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Question 1
Correct answer: A. Amyloidosis involving the small intestine
Rationale
This patient has a protein-losing enteropathy as indicated by his diarrhea, peripheral edema, and positive stool alpha-1 antitrypsin test. Multiple diseases, particularly in their later stages, can be associated with a protein-losing enteropathy including primary intestinal lymphangectasia, Crohn's disease of the small intestine, small intestinal bacterial overgrowth (SIBO), and amyloidosis of the small intestine (A). Celiac disease (B) is not associated with protein-losing enteropathy. While Crohn's disease can be associated with protein-losing enteropathy, ulcerative colitis (C) is not usually associated with it. Small bowel dysmotility (D) does not impact absorption or secretion unless associated with SIBO, making this a wrong answer.
Correct answer: A. Amyloidosis involving the small intestine
Rationale
This patient has a protein-losing enteropathy as indicated by his diarrhea, peripheral edema, and positive stool alpha-1 antitrypsin test. Multiple diseases, particularly in their later stages, can be associated with a protein-losing enteropathy including primary intestinal lymphangectasia, Crohn's disease of the small intestine, small intestinal bacterial overgrowth (SIBO), and amyloidosis of the small intestine (A). Celiac disease (B) is not associated with protein-losing enteropathy. While Crohn's disease can be associated with protein-losing enteropathy, ulcerative colitis (C) is not usually associated with it. Small bowel dysmotility (D) does not impact absorption or secretion unless associated with SIBO, making this a wrong answer.
Correct answer: A. Amyloidosis involving the small intestine
Rationale
This patient has a protein-losing enteropathy as indicated by his diarrhea, peripheral edema, and positive stool alpha-1 antitrypsin test. Multiple diseases, particularly in their later stages, can be associated with a protein-losing enteropathy including primary intestinal lymphangectasia, Crohn's disease of the small intestine, small intestinal bacterial overgrowth (SIBO), and amyloidosis of the small intestine (A). Celiac disease (B) is not associated with protein-losing enteropathy. While Crohn's disease can be associated with protein-losing enteropathy, ulcerative colitis (C) is not usually associated with it. Small bowel dysmotility (D) does not impact absorption or secretion unless associated with SIBO, making this a wrong answer.
A 65-year-old male with no significant past medical history presents with significant diarrhea. He reports that for the past 3 months, he has had four to five bowel movements a day. He characterizes them as greasy and foul smelling, but not entirely watery. He notices no blood or mucous in the stool. Over the same time period, he has also noticed increased swelling in both of his ankles. The physician sends a broad work-up.
Stool testing results include the following:
Clostridioides difficile - Negative.
Stool Ova and Parasite - Negative.
Stool Culture - Negative.
Stool Elastase - within normal limits.
Fecal Fat (spot test) - within normal limits.
Stool Alpha-1 Antitrypsin - Elevated.
A little-known offshoot of hem/onc opens pathway for professional development
Only a small number of pediatric hematologist oncologists and even fewer of our adult counterparts feel comfortable evaluating and treating vascular anomalies.
While admittedly rare, these conditions are still common enough that clinicians in many disciplines encounter them. Hematologist/oncologists are most likely to see vascular malformations, which often present as mass lesions. Complications of these disorders occur across the hematology-oncology spectrum and include clots, pulmonary emboli, cancer predisposition, and an array of functional and psychosocial disorders.
Vascular anomalies are broadly categorized as vascular tumors or malformations. The tumors include hemangiomas, locally aggressive lesions, and true cancers. Malformations can be isolated disorders of one or more blood vessel types (veins, arteries, capillaries or lymphatics), or they can be one part of syndromic disorders. Lymphedema also falls under the heading of vascular anomalies. To make the terminology less confusing, in 2018 the International Society for the Study of Vascular Anomalies refined its classification scheme.
Vascular malformations are thought to be congenital. Although some are obvious at birth, others aren’t apparent until adulthood. In most cases, they grow with a child and may do so disproportionately at puberty and with pregnancies. The fact that vascular malformations persist into adulthood is one reason why their care should be integral to medical hematology-oncology.
Although the cause of a vascular malformation is not always known, a wide range of genetic mutations thought to be pathogenic have been reported. These mutations are usually somatic (only within the involved tissues, not in the blood or germ cells and therefore, not heritable) and tend to cluster in the VEGF-PIK3CA and RAS-MAP signaling pathways.
These genes and pathways will be familiar to any oncologist who cares for patients with solid tumors, notably breast cancer or melanoma. However, unlike the clonal expansion seen in cancers, most vascular malformations will express pathogenic mutations in less than 20% of vascular endothelium within a malformation.
Since 2008, medical management has been limited to sirolimus (rapamycin), a mammalian target of rapamycin inhibitor, which can be effective even when mTOR mutations aren’t apparent. In a seminal phase 2 trial of 57 patients with complex vascular anomalies who were aged 0-29 years, 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. None had complete responses. These data highlight the need for more effective treatments.
Recently, vascular anomalists have begun to repurpose drugs from adult oncology that specifically target pathogenic mutations. Some studies underway include Novartis’ international Alpelisib (Piqray) clinical trial for adults and children with PIK3CA-related overgrowth syndromes (NCT04589650) and Merck’s follow-up study of the AKT inhibitor miransertib for PROS and Proteus syndrome. Doses tend to be lower than those used to treat cancers. To date, these have been generally well-tolerated, with sometimes striking but preliminary evidence of efficacy.
During the past 2 years, symposia on vascular anomalies at the annual meeting of the American Society of Hematology have launched what we are hoping is just the start of a broader discussion. In 2020, Fran Blei, MD, chaired Vascular Anomalies 101: Case-Based Discussion on the Diagnosis, Treatment and Lifelong Care of These Patients, and in 2021, Adrienne Hammill, MD, PhD, and Dr. Raj Kasthuri, MBBS, MD, chaired a more specialized symposium: Hereditary Hemorrhagic Telangiectasia (HHT): A Practical Guide to Management.
Dr. Blatt is in the division of pediatric hematology oncology at the University of North Carolina at Chapel Hill. She disclosed no relevant financial relationships.
Only a small number of pediatric hematologist oncologists and even fewer of our adult counterparts feel comfortable evaluating and treating vascular anomalies.
While admittedly rare, these conditions are still common enough that clinicians in many disciplines encounter them. Hematologist/oncologists are most likely to see vascular malformations, which often present as mass lesions. Complications of these disorders occur across the hematology-oncology spectrum and include clots, pulmonary emboli, cancer predisposition, and an array of functional and psychosocial disorders.
Vascular anomalies are broadly categorized as vascular tumors or malformations. The tumors include hemangiomas, locally aggressive lesions, and true cancers. Malformations can be isolated disorders of one or more blood vessel types (veins, arteries, capillaries or lymphatics), or they can be one part of syndromic disorders. Lymphedema also falls under the heading of vascular anomalies. To make the terminology less confusing, in 2018 the International Society for the Study of Vascular Anomalies refined its classification scheme.
Vascular malformations are thought to be congenital. Although some are obvious at birth, others aren’t apparent until adulthood. In most cases, they grow with a child and may do so disproportionately at puberty and with pregnancies. The fact that vascular malformations persist into adulthood is one reason why their care should be integral to medical hematology-oncology.
Although the cause of a vascular malformation is not always known, a wide range of genetic mutations thought to be pathogenic have been reported. These mutations are usually somatic (only within the involved tissues, not in the blood or germ cells and therefore, not heritable) and tend to cluster in the VEGF-PIK3CA and RAS-MAP signaling pathways.
These genes and pathways will be familiar to any oncologist who cares for patients with solid tumors, notably breast cancer or melanoma. However, unlike the clonal expansion seen in cancers, most vascular malformations will express pathogenic mutations in less than 20% of vascular endothelium within a malformation.
Since 2008, medical management has been limited to sirolimus (rapamycin), a mammalian target of rapamycin inhibitor, which can be effective even when mTOR mutations aren’t apparent. In a seminal phase 2 trial of 57 patients with complex vascular anomalies who were aged 0-29 years, 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. None had complete responses. These data highlight the need for more effective treatments.
Recently, vascular anomalists have begun to repurpose drugs from adult oncology that specifically target pathogenic mutations. Some studies underway include Novartis’ international Alpelisib (Piqray) clinical trial for adults and children with PIK3CA-related overgrowth syndromes (NCT04589650) and Merck’s follow-up study of the AKT inhibitor miransertib for PROS and Proteus syndrome. Doses tend to be lower than those used to treat cancers. To date, these have been generally well-tolerated, with sometimes striking but preliminary evidence of efficacy.
During the past 2 years, symposia on vascular anomalies at the annual meeting of the American Society of Hematology have launched what we are hoping is just the start of a broader discussion. In 2020, Fran Blei, MD, chaired Vascular Anomalies 101: Case-Based Discussion on the Diagnosis, Treatment and Lifelong Care of These Patients, and in 2021, Adrienne Hammill, MD, PhD, and Dr. Raj Kasthuri, MBBS, MD, chaired a more specialized symposium: Hereditary Hemorrhagic Telangiectasia (HHT): A Practical Guide to Management.
Dr. Blatt is in the division of pediatric hematology oncology at the University of North Carolina at Chapel Hill. She disclosed no relevant financial relationships.
Only a small number of pediatric hematologist oncologists and even fewer of our adult counterparts feel comfortable evaluating and treating vascular anomalies.
While admittedly rare, these conditions are still common enough that clinicians in many disciplines encounter them. Hematologist/oncologists are most likely to see vascular malformations, which often present as mass lesions. Complications of these disorders occur across the hematology-oncology spectrum and include clots, pulmonary emboli, cancer predisposition, and an array of functional and psychosocial disorders.
Vascular anomalies are broadly categorized as vascular tumors or malformations. The tumors include hemangiomas, locally aggressive lesions, and true cancers. Malformations can be isolated disorders of one or more blood vessel types (veins, arteries, capillaries or lymphatics), or they can be one part of syndromic disorders. Lymphedema also falls under the heading of vascular anomalies. To make the terminology less confusing, in 2018 the International Society for the Study of Vascular Anomalies refined its classification scheme.
Vascular malformations are thought to be congenital. Although some are obvious at birth, others aren’t apparent until adulthood. In most cases, they grow with a child and may do so disproportionately at puberty and with pregnancies. The fact that vascular malformations persist into adulthood is one reason why their care should be integral to medical hematology-oncology.
Although the cause of a vascular malformation is not always known, a wide range of genetic mutations thought to be pathogenic have been reported. These mutations are usually somatic (only within the involved tissues, not in the blood or germ cells and therefore, not heritable) and tend to cluster in the VEGF-PIK3CA and RAS-MAP signaling pathways.
These genes and pathways will be familiar to any oncologist who cares for patients with solid tumors, notably breast cancer or melanoma. However, unlike the clonal expansion seen in cancers, most vascular malformations will express pathogenic mutations in less than 20% of vascular endothelium within a malformation.
Since 2008, medical management has been limited to sirolimus (rapamycin), a mammalian target of rapamycin inhibitor, which can be effective even when mTOR mutations aren’t apparent. In a seminal phase 2 trial of 57 patients with complex vascular anomalies who were aged 0-29 years, 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. None had complete responses. These data highlight the need for more effective treatments.
Recently, vascular anomalists have begun to repurpose drugs from adult oncology that specifically target pathogenic mutations. Some studies underway include Novartis’ international Alpelisib (Piqray) clinical trial for adults and children with PIK3CA-related overgrowth syndromes (NCT04589650) and Merck’s follow-up study of the AKT inhibitor miransertib for PROS and Proteus syndrome. Doses tend to be lower than those used to treat cancers. To date, these have been generally well-tolerated, with sometimes striking but preliminary evidence of efficacy.
During the past 2 years, symposia on vascular anomalies at the annual meeting of the American Society of Hematology have launched what we are hoping is just the start of a broader discussion. In 2020, Fran Blei, MD, chaired Vascular Anomalies 101: Case-Based Discussion on the Diagnosis, Treatment and Lifelong Care of These Patients, and in 2021, Adrienne Hammill, MD, PhD, and Dr. Raj Kasthuri, MBBS, MD, chaired a more specialized symposium: Hereditary Hemorrhagic Telangiectasia (HHT): A Practical Guide to Management.
Dr. Blatt is in the division of pediatric hematology oncology at the University of North Carolina at Chapel Hill. She disclosed no relevant financial relationships.
Fingers take the fight to COVID-19
Pointing a finger at COVID-19
The battle against COVID-19 is seemingly never ending. It’s been 2 years and still we struggle against the virus. But now, a new hero rises against the eternal menace, a powerful weapon against this scourge of humanity. And that weapon? Finger length.
Before you break out the sad trombone, hear us out. One of the big questions around COVID-19 is the role testosterone plays in its severity: Does low testosterone increase or decrease the odds of contracting severe COVID-19? To help answer that question, English researchers have published a study analyzing finger length ratios in both COVID-19 patients and a healthy control group. That seems random, but high testosterone in the womb leads to longer ring fingers in adulthood, while high estrogen leads to longer index fingers.
According to the researchers, those who had significant left hand–right hand differences in the ratio between the second and fourth digits, as well as the third and fifth digits, were significantly more likely to have severe COVID-19 compared with those with more even ratios. Those with “feminized” short little fingers were also at risk. Those large ratio differences indicate low testosterone and high estrogen, which may explain why elderly men are at such high risk for severe COVID-19. Testosterone naturally falls off as men get older.
The results add credence to clinical trials looking to use testosterone-boosting drugs against COVID-19, the researchers said. It also gives credence to LOTME’s brand-new 12-step finger strength fitness routine and our branded finger weights. Now just $19.95! It’s the bargain of the century! Boost your testosterone naturally and protect yourself from COVID-19! We promise it’s not a scam.
Some emergencies need a superhero
Last week, we learned about the most boring person in the world. This week just happens to be opposite week, so we’re looking at a candidate for the most interesting person. Someone who can swoop down from the sky to save the injured and helpless. Someone who can go where helicopters fear to tread. Someone with jet engines for arms. Superhero-type stuff.
The Great North Air Ambulance Service (GNAAS), a charitable organization located in the United Kingdom, recently announced that one of its members has completed training on the Gravity Industries Jet Suit. The suit “has two engines on each arm and a larger engine on the back [that] provide up to 317 pounds of thrust,” Interesting Engineering explained.
GNAAS is putting the suit into operation in England’s Lake District National Park, which includes mountainous terrain that is not very hospitable to helicopter landings. A paramedic using the suit can reach hikers stranded on mountainsides much faster than rescuers who have to run or hike from the nearest helicopter landing site.
“Everyone looks at the wow factor and the fact we are the world’s first jet suit paramedics, but for us, it’s about delivering patient care,” GNAAS’ Andy Mawson told Interesting Engineering. Sounds like superhero-speak to us.
So if you’re in the Lake District and have taken a bit of a tumble, you can call a superhero on your cell phone or you can use this to summon one.
Why we’re rejecting food as medicine
Humans have been using food to treat ailments much longer than we’ve had the advances of modern medicine. So why have we rejected its worth in our treatment processes? And what can be done to change that? The Center for Food as Medicine and the Hunter College NYC Food Policy Center just released a 335-page report that answers those questions.
First, the why: Meals in health care settings are not medically designed to help with the specific needs of the patient. Produce-prescription and nutrition-incentive programs don’t have the government funds to fully support them. And a lot of medical schools don’t even require students to take a basic nutrition course. So there’s a lack of knowledge and a disconnect between health care providers and food as a resource.
Then there’s a lack of trust in the food industry and their validity. Social media uses food as a means of promoting “pseudoscientific alternative medicine” or spreading false info, pushing away legitimate providers. The food industry has had its fingers in food science studies and an almost mafia-esque chokehold on American dietary guidelines. No wonder food for medicine is getting the boot!
To change the situation, the report offers 10 key recommendations on how to advance the idea of incorporating food into medicine for treatment and prevention. They include boosting the funding for research, making hospitals more food-as-medicine focused, expanding federal programs, and improving public awareness on the role nutrition can play in medical treatment or prevention.
So maybe instead of rejecting food outright, we should be looking a little deeper at how we can use it to our advantage. Just a thought: Ice cream as an antidepressant.
Being rude is a good thing, apparently
If you’ve ever been called argumentative, stubborn, or unpleasant, then this LOTME is for you. Researchers at the University of Geneva have found that people who are more stubborn and hate to conform have brains that are more protected against Alzheimer’s disease. That type of personality seems to preserve the part of the brain that usually deteriorates as we grow older.
The original hypothesis that personality may have a protective effect against brain degeneration led the investigators to conduct cognitive and personality assessments of 65 elderly participants over a 5-year period. Researchers have been attempting to create vaccines to protect against Alzheimer’s disease, but these new findings offer a nonbiological way to help.
“For a long time, the brain is able to compensate by activating alternative networks; when the first clinical signs appear, however, it is unfortunately often too late. The identification of early biomarkers is therefore essential for … effective disease management,” lead author Panteleimon Giannakopoulos, MD, said in a Study Finds report.
You may be wondering how people with more agreeable and less confrontational personalities can seek help. Well, researchers are working on that, too. It’s a complex situation, but as always, we’re rooting for you, science!
At least now you can take solace in the fact that your elderly next-door neighbor who yells at you for stepping on his lawn is probably more protected against Alzheimer’s disease.
Pointing a finger at COVID-19
The battle against COVID-19 is seemingly never ending. It’s been 2 years and still we struggle against the virus. But now, a new hero rises against the eternal menace, a powerful weapon against this scourge of humanity. And that weapon? Finger length.
Before you break out the sad trombone, hear us out. One of the big questions around COVID-19 is the role testosterone plays in its severity: Does low testosterone increase or decrease the odds of contracting severe COVID-19? To help answer that question, English researchers have published a study analyzing finger length ratios in both COVID-19 patients and a healthy control group. That seems random, but high testosterone in the womb leads to longer ring fingers in adulthood, while high estrogen leads to longer index fingers.
According to the researchers, those who had significant left hand–right hand differences in the ratio between the second and fourth digits, as well as the third and fifth digits, were significantly more likely to have severe COVID-19 compared with those with more even ratios. Those with “feminized” short little fingers were also at risk. Those large ratio differences indicate low testosterone and high estrogen, which may explain why elderly men are at such high risk for severe COVID-19. Testosterone naturally falls off as men get older.
The results add credence to clinical trials looking to use testosterone-boosting drugs against COVID-19, the researchers said. It also gives credence to LOTME’s brand-new 12-step finger strength fitness routine and our branded finger weights. Now just $19.95! It’s the bargain of the century! Boost your testosterone naturally and protect yourself from COVID-19! We promise it’s not a scam.
Some emergencies need a superhero
Last week, we learned about the most boring person in the world. This week just happens to be opposite week, so we’re looking at a candidate for the most interesting person. Someone who can swoop down from the sky to save the injured and helpless. Someone who can go where helicopters fear to tread. Someone with jet engines for arms. Superhero-type stuff.
The Great North Air Ambulance Service (GNAAS), a charitable organization located in the United Kingdom, recently announced that one of its members has completed training on the Gravity Industries Jet Suit. The suit “has two engines on each arm and a larger engine on the back [that] provide up to 317 pounds of thrust,” Interesting Engineering explained.
GNAAS is putting the suit into operation in England’s Lake District National Park, which includes mountainous terrain that is not very hospitable to helicopter landings. A paramedic using the suit can reach hikers stranded on mountainsides much faster than rescuers who have to run or hike from the nearest helicopter landing site.
“Everyone looks at the wow factor and the fact we are the world’s first jet suit paramedics, but for us, it’s about delivering patient care,” GNAAS’ Andy Mawson told Interesting Engineering. Sounds like superhero-speak to us.
So if you’re in the Lake District and have taken a bit of a tumble, you can call a superhero on your cell phone or you can use this to summon one.
Why we’re rejecting food as medicine
Humans have been using food to treat ailments much longer than we’ve had the advances of modern medicine. So why have we rejected its worth in our treatment processes? And what can be done to change that? The Center for Food as Medicine and the Hunter College NYC Food Policy Center just released a 335-page report that answers those questions.
First, the why: Meals in health care settings are not medically designed to help with the specific needs of the patient. Produce-prescription and nutrition-incentive programs don’t have the government funds to fully support them. And a lot of medical schools don’t even require students to take a basic nutrition course. So there’s a lack of knowledge and a disconnect between health care providers and food as a resource.
Then there’s a lack of trust in the food industry and their validity. Social media uses food as a means of promoting “pseudoscientific alternative medicine” or spreading false info, pushing away legitimate providers. The food industry has had its fingers in food science studies and an almost mafia-esque chokehold on American dietary guidelines. No wonder food for medicine is getting the boot!
To change the situation, the report offers 10 key recommendations on how to advance the idea of incorporating food into medicine for treatment and prevention. They include boosting the funding for research, making hospitals more food-as-medicine focused, expanding federal programs, and improving public awareness on the role nutrition can play in medical treatment or prevention.
So maybe instead of rejecting food outright, we should be looking a little deeper at how we can use it to our advantage. Just a thought: Ice cream as an antidepressant.
Being rude is a good thing, apparently
If you’ve ever been called argumentative, stubborn, or unpleasant, then this LOTME is for you. Researchers at the University of Geneva have found that people who are more stubborn and hate to conform have brains that are more protected against Alzheimer’s disease. That type of personality seems to preserve the part of the brain that usually deteriorates as we grow older.
The original hypothesis that personality may have a protective effect against brain degeneration led the investigators to conduct cognitive and personality assessments of 65 elderly participants over a 5-year period. Researchers have been attempting to create vaccines to protect against Alzheimer’s disease, but these new findings offer a nonbiological way to help.
“For a long time, the brain is able to compensate by activating alternative networks; when the first clinical signs appear, however, it is unfortunately often too late. The identification of early biomarkers is therefore essential for … effective disease management,” lead author Panteleimon Giannakopoulos, MD, said in a Study Finds report.
You may be wondering how people with more agreeable and less confrontational personalities can seek help. Well, researchers are working on that, too. It’s a complex situation, but as always, we’re rooting for you, science!
At least now you can take solace in the fact that your elderly next-door neighbor who yells at you for stepping on his lawn is probably more protected against Alzheimer’s disease.
Pointing a finger at COVID-19
The battle against COVID-19 is seemingly never ending. It’s been 2 years and still we struggle against the virus. But now, a new hero rises against the eternal menace, a powerful weapon against this scourge of humanity. And that weapon? Finger length.
Before you break out the sad trombone, hear us out. One of the big questions around COVID-19 is the role testosterone plays in its severity: Does low testosterone increase or decrease the odds of contracting severe COVID-19? To help answer that question, English researchers have published a study analyzing finger length ratios in both COVID-19 patients and a healthy control group. That seems random, but high testosterone in the womb leads to longer ring fingers in adulthood, while high estrogen leads to longer index fingers.
According to the researchers, those who had significant left hand–right hand differences in the ratio between the second and fourth digits, as well as the third and fifth digits, were significantly more likely to have severe COVID-19 compared with those with more even ratios. Those with “feminized” short little fingers were also at risk. Those large ratio differences indicate low testosterone and high estrogen, which may explain why elderly men are at such high risk for severe COVID-19. Testosterone naturally falls off as men get older.
The results add credence to clinical trials looking to use testosterone-boosting drugs against COVID-19, the researchers said. It also gives credence to LOTME’s brand-new 12-step finger strength fitness routine and our branded finger weights. Now just $19.95! It’s the bargain of the century! Boost your testosterone naturally and protect yourself from COVID-19! We promise it’s not a scam.
Some emergencies need a superhero
Last week, we learned about the most boring person in the world. This week just happens to be opposite week, so we’re looking at a candidate for the most interesting person. Someone who can swoop down from the sky to save the injured and helpless. Someone who can go where helicopters fear to tread. Someone with jet engines for arms. Superhero-type stuff.
The Great North Air Ambulance Service (GNAAS), a charitable organization located in the United Kingdom, recently announced that one of its members has completed training on the Gravity Industries Jet Suit. The suit “has two engines on each arm and a larger engine on the back [that] provide up to 317 pounds of thrust,” Interesting Engineering explained.
GNAAS is putting the suit into operation in England’s Lake District National Park, which includes mountainous terrain that is not very hospitable to helicopter landings. A paramedic using the suit can reach hikers stranded on mountainsides much faster than rescuers who have to run or hike from the nearest helicopter landing site.
“Everyone looks at the wow factor and the fact we are the world’s first jet suit paramedics, but for us, it’s about delivering patient care,” GNAAS’ Andy Mawson told Interesting Engineering. Sounds like superhero-speak to us.
So if you’re in the Lake District and have taken a bit of a tumble, you can call a superhero on your cell phone or you can use this to summon one.
Why we’re rejecting food as medicine
Humans have been using food to treat ailments much longer than we’ve had the advances of modern medicine. So why have we rejected its worth in our treatment processes? And what can be done to change that? The Center for Food as Medicine and the Hunter College NYC Food Policy Center just released a 335-page report that answers those questions.
First, the why: Meals in health care settings are not medically designed to help with the specific needs of the patient. Produce-prescription and nutrition-incentive programs don’t have the government funds to fully support them. And a lot of medical schools don’t even require students to take a basic nutrition course. So there’s a lack of knowledge and a disconnect between health care providers and food as a resource.
Then there’s a lack of trust in the food industry and their validity. Social media uses food as a means of promoting “pseudoscientific alternative medicine” or spreading false info, pushing away legitimate providers. The food industry has had its fingers in food science studies and an almost mafia-esque chokehold on American dietary guidelines. No wonder food for medicine is getting the boot!
To change the situation, the report offers 10 key recommendations on how to advance the idea of incorporating food into medicine for treatment and prevention. They include boosting the funding for research, making hospitals more food-as-medicine focused, expanding federal programs, and improving public awareness on the role nutrition can play in medical treatment or prevention.
So maybe instead of rejecting food outright, we should be looking a little deeper at how we can use it to our advantage. Just a thought: Ice cream as an antidepressant.
Being rude is a good thing, apparently
If you’ve ever been called argumentative, stubborn, or unpleasant, then this LOTME is for you. Researchers at the University of Geneva have found that people who are more stubborn and hate to conform have brains that are more protected against Alzheimer’s disease. That type of personality seems to preserve the part of the brain that usually deteriorates as we grow older.
The original hypothesis that personality may have a protective effect against brain degeneration led the investigators to conduct cognitive and personality assessments of 65 elderly participants over a 5-year period. Researchers have been attempting to create vaccines to protect against Alzheimer’s disease, but these new findings offer a nonbiological way to help.
“For a long time, the brain is able to compensate by activating alternative networks; when the first clinical signs appear, however, it is unfortunately often too late. The identification of early biomarkers is therefore essential for … effective disease management,” lead author Panteleimon Giannakopoulos, MD, said in a Study Finds report.
You may be wondering how people with more agreeable and less confrontational personalities can seek help. Well, researchers are working on that, too. It’s a complex situation, but as always, we’re rooting for you, science!
At least now you can take solace in the fact that your elderly next-door neighbor who yells at you for stepping on his lawn is probably more protected against Alzheimer’s disease.
Science says this is the ‘most boring person in the world’
Apologies up front to anyone who spends their weekends bird-watching or doing math for fun. They are among the people expected to be boring, based on stereotypes about what they do for work or how they spend their spare time, new research reveals.
Researchers surveyed more than 500 people across five related experiments to identify what people perceive as the most boring jobs, traits, and hobbies. They also report how we could all be missing out by spending as little time as possible with our tax consultant, accountant, or financial adviser outside of work.
People who work in banking, finance, accounting, data analytics, and cleaning topped the most boring list in the study, published earlier this month in Personality and Social Psychology Bulletin.
Sleeping, religion, watching television, observing animals, and spending spare time on mathematics were the stereotypical most boring hobbies and activities. The “observing animals” group includes people who bird-watch or study ants.
On the flip side, the top five most exciting jobs, in order, were in the performing arts, science, journalism, health professions, and teaching.
The researchers also looked at the how likely people are to avoid spending time with stereotypical dullards.
“Are people who are stereotyped as being boring avoided, if possible? Our current research shows that this is likely,” says Wijnand A.P. Van Tilburg, PhD, one of the researchers who did the study.
Beyond specific traits and stereotypes, Dr. Van Tilburg and colleagues found that boring people are seen as lacking skills and warmth.
“To our surprise, it appears that they are seen as both unfriendly and incompetent,” says Dr. Van Tilburg, an experimental social psychologist at the University of Essex in the United Kingdom.
What qualities do people most often ascribe to boring people? Besides being “dull,” “dry,” “bland,” and “not interesting,” common stereotypes include thinking someone who is likely boring will have no sense of humor, lack opinions, or complain.
The people surveyed also were more likely to place boring people in towns and small cities rather than large metropolitan areas.
A vicious cycle?
What’s the possible harm of relying on boring stereotypes? If people are stereotyped as being boring solely based on professions and hobbies, “then that suggests that they will incur the negative consequences associated with being a stereotypically boring person -- even when others haven’t actually interacted with them,” Dr. Van Tilburg says.
“Having a stereotypically boring profession or hobby may come with the inability to prove the biased perceivers wrong,” he says.
So making distinctions between stereotypes and realities is important, Dr. Van Tilburg says. “Those who have hobbies or occupations that are stereotypically boring do, of course, not actually have to be boring.”
Mark Leary, PhD, a professor in the department of psychology and neuroscience at Duke University in Durham, N.C., agrees. “The research actually dealt with stereotypes about the kinds of people who hold certain jobs, have certain hobbies, and live in certain places -- and not about boring people per se,” he says.
Dr. Leary points out that few people encounter bankers, tax experts, and others perceived as most boring outside a professional setting.
“When we have interactions with data analysts, accountants, insurance agents, and bankers, for example, those interactions are often boring not because the people are boring, but rather because the context is not interesting.”
To get past the preconceptions, “the best advice might be to get people to try to separate people from their roles when forming impressions of them.”
“We need to recognize that many of our interactions with other people are tied up in particular roles and topics and, thus, don’t reveal much about the other people themselves,” Dr. Leary says. “Maybe my accountant is the life of the party in other contexts.”
Dollars to avoid the dull?
The researchers also found that as the perception of how boring a person is increased, people were more likely to say they would avoid them.
To find a way to measure this avoidance, they asked people in the study how much money they would have to be paid to pal around with a perceived bore for 1 to 7 days. The payments people said they would need varied by perceptions that their boredom would be low, intermediate, or high.
As an example, they would require an average of $50 to spend one day with a highly boring person. That amount would double to $100 to spend almost 4 days in their company, and up to $230 for the week.
Dr. Leary says boredom happens when people try to pay attention to an experience or event. This means boredom goes beyond simple disinterest or trying to pay attention to someone that is not “intrinsically captivating.” When it takes more brain power to pay attention, you’ll perceive the experience as even more boring.
“Perhaps the best way to see if other people are actually boring is to talk about interesting things and see how they respond,” Dr. Leary says. “But, be careful: The topics you think make interesting conversations may be boring to others.”
A version of this article first appeared on WebMD.com.
Apologies up front to anyone who spends their weekends bird-watching or doing math for fun. They are among the people expected to be boring, based on stereotypes about what they do for work or how they spend their spare time, new research reveals.
Researchers surveyed more than 500 people across five related experiments to identify what people perceive as the most boring jobs, traits, and hobbies. They also report how we could all be missing out by spending as little time as possible with our tax consultant, accountant, or financial adviser outside of work.
People who work in banking, finance, accounting, data analytics, and cleaning topped the most boring list in the study, published earlier this month in Personality and Social Psychology Bulletin.
Sleeping, religion, watching television, observing animals, and spending spare time on mathematics were the stereotypical most boring hobbies and activities. The “observing animals” group includes people who bird-watch or study ants.
On the flip side, the top five most exciting jobs, in order, were in the performing arts, science, journalism, health professions, and teaching.
The researchers also looked at the how likely people are to avoid spending time with stereotypical dullards.
“Are people who are stereotyped as being boring avoided, if possible? Our current research shows that this is likely,” says Wijnand A.P. Van Tilburg, PhD, one of the researchers who did the study.
Beyond specific traits and stereotypes, Dr. Van Tilburg and colleagues found that boring people are seen as lacking skills and warmth.
“To our surprise, it appears that they are seen as both unfriendly and incompetent,” says Dr. Van Tilburg, an experimental social psychologist at the University of Essex in the United Kingdom.
What qualities do people most often ascribe to boring people? Besides being “dull,” “dry,” “bland,” and “not interesting,” common stereotypes include thinking someone who is likely boring will have no sense of humor, lack opinions, or complain.
The people surveyed also were more likely to place boring people in towns and small cities rather than large metropolitan areas.
A vicious cycle?
What’s the possible harm of relying on boring stereotypes? If people are stereotyped as being boring solely based on professions and hobbies, “then that suggests that they will incur the negative consequences associated with being a stereotypically boring person -- even when others haven’t actually interacted with them,” Dr. Van Tilburg says.
“Having a stereotypically boring profession or hobby may come with the inability to prove the biased perceivers wrong,” he says.
So making distinctions between stereotypes and realities is important, Dr. Van Tilburg says. “Those who have hobbies or occupations that are stereotypically boring do, of course, not actually have to be boring.”
Mark Leary, PhD, a professor in the department of psychology and neuroscience at Duke University in Durham, N.C., agrees. “The research actually dealt with stereotypes about the kinds of people who hold certain jobs, have certain hobbies, and live in certain places -- and not about boring people per se,” he says.
Dr. Leary points out that few people encounter bankers, tax experts, and others perceived as most boring outside a professional setting.
“When we have interactions with data analysts, accountants, insurance agents, and bankers, for example, those interactions are often boring not because the people are boring, but rather because the context is not interesting.”
To get past the preconceptions, “the best advice might be to get people to try to separate people from their roles when forming impressions of them.”
“We need to recognize that many of our interactions with other people are tied up in particular roles and topics and, thus, don’t reveal much about the other people themselves,” Dr. Leary says. “Maybe my accountant is the life of the party in other contexts.”
Dollars to avoid the dull?
The researchers also found that as the perception of how boring a person is increased, people were more likely to say they would avoid them.
To find a way to measure this avoidance, they asked people in the study how much money they would have to be paid to pal around with a perceived bore for 1 to 7 days. The payments people said they would need varied by perceptions that their boredom would be low, intermediate, or high.
As an example, they would require an average of $50 to spend one day with a highly boring person. That amount would double to $100 to spend almost 4 days in their company, and up to $230 for the week.
Dr. Leary says boredom happens when people try to pay attention to an experience or event. This means boredom goes beyond simple disinterest or trying to pay attention to someone that is not “intrinsically captivating.” When it takes more brain power to pay attention, you’ll perceive the experience as even more boring.
“Perhaps the best way to see if other people are actually boring is to talk about interesting things and see how they respond,” Dr. Leary says. “But, be careful: The topics you think make interesting conversations may be boring to others.”
A version of this article first appeared on WebMD.com.
Apologies up front to anyone who spends their weekends bird-watching or doing math for fun. They are among the people expected to be boring, based on stereotypes about what they do for work or how they spend their spare time, new research reveals.
Researchers surveyed more than 500 people across five related experiments to identify what people perceive as the most boring jobs, traits, and hobbies. They also report how we could all be missing out by spending as little time as possible with our tax consultant, accountant, or financial adviser outside of work.
People who work in banking, finance, accounting, data analytics, and cleaning topped the most boring list in the study, published earlier this month in Personality and Social Psychology Bulletin.
Sleeping, religion, watching television, observing animals, and spending spare time on mathematics were the stereotypical most boring hobbies and activities. The “observing animals” group includes people who bird-watch or study ants.
On the flip side, the top five most exciting jobs, in order, were in the performing arts, science, journalism, health professions, and teaching.
The researchers also looked at the how likely people are to avoid spending time with stereotypical dullards.
“Are people who are stereotyped as being boring avoided, if possible? Our current research shows that this is likely,” says Wijnand A.P. Van Tilburg, PhD, one of the researchers who did the study.
Beyond specific traits and stereotypes, Dr. Van Tilburg and colleagues found that boring people are seen as lacking skills and warmth.
“To our surprise, it appears that they are seen as both unfriendly and incompetent,” says Dr. Van Tilburg, an experimental social psychologist at the University of Essex in the United Kingdom.
What qualities do people most often ascribe to boring people? Besides being “dull,” “dry,” “bland,” and “not interesting,” common stereotypes include thinking someone who is likely boring will have no sense of humor, lack opinions, or complain.
The people surveyed also were more likely to place boring people in towns and small cities rather than large metropolitan areas.
A vicious cycle?
What’s the possible harm of relying on boring stereotypes? If people are stereotyped as being boring solely based on professions and hobbies, “then that suggests that they will incur the negative consequences associated with being a stereotypically boring person -- even when others haven’t actually interacted with them,” Dr. Van Tilburg says.
“Having a stereotypically boring profession or hobby may come with the inability to prove the biased perceivers wrong,” he says.
So making distinctions between stereotypes and realities is important, Dr. Van Tilburg says. “Those who have hobbies or occupations that are stereotypically boring do, of course, not actually have to be boring.”
Mark Leary, PhD, a professor in the department of psychology and neuroscience at Duke University in Durham, N.C., agrees. “The research actually dealt with stereotypes about the kinds of people who hold certain jobs, have certain hobbies, and live in certain places -- and not about boring people per se,” he says.
Dr. Leary points out that few people encounter bankers, tax experts, and others perceived as most boring outside a professional setting.
“When we have interactions with data analysts, accountants, insurance agents, and bankers, for example, those interactions are often boring not because the people are boring, but rather because the context is not interesting.”
To get past the preconceptions, “the best advice might be to get people to try to separate people from their roles when forming impressions of them.”
“We need to recognize that many of our interactions with other people are tied up in particular roles and topics and, thus, don’t reveal much about the other people themselves,” Dr. Leary says. “Maybe my accountant is the life of the party in other contexts.”
Dollars to avoid the dull?
The researchers also found that as the perception of how boring a person is increased, people were more likely to say they would avoid them.
To find a way to measure this avoidance, they asked people in the study how much money they would have to be paid to pal around with a perceived bore for 1 to 7 days. The payments people said they would need varied by perceptions that their boredom would be low, intermediate, or high.
As an example, they would require an average of $50 to spend one day with a highly boring person. That amount would double to $100 to spend almost 4 days in their company, and up to $230 for the week.
Dr. Leary says boredom happens when people try to pay attention to an experience or event. This means boredom goes beyond simple disinterest or trying to pay attention to someone that is not “intrinsically captivating.” When it takes more brain power to pay attention, you’ll perceive the experience as even more boring.
“Perhaps the best way to see if other people are actually boring is to talk about interesting things and see how they respond,” Dr. Leary says. “But, be careful: The topics you think make interesting conversations may be boring to others.”
A version of this article first appeared on WebMD.com.
FROM PERSONALITY AND SOCIAL PSYCHOLOGY BULLETIN
TikTok trends: Sleepy lettuce water, cyst smacking, and prostaglandin pain
Spring is the time for new beginnings, cleaning out your dusty musty basement, battling seasonal allergies, and, of course, discovering the latest TikTok trends.
With potentially permanent daylight savings on the table, that extra time spent luxuriating in the sunshine could mean more time to scroll (and scroll and scroll) through the latest health fads on the platform – for better or for worse.
The good: Doctor explains menstrual pain in an unexpected place
For a long time, menstrual cycles were considered taboo, and discussing them is still seen as inappropriate in many parts of the world. Organizations and online resources such as Clue or Flo are seeking to normalize period-talk. Pixar has jumped on board with its latest film, Turning Red, which depicts a 13-year-old’s experience getting her first period. With a 95% rating on Rotten Tomatoes, it’s clear that the public is willing to talk about periods.
Many people feel shame around discussing their periods, but this is something that social media has actually handled positively (for once).
Karan Raj, MD, a National Health Service surgeon and educator at Imperial College London, uses his TikTok account to educate his followers and explain health concerns and issues. Dr. Raj stitched this video from someone else that was captioned, “When you’re on your [period] and feel the stab in your booty.”
In his video, Dr. Raj uses anatomical diagrams to explain exactly what’s going on with this pain in the butt. The pain, which Dr. Raj says is called proctalgia fugax, is caused by a type of hormone released during menstruation called prostaglandins. Prostaglandins tell the uterus to contract and shed its lining, but the uterus isn’t the only part of the body receiving that message from the prostaglandins.
“The prostaglandins also cause contraction of the rectum, pelvic floor muscles, and muscles around the anal canal,” Dr. Raj tells viewers. “These intense contractions can cause muscle spasms and anal cramps.”
The bad: Lettuce water sleep aid
This video from Elliott Norris (@callmebelly) shows him preparing an unusual sleep aid. It’s one of many videos of people trying the same trend, usually with the tag #lettucewater attached.
As Mr. Elliott explains, the rumor is that boiling romaine lettuce and then drinking the water is a way to help one fall asleep faster, or sleep better at night. At the end of the video, Mr. Elliott even said that it worked for him. So where does this come from, and is it just a placebo?
Videos on TikTok recreating this trend cite a 2017 study titled, “Sleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep” (there’s even a New York Times article about it). The star of the study is lactucarium, a milky white substance that›s found in lettuce, usually visible if you squeeze it or break the stalks. The study suggests that lactucarium has “sedative-hypnotic” properties after lettuce extract was used in tandem with pentobarbital on mice, and it was found that the mice›s sleep latency then decreased.
In an article from Parade discussing the trend, Rachel Salas, MD, MEd, weighs in. Dr. Salas is the assistant medical director at Johns Hopkins Center for Sleep and Wellness in Baltimore, so you could say she knows a thing or two about sleep. Her response to the mice study was that its limitations made the results not entirely reliable.
According to Dr. Salas, there was no control group, the extract the mice were given is much more concentrated than what’s found in lettuce, and the mice were given a sedative that was going to make them sleepy anyway: “The mice were drugged to put the animals to sleep soon after they took the lettuce water.”
So while Dr. Salas thinks it’s good that people are open to talking about sleeping solutions, “lettuce tea” just doesn’t have any evidence to back up what people claim it does.
The ugly: Using a book to pop ganglion cysts
Everyone knows how popular pimple popping, blackhead squeezing, and cyst squashing are on social media. Dermatologist Sandra Lee, better known as Dr. Pimple Popper, used her YouTube platform of the same name – which boasts over 7.42 million subscribers – to cinch a reality television show on TLC. Viewers on TikTok are no different and love the satisfying (and often gross) relief of clearing out a nasty pimple or two.
In this stitched TikTok from emergency medicine physician Fayez Ajib, DO, aka @lifeofadoctor, Dr. Ajib reacts to an original video of someone popping a ganglion cyst with a textbook.
There are plenty of other videos on TikTok of people using books to smack ganglion cysts, which develop on the wrist. People have looked for remedies for ganglion cysts since the 1700s, at which point many strange options arose, as discussed in BBC Future. The one that still holds up, however, is smacking the cyst with a heavy book, like a Bible (hence the ganglion cyst’s nickname, “Bible bump”).
In his video, Dr. Ajib explains why smacking the cyst is a bad idea, even if it appears to temporarily resolve the issue.
“Not only have people broken the delicate bones in their wrist from getting hit,” Dr. Ajib says, “but they actually have a high chance of recurrence. A doctor will actually remove the sac itself rather than just draining it from being hit.”
The lessons we glean from TikTok remain the same: Leave it up to the professionals.
A version of this article first appeared on Medscape.com.
Spring is the time for new beginnings, cleaning out your dusty musty basement, battling seasonal allergies, and, of course, discovering the latest TikTok trends.
With potentially permanent daylight savings on the table, that extra time spent luxuriating in the sunshine could mean more time to scroll (and scroll and scroll) through the latest health fads on the platform – for better or for worse.
The good: Doctor explains menstrual pain in an unexpected place
For a long time, menstrual cycles were considered taboo, and discussing them is still seen as inappropriate in many parts of the world. Organizations and online resources such as Clue or Flo are seeking to normalize period-talk. Pixar has jumped on board with its latest film, Turning Red, which depicts a 13-year-old’s experience getting her first period. With a 95% rating on Rotten Tomatoes, it’s clear that the public is willing to talk about periods.
Many people feel shame around discussing their periods, but this is something that social media has actually handled positively (for once).
Karan Raj, MD, a National Health Service surgeon and educator at Imperial College London, uses his TikTok account to educate his followers and explain health concerns and issues. Dr. Raj stitched this video from someone else that was captioned, “When you’re on your [period] and feel the stab in your booty.”
In his video, Dr. Raj uses anatomical diagrams to explain exactly what’s going on with this pain in the butt. The pain, which Dr. Raj says is called proctalgia fugax, is caused by a type of hormone released during menstruation called prostaglandins. Prostaglandins tell the uterus to contract and shed its lining, but the uterus isn’t the only part of the body receiving that message from the prostaglandins.
“The prostaglandins also cause contraction of the rectum, pelvic floor muscles, and muscles around the anal canal,” Dr. Raj tells viewers. “These intense contractions can cause muscle spasms and anal cramps.”
The bad: Lettuce water sleep aid
This video from Elliott Norris (@callmebelly) shows him preparing an unusual sleep aid. It’s one of many videos of people trying the same trend, usually with the tag #lettucewater attached.
As Mr. Elliott explains, the rumor is that boiling romaine lettuce and then drinking the water is a way to help one fall asleep faster, or sleep better at night. At the end of the video, Mr. Elliott even said that it worked for him. So where does this come from, and is it just a placebo?
Videos on TikTok recreating this trend cite a 2017 study titled, “Sleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep” (there’s even a New York Times article about it). The star of the study is lactucarium, a milky white substance that›s found in lettuce, usually visible if you squeeze it or break the stalks. The study suggests that lactucarium has “sedative-hypnotic” properties after lettuce extract was used in tandem with pentobarbital on mice, and it was found that the mice›s sleep latency then decreased.
In an article from Parade discussing the trend, Rachel Salas, MD, MEd, weighs in. Dr. Salas is the assistant medical director at Johns Hopkins Center for Sleep and Wellness in Baltimore, so you could say she knows a thing or two about sleep. Her response to the mice study was that its limitations made the results not entirely reliable.
According to Dr. Salas, there was no control group, the extract the mice were given is much more concentrated than what’s found in lettuce, and the mice were given a sedative that was going to make them sleepy anyway: “The mice were drugged to put the animals to sleep soon after they took the lettuce water.”
So while Dr. Salas thinks it’s good that people are open to talking about sleeping solutions, “lettuce tea” just doesn’t have any evidence to back up what people claim it does.
The ugly: Using a book to pop ganglion cysts
Everyone knows how popular pimple popping, blackhead squeezing, and cyst squashing are on social media. Dermatologist Sandra Lee, better known as Dr. Pimple Popper, used her YouTube platform of the same name – which boasts over 7.42 million subscribers – to cinch a reality television show on TLC. Viewers on TikTok are no different and love the satisfying (and often gross) relief of clearing out a nasty pimple or two.
In this stitched TikTok from emergency medicine physician Fayez Ajib, DO, aka @lifeofadoctor, Dr. Ajib reacts to an original video of someone popping a ganglion cyst with a textbook.
There are plenty of other videos on TikTok of people using books to smack ganglion cysts, which develop on the wrist. People have looked for remedies for ganglion cysts since the 1700s, at which point many strange options arose, as discussed in BBC Future. The one that still holds up, however, is smacking the cyst with a heavy book, like a Bible (hence the ganglion cyst’s nickname, “Bible bump”).
In his video, Dr. Ajib explains why smacking the cyst is a bad idea, even if it appears to temporarily resolve the issue.
“Not only have people broken the delicate bones in their wrist from getting hit,” Dr. Ajib says, “but they actually have a high chance of recurrence. A doctor will actually remove the sac itself rather than just draining it from being hit.”
The lessons we glean from TikTok remain the same: Leave it up to the professionals.
A version of this article first appeared on Medscape.com.
Spring is the time for new beginnings, cleaning out your dusty musty basement, battling seasonal allergies, and, of course, discovering the latest TikTok trends.
With potentially permanent daylight savings on the table, that extra time spent luxuriating in the sunshine could mean more time to scroll (and scroll and scroll) through the latest health fads on the platform – for better or for worse.
The good: Doctor explains menstrual pain in an unexpected place
For a long time, menstrual cycles were considered taboo, and discussing them is still seen as inappropriate in many parts of the world. Organizations and online resources such as Clue or Flo are seeking to normalize period-talk. Pixar has jumped on board with its latest film, Turning Red, which depicts a 13-year-old’s experience getting her first period. With a 95% rating on Rotten Tomatoes, it’s clear that the public is willing to talk about periods.
Many people feel shame around discussing their periods, but this is something that social media has actually handled positively (for once).
Karan Raj, MD, a National Health Service surgeon and educator at Imperial College London, uses his TikTok account to educate his followers and explain health concerns and issues. Dr. Raj stitched this video from someone else that was captioned, “When you’re on your [period] and feel the stab in your booty.”
In his video, Dr. Raj uses anatomical diagrams to explain exactly what’s going on with this pain in the butt. The pain, which Dr. Raj says is called proctalgia fugax, is caused by a type of hormone released during menstruation called prostaglandins. Prostaglandins tell the uterus to contract and shed its lining, but the uterus isn’t the only part of the body receiving that message from the prostaglandins.
“The prostaglandins also cause contraction of the rectum, pelvic floor muscles, and muscles around the anal canal,” Dr. Raj tells viewers. “These intense contractions can cause muscle spasms and anal cramps.”
The bad: Lettuce water sleep aid
This video from Elliott Norris (@callmebelly) shows him preparing an unusual sleep aid. It’s one of many videos of people trying the same trend, usually with the tag #lettucewater attached.
As Mr. Elliott explains, the rumor is that boiling romaine lettuce and then drinking the water is a way to help one fall asleep faster, or sleep better at night. At the end of the video, Mr. Elliott even said that it worked for him. So where does this come from, and is it just a placebo?
Videos on TikTok recreating this trend cite a 2017 study titled, “Sleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep” (there’s even a New York Times article about it). The star of the study is lactucarium, a milky white substance that›s found in lettuce, usually visible if you squeeze it or break the stalks. The study suggests that lactucarium has “sedative-hypnotic” properties after lettuce extract was used in tandem with pentobarbital on mice, and it was found that the mice›s sleep latency then decreased.
In an article from Parade discussing the trend, Rachel Salas, MD, MEd, weighs in. Dr. Salas is the assistant medical director at Johns Hopkins Center for Sleep and Wellness in Baltimore, so you could say she knows a thing or two about sleep. Her response to the mice study was that its limitations made the results not entirely reliable.
According to Dr. Salas, there was no control group, the extract the mice were given is much more concentrated than what’s found in lettuce, and the mice were given a sedative that was going to make them sleepy anyway: “The mice were drugged to put the animals to sleep soon after they took the lettuce water.”
So while Dr. Salas thinks it’s good that people are open to talking about sleeping solutions, “lettuce tea” just doesn’t have any evidence to back up what people claim it does.
The ugly: Using a book to pop ganglion cysts
Everyone knows how popular pimple popping, blackhead squeezing, and cyst squashing are on social media. Dermatologist Sandra Lee, better known as Dr. Pimple Popper, used her YouTube platform of the same name – which boasts over 7.42 million subscribers – to cinch a reality television show on TLC. Viewers on TikTok are no different and love the satisfying (and often gross) relief of clearing out a nasty pimple or two.
In this stitched TikTok from emergency medicine physician Fayez Ajib, DO, aka @lifeofadoctor, Dr. Ajib reacts to an original video of someone popping a ganglion cyst with a textbook.
There are plenty of other videos on TikTok of people using books to smack ganglion cysts, which develop on the wrist. People have looked for remedies for ganglion cysts since the 1700s, at which point many strange options arose, as discussed in BBC Future. The one that still holds up, however, is smacking the cyst with a heavy book, like a Bible (hence the ganglion cyst’s nickname, “Bible bump”).
In his video, Dr. Ajib explains why smacking the cyst is a bad idea, even if it appears to temporarily resolve the issue.
“Not only have people broken the delicate bones in their wrist from getting hit,” Dr. Ajib says, “but they actually have a high chance of recurrence. A doctor will actually remove the sac itself rather than just draining it from being hit.”
The lessons we glean from TikTok remain the same: Leave it up to the professionals.
A version of this article first appeared on Medscape.com.
Drugs used for nausea/vomiting linked to stroke risk
Antidopaminergic antiemetics (ADAs) that are widely used for nausea and vomiting, including that related to chemotherapy, have been associated with an increased risk of ischemic stroke in a new study from France.
The authors found that ADA users could be at a threefold increased risk of stroke shortly after the initiation of treatment.
Further analysis showed that all three ADAs studied (domperidone, metopimazine, and metoclopramide) were associated with an increased risk, especially in the first days of use, but the highest increase was found for metopimazine and metoclopramide.
The study was published online March 23, 2022, in the BMJ.
“Our results show that the risk of ischemic stroke appears to be associated with ADA use,” wrote the authors, led by Anne Bénard-Laribière, PharmD, MS, of the University of Bordeaux (France). They emphasized, however, that this is an observational study and cannot therefore establish causation.
One important note about this study is that patients with a history of cancer were specifically excluded. The authors did not elaborate on what the ADAs were being used for, other than to say that ADAs are used for nausea and vomiting of “variable origins,” and a press release noted that these drugs are often used by patients with migraine.
Hence it is not clear what relevance these findings have for patients with cancer, suggested an expert unrelated to the study, Ian Olver, MD, PhD, professorial research fellow, faculty of health and medical sciences, University of Adelaide.
“So the best that can be said, from my viewpoint, is that the ADAs studied have been associated with an increased risk of stroke in patients other than cancer patients,” he told this news organization.
In addition, he also emphasized that an observational study cannot establish causation.
For their study, the authors used data from the nationwide reimbursement database. Hence, they “needed to make the assumption that the date of reimbursement approximated to the date of administration, and that would not be the case for drugs used prophylactically prior to chemotherapy or radiotherapy,” Dr. Olver commented.
The authors were also unable to make any statement about dose and schedule. “Certainly chemotherapy-induced nausea and vomiting would require more intermittent dosing compared to noncancer uses,” Dr. Olver said. In addition, “metoclopramide in conventional doses is not very effective for this purpose and metopimazine is mainly used in Europe.”
Most patients with cancer would not be receiving these drugs, he suggested: “These days they would be receiving 5HT3 receptor antagonists and NK1 receptor antagonists and steroids.”
Study details
The French study investigated the risk of ischemic stroke associated with ADA use in a real-world setting. The authors conducted a case-time-control study using data from the nationwide French reimbursement health care system database Système National des Données de Santé.
They identified 2,612 patients from the database who had experienced a first ischemic stroke between 2012 and 2016 and had also received at least one reimbursement for domperidone, metopimazine, or metoclopramide during the 70-day period prior to their stroke.
The frequency of reimbursements for ADAs was compared with a risk period (1-14 days before a stroke) and three matched reference periods (57-70 days, 43-56 days, and 29-42 days before stroke).
Patients who had experienced a stroke were matched to a control group of 21,859 randomly selected healthy people who also received an ADA in the same time period.
Within the stroke cohort, 1,250 patients received an ADA at least once during the designated risk period and 1,060 in the reference periods. Among the controls, 5,128 and 13,165 received an ADA at least one time in the risk and reference periods, respectively.
This yielded a case-time-control ratio of adjusted odds ratios of 3.12, of a risk of stroke among new users. Stratification by age (<70 years and ≥70 years), sex, history of dementia, and gastroenteritis epidemic periods revealed similar results, although the highest case-time-control ratio observed in men(aOR, 3.59).
The risk of stroke appeared to increase for all ADAs, but the highest was for metopimazine (3.62-fold increase) and metoclopramide (a 3.53-fold increase), which are both drugs that have the ability to cross the blood-brain barrier.
The study was funded by Agence Nationale de Sécurité du Médicament et des Produits de Santé through a partnership with the Health Product Epidemiology Scientific Interest Group. All authors had financial support from ANSM for the submitted work; one coauthor disclosed relationships with Pfizer and Roche. Dr. Olver disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Antidopaminergic antiemetics (ADAs) that are widely used for nausea and vomiting, including that related to chemotherapy, have been associated with an increased risk of ischemic stroke in a new study from France.
The authors found that ADA users could be at a threefold increased risk of stroke shortly after the initiation of treatment.
Further analysis showed that all three ADAs studied (domperidone, metopimazine, and metoclopramide) were associated with an increased risk, especially in the first days of use, but the highest increase was found for metopimazine and metoclopramide.
The study was published online March 23, 2022, in the BMJ.
“Our results show that the risk of ischemic stroke appears to be associated with ADA use,” wrote the authors, led by Anne Bénard-Laribière, PharmD, MS, of the University of Bordeaux (France). They emphasized, however, that this is an observational study and cannot therefore establish causation.
One important note about this study is that patients with a history of cancer were specifically excluded. The authors did not elaborate on what the ADAs were being used for, other than to say that ADAs are used for nausea and vomiting of “variable origins,” and a press release noted that these drugs are often used by patients with migraine.
Hence it is not clear what relevance these findings have for patients with cancer, suggested an expert unrelated to the study, Ian Olver, MD, PhD, professorial research fellow, faculty of health and medical sciences, University of Adelaide.
“So the best that can be said, from my viewpoint, is that the ADAs studied have been associated with an increased risk of stroke in patients other than cancer patients,” he told this news organization.
In addition, he also emphasized that an observational study cannot establish causation.
For their study, the authors used data from the nationwide reimbursement database. Hence, they “needed to make the assumption that the date of reimbursement approximated to the date of administration, and that would not be the case for drugs used prophylactically prior to chemotherapy or radiotherapy,” Dr. Olver commented.
The authors were also unable to make any statement about dose and schedule. “Certainly chemotherapy-induced nausea and vomiting would require more intermittent dosing compared to noncancer uses,” Dr. Olver said. In addition, “metoclopramide in conventional doses is not very effective for this purpose and metopimazine is mainly used in Europe.”
Most patients with cancer would not be receiving these drugs, he suggested: “These days they would be receiving 5HT3 receptor antagonists and NK1 receptor antagonists and steroids.”
Study details
The French study investigated the risk of ischemic stroke associated with ADA use in a real-world setting. The authors conducted a case-time-control study using data from the nationwide French reimbursement health care system database Système National des Données de Santé.
They identified 2,612 patients from the database who had experienced a first ischemic stroke between 2012 and 2016 and had also received at least one reimbursement for domperidone, metopimazine, or metoclopramide during the 70-day period prior to their stroke.
The frequency of reimbursements for ADAs was compared with a risk period (1-14 days before a stroke) and three matched reference periods (57-70 days, 43-56 days, and 29-42 days before stroke).
Patients who had experienced a stroke were matched to a control group of 21,859 randomly selected healthy people who also received an ADA in the same time period.
Within the stroke cohort, 1,250 patients received an ADA at least once during the designated risk period and 1,060 in the reference periods. Among the controls, 5,128 and 13,165 received an ADA at least one time in the risk and reference periods, respectively.
This yielded a case-time-control ratio of adjusted odds ratios of 3.12, of a risk of stroke among new users. Stratification by age (<70 years and ≥70 years), sex, history of dementia, and gastroenteritis epidemic periods revealed similar results, although the highest case-time-control ratio observed in men(aOR, 3.59).
The risk of stroke appeared to increase for all ADAs, but the highest was for metopimazine (3.62-fold increase) and metoclopramide (a 3.53-fold increase), which are both drugs that have the ability to cross the blood-brain barrier.
The study was funded by Agence Nationale de Sécurité du Médicament et des Produits de Santé through a partnership with the Health Product Epidemiology Scientific Interest Group. All authors had financial support from ANSM for the submitted work; one coauthor disclosed relationships with Pfizer and Roche. Dr. Olver disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Antidopaminergic antiemetics (ADAs) that are widely used for nausea and vomiting, including that related to chemotherapy, have been associated with an increased risk of ischemic stroke in a new study from France.
The authors found that ADA users could be at a threefold increased risk of stroke shortly after the initiation of treatment.
Further analysis showed that all three ADAs studied (domperidone, metopimazine, and metoclopramide) were associated with an increased risk, especially in the first days of use, but the highest increase was found for metopimazine and metoclopramide.
The study was published online March 23, 2022, in the BMJ.
“Our results show that the risk of ischemic stroke appears to be associated with ADA use,” wrote the authors, led by Anne Bénard-Laribière, PharmD, MS, of the University of Bordeaux (France). They emphasized, however, that this is an observational study and cannot therefore establish causation.
One important note about this study is that patients with a history of cancer were specifically excluded. The authors did not elaborate on what the ADAs were being used for, other than to say that ADAs are used for nausea and vomiting of “variable origins,” and a press release noted that these drugs are often used by patients with migraine.
Hence it is not clear what relevance these findings have for patients with cancer, suggested an expert unrelated to the study, Ian Olver, MD, PhD, professorial research fellow, faculty of health and medical sciences, University of Adelaide.
“So the best that can be said, from my viewpoint, is that the ADAs studied have been associated with an increased risk of stroke in patients other than cancer patients,” he told this news organization.
In addition, he also emphasized that an observational study cannot establish causation.
For their study, the authors used data from the nationwide reimbursement database. Hence, they “needed to make the assumption that the date of reimbursement approximated to the date of administration, and that would not be the case for drugs used prophylactically prior to chemotherapy or radiotherapy,” Dr. Olver commented.
The authors were also unable to make any statement about dose and schedule. “Certainly chemotherapy-induced nausea and vomiting would require more intermittent dosing compared to noncancer uses,” Dr. Olver said. In addition, “metoclopramide in conventional doses is not very effective for this purpose and metopimazine is mainly used in Europe.”
Most patients with cancer would not be receiving these drugs, he suggested: “These days they would be receiving 5HT3 receptor antagonists and NK1 receptor antagonists and steroids.”
Study details
The French study investigated the risk of ischemic stroke associated with ADA use in a real-world setting. The authors conducted a case-time-control study using data from the nationwide French reimbursement health care system database Système National des Données de Santé.
They identified 2,612 patients from the database who had experienced a first ischemic stroke between 2012 and 2016 and had also received at least one reimbursement for domperidone, metopimazine, or metoclopramide during the 70-day period prior to their stroke.
The frequency of reimbursements for ADAs was compared with a risk period (1-14 days before a stroke) and three matched reference periods (57-70 days, 43-56 days, and 29-42 days before stroke).
Patients who had experienced a stroke were matched to a control group of 21,859 randomly selected healthy people who also received an ADA in the same time period.
Within the stroke cohort, 1,250 patients received an ADA at least once during the designated risk period and 1,060 in the reference periods. Among the controls, 5,128 and 13,165 received an ADA at least one time in the risk and reference periods, respectively.
This yielded a case-time-control ratio of adjusted odds ratios of 3.12, of a risk of stroke among new users. Stratification by age (<70 years and ≥70 years), sex, history of dementia, and gastroenteritis epidemic periods revealed similar results, although the highest case-time-control ratio observed in men(aOR, 3.59).
The risk of stroke appeared to increase for all ADAs, but the highest was for metopimazine (3.62-fold increase) and metoclopramide (a 3.53-fold increase), which are both drugs that have the ability to cross the blood-brain barrier.
The study was funded by Agence Nationale de Sécurité du Médicament et des Produits de Santé through a partnership with the Health Product Epidemiology Scientific Interest Group. All authors had financial support from ANSM for the submitted work; one coauthor disclosed relationships with Pfizer and Roche. Dr. Olver disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE BMJ
Does evidence support benefits of omega-3 fatty acids?
Dietary supplements that contain omega-3 fatty acids have been widely consumed for years. Researchers have been investigating the benefits of such preparations for cardiovascular, neurologic, and psychological conditions. A recently published study on omega-3 fatty acids and depression inspired neurologist Hans-Christoph Diener, MD, PhD, of the Institute for Epidemiology at the University Duisburg-Essen (Germany), to examine scientific publications concerning omega-3 fatty acids or fish-oil capsules in more detail.
Prevention of depression
Dr. Diener told the story of how he stumbled upon an interesting article in JAMA in December 2021. It was about a placebo-controlled study that investigated whether omega-3 fatty acids can prevent incident depression.
As the study authors reported, treatment with omega-3 preparations in adults aged 50 years or older without clinically relevant symptoms of depression at study initiation was associated with a small but statistically significant increase in the risk for depression or clinically relevant symptoms of depression. There was no difference in mood scale value, however, over a median follow-up of 5.3 years. According to the study authors, these results did not support the administration of omega-3 preparations for the prevention of depression.
This study was, as Dr. Diener said, somewhat negative, but it did arouse his interest in questions such as what biological effects omega-3 fatty acids have and what is known “about this topic with regard to neurology,” he said. When reviewing the literature, he noticed that there “were association studies, i.e., studies that describe that the intake of omega-3 fatty acids may possibly be associated with a lower risk of certain diseases.”
Beginning with the Inuit
It all started “with observations of the Inuit [population] in Greenland and Alaska after World War II, because it was remarked upon that these people ate a lot of fish and seal meat and had a very low incidence of cardiovascular diseases.” Over the years, a large number of association studies have been published, which may have encouraged the assumption that omega-3 fatty acids have positive health effects on various conditions, such as cardiovascular diseases, hyperlipidemia, type 2 diabetes, various malignancies, cognitive impairments, Alzheimer’s disease, depression and anxiety disorders, heart failure, slipped disks, ADHD, symptoms of menopause, rheumatoid arthritis, asthma, periodontitis, epilepsy, chemotherapy tolerance, premenstrual syndrome, and nonalcoholic fatty liver disease.
Dr. Diener believes that the problem is that these are association studies. But association does not mean that there is a causal relationship.
Disappointing study results
On the contrary, the results from the randomized placebo-controlled studies are truly frustrating, according to the neurologist. A meta-analysis of the use of omega-3 fatty acids in cardiovascular diseases included 86 studies with over 162,000 patients. According to Dr. Diener, it did not reveal any benefit for overall and cardiovascular mortality, nor any benefit for the reduction of myocardial infarction and stroke.
The results did indicate a trend, however, for reduced mortality in coronary heart disease. Even so, the number needed to treat for this was 334, which means that 334 people would have to take omega-3 fatty acids for years to prevent one fatal cardiac event.
Aside from this study, Dr. Diener found six studies on Alzheimer’s disease and three studies on dementia with patient populations between 600 and 800. In these studies, too, a positive effect of omega-3 fatty acids could not be identified. Then he discovered another 31 placebo-controlled studies of omega-3 fatty acids for the treatment or prevention of depression and anxiety disorder. Despite including 50,000 patients, these studies also did not show any positive effect.
“I see a significant discrepancy between the promotion of omega-3 fatty acids, whether it’s on television, in the ‘yellow’ [journalism] press, or in advertisements, and the actual scientific evidence,” said Dr. Diener. “At least from a neurological perspective, there is no evidence that omega-3 fatty acids have any benefit. This is true for strokes, dementia, Alzheimer’s disease, depression, and anxiety disorders.”
Potential adverse effects
Omega-3 fatty acids also have potentially adverse effects. The VITAL Rhythm study recently provided evidence that, depending on the dose, preparations with omega-3 fatty acids may increase the risk for atrial fibrillation. As the authors wrote, the results do not support taking omega-3 fatty acids to prevent atrial fibrillation.
In 2019, the global market for omega-3 fatty acids reached a value of $4.1 billion. This value is expected to double by 2025, according to a comment by Gregory Curfman, MD, deputy editor of JAMA and lecturer in health care policy at Harvard Medical School, Boston.
As Dr. Curfman wrote, this impressive amount of expenditure shows how beloved these products are and how strongly many people believe that omega-3 fatty acids are beneficial for their health. It is therefore important to know the potential risks of such preparations. One such example for this would be the risk for atrial fibrillation.
According to Dr. Curfman, in the last 2 years, four randomized clinical studies have provided data on the risk for atrial fibrillation associated with omega-3 fatty acids. In the STRENGTH study, 13,078 high-risk patients with cardiovascular diseases were randomly assigned to one of two groups. The subjects received either a high dose (4 g/day) of a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or corn oil. After a median of 42 months, there was no significant difference between the two groups in the primary composite cardiovascular endpoint, but more frequent atrial fibrillation in the omega-3 fatty acid group, compared with the corn oil group (2.2% vs. 1.3%; hazard ratio, 1.69; 95% confidence interval, 1.29-2.21; P < .001).
In the REDUCE-IT study, 8179 subjects were randomly assigned to a high dose (4 g/day, as in STRENGTH) of an omega-3 fatty acid preparation consisting of a purified EPA (icosapent ethyl) or mineral oil. After a median observation period of 4.9 years, icosapent ethyl was associated with a relative reduction of the primary composite cardiovascular endpoint by 25%, compared with mineral oil. As in the STRENGTH study, this study found that the risk for atrial fibrillation associated with omega-3 fatty acids, compared with mineral oil, was significantly higher (5.3% vs. 3.9%; P = .003).
In a third study (OMEMI), as Dr. Curfman reported, 1027 elderly patients who had recently had a myocardial infarction were randomly assigned to receive either a median dose of 1.8 g/day of omega-3 fatty acids (a combination of EPA and DHA) or corn oil. After 2 years, there was no significant difference between the two groups in primary composite cardiovascular endpoints, but 7.2% of the patients taking omega-3 fatty acids developed atrial fibrillation. In the corn oil group, this proportion was 4% (HR, 1.84; 95% CI, 0.98-3.45; P = .06).
The data from the four studies together indicate a potential dose-dependent risk for atrial fibrillation associated with omega-3 fatty acids, according to Dr. Curfman. At a dose of 4.0 g/day, there is a highly significant risk increase (almost double). With a median dose of 1.8 g/day, the risk increase (HR, 1.84) did not reach statistical significance. At a daily standard dose of 840 mg/day, an increase in risk could not be determined.
Dr. Curfman’s recommendation is that patients who take, or want to take, preparations with omega-3 fatty acids be informed of the potential development of arrhythmia at higher dosages. These patients also should undergo cardiological monitoring.
A version of this article first appeared on Medscape.com.
Dietary supplements that contain omega-3 fatty acids have been widely consumed for years. Researchers have been investigating the benefits of such preparations for cardiovascular, neurologic, and psychological conditions. A recently published study on omega-3 fatty acids and depression inspired neurologist Hans-Christoph Diener, MD, PhD, of the Institute for Epidemiology at the University Duisburg-Essen (Germany), to examine scientific publications concerning omega-3 fatty acids or fish-oil capsules in more detail.
Prevention of depression
Dr. Diener told the story of how he stumbled upon an interesting article in JAMA in December 2021. It was about a placebo-controlled study that investigated whether omega-3 fatty acids can prevent incident depression.
As the study authors reported, treatment with omega-3 preparations in adults aged 50 years or older without clinically relevant symptoms of depression at study initiation was associated with a small but statistically significant increase in the risk for depression or clinically relevant symptoms of depression. There was no difference in mood scale value, however, over a median follow-up of 5.3 years. According to the study authors, these results did not support the administration of omega-3 preparations for the prevention of depression.
This study was, as Dr. Diener said, somewhat negative, but it did arouse his interest in questions such as what biological effects omega-3 fatty acids have and what is known “about this topic with regard to neurology,” he said. When reviewing the literature, he noticed that there “were association studies, i.e., studies that describe that the intake of omega-3 fatty acids may possibly be associated with a lower risk of certain diseases.”
Beginning with the Inuit
It all started “with observations of the Inuit [population] in Greenland and Alaska after World War II, because it was remarked upon that these people ate a lot of fish and seal meat and had a very low incidence of cardiovascular diseases.” Over the years, a large number of association studies have been published, which may have encouraged the assumption that omega-3 fatty acids have positive health effects on various conditions, such as cardiovascular diseases, hyperlipidemia, type 2 diabetes, various malignancies, cognitive impairments, Alzheimer’s disease, depression and anxiety disorders, heart failure, slipped disks, ADHD, symptoms of menopause, rheumatoid arthritis, asthma, periodontitis, epilepsy, chemotherapy tolerance, premenstrual syndrome, and nonalcoholic fatty liver disease.
Dr. Diener believes that the problem is that these are association studies. But association does not mean that there is a causal relationship.
Disappointing study results
On the contrary, the results from the randomized placebo-controlled studies are truly frustrating, according to the neurologist. A meta-analysis of the use of omega-3 fatty acids in cardiovascular diseases included 86 studies with over 162,000 patients. According to Dr. Diener, it did not reveal any benefit for overall and cardiovascular mortality, nor any benefit for the reduction of myocardial infarction and stroke.
The results did indicate a trend, however, for reduced mortality in coronary heart disease. Even so, the number needed to treat for this was 334, which means that 334 people would have to take omega-3 fatty acids for years to prevent one fatal cardiac event.
Aside from this study, Dr. Diener found six studies on Alzheimer’s disease and three studies on dementia with patient populations between 600 and 800. In these studies, too, a positive effect of omega-3 fatty acids could not be identified. Then he discovered another 31 placebo-controlled studies of omega-3 fatty acids for the treatment or prevention of depression and anxiety disorder. Despite including 50,000 patients, these studies also did not show any positive effect.
“I see a significant discrepancy between the promotion of omega-3 fatty acids, whether it’s on television, in the ‘yellow’ [journalism] press, or in advertisements, and the actual scientific evidence,” said Dr. Diener. “At least from a neurological perspective, there is no evidence that omega-3 fatty acids have any benefit. This is true for strokes, dementia, Alzheimer’s disease, depression, and anxiety disorders.”
Potential adverse effects
Omega-3 fatty acids also have potentially adverse effects. The VITAL Rhythm study recently provided evidence that, depending on the dose, preparations with omega-3 fatty acids may increase the risk for atrial fibrillation. As the authors wrote, the results do not support taking omega-3 fatty acids to prevent atrial fibrillation.
In 2019, the global market for omega-3 fatty acids reached a value of $4.1 billion. This value is expected to double by 2025, according to a comment by Gregory Curfman, MD, deputy editor of JAMA and lecturer in health care policy at Harvard Medical School, Boston.
As Dr. Curfman wrote, this impressive amount of expenditure shows how beloved these products are and how strongly many people believe that omega-3 fatty acids are beneficial for their health. It is therefore important to know the potential risks of such preparations. One such example for this would be the risk for atrial fibrillation.
According to Dr. Curfman, in the last 2 years, four randomized clinical studies have provided data on the risk for atrial fibrillation associated with omega-3 fatty acids. In the STRENGTH study, 13,078 high-risk patients with cardiovascular diseases were randomly assigned to one of two groups. The subjects received either a high dose (4 g/day) of a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or corn oil. After a median of 42 months, there was no significant difference between the two groups in the primary composite cardiovascular endpoint, but more frequent atrial fibrillation in the omega-3 fatty acid group, compared with the corn oil group (2.2% vs. 1.3%; hazard ratio, 1.69; 95% confidence interval, 1.29-2.21; P < .001).
In the REDUCE-IT study, 8179 subjects were randomly assigned to a high dose (4 g/day, as in STRENGTH) of an omega-3 fatty acid preparation consisting of a purified EPA (icosapent ethyl) or mineral oil. After a median observation period of 4.9 years, icosapent ethyl was associated with a relative reduction of the primary composite cardiovascular endpoint by 25%, compared with mineral oil. As in the STRENGTH study, this study found that the risk for atrial fibrillation associated with omega-3 fatty acids, compared with mineral oil, was significantly higher (5.3% vs. 3.9%; P = .003).
In a third study (OMEMI), as Dr. Curfman reported, 1027 elderly patients who had recently had a myocardial infarction were randomly assigned to receive either a median dose of 1.8 g/day of omega-3 fatty acids (a combination of EPA and DHA) or corn oil. After 2 years, there was no significant difference between the two groups in primary composite cardiovascular endpoints, but 7.2% of the patients taking omega-3 fatty acids developed atrial fibrillation. In the corn oil group, this proportion was 4% (HR, 1.84; 95% CI, 0.98-3.45; P = .06).
The data from the four studies together indicate a potential dose-dependent risk for atrial fibrillation associated with omega-3 fatty acids, according to Dr. Curfman. At a dose of 4.0 g/day, there is a highly significant risk increase (almost double). With a median dose of 1.8 g/day, the risk increase (HR, 1.84) did not reach statistical significance. At a daily standard dose of 840 mg/day, an increase in risk could not be determined.
Dr. Curfman’s recommendation is that patients who take, or want to take, preparations with omega-3 fatty acids be informed of the potential development of arrhythmia at higher dosages. These patients also should undergo cardiological monitoring.
A version of this article first appeared on Medscape.com.
Dietary supplements that contain omega-3 fatty acids have been widely consumed for years. Researchers have been investigating the benefits of such preparations for cardiovascular, neurologic, and psychological conditions. A recently published study on omega-3 fatty acids and depression inspired neurologist Hans-Christoph Diener, MD, PhD, of the Institute for Epidemiology at the University Duisburg-Essen (Germany), to examine scientific publications concerning omega-3 fatty acids or fish-oil capsules in more detail.
Prevention of depression
Dr. Diener told the story of how he stumbled upon an interesting article in JAMA in December 2021. It was about a placebo-controlled study that investigated whether omega-3 fatty acids can prevent incident depression.
As the study authors reported, treatment with omega-3 preparations in adults aged 50 years or older without clinically relevant symptoms of depression at study initiation was associated with a small but statistically significant increase in the risk for depression or clinically relevant symptoms of depression. There was no difference in mood scale value, however, over a median follow-up of 5.3 years. According to the study authors, these results did not support the administration of omega-3 preparations for the prevention of depression.
This study was, as Dr. Diener said, somewhat negative, but it did arouse his interest in questions such as what biological effects omega-3 fatty acids have and what is known “about this topic with regard to neurology,” he said. When reviewing the literature, he noticed that there “were association studies, i.e., studies that describe that the intake of omega-3 fatty acids may possibly be associated with a lower risk of certain diseases.”
Beginning with the Inuit
It all started “with observations of the Inuit [population] in Greenland and Alaska after World War II, because it was remarked upon that these people ate a lot of fish and seal meat and had a very low incidence of cardiovascular diseases.” Over the years, a large number of association studies have been published, which may have encouraged the assumption that omega-3 fatty acids have positive health effects on various conditions, such as cardiovascular diseases, hyperlipidemia, type 2 diabetes, various malignancies, cognitive impairments, Alzheimer’s disease, depression and anxiety disorders, heart failure, slipped disks, ADHD, symptoms of menopause, rheumatoid arthritis, asthma, periodontitis, epilepsy, chemotherapy tolerance, premenstrual syndrome, and nonalcoholic fatty liver disease.
Dr. Diener believes that the problem is that these are association studies. But association does not mean that there is a causal relationship.
Disappointing study results
On the contrary, the results from the randomized placebo-controlled studies are truly frustrating, according to the neurologist. A meta-analysis of the use of omega-3 fatty acids in cardiovascular diseases included 86 studies with over 162,000 patients. According to Dr. Diener, it did not reveal any benefit for overall and cardiovascular mortality, nor any benefit for the reduction of myocardial infarction and stroke.
The results did indicate a trend, however, for reduced mortality in coronary heart disease. Even so, the number needed to treat for this was 334, which means that 334 people would have to take omega-3 fatty acids for years to prevent one fatal cardiac event.
Aside from this study, Dr. Diener found six studies on Alzheimer’s disease and three studies on dementia with patient populations between 600 and 800. In these studies, too, a positive effect of omega-3 fatty acids could not be identified. Then he discovered another 31 placebo-controlled studies of omega-3 fatty acids for the treatment or prevention of depression and anxiety disorder. Despite including 50,000 patients, these studies also did not show any positive effect.
“I see a significant discrepancy between the promotion of omega-3 fatty acids, whether it’s on television, in the ‘yellow’ [journalism] press, or in advertisements, and the actual scientific evidence,” said Dr. Diener. “At least from a neurological perspective, there is no evidence that omega-3 fatty acids have any benefit. This is true for strokes, dementia, Alzheimer’s disease, depression, and anxiety disorders.”
Potential adverse effects
Omega-3 fatty acids also have potentially adverse effects. The VITAL Rhythm study recently provided evidence that, depending on the dose, preparations with omega-3 fatty acids may increase the risk for atrial fibrillation. As the authors wrote, the results do not support taking omega-3 fatty acids to prevent atrial fibrillation.
In 2019, the global market for omega-3 fatty acids reached a value of $4.1 billion. This value is expected to double by 2025, according to a comment by Gregory Curfman, MD, deputy editor of JAMA and lecturer in health care policy at Harvard Medical School, Boston.
As Dr. Curfman wrote, this impressive amount of expenditure shows how beloved these products are and how strongly many people believe that omega-3 fatty acids are beneficial for their health. It is therefore important to know the potential risks of such preparations. One such example for this would be the risk for atrial fibrillation.
According to Dr. Curfman, in the last 2 years, four randomized clinical studies have provided data on the risk for atrial fibrillation associated with omega-3 fatty acids. In the STRENGTH study, 13,078 high-risk patients with cardiovascular diseases were randomly assigned to one of two groups. The subjects received either a high dose (4 g/day) of a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or corn oil. After a median of 42 months, there was no significant difference between the two groups in the primary composite cardiovascular endpoint, but more frequent atrial fibrillation in the omega-3 fatty acid group, compared with the corn oil group (2.2% vs. 1.3%; hazard ratio, 1.69; 95% confidence interval, 1.29-2.21; P < .001).
In the REDUCE-IT study, 8179 subjects were randomly assigned to a high dose (4 g/day, as in STRENGTH) of an omega-3 fatty acid preparation consisting of a purified EPA (icosapent ethyl) or mineral oil. After a median observation period of 4.9 years, icosapent ethyl was associated with a relative reduction of the primary composite cardiovascular endpoint by 25%, compared with mineral oil. As in the STRENGTH study, this study found that the risk for atrial fibrillation associated with omega-3 fatty acids, compared with mineral oil, was significantly higher (5.3% vs. 3.9%; P = .003).
In a third study (OMEMI), as Dr. Curfman reported, 1027 elderly patients who had recently had a myocardial infarction were randomly assigned to receive either a median dose of 1.8 g/day of omega-3 fatty acids (a combination of EPA and DHA) or corn oil. After 2 years, there was no significant difference between the two groups in primary composite cardiovascular endpoints, but 7.2% of the patients taking omega-3 fatty acids developed atrial fibrillation. In the corn oil group, this proportion was 4% (HR, 1.84; 95% CI, 0.98-3.45; P = .06).
The data from the four studies together indicate a potential dose-dependent risk for atrial fibrillation associated with omega-3 fatty acids, according to Dr. Curfman. At a dose of 4.0 g/day, there is a highly significant risk increase (almost double). With a median dose of 1.8 g/day, the risk increase (HR, 1.84) did not reach statistical significance. At a daily standard dose of 840 mg/day, an increase in risk could not be determined.
Dr. Curfman’s recommendation is that patients who take, or want to take, preparations with omega-3 fatty acids be informed of the potential development of arrhythmia at higher dosages. These patients also should undergo cardiological monitoring.
A version of this article first appeared on Medscape.com.
Late to the game: Parenting after 40
As they rolled me down the hallway to the OR, ceiling lights rhythmically passing above, I zoned out into a 1,000-mile stare. How did I get here? I started humming “Swing Low, Sweet Chariot,” praying for a miracle to happen. I thought back to my birth plan, meticulously crafted, a one-pager so that the no-nonsense labor and delivery nurses wouldn›t think me completely off my rocker. No C-section unless medically necessary. Those words laughed back at me – cackling, even. I’d planned out the whole birthing process and here we were, my team almost jogging me to the OR. I lay still, utterly gobsmacked and partially anesthetized.
If I squint my eyes and hallucinate just a bit, that is sort of what motherhood has been like.
It’s about knowing all the things that could go wrong and meeting the unplanned head-on. Motherhood has indeed been a whirlwind – so many physical, psychological, and emotional transformations. And to top it off, the added effort of giving birth in a pandemic. As an over-40 physician, you’d think I would have been better prepared.
I was, but in a sense, I was not. The knowledge, the wisdom, the experience of my medical training surrounded me, but even I panicked at times in the beginning: Am I feeding her correctly? Am I making enough food for her? Am I doing the best that I can for her? What more could I be doing for her?
Over time, I’ve learned to lighten up. Some. In those teachable moments with my daughter Gia, I’ve learned to not sugarcoat reality but encourage the hopeful. If Gia falls on the ground? “You’re okay, sweetie. Now get back up.” If Gia has a tantrum and starts hitting herself? “Honey, our hands are for hugs, not hurting ourselves. Let’s go play.” Eighty percent of motherhood right now is redirection and the other 20% is patience.
I remember this one time I was rushing out the door for work. After getting in the car with my keys, I realized I forgot my coffee back in the house. I left the car, went back in the house to grab the blessed joe, went back to the car, and couldn’t get in because it was locked. I panicked at that moment, went back inside the house, and found Gia playing with my extra key fob. My own daughter locked me out of my car. Of course, it wasn’t her fault. Deep breath and I offered her another kiss while simultaneously taking the key fob from her.
Before Gia could walk, she could climb the stairs in our home. Her father and I sometimes refer to her as “Lil Bamm-Bamm” because she is so strong. One day, Daddy was supposed to be watching her while Mommy was folding laundry upstairs. She was not allowed on the stairs, but what should I hear? Literally, the pitter-patter of little feet, running down the upstairs hallway. Her father had drifted off watching yet another episode of something Star Wars–related. My strong little girl made it up the stairs all by herself and Dad received a strong word. The Force was with me that day.
I would say that I feel like having a child ages you, but what does that really mean when you’re already old? I’ve become acutely aware of my lack of endurance, stamina, and bodily strength. My knees will creak when taking her upstairs to bed, an osseous dirge of a lullaby. Date nights become unintentionally less and less frequent. Friday night dress-up becomes Friday night dress-down. I’ve replaced stiletto heels with comfy sweats.
Once we put Gia down for the night, we are usually exhausted from the day, and the couch and TV are welcome respites. We exhale. As over-40 parents, we knew that having children late in life would bring its challenges. But I’d like to think that we are meeting them the best way that we can. Often I encourage my body to meet Gia at her eye level, see what she sees, play with her on her own terms, and match her energy. She absolutely loves it when I do this. I’m out of breath and my knees are sore by the end of our play session, but I wouldn’t have it any other way.
We are learning from each other. She has a bright and assertive personality, and I am protective of that innocence. Her innocence is without fear. I often wonder what she is thinking when I see her facial expressions. A side-eye, a fleeting giggle. Is she secretly contemplating the chronicity of the cosmos, or is it just gas? I look at her in stolen moments and still can’t believe that I grew a human inside me, and said human was extracted from me and is now walking around my house commanding her bidding. So surreal. The unromanticized, scientific ingredients that are at play from conception to delivery are nothing short of miraculous. And the miracles of parenting over 40 are present every day.
Dr. Tolliver is a family medicine physician at The Ohio State University Wexner Medical Center in Columbus. A version of this article first appeared on Medscape.com.
As they rolled me down the hallway to the OR, ceiling lights rhythmically passing above, I zoned out into a 1,000-mile stare. How did I get here? I started humming “Swing Low, Sweet Chariot,” praying for a miracle to happen. I thought back to my birth plan, meticulously crafted, a one-pager so that the no-nonsense labor and delivery nurses wouldn›t think me completely off my rocker. No C-section unless medically necessary. Those words laughed back at me – cackling, even. I’d planned out the whole birthing process and here we were, my team almost jogging me to the OR. I lay still, utterly gobsmacked and partially anesthetized.
If I squint my eyes and hallucinate just a bit, that is sort of what motherhood has been like.
It’s about knowing all the things that could go wrong and meeting the unplanned head-on. Motherhood has indeed been a whirlwind – so many physical, psychological, and emotional transformations. And to top it off, the added effort of giving birth in a pandemic. As an over-40 physician, you’d think I would have been better prepared.
I was, but in a sense, I was not. The knowledge, the wisdom, the experience of my medical training surrounded me, but even I panicked at times in the beginning: Am I feeding her correctly? Am I making enough food for her? Am I doing the best that I can for her? What more could I be doing for her?
Over time, I’ve learned to lighten up. Some. In those teachable moments with my daughter Gia, I’ve learned to not sugarcoat reality but encourage the hopeful. If Gia falls on the ground? “You’re okay, sweetie. Now get back up.” If Gia has a tantrum and starts hitting herself? “Honey, our hands are for hugs, not hurting ourselves. Let’s go play.” Eighty percent of motherhood right now is redirection and the other 20% is patience.
I remember this one time I was rushing out the door for work. After getting in the car with my keys, I realized I forgot my coffee back in the house. I left the car, went back in the house to grab the blessed joe, went back to the car, and couldn’t get in because it was locked. I panicked at that moment, went back inside the house, and found Gia playing with my extra key fob. My own daughter locked me out of my car. Of course, it wasn’t her fault. Deep breath and I offered her another kiss while simultaneously taking the key fob from her.
Before Gia could walk, she could climb the stairs in our home. Her father and I sometimes refer to her as “Lil Bamm-Bamm” because she is so strong. One day, Daddy was supposed to be watching her while Mommy was folding laundry upstairs. She was not allowed on the stairs, but what should I hear? Literally, the pitter-patter of little feet, running down the upstairs hallway. Her father had drifted off watching yet another episode of something Star Wars–related. My strong little girl made it up the stairs all by herself and Dad received a strong word. The Force was with me that day.
I would say that I feel like having a child ages you, but what does that really mean when you’re already old? I’ve become acutely aware of my lack of endurance, stamina, and bodily strength. My knees will creak when taking her upstairs to bed, an osseous dirge of a lullaby. Date nights become unintentionally less and less frequent. Friday night dress-up becomes Friday night dress-down. I’ve replaced stiletto heels with comfy sweats.
Once we put Gia down for the night, we are usually exhausted from the day, and the couch and TV are welcome respites. We exhale. As over-40 parents, we knew that having children late in life would bring its challenges. But I’d like to think that we are meeting them the best way that we can. Often I encourage my body to meet Gia at her eye level, see what she sees, play with her on her own terms, and match her energy. She absolutely loves it when I do this. I’m out of breath and my knees are sore by the end of our play session, but I wouldn’t have it any other way.
We are learning from each other. She has a bright and assertive personality, and I am protective of that innocence. Her innocence is without fear. I often wonder what she is thinking when I see her facial expressions. A side-eye, a fleeting giggle. Is she secretly contemplating the chronicity of the cosmos, or is it just gas? I look at her in stolen moments and still can’t believe that I grew a human inside me, and said human was extracted from me and is now walking around my house commanding her bidding. So surreal. The unromanticized, scientific ingredients that are at play from conception to delivery are nothing short of miraculous. And the miracles of parenting over 40 are present every day.
Dr. Tolliver is a family medicine physician at The Ohio State University Wexner Medical Center in Columbus. A version of this article first appeared on Medscape.com.
As they rolled me down the hallway to the OR, ceiling lights rhythmically passing above, I zoned out into a 1,000-mile stare. How did I get here? I started humming “Swing Low, Sweet Chariot,” praying for a miracle to happen. I thought back to my birth plan, meticulously crafted, a one-pager so that the no-nonsense labor and delivery nurses wouldn›t think me completely off my rocker. No C-section unless medically necessary. Those words laughed back at me – cackling, even. I’d planned out the whole birthing process and here we were, my team almost jogging me to the OR. I lay still, utterly gobsmacked and partially anesthetized.
If I squint my eyes and hallucinate just a bit, that is sort of what motherhood has been like.
It’s about knowing all the things that could go wrong and meeting the unplanned head-on. Motherhood has indeed been a whirlwind – so many physical, psychological, and emotional transformations. And to top it off, the added effort of giving birth in a pandemic. As an over-40 physician, you’d think I would have been better prepared.
I was, but in a sense, I was not. The knowledge, the wisdom, the experience of my medical training surrounded me, but even I panicked at times in the beginning: Am I feeding her correctly? Am I making enough food for her? Am I doing the best that I can for her? What more could I be doing for her?
Over time, I’ve learned to lighten up. Some. In those teachable moments with my daughter Gia, I’ve learned to not sugarcoat reality but encourage the hopeful. If Gia falls on the ground? “You’re okay, sweetie. Now get back up.” If Gia has a tantrum and starts hitting herself? “Honey, our hands are for hugs, not hurting ourselves. Let’s go play.” Eighty percent of motherhood right now is redirection and the other 20% is patience.
I remember this one time I was rushing out the door for work. After getting in the car with my keys, I realized I forgot my coffee back in the house. I left the car, went back in the house to grab the blessed joe, went back to the car, and couldn’t get in because it was locked. I panicked at that moment, went back inside the house, and found Gia playing with my extra key fob. My own daughter locked me out of my car. Of course, it wasn’t her fault. Deep breath and I offered her another kiss while simultaneously taking the key fob from her.
Before Gia could walk, she could climb the stairs in our home. Her father and I sometimes refer to her as “Lil Bamm-Bamm” because she is so strong. One day, Daddy was supposed to be watching her while Mommy was folding laundry upstairs. She was not allowed on the stairs, but what should I hear? Literally, the pitter-patter of little feet, running down the upstairs hallway. Her father had drifted off watching yet another episode of something Star Wars–related. My strong little girl made it up the stairs all by herself and Dad received a strong word. The Force was with me that day.
I would say that I feel like having a child ages you, but what does that really mean when you’re already old? I’ve become acutely aware of my lack of endurance, stamina, and bodily strength. My knees will creak when taking her upstairs to bed, an osseous dirge of a lullaby. Date nights become unintentionally less and less frequent. Friday night dress-up becomes Friday night dress-down. I’ve replaced stiletto heels with comfy sweats.
Once we put Gia down for the night, we are usually exhausted from the day, and the couch and TV are welcome respites. We exhale. As over-40 parents, we knew that having children late in life would bring its challenges. But I’d like to think that we are meeting them the best way that we can. Often I encourage my body to meet Gia at her eye level, see what she sees, play with her on her own terms, and match her energy. She absolutely loves it when I do this. I’m out of breath and my knees are sore by the end of our play session, but I wouldn’t have it any other way.
We are learning from each other. She has a bright and assertive personality, and I am protective of that innocence. Her innocence is without fear. I often wonder what she is thinking when I see her facial expressions. A side-eye, a fleeting giggle. Is she secretly contemplating the chronicity of the cosmos, or is it just gas? I look at her in stolen moments and still can’t believe that I grew a human inside me, and said human was extracted from me and is now walking around my house commanding her bidding. So surreal. The unromanticized, scientific ingredients that are at play from conception to delivery are nothing short of miraculous. And the miracles of parenting over 40 are present every day.
Dr. Tolliver is a family medicine physician at The Ohio State University Wexner Medical Center in Columbus. A version of this article first appeared on Medscape.com.
Will we ever outgrow the Goldwater rule?
Since it appeared in the first edition of the American Psychiatric Association’s Principles of Medical Ethics in 1973, the “Goldwater rule” – often referred to in terms of where in the APA’s guideline it can be found, Section 7.3 – has placed a stringent prohibition on psychiatrists offering professional opinions about public figures “unless he or she has conducted an examination and has been granted proper authorization for such a statement.”1
Some psychiatrists experienced the restrictive nature of Section 7.3 more acutely perhaps than ever during the Trump presidency. This spurred numerous articles criticizing the guideline as an outdated “gag rule”2 that harms the public image of psychiatry.3 Some psychiatrists violated the rule to warn the public of the dangers of a president with “incipient dementia”4 occupying the most powerful position on earth.
Following President Trump’s exit from the White House, the alarm bells surrounding his presidency have quieted. Criticisms of the Goldwater rule, on the other hand, have persisted. Many of these criticisms now call for the rule to be refined, allowing for psychiatrists to give their professional opinions about public figures, but with certain guidelines on how to do so.5 Few have yet to make a sober case for the outright abolition of Section 7.3.6
Self-regulating and internal policing are important factors in the continued independence of the medical profession, and we should continue to hold each other to high professional standards. That being said, do psychiatrists need training wheels to prevent us from devolving into unprofessional social commentators? Other medical specialties do not see the need to implement a rule preventing their colleagues from expressing expertise in fear of embarrassment. Do we not have faith in our ability to conduct ourselves professionally? Is the Goldwater rule an admission of a juvenile lack of self-control within our field?
Not only do other medical specialties not forcibly handhold their members in public settings, but other “providers” in the realm of mental health likewise do not implement such strict self-restraints. Psychiatry staying silent on the matter of public figures leaves a void filled by other, arguably less qualified, individuals. Subsequently, the public discord risks being flooded with pseudoscientific pontification and distorted views of psychiatric illness. The cycle of speculating on the mental fitness of the president has outlived President Trump, with concerns about Joe Biden’s incoherence and waning cognition.7 Therein is an important argument to be made for the public duty of psychiatrists, with their greater expertise and clinical acumen, to weigh in on matters of societal importance in an attempt to dispel dangerous misconceptions.
Practical limitations are often raised and serve as the cornerstone for the Goldwater rule. Specifically, the limitation being that a psychiatrist cannot provide a professional opinion about an individual without a proper in-person evaluation. The psychiatric interview could be considered the most in-depth and comprehensive evaluation in all of medicine. Even so, is a trained psychiatrist presented with grandiosity, flight-of-ideas, and pressured speech unable to comment on the possibility of mania without a lengthy and comprehensive evaluation? How much disorganization of behavior and dialogue does one need to observe to recognize psychosis? For the experienced psychiatrist, many of these behavioral hallmarks are akin to an ST elevation on an EKG representing a heart attack.
When considering less extreme examples of mental affliction, such as depression and anxiety, many signs – including demeanor, motor activity, manner of speaking, and other aspects of behavior – are apparent to the perceptive psychiatrist without needing an extensive interview that dives into the depths of a person’s social history and childhood. After all, our own criteria for depression and mania do not require the presence of social stressors or childhood trauma. Even personality disorders can be reasonably postulated when a person behaves in a particular fashion. The recognition of transitional objects, items used to provide psychological comfort, including the “teddy bear sign” are common and scientifically studied methods to recognize personality disorder.8
The necessity for an in-person evaluation has become less compelling over the years. In our modern age, important social moments are memorialized in countless videos that are arguably more relevant, more accurate, and less subjective than a psychiatric interview. Furthermore, forensic psychiatrists routinely comment on individuals they have not examined for a variety of reasons, from postmortem analysis to the refusal of the client to be interviewed. Moreover, and with significant contradiction, many leaders in the field of psychiatry view integrated care, the practice of psychiatrists advising primary care doctors, often without even seeing patients, to be the future of psychiatry.9
Some reading this may scoff at the above examples. Perhaps Section 7.3 speaks to an underlying insecurity in our field regarding our ability to accurately diagnose. That insecurity is not unfounded. In terms of the DSM-5, the bar for reliability has been lowered to a kappa of 0.2-0.4, from a previous standard of 0.6, in an attempt to avoid critiques of unreliability.10 Yet herein lies a powerful recognition of the necessity of the Goldwater rule. If psychiatrists cannot reliably agree on the presence of diagnoses in the controlled setting of scientific study, how can we expect to speak with coherence and consistency on highly mediatized and provoking topics?
The defense – that the difficulty psychiatrists have at providing an accurate diagnosis stems from the immense complexity of the system being evaluated, the human mind – is a valid one. Attempts to force such complex pathology, with all its many variables, into the check-box approach implemented in the DSM inevitably leads to problems with diagnostic reliability. Still, as psychiatrists we retain a level of expertise in assessing and treating complex disorders of the mind that no other field can claim.
The duty physicians have not only to work toward the health of their individual patients, but also to act in service of the public health and well-being of communities in which our patients live, is well established. How ethical is it then for psychiatry to absolve itself from duty when it comes to public figures at the center of shaping public opinion? There are numerous recent, high-profile instances where our expertise may have helped shine light in an otherwise murky public discussion filled with disinformation. The death of George Floyd and the year of turmoil that followed is a salient example. The conservatorship of Britney Spears and the resulting societal outcry is another. Even setting the matter of diagnosis aside, we can help illuminate the societal implications of conservatorship laws,11 in addition to providing input on how to safely and responsibly approach an individual who is in crisis, under the influence of multiple illicit substances, and possibly suffering from excited delirium.
Whether psychiatry has progressed enough as a medical specialty to trust ourselves with the option of providing professional opinions on public figures is an ongoing debate. The persistence of the Goldwater rule is a strong testament to the internal lack of confidence among psychiatrists regarding our ability to provide accurate diagnoses, act with integrity in the public space, and foster a positive public image. That lack of confidence may be well deserved. However, it is possible that our field will never go through the necessary pains of maturing as long as Section 7.3 remains in place.
Dr. Compton is a psychiatry resident at University of California, San Diego. His background includes medical education, mental health advocacy, work with underserved populations, and brain cancer research. Dr. Compton has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.
References
1. American Psychiatric Association. The principles of medical ethics with annotations especially applicable to psychiatry. Section 7. American Psychiatric Association; 2013 edition.
2. Glass LL. The Goldwater rule is broken. Here’s how to fix it. STAT News. 2018 June 18.
3. Plymyer D. The Goldwater rule paradox. 2020 Aug 7.
4. Lieberman JA. Trump’s brain and the 25th Amendment. Vice. 2017 Sep 8.
5. Blotcky AD et al. The Goldwater rule is fine, if refined. Here’s how to do it. Psychiatric Times. 2022 Jan 6;39(1).
6. Blotcky AD and Norrholm SD. After Trump, end the Goldwater rule once and for all. New York Daily News. 2020 Dec 22.
7. Stephens B. Biden should not run again – And he should say he won’t. New York Times. 2021 Dec 14.
8. Schmaling KB et al. The positive teddy bear sign: Transitional objects in the medical setting. J Nerv Ment Dis. 1994 Dec;182(12):725.
9. Badre N et al. Psychopharmacologic management in integrated care: Challenges for residency education. Acad Psychiatry. 2015; 39(4):466-9.
10. Kraemer HC et al. DSM-5: How reliable is reliable enough? Am J Psychiatry. 2012 Jan;169(1):13-5.
11. Badre N and Compton C. Britney Spears – Reflections on conservatorship. Clinical Psychiatry News. 2021 Nov 16.
Since it appeared in the first edition of the American Psychiatric Association’s Principles of Medical Ethics in 1973, the “Goldwater rule” – often referred to in terms of where in the APA’s guideline it can be found, Section 7.3 – has placed a stringent prohibition on psychiatrists offering professional opinions about public figures “unless he or she has conducted an examination and has been granted proper authorization for such a statement.”1
Some psychiatrists experienced the restrictive nature of Section 7.3 more acutely perhaps than ever during the Trump presidency. This spurred numerous articles criticizing the guideline as an outdated “gag rule”2 that harms the public image of psychiatry.3 Some psychiatrists violated the rule to warn the public of the dangers of a president with “incipient dementia”4 occupying the most powerful position on earth.
Following President Trump’s exit from the White House, the alarm bells surrounding his presidency have quieted. Criticisms of the Goldwater rule, on the other hand, have persisted. Many of these criticisms now call for the rule to be refined, allowing for psychiatrists to give their professional opinions about public figures, but with certain guidelines on how to do so.5 Few have yet to make a sober case for the outright abolition of Section 7.3.6
Self-regulating and internal policing are important factors in the continued independence of the medical profession, and we should continue to hold each other to high professional standards. That being said, do psychiatrists need training wheels to prevent us from devolving into unprofessional social commentators? Other medical specialties do not see the need to implement a rule preventing their colleagues from expressing expertise in fear of embarrassment. Do we not have faith in our ability to conduct ourselves professionally? Is the Goldwater rule an admission of a juvenile lack of self-control within our field?
Not only do other medical specialties not forcibly handhold their members in public settings, but other “providers” in the realm of mental health likewise do not implement such strict self-restraints. Psychiatry staying silent on the matter of public figures leaves a void filled by other, arguably less qualified, individuals. Subsequently, the public discord risks being flooded with pseudoscientific pontification and distorted views of psychiatric illness. The cycle of speculating on the mental fitness of the president has outlived President Trump, with concerns about Joe Biden’s incoherence and waning cognition.7 Therein is an important argument to be made for the public duty of psychiatrists, with their greater expertise and clinical acumen, to weigh in on matters of societal importance in an attempt to dispel dangerous misconceptions.
Practical limitations are often raised and serve as the cornerstone for the Goldwater rule. Specifically, the limitation being that a psychiatrist cannot provide a professional opinion about an individual without a proper in-person evaluation. The psychiatric interview could be considered the most in-depth and comprehensive evaluation in all of medicine. Even so, is a trained psychiatrist presented with grandiosity, flight-of-ideas, and pressured speech unable to comment on the possibility of mania without a lengthy and comprehensive evaluation? How much disorganization of behavior and dialogue does one need to observe to recognize psychosis? For the experienced psychiatrist, many of these behavioral hallmarks are akin to an ST elevation on an EKG representing a heart attack.
When considering less extreme examples of mental affliction, such as depression and anxiety, many signs – including demeanor, motor activity, manner of speaking, and other aspects of behavior – are apparent to the perceptive psychiatrist without needing an extensive interview that dives into the depths of a person’s social history and childhood. After all, our own criteria for depression and mania do not require the presence of social stressors or childhood trauma. Even personality disorders can be reasonably postulated when a person behaves in a particular fashion. The recognition of transitional objects, items used to provide psychological comfort, including the “teddy bear sign” are common and scientifically studied methods to recognize personality disorder.8
The necessity for an in-person evaluation has become less compelling over the years. In our modern age, important social moments are memorialized in countless videos that are arguably more relevant, more accurate, and less subjective than a psychiatric interview. Furthermore, forensic psychiatrists routinely comment on individuals they have not examined for a variety of reasons, from postmortem analysis to the refusal of the client to be interviewed. Moreover, and with significant contradiction, many leaders in the field of psychiatry view integrated care, the practice of psychiatrists advising primary care doctors, often without even seeing patients, to be the future of psychiatry.9
Some reading this may scoff at the above examples. Perhaps Section 7.3 speaks to an underlying insecurity in our field regarding our ability to accurately diagnose. That insecurity is not unfounded. In terms of the DSM-5, the bar for reliability has been lowered to a kappa of 0.2-0.4, from a previous standard of 0.6, in an attempt to avoid critiques of unreliability.10 Yet herein lies a powerful recognition of the necessity of the Goldwater rule. If psychiatrists cannot reliably agree on the presence of diagnoses in the controlled setting of scientific study, how can we expect to speak with coherence and consistency on highly mediatized and provoking topics?
The defense – that the difficulty psychiatrists have at providing an accurate diagnosis stems from the immense complexity of the system being evaluated, the human mind – is a valid one. Attempts to force such complex pathology, with all its many variables, into the check-box approach implemented in the DSM inevitably leads to problems with diagnostic reliability. Still, as psychiatrists we retain a level of expertise in assessing and treating complex disorders of the mind that no other field can claim.
The duty physicians have not only to work toward the health of their individual patients, but also to act in service of the public health and well-being of communities in which our patients live, is well established. How ethical is it then for psychiatry to absolve itself from duty when it comes to public figures at the center of shaping public opinion? There are numerous recent, high-profile instances where our expertise may have helped shine light in an otherwise murky public discussion filled with disinformation. The death of George Floyd and the year of turmoil that followed is a salient example. The conservatorship of Britney Spears and the resulting societal outcry is another. Even setting the matter of diagnosis aside, we can help illuminate the societal implications of conservatorship laws,11 in addition to providing input on how to safely and responsibly approach an individual who is in crisis, under the influence of multiple illicit substances, and possibly suffering from excited delirium.
Whether psychiatry has progressed enough as a medical specialty to trust ourselves with the option of providing professional opinions on public figures is an ongoing debate. The persistence of the Goldwater rule is a strong testament to the internal lack of confidence among psychiatrists regarding our ability to provide accurate diagnoses, act with integrity in the public space, and foster a positive public image. That lack of confidence may be well deserved. However, it is possible that our field will never go through the necessary pains of maturing as long as Section 7.3 remains in place.
Dr. Compton is a psychiatry resident at University of California, San Diego. His background includes medical education, mental health advocacy, work with underserved populations, and brain cancer research. Dr. Compton has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.
References
1. American Psychiatric Association. The principles of medical ethics with annotations especially applicable to psychiatry. Section 7. American Psychiatric Association; 2013 edition.
2. Glass LL. The Goldwater rule is broken. Here’s how to fix it. STAT News. 2018 June 18.
3. Plymyer D. The Goldwater rule paradox. 2020 Aug 7.
4. Lieberman JA. Trump’s brain and the 25th Amendment. Vice. 2017 Sep 8.
5. Blotcky AD et al. The Goldwater rule is fine, if refined. Here’s how to do it. Psychiatric Times. 2022 Jan 6;39(1).
6. Blotcky AD and Norrholm SD. After Trump, end the Goldwater rule once and for all. New York Daily News. 2020 Dec 22.
7. Stephens B. Biden should not run again – And he should say he won’t. New York Times. 2021 Dec 14.
8. Schmaling KB et al. The positive teddy bear sign: Transitional objects in the medical setting. J Nerv Ment Dis. 1994 Dec;182(12):725.
9. Badre N et al. Psychopharmacologic management in integrated care: Challenges for residency education. Acad Psychiatry. 2015; 39(4):466-9.
10. Kraemer HC et al. DSM-5: How reliable is reliable enough? Am J Psychiatry. 2012 Jan;169(1):13-5.
11. Badre N and Compton C. Britney Spears – Reflections on conservatorship. Clinical Psychiatry News. 2021 Nov 16.
Since it appeared in the first edition of the American Psychiatric Association’s Principles of Medical Ethics in 1973, the “Goldwater rule” – often referred to in terms of where in the APA’s guideline it can be found, Section 7.3 – has placed a stringent prohibition on psychiatrists offering professional opinions about public figures “unless he or she has conducted an examination and has been granted proper authorization for such a statement.”1
Some psychiatrists experienced the restrictive nature of Section 7.3 more acutely perhaps than ever during the Trump presidency. This spurred numerous articles criticizing the guideline as an outdated “gag rule”2 that harms the public image of psychiatry.3 Some psychiatrists violated the rule to warn the public of the dangers of a president with “incipient dementia”4 occupying the most powerful position on earth.
Following President Trump’s exit from the White House, the alarm bells surrounding his presidency have quieted. Criticisms of the Goldwater rule, on the other hand, have persisted. Many of these criticisms now call for the rule to be refined, allowing for psychiatrists to give their professional opinions about public figures, but with certain guidelines on how to do so.5 Few have yet to make a sober case for the outright abolition of Section 7.3.6
Self-regulating and internal policing are important factors in the continued independence of the medical profession, and we should continue to hold each other to high professional standards. That being said, do psychiatrists need training wheels to prevent us from devolving into unprofessional social commentators? Other medical specialties do not see the need to implement a rule preventing their colleagues from expressing expertise in fear of embarrassment. Do we not have faith in our ability to conduct ourselves professionally? Is the Goldwater rule an admission of a juvenile lack of self-control within our field?
Not only do other medical specialties not forcibly handhold their members in public settings, but other “providers” in the realm of mental health likewise do not implement such strict self-restraints. Psychiatry staying silent on the matter of public figures leaves a void filled by other, arguably less qualified, individuals. Subsequently, the public discord risks being flooded with pseudoscientific pontification and distorted views of psychiatric illness. The cycle of speculating on the mental fitness of the president has outlived President Trump, with concerns about Joe Biden’s incoherence and waning cognition.7 Therein is an important argument to be made for the public duty of psychiatrists, with their greater expertise and clinical acumen, to weigh in on matters of societal importance in an attempt to dispel dangerous misconceptions.
Practical limitations are often raised and serve as the cornerstone for the Goldwater rule. Specifically, the limitation being that a psychiatrist cannot provide a professional opinion about an individual without a proper in-person evaluation. The psychiatric interview could be considered the most in-depth and comprehensive evaluation in all of medicine. Even so, is a trained psychiatrist presented with grandiosity, flight-of-ideas, and pressured speech unable to comment on the possibility of mania without a lengthy and comprehensive evaluation? How much disorganization of behavior and dialogue does one need to observe to recognize psychosis? For the experienced psychiatrist, many of these behavioral hallmarks are akin to an ST elevation on an EKG representing a heart attack.
When considering less extreme examples of mental affliction, such as depression and anxiety, many signs – including demeanor, motor activity, manner of speaking, and other aspects of behavior – are apparent to the perceptive psychiatrist without needing an extensive interview that dives into the depths of a person’s social history and childhood. After all, our own criteria for depression and mania do not require the presence of social stressors or childhood trauma. Even personality disorders can be reasonably postulated when a person behaves in a particular fashion. The recognition of transitional objects, items used to provide psychological comfort, including the “teddy bear sign” are common and scientifically studied methods to recognize personality disorder.8
The necessity for an in-person evaluation has become less compelling over the years. In our modern age, important social moments are memorialized in countless videos that are arguably more relevant, more accurate, and less subjective than a psychiatric interview. Furthermore, forensic psychiatrists routinely comment on individuals they have not examined for a variety of reasons, from postmortem analysis to the refusal of the client to be interviewed. Moreover, and with significant contradiction, many leaders in the field of psychiatry view integrated care, the practice of psychiatrists advising primary care doctors, often without even seeing patients, to be the future of psychiatry.9
Some reading this may scoff at the above examples. Perhaps Section 7.3 speaks to an underlying insecurity in our field regarding our ability to accurately diagnose. That insecurity is not unfounded. In terms of the DSM-5, the bar for reliability has been lowered to a kappa of 0.2-0.4, from a previous standard of 0.6, in an attempt to avoid critiques of unreliability.10 Yet herein lies a powerful recognition of the necessity of the Goldwater rule. If psychiatrists cannot reliably agree on the presence of diagnoses in the controlled setting of scientific study, how can we expect to speak with coherence and consistency on highly mediatized and provoking topics?
The defense – that the difficulty psychiatrists have at providing an accurate diagnosis stems from the immense complexity of the system being evaluated, the human mind – is a valid one. Attempts to force such complex pathology, with all its many variables, into the check-box approach implemented in the DSM inevitably leads to problems with diagnostic reliability. Still, as psychiatrists we retain a level of expertise in assessing and treating complex disorders of the mind that no other field can claim.
The duty physicians have not only to work toward the health of their individual patients, but also to act in service of the public health and well-being of communities in which our patients live, is well established. How ethical is it then for psychiatry to absolve itself from duty when it comes to public figures at the center of shaping public opinion? There are numerous recent, high-profile instances where our expertise may have helped shine light in an otherwise murky public discussion filled with disinformation. The death of George Floyd and the year of turmoil that followed is a salient example. The conservatorship of Britney Spears and the resulting societal outcry is another. Even setting the matter of diagnosis aside, we can help illuminate the societal implications of conservatorship laws,11 in addition to providing input on how to safely and responsibly approach an individual who is in crisis, under the influence of multiple illicit substances, and possibly suffering from excited delirium.
Whether psychiatry has progressed enough as a medical specialty to trust ourselves with the option of providing professional opinions on public figures is an ongoing debate. The persistence of the Goldwater rule is a strong testament to the internal lack of confidence among psychiatrists regarding our ability to provide accurate diagnoses, act with integrity in the public space, and foster a positive public image. That lack of confidence may be well deserved. However, it is possible that our field will never go through the necessary pains of maturing as long as Section 7.3 remains in place.
Dr. Compton is a psychiatry resident at University of California, San Diego. His background includes medical education, mental health advocacy, work with underserved populations, and brain cancer research. Dr. Compton has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.
References
1. American Psychiatric Association. The principles of medical ethics with annotations especially applicable to psychiatry. Section 7. American Psychiatric Association; 2013 edition.
2. Glass LL. The Goldwater rule is broken. Here’s how to fix it. STAT News. 2018 June 18.
3. Plymyer D. The Goldwater rule paradox. 2020 Aug 7.
4. Lieberman JA. Trump’s brain and the 25th Amendment. Vice. 2017 Sep 8.
5. Blotcky AD et al. The Goldwater rule is fine, if refined. Here’s how to do it. Psychiatric Times. 2022 Jan 6;39(1).
6. Blotcky AD and Norrholm SD. After Trump, end the Goldwater rule once and for all. New York Daily News. 2020 Dec 22.
7. Stephens B. Biden should not run again – And he should say he won’t. New York Times. 2021 Dec 14.
8. Schmaling KB et al. The positive teddy bear sign: Transitional objects in the medical setting. J Nerv Ment Dis. 1994 Dec;182(12):725.
9. Badre N et al. Psychopharmacologic management in integrated care: Challenges for residency education. Acad Psychiatry. 2015; 39(4):466-9.
10. Kraemer HC et al. DSM-5: How reliable is reliable enough? Am J Psychiatry. 2012 Jan;169(1):13-5.
11. Badre N and Compton C. Britney Spears – Reflections on conservatorship. Clinical Psychiatry News. 2021 Nov 16.
Novel isotretinoin ointment for congenital ichthyosis shows promise
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
AT AAD 2022