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It’s time to retire the president question
The president question – “Who’s the current president?” – has been a standard one of basic neurology assessments for years, probably since the answer was Ulysses S. Grant. It’s routinely asked by doctors, nurses, EEG techs, medical students, and pretty much anyone else trying to figure out someone’s mental status.
When I first began doing this, the answer was “George Bush” (at that time there’d only been one president by that name, so clarification wasn’t needed). Back then people answered the question (right or wrong) and we moved on. I don’t recall ever getting a dirty look, political lecture, or eye roll as a response.
Unfortunately, it’s not that simple anymore. As people have become increasingly polarized, it’s become seemingly impossible to get a response without a statement of support or anger. At best I get a straight answer. At worst I get a lecture on the “perils of a non-White society” (that was last week). Then they want my opinion, and years of practice have taught me to never discuss politics with patients, regardless of which side they’re on.
I don’t recall this being a problem until the late ‘90s, when the answer was “Clinton.” Occasionally I’d get a sarcastic comment referring to the Lewinsky affair, but that was about it.
Since then it’s gradually escalated, to where the question has become worthless. I don’t have time to hear a political diatribe from either side. This is a doctor appointment, not a debate club. The insistence by some that Trump won leaves me guessing if the person is stubborn or serious, and either way it shouldn’t be my job to figure that out. I take your appointment seriously, so the least you can do is the same.
So I’ve ditched the question for good. The current date, the location of my office, and other less controversial things will have to do. I’m here to take care of you, not have you try to pick a fight or make a political statement.
You’d think such a simple, time-honored, assessment question wouldn’t become such a problem. But
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
The president question – “Who’s the current president?” – has been a standard one of basic neurology assessments for years, probably since the answer was Ulysses S. Grant. It’s routinely asked by doctors, nurses, EEG techs, medical students, and pretty much anyone else trying to figure out someone’s mental status.
When I first began doing this, the answer was “George Bush” (at that time there’d only been one president by that name, so clarification wasn’t needed). Back then people answered the question (right or wrong) and we moved on. I don’t recall ever getting a dirty look, political lecture, or eye roll as a response.
Unfortunately, it’s not that simple anymore. As people have become increasingly polarized, it’s become seemingly impossible to get a response without a statement of support or anger. At best I get a straight answer. At worst I get a lecture on the “perils of a non-White society” (that was last week). Then they want my opinion, and years of practice have taught me to never discuss politics with patients, regardless of which side they’re on.
I don’t recall this being a problem until the late ‘90s, when the answer was “Clinton.” Occasionally I’d get a sarcastic comment referring to the Lewinsky affair, but that was about it.
Since then it’s gradually escalated, to where the question has become worthless. I don’t have time to hear a political diatribe from either side. This is a doctor appointment, not a debate club. The insistence by some that Trump won leaves me guessing if the person is stubborn or serious, and either way it shouldn’t be my job to figure that out. I take your appointment seriously, so the least you can do is the same.
So I’ve ditched the question for good. The current date, the location of my office, and other less controversial things will have to do. I’m here to take care of you, not have you try to pick a fight or make a political statement.
You’d think such a simple, time-honored, assessment question wouldn’t become such a problem. But
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
The president question – “Who’s the current president?” – has been a standard one of basic neurology assessments for years, probably since the answer was Ulysses S. Grant. It’s routinely asked by doctors, nurses, EEG techs, medical students, and pretty much anyone else trying to figure out someone’s mental status.
When I first began doing this, the answer was “George Bush” (at that time there’d only been one president by that name, so clarification wasn’t needed). Back then people answered the question (right or wrong) and we moved on. I don’t recall ever getting a dirty look, political lecture, or eye roll as a response.
Unfortunately, it’s not that simple anymore. As people have become increasingly polarized, it’s become seemingly impossible to get a response without a statement of support or anger. At best I get a straight answer. At worst I get a lecture on the “perils of a non-White society” (that was last week). Then they want my opinion, and years of practice have taught me to never discuss politics with patients, regardless of which side they’re on.
I don’t recall this being a problem until the late ‘90s, when the answer was “Clinton.” Occasionally I’d get a sarcastic comment referring to the Lewinsky affair, but that was about it.
Since then it’s gradually escalated, to where the question has become worthless. I don’t have time to hear a political diatribe from either side. This is a doctor appointment, not a debate club. The insistence by some that Trump won leaves me guessing if the person is stubborn or serious, and either way it shouldn’t be my job to figure that out. I take your appointment seriously, so the least you can do is the same.
So I’ve ditched the question for good. The current date, the location of my office, and other less controversial things will have to do. I’m here to take care of you, not have you try to pick a fight or make a political statement.
You’d think such a simple, time-honored, assessment question wouldn’t become such a problem. But
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
A paleolithic raw bar, and the human brush with extinction
This essay is adapted from the newly released book, “A History of the Human Brain: From the Sea Sponge to CRISPR, How Our Brain Evolved.”
“He was a bold man that first ate an oyster.” – Jonathan Swift
That man or, just as likely, that woman, may have done so out of necessity. It was either eat this glistening, gray blob of briny goo or perish.
Beginning 190,000 years ago, a glacial age we identify today as Marine Isotope Stage 6, or MIS6, had set in, cooling and drying out much of the planet. There was widespread drought, leaving the African plains a harsher, more barren substrate for survival – an arena of competition, desperation, and starvation for many species, including ours. Some estimates have the sapiens population dipping to just a few hundred people during MIS6. Like other apes today, we were an endangered species. But through some nexus of intelligence, ecological exploitation, and luck, we managed. Anthropologists argue over what part of Africa would’ve been hospitable enough to rescue sapiens from Darwinian oblivion. Arizona State University archaeologist Curtis Marean, PhD, believes the continent’s southern shore is a good candidate.
For 2 decades, Dr. Marean has overseen excavations at a site called Pinnacle Point on the South African coast. The region has over 9,000 plant species, including the world’s most diverse population of geophytes, plants with underground energy-storage organs such as bulbs, tubers, and rhizomes. These subterranean stores are rich in calories and carbohydrates, and, by virtue of being buried, are protected from most other species (save the occasional tool-wielding chimpanzee). They are also adapted to cold climates and, when cooked, easily digested. All in all, a coup for hunter-gatherers.
The other enticement at Pinnacle Point could be found with a few easy steps toward the sea. Mollusks. Geological samples from MIS6 show South Africa’s shores were packed with mussels, oysters, clams, and a variety of sea snails. We almost certainly turned to them for nutrition.
Dr. Marean’s research suggests that, sometime around 160,000 years ago, at least one group of sapiens began supplementing their terrestrial diet by exploiting the region’s rich shellfish beds. This is the oldest evidence to date of humans consistently feasting on seafood – easy, predictable, immobile calories. No hunting required. As inland Africa dried up, learning to shuck mussels and oysters was a key adaptation to coastal living, one that supported our later migration out of the continent.
Dr. Marean believes the change in behavior was possible thanks to our already keen brains, which supported an ability to track tides, especially spring tides. Spring tides occur twice a month with each new and full moon and result in the greatest difference between high and low tidewaters. The people of Pinnacle Point learned to exploit this cycle. “By tracking tides, we would have had easy, reliable access to high-quality proteins and fats from shellfish every 2 weeks as the ocean receded,” he says. “Whereas you can’t rely on land animals to always be in the same place at the same time.” Work by Jan De Vynck, PhD, a professor at Nelson Mandela University in South Africa, supports this idea, showing that foraging shellfish beds under optimal tidal conditions can yield a staggering 3,500 calories per hour!
“I don’t know if we owe our existence to seafood, but it was certainly important for the population [that Dr.] Curtis studies. That place is full of mussels,” said Ian Tattersall, PhD, curator emeritus with the American Museum of Natural History in New York.
“And I like the idea that during a population bottleneck we got creative and learned how to focus on marine resources.” Innovations, Dr. Tattersall explained, typically occur in small, fixed populations. Large populations have too much genetic inertia to support radical innovation; the status quo is enough to survive. “If you’re looking for evolutionary innovation, you have to look at smaller groups.”
MIS6 wasn’t the only near-extinction in our past. During the Pleistocene epoch, roughly 2.5 million to 12,000 years ago, humans tended to maintain a small population, hovering around a million and later growing to maybe 8 million at most. Periodically, our numbers dipped as climate shifts, natural disasters, and food shortages brought us dangerously close to extinction. Modern humans are descended from the hearty survivors of these bottlenecks.
One especially dire stretch occurred around 1 million years ago. Our effective population (the number of breeding individuals) shriveled to around 18,000, smaller than that of other apes at the time. Worse, our genetic diversity – the insurance policy on evolutionary success and the ability to adapt – plummeted. A similar near extinction may have occurred around 75,000 years ago, the result of a massive volcanic eruption in Sumatra.
Our smarts and adaptability helped us endure these tough times – omnivorism helped us weather scarcity.
A sea of vitamins
Both Dr. Marean and Dr. Tattersall agree that the sapiens hanging on in southern Africa couldn’t have lived entirely on shellfish.
Most likely they also spent time hunting and foraging roots inland, making pilgrimages to the sea during spring tides. Dr. Marean believes coastal cuisine may have allowed a paltry human population to hang on until climate change led to more hospitable terrain. He’s not entirely sold on the idea that marine life was necessarily a driver of human brain evolution.
By the time we incorporated seafood into our diets we were already smart, our brains shaped through millennia of selection for intelligence. “Being a marine forager requires a certain degree of sophisticated smarts,” he said. It requires tracking the lunar cycle and planning excursions to the coast at the right times. Shellfish were simply another source of calories.
Unless you ask Michael Crawford.
Dr. Crawford is a professor at Imperial College London and a strident believer that our brains are those of sea creatures. Sort of.
In 1972, he copublished a paper concluding that the brain is structurally and functionally dependent on an omega-3 fatty acid called docosahexaenoic acid, or DHA. The human brain is composed of nearly 60% fat, so it’s not surprising that certain fats are important to brain health. Nearly 50 years after Dr. Crawford’s study, omega-3 supplements are now a multi-billion-dollar business.
Omega-3s, or more formally, omega-3 polyunsaturated fatty acids (PUFAs), are essential fats, meaning they aren’t produced by the body and must be obtained through diet. We get them from vegetable oils, nuts, seeds, and animals that eat such things. But take an informal poll, and you’ll find most people probably associate omega fatty acids with fish and other seafood.
In the 1970s and 1980s, scientists took notice of the low rates of heart disease in Eskimo communities. Research linked their cardiovascular health to a high-fish diet (though fish cannot produce omega-3s, they source them from algae), and eventually the medical and scientific communities began to rethink fat. Study after study found omega-3 fatty acids to be healthy. They were linked with a lower risk for heart disease and overall mortality. All those decades of parents forcing various fish oils on their grimacing children now had some science behind them. There is such a thing as a good fat.
, especially DHA and eicosapentaenoic acid, or EPA. Omega fats provide structure to neuronal cell membranes and are crucial in neuron-to-neuron communication. They increase levels of a protein called brain-derived neurotrophic factor (BDNF), which supports neuronal growth and survival. A growing body of evidence shows omega-3 supplementation may slow down the process of neurodegeneration, the gradual deterioration of the brain that results in Alzheimer’s disease and other forms of dementia.
Popping a daily omega-3 supplement or, better still, eating a seafood-rich diet, may increase blood flow to the brain. In 2019, the International Society for Nutritional Psychiatry Research recommended omega-3s as an adjunct therapy for major depressive disorder. PUFAs appear to reduce the risk for and severity of mood disorders such as depression and to boost attention in children with ADHD as effectively as drug therapies.
Many researchers claim there would’ve been plenty of DHA available on land to support early humans, and marine foods were just one of many sources.
Not Dr. Crawford.
He believes that brain development and function are not only dependent on DHA but, in fact, DHA sourced from the sea was critical to mammalian brain evolution. “The animal brain evolved 600 million years ago in the ocean and was dependent on DHA, as well as compounds such as iodine, which is also in short supply on land,” he said. “To build a brain, you need these building blocks, which were rich at sea and on rocky shores.”
Dr. Crawford cites his early biochemical work showing DHA isn’t readily accessible from the muscle tissue of land animals. Using DHA tagged with a radioactive isotope, he and his colleagues in the 1970s found that “ready-made” DHA, like that found in shellfish, is incorporated into the developing rat brain with 10-fold greater efficiency than plant- and land animal–sourced DHA, where it exists as its metabolic precursor alpha-linolenic acid. “I’m afraid the idea that ample DHA was available from the fats of animals on the savanna is just not true,” he disputes. According to Dr. Crawford, our tiny, wormlike ancestors were able to evolve primitive nervous systems and flit through the silt thanks to the abundance of healthy fat to be had by living in the ocean and consuming algae.
For over 40 years, Dr. Crawford has argued that rising rates of mental illness are a result of post–World War II dietary changes, especially the move toward land-sourced food and the medical community’s subsequent support of low-fat diets. He feels that omega-3s from seafood were critical to humans’ rapid neural march toward higher cognition, and are therefore critical to brain health. “The continued rise in mental illness is an incredibly important threat to mankind and society, and moving away from marine foods is a major contributor,” said Dr. Crawford.
University of Sherbrooke (Que.) physiology professor Stephen Cunnane, PhD, tends to agree that aquatically sourced nutrients were crucial to human evolution. It’s the importance of coastal living he’s not sure about. He believes hominins would’ve incorporated fish from lakes and rivers into their diet for millions of years. In his view, it wasn’t just omega-3s that contributed to our big brains, but a cluster of nutrients found in fish: iodine, iron, zinc, copper, and selenium among them. “I think DHA was hugely important to our evolution and brain health but I don’t think it was a magic bullet all by itself,” he said. “Numerous other nutrients found in fish and shellfish were very probably important, too, and are now known to be good for the brain.”
Dr. Marean agrees. “Accessing the marine food chain could have had a huge impact on fertility, survival, and overall health, including brain health, in part, due to the high return on omega-3 fatty acids and other nutrients.” But, he speculates, before MIS6, hominins would have had access to plenty of brain-healthy terrestrial nutrition, including meat from animals that consumed omega-3–rich plants and grains.
Dr. Cunnane agrees with Dr. Marean to a degree. He’s confident that higher intelligence evolved gradually over millions of years as mutations inching the cognitive needle forward conferred survival and reproductive advantages – but he maintains that certain advantages like, say, being able to shuck an oyster, allowed an already intelligent brain to thrive.
Foraging marine life in the waters off of Africa likely played an important role in keeping some of our ancestors alive and supported our subsequent propagation throughout the world. By this point, the human brain was already a marvel of consciousness and computing, not too dissimilar to the one we carry around today.
In all likelihood, Pleistocene humans probably got their nutrients and calories wherever they could. If we lived inland, we hunted. Maybe we speared the occasional catfish. We sourced nutrients from fruits, leaves, and nuts. A few times a month, those of us near the coast enjoyed a feast of mussels and oysters.
Dr. Stetka is an editorial director at Medscape.com, a former neuroscience researcher, and a nonpracticing physician. A version of this article first appeared on Medscape.
This essay is adapted from the newly released book, “A History of the Human Brain: From the Sea Sponge to CRISPR, How Our Brain Evolved.”
“He was a bold man that first ate an oyster.” – Jonathan Swift
That man or, just as likely, that woman, may have done so out of necessity. It was either eat this glistening, gray blob of briny goo or perish.
Beginning 190,000 years ago, a glacial age we identify today as Marine Isotope Stage 6, or MIS6, had set in, cooling and drying out much of the planet. There was widespread drought, leaving the African plains a harsher, more barren substrate for survival – an arena of competition, desperation, and starvation for many species, including ours. Some estimates have the sapiens population dipping to just a few hundred people during MIS6. Like other apes today, we were an endangered species. But through some nexus of intelligence, ecological exploitation, and luck, we managed. Anthropologists argue over what part of Africa would’ve been hospitable enough to rescue sapiens from Darwinian oblivion. Arizona State University archaeologist Curtis Marean, PhD, believes the continent’s southern shore is a good candidate.
For 2 decades, Dr. Marean has overseen excavations at a site called Pinnacle Point on the South African coast. The region has over 9,000 plant species, including the world’s most diverse population of geophytes, plants with underground energy-storage organs such as bulbs, tubers, and rhizomes. These subterranean stores are rich in calories and carbohydrates, and, by virtue of being buried, are protected from most other species (save the occasional tool-wielding chimpanzee). They are also adapted to cold climates and, when cooked, easily digested. All in all, a coup for hunter-gatherers.
The other enticement at Pinnacle Point could be found with a few easy steps toward the sea. Mollusks. Geological samples from MIS6 show South Africa’s shores were packed with mussels, oysters, clams, and a variety of sea snails. We almost certainly turned to them for nutrition.
Dr. Marean’s research suggests that, sometime around 160,000 years ago, at least one group of sapiens began supplementing their terrestrial diet by exploiting the region’s rich shellfish beds. This is the oldest evidence to date of humans consistently feasting on seafood – easy, predictable, immobile calories. No hunting required. As inland Africa dried up, learning to shuck mussels and oysters was a key adaptation to coastal living, one that supported our later migration out of the continent.
Dr. Marean believes the change in behavior was possible thanks to our already keen brains, which supported an ability to track tides, especially spring tides. Spring tides occur twice a month with each new and full moon and result in the greatest difference between high and low tidewaters. The people of Pinnacle Point learned to exploit this cycle. “By tracking tides, we would have had easy, reliable access to high-quality proteins and fats from shellfish every 2 weeks as the ocean receded,” he says. “Whereas you can’t rely on land animals to always be in the same place at the same time.” Work by Jan De Vynck, PhD, a professor at Nelson Mandela University in South Africa, supports this idea, showing that foraging shellfish beds under optimal tidal conditions can yield a staggering 3,500 calories per hour!
“I don’t know if we owe our existence to seafood, but it was certainly important for the population [that Dr.] Curtis studies. That place is full of mussels,” said Ian Tattersall, PhD, curator emeritus with the American Museum of Natural History in New York.
“And I like the idea that during a population bottleneck we got creative and learned how to focus on marine resources.” Innovations, Dr. Tattersall explained, typically occur in small, fixed populations. Large populations have too much genetic inertia to support radical innovation; the status quo is enough to survive. “If you’re looking for evolutionary innovation, you have to look at smaller groups.”
MIS6 wasn’t the only near-extinction in our past. During the Pleistocene epoch, roughly 2.5 million to 12,000 years ago, humans tended to maintain a small population, hovering around a million and later growing to maybe 8 million at most. Periodically, our numbers dipped as climate shifts, natural disasters, and food shortages brought us dangerously close to extinction. Modern humans are descended from the hearty survivors of these bottlenecks.
One especially dire stretch occurred around 1 million years ago. Our effective population (the number of breeding individuals) shriveled to around 18,000, smaller than that of other apes at the time. Worse, our genetic diversity – the insurance policy on evolutionary success and the ability to adapt – plummeted. A similar near extinction may have occurred around 75,000 years ago, the result of a massive volcanic eruption in Sumatra.
Our smarts and adaptability helped us endure these tough times – omnivorism helped us weather scarcity.
A sea of vitamins
Both Dr. Marean and Dr. Tattersall agree that the sapiens hanging on in southern Africa couldn’t have lived entirely on shellfish.
Most likely they also spent time hunting and foraging roots inland, making pilgrimages to the sea during spring tides. Dr. Marean believes coastal cuisine may have allowed a paltry human population to hang on until climate change led to more hospitable terrain. He’s not entirely sold on the idea that marine life was necessarily a driver of human brain evolution.
By the time we incorporated seafood into our diets we were already smart, our brains shaped through millennia of selection for intelligence. “Being a marine forager requires a certain degree of sophisticated smarts,” he said. It requires tracking the lunar cycle and planning excursions to the coast at the right times. Shellfish were simply another source of calories.
Unless you ask Michael Crawford.
Dr. Crawford is a professor at Imperial College London and a strident believer that our brains are those of sea creatures. Sort of.
In 1972, he copublished a paper concluding that the brain is structurally and functionally dependent on an omega-3 fatty acid called docosahexaenoic acid, or DHA. The human brain is composed of nearly 60% fat, so it’s not surprising that certain fats are important to brain health. Nearly 50 years after Dr. Crawford’s study, omega-3 supplements are now a multi-billion-dollar business.
Omega-3s, or more formally, omega-3 polyunsaturated fatty acids (PUFAs), are essential fats, meaning they aren’t produced by the body and must be obtained through diet. We get them from vegetable oils, nuts, seeds, and animals that eat such things. But take an informal poll, and you’ll find most people probably associate omega fatty acids with fish and other seafood.
In the 1970s and 1980s, scientists took notice of the low rates of heart disease in Eskimo communities. Research linked their cardiovascular health to a high-fish diet (though fish cannot produce omega-3s, they source them from algae), and eventually the medical and scientific communities began to rethink fat. Study after study found omega-3 fatty acids to be healthy. They were linked with a lower risk for heart disease and overall mortality. All those decades of parents forcing various fish oils on their grimacing children now had some science behind them. There is such a thing as a good fat.
, especially DHA and eicosapentaenoic acid, or EPA. Omega fats provide structure to neuronal cell membranes and are crucial in neuron-to-neuron communication. They increase levels of a protein called brain-derived neurotrophic factor (BDNF), which supports neuronal growth and survival. A growing body of evidence shows omega-3 supplementation may slow down the process of neurodegeneration, the gradual deterioration of the brain that results in Alzheimer’s disease and other forms of dementia.
Popping a daily omega-3 supplement or, better still, eating a seafood-rich diet, may increase blood flow to the brain. In 2019, the International Society for Nutritional Psychiatry Research recommended omega-3s as an adjunct therapy for major depressive disorder. PUFAs appear to reduce the risk for and severity of mood disorders such as depression and to boost attention in children with ADHD as effectively as drug therapies.
Many researchers claim there would’ve been plenty of DHA available on land to support early humans, and marine foods were just one of many sources.
Not Dr. Crawford.
He believes that brain development and function are not only dependent on DHA but, in fact, DHA sourced from the sea was critical to mammalian brain evolution. “The animal brain evolved 600 million years ago in the ocean and was dependent on DHA, as well as compounds such as iodine, which is also in short supply on land,” he said. “To build a brain, you need these building blocks, which were rich at sea and on rocky shores.”
Dr. Crawford cites his early biochemical work showing DHA isn’t readily accessible from the muscle tissue of land animals. Using DHA tagged with a radioactive isotope, he and his colleagues in the 1970s found that “ready-made” DHA, like that found in shellfish, is incorporated into the developing rat brain with 10-fold greater efficiency than plant- and land animal–sourced DHA, where it exists as its metabolic precursor alpha-linolenic acid. “I’m afraid the idea that ample DHA was available from the fats of animals on the savanna is just not true,” he disputes. According to Dr. Crawford, our tiny, wormlike ancestors were able to evolve primitive nervous systems and flit through the silt thanks to the abundance of healthy fat to be had by living in the ocean and consuming algae.
For over 40 years, Dr. Crawford has argued that rising rates of mental illness are a result of post–World War II dietary changes, especially the move toward land-sourced food and the medical community’s subsequent support of low-fat diets. He feels that omega-3s from seafood were critical to humans’ rapid neural march toward higher cognition, and are therefore critical to brain health. “The continued rise in mental illness is an incredibly important threat to mankind and society, and moving away from marine foods is a major contributor,” said Dr. Crawford.
University of Sherbrooke (Que.) physiology professor Stephen Cunnane, PhD, tends to agree that aquatically sourced nutrients were crucial to human evolution. It’s the importance of coastal living he’s not sure about. He believes hominins would’ve incorporated fish from lakes and rivers into their diet for millions of years. In his view, it wasn’t just omega-3s that contributed to our big brains, but a cluster of nutrients found in fish: iodine, iron, zinc, copper, and selenium among them. “I think DHA was hugely important to our evolution and brain health but I don’t think it was a magic bullet all by itself,” he said. “Numerous other nutrients found in fish and shellfish were very probably important, too, and are now known to be good for the brain.”
Dr. Marean agrees. “Accessing the marine food chain could have had a huge impact on fertility, survival, and overall health, including brain health, in part, due to the high return on omega-3 fatty acids and other nutrients.” But, he speculates, before MIS6, hominins would have had access to plenty of brain-healthy terrestrial nutrition, including meat from animals that consumed omega-3–rich plants and grains.
Dr. Cunnane agrees with Dr. Marean to a degree. He’s confident that higher intelligence evolved gradually over millions of years as mutations inching the cognitive needle forward conferred survival and reproductive advantages – but he maintains that certain advantages like, say, being able to shuck an oyster, allowed an already intelligent brain to thrive.
Foraging marine life in the waters off of Africa likely played an important role in keeping some of our ancestors alive and supported our subsequent propagation throughout the world. By this point, the human brain was already a marvel of consciousness and computing, not too dissimilar to the one we carry around today.
In all likelihood, Pleistocene humans probably got their nutrients and calories wherever they could. If we lived inland, we hunted. Maybe we speared the occasional catfish. We sourced nutrients from fruits, leaves, and nuts. A few times a month, those of us near the coast enjoyed a feast of mussels and oysters.
Dr. Stetka is an editorial director at Medscape.com, a former neuroscience researcher, and a nonpracticing physician. A version of this article first appeared on Medscape.
This essay is adapted from the newly released book, “A History of the Human Brain: From the Sea Sponge to CRISPR, How Our Brain Evolved.”
“He was a bold man that first ate an oyster.” – Jonathan Swift
That man or, just as likely, that woman, may have done so out of necessity. It was either eat this glistening, gray blob of briny goo or perish.
Beginning 190,000 years ago, a glacial age we identify today as Marine Isotope Stage 6, or MIS6, had set in, cooling and drying out much of the planet. There was widespread drought, leaving the African plains a harsher, more barren substrate for survival – an arena of competition, desperation, and starvation for many species, including ours. Some estimates have the sapiens population dipping to just a few hundred people during MIS6. Like other apes today, we were an endangered species. But through some nexus of intelligence, ecological exploitation, and luck, we managed. Anthropologists argue over what part of Africa would’ve been hospitable enough to rescue sapiens from Darwinian oblivion. Arizona State University archaeologist Curtis Marean, PhD, believes the continent’s southern shore is a good candidate.
For 2 decades, Dr. Marean has overseen excavations at a site called Pinnacle Point on the South African coast. The region has over 9,000 plant species, including the world’s most diverse population of geophytes, plants with underground energy-storage organs such as bulbs, tubers, and rhizomes. These subterranean stores are rich in calories and carbohydrates, and, by virtue of being buried, are protected from most other species (save the occasional tool-wielding chimpanzee). They are also adapted to cold climates and, when cooked, easily digested. All in all, a coup for hunter-gatherers.
The other enticement at Pinnacle Point could be found with a few easy steps toward the sea. Mollusks. Geological samples from MIS6 show South Africa’s shores were packed with mussels, oysters, clams, and a variety of sea snails. We almost certainly turned to them for nutrition.
Dr. Marean’s research suggests that, sometime around 160,000 years ago, at least one group of sapiens began supplementing their terrestrial diet by exploiting the region’s rich shellfish beds. This is the oldest evidence to date of humans consistently feasting on seafood – easy, predictable, immobile calories. No hunting required. As inland Africa dried up, learning to shuck mussels and oysters was a key adaptation to coastal living, one that supported our later migration out of the continent.
Dr. Marean believes the change in behavior was possible thanks to our already keen brains, which supported an ability to track tides, especially spring tides. Spring tides occur twice a month with each new and full moon and result in the greatest difference between high and low tidewaters. The people of Pinnacle Point learned to exploit this cycle. “By tracking tides, we would have had easy, reliable access to high-quality proteins and fats from shellfish every 2 weeks as the ocean receded,” he says. “Whereas you can’t rely on land animals to always be in the same place at the same time.” Work by Jan De Vynck, PhD, a professor at Nelson Mandela University in South Africa, supports this idea, showing that foraging shellfish beds under optimal tidal conditions can yield a staggering 3,500 calories per hour!
“I don’t know if we owe our existence to seafood, but it was certainly important for the population [that Dr.] Curtis studies. That place is full of mussels,” said Ian Tattersall, PhD, curator emeritus with the American Museum of Natural History in New York.
“And I like the idea that during a population bottleneck we got creative and learned how to focus on marine resources.” Innovations, Dr. Tattersall explained, typically occur in small, fixed populations. Large populations have too much genetic inertia to support radical innovation; the status quo is enough to survive. “If you’re looking for evolutionary innovation, you have to look at smaller groups.”
MIS6 wasn’t the only near-extinction in our past. During the Pleistocene epoch, roughly 2.5 million to 12,000 years ago, humans tended to maintain a small population, hovering around a million and later growing to maybe 8 million at most. Periodically, our numbers dipped as climate shifts, natural disasters, and food shortages brought us dangerously close to extinction. Modern humans are descended from the hearty survivors of these bottlenecks.
One especially dire stretch occurred around 1 million years ago. Our effective population (the number of breeding individuals) shriveled to around 18,000, smaller than that of other apes at the time. Worse, our genetic diversity – the insurance policy on evolutionary success and the ability to adapt – plummeted. A similar near extinction may have occurred around 75,000 years ago, the result of a massive volcanic eruption in Sumatra.
Our smarts and adaptability helped us endure these tough times – omnivorism helped us weather scarcity.
A sea of vitamins
Both Dr. Marean and Dr. Tattersall agree that the sapiens hanging on in southern Africa couldn’t have lived entirely on shellfish.
Most likely they also spent time hunting and foraging roots inland, making pilgrimages to the sea during spring tides. Dr. Marean believes coastal cuisine may have allowed a paltry human population to hang on until climate change led to more hospitable terrain. He’s not entirely sold on the idea that marine life was necessarily a driver of human brain evolution.
By the time we incorporated seafood into our diets we were already smart, our brains shaped through millennia of selection for intelligence. “Being a marine forager requires a certain degree of sophisticated smarts,” he said. It requires tracking the lunar cycle and planning excursions to the coast at the right times. Shellfish were simply another source of calories.
Unless you ask Michael Crawford.
Dr. Crawford is a professor at Imperial College London and a strident believer that our brains are those of sea creatures. Sort of.
In 1972, he copublished a paper concluding that the brain is structurally and functionally dependent on an omega-3 fatty acid called docosahexaenoic acid, or DHA. The human brain is composed of nearly 60% fat, so it’s not surprising that certain fats are important to brain health. Nearly 50 years after Dr. Crawford’s study, omega-3 supplements are now a multi-billion-dollar business.
Omega-3s, or more formally, omega-3 polyunsaturated fatty acids (PUFAs), are essential fats, meaning they aren’t produced by the body and must be obtained through diet. We get them from vegetable oils, nuts, seeds, and animals that eat such things. But take an informal poll, and you’ll find most people probably associate omega fatty acids with fish and other seafood.
In the 1970s and 1980s, scientists took notice of the low rates of heart disease in Eskimo communities. Research linked their cardiovascular health to a high-fish diet (though fish cannot produce omega-3s, they source them from algae), and eventually the medical and scientific communities began to rethink fat. Study after study found omega-3 fatty acids to be healthy. They were linked with a lower risk for heart disease and overall mortality. All those decades of parents forcing various fish oils on their grimacing children now had some science behind them. There is such a thing as a good fat.
, especially DHA and eicosapentaenoic acid, or EPA. Omega fats provide structure to neuronal cell membranes and are crucial in neuron-to-neuron communication. They increase levels of a protein called brain-derived neurotrophic factor (BDNF), which supports neuronal growth and survival. A growing body of evidence shows omega-3 supplementation may slow down the process of neurodegeneration, the gradual deterioration of the brain that results in Alzheimer’s disease and other forms of dementia.
Popping a daily omega-3 supplement or, better still, eating a seafood-rich diet, may increase blood flow to the brain. In 2019, the International Society for Nutritional Psychiatry Research recommended omega-3s as an adjunct therapy for major depressive disorder. PUFAs appear to reduce the risk for and severity of mood disorders such as depression and to boost attention in children with ADHD as effectively as drug therapies.
Many researchers claim there would’ve been plenty of DHA available on land to support early humans, and marine foods were just one of many sources.
Not Dr. Crawford.
He believes that brain development and function are not only dependent on DHA but, in fact, DHA sourced from the sea was critical to mammalian brain evolution. “The animal brain evolved 600 million years ago in the ocean and was dependent on DHA, as well as compounds such as iodine, which is also in short supply on land,” he said. “To build a brain, you need these building blocks, which were rich at sea and on rocky shores.”
Dr. Crawford cites his early biochemical work showing DHA isn’t readily accessible from the muscle tissue of land animals. Using DHA tagged with a radioactive isotope, he and his colleagues in the 1970s found that “ready-made” DHA, like that found in shellfish, is incorporated into the developing rat brain with 10-fold greater efficiency than plant- and land animal–sourced DHA, where it exists as its metabolic precursor alpha-linolenic acid. “I’m afraid the idea that ample DHA was available from the fats of animals on the savanna is just not true,” he disputes. According to Dr. Crawford, our tiny, wormlike ancestors were able to evolve primitive nervous systems and flit through the silt thanks to the abundance of healthy fat to be had by living in the ocean and consuming algae.
For over 40 years, Dr. Crawford has argued that rising rates of mental illness are a result of post–World War II dietary changes, especially the move toward land-sourced food and the medical community’s subsequent support of low-fat diets. He feels that omega-3s from seafood were critical to humans’ rapid neural march toward higher cognition, and are therefore critical to brain health. “The continued rise in mental illness is an incredibly important threat to mankind and society, and moving away from marine foods is a major contributor,” said Dr. Crawford.
University of Sherbrooke (Que.) physiology professor Stephen Cunnane, PhD, tends to agree that aquatically sourced nutrients were crucial to human evolution. It’s the importance of coastal living he’s not sure about. He believes hominins would’ve incorporated fish from lakes and rivers into their diet for millions of years. In his view, it wasn’t just omega-3s that contributed to our big brains, but a cluster of nutrients found in fish: iodine, iron, zinc, copper, and selenium among them. “I think DHA was hugely important to our evolution and brain health but I don’t think it was a magic bullet all by itself,” he said. “Numerous other nutrients found in fish and shellfish were very probably important, too, and are now known to be good for the brain.”
Dr. Marean agrees. “Accessing the marine food chain could have had a huge impact on fertility, survival, and overall health, including brain health, in part, due to the high return on omega-3 fatty acids and other nutrients.” But, he speculates, before MIS6, hominins would have had access to plenty of brain-healthy terrestrial nutrition, including meat from animals that consumed omega-3–rich plants and grains.
Dr. Cunnane agrees with Dr. Marean to a degree. He’s confident that higher intelligence evolved gradually over millions of years as mutations inching the cognitive needle forward conferred survival and reproductive advantages – but he maintains that certain advantages like, say, being able to shuck an oyster, allowed an already intelligent brain to thrive.
Foraging marine life in the waters off of Africa likely played an important role in keeping some of our ancestors alive and supported our subsequent propagation throughout the world. By this point, the human brain was already a marvel of consciousness and computing, not too dissimilar to the one we carry around today.
In all likelihood, Pleistocene humans probably got their nutrients and calories wherever they could. If we lived inland, we hunted. Maybe we speared the occasional catfish. We sourced nutrients from fruits, leaves, and nuts. A few times a month, those of us near the coast enjoyed a feast of mussels and oysters.
Dr. Stetka is an editorial director at Medscape.com, a former neuroscience researcher, and a nonpracticing physician. A version of this article first appeared on Medscape.
The significance of mismatch repair deficiency in endometrial cancer
Women with Lynch syndrome are known to carry an approximately 60% lifetime risk of endometrial cancer. These cancers result from inherited deleterious mutations in genes that code for mismatch repair proteins. However, mismatch repair deficiency (MMR-d) is not exclusively found in the tumors of patients with Lynch syndrome, and much is being learned about this group of endometrial cancers, their behavior, and their vulnerability to targeted therapies.
During the processes of DNA replication, recombination, or chemical and physical damage, mismatches in base pairs frequently occurs. Mismatch repair proteins function to identify and repair such errors, and the loss of their function causes the accumulation of the insertions or deletions of short, repetitive sequences of DNA. This phenomenon can be measured using polymerase chain reaction (PCR) screening of known microsatellites to look for the accumulation of errors, a phenotype which is called microsatellite instability (MSI). The accumulation of errors in DNA sequences is thought to lead to mutations in cancer-related genes.
The four predominant mismatch repair genes include MLH1, MSH2, MSH 6, and PMS2. These genes may possess loss of function through a germline/inherited mechanism, such as Lynch syndrome, or can be sporadically acquired. Approximately 20%-30% of endometrial cancers exhibit MMR-d with acquired, sporadic losses in function being the majority of cases and only approximately 10% a result of Lynch syndrome. Mutations in PMS2 are the dominant genotype of Lynch syndrome, whereas loss of function in MLH1 is most frequent aberration in sporadic cases of MMR-d endometrial cancer.1
Endometrial cancers can be tested for MMR-d by performing immunohistochemistry to look for loss of expression in the four most common MMR genes. If there is loss of expression of MLH1, additional triage testing can be performed to determine if this loss is caused by the epigenetic phenomenon of hypermethylation. When present, this excludes Lynch syndrome and suggests a sporadic form origin of the disease. If there is loss of expression of the MMR genes (including loss of MLH1 and subsequent negative testing for promotor methylation), the patient should receive genetic testing for the presence of a germline mutation indicating Lynch syndrome. As an adjunct or alternative to immunohistochemistry, PCR studies or next-generation sequencing can be used to measure the presence of microsatellite instability in a process that identifies the expansion or reduction in repetitive DNA sequences of the tumor, compared with normal tumor.2
It is of the highest importance to identify endometrial cancers caused by Lynch syndrome because this enables providers to offer cascade testing of relatives, and to intensify screening or preventative measures for the many other cancers (such as colon, upper gastrointestinal, breast, and urothelial) for which these patients are at risk. Therefore, routine screening for MMR-d tumors is recommended in all cases of endometrial cancer, not simply those of a young age at diagnosis or for whom a strong family history exists.3 Using family history factors, primary tumor site, and age as a trigger for screening for Lynch syndrome, such as the Bethesda Guidelines, is associated with a 82% sensitivity in identifying Lynch syndrome. In a meta-analysis including testing results from 1,159 women with endometrial cancer, 43% of patients who were diagnosed with Lynch syndrome via molecular analysis would have been missed by clinical screening using Bethesda Guidelines.2
Discovering cases of Lynch syndrome is not the only benefit of routine testing for MMR-d in endometrial cancers. There is also significant value in the characterization of sporadic mismatch repair–deficient tumors because this information provides prognostic information and guides therapy. Tumors with a microsatellite-high phenotype/MMR-d were identified as one of the four distinct molecular subgroups of endometrial cancer by the Cancer Genome Atlas.4 Patients with this molecular profile exhibited “intermediate” prognostic outcomes, performing better than the “serous-like” cancers with p53 mutations, yet worse than patients with a POLE ultramutated group who rarely experience recurrences or death, even in the setting of unfavorable histology.
Beyond prognostication, the molecular profile of endometrial cancers also influence their responsiveness to therapeutics, highlighting the importance of splitting, not lumping endometrial cancers into relevant molecular subgroups when designing research and practicing clinical medicine. The PORTEC-3 trial studied 410 women with high-risk endometrial cancer, and randomized participants to receive either adjuvant radiation alone, or radiation with chemotherapy.5 There were no differences in progression-free survival between the two therapeutic strategies when analyzed in aggregate. However, when analyzed by Cancer Genome Atlas molecular subgroup, it was noted that there was a clear benefit from chemotherapy for patients with p53 mutations. For patients with MMR-d tumors, no such benefit was observed. Patients assigned this molecular subgroup did no better with the addition of platinum and taxane chemotherapy over radiation alone. Unfortunately, for patients with MMR-d tumors, recurrence rates remained high, suggesting that we can and need to discover more effective therapies for these tumors than what is available with conventional radiation or platinum and taxane chemotherapy. Targeted therapy may be the solution to this problem. Through microsatellite instability, MMR-d tumors create somatic mutations which result in neoantigens, an immunogenic environment. This state up-regulates checkpoint inhibitor proteins, which serve as an actionable target for anti-PD-L1 antibodies, such as the drug pembrolizumab which has been shown to be highly active against MMR-d endometrial cancer. In the landmark, KEYNOTE-158 trial, patients with advanced, recurrent solid tumors that exhibited MMR-d were treated with pembrolizumab.6 This included 49 patients with endometrial cancer, among whom there was a 79% response rate. Subsequently, pembrolizumab was granted Food and Drug Administration approval for use in advanced, recurrent MMR-d/MSI-high endometrial cancer. Trials are currently enrolling patients to explore the utility of this drug in the up-front setting in both early- and late-stage disease with a hope that this targeted therapy can do what conventional cytotoxic chemotherapy has failed to do.
Therefore, given the clinical significance of mismatch repair deficiency, all patients with endometrial cancer should be investigated for loss of expression in these proteins, and if present, considered for the possibility of Lynch syndrome. While most will not have an inherited cause, this information regarding their tumor biology remains critically important in both prognostication and decision-making surrounding other therapies and their eligibility for promising clinical trials.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to declare. Email her at [email protected].
References
1. Simpkins SB et al. Hum. Mol. Genet. 1999;8:661-6.
2. Kahn R et al. Cancer. 2019 Sep 15;125(18):2172-3183.
3. SGO Clinical Practice Statement: Screening for Lynch Syndrome in Endometrial Cancer. https://www.sgo.org/clinical-practice/guidelines/screening-for-lynch-syndrome-in-endometrial-cancer/
4. Kandoth et al. Nature. 2013;497(7447):67-73.
5. Leon-Castillo A et al. J Clin Oncol. 2020 Oct 10;38(29):3388-97.
6. Marabelle A et al. J Clin Oncol. 2020 Jan 1;38(1):1-10.
Women with Lynch syndrome are known to carry an approximately 60% lifetime risk of endometrial cancer. These cancers result from inherited deleterious mutations in genes that code for mismatch repair proteins. However, mismatch repair deficiency (MMR-d) is not exclusively found in the tumors of patients with Lynch syndrome, and much is being learned about this group of endometrial cancers, their behavior, and their vulnerability to targeted therapies.
During the processes of DNA replication, recombination, or chemical and physical damage, mismatches in base pairs frequently occurs. Mismatch repair proteins function to identify and repair such errors, and the loss of their function causes the accumulation of the insertions or deletions of short, repetitive sequences of DNA. This phenomenon can be measured using polymerase chain reaction (PCR) screening of known microsatellites to look for the accumulation of errors, a phenotype which is called microsatellite instability (MSI). The accumulation of errors in DNA sequences is thought to lead to mutations in cancer-related genes.
The four predominant mismatch repair genes include MLH1, MSH2, MSH 6, and PMS2. These genes may possess loss of function through a germline/inherited mechanism, such as Lynch syndrome, or can be sporadically acquired. Approximately 20%-30% of endometrial cancers exhibit MMR-d with acquired, sporadic losses in function being the majority of cases and only approximately 10% a result of Lynch syndrome. Mutations in PMS2 are the dominant genotype of Lynch syndrome, whereas loss of function in MLH1 is most frequent aberration in sporadic cases of MMR-d endometrial cancer.1
Endometrial cancers can be tested for MMR-d by performing immunohistochemistry to look for loss of expression in the four most common MMR genes. If there is loss of expression of MLH1, additional triage testing can be performed to determine if this loss is caused by the epigenetic phenomenon of hypermethylation. When present, this excludes Lynch syndrome and suggests a sporadic form origin of the disease. If there is loss of expression of the MMR genes (including loss of MLH1 and subsequent negative testing for promotor methylation), the patient should receive genetic testing for the presence of a germline mutation indicating Lynch syndrome. As an adjunct or alternative to immunohistochemistry, PCR studies or next-generation sequencing can be used to measure the presence of microsatellite instability in a process that identifies the expansion or reduction in repetitive DNA sequences of the tumor, compared with normal tumor.2
It is of the highest importance to identify endometrial cancers caused by Lynch syndrome because this enables providers to offer cascade testing of relatives, and to intensify screening or preventative measures for the many other cancers (such as colon, upper gastrointestinal, breast, and urothelial) for which these patients are at risk. Therefore, routine screening for MMR-d tumors is recommended in all cases of endometrial cancer, not simply those of a young age at diagnosis or for whom a strong family history exists.3 Using family history factors, primary tumor site, and age as a trigger for screening for Lynch syndrome, such as the Bethesda Guidelines, is associated with a 82% sensitivity in identifying Lynch syndrome. In a meta-analysis including testing results from 1,159 women with endometrial cancer, 43% of patients who were diagnosed with Lynch syndrome via molecular analysis would have been missed by clinical screening using Bethesda Guidelines.2
Discovering cases of Lynch syndrome is not the only benefit of routine testing for MMR-d in endometrial cancers. There is also significant value in the characterization of sporadic mismatch repair–deficient tumors because this information provides prognostic information and guides therapy. Tumors with a microsatellite-high phenotype/MMR-d were identified as one of the four distinct molecular subgroups of endometrial cancer by the Cancer Genome Atlas.4 Patients with this molecular profile exhibited “intermediate” prognostic outcomes, performing better than the “serous-like” cancers with p53 mutations, yet worse than patients with a POLE ultramutated group who rarely experience recurrences or death, even in the setting of unfavorable histology.
Beyond prognostication, the molecular profile of endometrial cancers also influence their responsiveness to therapeutics, highlighting the importance of splitting, not lumping endometrial cancers into relevant molecular subgroups when designing research and practicing clinical medicine. The PORTEC-3 trial studied 410 women with high-risk endometrial cancer, and randomized participants to receive either adjuvant radiation alone, or radiation with chemotherapy.5 There were no differences in progression-free survival between the two therapeutic strategies when analyzed in aggregate. However, when analyzed by Cancer Genome Atlas molecular subgroup, it was noted that there was a clear benefit from chemotherapy for patients with p53 mutations. For patients with MMR-d tumors, no such benefit was observed. Patients assigned this molecular subgroup did no better with the addition of platinum and taxane chemotherapy over radiation alone. Unfortunately, for patients with MMR-d tumors, recurrence rates remained high, suggesting that we can and need to discover more effective therapies for these tumors than what is available with conventional radiation or platinum and taxane chemotherapy. Targeted therapy may be the solution to this problem. Through microsatellite instability, MMR-d tumors create somatic mutations which result in neoantigens, an immunogenic environment. This state up-regulates checkpoint inhibitor proteins, which serve as an actionable target for anti-PD-L1 antibodies, such as the drug pembrolizumab which has been shown to be highly active against MMR-d endometrial cancer. In the landmark, KEYNOTE-158 trial, patients with advanced, recurrent solid tumors that exhibited MMR-d were treated with pembrolizumab.6 This included 49 patients with endometrial cancer, among whom there was a 79% response rate. Subsequently, pembrolizumab was granted Food and Drug Administration approval for use in advanced, recurrent MMR-d/MSI-high endometrial cancer. Trials are currently enrolling patients to explore the utility of this drug in the up-front setting in both early- and late-stage disease with a hope that this targeted therapy can do what conventional cytotoxic chemotherapy has failed to do.
Therefore, given the clinical significance of mismatch repair deficiency, all patients with endometrial cancer should be investigated for loss of expression in these proteins, and if present, considered for the possibility of Lynch syndrome. While most will not have an inherited cause, this information regarding their tumor biology remains critically important in both prognostication and decision-making surrounding other therapies and their eligibility for promising clinical trials.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to declare. Email her at [email protected].
References
1. Simpkins SB et al. Hum. Mol. Genet. 1999;8:661-6.
2. Kahn R et al. Cancer. 2019 Sep 15;125(18):2172-3183.
3. SGO Clinical Practice Statement: Screening for Lynch Syndrome in Endometrial Cancer. https://www.sgo.org/clinical-practice/guidelines/screening-for-lynch-syndrome-in-endometrial-cancer/
4. Kandoth et al. Nature. 2013;497(7447):67-73.
5. Leon-Castillo A et al. J Clin Oncol. 2020 Oct 10;38(29):3388-97.
6. Marabelle A et al. J Clin Oncol. 2020 Jan 1;38(1):1-10.
Women with Lynch syndrome are known to carry an approximately 60% lifetime risk of endometrial cancer. These cancers result from inherited deleterious mutations in genes that code for mismatch repair proteins. However, mismatch repair deficiency (MMR-d) is not exclusively found in the tumors of patients with Lynch syndrome, and much is being learned about this group of endometrial cancers, their behavior, and their vulnerability to targeted therapies.
During the processes of DNA replication, recombination, or chemical and physical damage, mismatches in base pairs frequently occurs. Mismatch repair proteins function to identify and repair such errors, and the loss of their function causes the accumulation of the insertions or deletions of short, repetitive sequences of DNA. This phenomenon can be measured using polymerase chain reaction (PCR) screening of known microsatellites to look for the accumulation of errors, a phenotype which is called microsatellite instability (MSI). The accumulation of errors in DNA sequences is thought to lead to mutations in cancer-related genes.
The four predominant mismatch repair genes include MLH1, MSH2, MSH 6, and PMS2. These genes may possess loss of function through a germline/inherited mechanism, such as Lynch syndrome, or can be sporadically acquired. Approximately 20%-30% of endometrial cancers exhibit MMR-d with acquired, sporadic losses in function being the majority of cases and only approximately 10% a result of Lynch syndrome. Mutations in PMS2 are the dominant genotype of Lynch syndrome, whereas loss of function in MLH1 is most frequent aberration in sporadic cases of MMR-d endometrial cancer.1
Endometrial cancers can be tested for MMR-d by performing immunohistochemistry to look for loss of expression in the four most common MMR genes. If there is loss of expression of MLH1, additional triage testing can be performed to determine if this loss is caused by the epigenetic phenomenon of hypermethylation. When present, this excludes Lynch syndrome and suggests a sporadic form origin of the disease. If there is loss of expression of the MMR genes (including loss of MLH1 and subsequent negative testing for promotor methylation), the patient should receive genetic testing for the presence of a germline mutation indicating Lynch syndrome. As an adjunct or alternative to immunohistochemistry, PCR studies or next-generation sequencing can be used to measure the presence of microsatellite instability in a process that identifies the expansion or reduction in repetitive DNA sequences of the tumor, compared with normal tumor.2
It is of the highest importance to identify endometrial cancers caused by Lynch syndrome because this enables providers to offer cascade testing of relatives, and to intensify screening or preventative measures for the many other cancers (such as colon, upper gastrointestinal, breast, and urothelial) for which these patients are at risk. Therefore, routine screening for MMR-d tumors is recommended in all cases of endometrial cancer, not simply those of a young age at diagnosis or for whom a strong family history exists.3 Using family history factors, primary tumor site, and age as a trigger for screening for Lynch syndrome, such as the Bethesda Guidelines, is associated with a 82% sensitivity in identifying Lynch syndrome. In a meta-analysis including testing results from 1,159 women with endometrial cancer, 43% of patients who were diagnosed with Lynch syndrome via molecular analysis would have been missed by clinical screening using Bethesda Guidelines.2
Discovering cases of Lynch syndrome is not the only benefit of routine testing for MMR-d in endometrial cancers. There is also significant value in the characterization of sporadic mismatch repair–deficient tumors because this information provides prognostic information and guides therapy. Tumors with a microsatellite-high phenotype/MMR-d were identified as one of the four distinct molecular subgroups of endometrial cancer by the Cancer Genome Atlas.4 Patients with this molecular profile exhibited “intermediate” prognostic outcomes, performing better than the “serous-like” cancers with p53 mutations, yet worse than patients with a POLE ultramutated group who rarely experience recurrences or death, even in the setting of unfavorable histology.
Beyond prognostication, the molecular profile of endometrial cancers also influence their responsiveness to therapeutics, highlighting the importance of splitting, not lumping endometrial cancers into relevant molecular subgroups when designing research and practicing clinical medicine. The PORTEC-3 trial studied 410 women with high-risk endometrial cancer, and randomized participants to receive either adjuvant radiation alone, or radiation with chemotherapy.5 There were no differences in progression-free survival between the two therapeutic strategies when analyzed in aggregate. However, when analyzed by Cancer Genome Atlas molecular subgroup, it was noted that there was a clear benefit from chemotherapy for patients with p53 mutations. For patients with MMR-d tumors, no such benefit was observed. Patients assigned this molecular subgroup did no better with the addition of platinum and taxane chemotherapy over radiation alone. Unfortunately, for patients with MMR-d tumors, recurrence rates remained high, suggesting that we can and need to discover more effective therapies for these tumors than what is available with conventional radiation or platinum and taxane chemotherapy. Targeted therapy may be the solution to this problem. Through microsatellite instability, MMR-d tumors create somatic mutations which result in neoantigens, an immunogenic environment. This state up-regulates checkpoint inhibitor proteins, which serve as an actionable target for anti-PD-L1 antibodies, such as the drug pembrolizumab which has been shown to be highly active against MMR-d endometrial cancer. In the landmark, KEYNOTE-158 trial, patients with advanced, recurrent solid tumors that exhibited MMR-d were treated with pembrolizumab.6 This included 49 patients with endometrial cancer, among whom there was a 79% response rate. Subsequently, pembrolizumab was granted Food and Drug Administration approval for use in advanced, recurrent MMR-d/MSI-high endometrial cancer. Trials are currently enrolling patients to explore the utility of this drug in the up-front setting in both early- and late-stage disease with a hope that this targeted therapy can do what conventional cytotoxic chemotherapy has failed to do.
Therefore, given the clinical significance of mismatch repair deficiency, all patients with endometrial cancer should be investigated for loss of expression in these proteins, and if present, considered for the possibility of Lynch syndrome. While most will not have an inherited cause, this information regarding their tumor biology remains critically important in both prognostication and decision-making surrounding other therapies and their eligibility for promising clinical trials.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to declare. Email her at [email protected].
References
1. Simpkins SB et al. Hum. Mol. Genet. 1999;8:661-6.
2. Kahn R et al. Cancer. 2019 Sep 15;125(18):2172-3183.
3. SGO Clinical Practice Statement: Screening for Lynch Syndrome in Endometrial Cancer. https://www.sgo.org/clinical-practice/guidelines/screening-for-lynch-syndrome-in-endometrial-cancer/
4. Kandoth et al. Nature. 2013;497(7447):67-73.
5. Leon-Castillo A et al. J Clin Oncol. 2020 Oct 10;38(29):3388-97.
6. Marabelle A et al. J Clin Oncol. 2020 Jan 1;38(1):1-10.
Change is hard: Lessons from an EHR conversion
During this “go-live,” 5 hospitals and approximately 300 ambulatory service and physician practice locations made the transition, consolidating over 100 disparate electronic systems and dozens of interfaces into one world-class medical record.
If you’ve ever been part of such an event, you know it is anything but simple. On the contrary, it requires an enormous financial investment along with years of planning, hours of meetings, and months of training. No matter how much preparation goes into it, there are sure to be bumps along the way. It is a traumatic and stressful time for all involved, but the end result is well worth the effort. Still, there are lessons to be learned and wisdom to be gleaned, and this month we’d like to share a few that we found most important. We believe that many of these are useful lessons even to those who will never live through a go-live.
Safety always comes first
Patient safety is a term so often used that it has a tendency to be taken for granted. Health systems build processes and procedures to ensure safety – some even win awards and recognition for their efforts. But the best (and safest) health care institutions build patient safety into their cultures. More than just being taught to use checklists or buzzwords, the staff at these institutions are encouraged to put the welfare of patients first, making all other activities secondary to this pursuit. We had the opportunity to witness the benefits of such a culture during this go-live and were incredibly impressed with the results.
To be successful in an EHR transition of any magnitude, an organization needs to hold patient safety as a core value and provide its employees with the tools to execute on that value. This enables staff to prepare adequately and to identify risks and opportunities before the conversion takes place. Once go-live occurs, staff also must feel empowered to speak up when they identify problem areas that might jeopardize patients’ care. They also must be given a clear escalation path to ensure their voices can be heard. Most importantly, everyone must understand that the electronic health record itself is just one piece of a major operational change.
As workflows are modified to adapt to the new technology, unsafe processes should be called out and fixed quickly. While the EHR may offer the latest in decision support and system integration, no advancement in technology can make up for bad outcomes, nor justify processes that lead to patient harm.
Training is no substitute for good support
It takes a long time to train thousands of employees, especially when that training must occur during the era of social distancing in the midst of a pandemic. Still, even in the best of times, education should be married to hands-on experience in order to have a real impact. Unfortunately, this is extremely challenging.
Trainees forget much of what they’ve learned in the weeks or months between education and go-live, so they must be given immediately accessible support to bridge the gap. This is known as “at-the-elbow” (ATE) support, and as the name implies, it consists of individuals who are familiar with the new system and are always available to end users, answering their questions and helping them navigate. Since health care never sleeps, this support needs to be offered 24/7, and it should also be flexible and plentiful.
There are many areas that will require more support than anticipated to accommodate the number of clinical and other staff who will use the system, so support staff must be nimble and available for redeployment. In addition, ensuring high-quality support is essential. As many ATE experts are hired contractors, their knowledge base and communications skills can vary widely. Accountability is key, and end users should feel empowered to identify gaps in coverage and deficits in knowledge base in the ATE.
As employees become more familiar with the new system, the need for ATE will wane, but there will still be questions that arise for many weeks to months, and new EHR users will also be added all the time. A good after–go-live support system should remain available so clinical and clerical employees can get just-in-time assistance whenever they need it.
Users should be given clear expectations
Clinicians going through an EHR conversion may be frustrated to discover that the data transferred from their old system into the new one is not quite what they expected. While structured elements such as allergies and immunizations may transfer, unstructured patient histories may not come over at all.
There may be gaps in data, or the opposite may even be true: an overabundance of useless information may transfer over, leaving doctors with dozens of meaningless data points to sift through and eliminate to clean up the chart. This can be extremely time-consuming and discouraging and may jeopardize the success of the go-live.
Providers deserve clear expectations prior to conversion. They should be told what will and will not transfer and be informed that there will be extra work required for documentation at the outset. They may also want the option to preemptively reduce patient volumes to accommodate the additional effort involved in preparing charts. No matter what, this will be a heavy lift, and physicians should understand the implications long before go-live to prepare accordingly.
Old habits die hard
One of the most common complaints we’ve heard following EHR conversions is that “things just worked better in the old system.” We always respond with a question: “Were things better, or just different?” The truth may lie somewhere in the middle, but there is no question that muscle memory develops over many years, and change is difficult no matter how much better the new system is. Still, appropriate expectations, access to just-in-time support, and a continual focus on safety will ensure that the long-term benefits of a patient-centered and integrated electronic record will far outweigh the initial challenges of go-live.
Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
During this “go-live,” 5 hospitals and approximately 300 ambulatory service and physician practice locations made the transition, consolidating over 100 disparate electronic systems and dozens of interfaces into one world-class medical record.
If you’ve ever been part of such an event, you know it is anything but simple. On the contrary, it requires an enormous financial investment along with years of planning, hours of meetings, and months of training. No matter how much preparation goes into it, there are sure to be bumps along the way. It is a traumatic and stressful time for all involved, but the end result is well worth the effort. Still, there are lessons to be learned and wisdom to be gleaned, and this month we’d like to share a few that we found most important. We believe that many of these are useful lessons even to those who will never live through a go-live.
Safety always comes first
Patient safety is a term so often used that it has a tendency to be taken for granted. Health systems build processes and procedures to ensure safety – some even win awards and recognition for their efforts. But the best (and safest) health care institutions build patient safety into their cultures. More than just being taught to use checklists or buzzwords, the staff at these institutions are encouraged to put the welfare of patients first, making all other activities secondary to this pursuit. We had the opportunity to witness the benefits of such a culture during this go-live and were incredibly impressed with the results.
To be successful in an EHR transition of any magnitude, an organization needs to hold patient safety as a core value and provide its employees with the tools to execute on that value. This enables staff to prepare adequately and to identify risks and opportunities before the conversion takes place. Once go-live occurs, staff also must feel empowered to speak up when they identify problem areas that might jeopardize patients’ care. They also must be given a clear escalation path to ensure their voices can be heard. Most importantly, everyone must understand that the electronic health record itself is just one piece of a major operational change.
As workflows are modified to adapt to the new technology, unsafe processes should be called out and fixed quickly. While the EHR may offer the latest in decision support and system integration, no advancement in technology can make up for bad outcomes, nor justify processes that lead to patient harm.
Training is no substitute for good support
It takes a long time to train thousands of employees, especially when that training must occur during the era of social distancing in the midst of a pandemic. Still, even in the best of times, education should be married to hands-on experience in order to have a real impact. Unfortunately, this is extremely challenging.
Trainees forget much of what they’ve learned in the weeks or months between education and go-live, so they must be given immediately accessible support to bridge the gap. This is known as “at-the-elbow” (ATE) support, and as the name implies, it consists of individuals who are familiar with the new system and are always available to end users, answering their questions and helping them navigate. Since health care never sleeps, this support needs to be offered 24/7, and it should also be flexible and plentiful.
There are many areas that will require more support than anticipated to accommodate the number of clinical and other staff who will use the system, so support staff must be nimble and available for redeployment. In addition, ensuring high-quality support is essential. As many ATE experts are hired contractors, their knowledge base and communications skills can vary widely. Accountability is key, and end users should feel empowered to identify gaps in coverage and deficits in knowledge base in the ATE.
As employees become more familiar with the new system, the need for ATE will wane, but there will still be questions that arise for many weeks to months, and new EHR users will also be added all the time. A good after–go-live support system should remain available so clinical and clerical employees can get just-in-time assistance whenever they need it.
Users should be given clear expectations
Clinicians going through an EHR conversion may be frustrated to discover that the data transferred from their old system into the new one is not quite what they expected. While structured elements such as allergies and immunizations may transfer, unstructured patient histories may not come over at all.
There may be gaps in data, or the opposite may even be true: an overabundance of useless information may transfer over, leaving doctors with dozens of meaningless data points to sift through and eliminate to clean up the chart. This can be extremely time-consuming and discouraging and may jeopardize the success of the go-live.
Providers deserve clear expectations prior to conversion. They should be told what will and will not transfer and be informed that there will be extra work required for documentation at the outset. They may also want the option to preemptively reduce patient volumes to accommodate the additional effort involved in preparing charts. No matter what, this will be a heavy lift, and physicians should understand the implications long before go-live to prepare accordingly.
Old habits die hard
One of the most common complaints we’ve heard following EHR conversions is that “things just worked better in the old system.” We always respond with a question: “Were things better, or just different?” The truth may lie somewhere in the middle, but there is no question that muscle memory develops over many years, and change is difficult no matter how much better the new system is. Still, appropriate expectations, access to just-in-time support, and a continual focus on safety will ensure that the long-term benefits of a patient-centered and integrated electronic record will far outweigh the initial challenges of go-live.
Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
During this “go-live,” 5 hospitals and approximately 300 ambulatory service and physician practice locations made the transition, consolidating over 100 disparate electronic systems and dozens of interfaces into one world-class medical record.
If you’ve ever been part of such an event, you know it is anything but simple. On the contrary, it requires an enormous financial investment along with years of planning, hours of meetings, and months of training. No matter how much preparation goes into it, there are sure to be bumps along the way. It is a traumatic and stressful time for all involved, but the end result is well worth the effort. Still, there are lessons to be learned and wisdom to be gleaned, and this month we’d like to share a few that we found most important. We believe that many of these are useful lessons even to those who will never live through a go-live.
Safety always comes first
Patient safety is a term so often used that it has a tendency to be taken for granted. Health systems build processes and procedures to ensure safety – some even win awards and recognition for their efforts. But the best (and safest) health care institutions build patient safety into their cultures. More than just being taught to use checklists or buzzwords, the staff at these institutions are encouraged to put the welfare of patients first, making all other activities secondary to this pursuit. We had the opportunity to witness the benefits of such a culture during this go-live and were incredibly impressed with the results.
To be successful in an EHR transition of any magnitude, an organization needs to hold patient safety as a core value and provide its employees with the tools to execute on that value. This enables staff to prepare adequately and to identify risks and opportunities before the conversion takes place. Once go-live occurs, staff also must feel empowered to speak up when they identify problem areas that might jeopardize patients’ care. They also must be given a clear escalation path to ensure their voices can be heard. Most importantly, everyone must understand that the electronic health record itself is just one piece of a major operational change.
As workflows are modified to adapt to the new technology, unsafe processes should be called out and fixed quickly. While the EHR may offer the latest in decision support and system integration, no advancement in technology can make up for bad outcomes, nor justify processes that lead to patient harm.
Training is no substitute for good support
It takes a long time to train thousands of employees, especially when that training must occur during the era of social distancing in the midst of a pandemic. Still, even in the best of times, education should be married to hands-on experience in order to have a real impact. Unfortunately, this is extremely challenging.
Trainees forget much of what they’ve learned in the weeks or months between education and go-live, so they must be given immediately accessible support to bridge the gap. This is known as “at-the-elbow” (ATE) support, and as the name implies, it consists of individuals who are familiar with the new system and are always available to end users, answering their questions and helping them navigate. Since health care never sleeps, this support needs to be offered 24/7, and it should also be flexible and plentiful.
There are many areas that will require more support than anticipated to accommodate the number of clinical and other staff who will use the system, so support staff must be nimble and available for redeployment. In addition, ensuring high-quality support is essential. As many ATE experts are hired contractors, their knowledge base and communications skills can vary widely. Accountability is key, and end users should feel empowered to identify gaps in coverage and deficits in knowledge base in the ATE.
As employees become more familiar with the new system, the need for ATE will wane, but there will still be questions that arise for many weeks to months, and new EHR users will also be added all the time. A good after–go-live support system should remain available so clinical and clerical employees can get just-in-time assistance whenever they need it.
Users should be given clear expectations
Clinicians going through an EHR conversion may be frustrated to discover that the data transferred from their old system into the new one is not quite what they expected. While structured elements such as allergies and immunizations may transfer, unstructured patient histories may not come over at all.
There may be gaps in data, or the opposite may even be true: an overabundance of useless information may transfer over, leaving doctors with dozens of meaningless data points to sift through and eliminate to clean up the chart. This can be extremely time-consuming and discouraging and may jeopardize the success of the go-live.
Providers deserve clear expectations prior to conversion. They should be told what will and will not transfer and be informed that there will be extra work required for documentation at the outset. They may also want the option to preemptively reduce patient volumes to accommodate the additional effort involved in preparing charts. No matter what, this will be a heavy lift, and physicians should understand the implications long before go-live to prepare accordingly.
Old habits die hard
One of the most common complaints we’ve heard following EHR conversions is that “things just worked better in the old system.” We always respond with a question: “Were things better, or just different?” The truth may lie somewhere in the middle, but there is no question that muscle memory develops over many years, and change is difficult no matter how much better the new system is. Still, appropriate expectations, access to just-in-time support, and a continual focus on safety will ensure that the long-term benefits of a patient-centered and integrated electronic record will far outweigh the initial challenges of go-live.
Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
Artifactual hypoglycemia: When there’s a problem in the tube
If you are looking for zebras you might consider adrenal insufficiency, which could cause both hyperkalemia and hypoglycemia, but this would make no sense in someone asymptomatic.
This pattern is one I have seen commonly when I am on call, and I am contacted about abnormal labs. The lab reported no hemolysis seen, but this is the typical pattern seen with hemolytic specimens and/or specimens that have been held a long time before they are analyzed.
Lippi and colleagues reported on the clinically significant increase in potassium in samples that visually appeared not to be hemolyzed.1 Hemolyzed specimens can also drop glucose values, but not as profoundly as raising potassium values. When left unprocessed, glycolysis occurs in the white blood cells of a blood sample and may consume 5%-7% of the sample’s glucose content per hour.2
Khaled and colleagues looked at the drop in glucose levels in samples over time based on what anticoagulants were used.3 They found that, at 3 hours, glucose measurements were decreased by 28.4 mg/dL when sodium citrate is used, 58 mg/dL when EDTA was used, 15.4 mg/dL when fluoride oxalate was used, and 60.2 mg/dL when no anticoagulant is used.
Low blood sugars caused by elevated WBCs in blood samples has been well described.4 It has been described with moderate and very high WBC counts, as well as with the leukocytosis seen with polycythemia vera.5 The term “leukocyte larceny” has been used to describe high WBC counts that can not only utilize glucose, but also oxygen.
Saccheti and colleagues described a patient with a WBC greater than 500,000 who had repeatedly low oxygen levels on blood gases, that did not correlate with the normal oxygen saturations measured by pulse oximetry.6 This same issue has been seen in patients with extreme thrombocytosis.7Pearl: When labs don’t make sense clinically, always look at the possibility that there may be a problem in the tube and not in the person. Especially think of this when blood samples may have been held for a long time before they are run, such as with visiting nurse visits and blood draws at shelters and nursing homes.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Lippi G et al. Clin Chem Lab Med. 2006;44(3):311-6.
2. Mikesh LM and Bruns DE. Clin Chem. 2008 May;54(5):930-2.
3. Khaled S et al. Al-Mukhtar Journal of Sciences. 2018;33(2):100-6.
4. Goodenow TJ and Malarkey WB. JAMA. 1977;237(18):1961-2.
5. R Arem et al. Arch Intern Med. 1982 Nov;142(12):2199-201.
6. Sacchetti A et al. J Emerg Med. 1990;8:567–569.
7. A Mehta et al. Eur Respir J. 2008 Feb;31(2):469-72.
If you are looking for zebras you might consider adrenal insufficiency, which could cause both hyperkalemia and hypoglycemia, but this would make no sense in someone asymptomatic.
This pattern is one I have seen commonly when I am on call, and I am contacted about abnormal labs. The lab reported no hemolysis seen, but this is the typical pattern seen with hemolytic specimens and/or specimens that have been held a long time before they are analyzed.
Lippi and colleagues reported on the clinically significant increase in potassium in samples that visually appeared not to be hemolyzed.1 Hemolyzed specimens can also drop glucose values, but not as profoundly as raising potassium values. When left unprocessed, glycolysis occurs in the white blood cells of a blood sample and may consume 5%-7% of the sample’s glucose content per hour.2
Khaled and colleagues looked at the drop in glucose levels in samples over time based on what anticoagulants were used.3 They found that, at 3 hours, glucose measurements were decreased by 28.4 mg/dL when sodium citrate is used, 58 mg/dL when EDTA was used, 15.4 mg/dL when fluoride oxalate was used, and 60.2 mg/dL when no anticoagulant is used.
Low blood sugars caused by elevated WBCs in blood samples has been well described.4 It has been described with moderate and very high WBC counts, as well as with the leukocytosis seen with polycythemia vera.5 The term “leukocyte larceny” has been used to describe high WBC counts that can not only utilize glucose, but also oxygen.
Saccheti and colleagues described a patient with a WBC greater than 500,000 who had repeatedly low oxygen levels on blood gases, that did not correlate with the normal oxygen saturations measured by pulse oximetry.6 This same issue has been seen in patients with extreme thrombocytosis.7Pearl: When labs don’t make sense clinically, always look at the possibility that there may be a problem in the tube and not in the person. Especially think of this when blood samples may have been held for a long time before they are run, such as with visiting nurse visits and blood draws at shelters and nursing homes.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Lippi G et al. Clin Chem Lab Med. 2006;44(3):311-6.
2. Mikesh LM and Bruns DE. Clin Chem. 2008 May;54(5):930-2.
3. Khaled S et al. Al-Mukhtar Journal of Sciences. 2018;33(2):100-6.
4. Goodenow TJ and Malarkey WB. JAMA. 1977;237(18):1961-2.
5. R Arem et al. Arch Intern Med. 1982 Nov;142(12):2199-201.
6. Sacchetti A et al. J Emerg Med. 1990;8:567–569.
7. A Mehta et al. Eur Respir J. 2008 Feb;31(2):469-72.
If you are looking for zebras you might consider adrenal insufficiency, which could cause both hyperkalemia and hypoglycemia, but this would make no sense in someone asymptomatic.
This pattern is one I have seen commonly when I am on call, and I am contacted about abnormal labs. The lab reported no hemolysis seen, but this is the typical pattern seen with hemolytic specimens and/or specimens that have been held a long time before they are analyzed.
Lippi and colleagues reported on the clinically significant increase in potassium in samples that visually appeared not to be hemolyzed.1 Hemolyzed specimens can also drop glucose values, but not as profoundly as raising potassium values. When left unprocessed, glycolysis occurs in the white blood cells of a blood sample and may consume 5%-7% of the sample’s glucose content per hour.2
Khaled and colleagues looked at the drop in glucose levels in samples over time based on what anticoagulants were used.3 They found that, at 3 hours, glucose measurements were decreased by 28.4 mg/dL when sodium citrate is used, 58 mg/dL when EDTA was used, 15.4 mg/dL when fluoride oxalate was used, and 60.2 mg/dL when no anticoagulant is used.
Low blood sugars caused by elevated WBCs in blood samples has been well described.4 It has been described with moderate and very high WBC counts, as well as with the leukocytosis seen with polycythemia vera.5 The term “leukocyte larceny” has been used to describe high WBC counts that can not only utilize glucose, but also oxygen.
Saccheti and colleagues described a patient with a WBC greater than 500,000 who had repeatedly low oxygen levels on blood gases, that did not correlate with the normal oxygen saturations measured by pulse oximetry.6 This same issue has been seen in patients with extreme thrombocytosis.7Pearl: When labs don’t make sense clinically, always look at the possibility that there may be a problem in the tube and not in the person. Especially think of this when blood samples may have been held for a long time before they are run, such as with visiting nurse visits and blood draws at shelters and nursing homes.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Lippi G et al. Clin Chem Lab Med. 2006;44(3):311-6.
2. Mikesh LM and Bruns DE. Clin Chem. 2008 May;54(5):930-2.
3. Khaled S et al. Al-Mukhtar Journal of Sciences. 2018;33(2):100-6.
4. Goodenow TJ and Malarkey WB. JAMA. 1977;237(18):1961-2.
5. R Arem et al. Arch Intern Med. 1982 Nov;142(12):2199-201.
6. Sacchetti A et al. J Emerg Med. 1990;8:567–569.
7. A Mehta et al. Eur Respir J. 2008 Feb;31(2):469-72.
Recurrent miscarriage: What’s the evidence-based evaluation and management?
A pregnancy loss at any gestational age is devastating. Women and/or couples may, unfairly, self-blame as they desperately seek substantive answers. Their support systems, including health care providers, offer some, albeit fleeting, comfort. Conception is merely the start of an emotionally arduous first trimester that often results in a learned helplessness. This month, we focus on the comprehensive evaluation and the medical evidence–based approach to recurrent pregnancy loss (RPL).
RPL is defined by the American Society for Reproductive Medicine as two or more clinical pregnancy losses of less than 20 weeks’ gestation with a prevalence of approximately 5%. Embryo aneuploidy is the most common reason for a spontaneous miscarriage, occurring in 50%-70% of losses. The risk of spontaneous miscarriage during the reproductive years follows a J-shaped pattern. The lowest percentage is in women aged 25-29 years (9.8%), with a nadir at age 27 (9.5%), then an increasingly steep rise after age 35 to a peak at age 45 and over (53.6%). The loss rate is closer to 50% of all fertilizations since many spontaneous miscarriages occur at 2-4 weeks, before a pregnancy can be clinically diagnosed. The frequency of embryo aneuploidy significantly decreases and embryo euploidy increases with successive numbers of spontaneous miscarriages.
After three or more spontaneous miscarriages, nulliparous women appear to have a higher rate of subsequent pregnancy loss, compared with parous women (BMJ. 2000;320:1708). We recommend an evaluation following two losses given the lack of evidence for a difference in diagnostic yield following two versus three miscarriages and particularly because of the emotional effects of impact of RPL.
RPL causes, percentages of contribution, and evaluation
1. Genetic (2%-5%). Because of the risk of an embryo with an unbalanced chromosomal rearrangement inherited from a translocation present in either of the couple, a blood karyotype of the couple is essential despite a history of one or more successful live births. While in vitro fertilization (IVF) with preimplantation genetic testing for structural rearrangements (PGT-SR) can successfully diagnose affected embryos to avoid their intrauterine transfer, overall live birth rates are similar when comparing natural conception attempts with PGT-SR, although the latter may reduce miscarriages.
2. Anatomic (10%-15%). Hysteroscopy, hysterosalpingogram, or saline ultrasound can be used to image the uterine cavity to evaluate for polyps, fibroids, scarring, or a congenital septum – all of which can be surgically corrected. Chronic endometritis has been found in 27% of patients with recurrent miscarriage (and in 14% with recurrent implantation failure), therefore testing by biopsy is reasonable. An elevated level of homocysteine has been reported to impair DNA methylation and gene expression, causing defective chorionic villous vascularization in spontaneous miscarriage tissues. We recommend folic acid supplementation and the avoidance of testing for MTHFR (methylenetetrahydrofolate reductase). Of note, the recent TRUST study showed no significant benefit from metroplasty in comparison with expectant management in 12 months of observation resulting in a live birth rate of 31% versus 35%, respectively.
3. Acquired thrombophilias (20%). Medical evidence supports testing for the antiphospholipid antibody syndrome (APS), i.e., RPL with either the presence of lupus anticoagulant (LAC), anticardiolipin antibodies, or anti-beta2 glycoprotein for IgG and IgM. Persistent LAC or elevations of antibodies greater than 40 GPL or greater than the 99th percentile for more than 12 weeks justifies the use of low-molecular-weight heparin (LMWH). APS has been shown to cause RPL, thrombosis, and/or autoimmune thrombocytopenia. There is no definitive evidence to support testing for MTHFR or any other thrombophilias for first trimester RPL. APS has up to a 90% fetal loss rate without therapeutic intervention. Treatment includes low-dose aspirin (81 mg daily) and LMWH. These medications are thought to help prevent thrombosis in the placenta, helping to maintain pregnancies.
4. Hormonal (17%-20%). The most common hormonal disorders increasing the risk for miscarriage is thyroid dysfunction (both hyper- and hypothyroid), prolactin elevations, and lack of glucose control. While the concern for a luteal phase (LPD) prevails, there is no accepted definition or treatment. There is recent evidence that antibodies to thyroid peroxidase may increase miscarriage and that low-dose thyroid replacement may reduce this risk. One other important area is the polycystic ovarian syndrome (PCOS). This hormonal abnormality affects 6%-20% of all reproductive aged women and may increase miscarriage.
5. Unexplained (40%-50%). The most frustrating but most common reason for RPL. Nevertheless, close monitoring and supportive care throughout the first trimester has been demonstrated in medical studies to improve outcome.
Seven surprising facts about recurrent miscarriage
1. Folic acid 4 mg daily may decrease embryo chromosomal abnormalities and miscarriage.
Folic acid in doses of at least 0.4 mg daily have long been advocated to reduce spina bifida and neural tube defects. It is optimal to begin folic acid for several months prior to conception attempts. There is evidence it may help treat RPL by reducing the chance for chromosomal errors.
2. A randomized trial did not demonstrate an improved live birth rate using progesterone in the first trimester. However, women enrolled may not have begun progesterone until 6 weeks of pregnancy, begging the question if earlier progesterone would have demonstrated improvement.
Dydrogesterone, a progestogen that is highly selective for the progesterone receptor, lacks estrogenic, androgenic, anabolic, and corticoid properties. Although not available in the United States, dydrogesterone appears to reduce the rate of idiopathic recurrent miscarriage (two or more losses). Also, progesterone support has been shown to reduce loss in threatened miscarriage – 17 OHPC 500 mg IM weekly in the first trimester.
3. No benefit of aspirin and/or heparin to treat unexplained RM.
The use of aspirin and/or heparin-like medication has convincingly been shown to not improve live birth rates in RPL.
4. Inherited thrombophilias are NOT associated with RM and should not be tested.
Screening for factor V (Leiden mutation), factor II (Prothrombin G20210A), and MTHFR have not been shown to cause RM and no treatment, such as aspirin and/or heparin-like medications, improves the live birth rate.
5. Close monitoring and empathetic care improves outcomes.
For unknown reasons, clinics providing close monitoring, emotional support, and education to patients with unexplained RM report higher live birth rates, compared with patients not receiving this level of care.
6. Behavior changes reduce miscarriage.
Elevations in body mass index (BMI) and cigarette smoking both increase the risk of miscarriage. As a result, a healthy BMI and eliminating tobacco use reduce the risk of pregnancy loss. Excessive caffeine use (more than two equivalent cups of caffeine in coffee per day) also may increase spontaneous miscarriage.
7. Fertility medications, intrauterine insemination, in vitro fertilization, or preimplantation genetic testing for aneuploidy (PGT-A) do not improve outcomes.
While patients and, often, health care providers, feel compelled to proceed with fertility treatment, ovulation induction medications, intrauterine insemination, in vitro fertilization, or PGT-A have not been shown to improve the chance for a live birth. PGT-A did not reduce the risk of miscarriage in women with recurrent pregnancy loss.
In summary, following two or more pregnancy losses, I recommend obtaining chromosomal testing of the couple, viewing the uterine cavity, blood testing for thyroid, prolactin, and glucose control, and acquired thrombophilias (as above). Fortunately, when the cause is unexplained, the woman has a 70%-80% chance of a spontaneous live birth over the next 10 years from diagnosis. By further understanding, knowing how to diagnose, and, finally, treating the cause of RPL we can hopefully prevent the heartbreak women and couples endure.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
A pregnancy loss at any gestational age is devastating. Women and/or couples may, unfairly, self-blame as they desperately seek substantive answers. Their support systems, including health care providers, offer some, albeit fleeting, comfort. Conception is merely the start of an emotionally arduous first trimester that often results in a learned helplessness. This month, we focus on the comprehensive evaluation and the medical evidence–based approach to recurrent pregnancy loss (RPL).
RPL is defined by the American Society for Reproductive Medicine as two or more clinical pregnancy losses of less than 20 weeks’ gestation with a prevalence of approximately 5%. Embryo aneuploidy is the most common reason for a spontaneous miscarriage, occurring in 50%-70% of losses. The risk of spontaneous miscarriage during the reproductive years follows a J-shaped pattern. The lowest percentage is in women aged 25-29 years (9.8%), with a nadir at age 27 (9.5%), then an increasingly steep rise after age 35 to a peak at age 45 and over (53.6%). The loss rate is closer to 50% of all fertilizations since many spontaneous miscarriages occur at 2-4 weeks, before a pregnancy can be clinically diagnosed. The frequency of embryo aneuploidy significantly decreases and embryo euploidy increases with successive numbers of spontaneous miscarriages.
After three or more spontaneous miscarriages, nulliparous women appear to have a higher rate of subsequent pregnancy loss, compared with parous women (BMJ. 2000;320:1708). We recommend an evaluation following two losses given the lack of evidence for a difference in diagnostic yield following two versus three miscarriages and particularly because of the emotional effects of impact of RPL.
RPL causes, percentages of contribution, and evaluation
1. Genetic (2%-5%). Because of the risk of an embryo with an unbalanced chromosomal rearrangement inherited from a translocation present in either of the couple, a blood karyotype of the couple is essential despite a history of one or more successful live births. While in vitro fertilization (IVF) with preimplantation genetic testing for structural rearrangements (PGT-SR) can successfully diagnose affected embryos to avoid their intrauterine transfer, overall live birth rates are similar when comparing natural conception attempts with PGT-SR, although the latter may reduce miscarriages.
2. Anatomic (10%-15%). Hysteroscopy, hysterosalpingogram, or saline ultrasound can be used to image the uterine cavity to evaluate for polyps, fibroids, scarring, or a congenital septum – all of which can be surgically corrected. Chronic endometritis has been found in 27% of patients with recurrent miscarriage (and in 14% with recurrent implantation failure), therefore testing by biopsy is reasonable. An elevated level of homocysteine has been reported to impair DNA methylation and gene expression, causing defective chorionic villous vascularization in spontaneous miscarriage tissues. We recommend folic acid supplementation and the avoidance of testing for MTHFR (methylenetetrahydrofolate reductase). Of note, the recent TRUST study showed no significant benefit from metroplasty in comparison with expectant management in 12 months of observation resulting in a live birth rate of 31% versus 35%, respectively.
3. Acquired thrombophilias (20%). Medical evidence supports testing for the antiphospholipid antibody syndrome (APS), i.e., RPL with either the presence of lupus anticoagulant (LAC), anticardiolipin antibodies, or anti-beta2 glycoprotein for IgG and IgM. Persistent LAC or elevations of antibodies greater than 40 GPL or greater than the 99th percentile for more than 12 weeks justifies the use of low-molecular-weight heparin (LMWH). APS has been shown to cause RPL, thrombosis, and/or autoimmune thrombocytopenia. There is no definitive evidence to support testing for MTHFR or any other thrombophilias for first trimester RPL. APS has up to a 90% fetal loss rate without therapeutic intervention. Treatment includes low-dose aspirin (81 mg daily) and LMWH. These medications are thought to help prevent thrombosis in the placenta, helping to maintain pregnancies.
4. Hormonal (17%-20%). The most common hormonal disorders increasing the risk for miscarriage is thyroid dysfunction (both hyper- and hypothyroid), prolactin elevations, and lack of glucose control. While the concern for a luteal phase (LPD) prevails, there is no accepted definition or treatment. There is recent evidence that antibodies to thyroid peroxidase may increase miscarriage and that low-dose thyroid replacement may reduce this risk. One other important area is the polycystic ovarian syndrome (PCOS). This hormonal abnormality affects 6%-20% of all reproductive aged women and may increase miscarriage.
5. Unexplained (40%-50%). The most frustrating but most common reason for RPL. Nevertheless, close monitoring and supportive care throughout the first trimester has been demonstrated in medical studies to improve outcome.
Seven surprising facts about recurrent miscarriage
1. Folic acid 4 mg daily may decrease embryo chromosomal abnormalities and miscarriage.
Folic acid in doses of at least 0.4 mg daily have long been advocated to reduce spina bifida and neural tube defects. It is optimal to begin folic acid for several months prior to conception attempts. There is evidence it may help treat RPL by reducing the chance for chromosomal errors.
2. A randomized trial did not demonstrate an improved live birth rate using progesterone in the first trimester. However, women enrolled may not have begun progesterone until 6 weeks of pregnancy, begging the question if earlier progesterone would have demonstrated improvement.
Dydrogesterone, a progestogen that is highly selective for the progesterone receptor, lacks estrogenic, androgenic, anabolic, and corticoid properties. Although not available in the United States, dydrogesterone appears to reduce the rate of idiopathic recurrent miscarriage (two or more losses). Also, progesterone support has been shown to reduce loss in threatened miscarriage – 17 OHPC 500 mg IM weekly in the first trimester.
3. No benefit of aspirin and/or heparin to treat unexplained RM.
The use of aspirin and/or heparin-like medication has convincingly been shown to not improve live birth rates in RPL.
4. Inherited thrombophilias are NOT associated with RM and should not be tested.
Screening for factor V (Leiden mutation), factor II (Prothrombin G20210A), and MTHFR have not been shown to cause RM and no treatment, such as aspirin and/or heparin-like medications, improves the live birth rate.
5. Close monitoring and empathetic care improves outcomes.
For unknown reasons, clinics providing close monitoring, emotional support, and education to patients with unexplained RM report higher live birth rates, compared with patients not receiving this level of care.
6. Behavior changes reduce miscarriage.
Elevations in body mass index (BMI) and cigarette smoking both increase the risk of miscarriage. As a result, a healthy BMI and eliminating tobacco use reduce the risk of pregnancy loss. Excessive caffeine use (more than two equivalent cups of caffeine in coffee per day) also may increase spontaneous miscarriage.
7. Fertility medications, intrauterine insemination, in vitro fertilization, or preimplantation genetic testing for aneuploidy (PGT-A) do not improve outcomes.
While patients and, often, health care providers, feel compelled to proceed with fertility treatment, ovulation induction medications, intrauterine insemination, in vitro fertilization, or PGT-A have not been shown to improve the chance for a live birth. PGT-A did not reduce the risk of miscarriage in women with recurrent pregnancy loss.
In summary, following two or more pregnancy losses, I recommend obtaining chromosomal testing of the couple, viewing the uterine cavity, blood testing for thyroid, prolactin, and glucose control, and acquired thrombophilias (as above). Fortunately, when the cause is unexplained, the woman has a 70%-80% chance of a spontaneous live birth over the next 10 years from diagnosis. By further understanding, knowing how to diagnose, and, finally, treating the cause of RPL we can hopefully prevent the heartbreak women and couples endure.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
A pregnancy loss at any gestational age is devastating. Women and/or couples may, unfairly, self-blame as they desperately seek substantive answers. Their support systems, including health care providers, offer some, albeit fleeting, comfort. Conception is merely the start of an emotionally arduous first trimester that often results in a learned helplessness. This month, we focus on the comprehensive evaluation and the medical evidence–based approach to recurrent pregnancy loss (RPL).
RPL is defined by the American Society for Reproductive Medicine as two or more clinical pregnancy losses of less than 20 weeks’ gestation with a prevalence of approximately 5%. Embryo aneuploidy is the most common reason for a spontaneous miscarriage, occurring in 50%-70% of losses. The risk of spontaneous miscarriage during the reproductive years follows a J-shaped pattern. The lowest percentage is in women aged 25-29 years (9.8%), with a nadir at age 27 (9.5%), then an increasingly steep rise after age 35 to a peak at age 45 and over (53.6%). The loss rate is closer to 50% of all fertilizations since many spontaneous miscarriages occur at 2-4 weeks, before a pregnancy can be clinically diagnosed. The frequency of embryo aneuploidy significantly decreases and embryo euploidy increases with successive numbers of spontaneous miscarriages.
After three or more spontaneous miscarriages, nulliparous women appear to have a higher rate of subsequent pregnancy loss, compared with parous women (BMJ. 2000;320:1708). We recommend an evaluation following two losses given the lack of evidence for a difference in diagnostic yield following two versus three miscarriages and particularly because of the emotional effects of impact of RPL.
RPL causes, percentages of contribution, and evaluation
1. Genetic (2%-5%). Because of the risk of an embryo with an unbalanced chromosomal rearrangement inherited from a translocation present in either of the couple, a blood karyotype of the couple is essential despite a history of one or more successful live births. While in vitro fertilization (IVF) with preimplantation genetic testing for structural rearrangements (PGT-SR) can successfully diagnose affected embryos to avoid their intrauterine transfer, overall live birth rates are similar when comparing natural conception attempts with PGT-SR, although the latter may reduce miscarriages.
2. Anatomic (10%-15%). Hysteroscopy, hysterosalpingogram, or saline ultrasound can be used to image the uterine cavity to evaluate for polyps, fibroids, scarring, or a congenital septum – all of which can be surgically corrected. Chronic endometritis has been found in 27% of patients with recurrent miscarriage (and in 14% with recurrent implantation failure), therefore testing by biopsy is reasonable. An elevated level of homocysteine has been reported to impair DNA methylation and gene expression, causing defective chorionic villous vascularization in spontaneous miscarriage tissues. We recommend folic acid supplementation and the avoidance of testing for MTHFR (methylenetetrahydrofolate reductase). Of note, the recent TRUST study showed no significant benefit from metroplasty in comparison with expectant management in 12 months of observation resulting in a live birth rate of 31% versus 35%, respectively.
3. Acquired thrombophilias (20%). Medical evidence supports testing for the antiphospholipid antibody syndrome (APS), i.e., RPL with either the presence of lupus anticoagulant (LAC), anticardiolipin antibodies, or anti-beta2 glycoprotein for IgG and IgM. Persistent LAC or elevations of antibodies greater than 40 GPL or greater than the 99th percentile for more than 12 weeks justifies the use of low-molecular-weight heparin (LMWH). APS has been shown to cause RPL, thrombosis, and/or autoimmune thrombocytopenia. There is no definitive evidence to support testing for MTHFR or any other thrombophilias for first trimester RPL. APS has up to a 90% fetal loss rate without therapeutic intervention. Treatment includes low-dose aspirin (81 mg daily) and LMWH. These medications are thought to help prevent thrombosis in the placenta, helping to maintain pregnancies.
4. Hormonal (17%-20%). The most common hormonal disorders increasing the risk for miscarriage is thyroid dysfunction (both hyper- and hypothyroid), prolactin elevations, and lack of glucose control. While the concern for a luteal phase (LPD) prevails, there is no accepted definition or treatment. There is recent evidence that antibodies to thyroid peroxidase may increase miscarriage and that low-dose thyroid replacement may reduce this risk. One other important area is the polycystic ovarian syndrome (PCOS). This hormonal abnormality affects 6%-20% of all reproductive aged women and may increase miscarriage.
5. Unexplained (40%-50%). The most frustrating but most common reason for RPL. Nevertheless, close monitoring and supportive care throughout the first trimester has been demonstrated in medical studies to improve outcome.
Seven surprising facts about recurrent miscarriage
1. Folic acid 4 mg daily may decrease embryo chromosomal abnormalities and miscarriage.
Folic acid in doses of at least 0.4 mg daily have long been advocated to reduce spina bifida and neural tube defects. It is optimal to begin folic acid for several months prior to conception attempts. There is evidence it may help treat RPL by reducing the chance for chromosomal errors.
2. A randomized trial did not demonstrate an improved live birth rate using progesterone in the first trimester. However, women enrolled may not have begun progesterone until 6 weeks of pregnancy, begging the question if earlier progesterone would have demonstrated improvement.
Dydrogesterone, a progestogen that is highly selective for the progesterone receptor, lacks estrogenic, androgenic, anabolic, and corticoid properties. Although not available in the United States, dydrogesterone appears to reduce the rate of idiopathic recurrent miscarriage (two or more losses). Also, progesterone support has been shown to reduce loss in threatened miscarriage – 17 OHPC 500 mg IM weekly in the first trimester.
3. No benefit of aspirin and/or heparin to treat unexplained RM.
The use of aspirin and/or heparin-like medication has convincingly been shown to not improve live birth rates in RPL.
4. Inherited thrombophilias are NOT associated with RM and should not be tested.
Screening for factor V (Leiden mutation), factor II (Prothrombin G20210A), and MTHFR have not been shown to cause RM and no treatment, such as aspirin and/or heparin-like medications, improves the live birth rate.
5. Close monitoring and empathetic care improves outcomes.
For unknown reasons, clinics providing close monitoring, emotional support, and education to patients with unexplained RM report higher live birth rates, compared with patients not receiving this level of care.
6. Behavior changes reduce miscarriage.
Elevations in body mass index (BMI) and cigarette smoking both increase the risk of miscarriage. As a result, a healthy BMI and eliminating tobacco use reduce the risk of pregnancy loss. Excessive caffeine use (more than two equivalent cups of caffeine in coffee per day) also may increase spontaneous miscarriage.
7. Fertility medications, intrauterine insemination, in vitro fertilization, or preimplantation genetic testing for aneuploidy (PGT-A) do not improve outcomes.
While patients and, often, health care providers, feel compelled to proceed with fertility treatment, ovulation induction medications, intrauterine insemination, in vitro fertilization, or PGT-A have not been shown to improve the chance for a live birth. PGT-A did not reduce the risk of miscarriage in women with recurrent pregnancy loss.
In summary, following two or more pregnancy losses, I recommend obtaining chromosomal testing of the couple, viewing the uterine cavity, blood testing for thyroid, prolactin, and glucose control, and acquired thrombophilias (as above). Fortunately, when the cause is unexplained, the woman has a 70%-80% chance of a spontaneous live birth over the next 10 years from diagnosis. By further understanding, knowing how to diagnose, and, finally, treating the cause of RPL we can hopefully prevent the heartbreak women and couples endure.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
A ‘scary’ side effect
Memantine (aka Namenda) is Food and Drug Administration–approved for Alzheimer’s disease, though its benefits are modest, at best.
It’s also, 18 years after first coming to market, relatively inexpensive.
I occasionally use it off label, as neurologists tend to do with a wide variety of medications. There are small studies that suggest it’s effective for migraine prevention and painful neuropathies. It also has a relatively benign side-effect profile.
As a result, once in a while I prescribe it for migraines or neuropathy where more typical agents haven’t helped. Like any of these drugs, sometimes it works, sometimes it doesn’t. A lot of neurology, as one of my colleagues puts it, is “guessing and voodoo.”
Since I’ve started this, however, I’ve noticed an unusual, and somewhat scary, side effect – one that has nothing to do the drug reactions.
While I don’t use any type of commercial chart system, most doctors in my area do, as well as all the hospitals. So I often see my patients’ notes from their general practitioners or after they’ve been in the hospital for whatever reason.
Those notes often list – as they should – current medications. Which includes the memantine I’ve prescribed.
But in the patient problem list I often then see “Alzheimer’s disease” or “dementia” show up, even in people who clearly have no history of such.
I’ve seen it way too many times to think it’s an accident. So one of two things is happening:
1. The computer chart system, when it sees “memantine” entered, searches its database, finds what it’s FDA-approved for, and automatically puts that in a list of current diagnoses.
2. The person entering the data, upon hearing the patient takes memantine, just enters the more commonly used indication as well, without bothering to ask the patient why they’re taking it.
Neither of these is good.
At the very least, they show a lack of proper history taking (or interest in doing so) by the person entering things in the chart (which these days could be someone with no medical training at all). It doesn’t take that much effort to say “what are you on this for?” I do it several times a day. It’s part of my job.
It’s bad form for any incorrect diagnosis to get into a chart. It can have serious repercussions on someone’s ability to get health, disability, or life insurance, not to mention the immediate impact on their care when that shows up. Someone who doesn’t know the patient opens the chart and immediately assumes it’s what they’ve got. I mean, it’s the chart. People treat it like it’s infallible and inviolable.
This isn’t a new issue – I trained at the VA when sometimes an H&P simply said “see old chart” and there were four volumes of it. But now, in the age of digital records, entries are forever. The toe you fractured surfing 8 years ago still shows up as a “current problem,” and will likely follow you to the grave. The same with any other diagnosis entered – it’s yours to keep, regardless of accuracy.
Medicine, like life, is mostly gray. But computers, and many times those who enter their data, only see things as black and white. In this field that’s liable to backfire. I’m just seeing the tip of the iceberg by using memantine off-label.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Memantine (aka Namenda) is Food and Drug Administration–approved for Alzheimer’s disease, though its benefits are modest, at best.
It’s also, 18 years after first coming to market, relatively inexpensive.
I occasionally use it off label, as neurologists tend to do with a wide variety of medications. There are small studies that suggest it’s effective for migraine prevention and painful neuropathies. It also has a relatively benign side-effect profile.
As a result, once in a while I prescribe it for migraines or neuropathy where more typical agents haven’t helped. Like any of these drugs, sometimes it works, sometimes it doesn’t. A lot of neurology, as one of my colleagues puts it, is “guessing and voodoo.”
Since I’ve started this, however, I’ve noticed an unusual, and somewhat scary, side effect – one that has nothing to do the drug reactions.
While I don’t use any type of commercial chart system, most doctors in my area do, as well as all the hospitals. So I often see my patients’ notes from their general practitioners or after they’ve been in the hospital for whatever reason.
Those notes often list – as they should – current medications. Which includes the memantine I’ve prescribed.
But in the patient problem list I often then see “Alzheimer’s disease” or “dementia” show up, even in people who clearly have no history of such.
I’ve seen it way too many times to think it’s an accident. So one of two things is happening:
1. The computer chart system, when it sees “memantine” entered, searches its database, finds what it’s FDA-approved for, and automatically puts that in a list of current diagnoses.
2. The person entering the data, upon hearing the patient takes memantine, just enters the more commonly used indication as well, without bothering to ask the patient why they’re taking it.
Neither of these is good.
At the very least, they show a lack of proper history taking (or interest in doing so) by the person entering things in the chart (which these days could be someone with no medical training at all). It doesn’t take that much effort to say “what are you on this for?” I do it several times a day. It’s part of my job.
It’s bad form for any incorrect diagnosis to get into a chart. It can have serious repercussions on someone’s ability to get health, disability, or life insurance, not to mention the immediate impact on their care when that shows up. Someone who doesn’t know the patient opens the chart and immediately assumes it’s what they’ve got. I mean, it’s the chart. People treat it like it’s infallible and inviolable.
This isn’t a new issue – I trained at the VA when sometimes an H&P simply said “see old chart” and there were four volumes of it. But now, in the age of digital records, entries are forever. The toe you fractured surfing 8 years ago still shows up as a “current problem,” and will likely follow you to the grave. The same with any other diagnosis entered – it’s yours to keep, regardless of accuracy.
Medicine, like life, is mostly gray. But computers, and many times those who enter their data, only see things as black and white. In this field that’s liable to backfire. I’m just seeing the tip of the iceberg by using memantine off-label.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Memantine (aka Namenda) is Food and Drug Administration–approved for Alzheimer’s disease, though its benefits are modest, at best.
It’s also, 18 years after first coming to market, relatively inexpensive.
I occasionally use it off label, as neurologists tend to do with a wide variety of medications. There are small studies that suggest it’s effective for migraine prevention and painful neuropathies. It also has a relatively benign side-effect profile.
As a result, once in a while I prescribe it for migraines or neuropathy where more typical agents haven’t helped. Like any of these drugs, sometimes it works, sometimes it doesn’t. A lot of neurology, as one of my colleagues puts it, is “guessing and voodoo.”
Since I’ve started this, however, I’ve noticed an unusual, and somewhat scary, side effect – one that has nothing to do the drug reactions.
While I don’t use any type of commercial chart system, most doctors in my area do, as well as all the hospitals. So I often see my patients’ notes from their general practitioners or after they’ve been in the hospital for whatever reason.
Those notes often list – as they should – current medications. Which includes the memantine I’ve prescribed.
But in the patient problem list I often then see “Alzheimer’s disease” or “dementia” show up, even in people who clearly have no history of such.
I’ve seen it way too many times to think it’s an accident. So one of two things is happening:
1. The computer chart system, when it sees “memantine” entered, searches its database, finds what it’s FDA-approved for, and automatically puts that in a list of current diagnoses.
2. The person entering the data, upon hearing the patient takes memantine, just enters the more commonly used indication as well, without bothering to ask the patient why they’re taking it.
Neither of these is good.
At the very least, they show a lack of proper history taking (or interest in doing so) by the person entering things in the chart (which these days could be someone with no medical training at all). It doesn’t take that much effort to say “what are you on this for?” I do it several times a day. It’s part of my job.
It’s bad form for any incorrect diagnosis to get into a chart. It can have serious repercussions on someone’s ability to get health, disability, or life insurance, not to mention the immediate impact on their care when that shows up. Someone who doesn’t know the patient opens the chart and immediately assumes it’s what they’ve got. I mean, it’s the chart. People treat it like it’s infallible and inviolable.
This isn’t a new issue – I trained at the VA when sometimes an H&P simply said “see old chart” and there were four volumes of it. But now, in the age of digital records, entries are forever. The toe you fractured surfing 8 years ago still shows up as a “current problem,” and will likely follow you to the grave. The same with any other diagnosis entered – it’s yours to keep, regardless of accuracy.
Medicine, like life, is mostly gray. But computers, and many times those who enter their data, only see things as black and white. In this field that’s liable to backfire. I’m just seeing the tip of the iceberg by using memantine off-label.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Reproductive safety of treatments for women with bipolar disorder
Since March 2020, my colleagues and I have conducted Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital. It has been an opportunity to review the basic tenets of care for reproductive age women before, during, and after pregnancy, and also to learn of extraordinary cases being managed both in the outpatient setting and in the context of the COVID-19 pandemic.
As I’ve noted in previous columns, we have seen a heightening of symptoms of anxiety and insomnia during the pandemic in women who visit our center, and at the centers of the more than 100 clinicians who join Virtual Rounds each week. These colleagues represent people in rural areas, urban environments, and underserved communities across America that have been severely affected by the pandemic. It is clear that the stress of the pandemic is undeniable for patients both with and without psychiatric or mental health issues. We have also seen clinical roughening in women who have been well for a long period of time. In particular, we have noticed that postpartum women are struggling with the stressors of the postpartum period, such as figuring out the logistics of support with respect to childcare, managing maternity leave, and adapting to shifting of anticipated support systems.
Hundreds of women with bipolar disorder come to see us each year about the reproductive safety of the medicines on which they are maintained. Those patients are typically well, and we collaborate with them and their doctors about the safest treatment recommendations. With that said, women with bipolar disorder are at particular risk for postpartum worsening of their mood. The management of their medications during pregnancy requires extremely careful attention because relapse of psychiatric disorder during pregnancy is the strongest predictor of postpartum worsening of underlying psychiatric illness.
This is an opportunity to briefly review the reproductive safety of treatments for these women. We know through initiatives such as the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications that the most widely used medicines for bipolar women during pregnancy include lamotrigine, atypical antipsychotics, and lithium carbonate.
Lamotrigine
The last 15 years have generated the most consistent data on the reproductive safety of lamotrigine. One of the issues, however, with respect to lamotrigine is that its use requires very careful and slow titration and it is also more effective in patients who are well and in the maintenance phase of the illness versus those who are more acutely manic or who are suffering from frank bipolar depression.
Critically, the literature does not support the use of lamotrigine for patients with bipolar I or with more manic symptoms. That being said, it remains a mainstay of treatment for many patients with bipolar disorder, is easy to use across pregnancy, and has an attractive side-effect profile and a very strong reproductive safety profile, suggesting the absence of an increased risk for major malformations.
Atypical antipsychotics
We have less information but have a growing body of evidence about atypical antipsychotics. Both data from administrative databases as well a growing literature from pregnancy registries, such as the National Pregnancy Registry for Atypical Antipsychotics, fail to show a signal for teratogenicity with respect to use of the medicines as a class, and also with specific reference to some of the most widely used atypical antipsychotics, particularly quetiapine and aripiprazole. Our comfort level, compared with a decade ago, with using the second-generation antipsychotics is much greater. That’s a good thing considering the extent to which patients presenting on a combination of, for example, lamotrigine and atypical antipsychotics.
Lithium carbonate
Another mainstay of treatment for women with bipolar I disorder and prominent symptoms of mania is lithium carbonate. The data for efficacy of lithium carbonate used both acutely and for maintenance treatment of bipolar disorder has been unequivocal. Concerns about the teratogenicity of lithium go back to the 1970s and indicate a small increased absolute and relative risk for cardiovascular malformations. More recently, a meta-analysis of lithium exposure during pregnancy and the postpartum period supports this older data, which suggests this increased risk, and examines other outcomes concerning to women with bipolar disorder who use lithium, such as preterm labor, low birth weight, miscarriage, and other adverse neonatal outcomes.
In 2021, with the backdrop of the pandemic, what we actually see is that, for our pregnant and postpartum patients with bipolar disorder, the imperative to keep them well, keep them out of the hospital, and keep them safe has often required careful coadministration of drugs like lamotrigine, lithium, and atypical antipsychotics (and even benzodiazepines). Keeping this population well during the perinatal period is so critical. We were all trained to use the least number of medications when possible across psychiatric illnesses. But the years, data, and clinical experience have shown that polypharmacy may be required to sustain euthymia in many patients with bipolar disorder. The reflex historically has been to stop medications during pregnancy. We take pause, particularly during the pandemic, before reverting back to the practice of 25 years ago of abruptly stopping medicines such as lithium or atypical antipsychotics in patients with bipolar disorder because we know that the risk for relapse is very high following a shift from the regimen that got the patient well.
The COVID-19 pandemic in many respects has highlighted a need to clinically thread the needle with respect to developing a regimen that minimizes risk of reproductive safety concerns but maximizes the likelihood that we can sustain the emotional well-being of these women across pregnancy and into the postpartum period.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
Since March 2020, my colleagues and I have conducted Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital. It has been an opportunity to review the basic tenets of care for reproductive age women before, during, and after pregnancy, and also to learn of extraordinary cases being managed both in the outpatient setting and in the context of the COVID-19 pandemic.
As I’ve noted in previous columns, we have seen a heightening of symptoms of anxiety and insomnia during the pandemic in women who visit our center, and at the centers of the more than 100 clinicians who join Virtual Rounds each week. These colleagues represent people in rural areas, urban environments, and underserved communities across America that have been severely affected by the pandemic. It is clear that the stress of the pandemic is undeniable for patients both with and without psychiatric or mental health issues. We have also seen clinical roughening in women who have been well for a long period of time. In particular, we have noticed that postpartum women are struggling with the stressors of the postpartum period, such as figuring out the logistics of support with respect to childcare, managing maternity leave, and adapting to shifting of anticipated support systems.
Hundreds of women with bipolar disorder come to see us each year about the reproductive safety of the medicines on which they are maintained. Those patients are typically well, and we collaborate with them and their doctors about the safest treatment recommendations. With that said, women with bipolar disorder are at particular risk for postpartum worsening of their mood. The management of their medications during pregnancy requires extremely careful attention because relapse of psychiatric disorder during pregnancy is the strongest predictor of postpartum worsening of underlying psychiatric illness.
This is an opportunity to briefly review the reproductive safety of treatments for these women. We know through initiatives such as the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications that the most widely used medicines for bipolar women during pregnancy include lamotrigine, atypical antipsychotics, and lithium carbonate.
Lamotrigine
The last 15 years have generated the most consistent data on the reproductive safety of lamotrigine. One of the issues, however, with respect to lamotrigine is that its use requires very careful and slow titration and it is also more effective in patients who are well and in the maintenance phase of the illness versus those who are more acutely manic or who are suffering from frank bipolar depression.
Critically, the literature does not support the use of lamotrigine for patients with bipolar I or with more manic symptoms. That being said, it remains a mainstay of treatment for many patients with bipolar disorder, is easy to use across pregnancy, and has an attractive side-effect profile and a very strong reproductive safety profile, suggesting the absence of an increased risk for major malformations.
Atypical antipsychotics
We have less information but have a growing body of evidence about atypical antipsychotics. Both data from administrative databases as well a growing literature from pregnancy registries, such as the National Pregnancy Registry for Atypical Antipsychotics, fail to show a signal for teratogenicity with respect to use of the medicines as a class, and also with specific reference to some of the most widely used atypical antipsychotics, particularly quetiapine and aripiprazole. Our comfort level, compared with a decade ago, with using the second-generation antipsychotics is much greater. That’s a good thing considering the extent to which patients presenting on a combination of, for example, lamotrigine and atypical antipsychotics.
Lithium carbonate
Another mainstay of treatment for women with bipolar I disorder and prominent symptoms of mania is lithium carbonate. The data for efficacy of lithium carbonate used both acutely and for maintenance treatment of bipolar disorder has been unequivocal. Concerns about the teratogenicity of lithium go back to the 1970s and indicate a small increased absolute and relative risk for cardiovascular malformations. More recently, a meta-analysis of lithium exposure during pregnancy and the postpartum period supports this older data, which suggests this increased risk, and examines other outcomes concerning to women with bipolar disorder who use lithium, such as preterm labor, low birth weight, miscarriage, and other adverse neonatal outcomes.
In 2021, with the backdrop of the pandemic, what we actually see is that, for our pregnant and postpartum patients with bipolar disorder, the imperative to keep them well, keep them out of the hospital, and keep them safe has often required careful coadministration of drugs like lamotrigine, lithium, and atypical antipsychotics (and even benzodiazepines). Keeping this population well during the perinatal period is so critical. We were all trained to use the least number of medications when possible across psychiatric illnesses. But the years, data, and clinical experience have shown that polypharmacy may be required to sustain euthymia in many patients with bipolar disorder. The reflex historically has been to stop medications during pregnancy. We take pause, particularly during the pandemic, before reverting back to the practice of 25 years ago of abruptly stopping medicines such as lithium or atypical antipsychotics in patients with bipolar disorder because we know that the risk for relapse is very high following a shift from the regimen that got the patient well.
The COVID-19 pandemic in many respects has highlighted a need to clinically thread the needle with respect to developing a regimen that minimizes risk of reproductive safety concerns but maximizes the likelihood that we can sustain the emotional well-being of these women across pregnancy and into the postpartum period.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
Since March 2020, my colleagues and I have conducted Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital. It has been an opportunity to review the basic tenets of care for reproductive age women before, during, and after pregnancy, and also to learn of extraordinary cases being managed both in the outpatient setting and in the context of the COVID-19 pandemic.
As I’ve noted in previous columns, we have seen a heightening of symptoms of anxiety and insomnia during the pandemic in women who visit our center, and at the centers of the more than 100 clinicians who join Virtual Rounds each week. These colleagues represent people in rural areas, urban environments, and underserved communities across America that have been severely affected by the pandemic. It is clear that the stress of the pandemic is undeniable for patients both with and without psychiatric or mental health issues. We have also seen clinical roughening in women who have been well for a long period of time. In particular, we have noticed that postpartum women are struggling with the stressors of the postpartum period, such as figuring out the logistics of support with respect to childcare, managing maternity leave, and adapting to shifting of anticipated support systems.
Hundreds of women with bipolar disorder come to see us each year about the reproductive safety of the medicines on which they are maintained. Those patients are typically well, and we collaborate with them and their doctors about the safest treatment recommendations. With that said, women with bipolar disorder are at particular risk for postpartum worsening of their mood. The management of their medications during pregnancy requires extremely careful attention because relapse of psychiatric disorder during pregnancy is the strongest predictor of postpartum worsening of underlying psychiatric illness.
This is an opportunity to briefly review the reproductive safety of treatments for these women. We know through initiatives such as the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications that the most widely used medicines for bipolar women during pregnancy include lamotrigine, atypical antipsychotics, and lithium carbonate.
Lamotrigine
The last 15 years have generated the most consistent data on the reproductive safety of lamotrigine. One of the issues, however, with respect to lamotrigine is that its use requires very careful and slow titration and it is also more effective in patients who are well and in the maintenance phase of the illness versus those who are more acutely manic or who are suffering from frank bipolar depression.
Critically, the literature does not support the use of lamotrigine for patients with bipolar I or with more manic symptoms. That being said, it remains a mainstay of treatment for many patients with bipolar disorder, is easy to use across pregnancy, and has an attractive side-effect profile and a very strong reproductive safety profile, suggesting the absence of an increased risk for major malformations.
Atypical antipsychotics
We have less information but have a growing body of evidence about atypical antipsychotics. Both data from administrative databases as well a growing literature from pregnancy registries, such as the National Pregnancy Registry for Atypical Antipsychotics, fail to show a signal for teratogenicity with respect to use of the medicines as a class, and also with specific reference to some of the most widely used atypical antipsychotics, particularly quetiapine and aripiprazole. Our comfort level, compared with a decade ago, with using the second-generation antipsychotics is much greater. That’s a good thing considering the extent to which patients presenting on a combination of, for example, lamotrigine and atypical antipsychotics.
Lithium carbonate
Another mainstay of treatment for women with bipolar I disorder and prominent symptoms of mania is lithium carbonate. The data for efficacy of lithium carbonate used both acutely and for maintenance treatment of bipolar disorder has been unequivocal. Concerns about the teratogenicity of lithium go back to the 1970s and indicate a small increased absolute and relative risk for cardiovascular malformations. More recently, a meta-analysis of lithium exposure during pregnancy and the postpartum period supports this older data, which suggests this increased risk, and examines other outcomes concerning to women with bipolar disorder who use lithium, such as preterm labor, low birth weight, miscarriage, and other adverse neonatal outcomes.
In 2021, with the backdrop of the pandemic, what we actually see is that, for our pregnant and postpartum patients with bipolar disorder, the imperative to keep them well, keep them out of the hospital, and keep them safe has often required careful coadministration of drugs like lamotrigine, lithium, and atypical antipsychotics (and even benzodiazepines). Keeping this population well during the perinatal period is so critical. We were all trained to use the least number of medications when possible across psychiatric illnesses. But the years, data, and clinical experience have shown that polypharmacy may be required to sustain euthymia in many patients with bipolar disorder. The reflex historically has been to stop medications during pregnancy. We take pause, particularly during the pandemic, before reverting back to the practice of 25 years ago of abruptly stopping medicines such as lithium or atypical antipsychotics in patients with bipolar disorder because we know that the risk for relapse is very high following a shift from the regimen that got the patient well.
The COVID-19 pandemic in many respects has highlighted a need to clinically thread the needle with respect to developing a regimen that minimizes risk of reproductive safety concerns but maximizes the likelihood that we can sustain the emotional well-being of these women across pregnancy and into the postpartum period.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
The revenge of the ‘late COVID adopters’
The COVID-19 pandemic has stressed all aspects of the world’s health care systems. The sheer volume of pandemic-related research produced over the past year has been challenging to process. This is as it should be, given its unprecedented spread and related morbidity and mortality. However, such rapid production and application leaves little time for proper vetting. Large numbers of providers adopted suggested, but largely unproven, practices that deviated from pre–COVID-19 guidelines. These “early adopters” theorized that COVID-19–related disease processes were different, necessitating a modification to existing practices.
Other equally prominent researchers countered this argument. Martin Tobin drew on physiology, while Arthur Slutsky and Niall Ferguson used emerging data to make their case. Tobin and colleagues cautioned against early intubation for anyone who could be maintained using noninvasive support. In August 2020 (well into the pandemic and after more data were available), Slutsky and colleagues argued that ARDS caused by COVID-19 wasn’t much different from lung injury due to other causes.
Two more recent studies published online recently are relevant to the debate over COVID-19 ARDS. One was a prospective study and the other a retrospective study; both had comparison groups, and both came to the same conclusions. Overall, COVID-19 ARDS isn’t much different from ARDS due to other causes. These studies were comprehensive in their comparisons and measures of outcomes, but they were both rather small and included patients from one and two hospitals, respectively. The discussions of both provide a nice review of the existing literature on COVID-19 ARDS.
A second controversial, but unproven, COVID-19 practice is aggressive anticoagulation. Early reports of a high prevalence of venous thromboembolism (VTE) in patients with COVID-19 pushed many to recommend empirically increasing prophylaxis. Most of the data guiding this approach were from retrospective, observational studies that suffered from selection bias. Early on, many of the studies were from China, where baseline VTE prophylaxis rates were low. Despite these limitations, many physicians acted on the basis of these data. An arbitrarily defined “intermediate” or treatment dose for prophylaxis was used, with some measuring D-dimer to guide their approach. An evidence-based argument against this practice, published in the New England Journal of Medicine, failed to sway readers. (Look at the poll at the end of the article and you’ll see how readers answered.)
Two articles recently published online in CHEST attempted to bring clarity to the debate over COVID-19 and VTE prophylaxis. The first study evaluated critically ill patients in France, and researchers found that higher doses of anticoagulation reduced thrombotic complications without an associated increase in bleeding events. The study is well done but certainly has its flaws. It is observational and retrospective, and it essentially uses a before-after comparison technique. Such an approach is particularly prone to bias during COVID-19, given that practice patterns change quickly.
The second paper is a systematic review looking at VTE and bleeding rates among patients hospitalized with COVID-19. The authors found high rates of VTE (17.0% overall), with screening, admission to the ICU, and the prospective study design all being associated with increased rates. Of importance, unlike the retrospective trial cited in the previous paragraph, the authors of the systematic review found treatment-dose anticoagulation was associated with higher bleeding rates.
I admit, the title of this piece is a bit of a misnomer. The “late adopters” would truly have their revenge if deviation from guidelines for COVID-19–related ARDS and VTE prophylaxis proves to be harmful. It’s not clear that’s the case, and at least for VTE prophylaxis, results from several randomized, controlled trials (REMAP-CAP, ATTACC, and ACTIV-4a) will be released soon. These are sure to provide more definitive answers. If nothing else, the COVID-19–related ARDS and VTE data reinforce how difficult it is to obtain high-quality data that yield clear results. Until something more definitive is published and released, I will remain a “late adopter.” Standard non–COVID-19 guidelines for ARDS and VTE prophylaxis are good enough for me.
Dr. Holley is program director of the Pulmonary and Critical Care Medical Fellowship at Walter Reed National Military Medical Center, Bethesda, Md.
A version of this article first appeared on Medscape.com.
The COVID-19 pandemic has stressed all aspects of the world’s health care systems. The sheer volume of pandemic-related research produced over the past year has been challenging to process. This is as it should be, given its unprecedented spread and related morbidity and mortality. However, such rapid production and application leaves little time for proper vetting. Large numbers of providers adopted suggested, but largely unproven, practices that deviated from pre–COVID-19 guidelines. These “early adopters” theorized that COVID-19–related disease processes were different, necessitating a modification to existing practices.
Other equally prominent researchers countered this argument. Martin Tobin drew on physiology, while Arthur Slutsky and Niall Ferguson used emerging data to make their case. Tobin and colleagues cautioned against early intubation for anyone who could be maintained using noninvasive support. In August 2020 (well into the pandemic and after more data were available), Slutsky and colleagues argued that ARDS caused by COVID-19 wasn’t much different from lung injury due to other causes.
Two more recent studies published online recently are relevant to the debate over COVID-19 ARDS. One was a prospective study and the other a retrospective study; both had comparison groups, and both came to the same conclusions. Overall, COVID-19 ARDS isn’t much different from ARDS due to other causes. These studies were comprehensive in their comparisons and measures of outcomes, but they were both rather small and included patients from one and two hospitals, respectively. The discussions of both provide a nice review of the existing literature on COVID-19 ARDS.
A second controversial, but unproven, COVID-19 practice is aggressive anticoagulation. Early reports of a high prevalence of venous thromboembolism (VTE) in patients with COVID-19 pushed many to recommend empirically increasing prophylaxis. Most of the data guiding this approach were from retrospective, observational studies that suffered from selection bias. Early on, many of the studies were from China, where baseline VTE prophylaxis rates were low. Despite these limitations, many physicians acted on the basis of these data. An arbitrarily defined “intermediate” or treatment dose for prophylaxis was used, with some measuring D-dimer to guide their approach. An evidence-based argument against this practice, published in the New England Journal of Medicine, failed to sway readers. (Look at the poll at the end of the article and you’ll see how readers answered.)
Two articles recently published online in CHEST attempted to bring clarity to the debate over COVID-19 and VTE prophylaxis. The first study evaluated critically ill patients in France, and researchers found that higher doses of anticoagulation reduced thrombotic complications without an associated increase in bleeding events. The study is well done but certainly has its flaws. It is observational and retrospective, and it essentially uses a before-after comparison technique. Such an approach is particularly prone to bias during COVID-19, given that practice patterns change quickly.
The second paper is a systematic review looking at VTE and bleeding rates among patients hospitalized with COVID-19. The authors found high rates of VTE (17.0% overall), with screening, admission to the ICU, and the prospective study design all being associated with increased rates. Of importance, unlike the retrospective trial cited in the previous paragraph, the authors of the systematic review found treatment-dose anticoagulation was associated with higher bleeding rates.
I admit, the title of this piece is a bit of a misnomer. The “late adopters” would truly have their revenge if deviation from guidelines for COVID-19–related ARDS and VTE prophylaxis proves to be harmful. It’s not clear that’s the case, and at least for VTE prophylaxis, results from several randomized, controlled trials (REMAP-CAP, ATTACC, and ACTIV-4a) will be released soon. These are sure to provide more definitive answers. If nothing else, the COVID-19–related ARDS and VTE data reinforce how difficult it is to obtain high-quality data that yield clear results. Until something more definitive is published and released, I will remain a “late adopter.” Standard non–COVID-19 guidelines for ARDS and VTE prophylaxis are good enough for me.
Dr. Holley is program director of the Pulmonary and Critical Care Medical Fellowship at Walter Reed National Military Medical Center, Bethesda, Md.
A version of this article first appeared on Medscape.com.
The COVID-19 pandemic has stressed all aspects of the world’s health care systems. The sheer volume of pandemic-related research produced over the past year has been challenging to process. This is as it should be, given its unprecedented spread and related morbidity and mortality. However, such rapid production and application leaves little time for proper vetting. Large numbers of providers adopted suggested, but largely unproven, practices that deviated from pre–COVID-19 guidelines. These “early adopters” theorized that COVID-19–related disease processes were different, necessitating a modification to existing practices.
Other equally prominent researchers countered this argument. Martin Tobin drew on physiology, while Arthur Slutsky and Niall Ferguson used emerging data to make their case. Tobin and colleagues cautioned against early intubation for anyone who could be maintained using noninvasive support. In August 2020 (well into the pandemic and after more data were available), Slutsky and colleagues argued that ARDS caused by COVID-19 wasn’t much different from lung injury due to other causes.
Two more recent studies published online recently are relevant to the debate over COVID-19 ARDS. One was a prospective study and the other a retrospective study; both had comparison groups, and both came to the same conclusions. Overall, COVID-19 ARDS isn’t much different from ARDS due to other causes. These studies were comprehensive in their comparisons and measures of outcomes, but they were both rather small and included patients from one and two hospitals, respectively. The discussions of both provide a nice review of the existing literature on COVID-19 ARDS.
A second controversial, but unproven, COVID-19 practice is aggressive anticoagulation. Early reports of a high prevalence of venous thromboembolism (VTE) in patients with COVID-19 pushed many to recommend empirically increasing prophylaxis. Most of the data guiding this approach were from retrospective, observational studies that suffered from selection bias. Early on, many of the studies were from China, where baseline VTE prophylaxis rates were low. Despite these limitations, many physicians acted on the basis of these data. An arbitrarily defined “intermediate” or treatment dose for prophylaxis was used, with some measuring D-dimer to guide their approach. An evidence-based argument against this practice, published in the New England Journal of Medicine, failed to sway readers. (Look at the poll at the end of the article and you’ll see how readers answered.)
Two articles recently published online in CHEST attempted to bring clarity to the debate over COVID-19 and VTE prophylaxis. The first study evaluated critically ill patients in France, and researchers found that higher doses of anticoagulation reduced thrombotic complications without an associated increase in bleeding events. The study is well done but certainly has its flaws. It is observational and retrospective, and it essentially uses a before-after comparison technique. Such an approach is particularly prone to bias during COVID-19, given that practice patterns change quickly.
The second paper is a systematic review looking at VTE and bleeding rates among patients hospitalized with COVID-19. The authors found high rates of VTE (17.0% overall), with screening, admission to the ICU, and the prospective study design all being associated with increased rates. Of importance, unlike the retrospective trial cited in the previous paragraph, the authors of the systematic review found treatment-dose anticoagulation was associated with higher bleeding rates.
I admit, the title of this piece is a bit of a misnomer. The “late adopters” would truly have their revenge if deviation from guidelines for COVID-19–related ARDS and VTE prophylaxis proves to be harmful. It’s not clear that’s the case, and at least for VTE prophylaxis, results from several randomized, controlled trials (REMAP-CAP, ATTACC, and ACTIV-4a) will be released soon. These are sure to provide more definitive answers. If nothing else, the COVID-19–related ARDS and VTE data reinforce how difficult it is to obtain high-quality data that yield clear results. Until something more definitive is published and released, I will remain a “late adopter.” Standard non–COVID-19 guidelines for ARDS and VTE prophylaxis are good enough for me.
Dr. Holley is program director of the Pulmonary and Critical Care Medical Fellowship at Walter Reed National Military Medical Center, Bethesda, Md.
A version of this article first appeared on Medscape.com.
How has the pandemic changed your personal/professional priorities?
COVID-19: Remaining flexible amid the uncertainty
Editor’s Note: With 1 year of the COVID-19 pandemic in the rearview mirror, we decided to check in with the Editorial Advisory Board members of Clinical Psychiatry News about the impact it has had on their practices and lives.
Redefining how to engage
The COVID-19 pandemic has triggered a wave of mental health problems in our population, such as general stress, addiction, weight gain, depression, and social isolation, and these symptoms are exacerbated in mental health patients who are already struggling to cope with personal issues.
When the pandemic lockdown was announced in March 2020, many of my patients became overwhelmed and panicked at the idea of not being able to come to my office for in-person therapy. As an alternative, I started phone call sessions with my clients. These calls forced me to listen extra carefully to patient voice intonations to ascertain their true feelings, since I was unable to view the clients.
Soon thereafter, I transitioned to telemedicine over the Internet, and this visual helped me assess each patient. In addition, my patients became accustomed to telemedicine and embraced it once they saw me and were able to interact with me on the screen.
Although the pandemic disrupted my medical practice, it has redefined the way I can do therapy, as I can practice medicine from a distance. Telemedicine is time efficient for both my patients and me and it provides extreme social distancing, eliminating COVID-19 exposure between doctor and patient.
The pandemic has forced me to be adaptable and to recognize that, if you are open to changing habits, you can find a solution to any situation, including a pandemic.
Richard W. Cohen, MD
Private Practice
Philadelphia
Adjusting to fate
As it became clear in January 2020 that a pandemic was upon us, I made plans and prepared. I needed to remain healthy for my patients and my 102-year-old best friend, Doc.
I purchased PPE and 6 months’ of nonperishable groceries and toilet tissue from a commercial vendor. I made certain that Doc’s caregivers had what they needed to care for him and their families and preached to them, family, patients, and friends the public health guidelines of the day. Also, I needed to remain healthy for my patients who live in a dementia care facility, and I joined other workers there in being careful and proud that our facility remained COVID free.
By March 2020, I left my office, because it was in a building where both residents and staff were becoming ill with COVID. I started audio and video telemedicine as well as standing outside the windows of patients who only read lips and do not use digital technology. Under these new circumstances, patients (and Doc) revealed things about themselves that had remained hidden for decades. There was a sense of urgency and uncertainty.
I also started weekly COVID testing, at first at CVS and then in a public park. Doc, who had had congestive heart failure for 2 years, had celebrated his 103rd birthday in February, and continued to be a source of encouragement and support. We weathered through the spring and summer with him on lockdown in his senior residence. The dementia care facility remained free of COVID.
My plan had been to return to my office in July, however, the facility manager determined that they were not ready to receive my outpatients. I took on a short-term lease for August and was told I could return to my regular office Sept. 1, which I did.
On Aug. 31, 2020, Doc had a middle cerebral artery stroke. He received the clot buster within 40 minutes and was in surgery within 90 minutes. He regained consciousness and lucidity but would always have a left-sided disability. During his third postoperative day he was told that he would never again swallow properly, and he yanked out his nasogastric tube. He had always told me that he would not accept artificial feeding. M. Leslie Felmly, MD, a psychiatrist, died on Sept. 12, 2020, and I buried him beside his family in New Jersey, on Sept. 22, 2020.
After that, I needed routine and normalcy, and therefore, stayed out of work only on the day of Doc’s burial. I took on new patients and continued with my old patients. As the holidays neared I braced myself; for 26 years I had spent Thanksgiving and New Year’s with Doc and Christmas with my family in Texas. None of that was going to happen in 2020. My best female friend and her husband invited me to a socially distanced Thanksgiving meal with the two of them, and I accepted. Christmas and New Year’s I spent alone (I live alone and enjoy my company). Both of those holidays were made special because I spent the eve days at the dementia care facility.
I received my first Pfizer injection on Jan. 6, 2021. One day later, I went to a park to get COVID testing before I returned to the dementia care facility. There, I learned that I was COVID positive, and when I called into the dementia facility, I learned that one resident and several staff members had also tested positive. As I stood in the sunshine outside the testing facility I thought: “So, now what will I do with the rest of my life?”
I began to feel profoundly tired, and over time, developed what felt like a very bad head cold. I had no high temperature or difficulty breathing. Truly, the worst of it was the profound fatigue and the terrorizing fear that I would develop problems breathing. By Jan. 21, I had only symptoms of fatigue, and on the 23rd, I had a negative COVID test. I attributed my course and recovery to my whole-food plant-based diet and routine high-dose vitamin D3 – in spite of my being an overweight, older African American woman. Through it all, I learned to ask for help, and one of my colleagues brought me a thermometer and 2 days of vegan Pho. I learned to be resourceful and ordered myself a fruit basket from Edible Arrangements when I was too fatigued to arrange deliveries by computer. I told Edible Arrangements that I was too weak to cut up a pineapple, and the manager included a cut-up pineapple in the box. I am grateful for the kindness of others.
I returned to work Jan. 25, and for most of each day, I feel better than I have ever felt in my adult life. It is amazing what 2 solid weeks can do for 50 years of arrears of sleep. The overwhelming fatigue was such that I could not not sleep. Thankfully, my remaining fatigue is less and less each day.
On Jan. 27, 2021, I received my second COVID vaccine injection and had no adverse reaction. Then on the 28th, I learned that my male cousin, who was just 6 months younger than I am, died of complications of COVID. Later, I learned that a resident of the dementia care facility had died from the same outbreak that had sickened me.
Since the beginning of the pandemic, I had tried so hard to remain healthy and COVID free and have my family, friends, and patients do the same. I planned, prepared, and executed but fate had other plans in store. Doc and my cousin are gone; I was exposed to COVID in my dementia care facility; and I know what matters for the rest of my life. I will continue to pursue and espouse health for me, my family, my friends, and my patients, and I will endeavor to be the best family member, friend, and physician that I can. To help with this, I remember the wise words of Dr. Felmly, “Your level of frustration will rise directly with your level of expectation” and “Above all else, remain flexible.” Going forward, I am reminded that I am not in charge; I am grateful for so many things; and I will continue to be as flexible as I can be.
Thelissa A. Harris, MD
Private Practice
Hartford, Conn.
Taking time for reflection
One year into the pandemic, I continue to learn to expect the unexpected, anticipate that things may not go as planned, accept that it is not business as usual, appreciate what I have, and focus on what is most important in my life – my family and most especially my children.
Despite the disruptions in our daily lives from the lockdowns, quarantines, and social distancing, my Catholic faith has grown stronger. I am not overly religious, but since the pandemic my children and I have attended online Mass regularly, sometimes in far away churches with different languages. It seems like we listen better now, reflect more on the homilies, and are really more in touch with our spirituality.
Professionally, I have seen the pandemic bring together geriatric psychiatrists from around the globe to tackle issues relevant to the mental health care of older adults. Within the International Psychogeriatric Association, we were spurred into collaborative actions with international colleagues in advocating for human rights of older adults in the context of the pandemic, creating online educational activities, and contributing to the special COVID-19 issue of the International Psychogeriatrics journal.
Maria I. Lapid, MD
Mayo Clinic
Rochester, Minn.
Concentrating on safety
The first year of the pandemic is over. How have my personal and professional goals changed? How has my life changed? Let us start with the latter.
I have been very lucky. I have continued to go into work at my hospital every day, which provides structure and socializing. My hospital has supplied PPE, although, like everywhere else, the rules keep changing.
Masks, face shield, goggles, etc.: I try to loop the mask around my earrings just right so it does not catch and pull the hooks off. I think the goggles make me look cool, like an ant man.
My world has narrowed to work and home. Like all of us, I no longer go to conferences. I do outpatient treatment from my office desk. I see inpatients from 6 feet away, in mask and goggles. The cookies I pass out are now individually wrapped. Takeout instead of restaurants. A new home gym.
I have learned a lot. I now know how to manage psychiatric wards where COVID clusters occur. How to transfer psychiatric patients who convert to COVID positive over to the medicine ward. I faithfully swab my own nose twice a week.
I am constantly saying (very nicely): “Please pull your mask up over your nose.” “Six feet apart, please.”
I saved my surgical masks in case I needed to reuse them. Fortunately, I did not. Now I have three overflowing drawers of masks. Plus, the heavy homemade cloth ones that friends and family sent.
Back to how have my goals changed? Basically they have not. I fix my eyes straight ahead and concentrate on safety. Safety of patients, staff, my family, myself.
And daily add another yellow, or blue, or white, surgical mask to the drawers.
Elspeth Cameron Ritchie, MD, MPH
Washington
Awaiting project’s return
I had been actively involved in community service as the cofounder of The Bold Beauty Project since 2015. We are a Miami-based nonprofit, and we pair women with disabilities with volunteer photographers and create art shows. Our motto: Disability becomes Beauty becomes Art becomes Change.
I have dedicated about half of my time to the project, and it has been incredibly rewarding. It all came to a halt in March 2020, and it has left a real void in my daily schedule and my psyche. I am eagerly awaiting the return of the Bold Beauty Project with a renewed appreciation and enthusiasm. I hope you will check us out boldbeautyproject.com. If you are inspired to get involved, please contact me at [email protected].
Eva Ritvo, MD
Private Practice
Miami Beach, Fla.
COVID-19: Remaining flexible amid the uncertainty
COVID-19: Remaining flexible amid the uncertainty
Editor’s Note: With 1 year of the COVID-19 pandemic in the rearview mirror, we decided to check in with the Editorial Advisory Board members of Clinical Psychiatry News about the impact it has had on their practices and lives.
Redefining how to engage
The COVID-19 pandemic has triggered a wave of mental health problems in our population, such as general stress, addiction, weight gain, depression, and social isolation, and these symptoms are exacerbated in mental health patients who are already struggling to cope with personal issues.
When the pandemic lockdown was announced in March 2020, many of my patients became overwhelmed and panicked at the idea of not being able to come to my office for in-person therapy. As an alternative, I started phone call sessions with my clients. These calls forced me to listen extra carefully to patient voice intonations to ascertain their true feelings, since I was unable to view the clients.
Soon thereafter, I transitioned to telemedicine over the Internet, and this visual helped me assess each patient. In addition, my patients became accustomed to telemedicine and embraced it once they saw me and were able to interact with me on the screen.
Although the pandemic disrupted my medical practice, it has redefined the way I can do therapy, as I can practice medicine from a distance. Telemedicine is time efficient for both my patients and me and it provides extreme social distancing, eliminating COVID-19 exposure between doctor and patient.
The pandemic has forced me to be adaptable and to recognize that, if you are open to changing habits, you can find a solution to any situation, including a pandemic.
Richard W. Cohen, MD
Private Practice
Philadelphia
Adjusting to fate
As it became clear in January 2020 that a pandemic was upon us, I made plans and prepared. I needed to remain healthy for my patients and my 102-year-old best friend, Doc.
I purchased PPE and 6 months’ of nonperishable groceries and toilet tissue from a commercial vendor. I made certain that Doc’s caregivers had what they needed to care for him and their families and preached to them, family, patients, and friends the public health guidelines of the day. Also, I needed to remain healthy for my patients who live in a dementia care facility, and I joined other workers there in being careful and proud that our facility remained COVID free.
By March 2020, I left my office, because it was in a building where both residents and staff were becoming ill with COVID. I started audio and video telemedicine as well as standing outside the windows of patients who only read lips and do not use digital technology. Under these new circumstances, patients (and Doc) revealed things about themselves that had remained hidden for decades. There was a sense of urgency and uncertainty.
I also started weekly COVID testing, at first at CVS and then in a public park. Doc, who had had congestive heart failure for 2 years, had celebrated his 103rd birthday in February, and continued to be a source of encouragement and support. We weathered through the spring and summer with him on lockdown in his senior residence. The dementia care facility remained free of COVID.
My plan had been to return to my office in July, however, the facility manager determined that they were not ready to receive my outpatients. I took on a short-term lease for August and was told I could return to my regular office Sept. 1, which I did.
On Aug. 31, 2020, Doc had a middle cerebral artery stroke. He received the clot buster within 40 minutes and was in surgery within 90 minutes. He regained consciousness and lucidity but would always have a left-sided disability. During his third postoperative day he was told that he would never again swallow properly, and he yanked out his nasogastric tube. He had always told me that he would not accept artificial feeding. M. Leslie Felmly, MD, a psychiatrist, died on Sept. 12, 2020, and I buried him beside his family in New Jersey, on Sept. 22, 2020.
After that, I needed routine and normalcy, and therefore, stayed out of work only on the day of Doc’s burial. I took on new patients and continued with my old patients. As the holidays neared I braced myself; for 26 years I had spent Thanksgiving and New Year’s with Doc and Christmas with my family in Texas. None of that was going to happen in 2020. My best female friend and her husband invited me to a socially distanced Thanksgiving meal with the two of them, and I accepted. Christmas and New Year’s I spent alone (I live alone and enjoy my company). Both of those holidays were made special because I spent the eve days at the dementia care facility.
I received my first Pfizer injection on Jan. 6, 2021. One day later, I went to a park to get COVID testing before I returned to the dementia care facility. There, I learned that I was COVID positive, and when I called into the dementia facility, I learned that one resident and several staff members had also tested positive. As I stood in the sunshine outside the testing facility I thought: “So, now what will I do with the rest of my life?”
I began to feel profoundly tired, and over time, developed what felt like a very bad head cold. I had no high temperature or difficulty breathing. Truly, the worst of it was the profound fatigue and the terrorizing fear that I would develop problems breathing. By Jan. 21, I had only symptoms of fatigue, and on the 23rd, I had a negative COVID test. I attributed my course and recovery to my whole-food plant-based diet and routine high-dose vitamin D3 – in spite of my being an overweight, older African American woman. Through it all, I learned to ask for help, and one of my colleagues brought me a thermometer and 2 days of vegan Pho. I learned to be resourceful and ordered myself a fruit basket from Edible Arrangements when I was too fatigued to arrange deliveries by computer. I told Edible Arrangements that I was too weak to cut up a pineapple, and the manager included a cut-up pineapple in the box. I am grateful for the kindness of others.
I returned to work Jan. 25, and for most of each day, I feel better than I have ever felt in my adult life. It is amazing what 2 solid weeks can do for 50 years of arrears of sleep. The overwhelming fatigue was such that I could not not sleep. Thankfully, my remaining fatigue is less and less each day.
On Jan. 27, 2021, I received my second COVID vaccine injection and had no adverse reaction. Then on the 28th, I learned that my male cousin, who was just 6 months younger than I am, died of complications of COVID. Later, I learned that a resident of the dementia care facility had died from the same outbreak that had sickened me.
Since the beginning of the pandemic, I had tried so hard to remain healthy and COVID free and have my family, friends, and patients do the same. I planned, prepared, and executed but fate had other plans in store. Doc and my cousin are gone; I was exposed to COVID in my dementia care facility; and I know what matters for the rest of my life. I will continue to pursue and espouse health for me, my family, my friends, and my patients, and I will endeavor to be the best family member, friend, and physician that I can. To help with this, I remember the wise words of Dr. Felmly, “Your level of frustration will rise directly with your level of expectation” and “Above all else, remain flexible.” Going forward, I am reminded that I am not in charge; I am grateful for so many things; and I will continue to be as flexible as I can be.
Thelissa A. Harris, MD
Private Practice
Hartford, Conn.
Taking time for reflection
One year into the pandemic, I continue to learn to expect the unexpected, anticipate that things may not go as planned, accept that it is not business as usual, appreciate what I have, and focus on what is most important in my life – my family and most especially my children.
Despite the disruptions in our daily lives from the lockdowns, quarantines, and social distancing, my Catholic faith has grown stronger. I am not overly religious, but since the pandemic my children and I have attended online Mass regularly, sometimes in far away churches with different languages. It seems like we listen better now, reflect more on the homilies, and are really more in touch with our spirituality.
Professionally, I have seen the pandemic bring together geriatric psychiatrists from around the globe to tackle issues relevant to the mental health care of older adults. Within the International Psychogeriatric Association, we were spurred into collaborative actions with international colleagues in advocating for human rights of older adults in the context of the pandemic, creating online educational activities, and contributing to the special COVID-19 issue of the International Psychogeriatrics journal.
Maria I. Lapid, MD
Mayo Clinic
Rochester, Minn.
Concentrating on safety
The first year of the pandemic is over. How have my personal and professional goals changed? How has my life changed? Let us start with the latter.
I have been very lucky. I have continued to go into work at my hospital every day, which provides structure and socializing. My hospital has supplied PPE, although, like everywhere else, the rules keep changing.
Masks, face shield, goggles, etc.: I try to loop the mask around my earrings just right so it does not catch and pull the hooks off. I think the goggles make me look cool, like an ant man.
My world has narrowed to work and home. Like all of us, I no longer go to conferences. I do outpatient treatment from my office desk. I see inpatients from 6 feet away, in mask and goggles. The cookies I pass out are now individually wrapped. Takeout instead of restaurants. A new home gym.
I have learned a lot. I now know how to manage psychiatric wards where COVID clusters occur. How to transfer psychiatric patients who convert to COVID positive over to the medicine ward. I faithfully swab my own nose twice a week.
I am constantly saying (very nicely): “Please pull your mask up over your nose.” “Six feet apart, please.”
I saved my surgical masks in case I needed to reuse them. Fortunately, I did not. Now I have three overflowing drawers of masks. Plus, the heavy homemade cloth ones that friends and family sent.
Back to how have my goals changed? Basically they have not. I fix my eyes straight ahead and concentrate on safety. Safety of patients, staff, my family, myself.
And daily add another yellow, or blue, or white, surgical mask to the drawers.
Elspeth Cameron Ritchie, MD, MPH
Washington
Awaiting project’s return
I had been actively involved in community service as the cofounder of The Bold Beauty Project since 2015. We are a Miami-based nonprofit, and we pair women with disabilities with volunteer photographers and create art shows. Our motto: Disability becomes Beauty becomes Art becomes Change.
I have dedicated about half of my time to the project, and it has been incredibly rewarding. It all came to a halt in March 2020, and it has left a real void in my daily schedule and my psyche. I am eagerly awaiting the return of the Bold Beauty Project with a renewed appreciation and enthusiasm. I hope you will check us out boldbeautyproject.com. If you are inspired to get involved, please contact me at [email protected].
Eva Ritvo, MD
Private Practice
Miami Beach, Fla.
Editor’s Note: With 1 year of the COVID-19 pandemic in the rearview mirror, we decided to check in with the Editorial Advisory Board members of Clinical Psychiatry News about the impact it has had on their practices and lives.
Redefining how to engage
The COVID-19 pandemic has triggered a wave of mental health problems in our population, such as general stress, addiction, weight gain, depression, and social isolation, and these symptoms are exacerbated in mental health patients who are already struggling to cope with personal issues.
When the pandemic lockdown was announced in March 2020, many of my patients became overwhelmed and panicked at the idea of not being able to come to my office for in-person therapy. As an alternative, I started phone call sessions with my clients. These calls forced me to listen extra carefully to patient voice intonations to ascertain their true feelings, since I was unable to view the clients.
Soon thereafter, I transitioned to telemedicine over the Internet, and this visual helped me assess each patient. In addition, my patients became accustomed to telemedicine and embraced it once they saw me and were able to interact with me on the screen.
Although the pandemic disrupted my medical practice, it has redefined the way I can do therapy, as I can practice medicine from a distance. Telemedicine is time efficient for both my patients and me and it provides extreme social distancing, eliminating COVID-19 exposure between doctor and patient.
The pandemic has forced me to be adaptable and to recognize that, if you are open to changing habits, you can find a solution to any situation, including a pandemic.
Richard W. Cohen, MD
Private Practice
Philadelphia
Adjusting to fate
As it became clear in January 2020 that a pandemic was upon us, I made plans and prepared. I needed to remain healthy for my patients and my 102-year-old best friend, Doc.
I purchased PPE and 6 months’ of nonperishable groceries and toilet tissue from a commercial vendor. I made certain that Doc’s caregivers had what they needed to care for him and their families and preached to them, family, patients, and friends the public health guidelines of the day. Also, I needed to remain healthy for my patients who live in a dementia care facility, and I joined other workers there in being careful and proud that our facility remained COVID free.
By March 2020, I left my office, because it was in a building where both residents and staff were becoming ill with COVID. I started audio and video telemedicine as well as standing outside the windows of patients who only read lips and do not use digital technology. Under these new circumstances, patients (and Doc) revealed things about themselves that had remained hidden for decades. There was a sense of urgency and uncertainty.
I also started weekly COVID testing, at first at CVS and then in a public park. Doc, who had had congestive heart failure for 2 years, had celebrated his 103rd birthday in February, and continued to be a source of encouragement and support. We weathered through the spring and summer with him on lockdown in his senior residence. The dementia care facility remained free of COVID.
My plan had been to return to my office in July, however, the facility manager determined that they were not ready to receive my outpatients. I took on a short-term lease for August and was told I could return to my regular office Sept. 1, which I did.
On Aug. 31, 2020, Doc had a middle cerebral artery stroke. He received the clot buster within 40 minutes and was in surgery within 90 minutes. He regained consciousness and lucidity but would always have a left-sided disability. During his third postoperative day he was told that he would never again swallow properly, and he yanked out his nasogastric tube. He had always told me that he would not accept artificial feeding. M. Leslie Felmly, MD, a psychiatrist, died on Sept. 12, 2020, and I buried him beside his family in New Jersey, on Sept. 22, 2020.
After that, I needed routine and normalcy, and therefore, stayed out of work only on the day of Doc’s burial. I took on new patients and continued with my old patients. As the holidays neared I braced myself; for 26 years I had spent Thanksgiving and New Year’s with Doc and Christmas with my family in Texas. None of that was going to happen in 2020. My best female friend and her husband invited me to a socially distanced Thanksgiving meal with the two of them, and I accepted. Christmas and New Year’s I spent alone (I live alone and enjoy my company). Both of those holidays were made special because I spent the eve days at the dementia care facility.
I received my first Pfizer injection on Jan. 6, 2021. One day later, I went to a park to get COVID testing before I returned to the dementia care facility. There, I learned that I was COVID positive, and when I called into the dementia facility, I learned that one resident and several staff members had also tested positive. As I stood in the sunshine outside the testing facility I thought: “So, now what will I do with the rest of my life?”
I began to feel profoundly tired, and over time, developed what felt like a very bad head cold. I had no high temperature or difficulty breathing. Truly, the worst of it was the profound fatigue and the terrorizing fear that I would develop problems breathing. By Jan. 21, I had only symptoms of fatigue, and on the 23rd, I had a negative COVID test. I attributed my course and recovery to my whole-food plant-based diet and routine high-dose vitamin D3 – in spite of my being an overweight, older African American woman. Through it all, I learned to ask for help, and one of my colleagues brought me a thermometer and 2 days of vegan Pho. I learned to be resourceful and ordered myself a fruit basket from Edible Arrangements when I was too fatigued to arrange deliveries by computer. I told Edible Arrangements that I was too weak to cut up a pineapple, and the manager included a cut-up pineapple in the box. I am grateful for the kindness of others.
I returned to work Jan. 25, and for most of each day, I feel better than I have ever felt in my adult life. It is amazing what 2 solid weeks can do for 50 years of arrears of sleep. The overwhelming fatigue was such that I could not not sleep. Thankfully, my remaining fatigue is less and less each day.
On Jan. 27, 2021, I received my second COVID vaccine injection and had no adverse reaction. Then on the 28th, I learned that my male cousin, who was just 6 months younger than I am, died of complications of COVID. Later, I learned that a resident of the dementia care facility had died from the same outbreak that had sickened me.
Since the beginning of the pandemic, I had tried so hard to remain healthy and COVID free and have my family, friends, and patients do the same. I planned, prepared, and executed but fate had other plans in store. Doc and my cousin are gone; I was exposed to COVID in my dementia care facility; and I know what matters for the rest of my life. I will continue to pursue and espouse health for me, my family, my friends, and my patients, and I will endeavor to be the best family member, friend, and physician that I can. To help with this, I remember the wise words of Dr. Felmly, “Your level of frustration will rise directly with your level of expectation” and “Above all else, remain flexible.” Going forward, I am reminded that I am not in charge; I am grateful for so many things; and I will continue to be as flexible as I can be.
Thelissa A. Harris, MD
Private Practice
Hartford, Conn.
Taking time for reflection
One year into the pandemic, I continue to learn to expect the unexpected, anticipate that things may not go as planned, accept that it is not business as usual, appreciate what I have, and focus on what is most important in my life – my family and most especially my children.
Despite the disruptions in our daily lives from the lockdowns, quarantines, and social distancing, my Catholic faith has grown stronger. I am not overly religious, but since the pandemic my children and I have attended online Mass regularly, sometimes in far away churches with different languages. It seems like we listen better now, reflect more on the homilies, and are really more in touch with our spirituality.
Professionally, I have seen the pandemic bring together geriatric psychiatrists from around the globe to tackle issues relevant to the mental health care of older adults. Within the International Psychogeriatric Association, we were spurred into collaborative actions with international colleagues in advocating for human rights of older adults in the context of the pandemic, creating online educational activities, and contributing to the special COVID-19 issue of the International Psychogeriatrics journal.
Maria I. Lapid, MD
Mayo Clinic
Rochester, Minn.
Concentrating on safety
The first year of the pandemic is over. How have my personal and professional goals changed? How has my life changed? Let us start with the latter.
I have been very lucky. I have continued to go into work at my hospital every day, which provides structure and socializing. My hospital has supplied PPE, although, like everywhere else, the rules keep changing.
Masks, face shield, goggles, etc.: I try to loop the mask around my earrings just right so it does not catch and pull the hooks off. I think the goggles make me look cool, like an ant man.
My world has narrowed to work and home. Like all of us, I no longer go to conferences. I do outpatient treatment from my office desk. I see inpatients from 6 feet away, in mask and goggles. The cookies I pass out are now individually wrapped. Takeout instead of restaurants. A new home gym.
I have learned a lot. I now know how to manage psychiatric wards where COVID clusters occur. How to transfer psychiatric patients who convert to COVID positive over to the medicine ward. I faithfully swab my own nose twice a week.
I am constantly saying (very nicely): “Please pull your mask up over your nose.” “Six feet apart, please.”
I saved my surgical masks in case I needed to reuse them. Fortunately, I did not. Now I have three overflowing drawers of masks. Plus, the heavy homemade cloth ones that friends and family sent.
Back to how have my goals changed? Basically they have not. I fix my eyes straight ahead and concentrate on safety. Safety of patients, staff, my family, myself.
And daily add another yellow, or blue, or white, surgical mask to the drawers.
Elspeth Cameron Ritchie, MD, MPH
Washington
Awaiting project’s return
I had been actively involved in community service as the cofounder of The Bold Beauty Project since 2015. We are a Miami-based nonprofit, and we pair women with disabilities with volunteer photographers and create art shows. Our motto: Disability becomes Beauty becomes Art becomes Change.
I have dedicated about half of my time to the project, and it has been incredibly rewarding. It all came to a halt in March 2020, and it has left a real void in my daily schedule and my psyche. I am eagerly awaiting the return of the Bold Beauty Project with a renewed appreciation and enthusiasm. I hope you will check us out boldbeautyproject.com. If you are inspired to get involved, please contact me at [email protected].
Eva Ritvo, MD
Private Practice
Miami Beach, Fla.