Federal Practitioner

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.

People who don’t get vaccinated against COVID-19 should expect to be reinfected with the coronavirus every 16 to 17 months on average, according to a recent study published in The Lancet Microbe.

Since COVID-19 hasn’t existed for long enough to perform a long-term study, researchers at Yale University and the University of North Carolina at Charlotte looked at reinfection data for six other human-infecting coronaviruses, including SARS and MERS.

“Reinfection can reasonably happen in three months or less,” Jeffrey Townsend, PhD, lead study author and a biostatistics professor at the Yale School of Public Health, said in a statement.

“Therefore, those who have been naturally infected should get vaccinated,” he said. “Previous infection alone can offer very little long-term protection against subsequent infections.”

The research team looked at post-infection data for six coronaviruses between 1984-2020 and found reinfection ranged from 128 days to 28 years. They calculated that reinfection with COVID-19 would likely occur between 3 months to 5 years after peak antibody response, with an average of 16 months. This is less than half the duration seen for other coronaviruses that circulate among humans.

The risk of COVID-19 reinfection is about 5% at three months, which jumps to 50% after 17 months, the research team found. Reinfection could become increasingly common as immunity wanes and new variants develop, they said.

“We tend to think about immunity as being immune or not immune. Our study cautions that we instead should be more focused on the risk of reinfection through time,” Alex Dornburg, PhD, senior study author and assistant professor of bioinformatics and genomics at UNC, said in the statement.

“As new variants arise, previous immune responses become less effective at combating the virus,” he said. “Those who were naturally infected early in the pandemic are increasingly likely to become reinfected in the near future.”

Study estimates are based on average times of declining immunity across different coronaviruses, the researchers told the Yale Daily News. At the individual level, people have different levels of immunity, which can provide shorter or longer duration of protection based on immune status, immunity within a community, age, underlying health conditions, environmental exposure, and other factors.

The research team said that preventive health measures and global distribution of vaccines will be “critical” in minimizing reinfection and COVID-19 deaths. In areas with low vaccination rates, for instance, unvaccinated people should continue safety practices such as social distancing, wearing masks, and proper indoor ventilation to avoid reinfection.

“We need to be very aware of the fact that this disease is likely to be circulating over the long term and that we don’t have this long-term immunity that many people seem to be hoping to rely on in order to protect them from disease,” Dr. Townsend told the newspaper.

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

People who don’t get vaccinated against COVID-19 should expect to be reinfected with the coronavirus every 16 to 17 months on average, according to a recent study published in The Lancet Microbe.

Since COVID-19 hasn’t existed for long enough to perform a long-term study, researchers at Yale University and the University of North Carolina at Charlotte looked at reinfection data for six other human-infecting coronaviruses, including SARS and MERS.

“Reinfection can reasonably happen in three months or less,” Jeffrey Townsend, PhD, lead study author and a biostatistics professor at the Yale School of Public Health, said in a statement.

“Therefore, those who have been naturally infected should get vaccinated,” he said. “Previous infection alone can offer very little long-term protection against subsequent infections.”

The research team looked at post-infection data for six coronaviruses between 1984-2020 and found reinfection ranged from 128 days to 28 years. They calculated that reinfection with COVID-19 would likely occur between 3 months to 5 years after peak antibody response, with an average of 16 months. This is less than half the duration seen for other coronaviruses that circulate among humans.

The risk of COVID-19 reinfection is about 5% at three months, which jumps to 50% after 17 months, the research team found. Reinfection could become increasingly common as immunity wanes and new variants develop, they said.

“We tend to think about immunity as being immune or not immune. Our study cautions that we instead should be more focused on the risk of reinfection through time,” Alex Dornburg, PhD, senior study author and assistant professor of bioinformatics and genomics at UNC, said in the statement.

“As new variants arise, previous immune responses become less effective at combating the virus,” he said. “Those who were naturally infected early in the pandemic are increasingly likely to become reinfected in the near future.”

Study estimates are based on average times of declining immunity across different coronaviruses, the researchers told the Yale Daily News. At the individual level, people have different levels of immunity, which can provide shorter or longer duration of protection based on immune status, immunity within a community, age, underlying health conditions, environmental exposure, and other factors.

The research team said that preventive health measures and global distribution of vaccines will be “critical” in minimizing reinfection and COVID-19 deaths. In areas with low vaccination rates, for instance, unvaccinated people should continue safety practices such as social distancing, wearing masks, and proper indoor ventilation to avoid reinfection.

“We need to be very aware of the fact that this disease is likely to be circulating over the long term and that we don’t have this long-term immunity that many people seem to be hoping to rely on in order to protect them from disease,” Dr. Townsend told the newspaper.

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

People who don’t get vaccinated against COVID-19 should expect to be reinfected with the coronavirus every 16 to 17 months on average, according to a recent study published in The Lancet Microbe.

Since COVID-19 hasn’t existed for long enough to perform a long-term study, researchers at Yale University and the University of North Carolina at Charlotte looked at reinfection data for six other human-infecting coronaviruses, including SARS and MERS.

“Reinfection can reasonably happen in three months or less,” Jeffrey Townsend, PhD, lead study author and a biostatistics professor at the Yale School of Public Health, said in a statement.

“Therefore, those who have been naturally infected should get vaccinated,” he said. “Previous infection alone can offer very little long-term protection against subsequent infections.”

The research team looked at post-infection data for six coronaviruses between 1984-2020 and found reinfection ranged from 128 days to 28 years. They calculated that reinfection with COVID-19 would likely occur between 3 months to 5 years after peak antibody response, with an average of 16 months. This is less than half the duration seen for other coronaviruses that circulate among humans.

The risk of COVID-19 reinfection is about 5% at three months, which jumps to 50% after 17 months, the research team found. Reinfection could become increasingly common as immunity wanes and new variants develop, they said.

“We tend to think about immunity as being immune or not immune. Our study cautions that we instead should be more focused on the risk of reinfection through time,” Alex Dornburg, PhD, senior study author and assistant professor of bioinformatics and genomics at UNC, said in the statement.

“As new variants arise, previous immune responses become less effective at combating the virus,” he said. “Those who were naturally infected early in the pandemic are increasingly likely to become reinfected in the near future.”

Study estimates are based on average times of declining immunity across different coronaviruses, the researchers told the Yale Daily News. At the individual level, people have different levels of immunity, which can provide shorter or longer duration of protection based on immune status, immunity within a community, age, underlying health conditions, environmental exposure, and other factors.

The research team said that preventive health measures and global distribution of vaccines will be “critical” in minimizing reinfection and COVID-19 deaths. In areas with low vaccination rates, for instance, unvaccinated people should continue safety practices such as social distancing, wearing masks, and proper indoor ventilation to avoid reinfection.

“We need to be very aware of the fact that this disease is likely to be circulating over the long term and that we don’t have this long-term immunity that many people seem to be hoping to rely on in order to protect them from disease,” Dr. Townsend told the newspaper.

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

“We each come to public service in our own unique way,” ADM Rachel Levine, MD, Assistant Secretary for Health at the US Department of Health and Human Services (HHS), told the Senate Health, Education, Labor and Pensions Committee at her confirmation hearing in February 2021.

In her case, unique and history-making. Levine was confirmed on Tuesday as the first-ever openly transgender—and firstwoman—four-star admiral in the history of the US Public Health Service Commissioned Corps. She is also the first openly transgender four-star officer and the first openly transgender person to be confirmed by the Senate. In fact, she is the nation’s highest-ranking openly transgender official—the first such across any of the eight uniformed services.

All those firsts aside, in her confirmation hearing remarks, ADM. Levine said, “At its core, my career has been about helping people live healthy lives.” She began her career at Mt. Sinai Medical Center in New York, in pediatric and adolescent medicine, focusing on mental and physical health. Moving to the Penn State College of Medicine, ADM Levine was a professor of pediatrics and psychiatry and vice-chair for clinical affairs for the Department of Pediatrics. At Penn State, she initiated the Division of Adolescent Medicine for the care of complex teens with medical and psychological problems. As chief of the Division of Adolescent Medicine and Eating Disorders at Penn State Hershey Medical Center, she also founded an eating disorders program, offering multidisciplinary treatment for children, adolescents, and adults.

In 2015, Pennsylvania Governor Tom Wolf nominated ADM Levine to be Physician General of the Commonwealth of Pennsylvania and she was confirmed unanimously by the state senate. In 2018, she was named Pennsylvania’s Secretary of Health. In these roles, she tackled the state’s massive opioid misuse and overdose crisis. She focused on opioid stewardship, developed continuing medical education programs, and established prescribing guidelines and a “robust” prescription drug monitoring program. She traveled extensively throughout small communities, doing public events with local officials and residents to talk about opioid abuse. The efforts began, slowly, to pay off. In 2015, 3,383 people died of drug overdose in Pennsylvania, a 23% increase from 2014. By 2018, 65% of drug overdose deaths involved opioids, but the total number of deaths fell to 2,866.

One of her most significant accomplishments as Physician General, Levine said, was to issue the first-ever statewide standing order for distribution of the anti-overdose drug naloxone, allowing law enforcement to carry the drug and Pennsylvania citizens to buy itover the counter. According to the Pennsylvania Opioid Data Dashboard, between January 1, 2018, and October 9, 2021, 62,954 doses of naloxone were administered by EMS.

In another of Levine’s projects, the Pennsylvania Rural Health Model, the goal was to move rural hospitals from fee-for-service models to global budget payments, which she said, “aligned incentives for providers to deliver value-based care and for rural hospitals to transform their care to better meet community health needs.”

Working in tandem with HHS, Levine’s teams also set up a maternal mortality review committee “to better understand and respond to the causes of maternal deaths,” and worked to improve childhood immunization rates.

“Of course, our focus changed dramatically last year,” Levine said, “and COVID-19 became my most urgent and primary focus.” She concentrated on three key priorities: containment with expansion of testing and contact tracing; mitigation with masks and distancing; and medical countermeasures, including monoclonal antibodies and vaccines. To carry out the strategies, she oversaw a health equity task force, which included community stakeholders such as the Black Coalition Against COVID-19, the Latino Connection, and a faith-based program that allowed people to get tested at their places of worship.

When lesbian, gay, bisexual, transgender, queer; lesbian, gay, bisexual, transgender, queer (LGBTQ+) advocates charged that states were not collecting data early in the pandemic on sexual orientation or gender identity, in another historic move, Levine announced in March 2020 that Pennsylvania would begin collecting demographic data on the coronavirus, making it the first state in the country to do so.

Levine has garnered praise from many sources. “This is a proud moment for us,” HHS Secretary Xavier Becerra said in a statement, calling her a “cherished and critical partner in our work to build a healthier America.” Alphonso David, then president of the Human Rights Campaign, said in a statement that Levine’s nomination to be the HHS Assistant Secretary for Health represented “real change” in the government’s approach to the coronavirus and LGBTQ+ health issues. Levine “led Pennsylvania’s public health response to the COVID-19 pandemic superbly,” he said.

She has also triggered a significant amount of outrage in conservative quarters. She was routinely castigated for her early actions in the pandemic. Writing for The American Spectator in May 2020, Paul Kengor, a former UPMC researcher, said UPMC’s overall handling of the virus was “impressive and inspired confidence.” However, tracking the data on fatalities, he said, he found the disproportionate number of deaths in nursing homes “alarming and strange.” Citing an investigative article in the Bucks County Courier Times, he blamed Pennsylvania officials—including Levine—for guidelines that directed licensed long-term care facilities to continue admitting new patients, including those discharged from hospitals back to nursing homes. However, Kengor claimed, the “partisan press” would protect Wolf and Levine: “Levine is a liberal darling as the nation’s first (and arguably highest-ranking) transgender public official.”

At the February 2021 federal confirmation hearing, Levine was pressed on data discrepancies in Pennsylvania’s public reports on nursing home coronavirus deaths and cases. Sen. Susan Collins (R-ME) cited Spotlight PA reporting that found weekly reports released by the state health department were consistently missing data for more than 100 of the 693 nursing homes. Levine, in response, pointed to lags in the state’s electronic death reporting system and to slow uploads. Pennsylvania health officials also referred to a state law that prohibits the release of disease records by state or local authorities.

In a June 2020 opinion article, Levine wrote that the Pennsylvania Health Department had followed Centers for Disease Control and Prevention (CDC) guidance, including limiting outside people from entering long-term care facilities. The Pennsylvania Health Department also sent thousands of shipments of personal protective equipment and conducted virtual inspections, including on-site inspections as warranted.

Despite those efforts, Levine said, “staff members who have dedicated their lives to caring for these vulnerable Pennsylvanians unknowingly contracted COVID-19 in their communities and carried it into these facilities.” She pointed out that residents who returned from hospitals had been isolated if they contracted COVID-19. Patients returning to nursing homes did not introduce COVID-19, Levine said, “because it was there that they first came into contact with the virus.” Moreover, those patients were isolated, just as they had been before they required hospital-level care, she added.

When a long-term care facility reports a case of COVID-19, Levine noted, the Pennsylvania Health Department considers it an outbreak and offers a variety of resources to the facility, including mitigation measures and the services of an infection control consultant, or even deploying the Pennsylvania National Guard to assist with staffing. Pennsylvania cannot force facilities to accept these services, she pointed out, but some refuse out of fear of receiving citations. “[O]ur top priority,” Levine said, “is halting COVID-19, not issuing citations.”

Her decisions on health restrictions and closures to combat the pandemic created controversy in the state, but much of the criticism also took aim at Levine identifying openly as transgender. Her selection as the first openly transgender official to be confirmed by the Senate has been targeted by conservative groups as a political gesture by President Biden. Tom Fitton, president of the conservative legal group Judicial Watch, posted on Facebook: “Biden gang playing quota politics with public health service.”

In her remarks to the Senate committee, however, Levine calmly noted that her appointment by Gov. Wolf was confirmed unanimously and that she was approved twice more on a bipartisan basis to be Secretary of Health. She met with nearly all of the senators personally. Her confirmation by the senate Republicans was particularly meaningful, she told NBC Out. “[They] judged me strictly on my professional qualifications.”

Social media has made much of Levine’s transgender identification, both pro and con. The Twitterverse, predictably, is packed with anti-Levine and anti-LGBTQ+ rants. But Levine’s rise has energized the LGBTQ+ community, who hail it as a breakthrough. Scout, the single-named executive director of the National LGBT Cancer Network, said, “The fact that she is trans is an inspiration for the many of us who have never had a role model this senior before.” Levine herself is determined to be a “beacon” in representing the LGBTQ+ community in her latest role at the corps: “Diversity makes us stronger,” she said.

“What people don’t understand, they fear,” Levine, who is a frequent public speaker, has said. “The more we can educate people and show that we’re productive members of the community—with families, lives, careers—that helps people understand us better.” That includes education of medical professionals. “We need to do a better job educating medical students about LGBT issues and transgender medicine,” she told NBC Out. She may need to start with the members of Congress. At Levine’s confirmation hearing to serve as Assistant Secretary for Health, Sen. Rand Paul, for instance, compared transgender surgery to “genital mutilation.”

HHS Secretary Becerra called Levine’s appointment as the first openly transgender four-star officer “a giant step forward toward equality as a nation.” US Surgeon General VADM Vivek Murthy, MD, MBA, said her appointment represents “an important step towards a more inclusive future and her service will undoubtedly advance the US Public Health Service Commissioned Corps’ mission to protect, promote, and advance the health and safety of our nation.”

Levine told the Senate committee, “There is still so much more to do.”

“We each come to public service in our own unique way,” ADM Rachel Levine, MD, Assistant Secretary for Health at the US Department of Health and Human Services (HHS), told the Senate Health, Education, Labor and Pensions Committee at her confirmation hearing in February 2021.

In her case, unique and history-making. Levine was confirmed on Tuesday as the first-ever openly transgender—and firstwoman—four-star admiral in the history of the US Public Health Service Commissioned Corps. She is also the first openly transgender four-star officer and the first openly transgender person to be confirmed by the Senate. In fact, she is the nation’s highest-ranking openly transgender official—the first such across any of the eight uniformed services.

All those firsts aside, in her confirmation hearing remarks, ADM. Levine said, “At its core, my career has been about helping people live healthy lives.” She began her career at Mt. Sinai Medical Center in New York, in pediatric and adolescent medicine, focusing on mental and physical health. Moving to the Penn State College of Medicine, ADM Levine was a professor of pediatrics and psychiatry and vice-chair for clinical affairs for the Department of Pediatrics. At Penn State, she initiated the Division of Adolescent Medicine for the care of complex teens with medical and psychological problems. As chief of the Division of Adolescent Medicine and Eating Disorders at Penn State Hershey Medical Center, she also founded an eating disorders program, offering multidisciplinary treatment for children, adolescents, and adults.

In 2015, Pennsylvania Governor Tom Wolf nominated ADM Levine to be Physician General of the Commonwealth of Pennsylvania and she was confirmed unanimously by the state senate. In 2018, she was named Pennsylvania’s Secretary of Health. In these roles, she tackled the state’s massive opioid misuse and overdose crisis. She focused on opioid stewardship, developed continuing medical education programs, and established prescribing guidelines and a “robust” prescription drug monitoring program. She traveled extensively throughout small communities, doing public events with local officials and residents to talk about opioid abuse. The efforts began, slowly, to pay off. In 2015, 3,383 people died of drug overdose in Pennsylvania, a 23% increase from 2014. By 2018, 65% of drug overdose deaths involved opioids, but the total number of deaths fell to 2,866.

One of her most significant accomplishments as Physician General, Levine said, was to issue the first-ever statewide standing order for distribution of the anti-overdose drug naloxone, allowing law enforcement to carry the drug and Pennsylvania citizens to buy itover the counter. According to the Pennsylvania Opioid Data Dashboard, between January 1, 2018, and October 9, 2021, 62,954 doses of naloxone were administered by EMS.

In another of Levine’s projects, the Pennsylvania Rural Health Model, the goal was to move rural hospitals from fee-for-service models to global budget payments, which she said, “aligned incentives for providers to deliver value-based care and for rural hospitals to transform their care to better meet community health needs.”

Working in tandem with HHS, Levine’s teams also set up a maternal mortality review committee “to better understand and respond to the causes of maternal deaths,” and worked to improve childhood immunization rates.

“Of course, our focus changed dramatically last year,” Levine said, “and COVID-19 became my most urgent and primary focus.” She concentrated on three key priorities: containment with expansion of testing and contact tracing; mitigation with masks and distancing; and medical countermeasures, including monoclonal antibodies and vaccines. To carry out the strategies, she oversaw a health equity task force, which included community stakeholders such as the Black Coalition Against COVID-19, the Latino Connection, and a faith-based program that allowed people to get tested at their places of worship.

When lesbian, gay, bisexual, transgender, queer; lesbian, gay, bisexual, transgender, queer (LGBTQ+) advocates charged that states were not collecting data early in the pandemic on sexual orientation or gender identity, in another historic move, Levine announced in March 2020 that Pennsylvania would begin collecting demographic data on the coronavirus, making it the first state in the country to do so.

Levine has garnered praise from many sources. “This is a proud moment for us,” HHS Secretary Xavier Becerra said in a statement, calling her a “cherished and critical partner in our work to build a healthier America.” Alphonso David, then president of the Human Rights Campaign, said in a statement that Levine’s nomination to be the HHS Assistant Secretary for Health represented “real change” in the government’s approach to the coronavirus and LGBTQ+ health issues. Levine “led Pennsylvania’s public health response to the COVID-19 pandemic superbly,” he said.

She has also triggered a significant amount of outrage in conservative quarters. She was routinely castigated for her early actions in the pandemic. Writing for The American Spectator in May 2020, Paul Kengor, a former UPMC researcher, said UPMC’s overall handling of the virus was “impressive and inspired confidence.” However, tracking the data on fatalities, he said, he found the disproportionate number of deaths in nursing homes “alarming and strange.” Citing an investigative article in the Bucks County Courier Times, he blamed Pennsylvania officials—including Levine—for guidelines that directed licensed long-term care facilities to continue admitting new patients, including those discharged from hospitals back to nursing homes. However, Kengor claimed, the “partisan press” would protect Wolf and Levine: “Levine is a liberal darling as the nation’s first (and arguably highest-ranking) transgender public official.”

At the February 2021 federal confirmation hearing, Levine was pressed on data discrepancies in Pennsylvania’s public reports on nursing home coronavirus deaths and cases. Sen. Susan Collins (R-ME) cited Spotlight PA reporting that found weekly reports released by the state health department were consistently missing data for more than 100 of the 693 nursing homes. Levine, in response, pointed to lags in the state’s electronic death reporting system and to slow uploads. Pennsylvania health officials also referred to a state law that prohibits the release of disease records by state or local authorities.

In a June 2020 opinion article, Levine wrote that the Pennsylvania Health Department had followed Centers for Disease Control and Prevention (CDC) guidance, including limiting outside people from entering long-term care facilities. The Pennsylvania Health Department also sent thousands of shipments of personal protective equipment and conducted virtual inspections, including on-site inspections as warranted.

Despite those efforts, Levine said, “staff members who have dedicated their lives to caring for these vulnerable Pennsylvanians unknowingly contracted COVID-19 in their communities and carried it into these facilities.” She pointed out that residents who returned from hospitals had been isolated if they contracted COVID-19. Patients returning to nursing homes did not introduce COVID-19, Levine said, “because it was there that they first came into contact with the virus.” Moreover, those patients were isolated, just as they had been before they required hospital-level care, she added.

When a long-term care facility reports a case of COVID-19, Levine noted, the Pennsylvania Health Department considers it an outbreak and offers a variety of resources to the facility, including mitigation measures and the services of an infection control consultant, or even deploying the Pennsylvania National Guard to assist with staffing. Pennsylvania cannot force facilities to accept these services, she pointed out, but some refuse out of fear of receiving citations. “[O]ur top priority,” Levine said, “is halting COVID-19, not issuing citations.”

Her decisions on health restrictions and closures to combat the pandemic created controversy in the state, but much of the criticism also took aim at Levine identifying openly as transgender. Her selection as the first openly transgender official to be confirmed by the Senate has been targeted by conservative groups as a political gesture by President Biden. Tom Fitton, president of the conservative legal group Judicial Watch, posted on Facebook: “Biden gang playing quota politics with public health service.”

In her remarks to the Senate committee, however, Levine calmly noted that her appointment by Gov. Wolf was confirmed unanimously and that she was approved twice more on a bipartisan basis to be Secretary of Health. She met with nearly all of the senators personally. Her confirmation by the senate Republicans was particularly meaningful, she told NBC Out. “[They] judged me strictly on my professional qualifications.”

Social media has made much of Levine’s transgender identification, both pro and con. The Twitterverse, predictably, is packed with anti-Levine and anti-LGBTQ+ rants. But Levine’s rise has energized the LGBTQ+ community, who hail it as a breakthrough. Scout, the single-named executive director of the National LGBT Cancer Network, said, “The fact that she is trans is an inspiration for the many of us who have never had a role model this senior before.” Levine herself is determined to be a “beacon” in representing the LGBTQ+ community in her latest role at the corps: “Diversity makes us stronger,” she said.

“What people don’t understand, they fear,” Levine, who is a frequent public speaker, has said. “The more we can educate people and show that we’re productive members of the community—with families, lives, careers—that helps people understand us better.” That includes education of medical professionals. “We need to do a better job educating medical students about LGBT issues and transgender medicine,” she told NBC Out. She may need to start with the members of Congress. At Levine’s confirmation hearing to serve as Assistant Secretary for Health, Sen. Rand Paul, for instance, compared transgender surgery to “genital mutilation.”

HHS Secretary Becerra called Levine’s appointment as the first openly transgender four-star officer “a giant step forward toward equality as a nation.” US Surgeon General VADM Vivek Murthy, MD, MBA, said her appointment represents “an important step towards a more inclusive future and her service will undoubtedly advance the US Public Health Service Commissioned Corps’ mission to protect, promote, and advance the health and safety of our nation.”

Levine told the Senate committee, “There is still so much more to do.”

“We each come to public service in our own unique way,” ADM Rachel Levine, MD, Assistant Secretary for Health at the US Department of Health and Human Services (HHS), told the Senate Health, Education, Labor and Pensions Committee at her confirmation hearing in February 2021.

In her case, unique and history-making. Levine was confirmed on Tuesday as the first-ever openly transgender—and firstwoman—four-star admiral in the history of the US Public Health Service Commissioned Corps. She is also the first openly transgender four-star officer and the first openly transgender person to be confirmed by the Senate. In fact, she is the nation’s highest-ranking openly transgender official—the first such across any of the eight uniformed services.

All those firsts aside, in her confirmation hearing remarks, ADM. Levine said, “At its core, my career has been about helping people live healthy lives.” She began her career at Mt. Sinai Medical Center in New York, in pediatric and adolescent medicine, focusing on mental and physical health. Moving to the Penn State College of Medicine, ADM Levine was a professor of pediatrics and psychiatry and vice-chair for clinical affairs for the Department of Pediatrics. At Penn State, she initiated the Division of Adolescent Medicine for the care of complex teens with medical and psychological problems. As chief of the Division of Adolescent Medicine and Eating Disorders at Penn State Hershey Medical Center, she also founded an eating disorders program, offering multidisciplinary treatment for children, adolescents, and adults.

In 2015, Pennsylvania Governor Tom Wolf nominated ADM Levine to be Physician General of the Commonwealth of Pennsylvania and she was confirmed unanimously by the state senate. In 2018, she was named Pennsylvania’s Secretary of Health. In these roles, she tackled the state’s massive opioid misuse and overdose crisis. She focused on opioid stewardship, developed continuing medical education programs, and established prescribing guidelines and a “robust” prescription drug monitoring program. She traveled extensively throughout small communities, doing public events with local officials and residents to talk about opioid abuse. The efforts began, slowly, to pay off. In 2015, 3,383 people died of drug overdose in Pennsylvania, a 23% increase from 2014. By 2018, 65% of drug overdose deaths involved opioids, but the total number of deaths fell to 2,866.

One of her most significant accomplishments as Physician General, Levine said, was to issue the first-ever statewide standing order for distribution of the anti-overdose drug naloxone, allowing law enforcement to carry the drug and Pennsylvania citizens to buy itover the counter. According to the Pennsylvania Opioid Data Dashboard, between January 1, 2018, and October 9, 2021, 62,954 doses of naloxone were administered by EMS.

In another of Levine’s projects, the Pennsylvania Rural Health Model, the goal was to move rural hospitals from fee-for-service models to global budget payments, which she said, “aligned incentives for providers to deliver value-based care and for rural hospitals to transform their care to better meet community health needs.”

Working in tandem with HHS, Levine’s teams also set up a maternal mortality review committee “to better understand and respond to the causes of maternal deaths,” and worked to improve childhood immunization rates.

“Of course, our focus changed dramatically last year,” Levine said, “and COVID-19 became my most urgent and primary focus.” She concentrated on three key priorities: containment with expansion of testing and contact tracing; mitigation with masks and distancing; and medical countermeasures, including monoclonal antibodies and vaccines. To carry out the strategies, she oversaw a health equity task force, which included community stakeholders such as the Black Coalition Against COVID-19, the Latino Connection, and a faith-based program that allowed people to get tested at their places of worship.

When lesbian, gay, bisexual, transgender, queer; lesbian, gay, bisexual, transgender, queer (LGBTQ+) advocates charged that states were not collecting data early in the pandemic on sexual orientation or gender identity, in another historic move, Levine announced in March 2020 that Pennsylvania would begin collecting demographic data on the coronavirus, making it the first state in the country to do so.

Levine has garnered praise from many sources. “This is a proud moment for us,” HHS Secretary Xavier Becerra said in a statement, calling her a “cherished and critical partner in our work to build a healthier America.” Alphonso David, then president of the Human Rights Campaign, said in a statement that Levine’s nomination to be the HHS Assistant Secretary for Health represented “real change” in the government’s approach to the coronavirus and LGBTQ+ health issues. Levine “led Pennsylvania’s public health response to the COVID-19 pandemic superbly,” he said.

She has also triggered a significant amount of outrage in conservative quarters. She was routinely castigated for her early actions in the pandemic. Writing for The American Spectator in May 2020, Paul Kengor, a former UPMC researcher, said UPMC’s overall handling of the virus was “impressive and inspired confidence.” However, tracking the data on fatalities, he said, he found the disproportionate number of deaths in nursing homes “alarming and strange.” Citing an investigative article in the Bucks County Courier Times, he blamed Pennsylvania officials—including Levine—for guidelines that directed licensed long-term care facilities to continue admitting new patients, including those discharged from hospitals back to nursing homes. However, Kengor claimed, the “partisan press” would protect Wolf and Levine: “Levine is a liberal darling as the nation’s first (and arguably highest-ranking) transgender public official.”

At the February 2021 federal confirmation hearing, Levine was pressed on data discrepancies in Pennsylvania’s public reports on nursing home coronavirus deaths and cases. Sen. Susan Collins (R-ME) cited Spotlight PA reporting that found weekly reports released by the state health department were consistently missing data for more than 100 of the 693 nursing homes. Levine, in response, pointed to lags in the state’s electronic death reporting system and to slow uploads. Pennsylvania health officials also referred to a state law that prohibits the release of disease records by state or local authorities.

In a June 2020 opinion article, Levine wrote that the Pennsylvania Health Department had followed Centers for Disease Control and Prevention (CDC) guidance, including limiting outside people from entering long-term care facilities. The Pennsylvania Health Department also sent thousands of shipments of personal protective equipment and conducted virtual inspections, including on-site inspections as warranted.

Despite those efforts, Levine said, “staff members who have dedicated their lives to caring for these vulnerable Pennsylvanians unknowingly contracted COVID-19 in their communities and carried it into these facilities.” She pointed out that residents who returned from hospitals had been isolated if they contracted COVID-19. Patients returning to nursing homes did not introduce COVID-19, Levine said, “because it was there that they first came into contact with the virus.” Moreover, those patients were isolated, just as they had been before they required hospital-level care, she added.

When a long-term care facility reports a case of COVID-19, Levine noted, the Pennsylvania Health Department considers it an outbreak and offers a variety of resources to the facility, including mitigation measures and the services of an infection control consultant, or even deploying the Pennsylvania National Guard to assist with staffing. Pennsylvania cannot force facilities to accept these services, she pointed out, but some refuse out of fear of receiving citations. “[O]ur top priority,” Levine said, “is halting COVID-19, not issuing citations.”

Her decisions on health restrictions and closures to combat the pandemic created controversy in the state, but much of the criticism also took aim at Levine identifying openly as transgender. Her selection as the first openly transgender official to be confirmed by the Senate has been targeted by conservative groups as a political gesture by President Biden. Tom Fitton, president of the conservative legal group Judicial Watch, posted on Facebook: “Biden gang playing quota politics with public health service.”

In her remarks to the Senate committee, however, Levine calmly noted that her appointment by Gov. Wolf was confirmed unanimously and that she was approved twice more on a bipartisan basis to be Secretary of Health. She met with nearly all of the senators personally. Her confirmation by the senate Republicans was particularly meaningful, she told NBC Out. “[They] judged me strictly on my professional qualifications.”

Social media has made much of Levine’s transgender identification, both pro and con. The Twitterverse, predictably, is packed with anti-Levine and anti-LGBTQ+ rants. But Levine’s rise has energized the LGBTQ+ community, who hail it as a breakthrough. Scout, the single-named executive director of the National LGBT Cancer Network, said, “The fact that she is trans is an inspiration for the many of us who have never had a role model this senior before.” Levine herself is determined to be a “beacon” in representing the LGBTQ+ community in her latest role at the corps: “Diversity makes us stronger,” she said.

“What people don’t understand, they fear,” Levine, who is a frequent public speaker, has said. “The more we can educate people and show that we’re productive members of the community—with families, lives, careers—that helps people understand us better.” That includes education of medical professionals. “We need to do a better job educating medical students about LGBT issues and transgender medicine,” she told NBC Out. She may need to start with the members of Congress. At Levine’s confirmation hearing to serve as Assistant Secretary for Health, Sen. Rand Paul, for instance, compared transgender surgery to “genital mutilation.”

HHS Secretary Becerra called Levine’s appointment as the first openly transgender four-star officer “a giant step forward toward equality as a nation.” US Surgeon General VADM Vivek Murthy, MD, MBA, said her appointment represents “an important step towards a more inclusive future and her service will undoubtedly advance the US Public Health Service Commissioned Corps’ mission to protect, promote, and advance the health and safety of our nation.”

Levine told the Senate committee, “There is still so much more to do.”

Autologous hematopoietic stem cell transplantation for the treatment of active secondary progressive multiple sclerosis (MS) is associated with better disability outcomes than other immunotherapies, a new Italian study suggests.

In the study, stem cell transplant was associated with a slowing of disability progression and a higher likelihood of disability improvement in patients with secondary progressive MS compared with other disease-modifying therapies.

“Our study shows that, although limited, sustained disability improvement is still possible during early active secondary progressive MS and seems to be more likely with stem cell transplant than other disease-modifying treatments,” said lead author Giacomo Boffa, MD, University of Genoa, Italy.

“Brain penetrating–intent immune suppression in long-term immunological reconstitution within the central nervous system could be responsible for this clinical efficacy,” he added.

Dr. Boffa presented the research at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

He explained that compartmentalized inflation in the brain parenchyma, left meninges, and the cerebral spinal fluid (CSF) is a key driver of disability worsening in secondary progressive MS.

Although initial studies did not reveal an effect of disease-modifying therapies in secondary progressive MS, recent randomized trials have established some benefit of siponimod in reducing the risk of disability worsening, and consistent with this finding, observational studies have suggested that other available immunotherapies may also be beneficial for active secondary progressive MS, Dr. Boffa noted.

“Autologous hematopoietic stem cell transplantation has been widely investigated for the treatment of refractory MS, and although the ideal candidate for this procedure is a young patient with relapsing-remitting MS, there is some evidence to suggest that the procedure could also slow down neurological disability in patients with secondary progressive MS,” Dr. Boffa said.

“Indeed, all the drugs used in the transplant technology share the ability to cross the blood-brain barrier and exert a strong immunosuppressant effect within the brain parenchyma and CSF,” he added.  
 

Comparing treatment regimens

The aim of the current study was to compare the effect of autologous hematopoietic stem cell transplantation with other immunotherapies on disability worsening in patients with active secondary progressive MS.

Study endpoints included the Expanded Disability Status Scale (EDSS) score, 6-month worsening and improvement in disability, and sustained disability improvement over time.

The researchers studied patients with secondary progressive MS who had received autologous hematopoietic stem cell transplantation and were included in the Italian Bone Marrow Transplant Group. They were compared with a control group of patients in the Italian MS registry who had started a nontransplant disease-modifying therapy after the diagnosis of secondary progressive MS.

To control for many different variables, two separate analyses were preformed. One analyses was a propensity-score approach (patients were matched based on their propensity to receive bone marrow transplant or one of the other disease-modifying therapies). The other analysis used an overlap weighting approach (each patient was given a weight proportional to the probability of them belonging to the other treatment group).

The final cohort consisted of 79 bone marrow transplant recipients and 1,975 patients who had received other disease-modifying therapies.

Before matching, patients in the control group were older, had a longer disease duration, and had a lower annualized relapse rate than transplanted patients.

After propensity-score matching, there were 69 transplanted patients and 217 control patients who were well balanced in terms of clinical and demographic characteristics. After overlap weighting, the entire cohort was also well balanced for these variables.

In terms of the primary endpoint, stem cell transplant stabilized the EDSS score over time, while patients treated with other disease-modifying therapies had continuous progression of the EDSS score over time.

In the propensity-matched analysis, the EDSS score improved by 0.013 points per year in the stem cell transplant group compared with a worsening of 0.157 points per year in the control group. Similar results were seen in the overlap-weighting analysis.  

The effect of stem cell transplant on EDSS score translated into a significantly delayed time to confirmed disability progression in the stem cell transplant group compared with the control group (HR, 0.5; P = .005), Dr. Boffa reported.

Five years after the procedure, 62% of the transplant group were free of disability progression, compared with around 20% of the control group.  

Patients in the transplanted group were also more likely to show disability improvement over time. Five years after the procedure, almost 20% of the stem cell transplant group still maintained a disability improvement compared with only 4% of patients treated with other disease-modifying therapies.

“Our study population was composed of relatively young patients (average age 38 years) with clinical activity during secondary progressive MS, and the results of this study would not be applicable to patients with secondary progressive MS patients without signs of inflammatory activity,” Dr. Boffa commented.

“But on the other hand, our results reinforce the notion that ongoing inflammation during progressive MS requires adequate immunotherapy,” he added.   

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

Autologous hematopoietic stem cell transplantation for the treatment of active secondary progressive multiple sclerosis (MS) is associated with better disability outcomes than other immunotherapies, a new Italian study suggests.

In the study, stem cell transplant was associated with a slowing of disability progression and a higher likelihood of disability improvement in patients with secondary progressive MS compared with other disease-modifying therapies.

“Our study shows that, although limited, sustained disability improvement is still possible during early active secondary progressive MS and seems to be more likely with stem cell transplant than other disease-modifying treatments,” said lead author Giacomo Boffa, MD, University of Genoa, Italy.

“Brain penetrating–intent immune suppression in long-term immunological reconstitution within the central nervous system could be responsible for this clinical efficacy,” he added.

Dr. Boffa presented the research at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

He explained that compartmentalized inflation in the brain parenchyma, left meninges, and the cerebral spinal fluid (CSF) is a key driver of disability worsening in secondary progressive MS.

Although initial studies did not reveal an effect of disease-modifying therapies in secondary progressive MS, recent randomized trials have established some benefit of siponimod in reducing the risk of disability worsening, and consistent with this finding, observational studies have suggested that other available immunotherapies may also be beneficial for active secondary progressive MS, Dr. Boffa noted.

“Autologous hematopoietic stem cell transplantation has been widely investigated for the treatment of refractory MS, and although the ideal candidate for this procedure is a young patient with relapsing-remitting MS, there is some evidence to suggest that the procedure could also slow down neurological disability in patients with secondary progressive MS,” Dr. Boffa said.

“Indeed, all the drugs used in the transplant technology share the ability to cross the blood-brain barrier and exert a strong immunosuppressant effect within the brain parenchyma and CSF,” he added.  
 

Comparing treatment regimens

The aim of the current study was to compare the effect of autologous hematopoietic stem cell transplantation with other immunotherapies on disability worsening in patients with active secondary progressive MS.

Study endpoints included the Expanded Disability Status Scale (EDSS) score, 6-month worsening and improvement in disability, and sustained disability improvement over time.

The researchers studied patients with secondary progressive MS who had received autologous hematopoietic stem cell transplantation and were included in the Italian Bone Marrow Transplant Group. They were compared with a control group of patients in the Italian MS registry who had started a nontransplant disease-modifying therapy after the diagnosis of secondary progressive MS.

To control for many different variables, two separate analyses were preformed. One analyses was a propensity-score approach (patients were matched based on their propensity to receive bone marrow transplant or one of the other disease-modifying therapies). The other analysis used an overlap weighting approach (each patient was given a weight proportional to the probability of them belonging to the other treatment group).

The final cohort consisted of 79 bone marrow transplant recipients and 1,975 patients who had received other disease-modifying therapies.

Before matching, patients in the control group were older, had a longer disease duration, and had a lower annualized relapse rate than transplanted patients.

After propensity-score matching, there were 69 transplanted patients and 217 control patients who were well balanced in terms of clinical and demographic characteristics. After overlap weighting, the entire cohort was also well balanced for these variables.

In terms of the primary endpoint, stem cell transplant stabilized the EDSS score over time, while patients treated with other disease-modifying therapies had continuous progression of the EDSS score over time.

In the propensity-matched analysis, the EDSS score improved by 0.013 points per year in the stem cell transplant group compared with a worsening of 0.157 points per year in the control group. Similar results were seen in the overlap-weighting analysis.  

The effect of stem cell transplant on EDSS score translated into a significantly delayed time to confirmed disability progression in the stem cell transplant group compared with the control group (HR, 0.5; P = .005), Dr. Boffa reported.

Five years after the procedure, 62% of the transplant group were free of disability progression, compared with around 20% of the control group.  

Patients in the transplanted group were also more likely to show disability improvement over time. Five years after the procedure, almost 20% of the stem cell transplant group still maintained a disability improvement compared with only 4% of patients treated with other disease-modifying therapies.

“Our study population was composed of relatively young patients (average age 38 years) with clinical activity during secondary progressive MS, and the results of this study would not be applicable to patients with secondary progressive MS patients without signs of inflammatory activity,” Dr. Boffa commented.

“But on the other hand, our results reinforce the notion that ongoing inflammation during progressive MS requires adequate immunotherapy,” he added.   

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

Autologous hematopoietic stem cell transplantation for the treatment of active secondary progressive multiple sclerosis (MS) is associated with better disability outcomes than other immunotherapies, a new Italian study suggests.

In the study, stem cell transplant was associated with a slowing of disability progression and a higher likelihood of disability improvement in patients with secondary progressive MS compared with other disease-modifying therapies.

“Our study shows that, although limited, sustained disability improvement is still possible during early active secondary progressive MS and seems to be more likely with stem cell transplant than other disease-modifying treatments,” said lead author Giacomo Boffa, MD, University of Genoa, Italy.

“Brain penetrating–intent immune suppression in long-term immunological reconstitution within the central nervous system could be responsible for this clinical efficacy,” he added.

Dr. Boffa presented the research at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

He explained that compartmentalized inflation in the brain parenchyma, left meninges, and the cerebral spinal fluid (CSF) is a key driver of disability worsening in secondary progressive MS.

Although initial studies did not reveal an effect of disease-modifying therapies in secondary progressive MS, recent randomized trials have established some benefit of siponimod in reducing the risk of disability worsening, and consistent with this finding, observational studies have suggested that other available immunotherapies may also be beneficial for active secondary progressive MS, Dr. Boffa noted.

“Autologous hematopoietic stem cell transplantation has been widely investigated for the treatment of refractory MS, and although the ideal candidate for this procedure is a young patient with relapsing-remitting MS, there is some evidence to suggest that the procedure could also slow down neurological disability in patients with secondary progressive MS,” Dr. Boffa said.

“Indeed, all the drugs used in the transplant technology share the ability to cross the blood-brain barrier and exert a strong immunosuppressant effect within the brain parenchyma and CSF,” he added.  
 

Comparing treatment regimens

The aim of the current study was to compare the effect of autologous hematopoietic stem cell transplantation with other immunotherapies on disability worsening in patients with active secondary progressive MS.

Study endpoints included the Expanded Disability Status Scale (EDSS) score, 6-month worsening and improvement in disability, and sustained disability improvement over time.

The researchers studied patients with secondary progressive MS who had received autologous hematopoietic stem cell transplantation and were included in the Italian Bone Marrow Transplant Group. They were compared with a control group of patients in the Italian MS registry who had started a nontransplant disease-modifying therapy after the diagnosis of secondary progressive MS.

To control for many different variables, two separate analyses were preformed. One analyses was a propensity-score approach (patients were matched based on their propensity to receive bone marrow transplant or one of the other disease-modifying therapies). The other analysis used an overlap weighting approach (each patient was given a weight proportional to the probability of them belonging to the other treatment group).

The final cohort consisted of 79 bone marrow transplant recipients and 1,975 patients who had received other disease-modifying therapies.

Before matching, patients in the control group were older, had a longer disease duration, and had a lower annualized relapse rate than transplanted patients.

After propensity-score matching, there were 69 transplanted patients and 217 control patients who were well balanced in terms of clinical and demographic characteristics. After overlap weighting, the entire cohort was also well balanced for these variables.

In terms of the primary endpoint, stem cell transplant stabilized the EDSS score over time, while patients treated with other disease-modifying therapies had continuous progression of the EDSS score over time.

In the propensity-matched analysis, the EDSS score improved by 0.013 points per year in the stem cell transplant group compared with a worsening of 0.157 points per year in the control group. Similar results were seen in the overlap-weighting analysis.  

The effect of stem cell transplant on EDSS score translated into a significantly delayed time to confirmed disability progression in the stem cell transplant group compared with the control group (HR, 0.5; P = .005), Dr. Boffa reported.

Five years after the procedure, 62% of the transplant group were free of disability progression, compared with around 20% of the control group.  

Patients in the transplanted group were also more likely to show disability improvement over time. Five years after the procedure, almost 20% of the stem cell transplant group still maintained a disability improvement compared with only 4% of patients treated with other disease-modifying therapies.

“Our study population was composed of relatively young patients (average age 38 years) with clinical activity during secondary progressive MS, and the results of this study would not be applicable to patients with secondary progressive MS patients without signs of inflammatory activity,” Dr. Boffa commented.

“But on the other hand, our results reinforce the notion that ongoing inflammation during progressive MS requires adequate immunotherapy,” he added.   

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

Updated European guidelines on the treatment of patients with multiple sclerosis (MS) have been announced and include a recommendation for siponimod (Mayzent) in progressive MS, as well as a general emphasis toward earlier and more aggressive treatment.

The updated guidelines were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and are the result of a collaboration between ECTRIMS and the European Academy of Neurology (EAN).

Maria Pia Amato, MD, ECTRIMS president and co-chair of the guidelines steering committee, noted that the European MS treatment guidelines were last published in 2018. “Since then more trials have been published, and we felt this was a good time to incorporate the new evidence into updated guidelines,” she said.

“As before, the updated guidelines contain a number of core questions that address the efficacy of disease-modifying therapies, early treatment decisions, disease/treatment response monitoring and treatment modifications, treatment suspension and disease reactivation, and pregnancy and breastfeeding,” Dr. Amato said.
 

New recommendations

New features of the updated guidelines include a recommendation for siponimod for secondary progressive MS with evidence of disease inflammatory activity; in addition, there is more emphasis on starting treatment early, with greater consideration of higher efficacy drugs, depending on the characteristics of the disease and the patient, Dr. Amato commented.

“We also provided more detailed information on disease-modifying therapy use in pregnancy and breastfeeding and also for women with high disease activity who desire to become pregnant,” she added.

Other new features include the introduction of clinical questions dealing with treatment safety and monitoring (for example, for natalizumab) and also considering the current COVID-19 pandemic scenario; switching strategies with more detailed practical indications on timing; and long lasting effects of drugs such as alemtuzumab and cladribine, Dr. Amato said.

The updated guidelines include the following recommendations:

• The entire spectrum of disease-modifying drugs should be prescribed by a neurologist with expertise in MS and ready access to adequate infrastructure to provide proper monitoring of patents, comprehensive assessment, early detection of side effects, and the capacity to address those side effects promptly.
• Offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) highly suggestive of MS and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS.
• For patients with relapsing-remitting MS, the choice between a wide range of available drugs (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, fingolimod, ozanimod, ponesimod, natalizumab, alemtuzumab, ocrelizumab, rituximab, or ofatumumab), from modestly to highly effective, will depend on factors including: underlying disability progression, disease severity/clinical or radiological activity, patient characteristics and morbidity, drug safety profile, family planning, and patient preferences.

Progressive MS

• For patients with secondary progressive MS with evidence of inflammatory activity (relapses and/or MRI activity), offer treatment with siponimod. Treatment with other therapies used for relapsing remitting MS may also be considered.
• For secondary progressive MS without evidence of inflammatory activity, particularly in young patients and those in whom progression has started recently, consider treatment with siponimod or anti-CD20 monoclonal antibodies, taking into account that there is scarce evidence to support their use in this setting.  
• For patients with active secondary progressive MS when there is no other therapy available, consider treatment with mitoxantrone, taking into account the safety concerns and tolerability issues of this agent. 
• Consider ocrelizumab for patients with primary progressive MS, particularly early and active (clinically and/or radiologically) disease.

Emphasis toward higher-efficacy drugs

• Consider choosing a higher-efficacy disease-modifying drug early on, according to disease activity (either clinically or on MRI).
• Offer a more efficacious drug to patients who show evidence of disease activity with their current treatment.
• When treatment with a high-efficacy drug is stopped, whether because of inefficacy or risk of adverse effects, consider starting another high-efficacy drug, taking into account clinical and MRI disease activity before and during treatment, pharmacokinetics and biological activity of the previous drug, and the potential for resumed disease activity or even rebound syndrome (particularly with natalizumab and S1P modulators).
• In the stable patient (clinically and on MRI) who shows no safety or tolerability issues, consider continuing treatment with disease-modifying therapy, taking into account patient characteristics and comorbidities, drug safety profile, family planning, and patient preferences.

Recommendations for pregnancy and breastfeeding

Recommendations for pregnant women and mothers who choose to breastfeed include:

• Advise women who wish to become pregnant to plan their pregnancy beforehand.
• Advise women of childbearing potential that MS disease-modifying therapies are not licensed during pregnancy, with the exception of interferons and glatiramer acetate.
• For women planning a pregnancy, offer interferons and glatiramer acetate and consider continuing these agents during pregnancy after assessment of risk and benefits. Consider using dimethyl fumarate until pregnancy is confirmed and stopping during pregnancy after assessment of the risks and benefits. 
• For women with highly active disease who wish to become pregnant, there are a number of therapeutic options:

1)  treatment with long lasting effects such as alemtuzumab or cladribine provided that at least 4 or 6 months respectively have elapsed between the last dose and conception2)  treatment with anti-CD20 drugs before pregnancy with advice to wait for 2-6 months after the last infusion before becoming pregnant and to avoid further infusions during pregnancy, or3) for patients treated with natalizumab, consider continuing treatment during pregnancy using a 6-week extended dosage regimen until the end of the second trimester or up until week 34 and resuming after delivery (in newborns exposed to natalizumab, check for hematological abnormalities and liver function)

• Only interferons and ofatumumab are currently approved during breastfeeding.   
•  

Treatment safety/monitoring

• When treating patients with natalizumab and after a period of stability, consider switching to a 6-week interval regimen in order to minimize the risk of progressive multifocal leukoencephalopathy (PML).
• Consider treatment with high-efficacy drugs including natalizumab in patients with high disease activity, in whom a quick therapeutic effect is required, taking into account the risk of PML in John Cunningham virus (JCV)-positive patients, as well as the therapeutic lag of the different disease-modifying drugs.
• Ideally, prioritize vaccination against COVID-19 before starting immunosuppressive disease-modifying treatments to achieve the highest protection rate possible.
•  

Long-lasting treatments

• When using long-lasting treatments (alemtuzumab or cladribine) in patients who experience disease activity before the treatment is completed (between the first and second cycles), consider waiting until completion of the therapeutic regimen before switching to other drugs.
• Consider offering additional courses of alemtuzumab after the first two cycles at least 1 year apart from each other when disease activity has not remitted completely or reappears after a period of stability, taking into account the balance between the potential benefits and side effects.

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

Updated European guidelines on the treatment of patients with multiple sclerosis (MS) have been announced and include a recommendation for siponimod (Mayzent) in progressive MS, as well as a general emphasis toward earlier and more aggressive treatment.

The updated guidelines were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and are the result of a collaboration between ECTRIMS and the European Academy of Neurology (EAN).

Maria Pia Amato, MD, ECTRIMS president and co-chair of the guidelines steering committee, noted that the European MS treatment guidelines were last published in 2018. “Since then more trials have been published, and we felt this was a good time to incorporate the new evidence into updated guidelines,” she said.

“As before, the updated guidelines contain a number of core questions that address the efficacy of disease-modifying therapies, early treatment decisions, disease/treatment response monitoring and treatment modifications, treatment suspension and disease reactivation, and pregnancy and breastfeeding,” Dr. Amato said.
 

New recommendations

New features of the updated guidelines include a recommendation for siponimod for secondary progressive MS with evidence of disease inflammatory activity; in addition, there is more emphasis on starting treatment early, with greater consideration of higher efficacy drugs, depending on the characteristics of the disease and the patient, Dr. Amato commented.

“We also provided more detailed information on disease-modifying therapy use in pregnancy and breastfeeding and also for women with high disease activity who desire to become pregnant,” she added.

Other new features include the introduction of clinical questions dealing with treatment safety and monitoring (for example, for natalizumab) and also considering the current COVID-19 pandemic scenario; switching strategies with more detailed practical indications on timing; and long lasting effects of drugs such as alemtuzumab and cladribine, Dr. Amato said.

The updated guidelines include the following recommendations:

• The entire spectrum of disease-modifying drugs should be prescribed by a neurologist with expertise in MS and ready access to adequate infrastructure to provide proper monitoring of patents, comprehensive assessment, early detection of side effects, and the capacity to address those side effects promptly.
• Offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) highly suggestive of MS and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS.
• For patients with relapsing-remitting MS, the choice between a wide range of available drugs (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, fingolimod, ozanimod, ponesimod, natalizumab, alemtuzumab, ocrelizumab, rituximab, or ofatumumab), from modestly to highly effective, will depend on factors including: underlying disability progression, disease severity/clinical or radiological activity, patient characteristics and morbidity, drug safety profile, family planning, and patient preferences.

Progressive MS

• For patients with secondary progressive MS with evidence of inflammatory activity (relapses and/or MRI activity), offer treatment with siponimod. Treatment with other therapies used for relapsing remitting MS may also be considered.
• For secondary progressive MS without evidence of inflammatory activity, particularly in young patients and those in whom progression has started recently, consider treatment with siponimod or anti-CD20 monoclonal antibodies, taking into account that there is scarce evidence to support their use in this setting.  
• For patients with active secondary progressive MS when there is no other therapy available, consider treatment with mitoxantrone, taking into account the safety concerns and tolerability issues of this agent. 
• Consider ocrelizumab for patients with primary progressive MS, particularly early and active (clinically and/or radiologically) disease.

Emphasis toward higher-efficacy drugs

• Consider choosing a higher-efficacy disease-modifying drug early on, according to disease activity (either clinically or on MRI).
• Offer a more efficacious drug to patients who show evidence of disease activity with their current treatment.
• When treatment with a high-efficacy drug is stopped, whether because of inefficacy or risk of adverse effects, consider starting another high-efficacy drug, taking into account clinical and MRI disease activity before and during treatment, pharmacokinetics and biological activity of the previous drug, and the potential for resumed disease activity or even rebound syndrome (particularly with natalizumab and S1P modulators).
• In the stable patient (clinically and on MRI) who shows no safety or tolerability issues, consider continuing treatment with disease-modifying therapy, taking into account patient characteristics and comorbidities, drug safety profile, family planning, and patient preferences.

Recommendations for pregnancy and breastfeeding

Recommendations for pregnant women and mothers who choose to breastfeed include:

• Advise women who wish to become pregnant to plan their pregnancy beforehand.
• Advise women of childbearing potential that MS disease-modifying therapies are not licensed during pregnancy, with the exception of interferons and glatiramer acetate.
• For women planning a pregnancy, offer interferons and glatiramer acetate and consider continuing these agents during pregnancy after assessment of risk and benefits. Consider using dimethyl fumarate until pregnancy is confirmed and stopping during pregnancy after assessment of the risks and benefits. 
• For women with highly active disease who wish to become pregnant, there are a number of therapeutic options:

1)  treatment with long lasting effects such as alemtuzumab or cladribine provided that at least 4 or 6 months respectively have elapsed between the last dose and conception2)  treatment with anti-CD20 drugs before pregnancy with advice to wait for 2-6 months after the last infusion before becoming pregnant and to avoid further infusions during pregnancy, or3) for patients treated with natalizumab, consider continuing treatment during pregnancy using a 6-week extended dosage regimen until the end of the second trimester or up until week 34 and resuming after delivery (in newborns exposed to natalizumab, check for hematological abnormalities and liver function)

• Only interferons and ofatumumab are currently approved during breastfeeding.   
•  

Treatment safety/monitoring

• When treating patients with natalizumab and after a period of stability, consider switching to a 6-week interval regimen in order to minimize the risk of progressive multifocal leukoencephalopathy (PML).
• Consider treatment with high-efficacy drugs including natalizumab in patients with high disease activity, in whom a quick therapeutic effect is required, taking into account the risk of PML in John Cunningham virus (JCV)-positive patients, as well as the therapeutic lag of the different disease-modifying drugs.
• Ideally, prioritize vaccination against COVID-19 before starting immunosuppressive disease-modifying treatments to achieve the highest protection rate possible.
•  

Long-lasting treatments

• When using long-lasting treatments (alemtuzumab or cladribine) in patients who experience disease activity before the treatment is completed (between the first and second cycles), consider waiting until completion of the therapeutic regimen before switching to other drugs.
• Consider offering additional courses of alemtuzumab after the first two cycles at least 1 year apart from each other when disease activity has not remitted completely or reappears after a period of stability, taking into account the balance between the potential benefits and side effects.

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

Updated European guidelines on the treatment of patients with multiple sclerosis (MS) have been announced and include a recommendation for siponimod (Mayzent) in progressive MS, as well as a general emphasis toward earlier and more aggressive treatment.

The updated guidelines were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and are the result of a collaboration between ECTRIMS and the European Academy of Neurology (EAN).

Maria Pia Amato, MD, ECTRIMS president and co-chair of the guidelines steering committee, noted that the European MS treatment guidelines were last published in 2018. “Since then more trials have been published, and we felt this was a good time to incorporate the new evidence into updated guidelines,” she said.

“As before, the updated guidelines contain a number of core questions that address the efficacy of disease-modifying therapies, early treatment decisions, disease/treatment response monitoring and treatment modifications, treatment suspension and disease reactivation, and pregnancy and breastfeeding,” Dr. Amato said.
 

New recommendations

New features of the updated guidelines include a recommendation for siponimod for secondary progressive MS with evidence of disease inflammatory activity; in addition, there is more emphasis on starting treatment early, with greater consideration of higher efficacy drugs, depending on the characteristics of the disease and the patient, Dr. Amato commented.

“We also provided more detailed information on disease-modifying therapy use in pregnancy and breastfeeding and also for women with high disease activity who desire to become pregnant,” she added.

Other new features include the introduction of clinical questions dealing with treatment safety and monitoring (for example, for natalizumab) and also considering the current COVID-19 pandemic scenario; switching strategies with more detailed practical indications on timing; and long lasting effects of drugs such as alemtuzumab and cladribine, Dr. Amato said.

The updated guidelines include the following recommendations:

• The entire spectrum of disease-modifying drugs should be prescribed by a neurologist with expertise in MS and ready access to adequate infrastructure to provide proper monitoring of patents, comprehensive assessment, early detection of side effects, and the capacity to address those side effects promptly.
• Offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) highly suggestive of MS and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS.
• For patients with relapsing-remitting MS, the choice between a wide range of available drugs (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, fingolimod, ozanimod, ponesimod, natalizumab, alemtuzumab, ocrelizumab, rituximab, or ofatumumab), from modestly to highly effective, will depend on factors including: underlying disability progression, disease severity/clinical or radiological activity, patient characteristics and morbidity, drug safety profile, family planning, and patient preferences.

Progressive MS

• For patients with secondary progressive MS with evidence of inflammatory activity (relapses and/or MRI activity), offer treatment with siponimod. Treatment with other therapies used for relapsing remitting MS may also be considered.
• For secondary progressive MS without evidence of inflammatory activity, particularly in young patients and those in whom progression has started recently, consider treatment with siponimod or anti-CD20 monoclonal antibodies, taking into account that there is scarce evidence to support their use in this setting.  
• For patients with active secondary progressive MS when there is no other therapy available, consider treatment with mitoxantrone, taking into account the safety concerns and tolerability issues of this agent. 
• Consider ocrelizumab for patients with primary progressive MS, particularly early and active (clinically and/or radiologically) disease.

Emphasis toward higher-efficacy drugs

• Consider choosing a higher-efficacy disease-modifying drug early on, according to disease activity (either clinically or on MRI).
• Offer a more efficacious drug to patients who show evidence of disease activity with their current treatment.
• When treatment with a high-efficacy drug is stopped, whether because of inefficacy or risk of adverse effects, consider starting another high-efficacy drug, taking into account clinical and MRI disease activity before and during treatment, pharmacokinetics and biological activity of the previous drug, and the potential for resumed disease activity or even rebound syndrome (particularly with natalizumab and S1P modulators).
• In the stable patient (clinically and on MRI) who shows no safety or tolerability issues, consider continuing treatment with disease-modifying therapy, taking into account patient characteristics and comorbidities, drug safety profile, family planning, and patient preferences.

Recommendations for pregnancy and breastfeeding

Recommendations for pregnant women and mothers who choose to breastfeed include:

• Advise women who wish to become pregnant to plan their pregnancy beforehand.
• Advise women of childbearing potential that MS disease-modifying therapies are not licensed during pregnancy, with the exception of interferons and glatiramer acetate.
• For women planning a pregnancy, offer interferons and glatiramer acetate and consider continuing these agents during pregnancy after assessment of risk and benefits. Consider using dimethyl fumarate until pregnancy is confirmed and stopping during pregnancy after assessment of the risks and benefits. 
• For women with highly active disease who wish to become pregnant, there are a number of therapeutic options:

1)  treatment with long lasting effects such as alemtuzumab or cladribine provided that at least 4 or 6 months respectively have elapsed between the last dose and conception2)  treatment with anti-CD20 drugs before pregnancy with advice to wait for 2-6 months after the last infusion before becoming pregnant and to avoid further infusions during pregnancy, or3) for patients treated with natalizumab, consider continuing treatment during pregnancy using a 6-week extended dosage regimen until the end of the second trimester or up until week 34 and resuming after delivery (in newborns exposed to natalizumab, check for hematological abnormalities and liver function)

• Only interferons and ofatumumab are currently approved during breastfeeding.   
•  

Treatment safety/monitoring

• When treating patients with natalizumab and after a period of stability, consider switching to a 6-week interval regimen in order to minimize the risk of progressive multifocal leukoencephalopathy (PML).
• Consider treatment with high-efficacy drugs including natalizumab in patients with high disease activity, in whom a quick therapeutic effect is required, taking into account the risk of PML in John Cunningham virus (JCV)-positive patients, as well as the therapeutic lag of the different disease-modifying drugs.
• Ideally, prioritize vaccination against COVID-19 before starting immunosuppressive disease-modifying treatments to achieve the highest protection rate possible.
•  

Long-lasting treatments

• When using long-lasting treatments (alemtuzumab or cladribine) in patients who experience disease activity before the treatment is completed (between the first and second cycles), consider waiting until completion of the therapeutic regimen before switching to other drugs.
• Consider offering additional courses of alemtuzumab after the first two cycles at least 1 year apart from each other when disease activity has not remitted completely or reappears after a period of stability, taking into account the balance between the potential benefits and side effects.

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

Oral fluoroquinolone therapy to treat a respiratory infection is associated with an increased risk of sudden cardiac death (SCD) in patients on hemodialysis, particularly those taking other QT-prolonging medications, a large observational study suggests.

However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.

“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.

The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
 

Nearly twofold increased risk 

The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.

These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.

The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).

The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.

“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.

They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.

In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.

“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.

They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
 

Valuable study

Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.

“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.

Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.

“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.  

Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.

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

Oral fluoroquinolone therapy to treat a respiratory infection is associated with an increased risk of sudden cardiac death (SCD) in patients on hemodialysis, particularly those taking other QT-prolonging medications, a large observational study suggests.

However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.

“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.

The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
 

Nearly twofold increased risk 

The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.

These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.

The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).

The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.

“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.

They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.

In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.

“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.

They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
 

Valuable study

Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.

“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.

Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.

“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.  

Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.

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

Oral fluoroquinolone therapy to treat a respiratory infection is associated with an increased risk of sudden cardiac death (SCD) in patients on hemodialysis, particularly those taking other QT-prolonging medications, a large observational study suggests.

However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.

“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.

The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
 

Nearly twofold increased risk 

The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.

These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.

The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).

The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.

“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.

They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.

In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.

“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.

They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
 

Valuable study

Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.

“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.

Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.

“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.  

Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.

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

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
 

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

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
 

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

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
 

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

Gender-affirmation surgery refers to a collection of procedures by which a transgender individual physically alters characteristics to align with their gender identity. While not all patients who identify as transgender will choose to undergo surgery, the surgeries are considered medically necessary and lead to significant improvements in emotional and psychological well-being.¹ With increasing insurance coverage and improved access to care, more and more patients are seeking gender-affirming surgery, and it is incumbent for providers to familiarize themselves with preoperative recommendations and requirements.

Ob.gyns. play a key role in patients seeking surgical treatment as patients may inquire about available procedures and what steps are necessary prior to scheduling a visit with the appropriate surgeon. The World Professional Association of Transgender Health has established standards of care that provide multidisciplinary, evidence-based guidance for patients seeking a variety of gender-affirming services ranging from mental health, hormone therapy, and surgery.

Basic preoperative surgical prerequisites set forth by WPATH include being a patient with well-documented gender dysphoria, being the age of majority, and having the ability to provide informed consent.¹

As with any surgical candidate, it is also equally important for a patient to have well-controlled medical and psychiatric comorbidities, which should also include smoking cessation. A variety of surgical procedures are available to patients and include breast/chest surgery, genital (bottom) surgery, and nongenital surgery (facial feminization, pectoral implant placement, thyroid chondroplasty, lipofilling/liposuction, body contouring, and voice modification). Patients may choose to undergo chest/breast surgery and/or bottom surgery or forgo surgical procedures altogether.

For transmasculine patients, breast/chest surgery, otherwise known as top surgery, is the most common and desired procedure. According to a recent survey, approximately 97% of transmasculine patients had or wanted masculinizing chest surgery.² In addition to patients meeting the basic requirements set forth by WPATH, one referral from a mental health provider specializing in gender-affirming care is also needed prior to this procedure. It is also important to note that testosterone use is no longer a needed prior to masculinizing chest surgery.

Transmasculine bottom surgery, which includes hysterectomy, bilateral salpingo-oophorectomy, metoidioplasty, vaginectomy, scrotoplasty, testicular implant placement, and/or phalloplasty have additional nuances. Compared with transmasculine individuals seeking top surgery, the number of patients who have had or desire metoidioplasty and phalloplasty is much lower, which is mainly because of the high complication rates of these procedures. In the same survey, only 4% of patients had undergone a metoidioplasty procedure and 2% of patients had undergone a phalloplasty.²

In evaluating rates of hysterectomy with or without salpingo-oophorectomy, approximately 21% of transgender men underwent hysterectomy, with 58% desiring it in the future.² Unlike patients pursuing top surgery, patients who desire any form of bottom surgery need to be on 12 months of continuous hormone therapy.¹ They also must provide two letters from two different mental health providers, one of whom must have either an MD/DO or PhD. In cases in which a patient requests a hysterectomy for reasons other than gender dysphoria, such as pelvic pain or abnormal uterine bleeding, these criteria do not apply.

For transfeminine individuals, augmentation mammoplasty is performed following 12 months of continuous hormone therapy. This is to allow maximum breast growth, which occurs approximately 2-3 months after hormone initiation and peaks at 1-2 years.³ Rates of transfeminine individuals seeking augmentation mammoplasty is similar to that of their transmasculine counterparts at 74%.² One referral letter from a mental health provider is also needed prior to augmentation mammoplasty.

Transfeminine patients who desire bottom surgery, which can involve an orchiectomy or vaginoplasty (single-stage penile inversion, peritoneal, or colonic interposition), have the same additional requirements as transmasculine individuals seeking bottom surgery. Furthermore, it is interesting to note that 25% of transfeminine individuals had already undergone orchiectomy and 87% had either undergone or desired a vaginoplasty in the future.² This is in stark contrast to transmasculine patients and rates of bottom surgery.

Unless there is a specific medical contraindication to hormone therapy, emphasis is placed on 12 months of continuous hormone usage. Additional emphasis is placed on patients seeking bottom surgery to live for a minimum of 12 months in their congruent gender role. This also allows patients to further explore their gender identity and make appropriate preparations for surgery.

As with any surgical procedure, obtaining informed consent and reviewing patient expectations are key. In my clinical practice, I discuss with patients that the general surgical goals are to achieve both function and good aesthetic outcome but that their results are also tailored to their individual bodies. Assessing a patient’s support system and social factors is also equally important in the preoperative planning period. As this field continues to grow, it is essential for providers to understand the evolving distinctions in surgical care to improve access to patients.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no conflicts. Email her at [email protected].

References

1. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. https://www.wpath.org/publications/soc.

2. James SE et al. The report of the 2015 U.S. Transgender survey. Washington, D.C.: National Center for Transgender Equality. 2016.

3. Thomas TN. Overview of surgery for transgender patients, in “Comprehensive care for the transgender patient.” Philadelphia: Elsevier, 2020. pp. 48-53.

Gender-affirmation surgery refers to a collection of procedures by which a transgender individual physically alters characteristics to align with their gender identity. While not all patients who identify as transgender will choose to undergo surgery, the surgeries are considered medically necessary and lead to significant improvements in emotional and psychological well-being.¹ With increasing insurance coverage and improved access to care, more and more patients are seeking gender-affirming surgery, and it is incumbent for providers to familiarize themselves with preoperative recommendations and requirements.

Ob.gyns. play a key role in patients seeking surgical treatment as patients may inquire about available procedures and what steps are necessary prior to scheduling a visit with the appropriate surgeon. The World Professional Association of Transgender Health has established standards of care that provide multidisciplinary, evidence-based guidance for patients seeking a variety of gender-affirming services ranging from mental health, hormone therapy, and surgery.

Basic preoperative surgical prerequisites set forth by WPATH include being a patient with well-documented gender dysphoria, being the age of majority, and having the ability to provide informed consent.¹

As with any surgical candidate, it is also equally important for a patient to have well-controlled medical and psychiatric comorbidities, which should also include smoking cessation. A variety of surgical procedures are available to patients and include breast/chest surgery, genital (bottom) surgery, and nongenital surgery (facial feminization, pectoral implant placement, thyroid chondroplasty, lipofilling/liposuction, body contouring, and voice modification). Patients may choose to undergo chest/breast surgery and/or bottom surgery or forgo surgical procedures altogether.

For transmasculine patients, breast/chest surgery, otherwise known as top surgery, is the most common and desired procedure. According to a recent survey, approximately 97% of transmasculine patients had or wanted masculinizing chest surgery.² In addition to patients meeting the basic requirements set forth by WPATH, one referral from a mental health provider specializing in gender-affirming care is also needed prior to this procedure. It is also important to note that testosterone use is no longer a needed prior to masculinizing chest surgery.

Transmasculine bottom surgery, which includes hysterectomy, bilateral salpingo-oophorectomy, metoidioplasty, vaginectomy, scrotoplasty, testicular implant placement, and/or phalloplasty have additional nuances. Compared with transmasculine individuals seeking top surgery, the number of patients who have had or desire metoidioplasty and phalloplasty is much lower, which is mainly because of the high complication rates of these procedures. In the same survey, only 4% of patients had undergone a metoidioplasty procedure and 2% of patients had undergone a phalloplasty.²

In evaluating rates of hysterectomy with or without salpingo-oophorectomy, approximately 21% of transgender men underwent hysterectomy, with 58% desiring it in the future.² Unlike patients pursuing top surgery, patients who desire any form of bottom surgery need to be on 12 months of continuous hormone therapy.¹ They also must provide two letters from two different mental health providers, one of whom must have either an MD/DO or PhD. In cases in which a patient requests a hysterectomy for reasons other than gender dysphoria, such as pelvic pain or abnormal uterine bleeding, these criteria do not apply.

For transfeminine individuals, augmentation mammoplasty is performed following 12 months of continuous hormone therapy. This is to allow maximum breast growth, which occurs approximately 2-3 months after hormone initiation and peaks at 1-2 years.³ Rates of transfeminine individuals seeking augmentation mammoplasty is similar to that of their transmasculine counterparts at 74%.² One referral letter from a mental health provider is also needed prior to augmentation mammoplasty.

Transfeminine patients who desire bottom surgery, which can involve an orchiectomy or vaginoplasty (single-stage penile inversion, peritoneal, or colonic interposition), have the same additional requirements as transmasculine individuals seeking bottom surgery. Furthermore, it is interesting to note that 25% of transfeminine individuals had already undergone orchiectomy and 87% had either undergone or desired a vaginoplasty in the future.² This is in stark contrast to transmasculine patients and rates of bottom surgery.

Unless there is a specific medical contraindication to hormone therapy, emphasis is placed on 12 months of continuous hormone usage. Additional emphasis is placed on patients seeking bottom surgery to live for a minimum of 12 months in their congruent gender role. This also allows patients to further explore their gender identity and make appropriate preparations for surgery.

As with any surgical procedure, obtaining informed consent and reviewing patient expectations are key. In my clinical practice, I discuss with patients that the general surgical goals are to achieve both function and good aesthetic outcome but that their results are also tailored to their individual bodies. Assessing a patient’s support system and social factors is also equally important in the preoperative planning period. As this field continues to grow, it is essential for providers to understand the evolving distinctions in surgical care to improve access to patients.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no conflicts. Email her at [email protected].

References

1. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. https://www.wpath.org/publications/soc.

2. James SE et al. The report of the 2015 U.S. Transgender survey. Washington, D.C.: National Center for Transgender Equality. 2016.

3. Thomas TN. Overview of surgery for transgender patients, in “Comprehensive care for the transgender patient.” Philadelphia: Elsevier, 2020. pp. 48-53.

Gender-affirmation surgery refers to a collection of procedures by which a transgender individual physically alters characteristics to align with their gender identity. While not all patients who identify as transgender will choose to undergo surgery, the surgeries are considered medically necessary and lead to significant improvements in emotional and psychological well-being.¹ With increasing insurance coverage and improved access to care, more and more patients are seeking gender-affirming surgery, and it is incumbent for providers to familiarize themselves with preoperative recommendations and requirements.

Ob.gyns. play a key role in patients seeking surgical treatment as patients may inquire about available procedures and what steps are necessary prior to scheduling a visit with the appropriate surgeon. The World Professional Association of Transgender Health has established standards of care that provide multidisciplinary, evidence-based guidance for patients seeking a variety of gender-affirming services ranging from mental health, hormone therapy, and surgery.

Basic preoperative surgical prerequisites set forth by WPATH include being a patient with well-documented gender dysphoria, being the age of majority, and having the ability to provide informed consent.¹

As with any surgical candidate, it is also equally important for a patient to have well-controlled medical and psychiatric comorbidities, which should also include smoking cessation. A variety of surgical procedures are available to patients and include breast/chest surgery, genital (bottom) surgery, and nongenital surgery (facial feminization, pectoral implant placement, thyroid chondroplasty, lipofilling/liposuction, body contouring, and voice modification). Patients may choose to undergo chest/breast surgery and/or bottom surgery or forgo surgical procedures altogether.

For transmasculine patients, breast/chest surgery, otherwise known as top surgery, is the most common and desired procedure. According to a recent survey, approximately 97% of transmasculine patients had or wanted masculinizing chest surgery.² In addition to patients meeting the basic requirements set forth by WPATH, one referral from a mental health provider specializing in gender-affirming care is also needed prior to this procedure. It is also important to note that testosterone use is no longer a needed prior to masculinizing chest surgery.

Transmasculine bottom surgery, which includes hysterectomy, bilateral salpingo-oophorectomy, metoidioplasty, vaginectomy, scrotoplasty, testicular implant placement, and/or phalloplasty have additional nuances. Compared with transmasculine individuals seeking top surgery, the number of patients who have had or desire metoidioplasty and phalloplasty is much lower, which is mainly because of the high complication rates of these procedures. In the same survey, only 4% of patients had undergone a metoidioplasty procedure and 2% of patients had undergone a phalloplasty.²

In evaluating rates of hysterectomy with or without salpingo-oophorectomy, approximately 21% of transgender men underwent hysterectomy, with 58% desiring it in the future.² Unlike patients pursuing top surgery, patients who desire any form of bottom surgery need to be on 12 months of continuous hormone therapy.¹ They also must provide two letters from two different mental health providers, one of whom must have either an MD/DO or PhD. In cases in which a patient requests a hysterectomy for reasons other than gender dysphoria, such as pelvic pain or abnormal uterine bleeding, these criteria do not apply.

For transfeminine individuals, augmentation mammoplasty is performed following 12 months of continuous hormone therapy. This is to allow maximum breast growth, which occurs approximately 2-3 months after hormone initiation and peaks at 1-2 years.³ Rates of transfeminine individuals seeking augmentation mammoplasty is similar to that of their transmasculine counterparts at 74%.² One referral letter from a mental health provider is also needed prior to augmentation mammoplasty.

Transfeminine patients who desire bottom surgery, which can involve an orchiectomy or vaginoplasty (single-stage penile inversion, peritoneal, or colonic interposition), have the same additional requirements as transmasculine individuals seeking bottom surgery. Furthermore, it is interesting to note that 25% of transfeminine individuals had already undergone orchiectomy and 87% had either undergone or desired a vaginoplasty in the future.² This is in stark contrast to transmasculine patients and rates of bottom surgery.

Unless there is a specific medical contraindication to hormone therapy, emphasis is placed on 12 months of continuous hormone usage. Additional emphasis is placed on patients seeking bottom surgery to live for a minimum of 12 months in their congruent gender role. This also allows patients to further explore their gender identity and make appropriate preparations for surgery.

As with any surgical procedure, obtaining informed consent and reviewing patient expectations are key. In my clinical practice, I discuss with patients that the general surgical goals are to achieve both function and good aesthetic outcome but that their results are also tailored to their individual bodies. Assessing a patient’s support system and social factors is also equally important in the preoperative planning period. As this field continues to grow, it is essential for providers to understand the evolving distinctions in surgical care to improve access to patients.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no conflicts. Email her at [email protected].

References

1. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. https://www.wpath.org/publications/soc.

2. James SE et al. The report of the 2015 U.S. Transgender survey. Washington, D.C.: National Center for Transgender Equality. 2016.

3. Thomas TN. Overview of surgery for transgender patients, in “Comprehensive care for the transgender patient.” Philadelphia: Elsevier, 2020. pp. 48-53.

A new study suggests that tiny, clear nematodes can sniff out early-stage pancreatic cancer.

Research shows Caenorhabditis elegans are attracted to the odor certain chemicals give off – a behavior known as attractive chemotaxis – and early evidence indicates these scents may include human cancer cell secretions, cancer tissues, and urine from patients with colorectal, gastric, and breast cancers.

According to the recent analysis, published in Oncotarget, these small worms may be hot on the trail of pancreatic cancer–related compounds too. The researchers found that C. elegans were significantly more attracted to patients with early-stage pancreatic cancer versus healthy controls.

There is a huge need for research like this that explores strategies to detect pancreatic cancer early, but it’s far too soon to tell how, or if, this particular approach will be clinically relevant, according to Neeha Zaidi, MD, assistant professor of oncology and a medical oncologist specializing in pancreatic cancer at John Hopkins Medicine, Baltimore, who was not involved in the current analysis.

Right now, few diagnostic markers exist for identifying pancreatic ductal adenocarcinomas (PDACs), which account for 90% of pancreatic cancers. PDACs remain one of the deadliest cancers, with a 5-year survival rate of 9%.

A combination of surgical resection and chemotherapy is the only curative treatment, and just 20% of patients are eligible, Dr. Zaidi said. The majority are identified after the disease has metastasized.

However, patients’ 5-year survival rate improves markedly – as high as 85% – if the condition is caught sooner.

In the current study, the researchers first exposed C. elegans to the urine of 83 patients from cancer centers across Japan who had various stages of pancreatic cancer before and after undergoing surgical resection. Using an assay, which takes 30 minutes and 50-100 nematodes per test, C. elegans showed significantly higher chemotaxis toward preoperative urine, compared with postoperative urine.

In a second, closed-labeled arm, the nematodes were exposed to the urine of 28 randomized participants – 11 of whom had early-stage pancreatic cancer (0 or IA), plus 17 healthy volunteers. In this instance as well, C. elegans showed significantly higher chemotaxis in patients with early-stage pancreatic cancer, compared with healthy volunteers (P = .034). 

According to the authors, C. elegans “had a higher sensitivity for detecting early pancreatic cancer compared to existing diagnostic markers.” And while this strategy needs to be further validated, they believe early detection of pancreatic cancer using C. elegans “can certainly be expected in the near future.”

The study aligns with previous research, showing that wild-type C. elegans are sensitive to scent and that these critters can smell cancer. Other studies have also found that sniffer canines can detect volatile organic compounds – including biomarkers of certain cancers – in the urine and breath of cancer patients. But training an adequate number of these canines for the clinic isn’t feasible, while C. elegans are far more compact and affordable.

According to Dr. Zaidi, a scent test using C. elegans “seems pretty feasible” and cost effective, but whether this approach will “change our care has yet to be determined.”

The authors, for instance, don’t specify how the scent test will be used, though Dr. Zaidi suspects it would be most relevant for following patients with a higher risk of pancreatic cancer. Alternatively, it could be used as a screening test, but that’s a massive undertaking and “this is way too early to tell if it’s going to be helpful to use this test on a broad scale,” Dr. Zaidi said.

To validate the approach, researchers would also need to know what exactly the C. elegans are smelling and to test it in a much larger number of patients, Dr. Zaidi said. The mere 11 patients with cancer in the blinded portion of the study are not sufficient to draw any major conclusions.

The study also claims a high sensitivity, but what about specificity, Dr. Zaidi said. In other words, are there a lot of false positives? 

In addition, a deeper look at the participants shows the two groups – early PDAC and healthy volunteers – were not adequately balanced. The median age of the diseased patients was 70, and the healthy volunteers was 39.

“This is a big difference,” Eithne Costello, PhD, professor of molecular oncology at Liverpool (England) University, said in an interview. “It [also] appears the controls are all of one sex (either all male or all female), while the cancer group is mixed.”

The authors attributed these shortcomings to the small population they had to work with: There simply aren’t many patients whose pancreatic cancer is detected early. Dr. Zaidi agreed that patients with pancreatic cancer stage 0 or IA are extremely difficult to come by.

Even still, researchers need to understand the mechanisms behind this approach and see it work in a much larger group of patients, Dr. Zaidi said.

The study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology. The authors reported institutional endowments received from Hirotsu Bio Science, Kinshu-kai Medical, IDEA Consultants, Ono Pharmaceutical, and others. Two coauthors are employees of Hirotsu Bio Science.