Tara Haelle

Uncontrolled growth isn’t the only way cancers wreak havoc on the human body. These aggregations of freely dividing cells also release chemicals that can cause damage from a distance. But pinning down how they harm faraway healthy tissues isn’t straightforward.

Fortunately, biologists can turn to the tiny fruit fly to address some of these questions: This insect’s body is not as complex as ours in many ways, but we share important genes and organ functions.

Fruit flies already are a crucial and inexpensive animal for genetics research. Because their life span is about 7 weeks, investigators can track the effects of mutations across several generations in a short period. The animals also are proving useful for learning how chemicals released by malignant tumors can harm tissues in the body that are not near the cancer.

One recent lesson from the fruit flies involves the blood-brain barrier, which determines which molecules gain access to the brain. Researchers at the University of California, Berkeley, have found that malignant tumors in the tiny insects release interleukin 6 (IL-6), an inflammatory chemical that disrupts this important barrier. The investigators showed that the tumors act similarly in mice.

When the scientists blocked the effects of IL-6, both the fruit flies and the mice lived longer. Even if cancer cells persisted, damage related to IL-6 could be diminished.

Fruit flies and mice are only distant relatives of each other and of humans, and the relevance of this discovery to human cancers has not been established. One hurdle is that IL-6 has many important, normal functions related to health. Researchers need to learn how to target only its unwanted blood-brain barrier effects.

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

Uncontrolled growth isn’t the only way cancers wreak havoc on the human body. These aggregations of freely dividing cells also release chemicals that can cause damage from a distance. But pinning down how they harm faraway healthy tissues isn’t straightforward.

Fortunately, biologists can turn to the tiny fruit fly to address some of these questions: This insect’s body is not as complex as ours in many ways, but we share important genes and organ functions.

Fruit flies already are a crucial and inexpensive animal for genetics research. Because their life span is about 7 weeks, investigators can track the effects of mutations across several generations in a short period. The animals also are proving useful for learning how chemicals released by malignant tumors can harm tissues in the body that are not near the cancer.

One recent lesson from the fruit flies involves the blood-brain barrier, which determines which molecules gain access to the brain. Researchers at the University of California, Berkeley, have found that malignant tumors in the tiny insects release interleukin 6 (IL-6), an inflammatory chemical that disrupts this important barrier. The investigators showed that the tumors act similarly in mice.

When the scientists blocked the effects of IL-6, both the fruit flies and the mice lived longer. Even if cancer cells persisted, damage related to IL-6 could be diminished.

Fruit flies and mice are only distant relatives of each other and of humans, and the relevance of this discovery to human cancers has not been established. One hurdle is that IL-6 has many important, normal functions related to health. Researchers need to learn how to target only its unwanted blood-brain barrier effects.

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

Uncontrolled growth isn’t the only way cancers wreak havoc on the human body. These aggregations of freely dividing cells also release chemicals that can cause damage from a distance. But pinning down how they harm faraway healthy tissues isn’t straightforward.

Fortunately, biologists can turn to the tiny fruit fly to address some of these questions: This insect’s body is not as complex as ours in many ways, but we share important genes and organ functions.

Fruit flies already are a crucial and inexpensive animal for genetics research. Because their life span is about 7 weeks, investigators can track the effects of mutations across several generations in a short period. The animals also are proving useful for learning how chemicals released by malignant tumors can harm tissues in the body that are not near the cancer.

One recent lesson from the fruit flies involves the blood-brain barrier, which determines which molecules gain access to the brain. Researchers at the University of California, Berkeley, have found that malignant tumors in the tiny insects release interleukin 6 (IL-6), an inflammatory chemical that disrupts this important barrier. The investigators showed that the tumors act similarly in mice.

When the scientists blocked the effects of IL-6, both the fruit flies and the mice lived longer. Even if cancer cells persisted, damage related to IL-6 could be diminished.

Fruit flies and mice are only distant relatives of each other and of humans, and the relevance of this discovery to human cancers has not been established. One hurdle is that IL-6 has many important, normal functions related to health. Researchers need to learn how to target only its unwanted blood-brain barrier effects.

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

Years ago, when rheumatologist Leonard Sigal, MD, was undertaking research on Lyme disease and treating patients with the condition at the Robert Wood Johnson Medical School, New Brunswick, N.J., a regular stream of abuse and threats became the usual background noise of his work. He didn’t get used to it, but it never stopped.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

“I was accused of incredibly heinous crimes,” Dr. Sigal said in an interview. “I was accused of lying, cheating, of doing things to make money that were against the public interest and against the interest of patients in general.”

It’s an experience many doctors who treat Lyme disease have endured, so much so that some infectious disease doctors aren’t comfortable treating patients with Lyme disease, according to Timothy Flanigan, MD, a professor of infectious disease at Brown University, Providence, R.I.

But it wasn’t until Dr. Sigal left academia in 2003 that he realized the toll all that background abuse had been taking on him.

“It was a breath of fresh air,” he said. “I didn’t have to go into clinic and argue with people. I didn’t have to read articles in the newspaper that made no sense whatsoever. I didn’t have to hear through second and third parties how such and such was saying horrible things about me. I didn’t have to fight anymore. When I was in industry and working on stuff that had nothing to do with Lyme disease, I realized what a relief it was not to have that burden.”

So the last thing Dr. Sigal expected after all these years was to find himself named in a lawsuit alleging that he was part of a conspiracy to deny patients of what they claimed was appropriate treatment for Lyme disease. Yet, that’s exactly what happened in November 2017, when a group of 24 patients with Lyme disease, led by Texas resident Lisa Torrey, filed a lawsuit against the Infectious Diseases Society of America, eight insurance companies, and 7 of the doctors involved in producing the IDSA guidelines on Lyme disease diagnosis and management. Dr. Sigal himself had not even participated in writing the guidelines. He simply reviewed them, made a few grammatical suggestions, and said they looked good. Over the next 4 years, however, he and his fellow defendants rode an emotional roller coaster of seemingly endless motions, amendments, and other legal developments, waiting to find out whether they would owe millions of dollars for simply summarizing – or just reviewing – the available medical literature on Lyme disease.

“There were times I was on the verge of real anger. I was frustrated. There were times I was frightened, and, occasionally, I would just think of it as being silly. But when I thought of it as being silly, I had to remember I was being sued in Texas, because who knows what’s going to happen,” Dr. Sigal said. “It’s not as though I was being sued in a jurisdiction where anybody knew about Lyme disease. There are examples of physicians who are convicted of doing things they didn’t do because they were sued in the wrong jurisdiction.”

Several individuals who spoke with this news organization on condition of anonymity said that the district court where the suit was filed is notorious for being especially friendly to plaintiffs. But in legal rulings issued on Sept. 1 and Sept. 20, 2021, a federal judge in Texas dismissed all the patient group’s claims. The plaintiffs filed an appeal on Oct. 19. It’s unclear whether that has any reasonable chance of success.

“One of the things this court case does is validate the fact that our [guidelines] process is a legitimate process and there isn’t outside influence from insurance companies or pharma firms,” Daniel McQuillen, MD, president of IDSA, said in an interview. “We don’t really want anything other than to be vindicated, which we were, 100%.”

But that vindication came with a cost, both emotional and financial. Although IDSA’s insurance covered many of its legal costs, “it’s not a trivial expense,” Dr. McQuillen said. “We’re left with a baseless lawsuit with no facts that went on for 4 years, and our [medical] society basically bore all that expense, which isn’t really particularly fair.”
 

‘Preposterous’ accusations

The lawsuit alleged that the IDSA, the seven named physicians, and the insurance companies had “engaged in a decades-long conspiracy to deny the existence and prevent treatment of chronic Lyme disease.” The patient group claimed that the doctors knew that many patients with Lyme disease do not respond to short-term antibiotic treatment and instead need “long-term antibiotic treatment until the symptoms are resolved,” an assertion not supported by the scientific evidence.

What many patients call “chronic Lyme disease” is termed posttreatment Lyme disease syndrome (PTDLS), a constellation of symptoms that include pain, fatigue, and cognitive difficulties that some people experience after a 2- to 4-week course of antibiotics for Lyme disease. It took years of patient advocacy before the Centers for Disease Control and Prevention recognized PTLDS as a condition, but awareness of it has been increasing, said Dr. Flanigan, who was not involved in the lawsuit but treats patients with Lyme disease and PTLDS.

“Long haulers and sequelae of COVID have really opened the eyes of many practitioners that these long-term inflammatory conditions are real and very challenging to treat, and we need to work with patients to help them improve their health,” Dr. Flanigan said. “It’s a sad commentary on our society that the difficulty in treating patients with posttreatment Lyme disease syndrome, or what is commonly referred to by patients as chronic Lyme, ends up in a lawsuit in court.” He said he’s glad the lawsuit was dismissed but added that “there’s a crying need for additional high-quality, evidence-based research to help patients who are suffering from posttreatment Lyme disease syndrome.”

Patients fought for broader recognition of their condition, and some of them organized. They came up with their own ideas of what was causing their symptoms to persist. One that especially took hold was that infection from Borrelia burgdorferi, the bacteria that causes Lyme disease, persists after initial antibiotic treatment, causing so-called chronic Lyme disease. The cause of PTLDS is still under investigation, and the evidence does not support the idea of a persistent bacterial infection. Multiple studies from the National Institutes of Health have shown that long-term use of antibiotics does not benefit patients who continue to experience symptoms after initial treatment. Several studies have shown that severe adverse effects can result from extended intravenous antibiotic treatment, including death.

Nevertheless, the plaintiffs in the lawsuit argued that the insurance companies “enlisted the help of doctors who were researching Lyme disease – the IDSA panelists – and paid them large fees to develop arbitrary guidelines for testing Lyme disease,” thereby enabling the insurance companies to deny coverage for long-term antibiotic treatment to patients.

“The assertions were just preposterous,” Dr. McQuillen said.

In addition to the conspiracy charge, the plaintiffs brought additional accusations to the lawsuit over the years, including racketeering and claims that the guidelines contain false representations regarding Lyme disease testing and treatment. The plaintiffs claimed that the guidelines didn’t acknowledge that treatment can fail and included false information about how to test for Lyme disease. In reality, however, the guidelines do acknowledge that not all patients respond to the recommended 2- to 4-week course of antibiotics and that some diagnoses should be made clinically rather than on the basis of testing.

Regardless, guidelines are not stipulations. They’re a summation of the medical and scientific findings on Lyme disease based on careful review of hundreds of studies.

“They make really clear that adherence to the guidelines [is] voluntary. They aren’t a standard of care from which deviation of care is a problem,” Dr. McQuillen said. “You take those guidelines and apply it to the patient in front of you, and you see what fits best for that patient, because not every patient is going to fit into guidelines.”

Further, the authors said that IDSA vets their recommendations for any potential conflicts of interest in accordance with the organization’s guidelines practices.

“The point of the guidelines is to have people on the committee who don’t care what the guidelines are as long as we have good patient care,” Dr. McQuillen said.

Choosing to fight

Malpractice insurance does not cover this kind of lawsuit, because the doctors named in it did not personally treat any of the patients who filed it. Thus, the doctors were at risk of losing thousands, or millions, of dollars in legal fees, even if they ultimately prevail. Several of the physicians’ academic and health care institutions stepped in to cover some fees, and IDSA covered the rest in a joint defense.

“The IDSA provided me a lawyer at no cost to me, and I felt protected by them,” Dr. Sigal said. “They took care of me and made sure I was safe, and I am grateful to them for that.”

Dr. McQuillen said the expenses exceeded what the organization’s umbrella insurance covered. The physicians had invested their time and effort into the guidelines without any financial compensation.

“They’ve basically put a lot of sweat equity into producing guidelines” that follow the organization’s practices and ethics, Dr. McQuillen said. “To leave them out on an island by themselves is just not the right thing to do. We wouldn’t do that for any of our members who did something on behalf of our society.”

IDSA could have chosen to settle the lawsuit, as the insurance companies did.

“None of us on the board felt that was the right thing to do, because we believe in the process, and the science is right, and you shouldn’t be able to try to change that by having a lawsuit that’s baseless,” Dr. McQuillen said.

Several of the doctors named in the suit spoke with this news organization off the record about the exhaustion, frustration, and general suffering the suit has caused them over the past several years, including ongoing harassment that targeted their families and often became quite personal. But none expressed any wish that IDSA had chosen the faster, cheaper, easier route of settling.

“I love the organization for having done this rather than caving and paying,” Dr. Sigal said. “They showed real moral character, real integrity in fighting this suit, because they had done nothing wrong.”

Fighting the suit was about more than standing by the science, though. It’s essential to ensure physicians continue to conduct research and write clinical guidelines, even about ambiguous or controversial topics, said Raymond J. Dattwyler, MD, a professor of microbiology, immunology, and medicine at New York Medical College, Valhalla, who wrote the treatment part of the guidelines and was named in the suit.

“I was really surprised that someone would sue for scientific guidelines, because guidelines are common across medicine, and they’re just a roadmap to help practicing physicians understand how to handle evaluation or treatment of any number of particular problems,” Dr. Dattwyler said in an interview. But he wasn’t surprised that IDSA chose to fight the accusations, “because the principle involved is so compelling. It’s really standing up for all medical societies, and it’s very important to have guidelines. For the health and welfare of the American public, you need to have good information readily available to the practicing physicians.”

If the patient group had won in a settlement, it could potentially have led to less rigorous guidelines from other medical organizations, which would have had an adverse effect on public health, Dr. Dattwyler said. Such a chilling effect could reverberate far beyond the management of Lyme disease.

“One of the problems with our legal system is anybody can sue anybody, but it costs so much to defend yourself,” Dr. Dattwyler said. “This lawsuit costs millions, so that’s chilling. That’s going to inhibit guidelines, and it’s not only guidelines for infectious disease but it’s guidelines for cancer, guidelines for allergic diseases, guidelines for any number of things.”

To an extent, the threats and harassment that patient groups have directed toward different doctors have already had a chilling effect.

“For the people who gave of their time in good faith to generate these guidelines to get harassed everywhere, all the time, sometimes at home, sometimes at their place of work, it’s just unfair,” Dr. McQuillen said. “It also might discourage people from working in research to try to figure out better diagnostics or get a vaccine that actually works. Even if you really find it incredibly interesting, if laying over you is the threat that someone is going to sue you baselessly, and you’re going to have to put the time and effort into defending that, not to mention the money, I can’t see how that would be considered a positive that would encourage you to do it. In some ways, attacking people that are trying to help may drive them away from trying to help.

“At the same time, professional disagreements among practitioners – including a small minority who do treat patients with lengthy courses of antibiotics – can ultimately harm patient care, Dr. Flanigan said.

“There’s a lot of energy being expended fighting among different care providers, and often the individual needs of the patients seem to be not addressed,” Dr. Flanigan said. “The discord between different approaches often seems more important than spending time with the individual patient and trying to find a tailored approach to treatment which can benefit the patient best.”

At the same time, Dr. Sigal said he believes most of the clinicians who use non–evidence-based treatments for their patients do so because they genuinely believe it’s the right thing to do.

“I think they’re motivated by the same concerns that I have, and that is, I need to do what’s best for my patient,” Dr. Sigal said. Ultimately, the evidence should lead the way. “The only arbiter we possibly have in deciding these things is the medical scientific literature,” he added, “and if you can’t subscribe to that, then this way lies madness.”

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

Years ago, when rheumatologist Leonard Sigal, MD, was undertaking research on Lyme disease and treating patients with the condition at the Robert Wood Johnson Medical School, New Brunswick, N.J., a regular stream of abuse and threats became the usual background noise of his work. He didn’t get used to it, but it never stopped.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

“I was accused of incredibly heinous crimes,” Dr. Sigal said in an interview. “I was accused of lying, cheating, of doing things to make money that were against the public interest and against the interest of patients in general.”

It’s an experience many doctors who treat Lyme disease have endured, so much so that some infectious disease doctors aren’t comfortable treating patients with Lyme disease, according to Timothy Flanigan, MD, a professor of infectious disease at Brown University, Providence, R.I.

But it wasn’t until Dr. Sigal left academia in 2003 that he realized the toll all that background abuse had been taking on him.

“It was a breath of fresh air,” he said. “I didn’t have to go into clinic and argue with people. I didn’t have to read articles in the newspaper that made no sense whatsoever. I didn’t have to hear through second and third parties how such and such was saying horrible things about me. I didn’t have to fight anymore. When I was in industry and working on stuff that had nothing to do with Lyme disease, I realized what a relief it was not to have that burden.”

So the last thing Dr. Sigal expected after all these years was to find himself named in a lawsuit alleging that he was part of a conspiracy to deny patients of what they claimed was appropriate treatment for Lyme disease. Yet, that’s exactly what happened in November 2017, when a group of 24 patients with Lyme disease, led by Texas resident Lisa Torrey, filed a lawsuit against the Infectious Diseases Society of America, eight insurance companies, and 7 of the doctors involved in producing the IDSA guidelines on Lyme disease diagnosis and management. Dr. Sigal himself had not even participated in writing the guidelines. He simply reviewed them, made a few grammatical suggestions, and said they looked good. Over the next 4 years, however, he and his fellow defendants rode an emotional roller coaster of seemingly endless motions, amendments, and other legal developments, waiting to find out whether they would owe millions of dollars for simply summarizing – or just reviewing – the available medical literature on Lyme disease.

“There were times I was on the verge of real anger. I was frustrated. There were times I was frightened, and, occasionally, I would just think of it as being silly. But when I thought of it as being silly, I had to remember I was being sued in Texas, because who knows what’s going to happen,” Dr. Sigal said. “It’s not as though I was being sued in a jurisdiction where anybody knew about Lyme disease. There are examples of physicians who are convicted of doing things they didn’t do because they were sued in the wrong jurisdiction.”

Several individuals who spoke with this news organization on condition of anonymity said that the district court where the suit was filed is notorious for being especially friendly to plaintiffs. But in legal rulings issued on Sept. 1 and Sept. 20, 2021, a federal judge in Texas dismissed all the patient group’s claims. The plaintiffs filed an appeal on Oct. 19. It’s unclear whether that has any reasonable chance of success.

“One of the things this court case does is validate the fact that our [guidelines] process is a legitimate process and there isn’t outside influence from insurance companies or pharma firms,” Daniel McQuillen, MD, president of IDSA, said in an interview. “We don’t really want anything other than to be vindicated, which we were, 100%.”

But that vindication came with a cost, both emotional and financial. Although IDSA’s insurance covered many of its legal costs, “it’s not a trivial expense,” Dr. McQuillen said. “We’re left with a baseless lawsuit with no facts that went on for 4 years, and our [medical] society basically bore all that expense, which isn’t really particularly fair.”
 

‘Preposterous’ accusations

The lawsuit alleged that the IDSA, the seven named physicians, and the insurance companies had “engaged in a decades-long conspiracy to deny the existence and prevent treatment of chronic Lyme disease.” The patient group claimed that the doctors knew that many patients with Lyme disease do not respond to short-term antibiotic treatment and instead need “long-term antibiotic treatment until the symptoms are resolved,” an assertion not supported by the scientific evidence.

What many patients call “chronic Lyme disease” is termed posttreatment Lyme disease syndrome (PTDLS), a constellation of symptoms that include pain, fatigue, and cognitive difficulties that some people experience after a 2- to 4-week course of antibiotics for Lyme disease. It took years of patient advocacy before the Centers for Disease Control and Prevention recognized PTLDS as a condition, but awareness of it has been increasing, said Dr. Flanigan, who was not involved in the lawsuit but treats patients with Lyme disease and PTLDS.

“Long haulers and sequelae of COVID have really opened the eyes of many practitioners that these long-term inflammatory conditions are real and very challenging to treat, and we need to work with patients to help them improve their health,” Dr. Flanigan said. “It’s a sad commentary on our society that the difficulty in treating patients with posttreatment Lyme disease syndrome, or what is commonly referred to by patients as chronic Lyme, ends up in a lawsuit in court.” He said he’s glad the lawsuit was dismissed but added that “there’s a crying need for additional high-quality, evidence-based research to help patients who are suffering from posttreatment Lyme disease syndrome.”

Patients fought for broader recognition of their condition, and some of them organized. They came up with their own ideas of what was causing their symptoms to persist. One that especially took hold was that infection from Borrelia burgdorferi, the bacteria that causes Lyme disease, persists after initial antibiotic treatment, causing so-called chronic Lyme disease. The cause of PTLDS is still under investigation, and the evidence does not support the idea of a persistent bacterial infection. Multiple studies from the National Institutes of Health have shown that long-term use of antibiotics does not benefit patients who continue to experience symptoms after initial treatment. Several studies have shown that severe adverse effects can result from extended intravenous antibiotic treatment, including death.

Nevertheless, the plaintiffs in the lawsuit argued that the insurance companies “enlisted the help of doctors who were researching Lyme disease – the IDSA panelists – and paid them large fees to develop arbitrary guidelines for testing Lyme disease,” thereby enabling the insurance companies to deny coverage for long-term antibiotic treatment to patients.

“The assertions were just preposterous,” Dr. McQuillen said.

In addition to the conspiracy charge, the plaintiffs brought additional accusations to the lawsuit over the years, including racketeering and claims that the guidelines contain false representations regarding Lyme disease testing and treatment. The plaintiffs claimed that the guidelines didn’t acknowledge that treatment can fail and included false information about how to test for Lyme disease. In reality, however, the guidelines do acknowledge that not all patients respond to the recommended 2- to 4-week course of antibiotics and that some diagnoses should be made clinically rather than on the basis of testing.

Regardless, guidelines are not stipulations. They’re a summation of the medical and scientific findings on Lyme disease based on careful review of hundreds of studies.

“They make really clear that adherence to the guidelines [is] voluntary. They aren’t a standard of care from which deviation of care is a problem,” Dr. McQuillen said. “You take those guidelines and apply it to the patient in front of you, and you see what fits best for that patient, because not every patient is going to fit into guidelines.”

Further, the authors said that IDSA vets their recommendations for any potential conflicts of interest in accordance with the organization’s guidelines practices.

“The point of the guidelines is to have people on the committee who don’t care what the guidelines are as long as we have good patient care,” Dr. McQuillen said.

Choosing to fight

Malpractice insurance does not cover this kind of lawsuit, because the doctors named in it did not personally treat any of the patients who filed it. Thus, the doctors were at risk of losing thousands, or millions, of dollars in legal fees, even if they ultimately prevail. Several of the physicians’ academic and health care institutions stepped in to cover some fees, and IDSA covered the rest in a joint defense.

“The IDSA provided me a lawyer at no cost to me, and I felt protected by them,” Dr. Sigal said. “They took care of me and made sure I was safe, and I am grateful to them for that.”

Dr. McQuillen said the expenses exceeded what the organization’s umbrella insurance covered. The physicians had invested their time and effort into the guidelines without any financial compensation.

“They’ve basically put a lot of sweat equity into producing guidelines” that follow the organization’s practices and ethics, Dr. McQuillen said. “To leave them out on an island by themselves is just not the right thing to do. We wouldn’t do that for any of our members who did something on behalf of our society.”

IDSA could have chosen to settle the lawsuit, as the insurance companies did.

“None of us on the board felt that was the right thing to do, because we believe in the process, and the science is right, and you shouldn’t be able to try to change that by having a lawsuit that’s baseless,” Dr. McQuillen said.

Several of the doctors named in the suit spoke with this news organization off the record about the exhaustion, frustration, and general suffering the suit has caused them over the past several years, including ongoing harassment that targeted their families and often became quite personal. But none expressed any wish that IDSA had chosen the faster, cheaper, easier route of settling.

“I love the organization for having done this rather than caving and paying,” Dr. Sigal said. “They showed real moral character, real integrity in fighting this suit, because they had done nothing wrong.”

Fighting the suit was about more than standing by the science, though. It’s essential to ensure physicians continue to conduct research and write clinical guidelines, even about ambiguous or controversial topics, said Raymond J. Dattwyler, MD, a professor of microbiology, immunology, and medicine at New York Medical College, Valhalla, who wrote the treatment part of the guidelines and was named in the suit.

“I was really surprised that someone would sue for scientific guidelines, because guidelines are common across medicine, and they’re just a roadmap to help practicing physicians understand how to handle evaluation or treatment of any number of particular problems,” Dr. Dattwyler said in an interview. But he wasn’t surprised that IDSA chose to fight the accusations, “because the principle involved is so compelling. It’s really standing up for all medical societies, and it’s very important to have guidelines. For the health and welfare of the American public, you need to have good information readily available to the practicing physicians.”

If the patient group had won in a settlement, it could potentially have led to less rigorous guidelines from other medical organizations, which would have had an adverse effect on public health, Dr. Dattwyler said. Such a chilling effect could reverberate far beyond the management of Lyme disease.

“One of the problems with our legal system is anybody can sue anybody, but it costs so much to defend yourself,” Dr. Dattwyler said. “This lawsuit costs millions, so that’s chilling. That’s going to inhibit guidelines, and it’s not only guidelines for infectious disease but it’s guidelines for cancer, guidelines for allergic diseases, guidelines for any number of things.”

To an extent, the threats and harassment that patient groups have directed toward different doctors have already had a chilling effect.

“For the people who gave of their time in good faith to generate these guidelines to get harassed everywhere, all the time, sometimes at home, sometimes at their place of work, it’s just unfair,” Dr. McQuillen said. “It also might discourage people from working in research to try to figure out better diagnostics or get a vaccine that actually works. Even if you really find it incredibly interesting, if laying over you is the threat that someone is going to sue you baselessly, and you’re going to have to put the time and effort into defending that, not to mention the money, I can’t see how that would be considered a positive that would encourage you to do it. In some ways, attacking people that are trying to help may drive them away from trying to help.

“At the same time, professional disagreements among practitioners – including a small minority who do treat patients with lengthy courses of antibiotics – can ultimately harm patient care, Dr. Flanigan said.

“There’s a lot of energy being expended fighting among different care providers, and often the individual needs of the patients seem to be not addressed,” Dr. Flanigan said. “The discord between different approaches often seems more important than spending time with the individual patient and trying to find a tailored approach to treatment which can benefit the patient best.”

At the same time, Dr. Sigal said he believes most of the clinicians who use non–evidence-based treatments for their patients do so because they genuinely believe it’s the right thing to do.

“I think they’re motivated by the same concerns that I have, and that is, I need to do what’s best for my patient,” Dr. Sigal said. Ultimately, the evidence should lead the way. “The only arbiter we possibly have in deciding these things is the medical scientific literature,” he added, “and if you can’t subscribe to that, then this way lies madness.”

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

Years ago, when rheumatologist Leonard Sigal, MD, was undertaking research on Lyme disease and treating patients with the condition at the Robert Wood Johnson Medical School, New Brunswick, N.J., a regular stream of abuse and threats became the usual background noise of his work. He didn’t get used to it, but it never stopped.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

“I was accused of incredibly heinous crimes,” Dr. Sigal said in an interview. “I was accused of lying, cheating, of doing things to make money that were against the public interest and against the interest of patients in general.”

It’s an experience many doctors who treat Lyme disease have endured, so much so that some infectious disease doctors aren’t comfortable treating patients with Lyme disease, according to Timothy Flanigan, MD, a professor of infectious disease at Brown University, Providence, R.I.

But it wasn’t until Dr. Sigal left academia in 2003 that he realized the toll all that background abuse had been taking on him.

“It was a breath of fresh air,” he said. “I didn’t have to go into clinic and argue with people. I didn’t have to read articles in the newspaper that made no sense whatsoever. I didn’t have to hear through second and third parties how such and such was saying horrible things about me. I didn’t have to fight anymore. When I was in industry and working on stuff that had nothing to do with Lyme disease, I realized what a relief it was not to have that burden.”

So the last thing Dr. Sigal expected after all these years was to find himself named in a lawsuit alleging that he was part of a conspiracy to deny patients of what they claimed was appropriate treatment for Lyme disease. Yet, that’s exactly what happened in November 2017, when a group of 24 patients with Lyme disease, led by Texas resident Lisa Torrey, filed a lawsuit against the Infectious Diseases Society of America, eight insurance companies, and 7 of the doctors involved in producing the IDSA guidelines on Lyme disease diagnosis and management. Dr. Sigal himself had not even participated in writing the guidelines. He simply reviewed them, made a few grammatical suggestions, and said they looked good. Over the next 4 years, however, he and his fellow defendants rode an emotional roller coaster of seemingly endless motions, amendments, and other legal developments, waiting to find out whether they would owe millions of dollars for simply summarizing – or just reviewing – the available medical literature on Lyme disease.

“There were times I was on the verge of real anger. I was frustrated. There were times I was frightened, and, occasionally, I would just think of it as being silly. But when I thought of it as being silly, I had to remember I was being sued in Texas, because who knows what’s going to happen,” Dr. Sigal said. “It’s not as though I was being sued in a jurisdiction where anybody knew about Lyme disease. There are examples of physicians who are convicted of doing things they didn’t do because they were sued in the wrong jurisdiction.”

Several individuals who spoke with this news organization on condition of anonymity said that the district court where the suit was filed is notorious for being especially friendly to plaintiffs. But in legal rulings issued on Sept. 1 and Sept. 20, 2021, a federal judge in Texas dismissed all the patient group’s claims. The plaintiffs filed an appeal on Oct. 19. It’s unclear whether that has any reasonable chance of success.

“One of the things this court case does is validate the fact that our [guidelines] process is a legitimate process and there isn’t outside influence from insurance companies or pharma firms,” Daniel McQuillen, MD, president of IDSA, said in an interview. “We don’t really want anything other than to be vindicated, which we were, 100%.”

But that vindication came with a cost, both emotional and financial. Although IDSA’s insurance covered many of its legal costs, “it’s not a trivial expense,” Dr. McQuillen said. “We’re left with a baseless lawsuit with no facts that went on for 4 years, and our [medical] society basically bore all that expense, which isn’t really particularly fair.”
 

‘Preposterous’ accusations

The lawsuit alleged that the IDSA, the seven named physicians, and the insurance companies had “engaged in a decades-long conspiracy to deny the existence and prevent treatment of chronic Lyme disease.” The patient group claimed that the doctors knew that many patients with Lyme disease do not respond to short-term antibiotic treatment and instead need “long-term antibiotic treatment until the symptoms are resolved,” an assertion not supported by the scientific evidence.

What many patients call “chronic Lyme disease” is termed posttreatment Lyme disease syndrome (PTDLS), a constellation of symptoms that include pain, fatigue, and cognitive difficulties that some people experience after a 2- to 4-week course of antibiotics for Lyme disease. It took years of patient advocacy before the Centers for Disease Control and Prevention recognized PTLDS as a condition, but awareness of it has been increasing, said Dr. Flanigan, who was not involved in the lawsuit but treats patients with Lyme disease and PTLDS.

“Long haulers and sequelae of COVID have really opened the eyes of many practitioners that these long-term inflammatory conditions are real and very challenging to treat, and we need to work with patients to help them improve their health,” Dr. Flanigan said. “It’s a sad commentary on our society that the difficulty in treating patients with posttreatment Lyme disease syndrome, or what is commonly referred to by patients as chronic Lyme, ends up in a lawsuit in court.” He said he’s glad the lawsuit was dismissed but added that “there’s a crying need for additional high-quality, evidence-based research to help patients who are suffering from posttreatment Lyme disease syndrome.”

Patients fought for broader recognition of their condition, and some of them organized. They came up with their own ideas of what was causing their symptoms to persist. One that especially took hold was that infection from Borrelia burgdorferi, the bacteria that causes Lyme disease, persists after initial antibiotic treatment, causing so-called chronic Lyme disease. The cause of PTLDS is still under investigation, and the evidence does not support the idea of a persistent bacterial infection. Multiple studies from the National Institutes of Health have shown that long-term use of antibiotics does not benefit patients who continue to experience symptoms after initial treatment. Several studies have shown that severe adverse effects can result from extended intravenous antibiotic treatment, including death.

Nevertheless, the plaintiffs in the lawsuit argued that the insurance companies “enlisted the help of doctors who were researching Lyme disease – the IDSA panelists – and paid them large fees to develop arbitrary guidelines for testing Lyme disease,” thereby enabling the insurance companies to deny coverage for long-term antibiotic treatment to patients.

“The assertions were just preposterous,” Dr. McQuillen said.

In addition to the conspiracy charge, the plaintiffs brought additional accusations to the lawsuit over the years, including racketeering and claims that the guidelines contain false representations regarding Lyme disease testing and treatment. The plaintiffs claimed that the guidelines didn’t acknowledge that treatment can fail and included false information about how to test for Lyme disease. In reality, however, the guidelines do acknowledge that not all patients respond to the recommended 2- to 4-week course of antibiotics and that some diagnoses should be made clinically rather than on the basis of testing.

Regardless, guidelines are not stipulations. They’re a summation of the medical and scientific findings on Lyme disease based on careful review of hundreds of studies.

“They make really clear that adherence to the guidelines [is] voluntary. They aren’t a standard of care from which deviation of care is a problem,” Dr. McQuillen said. “You take those guidelines and apply it to the patient in front of you, and you see what fits best for that patient, because not every patient is going to fit into guidelines.”

Further, the authors said that IDSA vets their recommendations for any potential conflicts of interest in accordance with the organization’s guidelines practices.

“The point of the guidelines is to have people on the committee who don’t care what the guidelines are as long as we have good patient care,” Dr. McQuillen said.

Choosing to fight

Malpractice insurance does not cover this kind of lawsuit, because the doctors named in it did not personally treat any of the patients who filed it. Thus, the doctors were at risk of losing thousands, or millions, of dollars in legal fees, even if they ultimately prevail. Several of the physicians’ academic and health care institutions stepped in to cover some fees, and IDSA covered the rest in a joint defense.

“The IDSA provided me a lawyer at no cost to me, and I felt protected by them,” Dr. Sigal said. “They took care of me and made sure I was safe, and I am grateful to them for that.”

Dr. McQuillen said the expenses exceeded what the organization’s umbrella insurance covered. The physicians had invested their time and effort into the guidelines without any financial compensation.

“They’ve basically put a lot of sweat equity into producing guidelines” that follow the organization’s practices and ethics, Dr. McQuillen said. “To leave them out on an island by themselves is just not the right thing to do. We wouldn’t do that for any of our members who did something on behalf of our society.”

IDSA could have chosen to settle the lawsuit, as the insurance companies did.

“None of us on the board felt that was the right thing to do, because we believe in the process, and the science is right, and you shouldn’t be able to try to change that by having a lawsuit that’s baseless,” Dr. McQuillen said.

Several of the doctors named in the suit spoke with this news organization off the record about the exhaustion, frustration, and general suffering the suit has caused them over the past several years, including ongoing harassment that targeted their families and often became quite personal. But none expressed any wish that IDSA had chosen the faster, cheaper, easier route of settling.

“I love the organization for having done this rather than caving and paying,” Dr. Sigal said. “They showed real moral character, real integrity in fighting this suit, because they had done nothing wrong.”

Fighting the suit was about more than standing by the science, though. It’s essential to ensure physicians continue to conduct research and write clinical guidelines, even about ambiguous or controversial topics, said Raymond J. Dattwyler, MD, a professor of microbiology, immunology, and medicine at New York Medical College, Valhalla, who wrote the treatment part of the guidelines and was named in the suit.

“I was really surprised that someone would sue for scientific guidelines, because guidelines are common across medicine, and they’re just a roadmap to help practicing physicians understand how to handle evaluation or treatment of any number of particular problems,” Dr. Dattwyler said in an interview. But he wasn’t surprised that IDSA chose to fight the accusations, “because the principle involved is so compelling. It’s really standing up for all medical societies, and it’s very important to have guidelines. For the health and welfare of the American public, you need to have good information readily available to the practicing physicians.”

If the patient group had won in a settlement, it could potentially have led to less rigorous guidelines from other medical organizations, which would have had an adverse effect on public health, Dr. Dattwyler said. Such a chilling effect could reverberate far beyond the management of Lyme disease.

“One of the problems with our legal system is anybody can sue anybody, but it costs so much to defend yourself,” Dr. Dattwyler said. “This lawsuit costs millions, so that’s chilling. That’s going to inhibit guidelines, and it’s not only guidelines for infectious disease but it’s guidelines for cancer, guidelines for allergic diseases, guidelines for any number of things.”

To an extent, the threats and harassment that patient groups have directed toward different doctors have already had a chilling effect.

“For the people who gave of their time in good faith to generate these guidelines to get harassed everywhere, all the time, sometimes at home, sometimes at their place of work, it’s just unfair,” Dr. McQuillen said. “It also might discourage people from working in research to try to figure out better diagnostics or get a vaccine that actually works. Even if you really find it incredibly interesting, if laying over you is the threat that someone is going to sue you baselessly, and you’re going to have to put the time and effort into defending that, not to mention the money, I can’t see how that would be considered a positive that would encourage you to do it. In some ways, attacking people that are trying to help may drive them away from trying to help.

“At the same time, professional disagreements among practitioners – including a small minority who do treat patients with lengthy courses of antibiotics – can ultimately harm patient care, Dr. Flanigan said.

“There’s a lot of energy being expended fighting among different care providers, and often the individual needs of the patients seem to be not addressed,” Dr. Flanigan said. “The discord between different approaches often seems more important than spending time with the individual patient and trying to find a tailored approach to treatment which can benefit the patient best.”

At the same time, Dr. Sigal said he believes most of the clinicians who use non–evidence-based treatments for their patients do so because they genuinely believe it’s the right thing to do.

“I think they’re motivated by the same concerns that I have, and that is, I need to do what’s best for my patient,” Dr. Sigal said. Ultimately, the evidence should lead the way. “The only arbiter we possibly have in deciding these things is the medical scientific literature,” he added, “and if you can’t subscribe to that, then this way lies madness.”

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

Most people think of alcohol-level testers, commonly called Breathalyzers, as tools for measuring alcohol when someone exhales. But scientists have taken the technology well beyond DUI checkpoints, aiming it instead at detecting diseases.

The breath of someone who is sick often has a chemical profile that is specific to their health condition. Methane in a person’s exhalations, for example, could signal an intestinal issue. If these chemical profiles can be matched to specific illnesses, then these testing devices could become handy screening tools for some conditions.

But existing devices typically detect only a single compound, with results taking 10 minutes or more, leading to a quest for faster devices that can identify more chemicals at the same time. Researchers have turned to a tool called a frequency comb to solve this problem.

This tool, first developed in 2008, pings breath samples with laser pulses in distinct frequency ranges of the light spectrum, separated like the teeth of a comb. Every mini-cloud of droplets we exhale contains over 1,000 compounds. When researchers send the pulses through these exhaled droplets, each chemical absorbs the light in its own specific pattern, creating a light “signature.”

In a study published in the Proceedings of the National Academy of Sciences investigators report that an updated version of the frequency comb can detect at least four and possibly up to 10 compounds linked to a health condition. In addition to accurately sorting out methane, methanol, and two chemical forms of water in breath, the combs also might be able to identify formaldehyde and ammonia, among others.

Before frequency combs become common in the clinic, though, a few steps remain. Scientists must link chemical profiles to specific diseases and find a way to make a compact version of the combs. If all goes well, the result could be a device capable of rapid, inexpensive screening for some diseases, with no need for lab testing, which would be especially welcome where testing facilities are scarce.

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

Most people think of alcohol-level testers, commonly called Breathalyzers, as tools for measuring alcohol when someone exhales. But scientists have taken the technology well beyond DUI checkpoints, aiming it instead at detecting diseases.

The breath of someone who is sick often has a chemical profile that is specific to their health condition. Methane in a person’s exhalations, for example, could signal an intestinal issue. If these chemical profiles can be matched to specific illnesses, then these testing devices could become handy screening tools for some conditions.

But existing devices typically detect only a single compound, with results taking 10 minutes or more, leading to a quest for faster devices that can identify more chemicals at the same time. Researchers have turned to a tool called a frequency comb to solve this problem.

This tool, first developed in 2008, pings breath samples with laser pulses in distinct frequency ranges of the light spectrum, separated like the teeth of a comb. Every mini-cloud of droplets we exhale contains over 1,000 compounds. When researchers send the pulses through these exhaled droplets, each chemical absorbs the light in its own specific pattern, creating a light “signature.”

In a study published in the Proceedings of the National Academy of Sciences investigators report that an updated version of the frequency comb can detect at least four and possibly up to 10 compounds linked to a health condition. In addition to accurately sorting out methane, methanol, and two chemical forms of water in breath, the combs also might be able to identify formaldehyde and ammonia, among others.

Before frequency combs become common in the clinic, though, a few steps remain. Scientists must link chemical profiles to specific diseases and find a way to make a compact version of the combs. If all goes well, the result could be a device capable of rapid, inexpensive screening for some diseases, with no need for lab testing, which would be especially welcome where testing facilities are scarce.

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

Most people think of alcohol-level testers, commonly called Breathalyzers, as tools for measuring alcohol when someone exhales. But scientists have taken the technology well beyond DUI checkpoints, aiming it instead at detecting diseases.

The breath of someone who is sick often has a chemical profile that is specific to their health condition. Methane in a person’s exhalations, for example, could signal an intestinal issue. If these chemical profiles can be matched to specific illnesses, then these testing devices could become handy screening tools for some conditions.

But existing devices typically detect only a single compound, with results taking 10 minutes or more, leading to a quest for faster devices that can identify more chemicals at the same time. Researchers have turned to a tool called a frequency comb to solve this problem.

This tool, first developed in 2008, pings breath samples with laser pulses in distinct frequency ranges of the light spectrum, separated like the teeth of a comb. Every mini-cloud of droplets we exhale contains over 1,000 compounds. When researchers send the pulses through these exhaled droplets, each chemical absorbs the light in its own specific pattern, creating a light “signature.”

In a study published in the Proceedings of the National Academy of Sciences investigators report that an updated version of the frequency comb can detect at least four and possibly up to 10 compounds linked to a health condition. In addition to accurately sorting out methane, methanol, and two chemical forms of water in breath, the combs also might be able to identify formaldehyde and ammonia, among others.

Before frequency combs become common in the clinic, though, a few steps remain. Scientists must link chemical profiles to specific diseases and find a way to make a compact version of the combs. If all goes well, the result could be a device capable of rapid, inexpensive screening for some diseases, with no need for lab testing, which would be especially welcome where testing facilities are scarce.

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

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Northwestern University

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

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

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Northwestern University

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

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

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Northwestern University

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

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

Two biomarkers could potentially indicate which children with SARS-CoV-2 infection will develop severe disease, according to research presented at the American Academy of Pediatrics 2021 National Conference.

“Most children with COVID-19 present with common symptoms, such as fever, vomiting, and abdominal pain, which are very similar to other common viruses,” said senior researcher Usha Sethuraman, MD, professor of pediatric emergency medicine at Central Michigan University in Detroit.

“It is impossible, in many instances, to predict which child, even after identification of SARS-CoV-2 infection, is going to develop severe consequences, such as multisystem inflammatory syndrome [MIS-C] or severe pneumonia,” she said in an interview.

“In fact, many of these kids have been sent home the first time around as they appeared clinically well, only to return a couple of days later in cardiogenic shock and requiring invasive interventions,” she added. “It would be invaluable to have the ability to know which child is likely to develop severe infection so appropriate disposition can be made and treatment initiated.”

In their prospective observational cohort study, Dr. Sethuraman and her colleagues collected saliva samples from children and adolescents when they were diagnosed with SARS-CoV-2 infection. They assessed the saliva for micro (mi)RNAs, which are small noncoding RNAs that help regulate gene expression and are “thought to play a role in the regulation of inflammation following an infection,” the researchers write in their poster.

Of the 129 young people assessed, 32 (25%) developed severe infection and 97 (75%) did not. The researchers defined severe infection as an MIS-C diagnosis, death in the 30 days after diagnosis, or the need for at least 2 L of oxygen, inotropes, mechanical ventilation, or extracorporeal membrane oxygenation.

The expression of 63 miRNAs was significantly different between young people who developed severe infection and those who did not (P < .05). In cases of severe disease, expression was downregulated for 38 of the 63 miRNAs (60%).

“A model of six miRNAs was able to discriminate between severe and nonsevere infections with high sensitivity and accuracy in a preliminary analysis,” Dr. Sethuraman reported. “While salivary miRNA has been shown in other studies to help differentiate persistent concussion in children, we did not expect them to be downregulated in children with severe COVID-19.”

The significant differences in miRNA expression in those with and without severe disease is “striking,” despite this being an interim analysis in a fairly small sample size, said Sindhu Mohandas, MD, a pediatric infectious disease specialist at Children’s Hospital Los Angeles.

“It will be interesting to see if these findings persist when larger numbers are analyzed,” she told this news organization. “Biomarkers that can predict potential severity can be very useful in making risk and management determinations. A child who has the biomarkers that indicate increased severity can be monitored more closely and complications can be preempted and prevented.”

The largest difference between severe and nonsevere cases was in the expression of miRNA 4495. In addition, miRNA 6125 appears to have prognostic potential, the researchers conclude. And three cytokines from saliva samples were elevated in cases of severe infection, but cytokine levels could not distinguish between severe and nonsevere infections, Dr. Sethuraman said.

If further research confirms these findings and determines that these miRNAs truly can provide insight into the likely course of an infection, it “would be a game changer, clinically,” she added, particularly because saliva samples are less invasive and less painful than blood draws.

The potential applications of these biomarkers could extend beyond children admitted to the hospital, Dr. Mohandas noted.

“For example, it would be a noninvasive and easy method to predict potential severity in a child seen in the emergency room and could help with deciding between observation, admission to the general floor, or admission to the ICU,” she told this news organization. “However, this test is not easily or routinely available at present, and cost and accessibility will be the main factors that will have to be overcome before it can be used for this purpose.”

These findings are preliminary, from a small sample, and require confirmation and validation, Dr. Sethuraman cautioned. And the team only analyzed saliva collected at diagnosis, so they have no data on potential changes in cytokines or miRNAs that occur as the disease progresses.

The next step is to “better characterize what happens with time to these profiles,” she explained. “The role of age, race, and gender differences in saliva biomarker profiles needs additional investigation as well.”

It would also be interesting to see whether varied expression of miRNAs “can help differentiate the various complications after COVID-19, like acute respiratory failure, MIS-C, and long COVID,” said Dr. Mohandas. “That would mean it could be used not only to potentially predict severity, but also to predict longer-term outcomes.”

This study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx) program. Coauthor Steven D. Hicks, MD, PhD, reports being a paid consultant for Quadrant Biosciences.

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

Two biomarkers could potentially indicate which children with SARS-CoV-2 infection will develop severe disease, according to research presented at the American Academy of Pediatrics 2021 National Conference.

“Most children with COVID-19 present with common symptoms, such as fever, vomiting, and abdominal pain, which are very similar to other common viruses,” said senior researcher Usha Sethuraman, MD, professor of pediatric emergency medicine at Central Michigan University in Detroit.

“It is impossible, in many instances, to predict which child, even after identification of SARS-CoV-2 infection, is going to develop severe consequences, such as multisystem inflammatory syndrome [MIS-C] or severe pneumonia,” she said in an interview.

“In fact, many of these kids have been sent home the first time around as they appeared clinically well, only to return a couple of days later in cardiogenic shock and requiring invasive interventions,” she added. “It would be invaluable to have the ability to know which child is likely to develop severe infection so appropriate disposition can be made and treatment initiated.”

In their prospective observational cohort study, Dr. Sethuraman and her colleagues collected saliva samples from children and adolescents when they were diagnosed with SARS-CoV-2 infection. They assessed the saliva for micro (mi)RNAs, which are small noncoding RNAs that help regulate gene expression and are “thought to play a role in the regulation of inflammation following an infection,” the researchers write in their poster.

Of the 129 young people assessed, 32 (25%) developed severe infection and 97 (75%) did not. The researchers defined severe infection as an MIS-C diagnosis, death in the 30 days after diagnosis, or the need for at least 2 L of oxygen, inotropes, mechanical ventilation, or extracorporeal membrane oxygenation.

The expression of 63 miRNAs was significantly different between young people who developed severe infection and those who did not (P < .05). In cases of severe disease, expression was downregulated for 38 of the 63 miRNAs (60%).

“A model of six miRNAs was able to discriminate between severe and nonsevere infections with high sensitivity and accuracy in a preliminary analysis,” Dr. Sethuraman reported. “While salivary miRNA has been shown in other studies to help differentiate persistent concussion in children, we did not expect them to be downregulated in children with severe COVID-19.”

The significant differences in miRNA expression in those with and without severe disease is “striking,” despite this being an interim analysis in a fairly small sample size, said Sindhu Mohandas, MD, a pediatric infectious disease specialist at Children’s Hospital Los Angeles.

“It will be interesting to see if these findings persist when larger numbers are analyzed,” she told this news organization. “Biomarkers that can predict potential severity can be very useful in making risk and management determinations. A child who has the biomarkers that indicate increased severity can be monitored more closely and complications can be preempted and prevented.”

The largest difference between severe and nonsevere cases was in the expression of miRNA 4495. In addition, miRNA 6125 appears to have prognostic potential, the researchers conclude. And three cytokines from saliva samples were elevated in cases of severe infection, but cytokine levels could not distinguish between severe and nonsevere infections, Dr. Sethuraman said.

If further research confirms these findings and determines that these miRNAs truly can provide insight into the likely course of an infection, it “would be a game changer, clinically,” she added, particularly because saliva samples are less invasive and less painful than blood draws.

The potential applications of these biomarkers could extend beyond children admitted to the hospital, Dr. Mohandas noted.

“For example, it would be a noninvasive and easy method to predict potential severity in a child seen in the emergency room and could help with deciding between observation, admission to the general floor, or admission to the ICU,” she told this news organization. “However, this test is not easily or routinely available at present, and cost and accessibility will be the main factors that will have to be overcome before it can be used for this purpose.”

These findings are preliminary, from a small sample, and require confirmation and validation, Dr. Sethuraman cautioned. And the team only analyzed saliva collected at diagnosis, so they have no data on potential changes in cytokines or miRNAs that occur as the disease progresses.

The next step is to “better characterize what happens with time to these profiles,” she explained. “The role of age, race, and gender differences in saliva biomarker profiles needs additional investigation as well.”

It would also be interesting to see whether varied expression of miRNAs “can help differentiate the various complications after COVID-19, like acute respiratory failure, MIS-C, and long COVID,” said Dr. Mohandas. “That would mean it could be used not only to potentially predict severity, but also to predict longer-term outcomes.”

This study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx) program. Coauthor Steven D. Hicks, MD, PhD, reports being a paid consultant for Quadrant Biosciences.

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

Two biomarkers could potentially indicate which children with SARS-CoV-2 infection will develop severe disease, according to research presented at the American Academy of Pediatrics 2021 National Conference.

“Most children with COVID-19 present with common symptoms, such as fever, vomiting, and abdominal pain, which are very similar to other common viruses,” said senior researcher Usha Sethuraman, MD, professor of pediatric emergency medicine at Central Michigan University in Detroit.

“It is impossible, in many instances, to predict which child, even after identification of SARS-CoV-2 infection, is going to develop severe consequences, such as multisystem inflammatory syndrome [MIS-C] or severe pneumonia,” she said in an interview.

“In fact, many of these kids have been sent home the first time around as they appeared clinically well, only to return a couple of days later in cardiogenic shock and requiring invasive interventions,” she added. “It would be invaluable to have the ability to know which child is likely to develop severe infection so appropriate disposition can be made and treatment initiated.”

In their prospective observational cohort study, Dr. Sethuraman and her colleagues collected saliva samples from children and adolescents when they were diagnosed with SARS-CoV-2 infection. They assessed the saliva for micro (mi)RNAs, which are small noncoding RNAs that help regulate gene expression and are “thought to play a role in the regulation of inflammation following an infection,” the researchers write in their poster.

Of the 129 young people assessed, 32 (25%) developed severe infection and 97 (75%) did not. The researchers defined severe infection as an MIS-C diagnosis, death in the 30 days after diagnosis, or the need for at least 2 L of oxygen, inotropes, mechanical ventilation, or extracorporeal membrane oxygenation.

The expression of 63 miRNAs was significantly different between young people who developed severe infection and those who did not (P < .05). In cases of severe disease, expression was downregulated for 38 of the 63 miRNAs (60%).

“A model of six miRNAs was able to discriminate between severe and nonsevere infections with high sensitivity and accuracy in a preliminary analysis,” Dr. Sethuraman reported. “While salivary miRNA has been shown in other studies to help differentiate persistent concussion in children, we did not expect them to be downregulated in children with severe COVID-19.”

The significant differences in miRNA expression in those with and without severe disease is “striking,” despite this being an interim analysis in a fairly small sample size, said Sindhu Mohandas, MD, a pediatric infectious disease specialist at Children’s Hospital Los Angeles.

“It will be interesting to see if these findings persist when larger numbers are analyzed,” she told this news organization. “Biomarkers that can predict potential severity can be very useful in making risk and management determinations. A child who has the biomarkers that indicate increased severity can be monitored more closely and complications can be preempted and prevented.”

The largest difference between severe and nonsevere cases was in the expression of miRNA 4495. In addition, miRNA 6125 appears to have prognostic potential, the researchers conclude. And three cytokines from saliva samples were elevated in cases of severe infection, but cytokine levels could not distinguish between severe and nonsevere infections, Dr. Sethuraman said.

If further research confirms these findings and determines that these miRNAs truly can provide insight into the likely course of an infection, it “would be a game changer, clinically,” she added, particularly because saliva samples are less invasive and less painful than blood draws.

The potential applications of these biomarkers could extend beyond children admitted to the hospital, Dr. Mohandas noted.

“For example, it would be a noninvasive and easy method to predict potential severity in a child seen in the emergency room and could help with deciding between observation, admission to the general floor, or admission to the ICU,” she told this news organization. “However, this test is not easily or routinely available at present, and cost and accessibility will be the main factors that will have to be overcome before it can be used for this purpose.”

These findings are preliminary, from a small sample, and require confirmation and validation, Dr. Sethuraman cautioned. And the team only analyzed saliva collected at diagnosis, so they have no data on potential changes in cytokines or miRNAs that occur as the disease progresses.

The next step is to “better characterize what happens with time to these profiles,” she explained. “The role of age, race, and gender differences in saliva biomarker profiles needs additional investigation as well.”

It would also be interesting to see whether varied expression of miRNAs “can help differentiate the various complications after COVID-19, like acute respiratory failure, MIS-C, and long COVID,” said Dr. Mohandas. “That would mean it could be used not only to potentially predict severity, but also to predict longer-term outcomes.”

This study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx) program. Coauthor Steven D. Hicks, MD, PhD, reports being a paid consultant for Quadrant Biosciences.

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

Transgender and nonbinary young people experienced less depression and fewer suicidal thoughts after a year of gender-affirming care with hormones or puberty blockers, according to new research.

“Given the high rates of adverse mental health comorbidities, these data provide critical evidence that expansion of gender-affirming care can save lives,” said David J. Inwards-Breland, MD, MPH, chief of adolescent and young adult medicine and codirector of the Center for Gender-Affirming Care at Rady Children’s Hospital in San Diego, during his presentation.

The findings, presented October 11 at the American Academy of Pediatrics 2021 National Conference, were not at all surprising to Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

“The younger we can provide gender-affirming care, the less likely they’re going to have depression, and then the negative outcomes from untreated depression, which includes suicide intent or even suicide completion,” Dr. Breuner told this news organization. “It’s so obvious that we are saving lives by providing gender-affirming care.”

For their study, Dr. Inwards-Breland and his colleagues tracked depression, anxiety, and suicidality in 104 trans and nonbinary people 13 to 21 years of age who received care at the Seattle Children’s gender clinic between August 2017 and June 2018.

The study population consisted of 63 transgender male or male participants, 27 transgender female or female participants, 10 nonbinary participants, and four participants who had not defined their gender identity. Of this cohort, 62.5% were receiving mental health therapy, and 34.7% reported some substance use.

Participants completed the nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder scale (GAD-7) at baseline and then at 3, 6, and 12 months. The researchers defined severe depression and severe anxiety as a score of 10 or greater on either scale.

At baseline, 56.7% of the participants had moderate to severe depression, 43.3% reported thoughts of self-harm or suicidal in the previous 2 weeks, and 50.0% had moderate to severe anxiety.

After 12 months of care, participants experienced a 60% decrease in depression (adjusted odds ratio, 0.4) and a 73% decrease in suicidality (aOR, 0.27), after adjustment for temporal trends and sex assigned at birth, race/ethnicity, level of parental support, ongoing mental health therapy, substance use, and victimization, including bullying, interpersonal violence, neglect, and abuse.

Although the decline in depression and suicidality after gender-affirming treatment was not a surprise, “those drops are huge,” Dr. Inwards-Breland said in an interview.

He said he attributes the improvement to a health care system that “affirms who these young people are” and enables changes that allow their outward appearance to reflect “who they know they are inside.”

There were no significant changes in anxiety during the study period. “Anxiety, I think, is just a little harder to treat, and it takes a little longer to treat,” he explained. And a lot of factors can trigger anxiety, and those can continue during treatment.

The slow pace of changes to gender identity can have an effect on people’s moods. “Since they’re not happening quickly, these young people are still being misgendered, they’re still seeing the body that they don’t feel like they should have, and they have to go to school and go out in public. I think that continues to fuel anxiety with a lot of these young people.”

Family support is important in reducing depression and suicidal thoughts in this population. Parents will often see positive changes after their child receives gender-affirming care, which can help contribute to positive changes in parents’ attitudes, Dr. Inwards-Breland said.

Such changes reinforce “that protective factor of connectedness with family,” he noted. “Families are crucial for any health care, and if there’s that connectedness with families, we know that, clinically, patients do better.”
 

Balancing risks

Although there are risks associated with gender-affirming hormones and puberty blockers, the risks of not receiving treatment must also be considered.

“Our young people are killing themselves,” he said. “Our young people are developing severe eating disorders that are killing them. Our young people are increasing their substance abuse, homelessness, depression. The list just goes on.”

For trans-masculine and nonbinary masculine patients, the potential permanent changes of hormone therapy include a deeper voice, hair growth, enlargement of the clitoris, and, in some patients, the development of male pattern baldness. In trans and nonbinary feminine patients, potential long-term effects include breast development and an increased risk for fertility issues.

The consent forms required for young people who want gender-affirming hormones or puberty blockers are extensive, with every possible reversible and irreversible effect described in detail, Dr. Breuner said.

“Parents sign them because they want their child to stay alive,” she explained. “When you compare the cost of someone who has severe debilitating depression and dying by suicide with some of the risks associated with gender-affirming hormone therapy, that’s a no-brainer to me.”

This study is limited by the fact that screening tests, not diagnostic tests, were used to identify depression, anxiety, and suicidality, and the fact that the use of antidepression or antianxiety medications was not taken into account, Dr. Inwards-Breland acknowledged.

“I think future studies should look at a mental health evaluation and diagnosis by a mental health provider,” he added. And mental health, gender dysphoria, suicidality, and self-harm should be tracked over the course of treatment.

He also acknowledged the study’s selection bias. All participants sought care at a multidisciplinary gender clinic, so were likely to be privileged and to have supportive families. “There’s a good chance that if we had more trans and nonbinary youth of color, we may have different findings,” he said.

More qualitative research is needed to assess the effect of gender-affirming therapy on the mental health of these patients, Dr. Breuner said.

“Being able to finally come into who you think you are and enjoy expressing who you are in a gender-affirming way has to be positive in such a way that you’re not depressed anymore,” she added. “It has to be tragic for people who cannot stand the body they’re in and cannot talk about it to anybody or express themselves without fear of recourse, to the point that they would be so devastated that they’d want to die by suicide.”

This research was funded by the Seattle Children’s Center for Diversity and Health Equity and the Pacific Hospital Development and Port Authority. Dr. Inwards-Breland and Dr. Breuner have disclosed no relevant financial relationships.

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

Transgender and nonbinary young people experienced less depression and fewer suicidal thoughts after a year of gender-affirming care with hormones or puberty blockers, according to new research.

“Given the high rates of adverse mental health comorbidities, these data provide critical evidence that expansion of gender-affirming care can save lives,” said David J. Inwards-Breland, MD, MPH, chief of adolescent and young adult medicine and codirector of the Center for Gender-Affirming Care at Rady Children’s Hospital in San Diego, during his presentation.

The findings, presented October 11 at the American Academy of Pediatrics 2021 National Conference, were not at all surprising to Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

“The younger we can provide gender-affirming care, the less likely they’re going to have depression, and then the negative outcomes from untreated depression, which includes suicide intent or even suicide completion,” Dr. Breuner told this news organization. “It’s so obvious that we are saving lives by providing gender-affirming care.”

For their study, Dr. Inwards-Breland and his colleagues tracked depression, anxiety, and suicidality in 104 trans and nonbinary people 13 to 21 years of age who received care at the Seattle Children’s gender clinic between August 2017 and June 2018.

The study population consisted of 63 transgender male or male participants, 27 transgender female or female participants, 10 nonbinary participants, and four participants who had not defined their gender identity. Of this cohort, 62.5% were receiving mental health therapy, and 34.7% reported some substance use.

Participants completed the nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder scale (GAD-7) at baseline and then at 3, 6, and 12 months. The researchers defined severe depression and severe anxiety as a score of 10 or greater on either scale.

At baseline, 56.7% of the participants had moderate to severe depression, 43.3% reported thoughts of self-harm or suicidal in the previous 2 weeks, and 50.0% had moderate to severe anxiety.

After 12 months of care, participants experienced a 60% decrease in depression (adjusted odds ratio, 0.4) and a 73% decrease in suicidality (aOR, 0.27), after adjustment for temporal trends and sex assigned at birth, race/ethnicity, level of parental support, ongoing mental health therapy, substance use, and victimization, including bullying, interpersonal violence, neglect, and abuse.

Although the decline in depression and suicidality after gender-affirming treatment was not a surprise, “those drops are huge,” Dr. Inwards-Breland said in an interview.

He said he attributes the improvement to a health care system that “affirms who these young people are” and enables changes that allow their outward appearance to reflect “who they know they are inside.”

There were no significant changes in anxiety during the study period. “Anxiety, I think, is just a little harder to treat, and it takes a little longer to treat,” he explained. And a lot of factors can trigger anxiety, and those can continue during treatment.

The slow pace of changes to gender identity can have an effect on people’s moods. “Since they’re not happening quickly, these young people are still being misgendered, they’re still seeing the body that they don’t feel like they should have, and they have to go to school and go out in public. I think that continues to fuel anxiety with a lot of these young people.”

Family support is important in reducing depression and suicidal thoughts in this population. Parents will often see positive changes after their child receives gender-affirming care, which can help contribute to positive changes in parents’ attitudes, Dr. Inwards-Breland said.

Such changes reinforce “that protective factor of connectedness with family,” he noted. “Families are crucial for any health care, and if there’s that connectedness with families, we know that, clinically, patients do better.”
 

Balancing risks

Although there are risks associated with gender-affirming hormones and puberty blockers, the risks of not receiving treatment must also be considered.

“Our young people are killing themselves,” he said. “Our young people are developing severe eating disorders that are killing them. Our young people are increasing their substance abuse, homelessness, depression. The list just goes on.”

For trans-masculine and nonbinary masculine patients, the potential permanent changes of hormone therapy include a deeper voice, hair growth, enlargement of the clitoris, and, in some patients, the development of male pattern baldness. In trans and nonbinary feminine patients, potential long-term effects include breast development and an increased risk for fertility issues.

The consent forms required for young people who want gender-affirming hormones or puberty blockers are extensive, with every possible reversible and irreversible effect described in detail, Dr. Breuner said.

“Parents sign them because they want their child to stay alive,” she explained. “When you compare the cost of someone who has severe debilitating depression and dying by suicide with some of the risks associated with gender-affirming hormone therapy, that’s a no-brainer to me.”

This study is limited by the fact that screening tests, not diagnostic tests, were used to identify depression, anxiety, and suicidality, and the fact that the use of antidepression or antianxiety medications was not taken into account, Dr. Inwards-Breland acknowledged.

“I think future studies should look at a mental health evaluation and diagnosis by a mental health provider,” he added. And mental health, gender dysphoria, suicidality, and self-harm should be tracked over the course of treatment.

He also acknowledged the study’s selection bias. All participants sought care at a multidisciplinary gender clinic, so were likely to be privileged and to have supportive families. “There’s a good chance that if we had more trans and nonbinary youth of color, we may have different findings,” he said.

More qualitative research is needed to assess the effect of gender-affirming therapy on the mental health of these patients, Dr. Breuner said.

“Being able to finally come into who you think you are and enjoy expressing who you are in a gender-affirming way has to be positive in such a way that you’re not depressed anymore,” she added. “It has to be tragic for people who cannot stand the body they’re in and cannot talk about it to anybody or express themselves without fear of recourse, to the point that they would be so devastated that they’d want to die by suicide.”

This research was funded by the Seattle Children’s Center for Diversity and Health Equity and the Pacific Hospital Development and Port Authority. Dr. Inwards-Breland and Dr. Breuner have disclosed no relevant financial relationships.

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

Transgender and nonbinary young people experienced less depression and fewer suicidal thoughts after a year of gender-affirming care with hormones or puberty blockers, according to new research.

“Given the high rates of adverse mental health comorbidities, these data provide critical evidence that expansion of gender-affirming care can save lives,” said David J. Inwards-Breland, MD, MPH, chief of adolescent and young adult medicine and codirector of the Center for Gender-Affirming Care at Rady Children’s Hospital in San Diego, during his presentation.

The findings, presented October 11 at the American Academy of Pediatrics 2021 National Conference, were not at all surprising to Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

“The younger we can provide gender-affirming care, the less likely they’re going to have depression, and then the negative outcomes from untreated depression, which includes suicide intent or even suicide completion,” Dr. Breuner told this news organization. “It’s so obvious that we are saving lives by providing gender-affirming care.”

For their study, Dr. Inwards-Breland and his colleagues tracked depression, anxiety, and suicidality in 104 trans and nonbinary people 13 to 21 years of age who received care at the Seattle Children’s gender clinic between August 2017 and June 2018.

The study population consisted of 63 transgender male or male participants, 27 transgender female or female participants, 10 nonbinary participants, and four participants who had not defined their gender identity. Of this cohort, 62.5% were receiving mental health therapy, and 34.7% reported some substance use.

Participants completed the nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder scale (GAD-7) at baseline and then at 3, 6, and 12 months. The researchers defined severe depression and severe anxiety as a score of 10 or greater on either scale.

At baseline, 56.7% of the participants had moderate to severe depression, 43.3% reported thoughts of self-harm or suicidal in the previous 2 weeks, and 50.0% had moderate to severe anxiety.

After 12 months of care, participants experienced a 60% decrease in depression (adjusted odds ratio, 0.4) and a 73% decrease in suicidality (aOR, 0.27), after adjustment for temporal trends and sex assigned at birth, race/ethnicity, level of parental support, ongoing mental health therapy, substance use, and victimization, including bullying, interpersonal violence, neglect, and abuse.

Although the decline in depression and suicidality after gender-affirming treatment was not a surprise, “those drops are huge,” Dr. Inwards-Breland said in an interview.

He said he attributes the improvement to a health care system that “affirms who these young people are” and enables changes that allow their outward appearance to reflect “who they know they are inside.”

There were no significant changes in anxiety during the study period. “Anxiety, I think, is just a little harder to treat, and it takes a little longer to treat,” he explained. And a lot of factors can trigger anxiety, and those can continue during treatment.

The slow pace of changes to gender identity can have an effect on people’s moods. “Since they’re not happening quickly, these young people are still being misgendered, they’re still seeing the body that they don’t feel like they should have, and they have to go to school and go out in public. I think that continues to fuel anxiety with a lot of these young people.”

Family support is important in reducing depression and suicidal thoughts in this population. Parents will often see positive changes after their child receives gender-affirming care, which can help contribute to positive changes in parents’ attitudes, Dr. Inwards-Breland said.

Such changes reinforce “that protective factor of connectedness with family,” he noted. “Families are crucial for any health care, and if there’s that connectedness with families, we know that, clinically, patients do better.”
 

Balancing risks

Although there are risks associated with gender-affirming hormones and puberty blockers, the risks of not receiving treatment must also be considered.

“Our young people are killing themselves,” he said. “Our young people are developing severe eating disorders that are killing them. Our young people are increasing their substance abuse, homelessness, depression. The list just goes on.”

For trans-masculine and nonbinary masculine patients, the potential permanent changes of hormone therapy include a deeper voice, hair growth, enlargement of the clitoris, and, in some patients, the development of male pattern baldness. In trans and nonbinary feminine patients, potential long-term effects include breast development and an increased risk for fertility issues.

The consent forms required for young people who want gender-affirming hormones or puberty blockers are extensive, with every possible reversible and irreversible effect described in detail, Dr. Breuner said.

“Parents sign them because they want their child to stay alive,” she explained. “When you compare the cost of someone who has severe debilitating depression and dying by suicide with some of the risks associated with gender-affirming hormone therapy, that’s a no-brainer to me.”

This study is limited by the fact that screening tests, not diagnostic tests, were used to identify depression, anxiety, and suicidality, and the fact that the use of antidepression or antianxiety medications was not taken into account, Dr. Inwards-Breland acknowledged.

“I think future studies should look at a mental health evaluation and diagnosis by a mental health provider,” he added. And mental health, gender dysphoria, suicidality, and self-harm should be tracked over the course of treatment.

He also acknowledged the study’s selection bias. All participants sought care at a multidisciplinary gender clinic, so were likely to be privileged and to have supportive families. “There’s a good chance that if we had more trans and nonbinary youth of color, we may have different findings,” he said.

More qualitative research is needed to assess the effect of gender-affirming therapy on the mental health of these patients, Dr. Breuner said.

“Being able to finally come into who you think you are and enjoy expressing who you are in a gender-affirming way has to be positive in such a way that you’re not depressed anymore,” she added. “It has to be tragic for people who cannot stand the body they’re in and cannot talk about it to anybody or express themselves without fear of recourse, to the point that they would be so devastated that they’d want to die by suicide.”

This research was funded by the Seattle Children’s Center for Diversity and Health Equity and the Pacific Hospital Development and Port Authority. Dr. Inwards-Breland and Dr. Breuner have disclosed no relevant financial relationships.

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

Most vaccines are given with hypodermic needle injections. But shots aren’t necessarily the most efficient or effective way to deliver a vaccine. Scientists have been experimenting with microneedle patches to painlessly deliver a vaccine into the outermost layer of the skin with dozens of extremely tiny needles coated in the vaccine solution.

Now, researchers have found a three-dimensional printing method that lets them customize microneedle shapes in the patches for different pathogens, such as flu, measles, hepatitis, or COVID-19. In tests using mice, the patches led to stronger and longer-lasting immune responses than traditional shots under the skin. The research team described their findings in the Proceedings of the National Academy of Sciences.
 

Tiny needles, big advantages

Previous research has shown delivering vaccines into the skin can cause a stronger immune response because the skin has a high concentration of immune cells. But shots can be painful and require skilled medical providers.

Microneedles painlessly deliver the vaccine into the skin without the need for a trained clinician. In fact, a person can even give the vaccine to themselves.

The needles – made of metal, silicon, or plastic – are so tiny that they puncture only the tough outermost layer of skin. The prospect of a painless vaccination without a hypodermic needle may ease anxiety in people who fear needles.

Scientists also can store dried patches after coating them with the vaccine solution, so there’s no preparation needed before giving the vaccine and the patches may not even require cold storage. This latest study suggests that the patches generate a stronger immune response than standard shots, allowing for a smaller dose than traditional vaccine delivery methods and possibly fewer side effects.
 

Breaking the mold

Past methods of making microneedle patches often used molds, but that approach limited the ability to customize patches for different diseases. Repeatedly using same mold also can blunt the tiny needles.

For the three-dimensional–printed patches, Cassie Caudill at the University of North Carolina at Chapel Hill and colleagues used a printing technique that allows greater control over and consistency in the shape of the microneedles. The investigators printed two shapes: a slender pyramid microneedle that is similar to previous versions, and one with serrated grooves that resembles a pine tree.

The increased surface area from the grooves let researchers add 36% more of the ingredient that causes an immune response, compared with using only the pyramid shape, yet still less than a conventional shot. At only 1 cm by 1 cm, each patch contains 100 microneedles that are just over 1 mm long. The researchers found that in mice the patch drew a stronger immune response than a conventional shot, despite carrying a much smaller dose of vaccine ingredient.

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

Most vaccines are given with hypodermic needle injections. But shots aren’t necessarily the most efficient or effective way to deliver a vaccine. Scientists have been experimenting with microneedle patches to painlessly deliver a vaccine into the outermost layer of the skin with dozens of extremely tiny needles coated in the vaccine solution.

Now, researchers have found a three-dimensional printing method that lets them customize microneedle shapes in the patches for different pathogens, such as flu, measles, hepatitis, or COVID-19. In tests using mice, the patches led to stronger and longer-lasting immune responses than traditional shots under the skin. The research team described their findings in the Proceedings of the National Academy of Sciences.
 

Tiny needles, big advantages

Previous research has shown delivering vaccines into the skin can cause a stronger immune response because the skin has a high concentration of immune cells. But shots can be painful and require skilled medical providers.

Microneedles painlessly deliver the vaccine into the skin without the need for a trained clinician. In fact, a person can even give the vaccine to themselves.

The needles – made of metal, silicon, or plastic – are so tiny that they puncture only the tough outermost layer of skin. The prospect of a painless vaccination without a hypodermic needle may ease anxiety in people who fear needles.

Scientists also can store dried patches after coating them with the vaccine solution, so there’s no preparation needed before giving the vaccine and the patches may not even require cold storage. This latest study suggests that the patches generate a stronger immune response than standard shots, allowing for a smaller dose than traditional vaccine delivery methods and possibly fewer side effects.
 

Breaking the mold

Past methods of making microneedle patches often used molds, but that approach limited the ability to customize patches for different diseases. Repeatedly using same mold also can blunt the tiny needles.

For the three-dimensional–printed patches, Cassie Caudill at the University of North Carolina at Chapel Hill and colleagues used a printing technique that allows greater control over and consistency in the shape of the microneedles. The investigators printed two shapes: a slender pyramid microneedle that is similar to previous versions, and one with serrated grooves that resembles a pine tree.

The increased surface area from the grooves let researchers add 36% more of the ingredient that causes an immune response, compared with using only the pyramid shape, yet still less than a conventional shot. At only 1 cm by 1 cm, each patch contains 100 microneedles that are just over 1 mm long. The researchers found that in mice the patch drew a stronger immune response than a conventional shot, despite carrying a much smaller dose of vaccine ingredient.

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

Most vaccines are given with hypodermic needle injections. But shots aren’t necessarily the most efficient or effective way to deliver a vaccine. Scientists have been experimenting with microneedle patches to painlessly deliver a vaccine into the outermost layer of the skin with dozens of extremely tiny needles coated in the vaccine solution.

Now, researchers have found a three-dimensional printing method that lets them customize microneedle shapes in the patches for different pathogens, such as flu, measles, hepatitis, or COVID-19. In tests using mice, the patches led to stronger and longer-lasting immune responses than traditional shots under the skin. The research team described their findings in the Proceedings of the National Academy of Sciences.
 

Tiny needles, big advantages

Previous research has shown delivering vaccines into the skin can cause a stronger immune response because the skin has a high concentration of immune cells. But shots can be painful and require skilled medical providers.

Microneedles painlessly deliver the vaccine into the skin without the need for a trained clinician. In fact, a person can even give the vaccine to themselves.

The needles – made of metal, silicon, or plastic – are so tiny that they puncture only the tough outermost layer of skin. The prospect of a painless vaccination without a hypodermic needle may ease anxiety in people who fear needles.

Scientists also can store dried patches after coating them with the vaccine solution, so there’s no preparation needed before giving the vaccine and the patches may not even require cold storage. This latest study suggests that the patches generate a stronger immune response than standard shots, allowing for a smaller dose than traditional vaccine delivery methods and possibly fewer side effects.
 

Breaking the mold

Past methods of making microneedle patches often used molds, but that approach limited the ability to customize patches for different diseases. Repeatedly using same mold also can blunt the tiny needles.

For the three-dimensional–printed patches, Cassie Caudill at the University of North Carolina at Chapel Hill and colleagues used a printing technique that allows greater control over and consistency in the shape of the microneedles. The investigators printed two shapes: a slender pyramid microneedle that is similar to previous versions, and one with serrated grooves that resembles a pine tree.

The increased surface area from the grooves let researchers add 36% more of the ingredient that causes an immune response, compared with using only the pyramid shape, yet still less than a conventional shot. At only 1 cm by 1 cm, each patch contains 100 microneedles that are just over 1 mm long. The researchers found that in mice the patch drew a stronger immune response than a conventional shot, despite carrying a much smaller dose of vaccine ingredient.

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

With all the lockdowns and social distancing of the pandemic, millions of people have had a lot of time to themselves. Many may have filled that time with baking, long walks, or video games, but minds wandering during these periods was inevitable. Coincident with these experiences were increases in depression and anxiety, which could be linked to the same brain network that is thought to support a meandering mind, called the default mode network.

©Thinkstock

Scientists interested in this network wanted to understand how wandering thoughts can lead some people to a state of brooding in which the same negative thoughts resurface repeatedly. To gain some insight into these patterns, they recorded more than 2,000 thoughts spoken aloud by 78 study participants who did nothing but let their minds wander for 10 minutes.

Senior researcher Jessica Andrews-Hanna, PhD, assistant professor of psychology, University of Arizona, Tucson, and colleagues hoped that analyzing these stream-of-consciousness thoughts could yield insights into how people become stuck in negative mental spirals.

They found that most participants thought about the present or future in words that were neither particularly negative nor positive. Almost three-quarters of the thoughts were focused inward on the person or were imaginative.
 

Negativity breeds negativity

But the investigators found an interesting pattern with regard to negative thoughts. The more negative someone’s thoughts became, the more likely that their next idea would be related to their previous one. In other words, negative thoughts created a chain reaction of more negative thoughts.

Positive thoughts, in contrast, tended to be followed by completely unrelated ruminations, indicating true mental meandering. The pattern suggested that negativity tends to narrow the range of thoughts, whereas positivity tends to expand it during periods in which the mind wanders.

The researchers also found, unsurprisingly, that negative thoughts that were focused on the self and on the past were more likely to result in brooding and that positive thoughts were less likely to arise.

Most study participants were young and educated and may have only said things that they were comfortable allowing the researchers to hear. And because the authors didn’t ask participants about their moods, the investigators could not associate specific patterns of thought with any mental health conditions.

Although the findings, published in Scientific Reports, do not on their own point to solutions for depression or anxiety, they may offer a starting point for future research into how negative trains of thoughts begin – and perhaps how to derail them.

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

With all the lockdowns and social distancing of the pandemic, millions of people have had a lot of time to themselves. Many may have filled that time with baking, long walks, or video games, but minds wandering during these periods was inevitable. Coincident with these experiences were increases in depression and anxiety, which could be linked to the same brain network that is thought to support a meandering mind, called the default mode network.

©Thinkstock

Scientists interested in this network wanted to understand how wandering thoughts can lead some people to a state of brooding in which the same negative thoughts resurface repeatedly. To gain some insight into these patterns, they recorded more than 2,000 thoughts spoken aloud by 78 study participants who did nothing but let their minds wander for 10 minutes.

Senior researcher Jessica Andrews-Hanna, PhD, assistant professor of psychology, University of Arizona, Tucson, and colleagues hoped that analyzing these stream-of-consciousness thoughts could yield insights into how people become stuck in negative mental spirals.

They found that most participants thought about the present or future in words that were neither particularly negative nor positive. Almost three-quarters of the thoughts were focused inward on the person or were imaginative.
 

Negativity breeds negativity

But the investigators found an interesting pattern with regard to negative thoughts. The more negative someone’s thoughts became, the more likely that their next idea would be related to their previous one. In other words, negative thoughts created a chain reaction of more negative thoughts.

Positive thoughts, in contrast, tended to be followed by completely unrelated ruminations, indicating true mental meandering. The pattern suggested that negativity tends to narrow the range of thoughts, whereas positivity tends to expand it during periods in which the mind wanders.

The researchers also found, unsurprisingly, that negative thoughts that were focused on the self and on the past were more likely to result in brooding and that positive thoughts were less likely to arise.

Most study participants were young and educated and may have only said things that they were comfortable allowing the researchers to hear. And because the authors didn’t ask participants about their moods, the investigators could not associate specific patterns of thought with any mental health conditions.

Although the findings, published in Scientific Reports, do not on their own point to solutions for depression or anxiety, they may offer a starting point for future research into how negative trains of thoughts begin – and perhaps how to derail them.

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

With all the lockdowns and social distancing of the pandemic, millions of people have had a lot of time to themselves. Many may have filled that time with baking, long walks, or video games, but minds wandering during these periods was inevitable. Coincident with these experiences were increases in depression and anxiety, which could be linked to the same brain network that is thought to support a meandering mind, called the default mode network.

©Thinkstock

Scientists interested in this network wanted to understand how wandering thoughts can lead some people to a state of brooding in which the same negative thoughts resurface repeatedly. To gain some insight into these patterns, they recorded more than 2,000 thoughts spoken aloud by 78 study participants who did nothing but let their minds wander for 10 minutes.

Senior researcher Jessica Andrews-Hanna, PhD, assistant professor of psychology, University of Arizona, Tucson, and colleagues hoped that analyzing these stream-of-consciousness thoughts could yield insights into how people become stuck in negative mental spirals.

They found that most participants thought about the present or future in words that were neither particularly negative nor positive. Almost three-quarters of the thoughts were focused inward on the person or were imaginative.
 

Negativity breeds negativity

But the investigators found an interesting pattern with regard to negative thoughts. The more negative someone’s thoughts became, the more likely that their next idea would be related to their previous one. In other words, negative thoughts created a chain reaction of more negative thoughts.

Positive thoughts, in contrast, tended to be followed by completely unrelated ruminations, indicating true mental meandering. The pattern suggested that negativity tends to narrow the range of thoughts, whereas positivity tends to expand it during periods in which the mind wanders.

The researchers also found, unsurprisingly, that negative thoughts that were focused on the self and on the past were more likely to result in brooding and that positive thoughts were less likely to arise.

Most study participants were young and educated and may have only said things that they were comfortable allowing the researchers to hear. And because the authors didn’t ask participants about their moods, the investigators could not associate specific patterns of thought with any mental health conditions.

Although the findings, published in Scientific Reports, do not on their own point to solutions for depression or anxiety, they may offer a starting point for future research into how negative trains of thoughts begin – and perhaps how to derail them.

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

When pediatricians and other pediatric providers are given training and resource materials, levels of firearm screenings and anticipatory guidance about firearm safety increase significantly, according to two new studies presented at the annual meeting of the American Academy of Pediatrics.

“With the rise in firearm sales and injuries during the COVID-19 pandemic, it is more important than ever that pediatricians address the firearm epidemic,” said Alexandra Byrne, MD, a pediatric resident at the University of Florida in Gainesville, who presented one of the studies.

There were 4.3 million more firearms purchased from March through July 2020 than expected, a recent study estimates, and 4,075 more firearm injuries than expected from April through July 2020.

In states with more excess purchases, firearm injuries related to domestic violence increased in April (rate ratio, 2.60; 95% CI, 1.32-5.93) and May (RR, 1.79; 95% CI, 1.19-2.91) 2020. However, excess gun purchases had no effect on rates of firearm violence outside the home.

In addition to the link between firearms in the home and domestic violence, they are also linked to a three- to fourfold greater risk for teen suicide, and both depression and suicidal thoughts have risen in teens during the pandemic.

“The data are pretty clear that if you have an unlocked, loaded weapon in your home, and you have a kid who’s depressed or anxious or dysregulated or doing maladaptive things for the pandemic, they’re much more likely to inadvertently take their own or someone else’s life by grabbing [a gun],” said Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

However, there is no difference in gun ownership or gun-safety measures between homes with and without at-risk children, previous research shows.
 

Training, guidance, and locks

Previous research has also shown that there has been a reluctance by pediatricians to conduct firearm screenings and counsel parents about gun safety in the home.

For their two-step program, Dr. Byrne’s team used a plan-do-study-act approach. They started by providing training on firearm safety, evidence-based recommendations for firearm screening, and anticipatory guidance regarding safe firearm storage to members of the general pediatrics division at the University of Florida. And they supplied clinics with free firearm locks.

Next they supplied clinics with posters and educational cards from the Be SMART campaign, an initiative of the Everytown for Gun Safety Support Fund, which provides materials for anyone, including physicians, to use.

During their study, the researchers sent three anonymous six-question online surveys – at baseline and 3 to 4 months after each of the two steps – to pediatric residents, physician assistants, advanced practice registered nurses, and attendings to assess the project. There were 52 responses to the first survey, for a response rate of 58.4%, 42 responses to the second survey, for a response rate of 47.2%, and 23 responses to the third survey, for a rate of response 25.8%.

The program nearly doubled screenings during well-child visits and dramatically increased the proportion of families who received a firearm lock when they told providers they had a firearm at home.

Adding a social-history component

A program to increase firearm screening was also presented at the AAP conference.

After random review of medical records from 30 patients admitted to the hospital documented zero firearm screenings, Marjorie Farrington, MD, and Samantha Gunkelman, MD, from Akron Children’s Hospital in Ohio, implemented a program that they hope will increase firearm screenings during inpatient admissions to at least 50%.

They started their ongoing program in April 2020 by adding a social-history component to the history and physical (H&P) exam template and educating residents on how to screen and included guidance on safe firearm storage.

They also had physicians with firearm expertise give gun-safety lectures, and they plan to involve the Family Resource Center at their hospital in the creation of resources that can be incorporated into discharge instructions.

From April 2020 to June 2021, after the addition to the H&P template, 63% of the 5196 patients admitted to the hospital underwent a firearm screening. Of the 25% of patients who reported guns at home, 3% were not storing their firearms safely.

The pair used the “Store It Safe” Physician Handout provided by the Ohio chapter of the AAP.

Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic.

The BulletPoints Project — developed by the Violence Prevention Research Program at the University of California, Davis — can also help physicians talk to patients about guns.

“Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic,” Dr. Byrne said in an interview. “Additionally, it is a challenging topic that can often be met with resistance from patients and families. Lack of time during visits is also a huge barrier.”

Lack of training is an obstacle to greater firearm screenings, Dr. Greeley agreed, as are the feeling that guidance simply won’t make a difference and concerns about political pressure and divineness. The lack of research on firearm injuries and the impact of firearm screenings and anticipatory guidance is a challenge, he added, although that is starting to change.

Pediatricians need education on how to make a difference when it comes to firearm safety, and should follow AAP guidelines, Dr. Greeley said.

Counseling on firearm safety is in the same category as immunizations, seatbelts, substance use, helmets, and other public-health issues that are important to address at visits, regardless of how difficult it might be, Dr. Breuner told this news organization.

“It is our mission, as pediatricians, to provide every ounce of prevention in our well-child and anticipatory guidance visits,” she said. “It’s our job, so we shouldn’t shy away from it even though it’s hard.”

Doctors are more comfortable discussing firearm safety if they are firearm owners, previous research has shown, so she advises pediatricians who feel unqualified to discuss firearms to seek guidance from their peers on how to approach screenings and anticipatory guidance, she noted.

The firearm study being done in an academic center gives me great pause. The populations are often very different than private practice.

Both of these studies were conducted at single institutions and might not reflect what would work in private clinics.

“The firearm study being done in an academic center gives me great pause,” Dr. Greeley said. “The populations are often very different than private practice. I think that there is still a lot that remains unknown about decreasing household firearm injury and death.”

And the degree to which findings from these two gun-safety programs can be generalized to other academic centers or children’s hospitals is unclear.

“There are states where, I suspect, firearm screening is much more common. Some states have very pro-firearm cultures and others are anti-firearm,” Dr. Greeley said. “There are also likely differences within states,” particularly between urban and rural regions.

“Firearms are often a very personal issue for families, and pediatricians in ‘pro-firearm’ communities may have greater resistance to working on this,” he pointed out.

Nevertheless, Dr. Greeley said, “this is a promising strategy that could be part of a broad injury prevention initiative.”

Neither study noted any external funding. Dr. Byrne is a member of the Moms Demand Action Gainesville Chapter, which donated the firearm locks for the project. Dr. Breuner, Dr. Greeley, and Dr. Farrington have disclosed no relevant financial relationships.

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

When pediatricians and other pediatric providers are given training and resource materials, levels of firearm screenings and anticipatory guidance about firearm safety increase significantly, according to two new studies presented at the annual meeting of the American Academy of Pediatrics.

“With the rise in firearm sales and injuries during the COVID-19 pandemic, it is more important than ever that pediatricians address the firearm epidemic,” said Alexandra Byrne, MD, a pediatric resident at the University of Florida in Gainesville, who presented one of the studies.

There were 4.3 million more firearms purchased from March through July 2020 than expected, a recent study estimates, and 4,075 more firearm injuries than expected from April through July 2020.

In states with more excess purchases, firearm injuries related to domestic violence increased in April (rate ratio, 2.60; 95% CI, 1.32-5.93) and May (RR, 1.79; 95% CI, 1.19-2.91) 2020. However, excess gun purchases had no effect on rates of firearm violence outside the home.

In addition to the link between firearms in the home and domestic violence, they are also linked to a three- to fourfold greater risk for teen suicide, and both depression and suicidal thoughts have risen in teens during the pandemic.

“The data are pretty clear that if you have an unlocked, loaded weapon in your home, and you have a kid who’s depressed or anxious or dysregulated or doing maladaptive things for the pandemic, they’re much more likely to inadvertently take their own or someone else’s life by grabbing [a gun],” said Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

However, there is no difference in gun ownership or gun-safety measures between homes with and without at-risk children, previous research shows.
 

Training, guidance, and locks

Previous research has also shown that there has been a reluctance by pediatricians to conduct firearm screenings and counsel parents about gun safety in the home.

For their two-step program, Dr. Byrne’s team used a plan-do-study-act approach. They started by providing training on firearm safety, evidence-based recommendations for firearm screening, and anticipatory guidance regarding safe firearm storage to members of the general pediatrics division at the University of Florida. And they supplied clinics with free firearm locks.

Next they supplied clinics with posters and educational cards from the Be SMART campaign, an initiative of the Everytown for Gun Safety Support Fund, which provides materials for anyone, including physicians, to use.

During their study, the researchers sent three anonymous six-question online surveys – at baseline and 3 to 4 months after each of the two steps – to pediatric residents, physician assistants, advanced practice registered nurses, and attendings to assess the project. There were 52 responses to the first survey, for a response rate of 58.4%, 42 responses to the second survey, for a response rate of 47.2%, and 23 responses to the third survey, for a rate of response 25.8%.

The program nearly doubled screenings during well-child visits and dramatically increased the proportion of families who received a firearm lock when they told providers they had a firearm at home.

Adding a social-history component

A program to increase firearm screening was also presented at the AAP conference.

After random review of medical records from 30 patients admitted to the hospital documented zero firearm screenings, Marjorie Farrington, MD, and Samantha Gunkelman, MD, from Akron Children’s Hospital in Ohio, implemented a program that they hope will increase firearm screenings during inpatient admissions to at least 50%.

They started their ongoing program in April 2020 by adding a social-history component to the history and physical (H&P) exam template and educating residents on how to screen and included guidance on safe firearm storage.

They also had physicians with firearm expertise give gun-safety lectures, and they plan to involve the Family Resource Center at their hospital in the creation of resources that can be incorporated into discharge instructions.

From April 2020 to June 2021, after the addition to the H&P template, 63% of the 5196 patients admitted to the hospital underwent a firearm screening. Of the 25% of patients who reported guns at home, 3% were not storing their firearms safely.

The pair used the “Store It Safe” Physician Handout provided by the Ohio chapter of the AAP.

Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic.

The BulletPoints Project — developed by the Violence Prevention Research Program at the University of California, Davis — can also help physicians talk to patients about guns.

“Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic,” Dr. Byrne said in an interview. “Additionally, it is a challenging topic that can often be met with resistance from patients and families. Lack of time during visits is also a huge barrier.”

Lack of training is an obstacle to greater firearm screenings, Dr. Greeley agreed, as are the feeling that guidance simply won’t make a difference and concerns about political pressure and divineness. The lack of research on firearm injuries and the impact of firearm screenings and anticipatory guidance is a challenge, he added, although that is starting to change.

Pediatricians need education on how to make a difference when it comes to firearm safety, and should follow AAP guidelines, Dr. Greeley said.

Counseling on firearm safety is in the same category as immunizations, seatbelts, substance use, helmets, and other public-health issues that are important to address at visits, regardless of how difficult it might be, Dr. Breuner told this news organization.

“It is our mission, as pediatricians, to provide every ounce of prevention in our well-child and anticipatory guidance visits,” she said. “It’s our job, so we shouldn’t shy away from it even though it’s hard.”

Doctors are more comfortable discussing firearm safety if they are firearm owners, previous research has shown, so she advises pediatricians who feel unqualified to discuss firearms to seek guidance from their peers on how to approach screenings and anticipatory guidance, she noted.

The firearm study being done in an academic center gives me great pause. The populations are often very different than private practice.

Both of these studies were conducted at single institutions and might not reflect what would work in private clinics.

“The firearm study being done in an academic center gives me great pause,” Dr. Greeley said. “The populations are often very different than private practice. I think that there is still a lot that remains unknown about decreasing household firearm injury and death.”

And the degree to which findings from these two gun-safety programs can be generalized to other academic centers or children’s hospitals is unclear.

“There are states where, I suspect, firearm screening is much more common. Some states have very pro-firearm cultures and others are anti-firearm,” Dr. Greeley said. “There are also likely differences within states,” particularly between urban and rural regions.

“Firearms are often a very personal issue for families, and pediatricians in ‘pro-firearm’ communities may have greater resistance to working on this,” he pointed out.

Nevertheless, Dr. Greeley said, “this is a promising strategy that could be part of a broad injury prevention initiative.”

Neither study noted any external funding. Dr. Byrne is a member of the Moms Demand Action Gainesville Chapter, which donated the firearm locks for the project. Dr. Breuner, Dr. Greeley, and Dr. Farrington have disclosed no relevant financial relationships.

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

When pediatricians and other pediatric providers are given training and resource materials, levels of firearm screenings and anticipatory guidance about firearm safety increase significantly, according to two new studies presented at the annual meeting of the American Academy of Pediatrics.

“With the rise in firearm sales and injuries during the COVID-19 pandemic, it is more important than ever that pediatricians address the firearm epidemic,” said Alexandra Byrne, MD, a pediatric resident at the University of Florida in Gainesville, who presented one of the studies.

There were 4.3 million more firearms purchased from March through July 2020 than expected, a recent study estimates, and 4,075 more firearm injuries than expected from April through July 2020.

In states with more excess purchases, firearm injuries related to domestic violence increased in April (rate ratio, 2.60; 95% CI, 1.32-5.93) and May (RR, 1.79; 95% CI, 1.19-2.91) 2020. However, excess gun purchases had no effect on rates of firearm violence outside the home.

In addition to the link between firearms in the home and domestic violence, they are also linked to a three- to fourfold greater risk for teen suicide, and both depression and suicidal thoughts have risen in teens during the pandemic.

“The data are pretty clear that if you have an unlocked, loaded weapon in your home, and you have a kid who’s depressed or anxious or dysregulated or doing maladaptive things for the pandemic, they’re much more likely to inadvertently take their own or someone else’s life by grabbing [a gun],” said Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

However, there is no difference in gun ownership or gun-safety measures between homes with and without at-risk children, previous research shows.
 

Training, guidance, and locks

Previous research has also shown that there has been a reluctance by pediatricians to conduct firearm screenings and counsel parents about gun safety in the home.

For their two-step program, Dr. Byrne’s team used a plan-do-study-act approach. They started by providing training on firearm safety, evidence-based recommendations for firearm screening, and anticipatory guidance regarding safe firearm storage to members of the general pediatrics division at the University of Florida. And they supplied clinics with free firearm locks.

Next they supplied clinics with posters and educational cards from the Be SMART campaign, an initiative of the Everytown for Gun Safety Support Fund, which provides materials for anyone, including physicians, to use.

During their study, the researchers sent three anonymous six-question online surveys – at baseline and 3 to 4 months after each of the two steps – to pediatric residents, physician assistants, advanced practice registered nurses, and attendings to assess the project. There were 52 responses to the first survey, for a response rate of 58.4%, 42 responses to the second survey, for a response rate of 47.2%, and 23 responses to the third survey, for a rate of response 25.8%.

The program nearly doubled screenings during well-child visits and dramatically increased the proportion of families who received a firearm lock when they told providers they had a firearm at home.

Adding a social-history component

A program to increase firearm screening was also presented at the AAP conference.

After random review of medical records from 30 patients admitted to the hospital documented zero firearm screenings, Marjorie Farrington, MD, and Samantha Gunkelman, MD, from Akron Children’s Hospital in Ohio, implemented a program that they hope will increase firearm screenings during inpatient admissions to at least 50%.

They started their ongoing program in April 2020 by adding a social-history component to the history and physical (H&P) exam template and educating residents on how to screen and included guidance on safe firearm storage.

They also had physicians with firearm expertise give gun-safety lectures, and they plan to involve the Family Resource Center at their hospital in the creation of resources that can be incorporated into discharge instructions.

From April 2020 to June 2021, after the addition to the H&P template, 63% of the 5196 patients admitted to the hospital underwent a firearm screening. Of the 25% of patients who reported guns at home, 3% were not storing their firearms safely.

The pair used the “Store It Safe” Physician Handout provided by the Ohio chapter of the AAP.

Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic.

The BulletPoints Project — developed by the Violence Prevention Research Program at the University of California, Davis — can also help physicians talk to patients about guns.

“Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic,” Dr. Byrne said in an interview. “Additionally, it is a challenging topic that can often be met with resistance from patients and families. Lack of time during visits is also a huge barrier.”

Lack of training is an obstacle to greater firearm screenings, Dr. Greeley agreed, as are the feeling that guidance simply won’t make a difference and concerns about political pressure and divineness. The lack of research on firearm injuries and the impact of firearm screenings and anticipatory guidance is a challenge, he added, although that is starting to change.

Pediatricians need education on how to make a difference when it comes to firearm safety, and should follow AAP guidelines, Dr. Greeley said.

Counseling on firearm safety is in the same category as immunizations, seatbelts, substance use, helmets, and other public-health issues that are important to address at visits, regardless of how difficult it might be, Dr. Breuner told this news organization.

“It is our mission, as pediatricians, to provide every ounce of prevention in our well-child and anticipatory guidance visits,” she said. “It’s our job, so we shouldn’t shy away from it even though it’s hard.”

Doctors are more comfortable discussing firearm safety if they are firearm owners, previous research has shown, so she advises pediatricians who feel unqualified to discuss firearms to seek guidance from their peers on how to approach screenings and anticipatory guidance, she noted.

The firearm study being done in an academic center gives me great pause. The populations are often very different than private practice.

Both of these studies were conducted at single institutions and might not reflect what would work in private clinics.

“The firearm study being done in an academic center gives me great pause,” Dr. Greeley said. “The populations are often very different than private practice. I think that there is still a lot that remains unknown about decreasing household firearm injury and death.”

And the degree to which findings from these two gun-safety programs can be generalized to other academic centers or children’s hospitals is unclear.

“There are states where, I suspect, firearm screening is much more common. Some states have very pro-firearm cultures and others are anti-firearm,” Dr. Greeley said. “There are also likely differences within states,” particularly between urban and rural regions.

“Firearms are often a very personal issue for families, and pediatricians in ‘pro-firearm’ communities may have greater resistance to working on this,” he pointed out.

Nevertheless, Dr. Greeley said, “this is a promising strategy that could be part of a broad injury prevention initiative.”

Neither study noted any external funding. Dr. Byrne is a member of the Moms Demand Action Gainesville Chapter, which donated the firearm locks for the project. Dr. Breuner, Dr. Greeley, and Dr. Farrington have disclosed no relevant financial relationships.

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

The likelihood that a child will survive a near-drowning without long-term damage is substantially greater if a bystander attempts a rescue, even if that person doesn’t perform cardiopulmonary resuscitation (CPR), according to new research presented October 10 at the American Academy of Pediatrics (AAP) 2021 National Conference.

“The extent to which bystander rescue is associated with reduced odds of unfavorable drowning outcomes was surprising,” said lead investigator Rohit P. Shenoi, MD, professor of pediatrics at Baylor College of Medicine and attending physician at Texas Children’s Hospital, Houston.

“While we do know that early rescue and resuscitation is helpful in preventing severe drowning injury, the degree of benefit from bystander rescue in all cases of pediatric drowning has not been described so far,” he told this news organization.

The fact that a bystander’s rescue attempt improves a child’s odds of a good outcome is not surprising on its own, but the magnitude of the finding really affirms the importance of bystander intervention, said Benjamin Hoffman, MD, professor of pediatrics at the Oregon Health & Science University School of Medicine and medical director of the Tom Sargent Safety Center at the Doernbecher Children’s Hospital, Portland.

“If an adult finds a child in the water, even if they don’t administer formal CPR, they’re going to be doing things” to try to help, Dr. Hoffman, who was not involved in this research but who specializes in child injury prevention, said in an interview. The act of intervening – whether it’s formal CPR or a CPR attempt or even just calling appropriate first responders – “likely impacts the duration of the submersion” and “clearly makes a difference.”

Drowning is the leading cause of death for children younger than 4 years, Dr. Hoffman noted, adding that the AAP recommends swimming lessons for children older than 1 year to reduce that risk.

In their cross-sectional study, Dr. Shenoi and his colleagues analyzed data on drownings and near-drownings in children and adolescents younger than 18 years using hospital, emergency medical services, and child fatality records from Harris County, Texas.

They analyzed 237 incidents from 2010 to 2013 in which the young person was submerged. Median age of the victims was 3.2 years, 60% were male, 64% were Black, Hispanic, or Native American, and 78% occurred in a swimming pool.

Unfavorable outcomes – defined as death or severe impairment after hospital discharge – were experienced by 38 victims (16%) and were significantly associated with being submerged for longer than 5 minutes (P < .001).

The odds of an unfavorable outcome dropped by 80% if a bystander attempted a rescue, whether or not they performed CPR (adjusted odds ratio, 0.2; P = .004). If the bystander performed CPR, the odds of an unfavorable outcome dropped by a similar amount, but the difference was not statistically significant (aOR, 0.22; P = .07).

However, previous research has shown a significant reduction in poor outcomes when CPR is administered to children who have been submerged, Dr. Hoffman explained.

The most important thing a bystander can do is simply get a submerged child out of the water. “Early rescue in drowning terminates what is initially a respiratory arrest from progressing to a full cardiopulmonary arrest with severe hypoxic brain injury and death,” Dr. Shenoi said.

“CPR is also very important, and rescue and resuscitation go hand in hand. We encourage all laypersons to be trained in CPR so that they can administer correct CPR techniques,” he added.

Both Dr. Shenoi and Dr. Hoffman emphasized the value of CPR training for adults, as the AAP recommends, and the importance of other precautions that reduce the risk of drowning.

“Drowning prevention should consist of multiple layers of prevention,” Dr. Shenoi said. These consist of “close, constant, and attentive supervision; isolation fencing for swimming pools; and water competency, including water-safety knowledge, basic swim skills, and the ability to recognize and respond to a swimmer in trouble, use of life jackets, and early bystander CPR.”

The relative importance of each of those layers depends on geography and circumstances, Dr. Hoffman said. Pools are the most common drowning sites in the United States overall, but they’re much more common in warmer states, such as California, Florida, and Texas, which have more pools. In contrast, drownings in Oregon are more likely to occur in rivers, so prevention is more about access to life jackets and increasing access to swim lessons.

The findings from this study drive home how important it is for physicians to provide anticipatory guidance to families on reducing the risk of drowning. Pediatricians should convey to families the need for different layers of protection, he added.

“If your family spends a lot of time around water, whether open water or swimming pools, the more layers you can provide, the better off you’re going to be,” Dr. Hoffman said.

Dr. Shenoi echoed this sentiment.

“The take-home message is to be observant if you are entrusted with the care of a child around water,” Dr. Shenoi said. “If you notice the child to be drowning, either attempt rescue yourself if it is safe to do so or enlist the help of others to save the victim as soon as possible. However, the rescuer should not place himself or herself in danger when attempting rescue.”

The five steps in the “drowning chain of survival” – preventing drowning, recognizing distress, providing flotation, removing the victim from the water, and providing care and CPR as needed – are key to reducing drowning deaths and injury, Dr. Shenoi emphasized.

Dr. Shenoi has disclosed no relevant financial relationships. Dr. Hoffman is a paid consultant on child drowning prevention for the nonprofit Anonymous Philanthropy.

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

The likelihood that a child will survive a near-drowning without long-term damage is substantially greater if a bystander attempts a rescue, even if that person doesn’t perform cardiopulmonary resuscitation (CPR), according to new research presented October 10 at the American Academy of Pediatrics (AAP) 2021 National Conference.

“The extent to which bystander rescue is associated with reduced odds of unfavorable drowning outcomes was surprising,” said lead investigator Rohit P. Shenoi, MD, professor of pediatrics at Baylor College of Medicine and attending physician at Texas Children’s Hospital, Houston.

“While we do know that early rescue and resuscitation is helpful in preventing severe drowning injury, the degree of benefit from bystander rescue in all cases of pediatric drowning has not been described so far,” he told this news organization.

The fact that a bystander’s rescue attempt improves a child’s odds of a good outcome is not surprising on its own, but the magnitude of the finding really affirms the importance of bystander intervention, said Benjamin Hoffman, MD, professor of pediatrics at the Oregon Health & Science University School of Medicine and medical director of the Tom Sargent Safety Center at the Doernbecher Children’s Hospital, Portland.

“If an adult finds a child in the water, even if they don’t administer formal CPR, they’re going to be doing things” to try to help, Dr. Hoffman, who was not involved in this research but who specializes in child injury prevention, said in an interview. The act of intervening – whether it’s formal CPR or a CPR attempt or even just calling appropriate first responders – “likely impacts the duration of the submersion” and “clearly makes a difference.”

Drowning is the leading cause of death for children younger than 4 years, Dr. Hoffman noted, adding that the AAP recommends swimming lessons for children older than 1 year to reduce that risk.

In their cross-sectional study, Dr. Shenoi and his colleagues analyzed data on drownings and near-drownings in children and adolescents younger than 18 years using hospital, emergency medical services, and child fatality records from Harris County, Texas.

They analyzed 237 incidents from 2010 to 2013 in which the young person was submerged. Median age of the victims was 3.2 years, 60% were male, 64% were Black, Hispanic, or Native American, and 78% occurred in a swimming pool.

Unfavorable outcomes – defined as death or severe impairment after hospital discharge – were experienced by 38 victims (16%) and were significantly associated with being submerged for longer than 5 minutes (P < .001).

The odds of an unfavorable outcome dropped by 80% if a bystander attempted a rescue, whether or not they performed CPR (adjusted odds ratio, 0.2; P = .004). If the bystander performed CPR, the odds of an unfavorable outcome dropped by a similar amount, but the difference was not statistically significant (aOR, 0.22; P = .07).

However, previous research has shown a significant reduction in poor outcomes when CPR is administered to children who have been submerged, Dr. Hoffman explained.

The most important thing a bystander can do is simply get a submerged child out of the water. “Early rescue in drowning terminates what is initially a respiratory arrest from progressing to a full cardiopulmonary arrest with severe hypoxic brain injury and death,” Dr. Shenoi said.

“CPR is also very important, and rescue and resuscitation go hand in hand. We encourage all laypersons to be trained in CPR so that they can administer correct CPR techniques,” he added.

Both Dr. Shenoi and Dr. Hoffman emphasized the value of CPR training for adults, as the AAP recommends, and the importance of other precautions that reduce the risk of drowning.

“Drowning prevention should consist of multiple layers of prevention,” Dr. Shenoi said. These consist of “close, constant, and attentive supervision; isolation fencing for swimming pools; and water competency, including water-safety knowledge, basic swim skills, and the ability to recognize and respond to a swimmer in trouble, use of life jackets, and early bystander CPR.”

The relative importance of each of those layers depends on geography and circumstances, Dr. Hoffman said. Pools are the most common drowning sites in the United States overall, but they’re much more common in warmer states, such as California, Florida, and Texas, which have more pools. In contrast, drownings in Oregon are more likely to occur in rivers, so prevention is more about access to life jackets and increasing access to swim lessons.

The findings from this study drive home how important it is for physicians to provide anticipatory guidance to families on reducing the risk of drowning. Pediatricians should convey to families the need for different layers of protection, he added.

“If your family spends a lot of time around water, whether open water or swimming pools, the more layers you can provide, the better off you’re going to be,” Dr. Hoffman said.

Dr. Shenoi echoed this sentiment.

“The take-home message is to be observant if you are entrusted with the care of a child around water,” Dr. Shenoi said. “If you notice the child to be drowning, either attempt rescue yourself if it is safe to do so or enlist the help of others to save the victim as soon as possible. However, the rescuer should not place himself or herself in danger when attempting rescue.”

The five steps in the “drowning chain of survival” – preventing drowning, recognizing distress, providing flotation, removing the victim from the water, and providing care and CPR as needed – are key to reducing drowning deaths and injury, Dr. Shenoi emphasized.

Dr. Shenoi has disclosed no relevant financial relationships. Dr. Hoffman is a paid consultant on child drowning prevention for the nonprofit Anonymous Philanthropy.

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

The likelihood that a child will survive a near-drowning without long-term damage is substantially greater if a bystander attempts a rescue, even if that person doesn’t perform cardiopulmonary resuscitation (CPR), according to new research presented October 10 at the American Academy of Pediatrics (AAP) 2021 National Conference.

“The extent to which bystander rescue is associated with reduced odds of unfavorable drowning outcomes was surprising,” said lead investigator Rohit P. Shenoi, MD, professor of pediatrics at Baylor College of Medicine and attending physician at Texas Children’s Hospital, Houston.

“While we do know that early rescue and resuscitation is helpful in preventing severe drowning injury, the degree of benefit from bystander rescue in all cases of pediatric drowning has not been described so far,” he told this news organization.

The fact that a bystander’s rescue attempt improves a child’s odds of a good outcome is not surprising on its own, but the magnitude of the finding really affirms the importance of bystander intervention, said Benjamin Hoffman, MD, professor of pediatrics at the Oregon Health & Science University School of Medicine and medical director of the Tom Sargent Safety Center at the Doernbecher Children’s Hospital, Portland.

“If an adult finds a child in the water, even if they don’t administer formal CPR, they’re going to be doing things” to try to help, Dr. Hoffman, who was not involved in this research but who specializes in child injury prevention, said in an interview. The act of intervening – whether it’s formal CPR or a CPR attempt or even just calling appropriate first responders – “likely impacts the duration of the submersion” and “clearly makes a difference.”

Drowning is the leading cause of death for children younger than 4 years, Dr. Hoffman noted, adding that the AAP recommends swimming lessons for children older than 1 year to reduce that risk.

In their cross-sectional study, Dr. Shenoi and his colleagues analyzed data on drownings and near-drownings in children and adolescents younger than 18 years using hospital, emergency medical services, and child fatality records from Harris County, Texas.

They analyzed 237 incidents from 2010 to 2013 in which the young person was submerged. Median age of the victims was 3.2 years, 60% were male, 64% were Black, Hispanic, or Native American, and 78% occurred in a swimming pool.

Unfavorable outcomes – defined as death or severe impairment after hospital discharge – were experienced by 38 victims (16%) and were significantly associated with being submerged for longer than 5 minutes (P < .001).

The odds of an unfavorable outcome dropped by 80% if a bystander attempted a rescue, whether or not they performed CPR (adjusted odds ratio, 0.2; P = .004). If the bystander performed CPR, the odds of an unfavorable outcome dropped by a similar amount, but the difference was not statistically significant (aOR, 0.22; P = .07).

However, previous research has shown a significant reduction in poor outcomes when CPR is administered to children who have been submerged, Dr. Hoffman explained.

The most important thing a bystander can do is simply get a submerged child out of the water. “Early rescue in drowning terminates what is initially a respiratory arrest from progressing to a full cardiopulmonary arrest with severe hypoxic brain injury and death,” Dr. Shenoi said.

“CPR is also very important, and rescue and resuscitation go hand in hand. We encourage all laypersons to be trained in CPR so that they can administer correct CPR techniques,” he added.

Both Dr. Shenoi and Dr. Hoffman emphasized the value of CPR training for adults, as the AAP recommends, and the importance of other precautions that reduce the risk of drowning.

“Drowning prevention should consist of multiple layers of prevention,” Dr. Shenoi said. These consist of “close, constant, and attentive supervision; isolation fencing for swimming pools; and water competency, including water-safety knowledge, basic swim skills, and the ability to recognize and respond to a swimmer in trouble, use of life jackets, and early bystander CPR.”

The relative importance of each of those layers depends on geography and circumstances, Dr. Hoffman said. Pools are the most common drowning sites in the United States overall, but they’re much more common in warmer states, such as California, Florida, and Texas, which have more pools. In contrast, drownings in Oregon are more likely to occur in rivers, so prevention is more about access to life jackets and increasing access to swim lessons.

The findings from this study drive home how important it is for physicians to provide anticipatory guidance to families on reducing the risk of drowning. Pediatricians should convey to families the need for different layers of protection, he added.

“If your family spends a lot of time around water, whether open water or swimming pools, the more layers you can provide, the better off you’re going to be,” Dr. Hoffman said.

Dr. Shenoi echoed this sentiment.

“The take-home message is to be observant if you are entrusted with the care of a child around water,” Dr. Shenoi said. “If you notice the child to be drowning, either attempt rescue yourself if it is safe to do so or enlist the help of others to save the victim as soon as possible. However, the rescuer should not place himself or herself in danger when attempting rescue.”

The five steps in the “drowning chain of survival” – preventing drowning, recognizing distress, providing flotation, removing the victim from the water, and providing care and CPR as needed – are key to reducing drowning deaths and injury, Dr. Shenoi emphasized.

Dr. Shenoi has disclosed no relevant financial relationships. Dr. Hoffman is a paid consultant on child drowning prevention for the nonprofit Anonymous Philanthropy.

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