins further supports molecular mimicry as a potential mechanism behind such vaccine-induced disorders,” they write.

Anti-spike antibodies may react with antigens anywhere along the auditory pathway and fuel an inflammatory reaction, they point out.

“Therefore, understanding the phenomenon of cross-reactivity and molecular mimicry may be helpful in postulating potential treatment behind not only tinnitus but also the rare events of vaccination associated hearing loss and other otologic manifestations,” the authors say.

Genetic predispositions and associated conditions may also play a significant role in determining whether an individual develops vaccine-induced tinnitus.

Stress and anxiety following COVID vaccination may also play a role, inasmuch as anxiety-related adverse events following vaccination have been reported. Vaccine-related anxiety as a potential cause of tinnitus developing after vaccination needs to be explored, they write.
 

Jury out on best management

How best to manage COVID vaccine-associated tinnitus also remains unclear, but it starts with a well-established diagnosis, the authors say.

A well-focused and detailed history and examination are essential, with particular emphasis placed on preexisting health conditions, specifically, autoimmune diseases, such as Hashimoto thyroiditis; otologic conditions, such as sensorineural hearing loss; glaucoma; and psychological well-being. According to the review, patients often present with a history of one or more of these disorders.

“However, any such association has not yet been established and requires further investigation to be concluded as potential risk factors for vaccine-induced tinnitus,” they caution.

Routine cranial nerve examination, otoscopy, Weber test, and Rinne test, which are used for tinnitus diagnosis in general, may be helpful for confirmation of vaccine-associated tinnitus.

Owing to the significant association between tinnitus and hearing impairment, audiology should also performed, the authors say.

Although treatments for non–vaccine-induced tinnitus vary significantly, corticosteroids are the top treatment choice for SARS-CoV-2 vaccine-induced tinnitus reported in the literature.

Trials of other drug and nondrug interventions that may uniquely help with vaccine-associated tinnitus are urgently needed, the authors say.

Summing up, the reviewers say, “Although the incidence of COVID-19 vaccine-associated tinnitus is rare, there is an overwhelming need to discern the precise pathophysiology and clinical management as a better understanding of adverse events may help in encountering vaccine hesitancy and hence fostering the COVID-19 global vaccination program.

“Despite the incidence of adverse events, the benefits of the SARS-CoV-2 vaccine in reducing hospitalization and deaths continue to outweigh the rare ramifications,” they conclude.

The research had no specific funding. The authors have disclosed no relevant financial relationships.

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

The Biden administration’s new test-to-treat program is simple on the surface: if you feel like you may have COVID-19, go to a pharmacy, get tested, and, if positive, get treated with an antiviral medication on the spot.

But the program is not that simple to groups representing physicians and pharmacists.

One large physicians’ group is concerned that the program leaves doctors on the margins, and may put patients at risk if there are adverse effects from the medications. Pharmacists groups, on the other hand, say the program is too restrictive, according to an article by the research group Advisory Board.

Recently, the White House announced that more than 1,000 pharmacy clinics across the United States had registered to participate in the initiative, according to CNN. Ordering of the drugs is underway in many of these clinics, a White House official told the network.

Besides retail clinics in chain pharmacies, the antivirals will also be available in community health centers, long-term-care facilities, and Veterans Health Administration clinics, according to a statement from the U.S. Department of Health and Human Services.

The two antiviral pills authorized by the U.S. Food and Drug Administration include Pfizer’s Paxlovid, for people 12 and older, and Merck’s molnupiravir, for adults. Either drug has to be taken within 5 days after symptoms appear to be effective in preventing serious illness.

The need for speed is a major reason why the government chose to work with retail clinics that are more accessible than most primary care offices. However, the American Medical Association (AMA), the National Community Pharmacists Association (NCPA), and the American Pharmacists Association (APhA) have publicly criticized the administration’s approach.

The pharmacists’ groups are concerned that the program is limited only to pharmacies with clinics on site, thus restricting the number of pharmacies qualified to participate. Fourteen pharmacy groups, including the NCPA and the APhA, have also sent a letter to the Biden administration urging it to remove barriers to pharmacies ordering the medications.

The groups also want permission as “clinically trained medication experts” to prescribe the drugs and ensure their safe use.

The AMA on March 4 took issue with the prescribing component, saying that “the pharmacy-based clinic component of the test-to-treat plan flouts patient safety and risks significant negative health outcomes.”

In the AMA’s view, prescribing Paxlovid without a patient’s physician being present poses a risk for adverse drug interactions, as neither the nurse practitioners in retail clinics nor the pharmacists who dispense the drug have full knowledge of a patient›s medical history.

The next day, the AMA released another statement, saying it was reassured by comments from administration officials “that patients who have access to a regular source of care should contact their physician shortly after testing positive for COVID-19 to assess their treatment options.”
 

“Traditional doctor-only approach”

Having patients call their doctors after testing positive for COVID in a pharmacy “strikes me as unnecessary in the vast majority of cases, and it will delay treatment,” Robert Wachter, MD, professor and chair of the department of medicine at the University of California San Francisco, said in an interview. “In this case, it seems like the AMA is taking a very traditional doctor-only approach. And the world has changed. It’s much more of a team sport than an individual sport, the way it was years ago.”

Dr. Wachter said he has the utmost respect for pharmacists’ ability to screen prescriptions for adverse drug interactions. “We’re required to do medication reconciliation when patients see us,” he says. “And in many hospitals, we delegate that to pharmacists. They’re at least as good at it if not better than physicians are.”

While it’s essential to know what other medications a patient is taking, he noted, pharmacies have computer records of all the prescriptions they’ve filled for patients. In addition, pharmacies have access to complete medication histories through Surescripts, the company that enables electronic prescribing transactions between prescribers and pharmacies.
 

Drug interactions “not trivial”

Preeti Malani, MD, the chief health officer and a professor of medicine in the division of infectious diseases at the University of Michigan in Ann Arbor, told this news organization that the potential interactions between Paxlovid and some other medications are “not trivial.”

However, she said, “The really dangerous drugs are the ones for people who have had organ transplants and the like. Those aren’t individuals who are going to shop at a pharmacy.”

Besides the antirejection drugs, Dr. Wachter said, there can be serious interactions with cholesterol-lowering medications. If a person is taking Lipitor, for instance, “Someone would have to make the decision on whether it’s ok for me to stop it for a while, or to lower the dose. But I trust the pharmacist to do that as well as anybody.”

Except for these potential drug interactions with Paxlovid, the antiviral medications are “quite safe,” he said, adding that being able to treat people who test positive for COVID-19 right away is a big advantage of the test-to-treat program, considering how difficult it is for many people to get access to a doctor. That delay could mean that the antivirals are not prescribed and taken until they are no longer effective.

Both Dr. Wachter and Dr. Malani said that the widespread distribution of pharmacies and their extended hours are other big pluses, especially for people who can’t easily leave work or travel far to visit a physician.

Dr. Malani cautioned that there are still kinks to work out in the test-to-treat program. It will be a while before the retail clinics all have the antiviral drugs, and many pharmacies don’t have clinics on site.

Still, she said people can still go to their physicians to be tested, and presumably those doctors can also write antiviral prescriptions. But it’s not clear where the antivirals will be available in the near term.

“Right now, we’re playing catch-up,” Dr. Malani said. “But pharmacies are an important piece of the puzzle.”

Looking at the big picture, she said, “We know that neither vaccination nor natural infection provides long lasting immunity, and so there will be a role for antivirals in order to make this a manageable illness. And when you’re talking about millions of cases, as we were having a few months ago, the health system can’t field all those patients. So we do need a system where I can go to a pharmacy and get a test and treatment.”

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

The Biden administration’s new test-to-treat program is simple on the surface: if you feel like you may have COVID-19, go to a pharmacy, get tested, and, if positive, get treated with an antiviral medication on the spot.

But the program is not that simple to groups representing physicians and pharmacists.

One large physicians’ group is concerned that the program leaves doctors on the margins, and may put patients at risk if there are adverse effects from the medications. Pharmacists groups, on the other hand, say the program is too restrictive, according to an article by the research group Advisory Board.

Recently, the White House announced that more than 1,000 pharmacy clinics across the United States had registered to participate in the initiative, according to CNN. Ordering of the drugs is underway in many of these clinics, a White House official told the network.

Besides retail clinics in chain pharmacies, the antivirals will also be available in community health centers, long-term-care facilities, and Veterans Health Administration clinics, according to a statement from the U.S. Department of Health and Human Services.

The two antiviral pills authorized by the U.S. Food and Drug Administration include Pfizer’s Paxlovid, for people 12 and older, and Merck’s molnupiravir, for adults. Either drug has to be taken within 5 days after symptoms appear to be effective in preventing serious illness.

The need for speed is a major reason why the government chose to work with retail clinics that are more accessible than most primary care offices. However, the American Medical Association (AMA), the National Community Pharmacists Association (NCPA), and the American Pharmacists Association (APhA) have publicly criticized the administration’s approach.

The pharmacists’ groups are concerned that the program is limited only to pharmacies with clinics on site, thus restricting the number of pharmacies qualified to participate. Fourteen pharmacy groups, including the NCPA and the APhA, have also sent a letter to the Biden administration urging it to remove barriers to pharmacies ordering the medications.

The groups also want permission as “clinically trained medication experts” to prescribe the drugs and ensure their safe use.

The AMA on March 4 took issue with the prescribing component, saying that “the pharmacy-based clinic component of the test-to-treat plan flouts patient safety and risks significant negative health outcomes.”

In the AMA’s view, prescribing Paxlovid without a patient’s physician being present poses a risk for adverse drug interactions, as neither the nurse practitioners in retail clinics nor the pharmacists who dispense the drug have full knowledge of a patient›s medical history.

The next day, the AMA released another statement, saying it was reassured by comments from administration officials “that patients who have access to a regular source of care should contact their physician shortly after testing positive for COVID-19 to assess their treatment options.”
 

“Traditional doctor-only approach”

Having patients call their doctors after testing positive for COVID in a pharmacy “strikes me as unnecessary in the vast majority of cases, and it will delay treatment,” Robert Wachter, MD, professor and chair of the department of medicine at the University of California San Francisco, said in an interview. “In this case, it seems like the AMA is taking a very traditional doctor-only approach. And the world has changed. It’s much more of a team sport than an individual sport, the way it was years ago.”

Dr. Wachter said he has the utmost respect for pharmacists’ ability to screen prescriptions for adverse drug interactions. “We’re required to do medication reconciliation when patients see us,” he says. “And in many hospitals, we delegate that to pharmacists. They’re at least as good at it if not better than physicians are.”

While it’s essential to know what other medications a patient is taking, he noted, pharmacies have computer records of all the prescriptions they’ve filled for patients. In addition, pharmacies have access to complete medication histories through Surescripts, the company that enables electronic prescribing transactions between prescribers and pharmacies.
 

Drug interactions “not trivial”

Preeti Malani, MD, the chief health officer and a professor of medicine in the division of infectious diseases at the University of Michigan in Ann Arbor, told this news organization that the potential interactions between Paxlovid and some other medications are “not trivial.”

However, she said, “The really dangerous drugs are the ones for people who have had organ transplants and the like. Those aren’t individuals who are going to shop at a pharmacy.”

Besides the antirejection drugs, Dr. Wachter said, there can be serious interactions with cholesterol-lowering medications. If a person is taking Lipitor, for instance, “Someone would have to make the decision on whether it’s ok for me to stop it for a while, or to lower the dose. But I trust the pharmacist to do that as well as anybody.”

Except for these potential drug interactions with Paxlovid, the antiviral medications are “quite safe,” he said, adding that being able to treat people who test positive for COVID-19 right away is a big advantage of the test-to-treat program, considering how difficult it is for many people to get access to a doctor. That delay could mean that the antivirals are not prescribed and taken until they are no longer effective.

Both Dr. Wachter and Dr. Malani said that the widespread distribution of pharmacies and their extended hours are other big pluses, especially for people who can’t easily leave work or travel far to visit a physician.

Dr. Malani cautioned that there are still kinks to work out in the test-to-treat program. It will be a while before the retail clinics all have the antiviral drugs, and many pharmacies don’t have clinics on site.

Still, she said people can still go to their physicians to be tested, and presumably those doctors can also write antiviral prescriptions. But it’s not clear where the antivirals will be available in the near term.

“Right now, we’re playing catch-up,” Dr. Malani said. “But pharmacies are an important piece of the puzzle.”

Looking at the big picture, she said, “We know that neither vaccination nor natural infection provides long lasting immunity, and so there will be a role for antivirals in order to make this a manageable illness. And when you’re talking about millions of cases, as we were having a few months ago, the health system can’t field all those patients. So we do need a system where I can go to a pharmacy and get a test and treatment.”

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

The Biden administration’s new test-to-treat program is simple on the surface: if you feel like you may have COVID-19, go to a pharmacy, get tested, and, if positive, get treated with an antiviral medication on the spot.

But the program is not that simple to groups representing physicians and pharmacists.

One large physicians’ group is concerned that the program leaves doctors on the margins, and may put patients at risk if there are adverse effects from the medications. Pharmacists groups, on the other hand, say the program is too restrictive, according to an article by the research group Advisory Board.

Recently, the White House announced that more than 1,000 pharmacy clinics across the United States had registered to participate in the initiative, according to CNN. Ordering of the drugs is underway in many of these clinics, a White House official told the network.

Besides retail clinics in chain pharmacies, the antivirals will also be available in community health centers, long-term-care facilities, and Veterans Health Administration clinics, according to a statement from the U.S. Department of Health and Human Services.

The two antiviral pills authorized by the U.S. Food and Drug Administration include Pfizer’s Paxlovid, for people 12 and older, and Merck’s molnupiravir, for adults. Either drug has to be taken within 5 days after symptoms appear to be effective in preventing serious illness.

The need for speed is a major reason why the government chose to work with retail clinics that are more accessible than most primary care offices. However, the American Medical Association (AMA), the National Community Pharmacists Association (NCPA), and the American Pharmacists Association (APhA) have publicly criticized the administration’s approach.

The pharmacists’ groups are concerned that the program is limited only to pharmacies with clinics on site, thus restricting the number of pharmacies qualified to participate. Fourteen pharmacy groups, including the NCPA and the APhA, have also sent a letter to the Biden administration urging it to remove barriers to pharmacies ordering the medications.

The groups also want permission as “clinically trained medication experts” to prescribe the drugs and ensure their safe use.

The AMA on March 4 took issue with the prescribing component, saying that “the pharmacy-based clinic component of the test-to-treat plan flouts patient safety and risks significant negative health outcomes.”

In the AMA’s view, prescribing Paxlovid without a patient’s physician being present poses a risk for adverse drug interactions, as neither the nurse practitioners in retail clinics nor the pharmacists who dispense the drug have full knowledge of a patient›s medical history.

The next day, the AMA released another statement, saying it was reassured by comments from administration officials “that patients who have access to a regular source of care should contact their physician shortly after testing positive for COVID-19 to assess their treatment options.”
 

“Traditional doctor-only approach”

Having patients call their doctors after testing positive for COVID in a pharmacy “strikes me as unnecessary in the vast majority of cases, and it will delay treatment,” Robert Wachter, MD, professor and chair of the department of medicine at the University of California San Francisco, said in an interview. “In this case, it seems like the AMA is taking a very traditional doctor-only approach. And the world has changed. It’s much more of a team sport than an individual sport, the way it was years ago.”

Dr. Wachter said he has the utmost respect for pharmacists’ ability to screen prescriptions for adverse drug interactions. “We’re required to do medication reconciliation when patients see us,” he says. “And in many hospitals, we delegate that to pharmacists. They’re at least as good at it if not better than physicians are.”

While it’s essential to know what other medications a patient is taking, he noted, pharmacies have computer records of all the prescriptions they’ve filled for patients. In addition, pharmacies have access to complete medication histories through Surescripts, the company that enables electronic prescribing transactions between prescribers and pharmacies.
 

Drug interactions “not trivial”

Preeti Malani, MD, the chief health officer and a professor of medicine in the division of infectious diseases at the University of Michigan in Ann Arbor, told this news organization that the potential interactions between Paxlovid and some other medications are “not trivial.”

However, she said, “The really dangerous drugs are the ones for people who have had organ transplants and the like. Those aren’t individuals who are going to shop at a pharmacy.”

Besides the antirejection drugs, Dr. Wachter said, there can be serious interactions with cholesterol-lowering medications. If a person is taking Lipitor, for instance, “Someone would have to make the decision on whether it’s ok for me to stop it for a while, or to lower the dose. But I trust the pharmacist to do that as well as anybody.”

Except for these potential drug interactions with Paxlovid, the antiviral medications are “quite safe,” he said, adding that being able to treat people who test positive for COVID-19 right away is a big advantage of the test-to-treat program, considering how difficult it is for many people to get access to a doctor. That delay could mean that the antivirals are not prescribed and taken until they are no longer effective.

Both Dr. Wachter and Dr. Malani said that the widespread distribution of pharmacies and their extended hours are other big pluses, especially for people who can’t easily leave work or travel far to visit a physician.

Dr. Malani cautioned that there are still kinks to work out in the test-to-treat program. It will be a while before the retail clinics all have the antiviral drugs, and many pharmacies don’t have clinics on site.

Still, she said people can still go to their physicians to be tested, and presumably those doctors can also write antiviral prescriptions. But it’s not clear where the antivirals will be available in the near term.

“Right now, we’re playing catch-up,” Dr. Malani said. “But pharmacies are an important piece of the puzzle.”

Looking at the big picture, she said, “We know that neither vaccination nor natural infection provides long lasting immunity, and so there will be a role for antivirals in order to make this a manageable illness. And when you’re talking about millions of cases, as we were having a few months ago, the health system can’t field all those patients. So we do need a system where I can go to a pharmacy and get a test and treatment.”

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

Should pharmaceutical companies continue to do business in Russia, running ongoing clinical trials, starting new ones, or continuing to sell their products there?

Some argue that medicine and science must not get enmeshed in politics, staying above the fray to protect their independence and credibility. Other defenders of business-as-usual say the pharmaceutical industry deals in health and aids the vulnerable. Humanitarianism requires continued interaction with Russia.

I think both arguments fail. Pharma should follow the lead of other Western companies and suspend their involvement with Putin’s Russia.

We are fighting a war with Russia. It is a war of economic strangulation, social isolation, and pushing Russia as hard as we can to become a pariah state so that internal pressure on Putin will cause him to rethink his cruel, unjustified invasion or the Russian people to replace him. This pressure must be harsh and it must happen quickly. Why?

Having failed to rapidly defeat the Ukrainian army in the war’s first weeks, Russian commanders are now resorting to the horrible barbarism they used in previous wars in Chechnya and Syria: flattening cities, attacking civilians, killing children with massive and indiscriminate firepower.

To mention one recent horror among many, Russian shelling destroyed a maternity hospital in Mariupol. Ukraine’s president, Volodymyr Zelensky, in bemoaning the Russians for their continuing series of war crimes called on the world to act.

“Mariupol. Direct Strike of Russian troops at the maternity hospital,” he wrote in a Twitter post. “People, children are under the wreckage. Atrocity! How much longer will the world be an accomplice ignoring terror?”

The Russian government’s response: “It is not the first time we have seen pathetic outcries concerning the so-called atrocities,” said Minister of Foreign Affairs Sergei Lavrov, claiming the hospital was being used as a base by an “ultra-radical” Ukrainian battalion.

Health and its preservation are key parts of the aim of medicine and science. There is no way that medicine and science can ignore what war does to health, what attacks on hospitals do to the sick and those who serve them there, the psychological toll that intentional terrorism takes on civilians and their defenders, and what the destruction of infrastructure means for the long-term well-being of Ukrainians.

There can be no collusion with war criminals. There can be no denial of the inextricable link between medicine, science, and politics. Medicine and science are controlled by political forces; their use for good or evil is driven by political considerations, and each doctor, scientist, and scientific society must take a stand when politics corrodes the underlying aims of research and healing.

How far does noncooperation with Russia go? Very, very far. All research, both ongoing and new, must cease immediately. Whatever can be done to minimize harm to existing subjects in a short period of time ought to be done, but that is it.

Similarly, no sale of medicines or therapies ought to be occurring, be they life-saving or consumer products. Putin will see to it that such shipments go to the military or are sold on the black market for revenue, and there is nothing pharma companies can do to stop that.

The Russian people need to be pinched not only by the loss of cheeseburgers and boutique coffee but by products they use to maintain their well-being. War is cruel that way, but if you tolerate a government that is bombing and shelling a peaceful neighbor to oblivion, then pharma must ensure that efforts to make Putin and his kleptocratic goons feel the wrath of their fellow citizens.

Given the realities of nuclear Armageddon, the civilized world must fight obvious barbarity as best it can with sanctions, financial assaults, property seizures, and forgoing commerce, including important raw materials and health products. War, even in a fiscal form, is not without terrible costs; but achieving a rapid, just resolution against tyranny permits no exceptions for pharma or any other business if it is a war that must be fought.

Dr. Caplan is director of the division of medical ethics at New York University. He has consulted with Johnson & Johnson’s Panel for Compassionate Drug Use.



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

Should pharmaceutical companies continue to do business in Russia, running ongoing clinical trials, starting new ones, or continuing to sell their products there?

Some argue that medicine and science must not get enmeshed in politics, staying above the fray to protect their independence and credibility. Other defenders of business-as-usual say the pharmaceutical industry deals in health and aids the vulnerable. Humanitarianism requires continued interaction with Russia.

I think both arguments fail. Pharma should follow the lead of other Western companies and suspend their involvement with Putin’s Russia.

We are fighting a war with Russia. It is a war of economic strangulation, social isolation, and pushing Russia as hard as we can to become a pariah state so that internal pressure on Putin will cause him to rethink his cruel, unjustified invasion or the Russian people to replace him. This pressure must be harsh and it must happen quickly. Why?

Having failed to rapidly defeat the Ukrainian army in the war’s first weeks, Russian commanders are now resorting to the horrible barbarism they used in previous wars in Chechnya and Syria: flattening cities, attacking civilians, killing children with massive and indiscriminate firepower.

To mention one recent horror among many, Russian shelling destroyed a maternity hospital in Mariupol. Ukraine’s president, Volodymyr Zelensky, in bemoaning the Russians for their continuing series of war crimes called on the world to act.

“Mariupol. Direct Strike of Russian troops at the maternity hospital,” he wrote in a Twitter post. “People, children are under the wreckage. Atrocity! How much longer will the world be an accomplice ignoring terror?”

The Russian government’s response: “It is not the first time we have seen pathetic outcries concerning the so-called atrocities,” said Minister of Foreign Affairs Sergei Lavrov, claiming the hospital was being used as a base by an “ultra-radical” Ukrainian battalion.

Health and its preservation are key parts of the aim of medicine and science. There is no way that medicine and science can ignore what war does to health, what attacks on hospitals do to the sick and those who serve them there, the psychological toll that intentional terrorism takes on civilians and their defenders, and what the destruction of infrastructure means for the long-term well-being of Ukrainians.

There can be no collusion with war criminals. There can be no denial of the inextricable link between medicine, science, and politics. Medicine and science are controlled by political forces; their use for good or evil is driven by political considerations, and each doctor, scientist, and scientific society must take a stand when politics corrodes the underlying aims of research and healing.

How far does noncooperation with Russia go? Very, very far. All research, both ongoing and new, must cease immediately. Whatever can be done to minimize harm to existing subjects in a short period of time ought to be done, but that is it.

Similarly, no sale of medicines or therapies ought to be occurring, be they life-saving or consumer products. Putin will see to it that such shipments go to the military or are sold on the black market for revenue, and there is nothing pharma companies can do to stop that.

The Russian people need to be pinched not only by the loss of cheeseburgers and boutique coffee but by products they use to maintain their well-being. War is cruel that way, but if you tolerate a government that is bombing and shelling a peaceful neighbor to oblivion, then pharma must ensure that efforts to make Putin and his kleptocratic goons feel the wrath of their fellow citizens.

Given the realities of nuclear Armageddon, the civilized world must fight obvious barbarity as best it can with sanctions, financial assaults, property seizures, and forgoing commerce, including important raw materials and health products. War, even in a fiscal form, is not without terrible costs; but achieving a rapid, just resolution against tyranny permits no exceptions for pharma or any other business if it is a war that must be fought.

Dr. Caplan is director of the division of medical ethics at New York University. He has consulted with Johnson & Johnson’s Panel for Compassionate Drug Use.



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

Should pharmaceutical companies continue to do business in Russia, running ongoing clinical trials, starting new ones, or continuing to sell their products there?

Some argue that medicine and science must not get enmeshed in politics, staying above the fray to protect their independence and credibility. Other defenders of business-as-usual say the pharmaceutical industry deals in health and aids the vulnerable. Humanitarianism requires continued interaction with Russia.

I think both arguments fail. Pharma should follow the lead of other Western companies and suspend their involvement with Putin’s Russia.

We are fighting a war with Russia. It is a war of economic strangulation, social isolation, and pushing Russia as hard as we can to become a pariah state so that internal pressure on Putin will cause him to rethink his cruel, unjustified invasion or the Russian people to replace him. This pressure must be harsh and it must happen quickly. Why?

Having failed to rapidly defeat the Ukrainian army in the war’s first weeks, Russian commanders are now resorting to the horrible barbarism they used in previous wars in Chechnya and Syria: flattening cities, attacking civilians, killing children with massive and indiscriminate firepower.

To mention one recent horror among many, Russian shelling destroyed a maternity hospital in Mariupol. Ukraine’s president, Volodymyr Zelensky, in bemoaning the Russians for their continuing series of war crimes called on the world to act.

“Mariupol. Direct Strike of Russian troops at the maternity hospital,” he wrote in a Twitter post. “People, children are under the wreckage. Atrocity! How much longer will the world be an accomplice ignoring terror?”

The Russian government’s response: “It is not the first time we have seen pathetic outcries concerning the so-called atrocities,” said Minister of Foreign Affairs Sergei Lavrov, claiming the hospital was being used as a base by an “ultra-radical” Ukrainian battalion.

Health and its preservation are key parts of the aim of medicine and science. There is no way that medicine and science can ignore what war does to health, what attacks on hospitals do to the sick and those who serve them there, the psychological toll that intentional terrorism takes on civilians and their defenders, and what the destruction of infrastructure means for the long-term well-being of Ukrainians.

There can be no collusion with war criminals. There can be no denial of the inextricable link between medicine, science, and politics. Medicine and science are controlled by political forces; their use for good or evil is driven by political considerations, and each doctor, scientist, and scientific society must take a stand when politics corrodes the underlying aims of research and healing.

How far does noncooperation with Russia go? Very, very far. All research, both ongoing and new, must cease immediately. Whatever can be done to minimize harm to existing subjects in a short period of time ought to be done, but that is it.

Similarly, no sale of medicines or therapies ought to be occurring, be they life-saving or consumer products. Putin will see to it that such shipments go to the military or are sold on the black market for revenue, and there is nothing pharma companies can do to stop that.

The Russian people need to be pinched not only by the loss of cheeseburgers and boutique coffee but by products they use to maintain their well-being. War is cruel that way, but if you tolerate a government that is bombing and shelling a peaceful neighbor to oblivion, then pharma must ensure that efforts to make Putin and his kleptocratic goons feel the wrath of their fellow citizens.

Given the realities of nuclear Armageddon, the civilized world must fight obvious barbarity as best it can with sanctions, financial assaults, property seizures, and forgoing commerce, including important raw materials and health products. War, even in a fiscal form, is not without terrible costs; but achieving a rapid, just resolution against tyranny permits no exceptions for pharma or any other business if it is a war that must be fought.

Dr. Caplan is director of the division of medical ethics at New York University. He has consulted with Johnson & Johnson’s Panel for Compassionate Drug Use.



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

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

Even as the war in Ukraine has prompted an exodus of international companies — from fast-food chains and oil producers to luxury retailers — from Russia, U.S. and global drug companies said they would continue manufacturing and selling their products there.

Airlines, automakers, banks, and technology giants — at least 320 companies by one count — are among the businesses curtailing operations or making high-profile exits from Russia as its invasion of Ukraine intensifies. McDonald’s, Starbucks, and Coca-Cola announced a pause in sales recently.

But drugmakers, medical device manufacturers, and health care companies, which are exempted from U.S. and European sanctions, said Russians need access to medicines and medical equipment and contend that international humanitarian law requires they keep supply chains open.

“As a health care company, we have an important purpose, which is why at this time we continue to serve people in all countries in which we operate who depend on us for essential products, some life-sustaining,” said Scott Stoffel, divisional vice president for Illinois-based Abbott Laboratories, which manufactures and sells medicines in Russia for oncology, women’s health, pancreatic insufficiency, and liver health.

Johnson & Johnson — which has corporate offices in Moscow, Novosibirsk, St. Petersburg, and Yekaterinburg — said in a statement, “We remain committed to providing essential health products to those in need in Ukraine, Russia, and the region, in compliance with current sanctions and while adapting to the rapidly changing situation on the ground.”

The reluctance of drugmakers to pause operations in Russia is being met with a growing chorus of criticism.

Pharmaceutical companies that say they must continue to manufacture drugs in Russia for humanitarian reasons are “being misguided at best, cynical in the medium case, and outright deplorably misleading and deceptive,” said Jeffrey Sonnenfeld, DBA, a professor at the Yale School of Management who is tracking which companies have curtailed operations in Russia. He noted that banks and technology companies also provide essential services.

“Russians are put in a tragic position of unearned suffering. If we continue to make life palatable for them, then we are continuing to support the regime,” Dr. Sonnenfeld said. “These drug companies will be seen as complicit with the most vicious operation on the planet. Instead of protecting life, they are going to be seen as destroying life. The goal here is to show that Putin is not in control of all sectors of the economy.”

U.S. pharmaceutical and medical companies have operated in Russia for decades, and many ramped up operations after Russia invaded and annexed Crimea in 2014, navigating the fraught relationship between the United States and Russia amid sanctions. In 2010, Vladimir Putin, then Russian prime minister, announced an ambitious national plan for the Russian pharmaceutical industry that would be a pillar in his efforts to reestablish his country as an influential superpower and wean the country off Western pharmaceutical imports. Under the plan, called “Pharma-2020” and “Pharma-2030,” the government required Western pharmaceutical companies eager to sell to Russia’s growing middle class to locate production inside the country.

Pfizer, Johnson & Johnson, Novartis, and Abbott are among the drugmakers that manufacture pharmaceutical drugs at facilities in St. Petersburg and elsewhere in the country and typically sell those drugs as branded generics or under Russian brands.

Pfizer’s CEO, Albert Bourla, said on CBS that the giant drugmaker is not going to make further investments in Russia, but that it will not cut ties with Russia, as multinational companies in other industries are doing.

Pharmaceutical manufacturing plants in Kaluga, a major manufacturing center for Volkswagen and Volvo southwest of Moscow, have been funded through a partnership between Rusnano, a state-owned venture that promotes the development of high-tech enterprises, and U.S. venture capital firms.

Russia also has sought to position itself as an attractive research market, offering an inexpensive and lax regulatory environment for clinical drug trials. Last year, Pfizer conducted in Russia clinical trials of Paxlovid, its experimental antiviral pill to treat covid-19. Before the invasion began in late February, 3,072 trials were underway in Russia and 503 were underway in Ukraine, according to BioWorld, a reporting hub focused on drug development that features data from Cortellis.

AstraZeneca is the top sponsor of clinical trials in Russia, with 49 trials, followed by a subsidiary of Merck, with 48 trials.

So far, drugmakers’ response to the Ukraine invasion has largely centered on public pledges to donate essential medicines and vaccines to Ukrainian patients and refugees. They’ve also made general comments about the need to keep open the supply of medicines flowing within Russia.

Abbott has pledged $2 million to support humanitarian efforts in Ukraine, and Pfizer, based in New York, said it has supplied $1 million in humanitarian grants. Swiss drug maker Novartis said it was expanding humanitarian efforts in Ukraine and working to “ensure the continued supply of our medicines in Ukraine.”

But no major pharmaceutical or medical device maker has announced plans to shutter manufacturing plants or halt sales inside Russia.

In an open letter, hundreds of leaders of mainly smaller biotechnology companies have called on industry members to cease business activities in Russia, including “investment in Russian companies and new investment within the borders of Russia,” and to halt trade and collaboration with Russian companies, except for supplying food and medicines. How many of the signatories have business operations in Russia was unclear.

Ulrich Neumann, director for market access at Janssen, a Johnson & Johnson company, was among those who signed the letter, but whether he was speaking for the company was unclear. In its own statement posted on social media, the company said it’s “committed to providing access to our essential medical products in the countries where we operate, in compliance with current international sanctions.”

GlaxoSmithKline, headquartered in the United Kingdom, said in a statement that it’s stopping all advertising in Russia and will not enter into contracts that “directly support the Russian administration or military.” But the company said that as a “supplier of needed medicines, vaccines and everyday health products, we have a responsibility to do all we can to make them available. For this reason, we will continue to supply our products to the people of Russia, while we can.”

Nell Minow, vice chair of ValueEdge Advisors, an investment consulting firm, noted that drug companies have been treated differently than other industries during previous global conflicts. For example, some corporate ethicists advised against pharmaceutical companies’ total divestment from South Africa’s apartheid regime to ensure essential medicines flowed to the country.

“There is a difference between a hamburger and a pill,” Mr. Minow said. Companies should strongly condemn Russia’s actions, she said, but unless the United States enters directly into a war with Russia, companies that make essential medicines and health care products should continue to operate. Before U.S. involvement in World War II, she added, there were “some American companies that did business with Germany until the last minute.”
 

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. KHN senior correspondent Arthur Allen contributed to this article.

Even as the war in Ukraine has prompted an exodus of international companies — from fast-food chains and oil producers to luxury retailers — from Russia, U.S. and global drug companies said they would continue manufacturing and selling their products there.

Airlines, automakers, banks, and technology giants — at least 320 companies by one count — are among the businesses curtailing operations or making high-profile exits from Russia as its invasion of Ukraine intensifies. McDonald’s, Starbucks, and Coca-Cola announced a pause in sales recently.

But drugmakers, medical device manufacturers, and health care companies, which are exempted from U.S. and European sanctions, said Russians need access to medicines and medical equipment and contend that international humanitarian law requires they keep supply chains open.

“As a health care company, we have an important purpose, which is why at this time we continue to serve people in all countries in which we operate who depend on us for essential products, some life-sustaining,” said Scott Stoffel, divisional vice president for Illinois-based Abbott Laboratories, which manufactures and sells medicines in Russia for oncology, women’s health, pancreatic insufficiency, and liver health.

Johnson & Johnson — which has corporate offices in Moscow, Novosibirsk, St. Petersburg, and Yekaterinburg — said in a statement, “We remain committed to providing essential health products to those in need in Ukraine, Russia, and the region, in compliance with current sanctions and while adapting to the rapidly changing situation on the ground.”

The reluctance of drugmakers to pause operations in Russia is being met with a growing chorus of criticism.

Pharmaceutical companies that say they must continue to manufacture drugs in Russia for humanitarian reasons are “being misguided at best, cynical in the medium case, and outright deplorably misleading and deceptive,” said Jeffrey Sonnenfeld, DBA, a professor at the Yale School of Management who is tracking which companies have curtailed operations in Russia. He noted that banks and technology companies also provide essential services.

“Russians are put in a tragic position of unearned suffering. If we continue to make life palatable for them, then we are continuing to support the regime,” Dr. Sonnenfeld said. “These drug companies will be seen as complicit with the most vicious operation on the planet. Instead of protecting life, they are going to be seen as destroying life. The goal here is to show that Putin is not in control of all sectors of the economy.”

U.S. pharmaceutical and medical companies have operated in Russia for decades, and many ramped up operations after Russia invaded and annexed Crimea in 2014, navigating the fraught relationship between the United States and Russia amid sanctions. In 2010, Vladimir Putin, then Russian prime minister, announced an ambitious national plan for the Russian pharmaceutical industry that would be a pillar in his efforts to reestablish his country as an influential superpower and wean the country off Western pharmaceutical imports. Under the plan, called “Pharma-2020” and “Pharma-2030,” the government required Western pharmaceutical companies eager to sell to Russia’s growing middle class to locate production inside the country.

Pfizer, Johnson & Johnson, Novartis, and Abbott are among the drugmakers that manufacture pharmaceutical drugs at facilities in St. Petersburg and elsewhere in the country and typically sell those drugs as branded generics or under Russian brands.

Pfizer’s CEO, Albert Bourla, said on CBS that the giant drugmaker is not going to make further investments in Russia, but that it will not cut ties with Russia, as multinational companies in other industries are doing.

Pharmaceutical manufacturing plants in Kaluga, a major manufacturing center for Volkswagen and Volvo southwest of Moscow, have been funded through a partnership between Rusnano, a state-owned venture that promotes the development of high-tech enterprises, and U.S. venture capital firms.

Russia also has sought to position itself as an attractive research market, offering an inexpensive and lax regulatory environment for clinical drug trials. Last year, Pfizer conducted in Russia clinical trials of Paxlovid, its experimental antiviral pill to treat covid-19. Before the invasion began in late February, 3,072 trials were underway in Russia and 503 were underway in Ukraine, according to BioWorld, a reporting hub focused on drug development that features data from Cortellis.

AstraZeneca is the top sponsor of clinical trials in Russia, with 49 trials, followed by a subsidiary of Merck, with 48 trials.

So far, drugmakers’ response to the Ukraine invasion has largely centered on public pledges to donate essential medicines and vaccines to Ukrainian patients and refugees. They’ve also made general comments about the need to keep open the supply of medicines flowing within Russia.

Abbott has pledged $2 million to support humanitarian efforts in Ukraine, and Pfizer, based in New York, said it has supplied $1 million in humanitarian grants. Swiss drug maker Novartis said it was expanding humanitarian efforts in Ukraine and working to “ensure the continued supply of our medicines in Ukraine.”

But no major pharmaceutical or medical device maker has announced plans to shutter manufacturing plants or halt sales inside Russia.

In an open letter, hundreds of leaders of mainly smaller biotechnology companies have called on industry members to cease business activities in Russia, including “investment in Russian companies and new investment within the borders of Russia,” and to halt trade and collaboration with Russian companies, except for supplying food and medicines. How many of the signatories have business operations in Russia was unclear.

Ulrich Neumann, director for market access at Janssen, a Johnson & Johnson company, was among those who signed the letter, but whether he was speaking for the company was unclear. In its own statement posted on social media, the company said it’s “committed to providing access to our essential medical products in the countries where we operate, in compliance with current international sanctions.”

GlaxoSmithKline, headquartered in the United Kingdom, said in a statement that it’s stopping all advertising in Russia and will not enter into contracts that “directly support the Russian administration or military.” But the company said that as a “supplier of needed medicines, vaccines and everyday health products, we have a responsibility to do all we can to make them available. For this reason, we will continue to supply our products to the people of Russia, while we can.”

Nell Minow, vice chair of ValueEdge Advisors, an investment consulting firm, noted that drug companies have been treated differently than other industries during previous global conflicts. For example, some corporate ethicists advised against pharmaceutical companies’ total divestment from South Africa’s apartheid regime to ensure essential medicines flowed to the country.

“There is a difference between a hamburger and a pill,” Mr. Minow said. Companies should strongly condemn Russia’s actions, she said, but unless the United States enters directly into a war with Russia, companies that make essential medicines and health care products should continue to operate. Before U.S. involvement in World War II, she added, there were “some American companies that did business with Germany until the last minute.”
 

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. KHN senior correspondent Arthur Allen contributed to this article.

Even as the war in Ukraine has prompted an exodus of international companies — from fast-food chains and oil producers to luxury retailers — from Russia, U.S. and global drug companies said they would continue manufacturing and selling their products there.

Airlines, automakers, banks, and technology giants — at least 320 companies by one count — are among the businesses curtailing operations or making high-profile exits from Russia as its invasion of Ukraine intensifies. McDonald’s, Starbucks, and Coca-Cola announced a pause in sales recently.

But drugmakers, medical device manufacturers, and health care companies, which are exempted from U.S. and European sanctions, said Russians need access to medicines and medical equipment and contend that international humanitarian law requires they keep supply chains open.

“As a health care company, we have an important purpose, which is why at this time we continue to serve people in all countries in which we operate who depend on us for essential products, some life-sustaining,” said Scott Stoffel, divisional vice president for Illinois-based Abbott Laboratories, which manufactures and sells medicines in Russia for oncology, women’s health, pancreatic insufficiency, and liver health.

Johnson & Johnson — which has corporate offices in Moscow, Novosibirsk, St. Petersburg, and Yekaterinburg — said in a statement, “We remain committed to providing essential health products to those in need in Ukraine, Russia, and the region, in compliance with current sanctions and while adapting to the rapidly changing situation on the ground.”

The reluctance of drugmakers to pause operations in Russia is being met with a growing chorus of criticism.

Pharmaceutical companies that say they must continue to manufacture drugs in Russia for humanitarian reasons are “being misguided at best, cynical in the medium case, and outright deplorably misleading and deceptive,” said Jeffrey Sonnenfeld, DBA, a professor at the Yale School of Management who is tracking which companies have curtailed operations in Russia. He noted that banks and technology companies also provide essential services.

“Russians are put in a tragic position of unearned suffering. If we continue to make life palatable for them, then we are continuing to support the regime,” Dr. Sonnenfeld said. “These drug companies will be seen as complicit with the most vicious operation on the planet. Instead of protecting life, they are going to be seen as destroying life. The goal here is to show that Putin is not in control of all sectors of the economy.”

U.S. pharmaceutical and medical companies have operated in Russia for decades, and many ramped up operations after Russia invaded and annexed Crimea in 2014, navigating the fraught relationship between the United States and Russia amid sanctions. In 2010, Vladimir Putin, then Russian prime minister, announced an ambitious national plan for the Russian pharmaceutical industry that would be a pillar in his efforts to reestablish his country as an influential superpower and wean the country off Western pharmaceutical imports. Under the plan, called “Pharma-2020” and “Pharma-2030,” the government required Western pharmaceutical companies eager to sell to Russia’s growing middle class to locate production inside the country.

Pfizer, Johnson & Johnson, Novartis, and Abbott are among the drugmakers that manufacture pharmaceutical drugs at facilities in St. Petersburg and elsewhere in the country and typically sell those drugs as branded generics or under Russian brands.

Pfizer’s CEO, Albert Bourla, said on CBS that the giant drugmaker is not going to make further investments in Russia, but that it will not cut ties with Russia, as multinational companies in other industries are doing.

Pharmaceutical manufacturing plants in Kaluga, a major manufacturing center for Volkswagen and Volvo southwest of Moscow, have been funded through a partnership between Rusnano, a state-owned venture that promotes the development of high-tech enterprises, and U.S. venture capital firms.

Russia also has sought to position itself as an attractive research market, offering an inexpensive and lax regulatory environment for clinical drug trials. Last year, Pfizer conducted in Russia clinical trials of Paxlovid, its experimental antiviral pill to treat covid-19. Before the invasion began in late February, 3,072 trials were underway in Russia and 503 were underway in Ukraine, according to BioWorld, a reporting hub focused on drug development that features data from Cortellis.

AstraZeneca is the top sponsor of clinical trials in Russia, with 49 trials, followed by a subsidiary of Merck, with 48 trials.

So far, drugmakers’ response to the Ukraine invasion has largely centered on public pledges to donate essential medicines and vaccines to Ukrainian patients and refugees. They’ve also made general comments about the need to keep open the supply of medicines flowing within Russia.

Abbott has pledged $2 million to support humanitarian efforts in Ukraine, and Pfizer, based in New York, said it has supplied $1 million in humanitarian grants. Swiss drug maker Novartis said it was expanding humanitarian efforts in Ukraine and working to “ensure the continued supply of our medicines in Ukraine.”

But no major pharmaceutical or medical device maker has announced plans to shutter manufacturing plants or halt sales inside Russia.

In an open letter, hundreds of leaders of mainly smaller biotechnology companies have called on industry members to cease business activities in Russia, including “investment in Russian companies and new investment within the borders of Russia,” and to halt trade and collaboration with Russian companies, except for supplying food and medicines. How many of the signatories have business operations in Russia was unclear.

Ulrich Neumann, director for market access at Janssen, a Johnson & Johnson company, was among those who signed the letter, but whether he was speaking for the company was unclear. In its own statement posted on social media, the company said it’s “committed to providing access to our essential medical products in the countries where we operate, in compliance with current international sanctions.”

GlaxoSmithKline, headquartered in the United Kingdom, said in a statement that it’s stopping all advertising in Russia and will not enter into contracts that “directly support the Russian administration or military.” But the company said that as a “supplier of needed medicines, vaccines and everyday health products, we have a responsibility to do all we can to make them available. For this reason, we will continue to supply our products to the people of Russia, while we can.”

Nell Minow, vice chair of ValueEdge Advisors, an investment consulting firm, noted that drug companies have been treated differently than other industries during previous global conflicts. For example, some corporate ethicists advised against pharmaceutical companies’ total divestment from South Africa’s apartheid regime to ensure essential medicines flowed to the country.

“There is a difference between a hamburger and a pill,” Mr. Minow said. Companies should strongly condemn Russia’s actions, she said, but unless the United States enters directly into a war with Russia, companies that make essential medicines and health care products should continue to operate. Before U.S. involvement in World War II, she added, there were “some American companies that did business with Germany until the last minute.”
 

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. KHN senior correspondent Arthur Allen contributed to this article.

As public attention continues to focus on making insulin affordable, a new online guide is available to help clinicians approach discussions with patients about diabetes medication affordability and access.

The resource, “Having Healthcare Cost Conversations to Improve Patient Outcomes: A Practical Guide,” was jointly developed by the Association of Diabetes Care & Education Specialists and Beyond Type 1, the nonprofit patient advocacy organization.

Indeed, the guide appeared as President Biden discussed his proposal to cap insulin costs at $35 per insulin vial during the State of the Union address, during which he introduced a young boy with type 1 diabetes in the guest box, as reported by this news organization. On March 3, Civica, a nonprofit coalition of health systems and philanthropies, announced it plans to manufacture generic insulin at a deeply discounted price, as reported by this news organization.

“Just to see diabetes front and center at the State of the Union followed by these announcements is certainly reflective of our own advocacy effort to make sure that people have affordable options for insulin, diabetes medications, services,” Kate Thomas, ADCES chief advocacy and external affairs officer, said in an interview. She added that ADCES has also pushed for legislation in Congress that would expand access to diabetes self-management training under the Medicare program.

The guide includes advice about overcoming barriers to discussing treatment costs with patients, suggested questions to ask patients about specific costs, and determinants of health and conversational approaches. Links are provided to resources for obtaining affordable insulin, other diabetes medications, and continuous glucose monitoring and insulin pump equipment.

“We know that, especially during primary care visits, there is limited time along with numbers of issues to talk about, so I think our challenge is how do we prioritize these conversations with something that can lead to action, not just saying you should do this but how do you actually do it,” Ms. Thomas said.

The introduction summarizes results from a 2021 Beyond Type 1 survey confirming prior findings reported by this news organization that cost is a frequent barrier for many individuals living with diabetes. “Especially right now where we are in terms of the impact of the pandemic and with peoples’ job statuses changing, I think it’s worthwhile to raise this in patient encounters,” Ms. Thomas said.
 

Overcoming conversational barriers

The first of three tables in the guide provides a list of “barriers to having a cost conversation” in the first column and “suggested solutions” in the second. For example, for the barrier, “You have insufficient time and/or knowledge about cost,” the suggestion is, “request and share available faculty and resources, including benefits coordinators, social workers, and community-based organizations. Work with the pharmacists and other members of the diabetes care team to identify resources that lower cost of medications.”

And for another barrier, “patients are often embarrassed or ashamed to initiate discussions of affordability,” the suggested solution is: “Normalize the issue of cost of care barriers for patients.”

A second table offers specific questions to ask patients about costs of medications and care, determinants of health, and financial barriers. These include: “What are some challenges you’ve had to accessing your medications or taking them as prescribed? What are some out-of-pocket health care costs you need help with? What challenges do you have accessing healthy food for you and your family?”

A link to a screening tool for social determinants of health is also included.

Language suggestions include talking about “cost of care” rather than “money,” asking patients if they’ve understood everything correctly by repeating back what they’ve said, and asking for confirmation and discussing follow-up.

Overall, the tool is designed to be a “broad conversation starter,” and not just about medications, Ms. Thomas said. “This is for all audiences and it’s meant to be something that the provider can tailor depending on who they’re speaking to. ... It’s about medications, but also the entire cost of care, including services and devices, transportation to appointments, access to food. ... Diabetes care isn’t just taking medication. It’s so many more factors.”

Ms. Thomas reported no relevant financial relationships.

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

As public attention continues to focus on making insulin affordable, a new online guide is available to help clinicians approach discussions with patients about diabetes medication affordability and access.

The resource, “Having Healthcare Cost Conversations to Improve Patient Outcomes: A Practical Guide,” was jointly developed by the Association of Diabetes Care & Education Specialists and Beyond Type 1, the nonprofit patient advocacy organization.

Indeed, the guide appeared as President Biden discussed his proposal to cap insulin costs at $35 per insulin vial during the State of the Union address, during which he introduced a young boy with type 1 diabetes in the guest box, as reported by this news organization. On March 3, Civica, a nonprofit coalition of health systems and philanthropies, announced it plans to manufacture generic insulin at a deeply discounted price, as reported by this news organization.

“Just to see diabetes front and center at the State of the Union followed by these announcements is certainly reflective of our own advocacy effort to make sure that people have affordable options for insulin, diabetes medications, services,” Kate Thomas, ADCES chief advocacy and external affairs officer, said in an interview. She added that ADCES has also pushed for legislation in Congress that would expand access to diabetes self-management training under the Medicare program.

The guide includes advice about overcoming barriers to discussing treatment costs with patients, suggested questions to ask patients about specific costs, and determinants of health and conversational approaches. Links are provided to resources for obtaining affordable insulin, other diabetes medications, and continuous glucose monitoring and insulin pump equipment.

“We know that, especially during primary care visits, there is limited time along with numbers of issues to talk about, so I think our challenge is how do we prioritize these conversations with something that can lead to action, not just saying you should do this but how do you actually do it,” Ms. Thomas said.

The introduction summarizes results from a 2021 Beyond Type 1 survey confirming prior findings reported by this news organization that cost is a frequent barrier for many individuals living with diabetes. “Especially right now where we are in terms of the impact of the pandemic and with peoples’ job statuses changing, I think it’s worthwhile to raise this in patient encounters,” Ms. Thomas said.
 

Overcoming conversational barriers

The first of three tables in the guide provides a list of “barriers to having a cost conversation” in the first column and “suggested solutions” in the second. For example, for the barrier, “You have insufficient time and/or knowledge about cost,” the suggestion is, “request and share available faculty and resources, including benefits coordinators, social workers, and community-based organizations. Work with the pharmacists and other members of the diabetes care team to identify resources that lower cost of medications.”

And for another barrier, “patients are often embarrassed or ashamed to initiate discussions of affordability,” the suggested solution is: “Normalize the issue of cost of care barriers for patients.”

A second table offers specific questions to ask patients about costs of medications and care, determinants of health, and financial barriers. These include: “What are some challenges you’ve had to accessing your medications or taking them as prescribed? What are some out-of-pocket health care costs you need help with? What challenges do you have accessing healthy food for you and your family?”

A link to a screening tool for social determinants of health is also included.

Language suggestions include talking about “cost of care” rather than “money,” asking patients if they’ve understood everything correctly by repeating back what they’ve said, and asking for confirmation and discussing follow-up.

Overall, the tool is designed to be a “broad conversation starter,” and not just about medications, Ms. Thomas said. “This is for all audiences and it’s meant to be something that the provider can tailor depending on who they’re speaking to. ... It’s about medications, but also the entire cost of care, including services and devices, transportation to appointments, access to food. ... Diabetes care isn’t just taking medication. It’s so many more factors.”

Ms. Thomas reported no relevant financial relationships.

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

As public attention continues to focus on making insulin affordable, a new online guide is available to help clinicians approach discussions with patients about diabetes medication affordability and access.

The resource, “Having Healthcare Cost Conversations to Improve Patient Outcomes: A Practical Guide,” was jointly developed by the Association of Diabetes Care & Education Specialists and Beyond Type 1, the nonprofit patient advocacy organization.

Indeed, the guide appeared as President Biden discussed his proposal to cap insulin costs at $35 per insulin vial during the State of the Union address, during which he introduced a young boy with type 1 diabetes in the guest box, as reported by this news organization. On March 3, Civica, a nonprofit coalition of health systems and philanthropies, announced it plans to manufacture generic insulin at a deeply discounted price, as reported by this news organization.

“Just to see diabetes front and center at the State of the Union followed by these announcements is certainly reflective of our own advocacy effort to make sure that people have affordable options for insulin, diabetes medications, services,” Kate Thomas, ADCES chief advocacy and external affairs officer, said in an interview. She added that ADCES has also pushed for legislation in Congress that would expand access to diabetes self-management training under the Medicare program.

The guide includes advice about overcoming barriers to discussing treatment costs with patients, suggested questions to ask patients about specific costs, and determinants of health and conversational approaches. Links are provided to resources for obtaining affordable insulin, other diabetes medications, and continuous glucose monitoring and insulin pump equipment.

“We know that, especially during primary care visits, there is limited time along with numbers of issues to talk about, so I think our challenge is how do we prioritize these conversations with something that can lead to action, not just saying you should do this but how do you actually do it,” Ms. Thomas said.

The introduction summarizes results from a 2021 Beyond Type 1 survey confirming prior findings reported by this news organization that cost is a frequent barrier for many individuals living with diabetes. “Especially right now where we are in terms of the impact of the pandemic and with peoples’ job statuses changing, I think it’s worthwhile to raise this in patient encounters,” Ms. Thomas said.
 

Overcoming conversational barriers

The first of three tables in the guide provides a list of “barriers to having a cost conversation” in the first column and “suggested solutions” in the second. For example, for the barrier, “You have insufficient time and/or knowledge about cost,” the suggestion is, “request and share available faculty and resources, including benefits coordinators, social workers, and community-based organizations. Work with the pharmacists and other members of the diabetes care team to identify resources that lower cost of medications.”

And for another barrier, “patients are often embarrassed or ashamed to initiate discussions of affordability,” the suggested solution is: “Normalize the issue of cost of care barriers for patients.”

A second table offers specific questions to ask patients about costs of medications and care, determinants of health, and financial barriers. These include: “What are some challenges you’ve had to accessing your medications or taking them as prescribed? What are some out-of-pocket health care costs you need help with? What challenges do you have accessing healthy food for you and your family?”

A link to a screening tool for social determinants of health is also included.

Language suggestions include talking about “cost of care” rather than “money,” asking patients if they’ve understood everything correctly by repeating back what they’ve said, and asking for confirmation and discussing follow-up.

Overall, the tool is designed to be a “broad conversation starter,” and not just about medications, Ms. Thomas said. “This is for all audiences and it’s meant to be something that the provider can tailor depending on who they’re speaking to. ... It’s about medications, but also the entire cost of care, including services and devices, transportation to appointments, access to food. ... Diabetes care isn’t just taking medication. It’s so many more factors.”

Ms. Thomas reported no relevant financial relationships.

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

Adults with a congenital heart defect (CHD) are at increased risk for serious illness and death when hospitalized with COVID-19, making vaccination and other preventive measures even important in this population, say researchers with the Centers for Disease Control and Prevention.

“We found that hospitalized patients with heart defects are up to twice as likely to have critical outcomes of COVID-19 illness (admission to the intensive care unit, use of a ventilator to help with breathing, or death) compared to hospitalized COVID-19 patients without heart defects,” Karrie Downing, MPH, epidemiologist, with the CDC’s National Center on Birth Defects and Developmental Disabilities, said in an interview.

“Additionally, we learned that people with hearts defects who were older or who also had other conditions like heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity were the most likely to have critical COVID-19 illness, but children and adults with heart defects without these other conditions were still at increased risk,” Ms. Downing said.

The message for health care providers is clear: “Encourage your patients with heart defects to get vaccinated and discuss with your patients the need for other preventive measures to avoid infection that may progress to severe COVID-19 illness,” Ms. Downing added.

The study was published online March 7, 2022, in Circulation.

The researchers analyzed data on 235,638 patients hospitalized with COVID-19 between March 2020 and January 2021, including 421 (0.2%) with CHD. Most CHD patients were older than 30 years (73%) and 61% were men, with 55% non-Hispanic white, 19% Hispanic and 16% non-Hispanic Black.

Overall, 68% of CHD patients had at least one comorbidity, as did 59% of patients without CHD.

Rates of ICU admission were higher in the CHD group (54% vs. 43%), as were rates of invasive mechanical ventilation (24% vs. 15%) and in-hospital death (11% vs. 7%).

After accounting for patient characteristics, ICU admission, invasive mechanical ventilation and death were more prevalent among COVID-19 patients with rather than without CHD, with adjusted prevalence ratios of 1.4, 1.8 and 2.0, respectively.

When stratified by high-risk characteristics, prevalence estimates for ICU admission, invasive mechanical ventilation and death remained higher among patients with COVID-19 and CHD across nearly all strata, including younger age groups and those without heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity, the researchers reported.

Ms. Downing said more work is needed to identify why the clinical course of COVID-19 disease results in admission to the ICU, the need for a ventilator, or death for some hospitalized patients with CHD and not for others.

“There could be a number of social, environmental, economic, medical, and genetic factors playing a role. But staying up to date with COVID-19 vaccines and following preventive measures for COVID-19 are effective ways to reduce the risk of severe illness from COVID-19,” Ms. Downing said.

The study had no specific funding. The authors reported no relevant disclosures.

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

Adults with a congenital heart defect (CHD) are at increased risk for serious illness and death when hospitalized with COVID-19, making vaccination and other preventive measures even important in this population, say researchers with the Centers for Disease Control and Prevention.

“We found that hospitalized patients with heart defects are up to twice as likely to have critical outcomes of COVID-19 illness (admission to the intensive care unit, use of a ventilator to help with breathing, or death) compared to hospitalized COVID-19 patients without heart defects,” Karrie Downing, MPH, epidemiologist, with the CDC’s National Center on Birth Defects and Developmental Disabilities, said in an interview.

“Additionally, we learned that people with hearts defects who were older or who also had other conditions like heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity were the most likely to have critical COVID-19 illness, but children and adults with heart defects without these other conditions were still at increased risk,” Ms. Downing said.

The message for health care providers is clear: “Encourage your patients with heart defects to get vaccinated and discuss with your patients the need for other preventive measures to avoid infection that may progress to severe COVID-19 illness,” Ms. Downing added.

The study was published online March 7, 2022, in Circulation.

The researchers analyzed data on 235,638 patients hospitalized with COVID-19 between March 2020 and January 2021, including 421 (0.2%) with CHD. Most CHD patients were older than 30 years (73%) and 61% were men, with 55% non-Hispanic white, 19% Hispanic and 16% non-Hispanic Black.

Overall, 68% of CHD patients had at least one comorbidity, as did 59% of patients without CHD.

Rates of ICU admission were higher in the CHD group (54% vs. 43%), as were rates of invasive mechanical ventilation (24% vs. 15%) and in-hospital death (11% vs. 7%).

After accounting for patient characteristics, ICU admission, invasive mechanical ventilation and death were more prevalent among COVID-19 patients with rather than without CHD, with adjusted prevalence ratios of 1.4, 1.8 and 2.0, respectively.

When stratified by high-risk characteristics, prevalence estimates for ICU admission, invasive mechanical ventilation and death remained higher among patients with COVID-19 and CHD across nearly all strata, including younger age groups and those without heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity, the researchers reported.

Ms. Downing said more work is needed to identify why the clinical course of COVID-19 disease results in admission to the ICU, the need for a ventilator, or death for some hospitalized patients with CHD and not for others.

“There could be a number of social, environmental, economic, medical, and genetic factors playing a role. But staying up to date with COVID-19 vaccines and following preventive measures for COVID-19 are effective ways to reduce the risk of severe illness from COVID-19,” Ms. Downing said.

The study had no specific funding. The authors reported no relevant disclosures.

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

Adults with a congenital heart defect (CHD) are at increased risk for serious illness and death when hospitalized with COVID-19, making vaccination and other preventive measures even important in this population, say researchers with the Centers for Disease Control and Prevention.

“We found that hospitalized patients with heart defects are up to twice as likely to have critical outcomes of COVID-19 illness (admission to the intensive care unit, use of a ventilator to help with breathing, or death) compared to hospitalized COVID-19 patients without heart defects,” Karrie Downing, MPH, epidemiologist, with the CDC’s National Center on Birth Defects and Developmental Disabilities, said in an interview.

“Additionally, we learned that people with hearts defects who were older or who also had other conditions like heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity were the most likely to have critical COVID-19 illness, but children and adults with heart defects without these other conditions were still at increased risk,” Ms. Downing said.

The message for health care providers is clear: “Encourage your patients with heart defects to get vaccinated and discuss with your patients the need for other preventive measures to avoid infection that may progress to severe COVID-19 illness,” Ms. Downing added.

The study was published online March 7, 2022, in Circulation.

The researchers analyzed data on 235,638 patients hospitalized with COVID-19 between March 2020 and January 2021, including 421 (0.2%) with CHD. Most CHD patients were older than 30 years (73%) and 61% were men, with 55% non-Hispanic white, 19% Hispanic and 16% non-Hispanic Black.

Overall, 68% of CHD patients had at least one comorbidity, as did 59% of patients without CHD.

Rates of ICU admission were higher in the CHD group (54% vs. 43%), as were rates of invasive mechanical ventilation (24% vs. 15%) and in-hospital death (11% vs. 7%).

After accounting for patient characteristics, ICU admission, invasive mechanical ventilation and death were more prevalent among COVID-19 patients with rather than without CHD, with adjusted prevalence ratios of 1.4, 1.8 and 2.0, respectively.

When stratified by high-risk characteristics, prevalence estimates for ICU admission, invasive mechanical ventilation and death remained higher among patients with COVID-19 and CHD across nearly all strata, including younger age groups and those without heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity, the researchers reported.

Ms. Downing said more work is needed to identify why the clinical course of COVID-19 disease results in admission to the ICU, the need for a ventilator, or death for some hospitalized patients with CHD and not for others.

“There could be a number of social, environmental, economic, medical, and genetic factors playing a role. But staying up to date with COVID-19 vaccines and following preventive measures for COVID-19 are effective ways to reduce the risk of severe illness from COVID-19,” Ms. Downing said.

The study had no specific funding. The authors reported no relevant disclosures.

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