News

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

Oneirogens are substances that produce or enhance dreamlike states of consciousness—could one of those, ibogaine, be key to relieving the sequelae of traumatic brain injury (TBI) in veterans?

An extract from the root bark of Tabernanthe iboga, an African shrub, ibogaine has both pharmacological and psychological effects. Acting on opioid receptors and the serotonin and dopamine systems, it can relieve withdrawal symptoms and reduce drug cravings—reportedly, often, in just a few hours—and reduce the risk of regular use. The results can last for weeks, months, or sometimes longer.

In the US, ibogaine is a Schedule I drug. Few controlled studies of ibogaine are available; most data come from anecdotal reports and case studies. Clinical research into ibogaine stalled due to legal restrictions that come with a Schedule I drug, as well as concerns about possible cardiac consequences. For example, some reports have described QT interval prolongation, with instances of subsequent fatal arrhythmia.  

That may change now, with findings from the Magnesium–Ibogaine: the Stanford Traumatic Injury to the CNS protocol (MISTIC), which took place at a treatment center in Mexico. Researchers from Stanford School of Medicine and the Veterans Affairs Palo Alto Health Care System combined prophylactic intravenous magnesium with ibogaine, in hopes of mitigating the cardiac risks. Magnesium supplementation has been shown to protect against QT interval prolongation when coadministered with medications that ordinarily would have such an effect.

The researchers studied 30 male Special Operations Forces veterans (SOVs) who had predominantly mild TBI. Of those, 15 participants met the criteria for major depressive disorder, 14 for an anxiety disorder, and 23 for PTSD; 19 had past suicidal ideation and 7 had attempted suicide.

Special Operations Forces, the researchers note, are “deployed at a greater pace and to higher intensity combat than conventional military, exposing them to greater allostatic load and risk of injury, including from blast exposure.” This, they say, may result in a “unique pattern” of physical, cognitive, behavioral, psychiatric, and endocrine-related problems across several domains.

Participants received a mean (SD) of 12.1 (1.2) mg kg^-1 of oral ibogaine. The researchers assessed changes in the World Health Organization Disability Assessment Schedule at baseline, immediately after treatment, and 1 month after treatment. They also assessed changes in posttraumatic stress disorder (PTSD), depression, and anxiety.

The treatment significantly improved functioning both immediately and at 1 month after treatment and PTSD, depression, and anxiety at 1 month after treatment. There were no unexpected or serious treatment-emergent adverse effects, nor were there instances of bradycardia, tachycardia, clinically meaningful QT prolongation, or hemodynamic instability. All participants experienced transient cerebellar signs, such as mild ataxia and intention tremor, that resolved within 24 hours. While experiencing oneirogenic effects, 12 participants were treated for headache, 7 for nausea, 3 for anxiety, 2 for hypertension, and 1 for insomnia. 

At 1 month, suicidal ideation had declined from 47% to 7%—a statistically significant change. “Given the alarming rates of suicide in veterans, as well as evidence that military-related TBI increases the risk of suicide,” the researchers say, “the substantial reduction in SI that we observed—which must be interpreted cautiously as an exploratory analysis—is noteworthy.” TBI also is associated with increased impulsivity, a well-known risk factor for suicide, they note. MISTIC resulted in a measurable improvement in cognitive inhibition.

Results of a neuropsychological battery indicated statistically significant improvements in processing speed and executive functioning (including inhibition, cognitive flexibility, problem-solving, phonemic fluency, and working memory), both immediately after treatment and at 1 month. No declines were noted across any performance domain.

Interestingly, mean performances on these tests moved from the average to the high average score range relative to same-age peers and, in all but one instance, phonemic fluency was high average at baseline and improved to the superior range relative to same-age peers at the 1-month follow-up. Learning and memory tests showed a significant improvement in visual memory and verbal memory. Sustained attention showed a significant improvement in accuracy (detection) and a weak but significant slowing of reaction time, consistent with a prioritization of accuracy over speed and reduced impulsivity.

In a Scientific American article, lead researcher Nolan Williams said he suspects the powerful effects of psychedelics have to do with their “profound ability to increase plasticity in the brain” by “bringing it back to a more juvenile state where reorganization can occur.” People often experience a life review that appears in their minds almost like a slideshow. “It somehow drives a particular sort of psychological phenomenon that you don’t achieve through guidance,” Williams said.

The data from the MISTIC trial in Mexico may spur more research in the US. The National Defense Authorization Act, signed by President Joe Biden last December, authorizes service members diagnosed with PTSD or TBI to take part in clinical studies of any “qualified plant-based alternative therapies.”

“It’s all really timely,” Williams said. “From my perspective, we should have some traction to make a strong argument that the risk-benefit is right.”

Oneirogens are substances that produce or enhance dreamlike states of consciousness—could one of those, ibogaine, be key to relieving the sequelae of traumatic brain injury (TBI) in veterans?

An extract from the root bark of Tabernanthe iboga, an African shrub, ibogaine has both pharmacological and psychological effects. Acting on opioid receptors and the serotonin and dopamine systems, it can relieve withdrawal symptoms and reduce drug cravings—reportedly, often, in just a few hours—and reduce the risk of regular use. The results can last for weeks, months, or sometimes longer.

In the US, ibogaine is a Schedule I drug. Few controlled studies of ibogaine are available; most data come from anecdotal reports and case studies. Clinical research into ibogaine stalled due to legal restrictions that come with a Schedule I drug, as well as concerns about possible cardiac consequences. For example, some reports have described QT interval prolongation, with instances of subsequent fatal arrhythmia.  

That may change now, with findings from the Magnesium–Ibogaine: the Stanford Traumatic Injury to the CNS protocol (MISTIC), which took place at a treatment center in Mexico. Researchers from Stanford School of Medicine and the Veterans Affairs Palo Alto Health Care System combined prophylactic intravenous magnesium with ibogaine, in hopes of mitigating the cardiac risks. Magnesium supplementation has been shown to protect against QT interval prolongation when coadministered with medications that ordinarily would have such an effect.

The researchers studied 30 male Special Operations Forces veterans (SOVs) who had predominantly mild TBI. Of those, 15 participants met the criteria for major depressive disorder, 14 for an anxiety disorder, and 23 for PTSD; 19 had past suicidal ideation and 7 had attempted suicide.

Special Operations Forces, the researchers note, are “deployed at a greater pace and to higher intensity combat than conventional military, exposing them to greater allostatic load and risk of injury, including from blast exposure.” This, they say, may result in a “unique pattern” of physical, cognitive, behavioral, psychiatric, and endocrine-related problems across several domains.

Participants received a mean (SD) of 12.1 (1.2) mg kg^-1 of oral ibogaine. The researchers assessed changes in the World Health Organization Disability Assessment Schedule at baseline, immediately after treatment, and 1 month after treatment. They also assessed changes in posttraumatic stress disorder (PTSD), depression, and anxiety.

The treatment significantly improved functioning both immediately and at 1 month after treatment and PTSD, depression, and anxiety at 1 month after treatment. There were no unexpected or serious treatment-emergent adverse effects, nor were there instances of bradycardia, tachycardia, clinically meaningful QT prolongation, or hemodynamic instability. All participants experienced transient cerebellar signs, such as mild ataxia and intention tremor, that resolved within 24 hours. While experiencing oneirogenic effects, 12 participants were treated for headache, 7 for nausea, 3 for anxiety, 2 for hypertension, and 1 for insomnia. 

At 1 month, suicidal ideation had declined from 47% to 7%—a statistically significant change. “Given the alarming rates of suicide in veterans, as well as evidence that military-related TBI increases the risk of suicide,” the researchers say, “the substantial reduction in SI that we observed—which must be interpreted cautiously as an exploratory analysis—is noteworthy.” TBI also is associated with increased impulsivity, a well-known risk factor for suicide, they note. MISTIC resulted in a measurable improvement in cognitive inhibition.

Results of a neuropsychological battery indicated statistically significant improvements in processing speed and executive functioning (including inhibition, cognitive flexibility, problem-solving, phonemic fluency, and working memory), both immediately after treatment and at 1 month. No declines were noted across any performance domain.

Interestingly, mean performances on these tests moved from the average to the high average score range relative to same-age peers and, in all but one instance, phonemic fluency was high average at baseline and improved to the superior range relative to same-age peers at the 1-month follow-up. Learning and memory tests showed a significant improvement in visual memory and verbal memory. Sustained attention showed a significant improvement in accuracy (detection) and a weak but significant slowing of reaction time, consistent with a prioritization of accuracy over speed and reduced impulsivity.

In a Scientific American article, lead researcher Nolan Williams said he suspects the powerful effects of psychedelics have to do with their “profound ability to increase plasticity in the brain” by “bringing it back to a more juvenile state where reorganization can occur.” People often experience a life review that appears in their minds almost like a slideshow. “It somehow drives a particular sort of psychological phenomenon that you don’t achieve through guidance,” Williams said.

The data from the MISTIC trial in Mexico may spur more research in the US. The National Defense Authorization Act, signed by President Joe Biden last December, authorizes service members diagnosed with PTSD or TBI to take part in clinical studies of any “qualified plant-based alternative therapies.”

“It’s all really timely,” Williams said. “From my perspective, we should have some traction to make a strong argument that the risk-benefit is right.”

Oneirogens are substances that produce or enhance dreamlike states of consciousness—could one of those, ibogaine, be key to relieving the sequelae of traumatic brain injury (TBI) in veterans?

An extract from the root bark of Tabernanthe iboga, an African shrub, ibogaine has both pharmacological and psychological effects. Acting on opioid receptors and the serotonin and dopamine systems, it can relieve withdrawal symptoms and reduce drug cravings—reportedly, often, in just a few hours—and reduce the risk of regular use. The results can last for weeks, months, or sometimes longer.

In the US, ibogaine is a Schedule I drug. Few controlled studies of ibogaine are available; most data come from anecdotal reports and case studies. Clinical research into ibogaine stalled due to legal restrictions that come with a Schedule I drug, as well as concerns about possible cardiac consequences. For example, some reports have described QT interval prolongation, with instances of subsequent fatal arrhythmia.  

That may change now, with findings from the Magnesium–Ibogaine: the Stanford Traumatic Injury to the CNS protocol (MISTIC), which took place at a treatment center in Mexico. Researchers from Stanford School of Medicine and the Veterans Affairs Palo Alto Health Care System combined prophylactic intravenous magnesium with ibogaine, in hopes of mitigating the cardiac risks. Magnesium supplementation has been shown to protect against QT interval prolongation when coadministered with medications that ordinarily would have such an effect.

The researchers studied 30 male Special Operations Forces veterans (SOVs) who had predominantly mild TBI. Of those, 15 participants met the criteria for major depressive disorder, 14 for an anxiety disorder, and 23 for PTSD; 19 had past suicidal ideation and 7 had attempted suicide.

Special Operations Forces, the researchers note, are “deployed at a greater pace and to higher intensity combat than conventional military, exposing them to greater allostatic load and risk of injury, including from blast exposure.” This, they say, may result in a “unique pattern” of physical, cognitive, behavioral, psychiatric, and endocrine-related problems across several domains.

Participants received a mean (SD) of 12.1 (1.2) mg kg^-1 of oral ibogaine. The researchers assessed changes in the World Health Organization Disability Assessment Schedule at baseline, immediately after treatment, and 1 month after treatment. They also assessed changes in posttraumatic stress disorder (PTSD), depression, and anxiety.

The treatment significantly improved functioning both immediately and at 1 month after treatment and PTSD, depression, and anxiety at 1 month after treatment. There were no unexpected or serious treatment-emergent adverse effects, nor were there instances of bradycardia, tachycardia, clinically meaningful QT prolongation, or hemodynamic instability. All participants experienced transient cerebellar signs, such as mild ataxia and intention tremor, that resolved within 24 hours. While experiencing oneirogenic effects, 12 participants were treated for headache, 7 for nausea, 3 for anxiety, 2 for hypertension, and 1 for insomnia. 

At 1 month, suicidal ideation had declined from 47% to 7%—a statistically significant change. “Given the alarming rates of suicide in veterans, as well as evidence that military-related TBI increases the risk of suicide,” the researchers say, “the substantial reduction in SI that we observed—which must be interpreted cautiously as an exploratory analysis—is noteworthy.” TBI also is associated with increased impulsivity, a well-known risk factor for suicide, they note. MISTIC resulted in a measurable improvement in cognitive inhibition.

Results of a neuropsychological battery indicated statistically significant improvements in processing speed and executive functioning (including inhibition, cognitive flexibility, problem-solving, phonemic fluency, and working memory), both immediately after treatment and at 1 month. No declines were noted across any performance domain.

Interestingly, mean performances on these tests moved from the average to the high average score range relative to same-age peers and, in all but one instance, phonemic fluency was high average at baseline and improved to the superior range relative to same-age peers at the 1-month follow-up. Learning and memory tests showed a significant improvement in visual memory and verbal memory. Sustained attention showed a significant improvement in accuracy (detection) and a weak but significant slowing of reaction time, consistent with a prioritization of accuracy over speed and reduced impulsivity.

In a Scientific American article, lead researcher Nolan Williams said he suspects the powerful effects of psychedelics have to do with their “profound ability to increase plasticity in the brain” by “bringing it back to a more juvenile state where reorganization can occur.” People often experience a life review that appears in their minds almost like a slideshow. “It somehow drives a particular sort of psychological phenomenon that you don’t achieve through guidance,” Williams said.

The data from the MISTIC trial in Mexico may spur more research in the US. The National Defense Authorization Act, signed by President Joe Biden last December, authorizes service members diagnosed with PTSD or TBI to take part in clinical studies of any “qualified plant-based alternative therapies.”

“It’s all really timely,” Williams said. “From my perspective, we should have some traction to make a strong argument that the risk-benefit is right.”

Infection with COVID-19 conferred a nearly twofold risk of developing alopecia areata (AA), results from a large analysis of Korean patients demonstrated.

“There is a growing number of reports on new onset, exacerbation, and recurrence of AA after COVID-19,” corresponding author Jin Park, MD, PhD, of the department of dermatology at Jeonbuk National University Medical School, South Korea, and colleagues wrote in a research letter published online January 10, 2024, in JAMA Dermatology. “However, evidence supporting an association between COVID-19 and AA is limited.”

To investigate the association between COVID-19 and AA, the researchers used data from the Korea Disease Control and Prevention Agency–COVID-19–National Health Insurance Service cohort to conduct a propensity score–matched, nationwide, population-based cohort study from October 8, 2020, to September 30, 2021. They used Cox proportional hazards regression to calculate the incidence, prevalence, and adjusted hazard ratios (AHRs) for AA.

The cohort consisted of 259,369 patients with COVID-19 and 259,369 uninfected controls. The researchers observed an increased risk of telogen effluvium in patients with COVID-19 compared with the uninfected controls (AHR, 6.40; 95% CI, 4.92-8.33), while the incidence of epidermal cysts, benign skin tumors, and other negative control outcomes did not differ between groups.

Meanwhile, the incidence of AA in patients with COVID-19 was significantly higher compared with the uninfected controls (43.19 per 10,000 person-years [PY]), regardless of clinical subtype. This translated into an AHR of 1.82 (95% CI, 1.60-2.07). In other findings, the incidence of patchy AA and alopecia totalis and alopecia universalis (AT/AU) was 35.94 and 7.24 per 10,000 PY in patients with COVID-19 compared with 19.43 and 4.18 per 10,000 PY in uninfected controls, respectively.

“These findings support the possible role of COVID-19 in AA occurrence and exacerbation, although other environmental factors, such as psychological stress, may have also contributed to AA development during the pandemic,” the authors concluded. “Plausible mechanisms of AA following COVID-19 include antigenic molecular mimicry between SARS-CoV-2 and hair follicle autoantigens, cytokine shifting, and bystander activation.”

They acknowledged certain limitations of the analysis, including the potential for detection or misclassification bias and the fact that it did not evaluate causality between the two conditions.

Shari Lipner, MD, PhD, associate professor of dermatology at Weill Cornell Medicine, New York, who was asked to comment on the study, said that strengths of the study include the large sample size, and the use of positive and negative outcome controls, and that the incidence and prevalence of AA in Korea was stable during the prepandemic period. “A weakness of the study is that all alopecia areata cases may not have necessarily been confirmed,” Dr. Lipner told this news organization.

“Based on this study, dermatologists may consider AA in the differential diagnosis for a patient presenting with hair loss with recent COVID-19 diagnosis,” she added, noting that the potential for prevention of AA flares is also a reason to recommend COVID-19 vaccination for patients with a history of AA.

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was also asked to comment on the study, said that while the analysis suggests a definite epidemiologic association between COVID-19 and AA, “any causal relationship needs further study.” She added that she has no specific advice for patients who develop AA following a COVID-19 infection. “Any conversation about AA can be difficult because there is no way to prognosticate if someone will just have one small, localized area of hair loss,” or several small areas, versus loss of all hair on the head or even the body as well, Dr. Ko explained.

The study was supported with grants from the National Research Foundation of the Korean Government and the Ministry of Health and Welfare, Republic of Korea. The authors, as well as Dr. Lipner and Dr. Ko, reported having no relevant disclosures.

Infection with COVID-19 conferred a nearly twofold risk of developing alopecia areata (AA), results from a large analysis of Korean patients demonstrated.

“There is a growing number of reports on new onset, exacerbation, and recurrence of AA after COVID-19,” corresponding author Jin Park, MD, PhD, of the department of dermatology at Jeonbuk National University Medical School, South Korea, and colleagues wrote in a research letter published online January 10, 2024, in JAMA Dermatology. “However, evidence supporting an association between COVID-19 and AA is limited.”

To investigate the association between COVID-19 and AA, the researchers used data from the Korea Disease Control and Prevention Agency–COVID-19–National Health Insurance Service cohort to conduct a propensity score–matched, nationwide, population-based cohort study from October 8, 2020, to September 30, 2021. They used Cox proportional hazards regression to calculate the incidence, prevalence, and adjusted hazard ratios (AHRs) for AA.

The cohort consisted of 259,369 patients with COVID-19 and 259,369 uninfected controls. The researchers observed an increased risk of telogen effluvium in patients with COVID-19 compared with the uninfected controls (AHR, 6.40; 95% CI, 4.92-8.33), while the incidence of epidermal cysts, benign skin tumors, and other negative control outcomes did not differ between groups.

Meanwhile, the incidence of AA in patients with COVID-19 was significantly higher compared with the uninfected controls (43.19 per 10,000 person-years [PY]), regardless of clinical subtype. This translated into an AHR of 1.82 (95% CI, 1.60-2.07). In other findings, the incidence of patchy AA and alopecia totalis and alopecia universalis (AT/AU) was 35.94 and 7.24 per 10,000 PY in patients with COVID-19 compared with 19.43 and 4.18 per 10,000 PY in uninfected controls, respectively.

“These findings support the possible role of COVID-19 in AA occurrence and exacerbation, although other environmental factors, such as psychological stress, may have also contributed to AA development during the pandemic,” the authors concluded. “Plausible mechanisms of AA following COVID-19 include antigenic molecular mimicry between SARS-CoV-2 and hair follicle autoantigens, cytokine shifting, and bystander activation.”

They acknowledged certain limitations of the analysis, including the potential for detection or misclassification bias and the fact that it did not evaluate causality between the two conditions.

Shari Lipner, MD, PhD, associate professor of dermatology at Weill Cornell Medicine, New York, who was asked to comment on the study, said that strengths of the study include the large sample size, and the use of positive and negative outcome controls, and that the incidence and prevalence of AA in Korea was stable during the prepandemic period. “A weakness of the study is that all alopecia areata cases may not have necessarily been confirmed,” Dr. Lipner told this news organization.

“Based on this study, dermatologists may consider AA in the differential diagnosis for a patient presenting with hair loss with recent COVID-19 diagnosis,” she added, noting that the potential for prevention of AA flares is also a reason to recommend COVID-19 vaccination for patients with a history of AA.

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was also asked to comment on the study, said that while the analysis suggests a definite epidemiologic association between COVID-19 and AA, “any causal relationship needs further study.” She added that she has no specific advice for patients who develop AA following a COVID-19 infection. “Any conversation about AA can be difficult because there is no way to prognosticate if someone will just have one small, localized area of hair loss,” or several small areas, versus loss of all hair on the head or even the body as well, Dr. Ko explained.

The study was supported with grants from the National Research Foundation of the Korean Government and the Ministry of Health and Welfare, Republic of Korea. The authors, as well as Dr. Lipner and Dr. Ko, reported having no relevant disclosures.

Infection with COVID-19 conferred a nearly twofold risk of developing alopecia areata (AA), results from a large analysis of Korean patients demonstrated.

“There is a growing number of reports on new onset, exacerbation, and recurrence of AA after COVID-19,” corresponding author Jin Park, MD, PhD, of the department of dermatology at Jeonbuk National University Medical School, South Korea, and colleagues wrote in a research letter published online January 10, 2024, in JAMA Dermatology. “However, evidence supporting an association between COVID-19 and AA is limited.”

To investigate the association between COVID-19 and AA, the researchers used data from the Korea Disease Control and Prevention Agency–COVID-19–National Health Insurance Service cohort to conduct a propensity score–matched, nationwide, population-based cohort study from October 8, 2020, to September 30, 2021. They used Cox proportional hazards regression to calculate the incidence, prevalence, and adjusted hazard ratios (AHRs) for AA.

The cohort consisted of 259,369 patients with COVID-19 and 259,369 uninfected controls. The researchers observed an increased risk of telogen effluvium in patients with COVID-19 compared with the uninfected controls (AHR, 6.40; 95% CI, 4.92-8.33), while the incidence of epidermal cysts, benign skin tumors, and other negative control outcomes did not differ between groups.

Meanwhile, the incidence of AA in patients with COVID-19 was significantly higher compared with the uninfected controls (43.19 per 10,000 person-years [PY]), regardless of clinical subtype. This translated into an AHR of 1.82 (95% CI, 1.60-2.07). In other findings, the incidence of patchy AA and alopecia totalis and alopecia universalis (AT/AU) was 35.94 and 7.24 per 10,000 PY in patients with COVID-19 compared with 19.43 and 4.18 per 10,000 PY in uninfected controls, respectively.

“These findings support the possible role of COVID-19 in AA occurrence and exacerbation, although other environmental factors, such as psychological stress, may have also contributed to AA development during the pandemic,” the authors concluded. “Plausible mechanisms of AA following COVID-19 include antigenic molecular mimicry between SARS-CoV-2 and hair follicle autoantigens, cytokine shifting, and bystander activation.”

They acknowledged certain limitations of the analysis, including the potential for detection or misclassification bias and the fact that it did not evaluate causality between the two conditions.

Shari Lipner, MD, PhD, associate professor of dermatology at Weill Cornell Medicine, New York, who was asked to comment on the study, said that strengths of the study include the large sample size, and the use of positive and negative outcome controls, and that the incidence and prevalence of AA in Korea was stable during the prepandemic period. “A weakness of the study is that all alopecia areata cases may not have necessarily been confirmed,” Dr. Lipner told this news organization.

“Based on this study, dermatologists may consider AA in the differential diagnosis for a patient presenting with hair loss with recent COVID-19 diagnosis,” she added, noting that the potential for prevention of AA flares is also a reason to recommend COVID-19 vaccination for patients with a history of AA.

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was also asked to comment on the study, said that while the analysis suggests a definite epidemiologic association between COVID-19 and AA, “any causal relationship needs further study.” She added that she has no specific advice for patients who develop AA following a COVID-19 infection. “Any conversation about AA can be difficult because there is no way to prognosticate if someone will just have one small, localized area of hair loss,” or several small areas, versus loss of all hair on the head or even the body as well, Dr. Ko explained.

The study was supported with grants from the National Research Foundation of the Korean Government and the Ministry of Health and Welfare, Republic of Korea. The authors, as well as Dr. Lipner and Dr. Ko, reported having no relevant disclosures.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Two doses of the recombinant zoster vaccine (RZV) are effective against herpes zoster (HZ) for 4 years after vaccination, according to a new study published in Annals of Internal Medicine.

Findings from the prospective cohort study showed that people who received two doses of the vaccine, regardless of when they received their second dose, experienced 79% vaccine effectiveness (VE) during the first year, with effectiveness decreasing to 73% by year 4. By contrast, the rate of effectiveness during the first year was 70% for people who received a single dose, falling to 52% effectiveness by year 4.

The findings also showed that the rate of effectiveness was 65% for those taking corticosteroids.

The study was conducted between 2018 and 2022 using data from the Vaccine Safety Datalink, a collaboration between the US Centers for Disease Control and Prevention (CDC) and nine healthcare systems across the country.

Researchers evaluated the incidence of HZ, as determined by a diagnosis and prescription for antiviral medication within 7 days of diagnosis, and monitored RZV status over time.

The findings may quell fears that waiting too long for the second dose reduces the effectiveness of the herpes vaccine, according to Nicola Klein, MD, PhD, director of the Vaccine Study Center at Kaiser Permanente in Oakland, California, who led the study.

The long-term efficacy of the vaccine is especially important because older adults are now living much longer than in previous years, according to Alexandra Tien, MD, a family physician at Medical Associates of Rhode Island in Providence.

“People live these days into their 80s and even 90s,” Dr. Tien said. “That’s a large number of years to need protection for, so it’s really important to have a long-lasting vaccine.”

The CDC currently recommends two doses of RZV separated by 2-6 months for patients aged 50 years and older. Adults older than 19 years who are immunocompromised should receive two doses of RZV separated by 1-2 months, the agency said.

According to Dr. Klein, research does not show whether VE for RZV wanes after 4 years. But interim findings from another study following people in clinical trials found VE levels remained high after 7 years.

The risk for HZ increases with age, reaching a lifetime risk of 50% among adults aged 85 years. Complications like postherpetic neuralgia (PHN) — characterized by long-term tingling, numbness, and disabling pain at the site of the rash — can interfere with the quality of life and ability to function in older adults. The CDC estimates that up to 18% of people with shingles experience PHN, and the risk increases with age.

Just like with any other vaccine, patients sometimes have concerns about the potential side effects of RZV, said Dr. Tien. But those effects, such as muscle pain, nausea, and fever, are mild compared to shingles.

“I always tell patients, with any vaccine, immunization is one of the biggest bangs for your buck in healthcare because you’re preventing a problem,” Dr. Tien said.

This study was funded by the CDC through contracts with participating sites. Study authors reported no disclosures. Dr. Tien reported no disclosures.

A version of this article appeared on Medscape.com.

Two doses of the recombinant zoster vaccine (RZV) are effective against herpes zoster (HZ) for 4 years after vaccination, according to a new study published in Annals of Internal Medicine.

Findings from the prospective cohort study showed that people who received two doses of the vaccine, regardless of when they received their second dose, experienced 79% vaccine effectiveness (VE) during the first year, with effectiveness decreasing to 73% by year 4. By contrast, the rate of effectiveness during the first year was 70% for people who received a single dose, falling to 52% effectiveness by year 4.

The findings also showed that the rate of effectiveness was 65% for those taking corticosteroids.

The study was conducted between 2018 and 2022 using data from the Vaccine Safety Datalink, a collaboration between the US Centers for Disease Control and Prevention (CDC) and nine healthcare systems across the country.

Researchers evaluated the incidence of HZ, as determined by a diagnosis and prescription for antiviral medication within 7 days of diagnosis, and monitored RZV status over time.

The findings may quell fears that waiting too long for the second dose reduces the effectiveness of the herpes vaccine, according to Nicola Klein, MD, PhD, director of the Vaccine Study Center at Kaiser Permanente in Oakland, California, who led the study.

The long-term efficacy of the vaccine is especially important because older adults are now living much longer than in previous years, according to Alexandra Tien, MD, a family physician at Medical Associates of Rhode Island in Providence.

“People live these days into their 80s and even 90s,” Dr. Tien said. “That’s a large number of years to need protection for, so it’s really important to have a long-lasting vaccine.”

The CDC currently recommends two doses of RZV separated by 2-6 months for patients aged 50 years and older. Adults older than 19 years who are immunocompromised should receive two doses of RZV separated by 1-2 months, the agency said.

According to Dr. Klein, research does not show whether VE for RZV wanes after 4 years. But interim findings from another study following people in clinical trials found VE levels remained high after 7 years.

The risk for HZ increases with age, reaching a lifetime risk of 50% among adults aged 85 years. Complications like postherpetic neuralgia (PHN) — characterized by long-term tingling, numbness, and disabling pain at the site of the rash — can interfere with the quality of life and ability to function in older adults. The CDC estimates that up to 18% of people with shingles experience PHN, and the risk increases with age.

Just like with any other vaccine, patients sometimes have concerns about the potential side effects of RZV, said Dr. Tien. But those effects, such as muscle pain, nausea, and fever, are mild compared to shingles.

“I always tell patients, with any vaccine, immunization is one of the biggest bangs for your buck in healthcare because you’re preventing a problem,” Dr. Tien said.

This study was funded by the CDC through contracts with participating sites. Study authors reported no disclosures. Dr. Tien reported no disclosures.

A version of this article appeared on Medscape.com.

Two doses of the recombinant zoster vaccine (RZV) are effective against herpes zoster (HZ) for 4 years after vaccination, according to a new study published in Annals of Internal Medicine.

Findings from the prospective cohort study showed that people who received two doses of the vaccine, regardless of when they received their second dose, experienced 79% vaccine effectiveness (VE) during the first year, with effectiveness decreasing to 73% by year 4. By contrast, the rate of effectiveness during the first year was 70% for people who received a single dose, falling to 52% effectiveness by year 4.

The findings also showed that the rate of effectiveness was 65% for those taking corticosteroids.

The study was conducted between 2018 and 2022 using data from the Vaccine Safety Datalink, a collaboration between the US Centers for Disease Control and Prevention (CDC) and nine healthcare systems across the country.

Researchers evaluated the incidence of HZ, as determined by a diagnosis and prescription for antiviral medication within 7 days of diagnosis, and monitored RZV status over time.

The findings may quell fears that waiting too long for the second dose reduces the effectiveness of the herpes vaccine, according to Nicola Klein, MD, PhD, director of the Vaccine Study Center at Kaiser Permanente in Oakland, California, who led the study.

The long-term efficacy of the vaccine is especially important because older adults are now living much longer than in previous years, according to Alexandra Tien, MD, a family physician at Medical Associates of Rhode Island in Providence.

“People live these days into their 80s and even 90s,” Dr. Tien said. “That’s a large number of years to need protection for, so it’s really important to have a long-lasting vaccine.”

The CDC currently recommends two doses of RZV separated by 2-6 months for patients aged 50 years and older. Adults older than 19 years who are immunocompromised should receive two doses of RZV separated by 1-2 months, the agency said.

According to Dr. Klein, research does not show whether VE for RZV wanes after 4 years. But interim findings from another study following people in clinical trials found VE levels remained high after 7 years.

The risk for HZ increases with age, reaching a lifetime risk of 50% among adults aged 85 years. Complications like postherpetic neuralgia (PHN) — characterized by long-term tingling, numbness, and disabling pain at the site of the rash — can interfere with the quality of life and ability to function in older adults. The CDC estimates that up to 18% of people with shingles experience PHN, and the risk increases with age.

Just like with any other vaccine, patients sometimes have concerns about the potential side effects of RZV, said Dr. Tien. But those effects, such as muscle pain, nausea, and fever, are mild compared to shingles.

“I always tell patients, with any vaccine, immunization is one of the biggest bangs for your buck in healthcare because you’re preventing a problem,” Dr. Tien said.

This study was funded by the CDC through contracts with participating sites. Study authors reported no disclosures. Dr. Tien reported no disclosures.

A version of this article appeared on Medscape.com.

You may have never heard of it, but you may have had it. More evidence points to “long flu” being a real phenomenon, with a large study showing symptoms persist at least 4 weeks or more after some people are hospitalized for the flu.

Researchers compared long flu to long COVID-19 and found long flu happened less often and was less severe overall. This difference could be because the flu mostly affects the lungs whereas COVID can affect any number of organ systems in the body.

The investigators were surprised that both long flu and long COVID were linked to a greater burden of health loss, compared to either initial infection.

“I think COVID and long COVID made us realize that infections have long-term consequences, and often the toll of those long-term consequences is much larger than the toll of acute disease,” said Ziyad Al-Aly, MD, senior author of the study and chief of research and development at the VA St. Louis Health Care System.

“I know, having studied long COVID for the past 4 years, I should not be surprised. But I am in awe of what these infections can do to the long-term health of affected individuals,” said Dr. Al-Aly, who is also a clinical epidemiologist at Washington University in St. Louis.

Dr. Al-Aly and colleagues Yan Xie, PhD, and Taeyoung Choi, MS, analyzed US Department of Veterans Affairs medical records. They compared 81,280 people hospitalized with COVID to 10,985 people hospitalized with the flu before the COVID pandemic. They checked up to 18 months after initial infections to see who developed long flu or long COVID symptoms.

The study was published online in The Lancet Infectious Diseases.

It’s an interesting study, said Aaron E. Glatt, MD, chairman of the Department of Medicine and a hospital epidemiologist at Mount Sinai South Nassau in Oceanside, NY, who was not part of the research.

“There is a concern with many viruses that you can have long-term consequences,” said Dr. Glatt, who is also a fellow of the Infectious Diseases Society of America. He said the possibility of long-term symptoms with the flu is not new, “but it’s nice to have more data.”

People hospitalized with COVID had a 50% higher risk of death during the study period than people hospitalized with the flu. Put another way, for every 100 people admitted to the hospital with COVID, about eight more died than those hospitalized with the flu over the following 18 months. Hospital admissions and admissions to the intensive care unit were also higher in the long COVID group — 20 more people and nine more people, respectively, for every 100 people admitted to the hospital with COVID.

More research is needed, Dr. Glatt said. “With many of these viruses, we don’t understand what they do to the body.” A prospective study to see if antiviral treatments make a difference, for example, would be useful, he noted.

Dr. Al-Aly and colleagues would like to do more studies.

“We need to more deeply understand how and why acute infections cause long-term illness,” he said, noting that he also wants to investigate ways to prevent and treat the long-term effects.

“Much remains to be done, and we are deeply committed to doing our best to develop those answers.”

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

You may have never heard of it, but you may have had it. More evidence points to “long flu” being a real phenomenon, with a large study showing symptoms persist at least 4 weeks or more after some people are hospitalized for the flu.

Researchers compared long flu to long COVID-19 and found long flu happened less often and was less severe overall. This difference could be because the flu mostly affects the lungs whereas COVID can affect any number of organ systems in the body.

The investigators were surprised that both long flu and long COVID were linked to a greater burden of health loss, compared to either initial infection.

“I think COVID and long COVID made us realize that infections have long-term consequences, and often the toll of those long-term consequences is much larger than the toll of acute disease,” said Ziyad Al-Aly, MD, senior author of the study and chief of research and development at the VA St. Louis Health Care System.

“I know, having studied long COVID for the past 4 years, I should not be surprised. But I am in awe of what these infections can do to the long-term health of affected individuals,” said Dr. Al-Aly, who is also a clinical epidemiologist at Washington University in St. Louis.

Dr. Al-Aly and colleagues Yan Xie, PhD, and Taeyoung Choi, MS, analyzed US Department of Veterans Affairs medical records. They compared 81,280 people hospitalized with COVID to 10,985 people hospitalized with the flu before the COVID pandemic. They checked up to 18 months after initial infections to see who developed long flu or long COVID symptoms.

The study was published online in The Lancet Infectious Diseases.

It’s an interesting study, said Aaron E. Glatt, MD, chairman of the Department of Medicine and a hospital epidemiologist at Mount Sinai South Nassau in Oceanside, NY, who was not part of the research.

“There is a concern with many viruses that you can have long-term consequences,” said Dr. Glatt, who is also a fellow of the Infectious Diseases Society of America. He said the possibility of long-term symptoms with the flu is not new, “but it’s nice to have more data.”

People hospitalized with COVID had a 50% higher risk of death during the study period than people hospitalized with the flu. Put another way, for every 100 people admitted to the hospital with COVID, about eight more died than those hospitalized with the flu over the following 18 months. Hospital admissions and admissions to the intensive care unit were also higher in the long COVID group — 20 more people and nine more people, respectively, for every 100 people admitted to the hospital with COVID.

More research is needed, Dr. Glatt said. “With many of these viruses, we don’t understand what they do to the body.” A prospective study to see if antiviral treatments make a difference, for example, would be useful, he noted.

Dr. Al-Aly and colleagues would like to do more studies.

“We need to more deeply understand how and why acute infections cause long-term illness,” he said, noting that he also wants to investigate ways to prevent and treat the long-term effects.

“Much remains to be done, and we are deeply committed to doing our best to develop those answers.”

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

You may have never heard of it, but you may have had it. More evidence points to “long flu” being a real phenomenon, with a large study showing symptoms persist at least 4 weeks or more after some people are hospitalized for the flu.

Researchers compared long flu to long COVID-19 and found long flu happened less often and was less severe overall. This difference could be because the flu mostly affects the lungs whereas COVID can affect any number of organ systems in the body.

The investigators were surprised that both long flu and long COVID were linked to a greater burden of health loss, compared to either initial infection.

“I think COVID and long COVID made us realize that infections have long-term consequences, and often the toll of those long-term consequences is much larger than the toll of acute disease,” said Ziyad Al-Aly, MD, senior author of the study and chief of research and development at the VA St. Louis Health Care System.

“I know, having studied long COVID for the past 4 years, I should not be surprised. But I am in awe of what these infections can do to the long-term health of affected individuals,” said Dr. Al-Aly, who is also a clinical epidemiologist at Washington University in St. Louis.

Dr. Al-Aly and colleagues Yan Xie, PhD, and Taeyoung Choi, MS, analyzed US Department of Veterans Affairs medical records. They compared 81,280 people hospitalized with COVID to 10,985 people hospitalized with the flu before the COVID pandemic. They checked up to 18 months after initial infections to see who developed long flu or long COVID symptoms.

The study was published online in The Lancet Infectious Diseases.

It’s an interesting study, said Aaron E. Glatt, MD, chairman of the Department of Medicine and a hospital epidemiologist at Mount Sinai South Nassau in Oceanside, NY, who was not part of the research.

“There is a concern with many viruses that you can have long-term consequences,” said Dr. Glatt, who is also a fellow of the Infectious Diseases Society of America. He said the possibility of long-term symptoms with the flu is not new, “but it’s nice to have more data.”

People hospitalized with COVID had a 50% higher risk of death during the study period than people hospitalized with the flu. Put another way, for every 100 people admitted to the hospital with COVID, about eight more died than those hospitalized with the flu over the following 18 months. Hospital admissions and admissions to the intensive care unit were also higher in the long COVID group — 20 more people and nine more people, respectively, for every 100 people admitted to the hospital with COVID.

More research is needed, Dr. Glatt said. “With many of these viruses, we don’t understand what they do to the body.” A prospective study to see if antiviral treatments make a difference, for example, would be useful, he noted.

Dr. Al-Aly and colleagues would like to do more studies.

“We need to more deeply understand how and why acute infections cause long-term illness,” he said, noting that he also wants to investigate ways to prevent and treat the long-term effects.

“Much remains to be done, and we are deeply committed to doing our best to develop those answers.”

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

TOPLINE:

After lung cancer screening (LCS), imaging, and invasive procedures were performed 31.9% and 2.8% of the time, respectively. Complications during invasive procedures occurred in 30.6% of cases. 

METHODOLOGY:

• Researchers analyzed data from 9266 patients aged 55-80 years who completed at least one LCS with low-dose CT (LDCT) between 2014 and 2018.
• This study used data from the PROSPR Lung Consortium.
• Results were compared with findings from the National Lung Screening Trial (NLST), a large study of smokers published in 2011.

TAKEAWAY:

• In total, 2956 patients (31.9%) underwent follow-up imaging, including CT, LDCT, MRI, or PET; 180 (0.02%) had invasive procedures, including needle biopsy, bronchoscopy, mediastinoscopy or mediastinotomy, or thoracoscopy.
• Within 30 days after an invasive diagnostic procedure, 55 of 180 patients (30.6%) experienced complications; 20.6% were major, 8.3% were intermediate, and 1.7% were minor.
• Complication rates after invasive procedures were higher in PROSPR than the NLST (30.6% vs 17.7%).
• Compared with all patients, those with an abnormal LCS were slightly older, more likely to currently smoke, reported more packs of cigarettes smoked daily, and had more comorbid conditions.
• In 2013, the US Preventive Services Task Force recommended annual LCS for certain people who smoke, on the basis of findings from the NLST.

IN PRACTICE:

“We observed higher rates of both invasive procedures and complications than those observed in NLST, highlighting the need for practice-based strategies to assess variations in the quality of care and to prioritize LCS among those patients most likely to receive a net benefit from screening in relation to potential complications and other harms,” the researchers wrote. 

SOURCE:

Katharine A. Rendle, PhD, MSW, MPH, with Perelman School of Medicine, University of Pennsylvania, is the study’s corresponding author. The study was published online in Annals of Internal Medicine.

LIMITATIONS:

This study was retrospective, and data were analyzed using procedural coding. In addition, the NLST based abnormal findings on different criteria from those used in clinical practice (Lung-RADS), making direct comparison of patients difficult. Patients in PROSPR were older, more likely to be currently smoking, and had higher rates of comorbid conditions compared with patients in the NLST. 

DISCLOSURES:

This study was supported by grants from the National Cancer Institute and the Gordon and Betty Moore Foundation.

TOPLINE:

After lung cancer screening (LCS), imaging, and invasive procedures were performed 31.9% and 2.8% of the time, respectively. Complications during invasive procedures occurred in 30.6% of cases. 

METHODOLOGY:

• Researchers analyzed data from 9266 patients aged 55-80 years who completed at least one LCS with low-dose CT (LDCT) between 2014 and 2018.
• This study used data from the PROSPR Lung Consortium.
• Results were compared with findings from the National Lung Screening Trial (NLST), a large study of smokers published in 2011.

TAKEAWAY:

• In total, 2956 patients (31.9%) underwent follow-up imaging, including CT, LDCT, MRI, or PET; 180 (0.02%) had invasive procedures, including needle biopsy, bronchoscopy, mediastinoscopy or mediastinotomy, or thoracoscopy.
• Within 30 days after an invasive diagnostic procedure, 55 of 180 patients (30.6%) experienced complications; 20.6% were major, 8.3% were intermediate, and 1.7% were minor.
• Complication rates after invasive procedures were higher in PROSPR than the NLST (30.6% vs 17.7%).
• Compared with all patients, those with an abnormal LCS were slightly older, more likely to currently smoke, reported more packs of cigarettes smoked daily, and had more comorbid conditions.
• In 2013, the US Preventive Services Task Force recommended annual LCS for certain people who smoke, on the basis of findings from the NLST.

IN PRACTICE:

“We observed higher rates of both invasive procedures and complications than those observed in NLST, highlighting the need for practice-based strategies to assess variations in the quality of care and to prioritize LCS among those patients most likely to receive a net benefit from screening in relation to potential complications and other harms,” the researchers wrote. 

SOURCE:

Katharine A. Rendle, PhD, MSW, MPH, with Perelman School of Medicine, University of Pennsylvania, is the study’s corresponding author. The study was published online in Annals of Internal Medicine.

LIMITATIONS:

This study was retrospective, and data were analyzed using procedural coding. In addition, the NLST based abnormal findings on different criteria from those used in clinical practice (Lung-RADS), making direct comparison of patients difficult. Patients in PROSPR were older, more likely to be currently smoking, and had higher rates of comorbid conditions compared with patients in the NLST. 

DISCLOSURES:

This study was supported by grants from the National Cancer Institute and the Gordon and Betty Moore Foundation.

TOPLINE:

After lung cancer screening (LCS), imaging, and invasive procedures were performed 31.9% and 2.8% of the time, respectively. Complications during invasive procedures occurred in 30.6% of cases. 

METHODOLOGY:

• Researchers analyzed data from 9266 patients aged 55-80 years who completed at least one LCS with low-dose CT (LDCT) between 2014 and 2018.
• This study used data from the PROSPR Lung Consortium.
• Results were compared with findings from the National Lung Screening Trial (NLST), a large study of smokers published in 2011.

TAKEAWAY:

• In total, 2956 patients (31.9%) underwent follow-up imaging, including CT, LDCT, MRI, or PET; 180 (0.02%) had invasive procedures, including needle biopsy, bronchoscopy, mediastinoscopy or mediastinotomy, or thoracoscopy.
• Within 30 days after an invasive diagnostic procedure, 55 of 180 patients (30.6%) experienced complications; 20.6% were major, 8.3% were intermediate, and 1.7% were minor.
• Complication rates after invasive procedures were higher in PROSPR than the NLST (30.6% vs 17.7%).
• Compared with all patients, those with an abnormal LCS were slightly older, more likely to currently smoke, reported more packs of cigarettes smoked daily, and had more comorbid conditions.
• In 2013, the US Preventive Services Task Force recommended annual LCS for certain people who smoke, on the basis of findings from the NLST.

IN PRACTICE:

“We observed higher rates of both invasive procedures and complications than those observed in NLST, highlighting the need for practice-based strategies to assess variations in the quality of care and to prioritize LCS among those patients most likely to receive a net benefit from screening in relation to potential complications and other harms,” the researchers wrote. 

SOURCE:

Katharine A. Rendle, PhD, MSW, MPH, with Perelman School of Medicine, University of Pennsylvania, is the study’s corresponding author. The study was published online in Annals of Internal Medicine.

LIMITATIONS:

This study was retrospective, and data were analyzed using procedural coding. In addition, the NLST based abnormal findings on different criteria from those used in clinical practice (Lung-RADS), making direct comparison of patients difficult. Patients in PROSPR were older, more likely to be currently smoking, and had higher rates of comorbid conditions compared with patients in the NLST. 

DISCLOSURES:

This study was supported by grants from the National Cancer Institute and the Gordon and Betty Moore Foundation.

TOPLINE:

Surgery or radiation for advanced prostate cancer may improve survival but at the cost of treatment-related adverse effects, including gastrointestinal (GI) as well as sexual and urinary conditions, that may persist for years, a study of US veterans showed.

METHODOLOGY:

Recent evidence suggested that in men with advanced prostate cancer, local therapy with radical prostatectomy or radiation may improve survival outcomes; however, data on the long-term side effects from these local options were limited.

The retrospective cohort included 5502 men (mean age, 68 years) diagnosed with advanced (T4, N1, and/or M1) prostate cancer.

A total of 1705 men (31%) received initial local treatment, consisting of radical prostatectomy, (55%), radiation (39%), or both (5.6%), while 3797 (69%) opted for initial nonlocal treatment (hormone therapy, chemotherapy, or both). 

The main outcomes were treatment-related adverse effects, including GI, chronic pain, sexual dysfunction, and urinary symptoms, assessed at three timepoints after initial treatment — up to 1 year, between 1 and 2 years, and between 2 and 5 years.

TAKEAWAY:

Overall, 916 men (75%) who had initial local treatment and 897 men (67%) with initial nonlocal therapy reported at least one adverse condition up to 5 years after initial treatment.

In the first year after initial treatment, local therapy was associated with a higher prevalence of GI (9% vs 3%), pain (60% vs 38%), sexual (37% vs 8%), and urinary (46.5% vs 18%) conditions. Men receiving local therapy were more likely to experience GI (adjusted odds ratio [aOR], 4.08), pain (aOR, 1.57), sexual (aOR, 2.96), and urinary (aOR, 2.25) conditions.

Between 2 and 5 years after local therapy, certain conditions remained more prevalent — 7.8% vs 4.2% for GI, 40% vs 13% for sexual, and 40.5% vs 26% for urinary issues. Men receiving local vs nonlocal therapy were more likely to experience GI (aOR, 2.39), sexual (aOR, 3.36), and urinary (aOR, 1.39) issues over the long term.

The researchers found no difference in the prevalence of constitutional conditions such as hot flashes (36.5% vs 34.4%) in the first year following initial local or nonlocal therapy. However, local treatment followed by any secondary treatment was associated with a higher likelihood of developing constitutional conditions at 1-2 years (aOR, 1.50) and 2-5 years (aOR, 1.78) after initial treatment.

IN PRACTICE:

“These results suggest that patients and clinicians should consider the adverse effects of local treatment” alongside the potential for enhanced survival when making treatment decisions in the setting of advanced prostate cancer, the authors explained. Careful informed decision-making by both patients and practitioners is especially important because “there are currently no established guidelines regarding the use of local treatment among men with advanced prostate cancer.”

SOURCE:

The study, with first author Saira Khan, PhD, MPH, Washington University School of Medicine in St. Louis, Missouri, was published online in JAMA Network Open.

LIMITATIONS:

The authors noted that the study was limited by its retrospective design. Men who received local treatment were, on average, younger; older or lesser healthy patients who received local treatment may experience worse adverse effects than observed in the study. The study was limited to US veterans.

DISCLOSURES:

The study was supported by a grant from the US Department of Defense. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Surgery or radiation for advanced prostate cancer may improve survival but at the cost of treatment-related adverse effects, including gastrointestinal (GI) as well as sexual and urinary conditions, that may persist for years, a study of US veterans showed.

METHODOLOGY:

Recent evidence suggested that in men with advanced prostate cancer, local therapy with radical prostatectomy or radiation may improve survival outcomes; however, data on the long-term side effects from these local options were limited.

The retrospective cohort included 5502 men (mean age, 68 years) diagnosed with advanced (T4, N1, and/or M1) prostate cancer.

A total of 1705 men (31%) received initial local treatment, consisting of radical prostatectomy, (55%), radiation (39%), or both (5.6%), while 3797 (69%) opted for initial nonlocal treatment (hormone therapy, chemotherapy, or both). 

The main outcomes were treatment-related adverse effects, including GI, chronic pain, sexual dysfunction, and urinary symptoms, assessed at three timepoints after initial treatment — up to 1 year, between 1 and 2 years, and between 2 and 5 years.

TAKEAWAY:

Overall, 916 men (75%) who had initial local treatment and 897 men (67%) with initial nonlocal therapy reported at least one adverse condition up to 5 years after initial treatment.

In the first year after initial treatment, local therapy was associated with a higher prevalence of GI (9% vs 3%), pain (60% vs 38%), sexual (37% vs 8%), and urinary (46.5% vs 18%) conditions. Men receiving local therapy were more likely to experience GI (adjusted odds ratio [aOR], 4.08), pain (aOR, 1.57), sexual (aOR, 2.96), and urinary (aOR, 2.25) conditions.

Between 2 and 5 years after local therapy, certain conditions remained more prevalent — 7.8% vs 4.2% for GI, 40% vs 13% for sexual, and 40.5% vs 26% for urinary issues. Men receiving local vs nonlocal therapy were more likely to experience GI (aOR, 2.39), sexual (aOR, 3.36), and urinary (aOR, 1.39) issues over the long term.

The researchers found no difference in the prevalence of constitutional conditions such as hot flashes (36.5% vs 34.4%) in the first year following initial local or nonlocal therapy. However, local treatment followed by any secondary treatment was associated with a higher likelihood of developing constitutional conditions at 1-2 years (aOR, 1.50) and 2-5 years (aOR, 1.78) after initial treatment.

IN PRACTICE:

“These results suggest that patients and clinicians should consider the adverse effects of local treatment” alongside the potential for enhanced survival when making treatment decisions in the setting of advanced prostate cancer, the authors explained. Careful informed decision-making by both patients and practitioners is especially important because “there are currently no established guidelines regarding the use of local treatment among men with advanced prostate cancer.”

SOURCE:

The study, with first author Saira Khan, PhD, MPH, Washington University School of Medicine in St. Louis, Missouri, was published online in JAMA Network Open.

LIMITATIONS:

The authors noted that the study was limited by its retrospective design. Men who received local treatment were, on average, younger; older or lesser healthy patients who received local treatment may experience worse adverse effects than observed in the study. The study was limited to US veterans.

DISCLOSURES:

The study was supported by a grant from the US Department of Defense. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Surgery or radiation for advanced prostate cancer may improve survival but at the cost of treatment-related adverse effects, including gastrointestinal (GI) as well as sexual and urinary conditions, that may persist for years, a study of US veterans showed.

METHODOLOGY:

Recent evidence suggested that in men with advanced prostate cancer, local therapy with radical prostatectomy or radiation may improve survival outcomes; however, data on the long-term side effects from these local options were limited.

The retrospective cohort included 5502 men (mean age, 68 years) diagnosed with advanced (T4, N1, and/or M1) prostate cancer.

A total of 1705 men (31%) received initial local treatment, consisting of radical prostatectomy, (55%), radiation (39%), or both (5.6%), while 3797 (69%) opted for initial nonlocal treatment (hormone therapy, chemotherapy, or both). 

The main outcomes were treatment-related adverse effects, including GI, chronic pain, sexual dysfunction, and urinary symptoms, assessed at three timepoints after initial treatment — up to 1 year, between 1 and 2 years, and between 2 and 5 years.

TAKEAWAY:

Overall, 916 men (75%) who had initial local treatment and 897 men (67%) with initial nonlocal therapy reported at least one adverse condition up to 5 years after initial treatment.

In the first year after initial treatment, local therapy was associated with a higher prevalence of GI (9% vs 3%), pain (60% vs 38%), sexual (37% vs 8%), and urinary (46.5% vs 18%) conditions. Men receiving local therapy were more likely to experience GI (adjusted odds ratio [aOR], 4.08), pain (aOR, 1.57), sexual (aOR, 2.96), and urinary (aOR, 2.25) conditions.

Between 2 and 5 years after local therapy, certain conditions remained more prevalent — 7.8% vs 4.2% for GI, 40% vs 13% for sexual, and 40.5% vs 26% for urinary issues. Men receiving local vs nonlocal therapy were more likely to experience GI (aOR, 2.39), sexual (aOR, 3.36), and urinary (aOR, 1.39) issues over the long term.

The researchers found no difference in the prevalence of constitutional conditions such as hot flashes (36.5% vs 34.4%) in the first year following initial local or nonlocal therapy. However, local treatment followed by any secondary treatment was associated with a higher likelihood of developing constitutional conditions at 1-2 years (aOR, 1.50) and 2-5 years (aOR, 1.78) after initial treatment.

IN PRACTICE:

“These results suggest that patients and clinicians should consider the adverse effects of local treatment” alongside the potential for enhanced survival when making treatment decisions in the setting of advanced prostate cancer, the authors explained. Careful informed decision-making by both patients and practitioners is especially important because “there are currently no established guidelines regarding the use of local treatment among men with advanced prostate cancer.”

SOURCE:

The study, with first author Saira Khan, PhD, MPH, Washington University School of Medicine in St. Louis, Missouri, was published online in JAMA Network Open.

LIMITATIONS:

The authors noted that the study was limited by its retrospective design. Men who received local treatment were, on average, younger; older or lesser healthy patients who received local treatment may experience worse adverse effects than observed in the study. The study was limited to US veterans.

DISCLOSURES:

The study was supported by a grant from the US Department of Defense. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

In addition to better known risk factors such as diabetes, stroke, heart disease, and depression, findings of a large study suggested vitamin D deficiency, elevated C-reactive protein (CRP) levels, and social isolation increase the risk for young-onset dementia (YOD).

METHODOLOGY:

• The study included 356,052 participants younger than 65 years (mean baseline age, 54.6 years) without dementia from the UK Biobank, an ongoing prospective cohort study.
• Participants underwent a comprehensive baseline assessment, provided biological samples, completed touch screen questionnaires, and underwent a physical examination.
• Researchers identified incident all-cause YOD cases from hospital inpatient registers or death register linkage.
• The researchers detected 39 potential risk factors and grouped them into domains of sociodemographic, genetic, lifestyle, environmental, vitamin D and CRP levels, cardiometabolic, psychiatric, and other factors.
• Researchers analyzed incidence rates of YOD for 5-year age bands starting at age 40 years and separately for men and women.

TAKEAWAY:

• During a mean follow-up of 8.12 years, there were 485 incident YOD cases (incidence rate of 16.8 per 100,000 person-years; 95% CI 15.4-18.3).
• The final analysis identified 15 risk factors associated with significantly higher incidence of YOD, including traditional factors like stroke (hazard ratio [HR], 2.07), heart disease (HR, 1.61), diabetes (HR, 1.65), and depression (HR, 3.25) but also less-recognized risk factors like vitamin D deficiency (< 10 ng/mL; HR, 1.59), high CRP levels (> 1 mg/dL; HR, 1.54), and social isolation (infrequent visits to friends or family; HR, 1.53), with lower socioeconomic status (HR, 1.82), having two apolipoprotein E epsilon-4 alleles (HR, 1.87), orthostatic hypotension, which the authors said may be an early sign of Parkinson dementia or Lewy body dementia (HR, 4.20), and hearing impairment (HR, 1.56) also increasing risk.
• Interestingly, some alcohol use seemed to be protective (moderate or heavy alcohol use had a lower association with YOD than alcohol abstinence, possibly due to the “healthy drinker effect” where people who drink are healthier than abstainers who may have illnesses preventing them from drinking, said the authors), as was higher education level and higher than normative handgrip strength (less strength is a proxy for physical frailty).
• Men with diabetes had higher YOD risk than those without diabetes, while there was no association with diabetes in women; on the other hand, women with high CRP levels had greater YOD risk than those with low levels, while there was no association with CRP in men.

IN PRACTICE:

“While further exploration of these risk factors is necessary to identify potential underlying mechanisms, addressing these modifiable factors may prove effective in mitigating the risk of developing YOD and can be readily integrated in current dementia prevention initiatives,” the investigators wrote.

SOURCE:

The study was led by Stevie Hendriks, PhD, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands. It was published online in JAMA Neurology.

LIMITATIONS:

The study was observational and so can’t infer causality. Several factors were based on self-reported data, which might be a source of response bias. Factors not considered in the study, for example, family history of dementia and drug (other than alcohol) use disorder, may have confounded associations. Some factors including orthostatic hypotension had few exposed cases, leading to decreased power to detect associations. Hospital and death records may not have captured all YOD cases. The UK Biobank is overrepresented by healthy and White participants, so results may not be generalizable to other racial and ethnic groups. The analyses only focused on all-cause dementia.

DISCLOSURES:

The study was supported by Alzheimer Netherlands. Hendriks has no relevant conflicts of interest; see paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

TOPLINE:

In addition to better known risk factors such as diabetes, stroke, heart disease, and depression, findings of a large study suggested vitamin D deficiency, elevated C-reactive protein (CRP) levels, and social isolation increase the risk for young-onset dementia (YOD).

METHODOLOGY:

• The study included 356,052 participants younger than 65 years (mean baseline age, 54.6 years) without dementia from the UK Biobank, an ongoing prospective cohort study.
• Participants underwent a comprehensive baseline assessment, provided biological samples, completed touch screen questionnaires, and underwent a physical examination.
• Researchers identified incident all-cause YOD cases from hospital inpatient registers or death register linkage.
• The researchers detected 39 potential risk factors and grouped them into domains of sociodemographic, genetic, lifestyle, environmental, vitamin D and CRP levels, cardiometabolic, psychiatric, and other factors.
• Researchers analyzed incidence rates of YOD for 5-year age bands starting at age 40 years and separately for men and women.

TAKEAWAY:

• During a mean follow-up of 8.12 years, there were 485 incident YOD cases (incidence rate of 16.8 per 100,000 person-years; 95% CI 15.4-18.3).
• The final analysis identified 15 risk factors associated with significantly higher incidence of YOD, including traditional factors like stroke (hazard ratio [HR], 2.07), heart disease (HR, 1.61), diabetes (HR, 1.65), and depression (HR, 3.25) but also less-recognized risk factors like vitamin D deficiency (< 10 ng/mL; HR, 1.59), high CRP levels (> 1 mg/dL; HR, 1.54), and social isolation (infrequent visits to friends or family; HR, 1.53), with lower socioeconomic status (HR, 1.82), having two apolipoprotein E epsilon-4 alleles (HR, 1.87), orthostatic hypotension, which the authors said may be an early sign of Parkinson dementia or Lewy body dementia (HR, 4.20), and hearing impairment (HR, 1.56) also increasing risk.
• Interestingly, some alcohol use seemed to be protective (moderate or heavy alcohol use had a lower association with YOD than alcohol abstinence, possibly due to the “healthy drinker effect” where people who drink are healthier than abstainers who may have illnesses preventing them from drinking, said the authors), as was higher education level and higher than normative handgrip strength (less strength is a proxy for physical frailty).
• Men with diabetes had higher YOD risk than those without diabetes, while there was no association with diabetes in women; on the other hand, women with high CRP levels had greater YOD risk than those with low levels, while there was no association with CRP in men.

IN PRACTICE:

“While further exploration of these risk factors is necessary to identify potential underlying mechanisms, addressing these modifiable factors may prove effective in mitigating the risk of developing YOD and can be readily integrated in current dementia prevention initiatives,” the investigators wrote.

SOURCE:

The study was led by Stevie Hendriks, PhD, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands. It was published online in JAMA Neurology.

LIMITATIONS:

The study was observational and so can’t infer causality. Several factors were based on self-reported data, which might be a source of response bias. Factors not considered in the study, for example, family history of dementia and drug (other than alcohol) use disorder, may have confounded associations. Some factors including orthostatic hypotension had few exposed cases, leading to decreased power to detect associations. Hospital and death records may not have captured all YOD cases. The UK Biobank is overrepresented by healthy and White participants, so results may not be generalizable to other racial and ethnic groups. The analyses only focused on all-cause dementia.

DISCLOSURES:

The study was supported by Alzheimer Netherlands. Hendriks has no relevant conflicts of interest; see paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

TOPLINE:

In addition to better known risk factors such as diabetes, stroke, heart disease, and depression, findings of a large study suggested vitamin D deficiency, elevated C-reactive protein (CRP) levels, and social isolation increase the risk for young-onset dementia (YOD).

METHODOLOGY:

• The study included 356,052 participants younger than 65 years (mean baseline age, 54.6 years) without dementia from the UK Biobank, an ongoing prospective cohort study.
• Participants underwent a comprehensive baseline assessment, provided biological samples, completed touch screen questionnaires, and underwent a physical examination.
• Researchers identified incident all-cause YOD cases from hospital inpatient registers or death register linkage.
• The researchers detected 39 potential risk factors and grouped them into domains of sociodemographic, genetic, lifestyle, environmental, vitamin D and CRP levels, cardiometabolic, psychiatric, and other factors.
• Researchers analyzed incidence rates of YOD for 5-year age bands starting at age 40 years and separately for men and women.

TAKEAWAY:

• During a mean follow-up of 8.12 years, there were 485 incident YOD cases (incidence rate of 16.8 per 100,000 person-years; 95% CI 15.4-18.3).
• The final analysis identified 15 risk factors associated with significantly higher incidence of YOD, including traditional factors like stroke (hazard ratio [HR], 2.07), heart disease (HR, 1.61), diabetes (HR, 1.65), and depression (HR, 3.25) but also less-recognized risk factors like vitamin D deficiency (< 10 ng/mL; HR, 1.59), high CRP levels (> 1 mg/dL; HR, 1.54), and social isolation (infrequent visits to friends or family; HR, 1.53), with lower socioeconomic status (HR, 1.82), having two apolipoprotein E epsilon-4 alleles (HR, 1.87), orthostatic hypotension, which the authors said may be an early sign of Parkinson dementia or Lewy body dementia (HR, 4.20), and hearing impairment (HR, 1.56) also increasing risk.
• Interestingly, some alcohol use seemed to be protective (moderate or heavy alcohol use had a lower association with YOD than alcohol abstinence, possibly due to the “healthy drinker effect” where people who drink are healthier than abstainers who may have illnesses preventing them from drinking, said the authors), as was higher education level and higher than normative handgrip strength (less strength is a proxy for physical frailty).
• Men with diabetes had higher YOD risk than those without diabetes, while there was no association with diabetes in women; on the other hand, women with high CRP levels had greater YOD risk than those with low levels, while there was no association with CRP in men.

IN PRACTICE:

“While further exploration of these risk factors is necessary to identify potential underlying mechanisms, addressing these modifiable factors may prove effective in mitigating the risk of developing YOD and can be readily integrated in current dementia prevention initiatives,” the investigators wrote.

SOURCE:

The study was led by Stevie Hendriks, PhD, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands. It was published online in JAMA Neurology.

LIMITATIONS:

The study was observational and so can’t infer causality. Several factors were based on self-reported data, which might be a source of response bias. Factors not considered in the study, for example, family history of dementia and drug (other than alcohol) use disorder, may have confounded associations. Some factors including orthostatic hypotension had few exposed cases, leading to decreased power to detect associations. Hospital and death records may not have captured all YOD cases. The UK Biobank is overrepresented by healthy and White participants, so results may not be generalizable to other racial and ethnic groups. The analyses only focused on all-cause dementia.

DISCLOSURES:

The study was supported by Alzheimer Netherlands. Hendriks has no relevant conflicts of interest; see paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

The plant-based psychoactive compound ibogaine, combined with magnesium to protect the heart, is linked to improvement in severe psychiatric symptoms including depression, anxiety, and functioning in veterans with traumatic brain injury (TBI), early results from a small study showed.

“The most unique findings we observed are the improvements in disability and cognition. At the start of the study, participants had mild to moderate levels of disability. However, a month after treatment, their average disability rating indicated no disability and cognitive testing indicated improvements in concentration and memory,” study investigator Nolan Williams, MD, Stanford University, Stanford, California, told this news organization.

Also noteworthy were improvements across all participants in posttraumatic stress disorder (PTSD), depression, and anxiety — effects that lasted for at least 1 month after treatment, he said.

“These results are remarkable and exceeded our expectations. There is no drug today that can broadly relieve functional and neuropsychiatric symptoms of TBI as we observed with ibogaine,” Dr. Williams added.

The study was published online on January 5, 2024, in Nature Medicine.
 

‘The Storm Lifted’

Ibogaine is derived from the root bark of the Tabernanthe iboga shrub and related plants and is traditionally used in African spiritual and healing ceremonies.

It is known to interact with multiple neurotransmitter systems and has been studied primarily as a treatment of substance use disorders (SUDs). Some studies of ibogaine for SUDs have also noted improvements in self-reported measures of mood.

In the United States, ibogaine is classified as a Schedule I substance, but legal ibogaine treatments are offered in clinics in Canada and Mexico.

Dr. Williams noted that a handful of US veterans who went to Mexico for ibogaine treatment anecdotally reported improvements a variety of aspects of their lives.

The goal of the current study was to characterize those improvements with structured clinical and neurobiological assessments.

Participants included 30 US Special Operations Forces veterans (SOVs) with predominantly mild TBI from combat/blast exposures and psychiatric symptoms and functional limitations. All of them had independently scheduled themselves for treatment with magnesium and ibogaine at a clinic in Mexico.

Before treatment, the veterans had an average disability rating of 30.2 on the World Health Organization Disability Assessment Scale 2.0, equivalent to mild to moderate disability. One month after ibogaine treatment, that rating improved to 5.1, indicating no disability, the researchers reported.

One month after treatment, participants also experienced average reductions of 88% in PTSD symptoms, 87% in depression symptoms, and 81% in anxiety symptoms relative to before treatment.

Neuropsychological testing revealed improved concentration, information processing, memory, and impulsivity. There was also a substantial reduction in suicidal ideation.

“Before the treatment, I was living life in a blizzard with zero visibility and a cold, hopeless, listless feeling. After ibogaine, the storm lifted,” Sean, a 51-year-old veteran from Arizona with six combat deployments who participated in the study, said in a Stanford news release.

There were no serious side effects of ibogaine, and no instances of heart problems associated with the treatment.

Although the study findings are promising, additional research is needed to address some clear limitations, the researchers noted.

“Most importantly, the study was not controlled and so the relative contribution of any therapeutic benefits from non-ibogaine elements of the experience, such as complementary treatments, group activities, coaching, international travel, expectancy, or other nonspecific effects, cannot be determined,” they wrote.

In addition, follow-up was limited to 1 month, and longer-term data are needed to determine durability of the effects.

“We plan to study this compound further, as well as launch future studies to continue to understand how this drug can be used to treat TBI and possibly as a broader neuro-rehab drug. We will work towards a US-based set of trials to confirm efficacy with a multisite design,” said Dr. Williams.
 

Promising, but Very Preliminary

Commenting on the study for this news organization, Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the Clinical TBI Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, said the results are “promising, but very preliminary.”

Dr. Diaz-Arrastia noted that this was an open-label, nonrandomized study, early phase 2a study with “highly subjective outcome measures and the likelihood of it being a placebo effect is very high.”

Nonetheless, “there is a lot of interest in these ‘psychedelic’ alkaloids, and ibogaine is a good candidate for further study,” Dr. Diaz-Arrastia said.

Also providing perspective, Alan K. Davis, PhD, director of the Center for Psychedelic Drug Research and Education, Ohio State University, Columbus, said “mounting evidence supports the importance of studying this treatment in rigorous clinical trials in the US.”

Dr. Davis and colleagues recently observed that treatment with two naturally occurring psychedelics — ibogaine and 5-MeO-DMT — was associated with reduced depressive and anxiety symptoms in trauma-exposed SOVs, as previously reported by this news organization.

This new study “basically is a replication of what we’ve already published on this topic, and we published data from much larger samples and longer follow up,” said Dr. Davis.

Dr. Davis said it’s “important for the public to know that there are important and serious risks associated with ibogaine therapy, including the possibility of cardiac problems and death. These risks are compounded when people are in clinics or settings where proper screening and medical oversight are not completed.”

“Furthermore, the long-term effectiveness of this treatment is not well established. It may only help in the short term for most people. For many, ongoing clinical aftercare therapy and other forms of treatment may be needed,” Dr. Davis noted.

The study was independently funded by philanthropic gifts from Steve and Genevieve Jurvetson and another anonymous donor. Williams is an inventor on a patent application related to the safety of MISTIC administration as described in the paper and a separate patent related to the use of ibogaine to treat disorders associated with brain aging. Dr. Davis is a board member at Source Resource Foundation and a lead trainer at Fluence. Dr. Diaz-Arrastia has no relevant disclosures.

A version of this article appeared on Medscape.com.

The plant-based psychoactive compound ibogaine, combined with magnesium to protect the heart, is linked to improvement in severe psychiatric symptoms including depression, anxiety, and functioning in veterans with traumatic brain injury (TBI), early results from a small study showed.

“The most unique findings we observed are the improvements in disability and cognition. At the start of the study, participants had mild to moderate levels of disability. However, a month after treatment, their average disability rating indicated no disability and cognitive testing indicated improvements in concentration and memory,” study investigator Nolan Williams, MD, Stanford University, Stanford, California, told this news organization.

Also noteworthy were improvements across all participants in posttraumatic stress disorder (PTSD), depression, and anxiety — effects that lasted for at least 1 month after treatment, he said.

“These results are remarkable and exceeded our expectations. There is no drug today that can broadly relieve functional and neuropsychiatric symptoms of TBI as we observed with ibogaine,” Dr. Williams added.

The study was published online on January 5, 2024, in Nature Medicine.
 

‘The Storm Lifted’

Ibogaine is derived from the root bark of the Tabernanthe iboga shrub and related plants and is traditionally used in African spiritual and healing ceremonies.

It is known to interact with multiple neurotransmitter systems and has been studied primarily as a treatment of substance use disorders (SUDs). Some studies of ibogaine for SUDs have also noted improvements in self-reported measures of mood.

In the United States, ibogaine is classified as a Schedule I substance, but legal ibogaine treatments are offered in clinics in Canada and Mexico.

Dr. Williams noted that a handful of US veterans who went to Mexico for ibogaine treatment anecdotally reported improvements a variety of aspects of their lives.

The goal of the current study was to characterize those improvements with structured clinical and neurobiological assessments.

Participants included 30 US Special Operations Forces veterans (SOVs) with predominantly mild TBI from combat/blast exposures and psychiatric symptoms and functional limitations. All of them had independently scheduled themselves for treatment with magnesium and ibogaine at a clinic in Mexico.

Before treatment, the veterans had an average disability rating of 30.2 on the World Health Organization Disability Assessment Scale 2.0, equivalent to mild to moderate disability. One month after ibogaine treatment, that rating improved to 5.1, indicating no disability, the researchers reported.

One month after treatment, participants also experienced average reductions of 88% in PTSD symptoms, 87% in depression symptoms, and 81% in anxiety symptoms relative to before treatment.

Neuropsychological testing revealed improved concentration, information processing, memory, and impulsivity. There was also a substantial reduction in suicidal ideation.

“Before the treatment, I was living life in a blizzard with zero visibility and a cold, hopeless, listless feeling. After ibogaine, the storm lifted,” Sean, a 51-year-old veteran from Arizona with six combat deployments who participated in the study, said in a Stanford news release.

There were no serious side effects of ibogaine, and no instances of heart problems associated with the treatment.

Although the study findings are promising, additional research is needed to address some clear limitations, the researchers noted.

“Most importantly, the study was not controlled and so the relative contribution of any therapeutic benefits from non-ibogaine elements of the experience, such as complementary treatments, group activities, coaching, international travel, expectancy, or other nonspecific effects, cannot be determined,” they wrote.

In addition, follow-up was limited to 1 month, and longer-term data are needed to determine durability of the effects.

“We plan to study this compound further, as well as launch future studies to continue to understand how this drug can be used to treat TBI and possibly as a broader neuro-rehab drug. We will work towards a US-based set of trials to confirm efficacy with a multisite design,” said Dr. Williams.
 

Promising, but Very Preliminary

Commenting on the study for this news organization, Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the Clinical TBI Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, said the results are “promising, but very preliminary.”

Dr. Diaz-Arrastia noted that this was an open-label, nonrandomized study, early phase 2a study with “highly subjective outcome measures and the likelihood of it being a placebo effect is very high.”

Nonetheless, “there is a lot of interest in these ‘psychedelic’ alkaloids, and ibogaine is a good candidate for further study,” Dr. Diaz-Arrastia said.

Also providing perspective, Alan K. Davis, PhD, director of the Center for Psychedelic Drug Research and Education, Ohio State University, Columbus, said “mounting evidence supports the importance of studying this treatment in rigorous clinical trials in the US.”

Dr. Davis and colleagues recently observed that treatment with two naturally occurring psychedelics — ibogaine and 5-MeO-DMT — was associated with reduced depressive and anxiety symptoms in trauma-exposed SOVs, as previously reported by this news organization.

This new study “basically is a replication of what we’ve already published on this topic, and we published data from much larger samples and longer follow up,” said Dr. Davis.

Dr. Davis said it’s “important for the public to know that there are important and serious risks associated with ibogaine therapy, including the possibility of cardiac problems and death. These risks are compounded when people are in clinics or settings where proper screening and medical oversight are not completed.”

“Furthermore, the long-term effectiveness of this treatment is not well established. It may only help in the short term for most people. For many, ongoing clinical aftercare therapy and other forms of treatment may be needed,” Dr. Davis noted.

The study was independently funded by philanthropic gifts from Steve and Genevieve Jurvetson and another anonymous donor. Williams is an inventor on a patent application related to the safety of MISTIC administration as described in the paper and a separate patent related to the use of ibogaine to treat disorders associated with brain aging. Dr. Davis is a board member at Source Resource Foundation and a lead trainer at Fluence. Dr. Diaz-Arrastia has no relevant disclosures.

A version of this article appeared on Medscape.com.

The plant-based psychoactive compound ibogaine, combined with magnesium to protect the heart, is linked to improvement in severe psychiatric symptoms including depression, anxiety, and functioning in veterans with traumatic brain injury (TBI), early results from a small study showed.

“The most unique findings we observed are the improvements in disability and cognition. At the start of the study, participants had mild to moderate levels of disability. However, a month after treatment, their average disability rating indicated no disability and cognitive testing indicated improvements in concentration and memory,” study investigator Nolan Williams, MD, Stanford University, Stanford, California, told this news organization.

Also noteworthy were improvements across all participants in posttraumatic stress disorder (PTSD), depression, and anxiety — effects that lasted for at least 1 month after treatment, he said.

“These results are remarkable and exceeded our expectations. There is no drug today that can broadly relieve functional and neuropsychiatric symptoms of TBI as we observed with ibogaine,” Dr. Williams added.

The study was published online on January 5, 2024, in Nature Medicine.
 

‘The Storm Lifted’

Ibogaine is derived from the root bark of the Tabernanthe iboga shrub and related plants and is traditionally used in African spiritual and healing ceremonies.

It is known to interact with multiple neurotransmitter systems and has been studied primarily as a treatment of substance use disorders (SUDs). Some studies of ibogaine for SUDs have also noted improvements in self-reported measures of mood.

In the United States, ibogaine is classified as a Schedule I substance, but legal ibogaine treatments are offered in clinics in Canada and Mexico.

Dr. Williams noted that a handful of US veterans who went to Mexico for ibogaine treatment anecdotally reported improvements a variety of aspects of their lives.

The goal of the current study was to characterize those improvements with structured clinical and neurobiological assessments.

Participants included 30 US Special Operations Forces veterans (SOVs) with predominantly mild TBI from combat/blast exposures and psychiatric symptoms and functional limitations. All of them had independently scheduled themselves for treatment with magnesium and ibogaine at a clinic in Mexico.

Before treatment, the veterans had an average disability rating of 30.2 on the World Health Organization Disability Assessment Scale 2.0, equivalent to mild to moderate disability. One month after ibogaine treatment, that rating improved to 5.1, indicating no disability, the researchers reported.

One month after treatment, participants also experienced average reductions of 88% in PTSD symptoms, 87% in depression symptoms, and 81% in anxiety symptoms relative to before treatment.

Neuropsychological testing revealed improved concentration, information processing, memory, and impulsivity. There was also a substantial reduction in suicidal ideation.

“Before the treatment, I was living life in a blizzard with zero visibility and a cold, hopeless, listless feeling. After ibogaine, the storm lifted,” Sean, a 51-year-old veteran from Arizona with six combat deployments who participated in the study, said in a Stanford news release.

There were no serious side effects of ibogaine, and no instances of heart problems associated with the treatment.

Although the study findings are promising, additional research is needed to address some clear limitations, the researchers noted.

“Most importantly, the study was not controlled and so the relative contribution of any therapeutic benefits from non-ibogaine elements of the experience, such as complementary treatments, group activities, coaching, international travel, expectancy, or other nonspecific effects, cannot be determined,” they wrote.

In addition, follow-up was limited to 1 month, and longer-term data are needed to determine durability of the effects.

“We plan to study this compound further, as well as launch future studies to continue to understand how this drug can be used to treat TBI and possibly as a broader neuro-rehab drug. We will work towards a US-based set of trials to confirm efficacy with a multisite design,” said Dr. Williams.
 

Promising, but Very Preliminary

Commenting on the study for this news organization, Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the Clinical TBI Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, said the results are “promising, but very preliminary.”

Dr. Diaz-Arrastia noted that this was an open-label, nonrandomized study, early phase 2a study with “highly subjective outcome measures and the likelihood of it being a placebo effect is very high.”

Nonetheless, “there is a lot of interest in these ‘psychedelic’ alkaloids, and ibogaine is a good candidate for further study,” Dr. Diaz-Arrastia said.

Also providing perspective, Alan K. Davis, PhD, director of the Center for Psychedelic Drug Research and Education, Ohio State University, Columbus, said “mounting evidence supports the importance of studying this treatment in rigorous clinical trials in the US.”

Dr. Davis and colleagues recently observed that treatment with two naturally occurring psychedelics — ibogaine and 5-MeO-DMT — was associated with reduced depressive and anxiety symptoms in trauma-exposed SOVs, as previously reported by this news organization.

This new study “basically is a replication of what we’ve already published on this topic, and we published data from much larger samples and longer follow up,” said Dr. Davis.

Dr. Davis said it’s “important for the public to know that there are important and serious risks associated with ibogaine therapy, including the possibility of cardiac problems and death. These risks are compounded when people are in clinics or settings where proper screening and medical oversight are not completed.”

“Furthermore, the long-term effectiveness of this treatment is not well established. It may only help in the short term for most people. For many, ongoing clinical aftercare therapy and other forms of treatment may be needed,” Dr. Davis noted.

The study was independently funded by philanthropic gifts from Steve and Genevieve Jurvetson and another anonymous donor. Williams is an inventor on a patent application related to the safety of MISTIC administration as described in the paper and a separate patent related to the use of ibogaine to treat disorders associated with brain aging. Dr. Davis is a board member at Source Resource Foundation and a lead trainer at Fluence. Dr. Diaz-Arrastia has no relevant disclosures.

A version of this article appeared on Medscape.com.