Despite the recent uptick in leprosy cases in Central Florida, the disease is very rare, and casual contact with an infected person is likely to not result in transmission, according to Jose A. Lucar, MD.
“Contrary to historical beliefs, leprosy is not highly contagious,” Dr. Lucar, an infectious disease physician and associate professor of medicine at George Washington University, Washington, said in an interview. “For reasons that have to do with the makeup of genes that affect their immune system, most people are not susceptible to acquire leprosy. It’s really a small percentage of the population. It does require prolonged contact with someone with untreated leprosy – over several months – to acquire an infection. So, the risk from any type of casual contact is low.”
Dr. Lucar
Dr. Jose A. Lucar
According to a research letter published in the CDC’s Emerging Infectious Diseases, the number of reported leprosy cases has more than doubled in the past decade. Of the 159 new cases reported nationwide in 2020, Florida accounted for about one-fifth of cases, with most limited to the central part of the state. “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born," and currently, about one-third of leprosy cases are in individuals born in the United States, he noted.
The research letter described a case of leprosy in a 54-year-old man who worked in landscaping, who sought treatment at a dermatology clinic in Central Florida in 2022 for a painful and progressive erythematous rash. The lesions began on his distal extensor extremities and progressed to involve his trunk and face. According to the report, the man denied any domestic or foreign travel, exposure to armadillos (a known source of transmission), prolonged contact with immigrants from leprosy-endemic countries, or connections with someone known to have leprosy. The authors concluded that the case “adds to the growing body of literature suggesting that central Florida represents an endemic location for leprosy. Travel to this area, even in the absence of other risk factors, should prompt consideration of leprosy in the appropriate clinical context.”
Dr. Lucar said that the mechanism of leprosy transmission is not fully understood, but armadillos, which typically traverse the southern United States, are naturally infected with the bacteria that causes leprosy. “It’s possible that they can spread it to people,” he said. “People who have occupations or hobbies that put them in potential contact with wildlife should avoid any close contact with armadillos. There’s also a discussion of whether [the spike in leprosy cases] may have to do with climate change. That is not yet confirmed. It’s not entirely clear why there’s been a recent rise. It remains an area of investigation.”
Meanwhile, clinicians should keep a high level of suspicion in patients who present with skin lesions compatible with leprosy. “These are typically discolored or numb patches on the skin,” Dr. Lucar said. “This can range from a single or a few lesions to very extensive involvement of the skin. The diminished sensation or loss of sensation within those skin patches is an important sign. There’s a loss of skin color but sometimes they can be reddish.” He emphasized that leprosy “does not spread easily from person to person; casual contact will not spread leprosy. It’s important for the public to understand that.”
Despite the recent uptick in leprosy cases in Central Florida, the disease is very rare, and casual contact with an infected person is likely to not result in transmission, according to Jose A. Lucar, MD.
“Contrary to historical beliefs, leprosy is not highly contagious,” Dr. Lucar, an infectious disease physician and associate professor of medicine at George Washington University, Washington, said in an interview. “For reasons that have to do with the makeup of genes that affect their immune system, most people are not susceptible to acquire leprosy. It’s really a small percentage of the population. It does require prolonged contact with someone with untreated leprosy – over several months – to acquire an infection. So, the risk from any type of casual contact is low.”
Dr. Lucar
Dr. Jose A. Lucar
According to a research letter published in the CDC’s Emerging Infectious Diseases, the number of reported leprosy cases has more than doubled in the past decade. Of the 159 new cases reported nationwide in 2020, Florida accounted for about one-fifth of cases, with most limited to the central part of the state. “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born," and currently, about one-third of leprosy cases are in individuals born in the United States, he noted.
The research letter described a case of leprosy in a 54-year-old man who worked in landscaping, who sought treatment at a dermatology clinic in Central Florida in 2022 for a painful and progressive erythematous rash. The lesions began on his distal extensor extremities and progressed to involve his trunk and face. According to the report, the man denied any domestic or foreign travel, exposure to armadillos (a known source of transmission), prolonged contact with immigrants from leprosy-endemic countries, or connections with someone known to have leprosy. The authors concluded that the case “adds to the growing body of literature suggesting that central Florida represents an endemic location for leprosy. Travel to this area, even in the absence of other risk factors, should prompt consideration of leprosy in the appropriate clinical context.”
Dr. Lucar said that the mechanism of leprosy transmission is not fully understood, but armadillos, which typically traverse the southern United States, are naturally infected with the bacteria that causes leprosy. “It’s possible that they can spread it to people,” he said. “People who have occupations or hobbies that put them in potential contact with wildlife should avoid any close contact with armadillos. There’s also a discussion of whether [the spike in leprosy cases] may have to do with climate change. That is not yet confirmed. It’s not entirely clear why there’s been a recent rise. It remains an area of investigation.”
Meanwhile, clinicians should keep a high level of suspicion in patients who present with skin lesions compatible with leprosy. “These are typically discolored or numb patches on the skin,” Dr. Lucar said. “This can range from a single or a few lesions to very extensive involvement of the skin. The diminished sensation or loss of sensation within those skin patches is an important sign. There’s a loss of skin color but sometimes they can be reddish.” He emphasized that leprosy “does not spread easily from person to person; casual contact will not spread leprosy. It’s important for the public to understand that.”
Dr. Lucar reported no disclosures.
Despite the recent uptick in leprosy cases in Central Florida, the disease is very rare, and casual contact with an infected person is likely to not result in transmission, according to Jose A. Lucar, MD.
“Contrary to historical beliefs, leprosy is not highly contagious,” Dr. Lucar, an infectious disease physician and associate professor of medicine at George Washington University, Washington, said in an interview. “For reasons that have to do with the makeup of genes that affect their immune system, most people are not susceptible to acquire leprosy. It’s really a small percentage of the population. It does require prolonged contact with someone with untreated leprosy – over several months – to acquire an infection. So, the risk from any type of casual contact is low.”
Dr. Lucar
Dr. Jose A. Lucar
According to a research letter published in the CDC’s Emerging Infectious Diseases, the number of reported leprosy cases has more than doubled in the past decade. Of the 159 new cases reported nationwide in 2020, Florida accounted for about one-fifth of cases, with most limited to the central part of the state. “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born “In the U.S., there have been 150-250 cases reported each year over the past several years,” said Dr. Lucar, who was not affiliated with the research letter. “What seems to have changed is that since 2015, there has been a rise in cases in people who are U.S.-born," and currently, about one-third of leprosy cases are in individuals born in the United States, he noted.
The research letter described a case of leprosy in a 54-year-old man who worked in landscaping, who sought treatment at a dermatology clinic in Central Florida in 2022 for a painful and progressive erythematous rash. The lesions began on his distal extensor extremities and progressed to involve his trunk and face. According to the report, the man denied any domestic or foreign travel, exposure to armadillos (a known source of transmission), prolonged contact with immigrants from leprosy-endemic countries, or connections with someone known to have leprosy. The authors concluded that the case “adds to the growing body of literature suggesting that central Florida represents an endemic location for leprosy. Travel to this area, even in the absence of other risk factors, should prompt consideration of leprosy in the appropriate clinical context.”
Dr. Lucar said that the mechanism of leprosy transmission is not fully understood, but armadillos, which typically traverse the southern United States, are naturally infected with the bacteria that causes leprosy. “It’s possible that they can spread it to people,” he said. “People who have occupations or hobbies that put them in potential contact with wildlife should avoid any close contact with armadillos. There’s also a discussion of whether [the spike in leprosy cases] may have to do with climate change. That is not yet confirmed. It’s not entirely clear why there’s been a recent rise. It remains an area of investigation.”
Meanwhile, clinicians should keep a high level of suspicion in patients who present with skin lesions compatible with leprosy. “These are typically discolored or numb patches on the skin,” Dr. Lucar said. “This can range from a single or a few lesions to very extensive involvement of the skin. The diminished sensation or loss of sensation within those skin patches is an important sign. There’s a loss of skin color but sometimes they can be reddish.” He emphasized that leprosy “does not spread easily from person to person; casual contact will not spread leprosy. It’s important for the public to understand that.”
Medical education has changed drastically over the years. As theories and practices continue to change, what was once standard 10 or 20 years ago has been replaced with newer ideologies, processes, or technology. It seems likely, then, that you may disagree with some of the things that you learned as medical school has evolved.
This news organization asked physicians what they learned in med school that they now contest. Many of their answers include newer philosophies and practice methods.
Treat appropriately for pain
Jacqui O’Kane, DO, a 2013 med school graduate, was taught to avoid prescribing controlled medications whenever possible.
“Initially this attitude made sense to me,” says Dr. O’Kane, “but as I became an experienced physician – and patient – I saw the harm that such an attitude could cause. Patients on controlled medication long-term were often viewed as drug-seekers and treated as such, even if their regimen was largely regarded as appropriate. Likewise, those who could benefit from short-term controlled prescriptions were sometimes denied them because of their clinician’s fear.”
Today, Dr. O’Kane believes controlled medications should seldom be the first option for patients suffering pain, anxiety, or insomnia. But, she says, “they should remain on the table and without judgment for those who fail first-line treatment or for whom alternatives are contraindicated.”
Amy Baxter, MD, believes that the amount of time spent on pain education in school needs to change.
“Doctors in the U.S. get only 12 hours of pain education, and most of it is on pharmacology,” says Dr. Baxter, who graduated from med school in 1995. “In addition to incorrect information on home opioids and addiction, I was left with the impression that medication could treat chronic pain. I now have a completely different understanding of pain as a whole-brain warning system. The goal shouldn’t be pain-free, just more comfortable.”
Practice lifestyle and preventive medicine
Dolapo Babalola, MD, went to medical school eager to learn how to care for the human body and her family members’ illnesses, such as the debilitating effects of arthritic pain and other chronic diseases.
“I was taught the pathology behind arthritic pain, symptoms, signs, and treatment – that it has a genetic component and is inevitable to avoid – but nothing about how to prevent it,” says Dr. Babalola, a 2000 graduate.
Twenty years later, she discovered lifestyle medicine when she began to experience knee pain.
“I was introduced to the power of health restoration by discovering the root cause of diseases such as inflammation, hormonal imbalance, and insulin resistance due to poor lifestyle choices such as diet, inactivity, stress, inadequate sleep, and substance abuse,” she says.
Adebisi Alli, DO, who graduated in 2011, remembers being taught to treat type 2 diabetes by delaying progression rather than aiming for remission. But today, “lifestyle-led, team-based approaches are steadily becoming a first prescription across medical training with the goal to put diabetes in remission,” she says.
Patient care is at the core of medicine
Tracey O’Connell, MD, recalls her radiology residency in the early to mid-90s, when radiologists were integral to the health care team.
“We interacted with referrers and followed the course of patients’ diseases,” says Dr. O’Connell. “We knew patient histories, their stories. We were connected to other humans, doctors, nurses, teams, and the patients themselves.”
But with the advent of picture archiving and communication systems, high-speed CT and MRI, digital radiography, and voice recognition, the practice of radiology has changed dramatically.
“There’s no time to review or discuss cases anymore,” she says. “Reports went from eloquent and articulate documents with lists of differential diagnoses to short checklists and templates. The whole field of patient care has become dehumanizing, exactly the opposite of what humans need.”
Mache Seibel, MD, who graduated almost 50 years ago, agrees that patient care has lost its focus, to the detriment of patients.
“What I learned in medical school that is forgotten today is how to listen to patients, take a history, and do an examination using my hands and a stethoscope,” says Dr. Seibel. “Today with technology and time constraints, the focus is too much on the symptom without context, ordering a test, and getting the EMR boxes filled out.”
Physician, heal thyself
Priya Radhakrishnan, MD, remembers learning that a physician’s well-being was their responsibility. “We now know that well-being is the health system’s responsibility and that we need to diagnose ourselves and support each other, especially our trainees,” says Dr. Radhakrishna. She graduated in 1992. “Destigmatizing mental health is essential to well-being.”
Rachel Miller, MD, a 2009 med school graduate was taught that learning about health care systems and policy wasn’t necessary. Dr. Miller says they learned that policy knowledge would come in time. “I currently disagree. It is vital to understand aspects of health care systems and policy. Not knowing these things has partly contributed to the pervasiveness of burnout among physicians and other health care providers.”
Practice with gender at the forefront
Janice L. Werbinski, MD, an ob.gyn., and Elizabeth Anne Comen, MD, a breast cancer oncologist, remember when nearly all medical research was performed on the 140-lb White man. Doctors learned to treat patients through that male lens.
“The majority of the anatomy we saw in medical school was on a male figure,” says Dr. Comen, author of “All in Her Head,” a HarperCollins book slated to be released in February 2024. She graduated from med school in 2004. “The only time we saw anatomy for females was in the female reproductive system. That’s changing for the better.”
Dr. Werbinski chose a residency in obstetrics and gynecology in 1975 because she thought it was the only way she could serve female patients.
“I really thought that was the place for women’s health,” says Dr. Werbinski, cochair of the American Medical Women’s Association Sex & Gender Health Coalition.
“I am happy to say that significant awareness has grown since I graduated from medical school. I hope that when this question is asked of current medical students, they will be able to say that they know to practice with a sex- and gender-focused lens.”
Talk about racial disparities
John McHugh, MD, an ob.gyn., recalls learning little about the social determinants of health when he attended med school more than 30 years ago.
“We saw disparities in outcomes based on race and class but assumed that we would overcome them when we were in practice,” says Dr. McHugh, an AMWA Action Coalition for Equity member. “We didn’t understand the root causes of disparities and had never heard of concepts like epigenetics or weathering. I’m hopeful current research will help our understanding and today’s medical students will serve a safer, healthier, and more equitable world.”
Curtiland Deville, MD, an associate professor of radiation oncology, recalls having few conversations around race; racial disparities; and diversity, equity, and inclusion.
“When I went to medical school, it often felt like you weren’t supposed to talk about the differences in race,” says Dr. Deville, who graduated in 2005. But today, in the post-2020 era between COVID, during which health disparities got highlighted, and calls for racial justice taking center stage, Dr. Deville says many of the things they didn’t talk about have come to the forefront in our medical institutions.
Information at your fingertips
For Paru David, MD, a 1996 graduate, the most significant change is the amount of health and medical information available today. “Before, the information that was taught in medical school was obtained through textbooks or within journal articles,” says Dr. David.
“Now, we have databases of information. The key to success is being able to navigate the information available to us, digest it with a keen eye, and then apply it to patient care in a timely manner.”
A version of this article first appeared on Medscape.com.
Medical education has changed drastically over the years. As theories and practices continue to change, what was once standard 10 or 20 years ago has been replaced with newer ideologies, processes, or technology. It seems likely, then, that you may disagree with some of the things that you learned as medical school has evolved.
This news organization asked physicians what they learned in med school that they now contest. Many of their answers include newer philosophies and practice methods.
Treat appropriately for pain
Jacqui O’Kane, DO, a 2013 med school graduate, was taught to avoid prescribing controlled medications whenever possible.
“Initially this attitude made sense to me,” says Dr. O’Kane, “but as I became an experienced physician – and patient – I saw the harm that such an attitude could cause. Patients on controlled medication long-term were often viewed as drug-seekers and treated as such, even if their regimen was largely regarded as appropriate. Likewise, those who could benefit from short-term controlled prescriptions were sometimes denied them because of their clinician’s fear.”
Today, Dr. O’Kane believes controlled medications should seldom be the first option for patients suffering pain, anxiety, or insomnia. But, she says, “they should remain on the table and without judgment for those who fail first-line treatment or for whom alternatives are contraindicated.”
Amy Baxter, MD, believes that the amount of time spent on pain education in school needs to change.
“Doctors in the U.S. get only 12 hours of pain education, and most of it is on pharmacology,” says Dr. Baxter, who graduated from med school in 1995. “In addition to incorrect information on home opioids and addiction, I was left with the impression that medication could treat chronic pain. I now have a completely different understanding of pain as a whole-brain warning system. The goal shouldn’t be pain-free, just more comfortable.”
Practice lifestyle and preventive medicine
Dolapo Babalola, MD, went to medical school eager to learn how to care for the human body and her family members’ illnesses, such as the debilitating effects of arthritic pain and other chronic diseases.
“I was taught the pathology behind arthritic pain, symptoms, signs, and treatment – that it has a genetic component and is inevitable to avoid – but nothing about how to prevent it,” says Dr. Babalola, a 2000 graduate.
Twenty years later, she discovered lifestyle medicine when she began to experience knee pain.
“I was introduced to the power of health restoration by discovering the root cause of diseases such as inflammation, hormonal imbalance, and insulin resistance due to poor lifestyle choices such as diet, inactivity, stress, inadequate sleep, and substance abuse,” she says.
Adebisi Alli, DO, who graduated in 2011, remembers being taught to treat type 2 diabetes by delaying progression rather than aiming for remission. But today, “lifestyle-led, team-based approaches are steadily becoming a first prescription across medical training with the goal to put diabetes in remission,” she says.
Patient care is at the core of medicine
Tracey O’Connell, MD, recalls her radiology residency in the early to mid-90s, when radiologists were integral to the health care team.
“We interacted with referrers and followed the course of patients’ diseases,” says Dr. O’Connell. “We knew patient histories, their stories. We were connected to other humans, doctors, nurses, teams, and the patients themselves.”
But with the advent of picture archiving and communication systems, high-speed CT and MRI, digital radiography, and voice recognition, the practice of radiology has changed dramatically.
“There’s no time to review or discuss cases anymore,” she says. “Reports went from eloquent and articulate documents with lists of differential diagnoses to short checklists and templates. The whole field of patient care has become dehumanizing, exactly the opposite of what humans need.”
Mache Seibel, MD, who graduated almost 50 years ago, agrees that patient care has lost its focus, to the detriment of patients.
“What I learned in medical school that is forgotten today is how to listen to patients, take a history, and do an examination using my hands and a stethoscope,” says Dr. Seibel. “Today with technology and time constraints, the focus is too much on the symptom without context, ordering a test, and getting the EMR boxes filled out.”
Physician, heal thyself
Priya Radhakrishnan, MD, remembers learning that a physician’s well-being was their responsibility. “We now know that well-being is the health system’s responsibility and that we need to diagnose ourselves and support each other, especially our trainees,” says Dr. Radhakrishna. She graduated in 1992. “Destigmatizing mental health is essential to well-being.”
Rachel Miller, MD, a 2009 med school graduate was taught that learning about health care systems and policy wasn’t necessary. Dr. Miller says they learned that policy knowledge would come in time. “I currently disagree. It is vital to understand aspects of health care systems and policy. Not knowing these things has partly contributed to the pervasiveness of burnout among physicians and other health care providers.”
Practice with gender at the forefront
Janice L. Werbinski, MD, an ob.gyn., and Elizabeth Anne Comen, MD, a breast cancer oncologist, remember when nearly all medical research was performed on the 140-lb White man. Doctors learned to treat patients through that male lens.
“The majority of the anatomy we saw in medical school was on a male figure,” says Dr. Comen, author of “All in Her Head,” a HarperCollins book slated to be released in February 2024. She graduated from med school in 2004. “The only time we saw anatomy for females was in the female reproductive system. That’s changing for the better.”
Dr. Werbinski chose a residency in obstetrics and gynecology in 1975 because she thought it was the only way she could serve female patients.
“I really thought that was the place for women’s health,” says Dr. Werbinski, cochair of the American Medical Women’s Association Sex & Gender Health Coalition.
“I am happy to say that significant awareness has grown since I graduated from medical school. I hope that when this question is asked of current medical students, they will be able to say that they know to practice with a sex- and gender-focused lens.”
Talk about racial disparities
John McHugh, MD, an ob.gyn., recalls learning little about the social determinants of health when he attended med school more than 30 years ago.
“We saw disparities in outcomes based on race and class but assumed that we would overcome them when we were in practice,” says Dr. McHugh, an AMWA Action Coalition for Equity member. “We didn’t understand the root causes of disparities and had never heard of concepts like epigenetics or weathering. I’m hopeful current research will help our understanding and today’s medical students will serve a safer, healthier, and more equitable world.”
Curtiland Deville, MD, an associate professor of radiation oncology, recalls having few conversations around race; racial disparities; and diversity, equity, and inclusion.
“When I went to medical school, it often felt like you weren’t supposed to talk about the differences in race,” says Dr. Deville, who graduated in 2005. But today, in the post-2020 era between COVID, during which health disparities got highlighted, and calls for racial justice taking center stage, Dr. Deville says many of the things they didn’t talk about have come to the forefront in our medical institutions.
Information at your fingertips
For Paru David, MD, a 1996 graduate, the most significant change is the amount of health and medical information available today. “Before, the information that was taught in medical school was obtained through textbooks or within journal articles,” says Dr. David.
“Now, we have databases of information. The key to success is being able to navigate the information available to us, digest it with a keen eye, and then apply it to patient care in a timely manner.”
A version of this article first appeared on Medscape.com.
Medical education has changed drastically over the years. As theories and practices continue to change, what was once standard 10 or 20 years ago has been replaced with newer ideologies, processes, or technology. It seems likely, then, that you may disagree with some of the things that you learned as medical school has evolved.
This news organization asked physicians what they learned in med school that they now contest. Many of their answers include newer philosophies and practice methods.
Treat appropriately for pain
Jacqui O’Kane, DO, a 2013 med school graduate, was taught to avoid prescribing controlled medications whenever possible.
“Initially this attitude made sense to me,” says Dr. O’Kane, “but as I became an experienced physician – and patient – I saw the harm that such an attitude could cause. Patients on controlled medication long-term were often viewed as drug-seekers and treated as such, even if their regimen was largely regarded as appropriate. Likewise, those who could benefit from short-term controlled prescriptions were sometimes denied them because of their clinician’s fear.”
Today, Dr. O’Kane believes controlled medications should seldom be the first option for patients suffering pain, anxiety, or insomnia. But, she says, “they should remain on the table and without judgment for those who fail first-line treatment or for whom alternatives are contraindicated.”
Amy Baxter, MD, believes that the amount of time spent on pain education in school needs to change.
“Doctors in the U.S. get only 12 hours of pain education, and most of it is on pharmacology,” says Dr. Baxter, who graduated from med school in 1995. “In addition to incorrect information on home opioids and addiction, I was left with the impression that medication could treat chronic pain. I now have a completely different understanding of pain as a whole-brain warning system. The goal shouldn’t be pain-free, just more comfortable.”
Practice lifestyle and preventive medicine
Dolapo Babalola, MD, went to medical school eager to learn how to care for the human body and her family members’ illnesses, such as the debilitating effects of arthritic pain and other chronic diseases.
“I was taught the pathology behind arthritic pain, symptoms, signs, and treatment – that it has a genetic component and is inevitable to avoid – but nothing about how to prevent it,” says Dr. Babalola, a 2000 graduate.
Twenty years later, she discovered lifestyle medicine when she began to experience knee pain.
“I was introduced to the power of health restoration by discovering the root cause of diseases such as inflammation, hormonal imbalance, and insulin resistance due to poor lifestyle choices such as diet, inactivity, stress, inadequate sleep, and substance abuse,” she says.
Adebisi Alli, DO, who graduated in 2011, remembers being taught to treat type 2 diabetes by delaying progression rather than aiming for remission. But today, “lifestyle-led, team-based approaches are steadily becoming a first prescription across medical training with the goal to put diabetes in remission,” she says.
Patient care is at the core of medicine
Tracey O’Connell, MD, recalls her radiology residency in the early to mid-90s, when radiologists were integral to the health care team.
“We interacted with referrers and followed the course of patients’ diseases,” says Dr. O’Connell. “We knew patient histories, their stories. We were connected to other humans, doctors, nurses, teams, and the patients themselves.”
But with the advent of picture archiving and communication systems, high-speed CT and MRI, digital radiography, and voice recognition, the practice of radiology has changed dramatically.
“There’s no time to review or discuss cases anymore,” she says. “Reports went from eloquent and articulate documents with lists of differential diagnoses to short checklists and templates. The whole field of patient care has become dehumanizing, exactly the opposite of what humans need.”
Mache Seibel, MD, who graduated almost 50 years ago, agrees that patient care has lost its focus, to the detriment of patients.
“What I learned in medical school that is forgotten today is how to listen to patients, take a history, and do an examination using my hands and a stethoscope,” says Dr. Seibel. “Today with technology and time constraints, the focus is too much on the symptom without context, ordering a test, and getting the EMR boxes filled out.”
Physician, heal thyself
Priya Radhakrishnan, MD, remembers learning that a physician’s well-being was their responsibility. “We now know that well-being is the health system’s responsibility and that we need to diagnose ourselves and support each other, especially our trainees,” says Dr. Radhakrishna. She graduated in 1992. “Destigmatizing mental health is essential to well-being.”
Rachel Miller, MD, a 2009 med school graduate was taught that learning about health care systems and policy wasn’t necessary. Dr. Miller says they learned that policy knowledge would come in time. “I currently disagree. It is vital to understand aspects of health care systems and policy. Not knowing these things has partly contributed to the pervasiveness of burnout among physicians and other health care providers.”
Practice with gender at the forefront
Janice L. Werbinski, MD, an ob.gyn., and Elizabeth Anne Comen, MD, a breast cancer oncologist, remember when nearly all medical research was performed on the 140-lb White man. Doctors learned to treat patients through that male lens.
“The majority of the anatomy we saw in medical school was on a male figure,” says Dr. Comen, author of “All in Her Head,” a HarperCollins book slated to be released in February 2024. She graduated from med school in 2004. “The only time we saw anatomy for females was in the female reproductive system. That’s changing for the better.”
Dr. Werbinski chose a residency in obstetrics and gynecology in 1975 because she thought it was the only way she could serve female patients.
“I really thought that was the place for women’s health,” says Dr. Werbinski, cochair of the American Medical Women’s Association Sex & Gender Health Coalition.
“I am happy to say that significant awareness has grown since I graduated from medical school. I hope that when this question is asked of current medical students, they will be able to say that they know to practice with a sex- and gender-focused lens.”
Talk about racial disparities
John McHugh, MD, an ob.gyn., recalls learning little about the social determinants of health when he attended med school more than 30 years ago.
“We saw disparities in outcomes based on race and class but assumed that we would overcome them when we were in practice,” says Dr. McHugh, an AMWA Action Coalition for Equity member. “We didn’t understand the root causes of disparities and had never heard of concepts like epigenetics or weathering. I’m hopeful current research will help our understanding and today’s medical students will serve a safer, healthier, and more equitable world.”
Curtiland Deville, MD, an associate professor of radiation oncology, recalls having few conversations around race; racial disparities; and diversity, equity, and inclusion.
“When I went to medical school, it often felt like you weren’t supposed to talk about the differences in race,” says Dr. Deville, who graduated in 2005. But today, in the post-2020 era between COVID, during which health disparities got highlighted, and calls for racial justice taking center stage, Dr. Deville says many of the things they didn’t talk about have come to the forefront in our medical institutions.
Information at your fingertips
For Paru David, MD, a 1996 graduate, the most significant change is the amount of health and medical information available today. “Before, the information that was taught in medical school was obtained through textbooks or within journal articles,” says Dr. David.
“Now, we have databases of information. The key to success is being able to navigate the information available to us, digest it with a keen eye, and then apply it to patient care in a timely manner.”
A version of this article first appeared on Medscape.com.
Yeung LK, Alschuler DM, Wall M, et al. Multivitamin supplementation improves memory in older adults: a randomized clinical trial. Am J Clin Nutrition. 2023;118:273-282. doi:10.1016/j.ajcnut.2023.05.011.
EXPERT COMMENTARY
Preservation of function, both physical and cognitive, is key to long-term health and well-being. Age-related loss of function drives millions of people to spend an enormous amount of money each year on unregulated therapies—vitamins, supplements, infusions, hormones, and “natural” products—all toward the promise of improvement or preservation of physical strength, sexual function, and maintenance of lean body mass and cognitive abilities. Yeung and colleagues set out to determine whether the daily use of a multivitamin/mineral supplement (Centrum Silver) would impact memory in older adults.1
PHOTO: KLAVDIYAV/SHUTTERSTOCK
Details of the study
The COSMOS-Web study was designed to test the authors’ primary hypothesis that daily dietary flavanols would improve memory over 1 year.1 This study was embedded within the larger COSMOS (COcoa Supplement and Multivitamin Outcomes Study) trial, in which 21,442 people were recruited to assess the impact of flavanols and multivitamin supplements on cardiovascular and cancer outcomes.
Results of another ancillary study, the COSMOS-Mind trial (n = 2,262, average age 73, 60% female), reported no improvement with flavanols compared with placebo on a battery of tests of cognitive function administered by phone. In COSMOS-Mind, however, it was concluded that a daily multivitamin/mineral supplement improved the composite score of cognitive tests compared with placebo, particularly in participants with a history of cardiovascular disease.2
The COSMOS-Web trial recruited an additional cohort within the larger COSMOS trial from 2016–2017 (n = 3,562, average age 71, 67% female) to participate in this study specifically geared to assess memory, using the web-based ModRey test (a test of memory validated for use in a nonimpaired population). To qualify for enrollment, participants had to have access to an internet-connected computer. They were randomly assigned in a 2 x 2 study design to receive a daily multivitamin supplement or placebo; each of these cohorts was further divided into a flavanol supplementation or a placebo group. Analysis of the data showed no association between flavanol use and performance on any of the measures of memory or cognitive function.3
The COSMOS-Web trial assessed episodic recall, a function of hippocampus-mediated cognition that is particularly vulnerable to the effects of aging as demonstrated previously by neuroimaging and neuropsychological studies. The authors deployed a battery of 3 tests via a web platform for patients to complete online and independently.
The prespecified primary outcome was performance on episodic recall as measured by the ModRey test after 1 year of supplementation with multivitamins versus placebo. The ModRey test presents a series of 20 words at 3-second intervals to participants. At the conclusion of the last word, participants were asked to recall as many words as they could; after completing the 2 additional tasks, participants were asked again to recall the words. A secondary outcome of this test is the ratio of delayed to immediate recall.
Two additional tests were administered to assess cognitive performance related to different brain regions, the ModBent test (assessing novel object recognition) and the Flanker task (a measure of executive function). There was a placebo run-in phase during which participants’ adherence to daily supplement intake was ascertained. Participants were excluded if they demonstrated less than 75% adherence to study pills during the run-in placebo phase. The cognitive tasks were presented at study initiation and at yearly intervals for 3 years. The authors chose to use the results at 1 year as their primary outcome to assess the impact of supplementation during the period when adherence would be highest.
Results.At baseline, the placebo cohort recalled 7.2 words of 20 compared with 7.1 in the supplement group. In both groups there was a practice effect, with improvement in scores in the placebo group to 7.65 words and in the multivitamin group to 7.81 words. The improvement from baseline was statistically significantly better (0.71 words) in the multivitamin cohort than in the placebo group (0.45 words). There was no improvement in either group in the ModRey memory retention test (ability to recall the words after 15 minutes) or in the ModBent or Flanker tests. At 3 years of treatment, the placebo group improved by 0.92 words (SD, 3.22) whereas the multivitamin group improved by 1.13 words (SD, 3.39). These changes remained statistically significant.
The group with cardiovascular disease had lower baseline performance on the ModRey test. With supplementation, however, the improvement in this cohort was significantly greater than in those without cardiovascular disease at 1 year. The authors acknowledged that the changes were small and may not have been noticeable to the individuals, but they argued that even small changes as demonstrated in this study can have large health benefits at a population level.
The results of the COSMOS-Web trial corroborate the findings of the COSMOS-Mind study with respect to the benefits of multivitamin/mineral supplementation on cognitive test performance, particularly in a population with preexisting cardiovascular disease. The tests used across the 2 studies were different, which lends greater reliability to the findings.
Study strengths and limitations
A major strength of this study is its careful, rigorous design as a double-blind, placebo-controlled trial in a large patient population. Great care was devoted to ensuring study medication adherence. Another strength is that the cognitive tests chosen for the COSMOS-Web trial have been validated in cognitively normal populations, not those already impaired.
A limitation, however, is in the demographics of the study. The patient population was overwhelmingly White (93%), 67% were female, and they were well educated (94.8% having completed some college or beyond). Their baseline health was good; only 4.7% had a history of cardiovascular disease. Although generalizability of the study results from this population may be concerning,relative benefits of supplementation in this healthy, generally well-nourished and educated group may be lower than might be expected in a more nutritionally and educationally challenged population.
Finally, the difference between the placebo and active supplementation groups was small. Whether this less-than-1-word difference in immediate memory recall is noticeable by a patient is questionable. Both groups improved in their test performance over time—a consequence of serial cognitive tests of any kind. Although the authors calculated that the difference in recall translates to a 3-year reduction in age-related memory decline, it is hard to reconcile that with the fact that both groups actually improved over the 3 years of the study. ●
Acknowledgement
The author would like to thank JoAnn Manson, MD, DrPH, NCMP, for her assistance in evaluating the study.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
In this well-designed, randomized controlled trial by Yeung and colleagues, multivitamin/mineral supplementation improved performance on a test of immediate episodic memory at 1, 2, and 3 years compared with placebo. Given the simplicity and safety of this intervention, even with a small effect size, it makes sense to advise older patients that daily multivitamin use provides micronutrients and vitamins that may be absent in the diet or poorly absorbed by older adults. Whether this highly specific improvement in a test of hippocampal function translates into overall cognitive performance with aging remains a question.
BARBARA LEVY, MD
References
Yeung LK, Alschuler DM, Wall M, et al. Multivitamin supplementation improves memory in older adults: a randomized clinical trial. Am J Clin Nutrition. 2023;118:273282. doi:10.1016/j.ajcnut.2023.05.011.
Baker LD, Manson JE, Rapp SR, et al. Effects of cocoa extract and a multivitamin on cognitive function: a randomized clinical trial. Alzheimers Dement. 2023;19:1308-1319. doi:10.1002/alz.12767.
Brickman AM, Yeung LK, Alshuler DM, et al. Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption. Proc Natl Acad Sci USA. 2023:120:e2216932120. doi:10.1073/ pnas.2216932120.
Barbara Levy, MD, is Clinical Professor of Obstetrics and Gynecology, George Washington University School of Medicine and Health Sciences, Washington, DC, and Voluntary Clinical Professor of Obstetrics, Gynecology and Reproductive Sciences, UC San Diego School of Medicine. She serves on the OBG Management Board of Editors.
The author reports no financial relationships relevant to this article.
Barbara Levy, MD, is Clinical Professor of Obstetrics and Gynecology, George Washington University School of Medicine and Health Sciences, Washington, DC, and Voluntary Clinical Professor of Obstetrics, Gynecology and Reproductive Sciences, UC San Diego School of Medicine. She serves on the OBG Management Board of Editors.
The author reports no financial relationships relevant to this article.
Author and Disclosure Information
Barbara Levy, MD, is Clinical Professor of Obstetrics and Gynecology, George Washington University School of Medicine and Health Sciences, Washington, DC, and Voluntary Clinical Professor of Obstetrics, Gynecology and Reproductive Sciences, UC San Diego School of Medicine. She serves on the OBG Management Board of Editors.
The author reports no financial relationships relevant to this article.
Yeung LK, Alschuler DM, Wall M, et al. Multivitamin supplementation improves memory in older adults: a randomized clinical trial. Am J Clin Nutrition. 2023;118:273-282. doi:10.1016/j.ajcnut.2023.05.011.
EXPERT COMMENTARY
Preservation of function, both physical and cognitive, is key to long-term health and well-being. Age-related loss of function drives millions of people to spend an enormous amount of money each year on unregulated therapies—vitamins, supplements, infusions, hormones, and “natural” products—all toward the promise of improvement or preservation of physical strength, sexual function, and maintenance of lean body mass and cognitive abilities. Yeung and colleagues set out to determine whether the daily use of a multivitamin/mineral supplement (Centrum Silver) would impact memory in older adults.1
PHOTO: KLAVDIYAV/SHUTTERSTOCK
Details of the study
The COSMOS-Web study was designed to test the authors’ primary hypothesis that daily dietary flavanols would improve memory over 1 year.1 This study was embedded within the larger COSMOS (COcoa Supplement and Multivitamin Outcomes Study) trial, in which 21,442 people were recruited to assess the impact of flavanols and multivitamin supplements on cardiovascular and cancer outcomes.
Results of another ancillary study, the COSMOS-Mind trial (n = 2,262, average age 73, 60% female), reported no improvement with flavanols compared with placebo on a battery of tests of cognitive function administered by phone. In COSMOS-Mind, however, it was concluded that a daily multivitamin/mineral supplement improved the composite score of cognitive tests compared with placebo, particularly in participants with a history of cardiovascular disease.2
The COSMOS-Web trial recruited an additional cohort within the larger COSMOS trial from 2016–2017 (n = 3,562, average age 71, 67% female) to participate in this study specifically geared to assess memory, using the web-based ModRey test (a test of memory validated for use in a nonimpaired population). To qualify for enrollment, participants had to have access to an internet-connected computer. They were randomly assigned in a 2 x 2 study design to receive a daily multivitamin supplement or placebo; each of these cohorts was further divided into a flavanol supplementation or a placebo group. Analysis of the data showed no association between flavanol use and performance on any of the measures of memory or cognitive function.3
The COSMOS-Web trial assessed episodic recall, a function of hippocampus-mediated cognition that is particularly vulnerable to the effects of aging as demonstrated previously by neuroimaging and neuropsychological studies. The authors deployed a battery of 3 tests via a web platform for patients to complete online and independently.
The prespecified primary outcome was performance on episodic recall as measured by the ModRey test after 1 year of supplementation with multivitamins versus placebo. The ModRey test presents a series of 20 words at 3-second intervals to participants. At the conclusion of the last word, participants were asked to recall as many words as they could; after completing the 2 additional tasks, participants were asked again to recall the words. A secondary outcome of this test is the ratio of delayed to immediate recall.
Two additional tests were administered to assess cognitive performance related to different brain regions, the ModBent test (assessing novel object recognition) and the Flanker task (a measure of executive function). There was a placebo run-in phase during which participants’ adherence to daily supplement intake was ascertained. Participants were excluded if they demonstrated less than 75% adherence to study pills during the run-in placebo phase. The cognitive tasks were presented at study initiation and at yearly intervals for 3 years. The authors chose to use the results at 1 year as their primary outcome to assess the impact of supplementation during the period when adherence would be highest.
Results.At baseline, the placebo cohort recalled 7.2 words of 20 compared with 7.1 in the supplement group. In both groups there was a practice effect, with improvement in scores in the placebo group to 7.65 words and in the multivitamin group to 7.81 words. The improvement from baseline was statistically significantly better (0.71 words) in the multivitamin cohort than in the placebo group (0.45 words). There was no improvement in either group in the ModRey memory retention test (ability to recall the words after 15 minutes) or in the ModBent or Flanker tests. At 3 years of treatment, the placebo group improved by 0.92 words (SD, 3.22) whereas the multivitamin group improved by 1.13 words (SD, 3.39). These changes remained statistically significant.
The group with cardiovascular disease had lower baseline performance on the ModRey test. With supplementation, however, the improvement in this cohort was significantly greater than in those without cardiovascular disease at 1 year. The authors acknowledged that the changes were small and may not have been noticeable to the individuals, but they argued that even small changes as demonstrated in this study can have large health benefits at a population level.
The results of the COSMOS-Web trial corroborate the findings of the COSMOS-Mind study with respect to the benefits of multivitamin/mineral supplementation on cognitive test performance, particularly in a population with preexisting cardiovascular disease. The tests used across the 2 studies were different, which lends greater reliability to the findings.
Study strengths and limitations
A major strength of this study is its careful, rigorous design as a double-blind, placebo-controlled trial in a large patient population. Great care was devoted to ensuring study medication adherence. Another strength is that the cognitive tests chosen for the COSMOS-Web trial have been validated in cognitively normal populations, not those already impaired.
A limitation, however, is in the demographics of the study. The patient population was overwhelmingly White (93%), 67% were female, and they were well educated (94.8% having completed some college or beyond). Their baseline health was good; only 4.7% had a history of cardiovascular disease. Although generalizability of the study results from this population may be concerning,relative benefits of supplementation in this healthy, generally well-nourished and educated group may be lower than might be expected in a more nutritionally and educationally challenged population.
Finally, the difference between the placebo and active supplementation groups was small. Whether this less-than-1-word difference in immediate memory recall is noticeable by a patient is questionable. Both groups improved in their test performance over time—a consequence of serial cognitive tests of any kind. Although the authors calculated that the difference in recall translates to a 3-year reduction in age-related memory decline, it is hard to reconcile that with the fact that both groups actually improved over the 3 years of the study. ●
Acknowledgement
The author would like to thank JoAnn Manson, MD, DrPH, NCMP, for her assistance in evaluating the study.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
In this well-designed, randomized controlled trial by Yeung and colleagues, multivitamin/mineral supplementation improved performance on a test of immediate episodic memory at 1, 2, and 3 years compared with placebo. Given the simplicity and safety of this intervention, even with a small effect size, it makes sense to advise older patients that daily multivitamin use provides micronutrients and vitamins that may be absent in the diet or poorly absorbed by older adults. Whether this highly specific improvement in a test of hippocampal function translates into overall cognitive performance with aging remains a question.
BARBARA LEVY, MD
Yeung LK, Alschuler DM, Wall M, et al. Multivitamin supplementation improves memory in older adults: a randomized clinical trial. Am J Clin Nutrition. 2023;118:273-282. doi:10.1016/j.ajcnut.2023.05.011.
EXPERT COMMENTARY
Preservation of function, both physical and cognitive, is key to long-term health and well-being. Age-related loss of function drives millions of people to spend an enormous amount of money each year on unregulated therapies—vitamins, supplements, infusions, hormones, and “natural” products—all toward the promise of improvement or preservation of physical strength, sexual function, and maintenance of lean body mass and cognitive abilities. Yeung and colleagues set out to determine whether the daily use of a multivitamin/mineral supplement (Centrum Silver) would impact memory in older adults.1
PHOTO: KLAVDIYAV/SHUTTERSTOCK
Details of the study
The COSMOS-Web study was designed to test the authors’ primary hypothesis that daily dietary flavanols would improve memory over 1 year.1 This study was embedded within the larger COSMOS (COcoa Supplement and Multivitamin Outcomes Study) trial, in which 21,442 people were recruited to assess the impact of flavanols and multivitamin supplements on cardiovascular and cancer outcomes.
Results of another ancillary study, the COSMOS-Mind trial (n = 2,262, average age 73, 60% female), reported no improvement with flavanols compared with placebo on a battery of tests of cognitive function administered by phone. In COSMOS-Mind, however, it was concluded that a daily multivitamin/mineral supplement improved the composite score of cognitive tests compared with placebo, particularly in participants with a history of cardiovascular disease.2
The COSMOS-Web trial recruited an additional cohort within the larger COSMOS trial from 2016–2017 (n = 3,562, average age 71, 67% female) to participate in this study specifically geared to assess memory, using the web-based ModRey test (a test of memory validated for use in a nonimpaired population). To qualify for enrollment, participants had to have access to an internet-connected computer. They were randomly assigned in a 2 x 2 study design to receive a daily multivitamin supplement or placebo; each of these cohorts was further divided into a flavanol supplementation or a placebo group. Analysis of the data showed no association between flavanol use and performance on any of the measures of memory or cognitive function.3
The COSMOS-Web trial assessed episodic recall, a function of hippocampus-mediated cognition that is particularly vulnerable to the effects of aging as demonstrated previously by neuroimaging and neuropsychological studies. The authors deployed a battery of 3 tests via a web platform for patients to complete online and independently.
The prespecified primary outcome was performance on episodic recall as measured by the ModRey test after 1 year of supplementation with multivitamins versus placebo. The ModRey test presents a series of 20 words at 3-second intervals to participants. At the conclusion of the last word, participants were asked to recall as many words as they could; after completing the 2 additional tasks, participants were asked again to recall the words. A secondary outcome of this test is the ratio of delayed to immediate recall.
Two additional tests were administered to assess cognitive performance related to different brain regions, the ModBent test (assessing novel object recognition) and the Flanker task (a measure of executive function). There was a placebo run-in phase during which participants’ adherence to daily supplement intake was ascertained. Participants were excluded if they demonstrated less than 75% adherence to study pills during the run-in placebo phase. The cognitive tasks were presented at study initiation and at yearly intervals for 3 years. The authors chose to use the results at 1 year as their primary outcome to assess the impact of supplementation during the period when adherence would be highest.
Results.At baseline, the placebo cohort recalled 7.2 words of 20 compared with 7.1 in the supplement group. In both groups there was a practice effect, with improvement in scores in the placebo group to 7.65 words and in the multivitamin group to 7.81 words. The improvement from baseline was statistically significantly better (0.71 words) in the multivitamin cohort than in the placebo group (0.45 words). There was no improvement in either group in the ModRey memory retention test (ability to recall the words after 15 minutes) or in the ModBent or Flanker tests. At 3 years of treatment, the placebo group improved by 0.92 words (SD, 3.22) whereas the multivitamin group improved by 1.13 words (SD, 3.39). These changes remained statistically significant.
The group with cardiovascular disease had lower baseline performance on the ModRey test. With supplementation, however, the improvement in this cohort was significantly greater than in those without cardiovascular disease at 1 year. The authors acknowledged that the changes were small and may not have been noticeable to the individuals, but they argued that even small changes as demonstrated in this study can have large health benefits at a population level.
The results of the COSMOS-Web trial corroborate the findings of the COSMOS-Mind study with respect to the benefits of multivitamin/mineral supplementation on cognitive test performance, particularly in a population with preexisting cardiovascular disease. The tests used across the 2 studies were different, which lends greater reliability to the findings.
Study strengths and limitations
A major strength of this study is its careful, rigorous design as a double-blind, placebo-controlled trial in a large patient population. Great care was devoted to ensuring study medication adherence. Another strength is that the cognitive tests chosen for the COSMOS-Web trial have been validated in cognitively normal populations, not those already impaired.
A limitation, however, is in the demographics of the study. The patient population was overwhelmingly White (93%), 67% were female, and they were well educated (94.8% having completed some college or beyond). Their baseline health was good; only 4.7% had a history of cardiovascular disease. Although generalizability of the study results from this population may be concerning,relative benefits of supplementation in this healthy, generally well-nourished and educated group may be lower than might be expected in a more nutritionally and educationally challenged population.
Finally, the difference between the placebo and active supplementation groups was small. Whether this less-than-1-word difference in immediate memory recall is noticeable by a patient is questionable. Both groups improved in their test performance over time—a consequence of serial cognitive tests of any kind. Although the authors calculated that the difference in recall translates to a 3-year reduction in age-related memory decline, it is hard to reconcile that with the fact that both groups actually improved over the 3 years of the study. ●
Acknowledgement
The author would like to thank JoAnn Manson, MD, DrPH, NCMP, for her assistance in evaluating the study.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
In this well-designed, randomized controlled trial by Yeung and colleagues, multivitamin/mineral supplementation improved performance on a test of immediate episodic memory at 1, 2, and 3 years compared with placebo. Given the simplicity and safety of this intervention, even with a small effect size, it makes sense to advise older patients that daily multivitamin use provides micronutrients and vitamins that may be absent in the diet or poorly absorbed by older adults. Whether this highly specific improvement in a test of hippocampal function translates into overall cognitive performance with aging remains a question.
BARBARA LEVY, MD
References
Yeung LK, Alschuler DM, Wall M, et al. Multivitamin supplementation improves memory in older adults: a randomized clinical trial. Am J Clin Nutrition. 2023;118:273282. doi:10.1016/j.ajcnut.2023.05.011.
Baker LD, Manson JE, Rapp SR, et al. Effects of cocoa extract and a multivitamin on cognitive function: a randomized clinical trial. Alzheimers Dement. 2023;19:1308-1319. doi:10.1002/alz.12767.
Brickman AM, Yeung LK, Alshuler DM, et al. Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption. Proc Natl Acad Sci USA. 2023:120:e2216932120. doi:10.1073/ pnas.2216932120.
References
Yeung LK, Alschuler DM, Wall M, et al. Multivitamin supplementation improves memory in older adults: a randomized clinical trial. Am J Clin Nutrition. 2023;118:273282. doi:10.1016/j.ajcnut.2023.05.011.
Baker LD, Manson JE, Rapp SR, et al. Effects of cocoa extract and a multivitamin on cognitive function: a randomized clinical trial. Alzheimers Dement. 2023;19:1308-1319. doi:10.1002/alz.12767.
Brickman AM, Yeung LK, Alshuler DM, et al. Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption. Proc Natl Acad Sci USA. 2023:120:e2216932120. doi:10.1073/ pnas.2216932120.
FRANCE – Did you know that, long before anyone else, Leonardo da Vinci called into question Galen’s description of how the heart works?
This is just one of the many interesting tidbits featured in “Leonardo da Vinci and Anatomy, the Mechanics of Life,” an exhibition that runs until Sept. 17 at the Château du Clos Lucé – a home once owned by da Vinci – in Amboise, France.
In his book about this exhibition, Jean-Jacques Monsuez, MD, a cardiologist at Paris’ René-Muret Hospital, noted, “For a long time, very few people knew about Leonardo’s observations on the cardiovascular system’s anatomy or his rather physiological analysis of its hemodynamics. Had this not been the case, his work would, very likely, have had a significant influence on the subsequent development of knowledge about the cardiovascular system.”
A visionary view
In the second century AD, Galen put forth the following novel theory: The liver transforms food into blood. The blood is carried through veins to the various organs and is sent to the right ventricle through ebb and flow and to the left ventricle through intraventricular pores [which, we now know, do not exist].
In the left ventricle, the blood mixes with air – “pneuma” – from the lungs and is transformed into vital spirits. Clear blood, enriched with vital heat, is then carried by the arteries to peripheral tissues.
This erroneous explanation of how blood circulates went unchallenged for hundreds and hundreds of years.
And then along came Leonardo, anatomy pioneer and experimenter extraordinaire. Around 1513, after looking more closely at the heart chambers and the aortic valve, he arrived at the belief that, contrary to Galen’s theory, blood flow starts in the heart, not the liver.
“The heart in itself is not the origin of life, but [simply] a vessel made of dense muscle vivified and nourished by an artery and a vein, as are other muscles.”
He arrived at this insight through his in-depth dissections and studies of pig, ox, and human hearts.
A vast number of folios came about, all dedicated to the functioning of the heart. Taking his lead from Galen and Avicenna, Leonardo started off by drawing two atria and two ventricles along with Galen’s intraventricular pores.
But he quickly moved in a different direction when it came to the question of what enables the heart to produce vital spirits from blood flow.
On a double sheet showing several views of an ox heart, he drew all the components – this time with the aortic valve both open and closed.
“The accuracy of the description of the aortic valve is impressive, considering that, in a normal subject, its surface is on the order of 3 cm²,” Monsuez noted.
But Leonardo went even further, explaining the sequence of the opening and closing of the valve. To complete his demonstration, he even used a model from one of his experiments. He took some water with a suspension of grass seeds and pumped it through a glass tube that had a bulge representing the aortic sinuses. He tracked the resultant flow and eddies that mimic the hemodynamics enabling the valve to open and close.
“Recently, Professor Choudhury’s team at Oxford took Leonardo’s sketch illustrating this ingenious description and superimposed it on the 4D-MRI image of systolic flow vortices. They confirmed that Leonardo was accurate,” Monsuez reported.
But Leonardo’s ideas about the heart didn’t stop there. The polymath also provided a description of cardiac contraction. This was based on observations he had made by watching the movement of spiles that had been driven into the hearts of pigs at a slaughterhouse. He made an ancillary diagram confirming his interpretation. “N, the firm muscle is pulled back, and it’s the first cause of the heart’s movement, for, thus pulled, it lengthens, and lengthening, it shortens.”
Leonardo was the first to explain the role of the atria. “The atria are the antechambers that receive the blood from the heart when it escapes from its ventricle from the beginning until the end of the pressure.”
In addition, he showed, for the first time, the round crown-like appearance of the heart’s vasculature. “The heart has its surface divided into three parts by three veins which descend from its base, of which veins two terminate the extremities of the right ventricle and have two arteries in contact below them […] the surface space of the heart enclosed within its arteries occupies half the surface circle of the thickness of the heart […].”
Finally, Leonardo was the first to give a description and sketch of a bicuspid aortic valve, as can be seen on a 500-year-old plate in the Royal Collection Trust.
Wealth of knowledge
Because Leonardo’s discoveries about the cardiovascular system remained in the shadows, they did not factor into the thinking of physicians and surgeons during his lifetime or in the years that followed.
That is, until 1773, when Scottish anatomist Dr. William Hunter found out that the collection of King Charles II of England contained folios on the human body – folios that were made by Leonardo da Vinci.
The world would have to wait until the 19th century for a complete facsimile edition of the collection kept at Windsor Castle.
FRANCE – Did you know that, long before anyone else, Leonardo da Vinci called into question Galen’s description of how the heart works?
This is just one of the many interesting tidbits featured in “Leonardo da Vinci and Anatomy, the Mechanics of Life,” an exhibition that runs until Sept. 17 at the Château du Clos Lucé – a home once owned by da Vinci – in Amboise, France.
In his book about this exhibition, Jean-Jacques Monsuez, MD, a cardiologist at Paris’ René-Muret Hospital, noted, “For a long time, very few people knew about Leonardo’s observations on the cardiovascular system’s anatomy or his rather physiological analysis of its hemodynamics. Had this not been the case, his work would, very likely, have had a significant influence on the subsequent development of knowledge about the cardiovascular system.”
A visionary view
In the second century AD, Galen put forth the following novel theory: The liver transforms food into blood. The blood is carried through veins to the various organs and is sent to the right ventricle through ebb and flow and to the left ventricle through intraventricular pores [which, we now know, do not exist].
In the left ventricle, the blood mixes with air – “pneuma” – from the lungs and is transformed into vital spirits. Clear blood, enriched with vital heat, is then carried by the arteries to peripheral tissues.
This erroneous explanation of how blood circulates went unchallenged for hundreds and hundreds of years.
And then along came Leonardo, anatomy pioneer and experimenter extraordinaire. Around 1513, after looking more closely at the heart chambers and the aortic valve, he arrived at the belief that, contrary to Galen’s theory, blood flow starts in the heart, not the liver.
“The heart in itself is not the origin of life, but [simply] a vessel made of dense muscle vivified and nourished by an artery and a vein, as are other muscles.”
He arrived at this insight through his in-depth dissections and studies of pig, ox, and human hearts.
A vast number of folios came about, all dedicated to the functioning of the heart. Taking his lead from Galen and Avicenna, Leonardo started off by drawing two atria and two ventricles along with Galen’s intraventricular pores.
But he quickly moved in a different direction when it came to the question of what enables the heart to produce vital spirits from blood flow.
On a double sheet showing several views of an ox heart, he drew all the components – this time with the aortic valve both open and closed.
“The accuracy of the description of the aortic valve is impressive, considering that, in a normal subject, its surface is on the order of 3 cm²,” Monsuez noted.
But Leonardo went even further, explaining the sequence of the opening and closing of the valve. To complete his demonstration, he even used a model from one of his experiments. He took some water with a suspension of grass seeds and pumped it through a glass tube that had a bulge representing the aortic sinuses. He tracked the resultant flow and eddies that mimic the hemodynamics enabling the valve to open and close.
“Recently, Professor Choudhury’s team at Oxford took Leonardo’s sketch illustrating this ingenious description and superimposed it on the 4D-MRI image of systolic flow vortices. They confirmed that Leonardo was accurate,” Monsuez reported.
But Leonardo’s ideas about the heart didn’t stop there. The polymath also provided a description of cardiac contraction. This was based on observations he had made by watching the movement of spiles that had been driven into the hearts of pigs at a slaughterhouse. He made an ancillary diagram confirming his interpretation. “N, the firm muscle is pulled back, and it’s the first cause of the heart’s movement, for, thus pulled, it lengthens, and lengthening, it shortens.”
Leonardo was the first to explain the role of the atria. “The atria are the antechambers that receive the blood from the heart when it escapes from its ventricle from the beginning until the end of the pressure.”
In addition, he showed, for the first time, the round crown-like appearance of the heart’s vasculature. “The heart has its surface divided into three parts by three veins which descend from its base, of which veins two terminate the extremities of the right ventricle and have two arteries in contact below them […] the surface space of the heart enclosed within its arteries occupies half the surface circle of the thickness of the heart […].”
Finally, Leonardo was the first to give a description and sketch of a bicuspid aortic valve, as can be seen on a 500-year-old plate in the Royal Collection Trust.
Wealth of knowledge
Because Leonardo’s discoveries about the cardiovascular system remained in the shadows, they did not factor into the thinking of physicians and surgeons during his lifetime or in the years that followed.
That is, until 1773, when Scottish anatomist Dr. William Hunter found out that the collection of King Charles II of England contained folios on the human body – folios that were made by Leonardo da Vinci.
The world would have to wait until the 19th century for a complete facsimile edition of the collection kept at Windsor Castle.
FRANCE – Did you know that, long before anyone else, Leonardo da Vinci called into question Galen’s description of how the heart works?
This is just one of the many interesting tidbits featured in “Leonardo da Vinci and Anatomy, the Mechanics of Life,” an exhibition that runs until Sept. 17 at the Château du Clos Lucé – a home once owned by da Vinci – in Amboise, France.
In his book about this exhibition, Jean-Jacques Monsuez, MD, a cardiologist at Paris’ René-Muret Hospital, noted, “For a long time, very few people knew about Leonardo’s observations on the cardiovascular system’s anatomy or his rather physiological analysis of its hemodynamics. Had this not been the case, his work would, very likely, have had a significant influence on the subsequent development of knowledge about the cardiovascular system.”
A visionary view
In the second century AD, Galen put forth the following novel theory: The liver transforms food into blood. The blood is carried through veins to the various organs and is sent to the right ventricle through ebb and flow and to the left ventricle through intraventricular pores [which, we now know, do not exist].
In the left ventricle, the blood mixes with air – “pneuma” – from the lungs and is transformed into vital spirits. Clear blood, enriched with vital heat, is then carried by the arteries to peripheral tissues.
This erroneous explanation of how blood circulates went unchallenged for hundreds and hundreds of years.
And then along came Leonardo, anatomy pioneer and experimenter extraordinaire. Around 1513, after looking more closely at the heart chambers and the aortic valve, he arrived at the belief that, contrary to Galen’s theory, blood flow starts in the heart, not the liver.
“The heart in itself is not the origin of life, but [simply] a vessel made of dense muscle vivified and nourished by an artery and a vein, as are other muscles.”
He arrived at this insight through his in-depth dissections and studies of pig, ox, and human hearts.
A vast number of folios came about, all dedicated to the functioning of the heart. Taking his lead from Galen and Avicenna, Leonardo started off by drawing two atria and two ventricles along with Galen’s intraventricular pores.
But he quickly moved in a different direction when it came to the question of what enables the heart to produce vital spirits from blood flow.
On a double sheet showing several views of an ox heart, he drew all the components – this time with the aortic valve both open and closed.
“The accuracy of the description of the aortic valve is impressive, considering that, in a normal subject, its surface is on the order of 3 cm²,” Monsuez noted.
But Leonardo went even further, explaining the sequence of the opening and closing of the valve. To complete his demonstration, he even used a model from one of his experiments. He took some water with a suspension of grass seeds and pumped it through a glass tube that had a bulge representing the aortic sinuses. He tracked the resultant flow and eddies that mimic the hemodynamics enabling the valve to open and close.
“Recently, Professor Choudhury’s team at Oxford took Leonardo’s sketch illustrating this ingenious description and superimposed it on the 4D-MRI image of systolic flow vortices. They confirmed that Leonardo was accurate,” Monsuez reported.
But Leonardo’s ideas about the heart didn’t stop there. The polymath also provided a description of cardiac contraction. This was based on observations he had made by watching the movement of spiles that had been driven into the hearts of pigs at a slaughterhouse. He made an ancillary diagram confirming his interpretation. “N, the firm muscle is pulled back, and it’s the first cause of the heart’s movement, for, thus pulled, it lengthens, and lengthening, it shortens.”
Leonardo was the first to explain the role of the atria. “The atria are the antechambers that receive the blood from the heart when it escapes from its ventricle from the beginning until the end of the pressure.”
In addition, he showed, for the first time, the round crown-like appearance of the heart’s vasculature. “The heart has its surface divided into three parts by three veins which descend from its base, of which veins two terminate the extremities of the right ventricle and have two arteries in contact below them […] the surface space of the heart enclosed within its arteries occupies half the surface circle of the thickness of the heart […].”
Finally, Leonardo was the first to give a description and sketch of a bicuspid aortic valve, as can be seen on a 500-year-old plate in the Royal Collection Trust.
Wealth of knowledge
Because Leonardo’s discoveries about the cardiovascular system remained in the shadows, they did not factor into the thinking of physicians and surgeons during his lifetime or in the years that followed.
That is, until 1773, when Scottish anatomist Dr. William Hunter found out that the collection of King Charles II of England contained folios on the human body – folios that were made by Leonardo da Vinci.
The world would have to wait until the 19th century for a complete facsimile edition of the collection kept at Windsor Castle.
A woman’s quest to become pregnant resulted in lead poisoning from an Ayurvedic treatment. The case triggered the seizure of pills from an Ontario natural-products clinic and the issuance of government warnings about the risks of products from this business, according to a new report.
The case highlights the need for collaboration between clinicians and public health authorities to address the potential health risks of supplements, including the presence of lead and other metals in Ayurvedic products, according to the report.
“When consumer products may be contaminated with lead, or when lead exposure is linked to sources in the community, involving public health can facilitate broader actions to reduce and prevent exposures to other people at risk,” wrote report author Julian Gitelman, MD, MPH, a resident physician at the University of Toronto Dalla Lana School of Public Health, and colleagues.
Their case study was published in the Canadian Medical Association Journal.
The researchers detailed what happened after a 39-year-old woman sought medical care for abdominal pain, constipation, nausea, and vomiting. The woman underwent a series of tests, including colonoscopy, laparoscopy, and biopsies of bone marrow and ovarian cysts.
Only later did clinicians home in on the cause of her ailments: the Ayurvedic medications that the patient had been taking daily for more than a year for infertility. Her daily regimen had varied, ranging from a few pills to a dozen pills.
Heavy metals are sometimes intentionally added to Ayurvedic supplements for perceived healing properties, wrote the authors. They cited a previous study of a sample of Ayurvedic pills bought on the Internet from manufacturers based in the United States and India that showed that 21% contained lead, mercury, or arsenic.
Regulators in many countries struggle to help consumers understand the risks of natural health supplements, and the challenge extends well beyond Ayurvedic products.
There has been a “huge and very troubling increase” in U.S. poison control calls associated with gummy-bear products containing melatonin, said Canadian Senator Stan Kutcher, MD, at a May 11 meeting of Canada’s Standing Senate Committee on Social Affairs, Science, and Technology.
In April, JAMA published a U.S. analysis of melatonin gummy products, Dr. Kutcher noted. In this research letter, investigators reported that one product did not contain detectable levels of melatonin but did contain 31.3 mg of cannabidiol.
In other products, the quantity of melatonin ranged from 74% to 347% of the labeled quantity. A previous Canadian study of 16 melatonin brands found that the actual dose of melatonin ranged from 17% to 478% of the declared quantity, the letter noted.
The May 11 Senate meeting provided a forum for many of the recurring debates about supplements, which also are known as natural health products.
Barry Power, PharmD, editor in chief for the Canadian Pharmacists Association, said that his group was disappointed when Canada excluded natural health products from Vanessa’s Law, which was passed in 2014. This law sought to improve the reporting of adverse reactions to drugs.
“We’re glad this is being revisited now,” Dr. Power told the Senate committee. “Although natural health products are often seen as low risk, we need to keep in mind that ‘low risk’ does not mean ‘no risk,’ and ‘natural’ does not mean ‘safe.’ ”
In contrast, Aaron Skelton, chief executive of the Canadian Health Food Association, spoke against this bid to expand the reach of Vanessa’s Law into natural health products. Canadian lawmakers attached provisions regarding increased oversight of natural health products to a budget package instead of considering them as part of a stand-alone bill.
“Our concern is that the powers that are being discussed have not been reviewed and debated,” Mr. Skelton told Dr. Kutcher. “The potential for overreach and unnecessary regulation is significant, and that deserves debate.”
“Profits should not trump Canadians’ health,” answered Dr. Kutcher, who earlier served as head of the psychiatry department at Dalhousie University in Halifax, N.S.
By June, Vanessa’s Law had been expanded with provisions that address natural health products, including the reporting of products that present a serious risk to consumers.
Educating consumers
Many consumers overestimate the level of government regulation of supplements, said Pieter A. Cohen, MD, leader of the Supplement Research Program at Cambridge Health Alliance in Massachusetts. Dr. Cohen was the lead author of the JAMA research letter about melatonin products.
Supplements often share shelves in pharmacies with medicines that are subject to more strict regulation, which causes confusion.
“It’s really hard to wrap your brain around [the fact] that a health product is being sold in pharmacies in the United States and it’s not being vetted by the FDA [U.S. Food and Drug Administration]”, Dr. Cohen said in an interview
The confusion extends across borders. Many consumers in other countries will assume that the FDA performed premarket screening of U.S.-made supplements, but that is not the case, he said.
People who want to take supplements should look for reputable sources of information about them, such as the website of the National Institutes of Health’s Office of Dietary Supplements, Dr. Cohen said. But patients often forget or fail to do this, which can create medical puzzles, such as the case of the woman in the Ontario case study, said Peter Lurie, MD, MPH, executive director of the nonprofit Center for Science in the Public Interest, which has pressed for increased regulation of supplements.
Clinicians need to keep in mind that patients may need prodding to reveal what supplements they are taking, he said.
“They just think of them as different, somehow not the province of the doctor,” Dr. Lurie said. “For others, they are concerned that the doctors will disapprove. So, they hide it.”
A version of this article first appeared on Medscape.com.
A woman’s quest to become pregnant resulted in lead poisoning from an Ayurvedic treatment. The case triggered the seizure of pills from an Ontario natural-products clinic and the issuance of government warnings about the risks of products from this business, according to a new report.
The case highlights the need for collaboration between clinicians and public health authorities to address the potential health risks of supplements, including the presence of lead and other metals in Ayurvedic products, according to the report.
“When consumer products may be contaminated with lead, or when lead exposure is linked to sources in the community, involving public health can facilitate broader actions to reduce and prevent exposures to other people at risk,” wrote report author Julian Gitelman, MD, MPH, a resident physician at the University of Toronto Dalla Lana School of Public Health, and colleagues.
Their case study was published in the Canadian Medical Association Journal.
The researchers detailed what happened after a 39-year-old woman sought medical care for abdominal pain, constipation, nausea, and vomiting. The woman underwent a series of tests, including colonoscopy, laparoscopy, and biopsies of bone marrow and ovarian cysts.
Only later did clinicians home in on the cause of her ailments: the Ayurvedic medications that the patient had been taking daily for more than a year for infertility. Her daily regimen had varied, ranging from a few pills to a dozen pills.
Heavy metals are sometimes intentionally added to Ayurvedic supplements for perceived healing properties, wrote the authors. They cited a previous study of a sample of Ayurvedic pills bought on the Internet from manufacturers based in the United States and India that showed that 21% contained lead, mercury, or arsenic.
Regulators in many countries struggle to help consumers understand the risks of natural health supplements, and the challenge extends well beyond Ayurvedic products.
There has been a “huge and very troubling increase” in U.S. poison control calls associated with gummy-bear products containing melatonin, said Canadian Senator Stan Kutcher, MD, at a May 11 meeting of Canada’s Standing Senate Committee on Social Affairs, Science, and Technology.
In April, JAMA published a U.S. analysis of melatonin gummy products, Dr. Kutcher noted. In this research letter, investigators reported that one product did not contain detectable levels of melatonin but did contain 31.3 mg of cannabidiol.
In other products, the quantity of melatonin ranged from 74% to 347% of the labeled quantity. A previous Canadian study of 16 melatonin brands found that the actual dose of melatonin ranged from 17% to 478% of the declared quantity, the letter noted.
The May 11 Senate meeting provided a forum for many of the recurring debates about supplements, which also are known as natural health products.
Barry Power, PharmD, editor in chief for the Canadian Pharmacists Association, said that his group was disappointed when Canada excluded natural health products from Vanessa’s Law, which was passed in 2014. This law sought to improve the reporting of adverse reactions to drugs.
“We’re glad this is being revisited now,” Dr. Power told the Senate committee. “Although natural health products are often seen as low risk, we need to keep in mind that ‘low risk’ does not mean ‘no risk,’ and ‘natural’ does not mean ‘safe.’ ”
In contrast, Aaron Skelton, chief executive of the Canadian Health Food Association, spoke against this bid to expand the reach of Vanessa’s Law into natural health products. Canadian lawmakers attached provisions regarding increased oversight of natural health products to a budget package instead of considering them as part of a stand-alone bill.
“Our concern is that the powers that are being discussed have not been reviewed and debated,” Mr. Skelton told Dr. Kutcher. “The potential for overreach and unnecessary regulation is significant, and that deserves debate.”
“Profits should not trump Canadians’ health,” answered Dr. Kutcher, who earlier served as head of the psychiatry department at Dalhousie University in Halifax, N.S.
By June, Vanessa’s Law had been expanded with provisions that address natural health products, including the reporting of products that present a serious risk to consumers.
Educating consumers
Many consumers overestimate the level of government regulation of supplements, said Pieter A. Cohen, MD, leader of the Supplement Research Program at Cambridge Health Alliance in Massachusetts. Dr. Cohen was the lead author of the JAMA research letter about melatonin products.
Supplements often share shelves in pharmacies with medicines that are subject to more strict regulation, which causes confusion.
“It’s really hard to wrap your brain around [the fact] that a health product is being sold in pharmacies in the United States and it’s not being vetted by the FDA [U.S. Food and Drug Administration]”, Dr. Cohen said in an interview
The confusion extends across borders. Many consumers in other countries will assume that the FDA performed premarket screening of U.S.-made supplements, but that is not the case, he said.
People who want to take supplements should look for reputable sources of information about them, such as the website of the National Institutes of Health’s Office of Dietary Supplements, Dr. Cohen said. But patients often forget or fail to do this, which can create medical puzzles, such as the case of the woman in the Ontario case study, said Peter Lurie, MD, MPH, executive director of the nonprofit Center for Science in the Public Interest, which has pressed for increased regulation of supplements.
Clinicians need to keep in mind that patients may need prodding to reveal what supplements they are taking, he said.
“They just think of them as different, somehow not the province of the doctor,” Dr. Lurie said. “For others, they are concerned that the doctors will disapprove. So, they hide it.”
A version of this article first appeared on Medscape.com.
A woman’s quest to become pregnant resulted in lead poisoning from an Ayurvedic treatment. The case triggered the seizure of pills from an Ontario natural-products clinic and the issuance of government warnings about the risks of products from this business, according to a new report.
The case highlights the need for collaboration between clinicians and public health authorities to address the potential health risks of supplements, including the presence of lead and other metals in Ayurvedic products, according to the report.
“When consumer products may be contaminated with lead, or when lead exposure is linked to sources in the community, involving public health can facilitate broader actions to reduce and prevent exposures to other people at risk,” wrote report author Julian Gitelman, MD, MPH, a resident physician at the University of Toronto Dalla Lana School of Public Health, and colleagues.
Their case study was published in the Canadian Medical Association Journal.
The researchers detailed what happened after a 39-year-old woman sought medical care for abdominal pain, constipation, nausea, and vomiting. The woman underwent a series of tests, including colonoscopy, laparoscopy, and biopsies of bone marrow and ovarian cysts.
Only later did clinicians home in on the cause of her ailments: the Ayurvedic medications that the patient had been taking daily for more than a year for infertility. Her daily regimen had varied, ranging from a few pills to a dozen pills.
Heavy metals are sometimes intentionally added to Ayurvedic supplements for perceived healing properties, wrote the authors. They cited a previous study of a sample of Ayurvedic pills bought on the Internet from manufacturers based in the United States and India that showed that 21% contained lead, mercury, or arsenic.
Regulators in many countries struggle to help consumers understand the risks of natural health supplements, and the challenge extends well beyond Ayurvedic products.
There has been a “huge and very troubling increase” in U.S. poison control calls associated with gummy-bear products containing melatonin, said Canadian Senator Stan Kutcher, MD, at a May 11 meeting of Canada’s Standing Senate Committee on Social Affairs, Science, and Technology.
In April, JAMA published a U.S. analysis of melatonin gummy products, Dr. Kutcher noted. In this research letter, investigators reported that one product did not contain detectable levels of melatonin but did contain 31.3 mg of cannabidiol.
In other products, the quantity of melatonin ranged from 74% to 347% of the labeled quantity. A previous Canadian study of 16 melatonin brands found that the actual dose of melatonin ranged from 17% to 478% of the declared quantity, the letter noted.
The May 11 Senate meeting provided a forum for many of the recurring debates about supplements, which also are known as natural health products.
Barry Power, PharmD, editor in chief for the Canadian Pharmacists Association, said that his group was disappointed when Canada excluded natural health products from Vanessa’s Law, which was passed in 2014. This law sought to improve the reporting of adverse reactions to drugs.
“We’re glad this is being revisited now,” Dr. Power told the Senate committee. “Although natural health products are often seen as low risk, we need to keep in mind that ‘low risk’ does not mean ‘no risk,’ and ‘natural’ does not mean ‘safe.’ ”
In contrast, Aaron Skelton, chief executive of the Canadian Health Food Association, spoke against this bid to expand the reach of Vanessa’s Law into natural health products. Canadian lawmakers attached provisions regarding increased oversight of natural health products to a budget package instead of considering them as part of a stand-alone bill.
“Our concern is that the powers that are being discussed have not been reviewed and debated,” Mr. Skelton told Dr. Kutcher. “The potential for overreach and unnecessary regulation is significant, and that deserves debate.”
“Profits should not trump Canadians’ health,” answered Dr. Kutcher, who earlier served as head of the psychiatry department at Dalhousie University in Halifax, N.S.
By June, Vanessa’s Law had been expanded with provisions that address natural health products, including the reporting of products that present a serious risk to consumers.
Educating consumers
Many consumers overestimate the level of government regulation of supplements, said Pieter A. Cohen, MD, leader of the Supplement Research Program at Cambridge Health Alliance in Massachusetts. Dr. Cohen was the lead author of the JAMA research letter about melatonin products.
Supplements often share shelves in pharmacies with medicines that are subject to more strict regulation, which causes confusion.
“It’s really hard to wrap your brain around [the fact] that a health product is being sold in pharmacies in the United States and it’s not being vetted by the FDA [U.S. Food and Drug Administration]”, Dr. Cohen said in an interview
The confusion extends across borders. Many consumers in other countries will assume that the FDA performed premarket screening of U.S.-made supplements, but that is not the case, he said.
People who want to take supplements should look for reputable sources of information about them, such as the website of the National Institutes of Health’s Office of Dietary Supplements, Dr. Cohen said. But patients often forget or fail to do this, which can create medical puzzles, such as the case of the woman in the Ontario case study, said Peter Lurie, MD, MPH, executive director of the nonprofit Center for Science in the Public Interest, which has pressed for increased regulation of supplements.
Clinicians need to keep in mind that patients may need prodding to reveal what supplements they are taking, he said.
“They just think of them as different, somehow not the province of the doctor,” Dr. Lurie said. “For others, they are concerned that the doctors will disapprove. So, they hide it.”
A version of this article first appeared on Medscape.com.
Point-of-care ultrasound (POCUS) is integral to the delivery of high-quality patient care. The benefits of POCUS for timely diagnosis and procedural assistance are well documented. With continued innovation, its novel benefits can extend to the upper airway evaluation in both inpatient and outpatient settings.
Adi et al notes that POCUS can serve as an adjunct to traditional airway checklists and help intensivists/anesthesiologists identify potentially difficult laryngoscopies, choose the correct endotracheal tube size to reduce the risk of subglottic stenosis, and help confirm appropriate endotracheal tube placement (Adi, et al. J Emerg Crit Care Med. 2019;3:31).
The prediction of a difficult airway is a potentially lifesaving use for this technology. The authors note that smaller studies demonstrate promising results in four techniques: the inability to visualize the hyoid bone using the sublingual approach, a shorter hyomental distance in morbidly obese patients, anterior neck thickness at different anatomical levels (vocal cords, hyoid bone, and thyroid membrane), and a tongue thickness of more than 6.1 cm from the submental approach were all capable of predicting difficult tracheal intubation with varying degrees of sensitivity and specificity.
In the outpatient setting, an understanding of the upper airway anatomy can help with sleep apnea screenings. Korotun, et al. demonstrated in a small sample that ultrasound evaluation of hyoid bone excursion during hypoglossal nerve stimulation may be a useful tool to predict response to therapy and guide hypoglossal nerve stimulator settings (Korotun, et al. Sleep. 2020;43[Suppl_1]:A247-A248).Upper airway ultrasound is easy to learn. The anatomical landmarks are similar in most patients. This convenient tool can be added to your patient care repertoire in a variety of clinical settings.
Point-of-care ultrasound (POCUS) is integral to the delivery of high-quality patient care. The benefits of POCUS for timely diagnosis and procedural assistance are well documented. With continued innovation, its novel benefits can extend to the upper airway evaluation in both inpatient and outpatient settings.
Adi et al notes that POCUS can serve as an adjunct to traditional airway checklists and help intensivists/anesthesiologists identify potentially difficult laryngoscopies, choose the correct endotracheal tube size to reduce the risk of subglottic stenosis, and help confirm appropriate endotracheal tube placement (Adi, et al. J Emerg Crit Care Med. 2019;3:31).
The prediction of a difficult airway is a potentially lifesaving use for this technology. The authors note that smaller studies demonstrate promising results in four techniques: the inability to visualize the hyoid bone using the sublingual approach, a shorter hyomental distance in morbidly obese patients, anterior neck thickness at different anatomical levels (vocal cords, hyoid bone, and thyroid membrane), and a tongue thickness of more than 6.1 cm from the submental approach were all capable of predicting difficult tracheal intubation with varying degrees of sensitivity and specificity.
In the outpatient setting, an understanding of the upper airway anatomy can help with sleep apnea screenings. Korotun, et al. demonstrated in a small sample that ultrasound evaluation of hyoid bone excursion during hypoglossal nerve stimulation may be a useful tool to predict response to therapy and guide hypoglossal nerve stimulator settings (Korotun, et al. Sleep. 2020;43[Suppl_1]:A247-A248).Upper airway ultrasound is easy to learn. The anatomical landmarks are similar in most patients. This convenient tool can be added to your patient care repertoire in a variety of clinical settings.
Sameer Khanijo, MD, FCCP Section Member-at-Large
Navitha Ramesh, MD, FCCP Section Vice-Chair
Thoracic Oncology & Chest Procedures Network
Ultrasound & Chest Imaging Section
Point-of-care ultrasound (POCUS) is integral to the delivery of high-quality patient care. The benefits of POCUS for timely diagnosis and procedural assistance are well documented. With continued innovation, its novel benefits can extend to the upper airway evaluation in both inpatient and outpatient settings.
Adi et al notes that POCUS can serve as an adjunct to traditional airway checklists and help intensivists/anesthesiologists identify potentially difficult laryngoscopies, choose the correct endotracheal tube size to reduce the risk of subglottic stenosis, and help confirm appropriate endotracheal tube placement (Adi, et al. J Emerg Crit Care Med. 2019;3:31).
The prediction of a difficult airway is a potentially lifesaving use for this technology. The authors note that smaller studies demonstrate promising results in four techniques: the inability to visualize the hyoid bone using the sublingual approach, a shorter hyomental distance in morbidly obese patients, anterior neck thickness at different anatomical levels (vocal cords, hyoid bone, and thyroid membrane), and a tongue thickness of more than 6.1 cm from the submental approach were all capable of predicting difficult tracheal intubation with varying degrees of sensitivity and specificity.
In the outpatient setting, an understanding of the upper airway anatomy can help with sleep apnea screenings. Korotun, et al. demonstrated in a small sample that ultrasound evaluation of hyoid bone excursion during hypoglossal nerve stimulation may be a useful tool to predict response to therapy and guide hypoglossal nerve stimulator settings (Korotun, et al. Sleep. 2020;43[Suppl_1]:A247-A248).Upper airway ultrasound is easy to learn. The anatomical landmarks are similar in most patients. This convenient tool can be added to your patient care repertoire in a variety of clinical settings.
I’m going to talk about something important to a lot of us, based on a new study that has just come out that promises to tell us the right way to exercise. This is a major issue as we think about the best ways to stay healthy.
There are basically two main types of exercise that exercise physiologists think about. There are aerobic exercises: the cardiovascular things like running on a treadmill or outside. Then there are muscle-strengthening exercises: lifting weights, calisthenics, and so on. And of course, plenty of exercises do both at the same time.
It seems that the era of aerobic exercise as the main way to improve health was the 1980s and early 1990s. Then we started to increasingly recognize that muscle-strengthening exercise was really important too. We’ve got a ton of data on the benefits of cardiovascular and aerobic exercise (a reduced risk for cardiovascular disease, cancer, and all-cause mortality, and even improved cognitive function) across a variety of study designs, including cohort studies, but also some randomized controlled trials where people were randomized to aerobic activity.
We’re starting to get more data on the benefits of muscle-strengthening exercises, although it hasn’t been in the zeitgeist as much. Obviously, this increases strength and may reduce visceral fat, increase anaerobic capacity and muscle mass, and therefore [increase the] basal metabolic rate. What is really interesting about muscle strengthening is that muscle just takes up more energy at rest, so building bigger muscles increases your basal energy expenditure and increases insulin sensitivity because muscle is a good insulin sensitizer.
So, do you do both? Do you do one? Do you do the other? What’s the right answer here?
it depends on who you ask. The Center for Disease Control and Prevention’s recommendation, which changes from time to time, is that you should do at least 150 minutes a week of moderate-intensity aerobic activity. Anything that gets your heart beating faster counts here. So that’s 30 minutes, 5 days a week. They also say you can do 75 minutes a week of vigorous-intensity aerobic activity – something that really gets your heart rate up and you are breaking a sweat. Now they also recommend at least 2 days a week of a muscle-strengthening activity that makes your muscles work harder than usual, whether that’s push-ups or lifting weights or something like that.
The World Health Organization is similar. They don’t target 150 minutes a week. They actually say at least 150 and up to 300 minutes of moderate-intensity physical activity or 75-150 minutes of vigorous intensity aerobic physical activity. They are setting the floor, whereas the CDC sets its target and then they go a bit higher. They also recommend 2 days of muscle strengthening per week for optimal health.
But what do the data show? Why am I talking about this? It’s because of this new study in JAMA Internal Medicine by Ruben Lopez Bueno and colleagues. I’m going to focus on all-cause mortality for brevity, but the results are broadly similar.
The data source is the U.S. National Health Interview Survey. A total of 500,705 people took part in the survey and answered a slew of questions (including self-reports on their exercise amounts), with a median follow-up of about 10 years looking for things like cardiovascular deaths, cancer deaths, and so on.
The survey classified people into different exercise categories – how much time they spent doing moderate physical activity (MPA), vigorous physical activity (VPA), or muscle-strengthening activity (MSA).
Dr. Wilson
There are six categories based on duration of MPA (the WHO targets are highlighted in green), four categories based on length of time of VPA, and two categories of MSA (≥ or < two times per week). This gives a total of 48 possible combinations of exercise you could do in a typical week.
JAMA Internal Medicine
Here are the percentages of people who fell into each of these 48 potential categories. The largest is the 35% of people who fell into the “nothing” category (no MPA, no VPA, and less than two sessions per week of MSA). These “nothing” people are going to be a reference category moving forward.
JAMA Internal Medicine
So who are these people? On the far left are the 361,000 people (the vast majority) who don’t hit that 150 minutes a week of MPA or 75 minutes a week of VPA, and they don’t do 2 days a week of MSA. The other three categories are increasing amounts of exercise. Younger people seem to be doing more exercise at the higher ends, and men are more likely to be doing exercise at the higher end. There are also some interesting findings from the alcohol drinking survey. The people who do more exercise are more likely to be current drinkers. This is interesting. I confirmed these data with the investigator. This might suggest one of the reasons why some studies have shown that drinkers have better outcomes in terms of either cardiovascular or cognitive outcomes over time. There’s a lot of conflicting data there, but in part, it might be that healthier people might drink more alcohol. It could be a socioeconomic phenomenon as well.
Now, what blew my mind were these smoker numbers, but don’t get too excited about it. What it looks like from the table in JAMA Internal Medicine is that 20% of the people who don’t do much exercise smoke, and then something like 60% of the people who do more exercise smoke. That can’t be right. So I checked with the lead study author. There is a mistake in these columns for smoking. They were supposed to flip the “never smoker” and “current smoker” numbers. You can actually see that just 15.2% of those who exercise a lot are current smokers, not 63.8%. This has been fixed online, but just in case you saw this and you were as confused as I was that these incredibly healthy smokers are out there exercising all the time, it was just a typo.
Dr. Wilson
There is bias here. One of the big ones is called reverse causation bias. This is what might happen if, let’s say you’re already sick, you have cancer, you have some serious cardiovascular disease, or heart failure. You can’t exercise that much. You physically can’t do it. And then if you die, we wouldn’t find that exercise is beneficial. We would see that sicker people aren’t as able to exercise. The investigators got around this a bit by excluding mortality events within 2 years of the initial survey. Anyone who died within 2 years after saying how often they exercised was not included in this analysis.
This is known as the healthy exerciser or healthy user effect. Sometimes this means that people who exercise a lot probably do other healthy things; they might eat better or get out in the sun more. Researchers try to get around this through multivariable adjustment. They adjust for age, sex, race, marital status, etc. No adjustment is perfect. There’s always residual confounding. But this is probably the best you can do with the dataset like the one they had access to.
JAMA Internal Medicine
Let’s go to the results, which are nicely heat-mapped in the paper. They’re divided into people who have less or more than 2 days of MSA. Our reference groups that we want to pay attention to are the people who don’t do anything. The highest mortality of 9.8 individuals per 1,000 person-years is seen in the group that reported no moderate physical activity, no VPA, and less than 2 days a week of MSA.
As you move up and to the right (more VPA and MPA), you see lower numbers. The lowest number was 4.9 among people who reported more than 150 minutes per week of VPA and 2 days of MSA.
Looking at these data, the benefit, or the bang for your buck is higher for VPA than for MPA. Getting 2 days of MSA does have a tendency to reduce overall mortality. This is not necessarily causal, but it is rather potent and consistent across all the different groups.
So, what are we supposed to do here? I think the most clear finding from the study is that anything is better than nothing. This study suggests that if you are going to get activity, push on the vigorous activity if you’re physically able to do it. And of course, layering in the MSA as well seems to be associated with benefit.
Like everything in life, there’s no one simple solution. It’s a mix. But telling ourselves and our patients to get out there if you can and break a sweat as often as you can during the week, and take a couple of days to get those muscles a little bigger, may increase insulin sensitivity and basal metabolic rate – is it guaranteed to extend life? No. This is an observational study. We can’t say; we don’t have causal data here, but it’s unlikely to cause much harm. I’m particularly happy that people are doing a much better job now of really dissecting out the kinds of physical activity that are beneficial. It turns out that all of it is, and probably a mixture is best.
Dr. Wilson is associate professor, department of medicine, and interim director, program of applied translational research, Yale University, New Haven, Conn. He disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
I’m going to talk about something important to a lot of us, based on a new study that has just come out that promises to tell us the right way to exercise. This is a major issue as we think about the best ways to stay healthy.
There are basically two main types of exercise that exercise physiologists think about. There are aerobic exercises: the cardiovascular things like running on a treadmill or outside. Then there are muscle-strengthening exercises: lifting weights, calisthenics, and so on. And of course, plenty of exercises do both at the same time.
It seems that the era of aerobic exercise as the main way to improve health was the 1980s and early 1990s. Then we started to increasingly recognize that muscle-strengthening exercise was really important too. We’ve got a ton of data on the benefits of cardiovascular and aerobic exercise (a reduced risk for cardiovascular disease, cancer, and all-cause mortality, and even improved cognitive function) across a variety of study designs, including cohort studies, but also some randomized controlled trials where people were randomized to aerobic activity.
We’re starting to get more data on the benefits of muscle-strengthening exercises, although it hasn’t been in the zeitgeist as much. Obviously, this increases strength and may reduce visceral fat, increase anaerobic capacity and muscle mass, and therefore [increase the] basal metabolic rate. What is really interesting about muscle strengthening is that muscle just takes up more energy at rest, so building bigger muscles increases your basal energy expenditure and increases insulin sensitivity because muscle is a good insulin sensitizer.
So, do you do both? Do you do one? Do you do the other? What’s the right answer here?
it depends on who you ask. The Center for Disease Control and Prevention’s recommendation, which changes from time to time, is that you should do at least 150 minutes a week of moderate-intensity aerobic activity. Anything that gets your heart beating faster counts here. So that’s 30 minutes, 5 days a week. They also say you can do 75 minutes a week of vigorous-intensity aerobic activity – something that really gets your heart rate up and you are breaking a sweat. Now they also recommend at least 2 days a week of a muscle-strengthening activity that makes your muscles work harder than usual, whether that’s push-ups or lifting weights or something like that.
The World Health Organization is similar. They don’t target 150 minutes a week. They actually say at least 150 and up to 300 minutes of moderate-intensity physical activity or 75-150 minutes of vigorous intensity aerobic physical activity. They are setting the floor, whereas the CDC sets its target and then they go a bit higher. They also recommend 2 days of muscle strengthening per week for optimal health.
But what do the data show? Why am I talking about this? It’s because of this new study in JAMA Internal Medicine by Ruben Lopez Bueno and colleagues. I’m going to focus on all-cause mortality for brevity, but the results are broadly similar.
The data source is the U.S. National Health Interview Survey. A total of 500,705 people took part in the survey and answered a slew of questions (including self-reports on their exercise amounts), with a median follow-up of about 10 years looking for things like cardiovascular deaths, cancer deaths, and so on.
The survey classified people into different exercise categories – how much time they spent doing moderate physical activity (MPA), vigorous physical activity (VPA), or muscle-strengthening activity (MSA).
Dr. Wilson
There are six categories based on duration of MPA (the WHO targets are highlighted in green), four categories based on length of time of VPA, and two categories of MSA (≥ or < two times per week). This gives a total of 48 possible combinations of exercise you could do in a typical week.
JAMA Internal Medicine
Here are the percentages of people who fell into each of these 48 potential categories. The largest is the 35% of people who fell into the “nothing” category (no MPA, no VPA, and less than two sessions per week of MSA). These “nothing” people are going to be a reference category moving forward.
JAMA Internal Medicine
So who are these people? On the far left are the 361,000 people (the vast majority) who don’t hit that 150 minutes a week of MPA or 75 minutes a week of VPA, and they don’t do 2 days a week of MSA. The other three categories are increasing amounts of exercise. Younger people seem to be doing more exercise at the higher ends, and men are more likely to be doing exercise at the higher end. There are also some interesting findings from the alcohol drinking survey. The people who do more exercise are more likely to be current drinkers. This is interesting. I confirmed these data with the investigator. This might suggest one of the reasons why some studies have shown that drinkers have better outcomes in terms of either cardiovascular or cognitive outcomes over time. There’s a lot of conflicting data there, but in part, it might be that healthier people might drink more alcohol. It could be a socioeconomic phenomenon as well.
Now, what blew my mind were these smoker numbers, but don’t get too excited about it. What it looks like from the table in JAMA Internal Medicine is that 20% of the people who don’t do much exercise smoke, and then something like 60% of the people who do more exercise smoke. That can’t be right. So I checked with the lead study author. There is a mistake in these columns for smoking. They were supposed to flip the “never smoker” and “current smoker” numbers. You can actually see that just 15.2% of those who exercise a lot are current smokers, not 63.8%. This has been fixed online, but just in case you saw this and you were as confused as I was that these incredibly healthy smokers are out there exercising all the time, it was just a typo.
Dr. Wilson
There is bias here. One of the big ones is called reverse causation bias. This is what might happen if, let’s say you’re already sick, you have cancer, you have some serious cardiovascular disease, or heart failure. You can’t exercise that much. You physically can’t do it. And then if you die, we wouldn’t find that exercise is beneficial. We would see that sicker people aren’t as able to exercise. The investigators got around this a bit by excluding mortality events within 2 years of the initial survey. Anyone who died within 2 years after saying how often they exercised was not included in this analysis.
This is known as the healthy exerciser or healthy user effect. Sometimes this means that people who exercise a lot probably do other healthy things; they might eat better or get out in the sun more. Researchers try to get around this through multivariable adjustment. They adjust for age, sex, race, marital status, etc. No adjustment is perfect. There’s always residual confounding. But this is probably the best you can do with the dataset like the one they had access to.
JAMA Internal Medicine
Let’s go to the results, which are nicely heat-mapped in the paper. They’re divided into people who have less or more than 2 days of MSA. Our reference groups that we want to pay attention to are the people who don’t do anything. The highest mortality of 9.8 individuals per 1,000 person-years is seen in the group that reported no moderate physical activity, no VPA, and less than 2 days a week of MSA.
As you move up and to the right (more VPA and MPA), you see lower numbers. The lowest number was 4.9 among people who reported more than 150 minutes per week of VPA and 2 days of MSA.
Looking at these data, the benefit, or the bang for your buck is higher for VPA than for MPA. Getting 2 days of MSA does have a tendency to reduce overall mortality. This is not necessarily causal, but it is rather potent and consistent across all the different groups.
So, what are we supposed to do here? I think the most clear finding from the study is that anything is better than nothing. This study suggests that if you are going to get activity, push on the vigorous activity if you’re physically able to do it. And of course, layering in the MSA as well seems to be associated with benefit.
Like everything in life, there’s no one simple solution. It’s a mix. But telling ourselves and our patients to get out there if you can and break a sweat as often as you can during the week, and take a couple of days to get those muscles a little bigger, may increase insulin sensitivity and basal metabolic rate – is it guaranteed to extend life? No. This is an observational study. We can’t say; we don’t have causal data here, but it’s unlikely to cause much harm. I’m particularly happy that people are doing a much better job now of really dissecting out the kinds of physical activity that are beneficial. It turns out that all of it is, and probably a mixture is best.
Dr. Wilson is associate professor, department of medicine, and interim director, program of applied translational research, Yale University, New Haven, Conn. He disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I’m going to talk about something important to a lot of us, based on a new study that has just come out that promises to tell us the right way to exercise. This is a major issue as we think about the best ways to stay healthy.
There are basically two main types of exercise that exercise physiologists think about. There are aerobic exercises: the cardiovascular things like running on a treadmill or outside. Then there are muscle-strengthening exercises: lifting weights, calisthenics, and so on. And of course, plenty of exercises do both at the same time.
It seems that the era of aerobic exercise as the main way to improve health was the 1980s and early 1990s. Then we started to increasingly recognize that muscle-strengthening exercise was really important too. We’ve got a ton of data on the benefits of cardiovascular and aerobic exercise (a reduced risk for cardiovascular disease, cancer, and all-cause mortality, and even improved cognitive function) across a variety of study designs, including cohort studies, but also some randomized controlled trials where people were randomized to aerobic activity.
We’re starting to get more data on the benefits of muscle-strengthening exercises, although it hasn’t been in the zeitgeist as much. Obviously, this increases strength and may reduce visceral fat, increase anaerobic capacity and muscle mass, and therefore [increase the] basal metabolic rate. What is really interesting about muscle strengthening is that muscle just takes up more energy at rest, so building bigger muscles increases your basal energy expenditure and increases insulin sensitivity because muscle is a good insulin sensitizer.
So, do you do both? Do you do one? Do you do the other? What’s the right answer here?
it depends on who you ask. The Center for Disease Control and Prevention’s recommendation, which changes from time to time, is that you should do at least 150 minutes a week of moderate-intensity aerobic activity. Anything that gets your heart beating faster counts here. So that’s 30 minutes, 5 days a week. They also say you can do 75 minutes a week of vigorous-intensity aerobic activity – something that really gets your heart rate up and you are breaking a sweat. Now they also recommend at least 2 days a week of a muscle-strengthening activity that makes your muscles work harder than usual, whether that’s push-ups or lifting weights or something like that.
The World Health Organization is similar. They don’t target 150 minutes a week. They actually say at least 150 and up to 300 minutes of moderate-intensity physical activity or 75-150 minutes of vigorous intensity aerobic physical activity. They are setting the floor, whereas the CDC sets its target and then they go a bit higher. They also recommend 2 days of muscle strengthening per week for optimal health.
But what do the data show? Why am I talking about this? It’s because of this new study in JAMA Internal Medicine by Ruben Lopez Bueno and colleagues. I’m going to focus on all-cause mortality for brevity, but the results are broadly similar.
The data source is the U.S. National Health Interview Survey. A total of 500,705 people took part in the survey and answered a slew of questions (including self-reports on their exercise amounts), with a median follow-up of about 10 years looking for things like cardiovascular deaths, cancer deaths, and so on.
The survey classified people into different exercise categories – how much time they spent doing moderate physical activity (MPA), vigorous physical activity (VPA), or muscle-strengthening activity (MSA).
Dr. Wilson
There are six categories based on duration of MPA (the WHO targets are highlighted in green), four categories based on length of time of VPA, and two categories of MSA (≥ or < two times per week). This gives a total of 48 possible combinations of exercise you could do in a typical week.
JAMA Internal Medicine
Here are the percentages of people who fell into each of these 48 potential categories. The largest is the 35% of people who fell into the “nothing” category (no MPA, no VPA, and less than two sessions per week of MSA). These “nothing” people are going to be a reference category moving forward.
JAMA Internal Medicine
So who are these people? On the far left are the 361,000 people (the vast majority) who don’t hit that 150 minutes a week of MPA or 75 minutes a week of VPA, and they don’t do 2 days a week of MSA. The other three categories are increasing amounts of exercise. Younger people seem to be doing more exercise at the higher ends, and men are more likely to be doing exercise at the higher end. There are also some interesting findings from the alcohol drinking survey. The people who do more exercise are more likely to be current drinkers. This is interesting. I confirmed these data with the investigator. This might suggest one of the reasons why some studies have shown that drinkers have better outcomes in terms of either cardiovascular or cognitive outcomes over time. There’s a lot of conflicting data there, but in part, it might be that healthier people might drink more alcohol. It could be a socioeconomic phenomenon as well.
Now, what blew my mind were these smoker numbers, but don’t get too excited about it. What it looks like from the table in JAMA Internal Medicine is that 20% of the people who don’t do much exercise smoke, and then something like 60% of the people who do more exercise smoke. That can’t be right. So I checked with the lead study author. There is a mistake in these columns for smoking. They were supposed to flip the “never smoker” and “current smoker” numbers. You can actually see that just 15.2% of those who exercise a lot are current smokers, not 63.8%. This has been fixed online, but just in case you saw this and you were as confused as I was that these incredibly healthy smokers are out there exercising all the time, it was just a typo.
Dr. Wilson
There is bias here. One of the big ones is called reverse causation bias. This is what might happen if, let’s say you’re already sick, you have cancer, you have some serious cardiovascular disease, or heart failure. You can’t exercise that much. You physically can’t do it. And then if you die, we wouldn’t find that exercise is beneficial. We would see that sicker people aren’t as able to exercise. The investigators got around this a bit by excluding mortality events within 2 years of the initial survey. Anyone who died within 2 years after saying how often they exercised was not included in this analysis.
This is known as the healthy exerciser or healthy user effect. Sometimes this means that people who exercise a lot probably do other healthy things; they might eat better or get out in the sun more. Researchers try to get around this through multivariable adjustment. They adjust for age, sex, race, marital status, etc. No adjustment is perfect. There’s always residual confounding. But this is probably the best you can do with the dataset like the one they had access to.
JAMA Internal Medicine
Let’s go to the results, which are nicely heat-mapped in the paper. They’re divided into people who have less or more than 2 days of MSA. Our reference groups that we want to pay attention to are the people who don’t do anything. The highest mortality of 9.8 individuals per 1,000 person-years is seen in the group that reported no moderate physical activity, no VPA, and less than 2 days a week of MSA.
As you move up and to the right (more VPA and MPA), you see lower numbers. The lowest number was 4.9 among people who reported more than 150 minutes per week of VPA and 2 days of MSA.
Looking at these data, the benefit, or the bang for your buck is higher for VPA than for MPA. Getting 2 days of MSA does have a tendency to reduce overall mortality. This is not necessarily causal, but it is rather potent and consistent across all the different groups.
So, what are we supposed to do here? I think the most clear finding from the study is that anything is better than nothing. This study suggests that if you are going to get activity, push on the vigorous activity if you’re physically able to do it. And of course, layering in the MSA as well seems to be associated with benefit.
Like everything in life, there’s no one simple solution. It’s a mix. But telling ourselves and our patients to get out there if you can and break a sweat as often as you can during the week, and take a couple of days to get those muscles a little bigger, may increase insulin sensitivity and basal metabolic rate – is it guaranteed to extend life? No. This is an observational study. We can’t say; we don’t have causal data here, but it’s unlikely to cause much harm. I’m particularly happy that people are doing a much better job now of really dissecting out the kinds of physical activity that are beneficial. It turns out that all of it is, and probably a mixture is best.
Dr. Wilson is associate professor, department of medicine, and interim director, program of applied translational research, Yale University, New Haven, Conn. He disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Zolpidem (Ambien) is a well-known sedative for sleep. Letairis (Ambrisentan) is a vasodilator for the treatment of pulmonary arterial hypertension. Citalopram (Celexa) is an antidepressant; escitalopram (Lexapro) is prescribed for anxiety and depression.
Those are just 4 of the more than 80 pairs of drug names that the Institute for Safe Medication Practices recently added to its list of confusing drug names. The aim is to increase awareness about the potential for a serious medication mistake when the wrong drug is given because of drug names that look and sound similar.
Awareness of these drug names, however, is just the first step in preventing medication mistakes. Health care providers should take a number of other steps as well, experts said.
ISMP launched its confusing drug names list, previously called look-alike, sound-alike (LASA) drugs, in 2008. The new list is an update of the 2019 version, said Michael J. Gaunt, PharmD, senior manager of error reporting programs for the ISMP, which focuses on the prevention of medication mistakes. The new entries were chosen on the basis of a number of factors, including ISMP’s analysis of recent medication mishap reports that were submitted to it.
The ISMP list now includes about 528 drug pairs, Dr. Gaunt said. The list is long, he said, partly because each pair is listed twice, so readers can cross reference. For instance, hydralazine and hydroxyzine are listed in one entry in the list, and hydroxyzine and hydralazine are listed in another.
Brand Institute in Miami has named, among other drugs, Entresto, Rybelsus, and Lunesta. The regulatory arm of the company, the Drug Safety Institute, “considers drug names that have been confused as an important part of our comprehensive drug name assessments,” Todd Bridges, global president of the institute, said in an emailed statement. Information on the confusing drug names are incorporated into the company’s proprietary algorithm and is used when developing brand names for drugs. “We continually update this algorithm as new drug names that are often confused are identified,” Mr. Bridges said.
Confusing drug names: Ongoing issue
The length of the list, as well as the latest additions, are not surprising, said Mary Ann Kliethermes, PharmD, director of medication safety and quality for the American Society of Health-System Pharmacists, a membership organization of about 60,000 pharmacists who practice in inpatient and outpatient settings.
“I’ve been in practice over 45 years,” she said, “and this has been a problem ever since I have been in practice.” The sheer volume of new drugs is one reason, she said. From 2013 through 2022, the U.S. Food and Drug Administration approved an average of 43 novel drugs per year, according to a report from its Center for Drug Evaluation and Research. “Since the 90s, this [confusion about similar drug names] has happened,” Dr. Kliethermes said.
According to a 2023 report, about 7,000-9,000 people die each year in the United States as the result of a medication error. However, it’s impossible to say for sure what percentage of those errors involve name confusion, Dr. Gaunt said.
Not all the mistakes are reported. Some that are reported are dramatic and deadly. In 2022, a Tennessee nurse was convicted of gross neglect and negligent homicide. She was sentenced to 3 years’ probation after she mistakenly gave vercuronium, an anesthetic agent, instead of the sedative Versed to a patient, and the woman died.
Updated list: A closer look
Many of the new drug pairs that are listed in the update are cephalosporins, said Dr. Kliethermes, who reviewed the new list for this news organization. In all, 20 of the latest 82 additions are cephalosporins. These include drugs such as cefazolin, which can be confused with cefotetan, and vice versa. These drugs have been around since the 1980s, she said, but “they needed to be on there.” Even in the 1980s, it was becoming difficult to differentiate them, and there were fewer drugs in that class then, she said.
Influenza vaccines made the new list, too. Fluzone High-Dose Quadrivalent can be confused with fluzone quadrivalent. Other new additions: hydrochlorothiazide and hydroxychloroquine, Lasik and Wakix, Pitressin and Pitocin, Remeron and Rozerem.
Beyond the list
While it’s not possible to pinpoint how big a problem name confusion is in causing medication mistakes, “it is certainly still an issue,” Dr. Gaunt said. A variety of practices can reduce that risk substantially, Dr. Gaunt and Dr. Kliethermes agreed.
Tall-man lettering. Both the FDA and the ISMP recommend the use of so-called tall-man lettering (TML), which involves the use of uppercase letters, sometimes in boldface, to distinguish similar names on product labels and elsewhere. Examples include vinBLAStine and vinCRIStine.
Electronic prescribing. “It eliminates the risk of handwriting confusion,” Dr. Gaunt said. However, electronic prescribing can have a downside, Dr. Kliethermes said. When ordering medication, a person may type in a few letters and may then be presented with a prompt that lists several drug names, and it can be easy to click the wrong one. For that reason, ISMP and other experts recommend typing at least five letters when searching for a medication in an electronic system.
Use both brand and generic names on labels and prescriptions.
Write the indication. That can serve as a double check. If a prescription for Ambien says “For sleep,” there’s probably less risk of filling a prescription for ambrisentan, the vasodilator.
Smart formulary additions. When hospitals add medications to their formularies, “part of that formulary assessment should include looking at the potential risk for errors,” Dr. Gaunt said. This involves keeping an eye out for confusing names and similar packaging. “Do that analysis up front and put in strategies to minimize that. Maybe you look for a different drug [for the same use] that has a different name.” Or choose a different manufacturer, so the medication would at least have a different container.
Use bar code scanning. Suppose a pharmacist goes to the shelf and pulls the wrong drug. “Bar code scanning provides the opportunity to catch the error,” Dr. Gaunt said. Many community pharmacies now have bar code scanning. ISMP just issued best practices for community pharmacies, Dr. Gaunt said, and these include the use of bar code scanning and other measures.
Educate consumers. Health care providers can educate consumers on how to minimize the risk of getting the wrong drug, Dr. Gaunt said. When patients are picking up a prescription, suggest they look at the container label; if it looks different from previous prescriptions of the same medicine, ask the pharmacist for an explanation. Some patients just pass it off, Dr. Gaunt said, figuring the pharmacist or health plan switched manufacturers of their medication.
Access the list. The entire list is on the ISMP site and is accessible after free registration.
Goal: Preventing confusion
The FDA has provided guidance for industry on naming drugs not yet approved so that the proposed names are not too similar in sound or appearance to those already on the market. Included in the lengthy document are checklists, such as, “Across a range of dialects, are the names consistently pronounced differently?” and “Are the lengths of the names dissimilar when scripted?” (Lengths are considered different if they differ by two or more letters.)
The FDA also offers the phonetic and orthographic computer analysis (POCA) program, a software tool that employs an advanced algorithm to evaluate similarities between two drug names. The data sources are updated regularly as new drugs are approved.
Liability update
The problem may be decreasing. In a 2020 report, researchers used pharmacists’ professional liability claim data from the Healthcare Providers Service Organization. They compared 2018 data on claims with 2013 data. The percentage of claims associated with wrong drug dispensing errors declined from 43.8% in 2013 to 36.8% in 2018. Wrong dose claims also declined, from 31.5% to 15.3%.
These researchers concluded that technology and automation have contributed to the prevention of medication errors caused by the use of the wrong drug and the wrong dose, but mistakes continue, owing to system and human errors.
A version of this article first appeared on Medscape.com.
Zolpidem (Ambien) is a well-known sedative for sleep. Letairis (Ambrisentan) is a vasodilator for the treatment of pulmonary arterial hypertension. Citalopram (Celexa) is an antidepressant; escitalopram (Lexapro) is prescribed for anxiety and depression.
Those are just 4 of the more than 80 pairs of drug names that the Institute for Safe Medication Practices recently added to its list of confusing drug names. The aim is to increase awareness about the potential for a serious medication mistake when the wrong drug is given because of drug names that look and sound similar.
Awareness of these drug names, however, is just the first step in preventing medication mistakes. Health care providers should take a number of other steps as well, experts said.
ISMP launched its confusing drug names list, previously called look-alike, sound-alike (LASA) drugs, in 2008. The new list is an update of the 2019 version, said Michael J. Gaunt, PharmD, senior manager of error reporting programs for the ISMP, which focuses on the prevention of medication mistakes. The new entries were chosen on the basis of a number of factors, including ISMP’s analysis of recent medication mishap reports that were submitted to it.
The ISMP list now includes about 528 drug pairs, Dr. Gaunt said. The list is long, he said, partly because each pair is listed twice, so readers can cross reference. For instance, hydralazine and hydroxyzine are listed in one entry in the list, and hydroxyzine and hydralazine are listed in another.
Brand Institute in Miami has named, among other drugs, Entresto, Rybelsus, and Lunesta. The regulatory arm of the company, the Drug Safety Institute, “considers drug names that have been confused as an important part of our comprehensive drug name assessments,” Todd Bridges, global president of the institute, said in an emailed statement. Information on the confusing drug names are incorporated into the company’s proprietary algorithm and is used when developing brand names for drugs. “We continually update this algorithm as new drug names that are often confused are identified,” Mr. Bridges said.
Confusing drug names: Ongoing issue
The length of the list, as well as the latest additions, are not surprising, said Mary Ann Kliethermes, PharmD, director of medication safety and quality for the American Society of Health-System Pharmacists, a membership organization of about 60,000 pharmacists who practice in inpatient and outpatient settings.
“I’ve been in practice over 45 years,” she said, “and this has been a problem ever since I have been in practice.” The sheer volume of new drugs is one reason, she said. From 2013 through 2022, the U.S. Food and Drug Administration approved an average of 43 novel drugs per year, according to a report from its Center for Drug Evaluation and Research. “Since the 90s, this [confusion about similar drug names] has happened,” Dr. Kliethermes said.
According to a 2023 report, about 7,000-9,000 people die each year in the United States as the result of a medication error. However, it’s impossible to say for sure what percentage of those errors involve name confusion, Dr. Gaunt said.
Not all the mistakes are reported. Some that are reported are dramatic and deadly. In 2022, a Tennessee nurse was convicted of gross neglect and negligent homicide. She was sentenced to 3 years’ probation after she mistakenly gave vercuronium, an anesthetic agent, instead of the sedative Versed to a patient, and the woman died.
Updated list: A closer look
Many of the new drug pairs that are listed in the update are cephalosporins, said Dr. Kliethermes, who reviewed the new list for this news organization. In all, 20 of the latest 82 additions are cephalosporins. These include drugs such as cefazolin, which can be confused with cefotetan, and vice versa. These drugs have been around since the 1980s, she said, but “they needed to be on there.” Even in the 1980s, it was becoming difficult to differentiate them, and there were fewer drugs in that class then, she said.
Influenza vaccines made the new list, too. Fluzone High-Dose Quadrivalent can be confused with fluzone quadrivalent. Other new additions: hydrochlorothiazide and hydroxychloroquine, Lasik and Wakix, Pitressin and Pitocin, Remeron and Rozerem.
Beyond the list
While it’s not possible to pinpoint how big a problem name confusion is in causing medication mistakes, “it is certainly still an issue,” Dr. Gaunt said. A variety of practices can reduce that risk substantially, Dr. Gaunt and Dr. Kliethermes agreed.
Tall-man lettering. Both the FDA and the ISMP recommend the use of so-called tall-man lettering (TML), which involves the use of uppercase letters, sometimes in boldface, to distinguish similar names on product labels and elsewhere. Examples include vinBLAStine and vinCRIStine.
Electronic prescribing. “It eliminates the risk of handwriting confusion,” Dr. Gaunt said. However, electronic prescribing can have a downside, Dr. Kliethermes said. When ordering medication, a person may type in a few letters and may then be presented with a prompt that lists several drug names, and it can be easy to click the wrong one. For that reason, ISMP and other experts recommend typing at least five letters when searching for a medication in an electronic system.
Use both brand and generic names on labels and prescriptions.
Write the indication. That can serve as a double check. If a prescription for Ambien says “For sleep,” there’s probably less risk of filling a prescription for ambrisentan, the vasodilator.
Smart formulary additions. When hospitals add medications to their formularies, “part of that formulary assessment should include looking at the potential risk for errors,” Dr. Gaunt said. This involves keeping an eye out for confusing names and similar packaging. “Do that analysis up front and put in strategies to minimize that. Maybe you look for a different drug [for the same use] that has a different name.” Or choose a different manufacturer, so the medication would at least have a different container.
Use bar code scanning. Suppose a pharmacist goes to the shelf and pulls the wrong drug. “Bar code scanning provides the opportunity to catch the error,” Dr. Gaunt said. Many community pharmacies now have bar code scanning. ISMP just issued best practices for community pharmacies, Dr. Gaunt said, and these include the use of bar code scanning and other measures.
Educate consumers. Health care providers can educate consumers on how to minimize the risk of getting the wrong drug, Dr. Gaunt said. When patients are picking up a prescription, suggest they look at the container label; if it looks different from previous prescriptions of the same medicine, ask the pharmacist for an explanation. Some patients just pass it off, Dr. Gaunt said, figuring the pharmacist or health plan switched manufacturers of their medication.
Access the list. The entire list is on the ISMP site and is accessible after free registration.
Goal: Preventing confusion
The FDA has provided guidance for industry on naming drugs not yet approved so that the proposed names are not too similar in sound or appearance to those already on the market. Included in the lengthy document are checklists, such as, “Across a range of dialects, are the names consistently pronounced differently?” and “Are the lengths of the names dissimilar when scripted?” (Lengths are considered different if they differ by two or more letters.)
The FDA also offers the phonetic and orthographic computer analysis (POCA) program, a software tool that employs an advanced algorithm to evaluate similarities between two drug names. The data sources are updated regularly as new drugs are approved.
Liability update
The problem may be decreasing. In a 2020 report, researchers used pharmacists’ professional liability claim data from the Healthcare Providers Service Organization. They compared 2018 data on claims with 2013 data. The percentage of claims associated with wrong drug dispensing errors declined from 43.8% in 2013 to 36.8% in 2018. Wrong dose claims also declined, from 31.5% to 15.3%.
These researchers concluded that technology and automation have contributed to the prevention of medication errors caused by the use of the wrong drug and the wrong dose, but mistakes continue, owing to system and human errors.
A version of this article first appeared on Medscape.com.
Zolpidem (Ambien) is a well-known sedative for sleep. Letairis (Ambrisentan) is a vasodilator for the treatment of pulmonary arterial hypertension. Citalopram (Celexa) is an antidepressant; escitalopram (Lexapro) is prescribed for anxiety and depression.
Those are just 4 of the more than 80 pairs of drug names that the Institute for Safe Medication Practices recently added to its list of confusing drug names. The aim is to increase awareness about the potential for a serious medication mistake when the wrong drug is given because of drug names that look and sound similar.
Awareness of these drug names, however, is just the first step in preventing medication mistakes. Health care providers should take a number of other steps as well, experts said.
ISMP launched its confusing drug names list, previously called look-alike, sound-alike (LASA) drugs, in 2008. The new list is an update of the 2019 version, said Michael J. Gaunt, PharmD, senior manager of error reporting programs for the ISMP, which focuses on the prevention of medication mistakes. The new entries were chosen on the basis of a number of factors, including ISMP’s analysis of recent medication mishap reports that were submitted to it.
The ISMP list now includes about 528 drug pairs, Dr. Gaunt said. The list is long, he said, partly because each pair is listed twice, so readers can cross reference. For instance, hydralazine and hydroxyzine are listed in one entry in the list, and hydroxyzine and hydralazine are listed in another.
Brand Institute in Miami has named, among other drugs, Entresto, Rybelsus, and Lunesta. The regulatory arm of the company, the Drug Safety Institute, “considers drug names that have been confused as an important part of our comprehensive drug name assessments,” Todd Bridges, global president of the institute, said in an emailed statement. Information on the confusing drug names are incorporated into the company’s proprietary algorithm and is used when developing brand names for drugs. “We continually update this algorithm as new drug names that are often confused are identified,” Mr. Bridges said.
Confusing drug names: Ongoing issue
The length of the list, as well as the latest additions, are not surprising, said Mary Ann Kliethermes, PharmD, director of medication safety and quality for the American Society of Health-System Pharmacists, a membership organization of about 60,000 pharmacists who practice in inpatient and outpatient settings.
“I’ve been in practice over 45 years,” she said, “and this has been a problem ever since I have been in practice.” The sheer volume of new drugs is one reason, she said. From 2013 through 2022, the U.S. Food and Drug Administration approved an average of 43 novel drugs per year, according to a report from its Center for Drug Evaluation and Research. “Since the 90s, this [confusion about similar drug names] has happened,” Dr. Kliethermes said.
According to a 2023 report, about 7,000-9,000 people die each year in the United States as the result of a medication error. However, it’s impossible to say for sure what percentage of those errors involve name confusion, Dr. Gaunt said.
Not all the mistakes are reported. Some that are reported are dramatic and deadly. In 2022, a Tennessee nurse was convicted of gross neglect and negligent homicide. She was sentenced to 3 years’ probation after she mistakenly gave vercuronium, an anesthetic agent, instead of the sedative Versed to a patient, and the woman died.
Updated list: A closer look
Many of the new drug pairs that are listed in the update are cephalosporins, said Dr. Kliethermes, who reviewed the new list for this news organization. In all, 20 of the latest 82 additions are cephalosporins. These include drugs such as cefazolin, which can be confused with cefotetan, and vice versa. These drugs have been around since the 1980s, she said, but “they needed to be on there.” Even in the 1980s, it was becoming difficult to differentiate them, and there were fewer drugs in that class then, she said.
Influenza vaccines made the new list, too. Fluzone High-Dose Quadrivalent can be confused with fluzone quadrivalent. Other new additions: hydrochlorothiazide and hydroxychloroquine, Lasik and Wakix, Pitressin and Pitocin, Remeron and Rozerem.
Beyond the list
While it’s not possible to pinpoint how big a problem name confusion is in causing medication mistakes, “it is certainly still an issue,” Dr. Gaunt said. A variety of practices can reduce that risk substantially, Dr. Gaunt and Dr. Kliethermes agreed.
Tall-man lettering. Both the FDA and the ISMP recommend the use of so-called tall-man lettering (TML), which involves the use of uppercase letters, sometimes in boldface, to distinguish similar names on product labels and elsewhere. Examples include vinBLAStine and vinCRIStine.
Electronic prescribing. “It eliminates the risk of handwriting confusion,” Dr. Gaunt said. However, electronic prescribing can have a downside, Dr. Kliethermes said. When ordering medication, a person may type in a few letters and may then be presented with a prompt that lists several drug names, and it can be easy to click the wrong one. For that reason, ISMP and other experts recommend typing at least five letters when searching for a medication in an electronic system.
Use both brand and generic names on labels and prescriptions.
Write the indication. That can serve as a double check. If a prescription for Ambien says “For sleep,” there’s probably less risk of filling a prescription for ambrisentan, the vasodilator.
Smart formulary additions. When hospitals add medications to their formularies, “part of that formulary assessment should include looking at the potential risk for errors,” Dr. Gaunt said. This involves keeping an eye out for confusing names and similar packaging. “Do that analysis up front and put in strategies to minimize that. Maybe you look for a different drug [for the same use] that has a different name.” Or choose a different manufacturer, so the medication would at least have a different container.
Use bar code scanning. Suppose a pharmacist goes to the shelf and pulls the wrong drug. “Bar code scanning provides the opportunity to catch the error,” Dr. Gaunt said. Many community pharmacies now have bar code scanning. ISMP just issued best practices for community pharmacies, Dr. Gaunt said, and these include the use of bar code scanning and other measures.
Educate consumers. Health care providers can educate consumers on how to minimize the risk of getting the wrong drug, Dr. Gaunt said. When patients are picking up a prescription, suggest they look at the container label; if it looks different from previous prescriptions of the same medicine, ask the pharmacist for an explanation. Some patients just pass it off, Dr. Gaunt said, figuring the pharmacist or health plan switched manufacturers of their medication.
Access the list. The entire list is on the ISMP site and is accessible after free registration.
Goal: Preventing confusion
The FDA has provided guidance for industry on naming drugs not yet approved so that the proposed names are not too similar in sound or appearance to those already on the market. Included in the lengthy document are checklists, such as, “Across a range of dialects, are the names consistently pronounced differently?” and “Are the lengths of the names dissimilar when scripted?” (Lengths are considered different if they differ by two or more letters.)
The FDA also offers the phonetic and orthographic computer analysis (POCA) program, a software tool that employs an advanced algorithm to evaluate similarities between two drug names. The data sources are updated regularly as new drugs are approved.
Liability update
The problem may be decreasing. In a 2020 report, researchers used pharmacists’ professional liability claim data from the Healthcare Providers Service Organization. They compared 2018 data on claims with 2013 data. The percentage of claims associated with wrong drug dispensing errors declined from 43.8% in 2013 to 36.8% in 2018. Wrong dose claims also declined, from 31.5% to 15.3%.
These researchers concluded that technology and automation have contributed to the prevention of medication errors caused by the use of the wrong drug and the wrong dose, but mistakes continue, owing to system and human errors.
A version of this article first appeared on Medscape.com.
Early, intriguing research suggests that preventing acute graft-versus-host disease (GVHD) in the gut – a potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) – could be accomplished by the administration of a single antibody that targets the anti-DLL4 Notch signaling pathway, without compromising the stem cell transplant.
“The major surprise was that none of the anti–DLL4-treated animals developed acute gastrointestinal GVHD for the entire duration of the study. This was a remarkable finding, given that intestinal GVHD is otherwise seen in the vast majority of nonhuman primate transplant recipients that receive either no prophylaxis, or prophylaxis with agents other than anti-DLL4 antibodies,” co–senior author Ivan Maillard, MD, PhD, a professor of medicine and vice chief for research in hematology-oncology at the University of Pennsylvania, Philadelphia, said in an interview.
“The timing was critical,” the authors noted in the study, recently published in Science Translational Medicine. “Intervening before any symptoms of GvHD appear made the long-term protection possible.”
While GVHD may be mild to moderate in chronic forms, acute cases can be serious, if not fatal, and nearly all severe acute GVHD prominently involves the gastrointestinal tract, which can drive activation of pathogenic T cells and potentially lead to tissue damage following allo-HCT.
Systemic corticosteroids are standard first-line treatment for acute GVHD. However, response rates generally range only from 40% to 60%, and there are concerns of side effects. Meanwhile, second-line treatments are of inconsistent benefit.
With previous studies on mice showing benefits of targeting Notch pathway inhibition, particularly DLL4, Dr. Maillard and colleagues further investigated the effects in nonhuman primates that were allo-HCT recipients, using the anti-DLL4 antibody REGN421, which has pharmacokinetic and toxicity information available from previous studies.
The nonhuman primates were treated with one of two dosing regimens: a single dose of REGN421 3 mg/kg at baseline, post HCT, (n = 7) or three weekly doses at days 0, 7 and 14, post transplant (n = 4). Those primates were compared with 11 primates receiving allo-HCT transplants that received supportive care only.
Primates receiving three weekly doses of REGN421 showed antibody concentrations of greater than 2 mcg/mL for more than 30 days post HCT. A single dose of REGN421 was associated with protection from acute GVHD at day 0, while three weekly doses showed protection at day 0, 7, and 14, consistent with an impact of REGN421 during the early phases of T-cell activation.
Compared with animals receiving only supportive care, prophylaxis with REGN421 was associated with delayed acute GVHD onset and lengthened survival.
Of the 11 primates treated with REGN421, none developed clinical signs of gastrointestinal acute GVHD, whereas the majority of those receiving standard care or other preventive interventions did.
“Detailed analysis of acute GVHD clinical presentations in REGN421-treated animals in comparison to no treatment controls revealed near complete protection from GI-acute GvHD with REGN421,” the authors reported.
Furthermore, pathology scores in the gastrointestinal tract were lower with REGN421 treatment, compared with the no-treatment cohort, and the scores matched those of healthy nontransplanted nonhuman primates.
The primates treated with REGN421 did ultimately develop other clinical and pathologic signs of skin, hepatic or pulmonary acute GVHD, but without gastrointestinal disease.
The treatment was not associated with any adverse effects on the allo-HCT, with primates receiving either a single dose or three weekly doses of REGN421 showing rapid donor engraftment after allo-HCT, including high bone marrow, whole blood, and T-cell donor chimerism.
“Reassuringly, short-term systemic DLL4 blockade with REGN421 did not trigger unexpected side effects in our nonhuman primate model, while preserving rapid engraftment as well hematopoietic and immune reconstitution.”
The mechanism preserving the engraftment, described as a “major surprise,” specifically involved DLL4 inhibition blocking the homing of pathogenic T cells to the gut while preserving homing of regulatory T cells that dampen the immune response, Dr. Maillard explained.
“This effect turned out to be at least in part through a posttranslational effect of DLL4/Notch blockade on integrin pairing at the T-cell surface,” he explained. “This was a novel and quite unexpected mechanism of action conserved from mice to nonhuman primates.”
The results are encouraging in terms of translating to humans because of their closer similarities in various physiological factors, Dr. Maillard said.
“The nonhuman primate model of transplantation [offers] a transplantation model very close to what is being performed in humans, as well as the opportunity to study an immune system very similar to that of humans in nonhuman primates,” he said.
Dr. Maillard noted that, while trials in humans are not underway yet, “we are in active discussions about it,” and the team is indeed interested in testing REGN421 itself, with the effects likely to be as a prophylactic strategy.
There are currently no approved anti-DLL4 antibody drugs for use in humans.
“Our approach is mostly promising as a preventive treatment, rather than as a secondary treatment for GVHD, because DLL4/Notch blockade seems most active when applied early after transplantation during the time of initial seeding of the gut by T cells (in mice, we had observed the critical time window for a successful intervention to be within 48 hours of transplantation),” Dr. Maillard said.“There remain questions about which other prophylactic treatments we should ideally combine anti-DLL4 antibodies with.”
Dr. Maillard has received research funding from Regeneron and Genentech and is a member of Garuda Therapeutics’s scientific advisory board.
Early, intriguing research suggests that preventing acute graft-versus-host disease (GVHD) in the gut – a potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) – could be accomplished by the administration of a single antibody that targets the anti-DLL4 Notch signaling pathway, without compromising the stem cell transplant.
“The major surprise was that none of the anti–DLL4-treated animals developed acute gastrointestinal GVHD for the entire duration of the study. This was a remarkable finding, given that intestinal GVHD is otherwise seen in the vast majority of nonhuman primate transplant recipients that receive either no prophylaxis, or prophylaxis with agents other than anti-DLL4 antibodies,” co–senior author Ivan Maillard, MD, PhD, a professor of medicine and vice chief for research in hematology-oncology at the University of Pennsylvania, Philadelphia, said in an interview.
“The timing was critical,” the authors noted in the study, recently published in Science Translational Medicine. “Intervening before any symptoms of GvHD appear made the long-term protection possible.”
While GVHD may be mild to moderate in chronic forms, acute cases can be serious, if not fatal, and nearly all severe acute GVHD prominently involves the gastrointestinal tract, which can drive activation of pathogenic T cells and potentially lead to tissue damage following allo-HCT.
Systemic corticosteroids are standard first-line treatment for acute GVHD. However, response rates generally range only from 40% to 60%, and there are concerns of side effects. Meanwhile, second-line treatments are of inconsistent benefit.
With previous studies on mice showing benefits of targeting Notch pathway inhibition, particularly DLL4, Dr. Maillard and colleagues further investigated the effects in nonhuman primates that were allo-HCT recipients, using the anti-DLL4 antibody REGN421, which has pharmacokinetic and toxicity information available from previous studies.
The nonhuman primates were treated with one of two dosing regimens: a single dose of REGN421 3 mg/kg at baseline, post HCT, (n = 7) or three weekly doses at days 0, 7 and 14, post transplant (n = 4). Those primates were compared with 11 primates receiving allo-HCT transplants that received supportive care only.
Primates receiving three weekly doses of REGN421 showed antibody concentrations of greater than 2 mcg/mL for more than 30 days post HCT. A single dose of REGN421 was associated with protection from acute GVHD at day 0, while three weekly doses showed protection at day 0, 7, and 14, consistent with an impact of REGN421 during the early phases of T-cell activation.
Compared with animals receiving only supportive care, prophylaxis with REGN421 was associated with delayed acute GVHD onset and lengthened survival.
Of the 11 primates treated with REGN421, none developed clinical signs of gastrointestinal acute GVHD, whereas the majority of those receiving standard care or other preventive interventions did.
“Detailed analysis of acute GVHD clinical presentations in REGN421-treated animals in comparison to no treatment controls revealed near complete protection from GI-acute GvHD with REGN421,” the authors reported.
Furthermore, pathology scores in the gastrointestinal tract were lower with REGN421 treatment, compared with the no-treatment cohort, and the scores matched those of healthy nontransplanted nonhuman primates.
The primates treated with REGN421 did ultimately develop other clinical and pathologic signs of skin, hepatic or pulmonary acute GVHD, but without gastrointestinal disease.
The treatment was not associated with any adverse effects on the allo-HCT, with primates receiving either a single dose or three weekly doses of REGN421 showing rapid donor engraftment after allo-HCT, including high bone marrow, whole blood, and T-cell donor chimerism.
“Reassuringly, short-term systemic DLL4 blockade with REGN421 did not trigger unexpected side effects in our nonhuman primate model, while preserving rapid engraftment as well hematopoietic and immune reconstitution.”
The mechanism preserving the engraftment, described as a “major surprise,” specifically involved DLL4 inhibition blocking the homing of pathogenic T cells to the gut while preserving homing of regulatory T cells that dampen the immune response, Dr. Maillard explained.
“This effect turned out to be at least in part through a posttranslational effect of DLL4/Notch blockade on integrin pairing at the T-cell surface,” he explained. “This was a novel and quite unexpected mechanism of action conserved from mice to nonhuman primates.”
The results are encouraging in terms of translating to humans because of their closer similarities in various physiological factors, Dr. Maillard said.
“The nonhuman primate model of transplantation [offers] a transplantation model very close to what is being performed in humans, as well as the opportunity to study an immune system very similar to that of humans in nonhuman primates,” he said.
Dr. Maillard noted that, while trials in humans are not underway yet, “we are in active discussions about it,” and the team is indeed interested in testing REGN421 itself, with the effects likely to be as a prophylactic strategy.
There are currently no approved anti-DLL4 antibody drugs for use in humans.
“Our approach is mostly promising as a preventive treatment, rather than as a secondary treatment for GVHD, because DLL4/Notch blockade seems most active when applied early after transplantation during the time of initial seeding of the gut by T cells (in mice, we had observed the critical time window for a successful intervention to be within 48 hours of transplantation),” Dr. Maillard said.“There remain questions about which other prophylactic treatments we should ideally combine anti-DLL4 antibodies with.”
Dr. Maillard has received research funding from Regeneron and Genentech and is a member of Garuda Therapeutics’s scientific advisory board.
Early, intriguing research suggests that preventing acute graft-versus-host disease (GVHD) in the gut – a potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) – could be accomplished by the administration of a single antibody that targets the anti-DLL4 Notch signaling pathway, without compromising the stem cell transplant.
“The major surprise was that none of the anti–DLL4-treated animals developed acute gastrointestinal GVHD for the entire duration of the study. This was a remarkable finding, given that intestinal GVHD is otherwise seen in the vast majority of nonhuman primate transplant recipients that receive either no prophylaxis, or prophylaxis with agents other than anti-DLL4 antibodies,” co–senior author Ivan Maillard, MD, PhD, a professor of medicine and vice chief for research in hematology-oncology at the University of Pennsylvania, Philadelphia, said in an interview.
“The timing was critical,” the authors noted in the study, recently published in Science Translational Medicine. “Intervening before any symptoms of GvHD appear made the long-term protection possible.”
While GVHD may be mild to moderate in chronic forms, acute cases can be serious, if not fatal, and nearly all severe acute GVHD prominently involves the gastrointestinal tract, which can drive activation of pathogenic T cells and potentially lead to tissue damage following allo-HCT.
Systemic corticosteroids are standard first-line treatment for acute GVHD. However, response rates generally range only from 40% to 60%, and there are concerns of side effects. Meanwhile, second-line treatments are of inconsistent benefit.
With previous studies on mice showing benefits of targeting Notch pathway inhibition, particularly DLL4, Dr. Maillard and colleagues further investigated the effects in nonhuman primates that were allo-HCT recipients, using the anti-DLL4 antibody REGN421, which has pharmacokinetic and toxicity information available from previous studies.
The nonhuman primates were treated with one of two dosing regimens: a single dose of REGN421 3 mg/kg at baseline, post HCT, (n = 7) or three weekly doses at days 0, 7 and 14, post transplant (n = 4). Those primates were compared with 11 primates receiving allo-HCT transplants that received supportive care only.
Primates receiving three weekly doses of REGN421 showed antibody concentrations of greater than 2 mcg/mL for more than 30 days post HCT. A single dose of REGN421 was associated with protection from acute GVHD at day 0, while three weekly doses showed protection at day 0, 7, and 14, consistent with an impact of REGN421 during the early phases of T-cell activation.
Compared with animals receiving only supportive care, prophylaxis with REGN421 was associated with delayed acute GVHD onset and lengthened survival.
Of the 11 primates treated with REGN421, none developed clinical signs of gastrointestinal acute GVHD, whereas the majority of those receiving standard care or other preventive interventions did.
“Detailed analysis of acute GVHD clinical presentations in REGN421-treated animals in comparison to no treatment controls revealed near complete protection from GI-acute GvHD with REGN421,” the authors reported.
Furthermore, pathology scores in the gastrointestinal tract were lower with REGN421 treatment, compared with the no-treatment cohort, and the scores matched those of healthy nontransplanted nonhuman primates.
The primates treated with REGN421 did ultimately develop other clinical and pathologic signs of skin, hepatic or pulmonary acute GVHD, but without gastrointestinal disease.
The treatment was not associated with any adverse effects on the allo-HCT, with primates receiving either a single dose or three weekly doses of REGN421 showing rapid donor engraftment after allo-HCT, including high bone marrow, whole blood, and T-cell donor chimerism.
“Reassuringly, short-term systemic DLL4 blockade with REGN421 did not trigger unexpected side effects in our nonhuman primate model, while preserving rapid engraftment as well hematopoietic and immune reconstitution.”
The mechanism preserving the engraftment, described as a “major surprise,” specifically involved DLL4 inhibition blocking the homing of pathogenic T cells to the gut while preserving homing of regulatory T cells that dampen the immune response, Dr. Maillard explained.
“This effect turned out to be at least in part through a posttranslational effect of DLL4/Notch blockade on integrin pairing at the T-cell surface,” he explained. “This was a novel and quite unexpected mechanism of action conserved from mice to nonhuman primates.”
The results are encouraging in terms of translating to humans because of their closer similarities in various physiological factors, Dr. Maillard said.
“The nonhuman primate model of transplantation [offers] a transplantation model very close to what is being performed in humans, as well as the opportunity to study an immune system very similar to that of humans in nonhuman primates,” he said.
Dr. Maillard noted that, while trials in humans are not underway yet, “we are in active discussions about it,” and the team is indeed interested in testing REGN421 itself, with the effects likely to be as a prophylactic strategy.
There are currently no approved anti-DLL4 antibody drugs for use in humans.
“Our approach is mostly promising as a preventive treatment, rather than as a secondary treatment for GVHD, because DLL4/Notch blockade seems most active when applied early after transplantation during the time of initial seeding of the gut by T cells (in mice, we had observed the critical time window for a successful intervention to be within 48 hours of transplantation),” Dr. Maillard said.“There remain questions about which other prophylactic treatments we should ideally combine anti-DLL4 antibodies with.”
Dr. Maillard has received research funding from Regeneron and Genentech and is a member of Garuda Therapeutics’s scientific advisory board.
Thousands of children are being exposed to the dangers of liquid nicotine in e-cigarettes each year, and the number of exposures reported reached an all-time high last year.
Doctors say a 2016 law aimed at lowering the risk contained a big flaw, NBC News reported. The Child Nicotine Poisoning Prevention Act required child-resistant packaging on vaping liquid – but not on the vaping devices themselves.
Contact with the vaping liquid, or liquid nicotine, can cause children to get dizzy, pass out, and suffer drops in blood pressure. A few drops of the liquid can be fatal for a toddler.
Last year, 6,731 cases of vaping-related nicotine exposure were reported, according to Poison Help. “As of June 30, 2023, poison centers have managed 3,863 exposure cases about e-cigarette devices and liquid nicotine,” the organization said.
“Poison centers began receiving calls about e-cigarettes and liquid nicotine products in 2011, which coincides with the initial period where these products reached the U.S. market,” according to Poison Help.
“These products often contain a greater concentration of nicotine, a stimulant, than other nicotine/tobacco products on the market. Some children and toddlers who come in contact with e-cigarette devices or liquid nicotine have become very ill; some even requiring emergency department visits with nausea and vomiting being the most significant symptoms.”
Toxicologist Ryan Marino, MD, told NBC that refillable vapes are designed to hold liquid nicotine in a central reservoir, making them dangerous to children.
“Even vapes that appear more child-resistant – because their nicotine is sealed inside a removable cartridge – present a risk, because the cartridges can be pried open,” NBC said. “And some disposable e-cigarettes, now the top-selling type on the market, allow users to take thousands of ‘puffs’ and contain as much nicotine as multiple packs of cigarettes.”
A spokesperson for the vaping industry said all e-liquid bottles made in this country conform to U.S. law.
“Not only are the caps child-resistant, but the flow of liquid is restricted so that only small amounts can be dispensed,” said April Meyers of the Smoke-Free Alternatives Trade Association, which represents the vaping industry.
A version of this article first appeared on WebMD.com.
Thousands of children are being exposed to the dangers of liquid nicotine in e-cigarettes each year, and the number of exposures reported reached an all-time high last year.
Doctors say a 2016 law aimed at lowering the risk contained a big flaw, NBC News reported. The Child Nicotine Poisoning Prevention Act required child-resistant packaging on vaping liquid – but not on the vaping devices themselves.
Contact with the vaping liquid, or liquid nicotine, can cause children to get dizzy, pass out, and suffer drops in blood pressure. A few drops of the liquid can be fatal for a toddler.
Last year, 6,731 cases of vaping-related nicotine exposure were reported, according to Poison Help. “As of June 30, 2023, poison centers have managed 3,863 exposure cases about e-cigarette devices and liquid nicotine,” the organization said.
“Poison centers began receiving calls about e-cigarettes and liquid nicotine products in 2011, which coincides with the initial period where these products reached the U.S. market,” according to Poison Help.
“These products often contain a greater concentration of nicotine, a stimulant, than other nicotine/tobacco products on the market. Some children and toddlers who come in contact with e-cigarette devices or liquid nicotine have become very ill; some even requiring emergency department visits with nausea and vomiting being the most significant symptoms.”
Toxicologist Ryan Marino, MD, told NBC that refillable vapes are designed to hold liquid nicotine in a central reservoir, making them dangerous to children.
“Even vapes that appear more child-resistant – because their nicotine is sealed inside a removable cartridge – present a risk, because the cartridges can be pried open,” NBC said. “And some disposable e-cigarettes, now the top-selling type on the market, allow users to take thousands of ‘puffs’ and contain as much nicotine as multiple packs of cigarettes.”
A spokesperson for the vaping industry said all e-liquid bottles made in this country conform to U.S. law.
“Not only are the caps child-resistant, but the flow of liquid is restricted so that only small amounts can be dispensed,” said April Meyers of the Smoke-Free Alternatives Trade Association, which represents the vaping industry.
A version of this article first appeared on WebMD.com.
Thousands of children are being exposed to the dangers of liquid nicotine in e-cigarettes each year, and the number of exposures reported reached an all-time high last year.
Doctors say a 2016 law aimed at lowering the risk contained a big flaw, NBC News reported. The Child Nicotine Poisoning Prevention Act required child-resistant packaging on vaping liquid – but not on the vaping devices themselves.
Contact with the vaping liquid, or liquid nicotine, can cause children to get dizzy, pass out, and suffer drops in blood pressure. A few drops of the liquid can be fatal for a toddler.
Last year, 6,731 cases of vaping-related nicotine exposure were reported, according to Poison Help. “As of June 30, 2023, poison centers have managed 3,863 exposure cases about e-cigarette devices and liquid nicotine,” the organization said.
“Poison centers began receiving calls about e-cigarettes and liquid nicotine products in 2011, which coincides with the initial period where these products reached the U.S. market,” according to Poison Help.
“These products often contain a greater concentration of nicotine, a stimulant, than other nicotine/tobacco products on the market. Some children and toddlers who come in contact with e-cigarette devices or liquid nicotine have become very ill; some even requiring emergency department visits with nausea and vomiting being the most significant symptoms.”
Toxicologist Ryan Marino, MD, told NBC that refillable vapes are designed to hold liquid nicotine in a central reservoir, making them dangerous to children.
“Even vapes that appear more child-resistant – because their nicotine is sealed inside a removable cartridge – present a risk, because the cartridges can be pried open,” NBC said. “And some disposable e-cigarettes, now the top-selling type on the market, allow users to take thousands of ‘puffs’ and contain as much nicotine as multiple packs of cigarettes.”
A spokesperson for the vaping industry said all e-liquid bottles made in this country conform to U.S. law.
“Not only are the caps child-resistant, but the flow of liquid is restricted so that only small amounts can be dispensed,” said April Meyers of the Smoke-Free Alternatives Trade Association, which represents the vaping industry.
A version of this article first appeared on WebMD.com.
