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What are the healthiest drinks for patients with type 2 diabetes?
The researchers examined data on almost 15,500 participants with type 2 diabetes from two major studies, finding that the highest level of consumption of SSBs was associated with a 20% increased risk of all-cause mortality and a 25% raised risk of cardiovascular disease, compared with consumption of the least amounts of these products.
The research, published in BMJ, also showed that drinking coffee, tea, plain water, and low-fat milk reduced the risk of all-cause death and that switching from SSBs to the other beverages was linked to lower mortality.
“Overall, these results provide additional evidence that emphasizes the importance of beverage choices in maintaining overall health among adults with diabetes,” say senior author Le Ma, PhD, department of nutrition, Harvard School of Public Health, Boston, and colleagues.
“Collectively, these findings all point in the same direction. Lower consumption of SSBs and higher consumption of coffee, tea, plain water, or low-fat milk are optimal for better health outcomes in adults with type 2 diabetes,” Nita G. Forouhi, MD, PhD, emphasizes in an accompanying editorial.
Choice of drink matters
Dr. Forouhi, from the University of Cambridge (England), warned, however, that the findings “cannot be considered cause and effect,” despite the large-scale analysis.
Moreover, “questions remain,” such as the impact of beverage consumption on coronary heart disease and stroke risk, and cancer mortality, with the current study providing “inconclusive” data on the latter.
There was also no data on the addition of sugar to tea or coffee, “so the comparative health effects of unsweetened and sweetened hot beverages remain unclear,” Dr. Forouhi points out. Also unknown is whether the type of tea consumed has a differential effect.
Despite these and other reservations, she says that overall, “Choice of beverage clearly matters.”
“The case for avoiding sugar-sweetened beverages is compelling, and it is supported by various fiscal measures in more than 45 countries. It is reasonable to shift the focus to drinks that are most likely to have positive health impacts: coffee, tea, plain water, and low-fat milk,” she notes.
Dr. Forouhi ends by underlining that the current findings tally with those seen in the general population, so “one important message is that having diabetes does not have to be especially restrictive.”
Expanding the evidence
It was estimated that 537 million adults worldwide had type 2 diabetes in 2021, a figure set to increase to 783 million by 2045, say the authors.
Individuals with type 2 diabetes have an increased risk of cardiovascular disease, among many other comorbidities, as well as premature death. Dietary interventions can play an important role in managing these risks.
Recommendations on the healthiest beverages to drink are largely based on evidence from the general population, and data are limited on the best options for adults with type 2 diabetes, who have altered metabolism, the researchers note.
To expand on this, they examined data from the Nurses’ Health Study, which enrolled female registered nurses aged 30-55 years and was initiated in 1976, and the Health Professionals Follow-Up Study, which included male health professionals aged 40-75 years and was initiated in 1996.
For the current analysis, 11,399 women and 4,087 men with type 2 diabetes were included from the two studies, of whom 2,715 were diagnosed before study entry.
Participants’ average daily beverage intake was assessed using a validated food frequency questionnaire administered every 2-4 years. SSBs included caffeinated and caffeine-free colas, other carbonated SSBs, and noncarbonated SSBs, such as fruit punches, lemonades, or other fruit drinks.
During 285,967 person-years of follow-up, there were 7,638 (49.3%) deaths, and 3,447 (22.3%) cases of incident cardiovascular disease were documented during 248,447 person-years of follow-up.
Fully adjusted multivariate analysis comparing the lowest and highest beverage intake indicated that SSBs were associated with a significant increase in all-cause mortality, at a pooled hazard ratio of 1.20, or 1.08 for each additional serving per day (P = .01).
In contrast, the associations between all-cause mortality and consumption of artificially sweetened beverages, fruit juice, and full-fat milk were not significant, whereas coffee (HR, 0.74), tea (HR, 0.79), plain water (HR, 0.77), and low-fat milk (HR, 0.88) were linked to a reduced risk.
The team reported that there were similar associations between beverage intake and cardiovascular disease incidence, at an HR of 1.25 for SSBs, as well as for cardiovascular disease mortality, at an HR of 1.29.
Participants who increased their tea, coffee, and low-fat milk consumption during the course of the study had lower all-cause mortality than those who did not. Switching from SSBs to other beverages was also associated with lower mortality.
The researchers note, however, that there are “several potential limitations” to their study, including that “individual beverage consumption may be correlated with other dietary and lifestyle risk factors for cardiovascular disease incidence and mortality among adults with [type 2] diabetes.”
The study was sponsored by the National Institutes of Health. Dr. Ma has reported no relevant financial relationships. Disclosures for the other authors are listed with the article. Dr. Forouhi has declared receiving support from the U.K. Medical Research Council Epidemiology Unit and U.K. National Institute for Health and Care Research Biomedical Research Centre Cambridge.
A version of this article first appeared on Medscape.com.
The researchers examined data on almost 15,500 participants with type 2 diabetes from two major studies, finding that the highest level of consumption of SSBs was associated with a 20% increased risk of all-cause mortality and a 25% raised risk of cardiovascular disease, compared with consumption of the least amounts of these products.
The research, published in BMJ, also showed that drinking coffee, tea, plain water, and low-fat milk reduced the risk of all-cause death and that switching from SSBs to the other beverages was linked to lower mortality.
“Overall, these results provide additional evidence that emphasizes the importance of beverage choices in maintaining overall health among adults with diabetes,” say senior author Le Ma, PhD, department of nutrition, Harvard School of Public Health, Boston, and colleagues.
“Collectively, these findings all point in the same direction. Lower consumption of SSBs and higher consumption of coffee, tea, plain water, or low-fat milk are optimal for better health outcomes in adults with type 2 diabetes,” Nita G. Forouhi, MD, PhD, emphasizes in an accompanying editorial.
Choice of drink matters
Dr. Forouhi, from the University of Cambridge (England), warned, however, that the findings “cannot be considered cause and effect,” despite the large-scale analysis.
Moreover, “questions remain,” such as the impact of beverage consumption on coronary heart disease and stroke risk, and cancer mortality, with the current study providing “inconclusive” data on the latter.
There was also no data on the addition of sugar to tea or coffee, “so the comparative health effects of unsweetened and sweetened hot beverages remain unclear,” Dr. Forouhi points out. Also unknown is whether the type of tea consumed has a differential effect.
Despite these and other reservations, she says that overall, “Choice of beverage clearly matters.”
“The case for avoiding sugar-sweetened beverages is compelling, and it is supported by various fiscal measures in more than 45 countries. It is reasonable to shift the focus to drinks that are most likely to have positive health impacts: coffee, tea, plain water, and low-fat milk,” she notes.
Dr. Forouhi ends by underlining that the current findings tally with those seen in the general population, so “one important message is that having diabetes does not have to be especially restrictive.”
Expanding the evidence
It was estimated that 537 million adults worldwide had type 2 diabetes in 2021, a figure set to increase to 783 million by 2045, say the authors.
Individuals with type 2 diabetes have an increased risk of cardiovascular disease, among many other comorbidities, as well as premature death. Dietary interventions can play an important role in managing these risks.
Recommendations on the healthiest beverages to drink are largely based on evidence from the general population, and data are limited on the best options for adults with type 2 diabetes, who have altered metabolism, the researchers note.
To expand on this, they examined data from the Nurses’ Health Study, which enrolled female registered nurses aged 30-55 years and was initiated in 1976, and the Health Professionals Follow-Up Study, which included male health professionals aged 40-75 years and was initiated in 1996.
For the current analysis, 11,399 women and 4,087 men with type 2 diabetes were included from the two studies, of whom 2,715 were diagnosed before study entry.
Participants’ average daily beverage intake was assessed using a validated food frequency questionnaire administered every 2-4 years. SSBs included caffeinated and caffeine-free colas, other carbonated SSBs, and noncarbonated SSBs, such as fruit punches, lemonades, or other fruit drinks.
During 285,967 person-years of follow-up, there were 7,638 (49.3%) deaths, and 3,447 (22.3%) cases of incident cardiovascular disease were documented during 248,447 person-years of follow-up.
Fully adjusted multivariate analysis comparing the lowest and highest beverage intake indicated that SSBs were associated with a significant increase in all-cause mortality, at a pooled hazard ratio of 1.20, or 1.08 for each additional serving per day (P = .01).
In contrast, the associations between all-cause mortality and consumption of artificially sweetened beverages, fruit juice, and full-fat milk were not significant, whereas coffee (HR, 0.74), tea (HR, 0.79), plain water (HR, 0.77), and low-fat milk (HR, 0.88) were linked to a reduced risk.
The team reported that there were similar associations between beverage intake and cardiovascular disease incidence, at an HR of 1.25 for SSBs, as well as for cardiovascular disease mortality, at an HR of 1.29.
Participants who increased their tea, coffee, and low-fat milk consumption during the course of the study had lower all-cause mortality than those who did not. Switching from SSBs to other beverages was also associated with lower mortality.
The researchers note, however, that there are “several potential limitations” to their study, including that “individual beverage consumption may be correlated with other dietary and lifestyle risk factors for cardiovascular disease incidence and mortality among adults with [type 2] diabetes.”
The study was sponsored by the National Institutes of Health. Dr. Ma has reported no relevant financial relationships. Disclosures for the other authors are listed with the article. Dr. Forouhi has declared receiving support from the U.K. Medical Research Council Epidemiology Unit and U.K. National Institute for Health and Care Research Biomedical Research Centre Cambridge.
A version of this article first appeared on Medscape.com.
The researchers examined data on almost 15,500 participants with type 2 diabetes from two major studies, finding that the highest level of consumption of SSBs was associated with a 20% increased risk of all-cause mortality and a 25% raised risk of cardiovascular disease, compared with consumption of the least amounts of these products.
The research, published in BMJ, also showed that drinking coffee, tea, plain water, and low-fat milk reduced the risk of all-cause death and that switching from SSBs to the other beverages was linked to lower mortality.
“Overall, these results provide additional evidence that emphasizes the importance of beverage choices in maintaining overall health among adults with diabetes,” say senior author Le Ma, PhD, department of nutrition, Harvard School of Public Health, Boston, and colleagues.
“Collectively, these findings all point in the same direction. Lower consumption of SSBs and higher consumption of coffee, tea, plain water, or low-fat milk are optimal for better health outcomes in adults with type 2 diabetes,” Nita G. Forouhi, MD, PhD, emphasizes in an accompanying editorial.
Choice of drink matters
Dr. Forouhi, from the University of Cambridge (England), warned, however, that the findings “cannot be considered cause and effect,” despite the large-scale analysis.
Moreover, “questions remain,” such as the impact of beverage consumption on coronary heart disease and stroke risk, and cancer mortality, with the current study providing “inconclusive” data on the latter.
There was also no data on the addition of sugar to tea or coffee, “so the comparative health effects of unsweetened and sweetened hot beverages remain unclear,” Dr. Forouhi points out. Also unknown is whether the type of tea consumed has a differential effect.
Despite these and other reservations, she says that overall, “Choice of beverage clearly matters.”
“The case for avoiding sugar-sweetened beverages is compelling, and it is supported by various fiscal measures in more than 45 countries. It is reasonable to shift the focus to drinks that are most likely to have positive health impacts: coffee, tea, plain water, and low-fat milk,” she notes.
Dr. Forouhi ends by underlining that the current findings tally with those seen in the general population, so “one important message is that having diabetes does not have to be especially restrictive.”
Expanding the evidence
It was estimated that 537 million adults worldwide had type 2 diabetes in 2021, a figure set to increase to 783 million by 2045, say the authors.
Individuals with type 2 diabetes have an increased risk of cardiovascular disease, among many other comorbidities, as well as premature death. Dietary interventions can play an important role in managing these risks.
Recommendations on the healthiest beverages to drink are largely based on evidence from the general population, and data are limited on the best options for adults with type 2 diabetes, who have altered metabolism, the researchers note.
To expand on this, they examined data from the Nurses’ Health Study, which enrolled female registered nurses aged 30-55 years and was initiated in 1976, and the Health Professionals Follow-Up Study, which included male health professionals aged 40-75 years and was initiated in 1996.
For the current analysis, 11,399 women and 4,087 men with type 2 diabetes were included from the two studies, of whom 2,715 were diagnosed before study entry.
Participants’ average daily beverage intake was assessed using a validated food frequency questionnaire administered every 2-4 years. SSBs included caffeinated and caffeine-free colas, other carbonated SSBs, and noncarbonated SSBs, such as fruit punches, lemonades, or other fruit drinks.
During 285,967 person-years of follow-up, there were 7,638 (49.3%) deaths, and 3,447 (22.3%) cases of incident cardiovascular disease were documented during 248,447 person-years of follow-up.
Fully adjusted multivariate analysis comparing the lowest and highest beverage intake indicated that SSBs were associated with a significant increase in all-cause mortality, at a pooled hazard ratio of 1.20, or 1.08 for each additional serving per day (P = .01).
In contrast, the associations between all-cause mortality and consumption of artificially sweetened beverages, fruit juice, and full-fat milk were not significant, whereas coffee (HR, 0.74), tea (HR, 0.79), plain water (HR, 0.77), and low-fat milk (HR, 0.88) were linked to a reduced risk.
The team reported that there were similar associations between beverage intake and cardiovascular disease incidence, at an HR of 1.25 for SSBs, as well as for cardiovascular disease mortality, at an HR of 1.29.
Participants who increased their tea, coffee, and low-fat milk consumption during the course of the study had lower all-cause mortality than those who did not. Switching from SSBs to other beverages was also associated with lower mortality.
The researchers note, however, that there are “several potential limitations” to their study, including that “individual beverage consumption may be correlated with other dietary and lifestyle risk factors for cardiovascular disease incidence and mortality among adults with [type 2] diabetes.”
The study was sponsored by the National Institutes of Health. Dr. Ma has reported no relevant financial relationships. Disclosures for the other authors are listed with the article. Dr. Forouhi has declared receiving support from the U.K. Medical Research Council Epidemiology Unit and U.K. National Institute for Health and Care Research Biomedical Research Centre Cambridge.
A version of this article first appeared on Medscape.com.
FROM THE BMJ
Thirty years of epilepsy therapy: ‘Plus ça change, plus c’est la même chose’?
Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, , with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.
But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
Simpler times
In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.
“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.
Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”
Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”
For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
More drug options
Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”
Disease-modifying therapies
Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”
Improving patients’ lives
While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.
Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”
Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, , with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.
But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
Simpler times
In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.
“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.
Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”
Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”
For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
More drug options
Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”
Disease-modifying therapies
Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”
Improving patients’ lives
While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.
Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”
Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, , with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.
But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
Simpler times
In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.
“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.
Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”
Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”
For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
More drug options
Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”
Disease-modifying therapies
Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”
Improving patients’ lives
While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.
Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”
What happens when newer weight loss meds are stopped?
Some of these medicines are approved for treating obesity (Wegovy), whereas others are approved for type 2 diabetes (Ozempic and Mounjaro). Tirzepatide (Mounjaro) has been fast-tracked for approval for weight loss by the U.S. Food and Drug Administration this year, and in the first of the series of studies looking at its effect on obesity, the SURMOUNT-1 trial, tirzepatide demonstrated a mean weight loss of around 22% in people without diabetes, spurring significant off-label use.
Our offices are full of patients who have taken these medications, with unprecedented improvements in their weight, cardiometabolic health, and quality of life. What happens when patients stop taking these medications? Or more importantly, why stop them?
Although these drugs are very effective for weight loss and treating diabetes, there can be adverse effects, primarily gastrointestinal, that limit treatment continuation. Nausea is the most common side effect and usually diminishes over time. Slow dose titration and dietary modification can minimize unwanted gastrointestinal side effects.
Drug-induced acute pancreatitis, a rare adverse event requiring patients to stop therapy, was seen in approximately 0.2% of people in clinical trials.
Medications effective but cost prohibitive?
Beyond adverse effects, patients may be forced to stop treatment because of medication cost, changes in insurance coverage, or issues with drug availability.
Two incretin therapies currently approved for treating obesity – liraglutide (Saxenda) and semaglutide (Wegovy) – cost around $1,400 per month. Insurance coverage and manufacturer discounts can make treatment affordable, but anti-obesity medicines aren’t covered by Medicare or by many employer-sponsored commercial plans.
Changes in employment or insurance coverage, or expiration of manufacturer copay cards, may require patients to stop or change therapies. The increased prescribing and overall expense of these drugs have prompted insurance plans and self-insured groups to consider whether providing coverage for these medications is sustainable.
Limited coverage has led to significant off-label prescribing of incretin therapies that aren’t approved for treating obesity (for instance, Ozempic and Mounjaro) and compounding pharmacies selling peptides that allegedly contain the active pharmaceutical ingredients. High demand for these medications has created significant supply shortages over the past year, causing many people to be without treatment for significant periods of time, as reported by this news organization.
Recently, I saw a patient who lost more than 30 pounds with semaglutide (Wegovy). She then changed employers and the medication was no longer covered. She gained back almost 10 pounds over 3 months and was prescribed tirzepatide (Mounjaro) off-label for weight loss by another provider, using a manufacturer discount card to make the medication affordable. The patient did well with the new regimen and lost about 20 pounds, but the pharmacy stopped filling the prescription when changes were made to the discount card. Afraid of regaining the weight, she came to see us as a new patient to discuss her options with her lack of coverage for anti-obesity medications.
Stopping equals weight regain
Obesity is a chronic disease like hypertension. It responds to treatment and when people stop taking these anti-obesity medications, this is generally associated with increased appetite and less satiety, and there is subsequent weight regain and a recurrence in excess weight-related complications.
The STEP-1 trial extension showed an initial mean body weight reduction of 17.3% with weekly semaglutide 2.4 mg over 1 year. On average, two-thirds of the weight lost was regained by participants within 1 year of stopping semaglutide and the study’s lifestyle intervention. Many of the improvements seen in cardiometabolic variables, like blood glucose and blood pressure, similarly reverted to baseline.
There are also 2-year data from the STEP-5 trial with semaglutide; 3-year data from the SCALE trial with liraglutide; and 5-year nonrandomized data with multiple agents that show durable, clinically significant weight loss from medical therapies for obesity.
These data together demonstrate that medications are effective for durable weight loss if they are continued. However, this is not how obesity is currently treated. Anti-obesity medications are prescribed to less than 3% of eligible people in the United States, and the average duration of therapy is less than 90 days. This treatment length isn’t sufficient to see the full benefits most medications offer and certainly doesn’t support long-term weight maintenance.
A recent study showed that, in addition to maintaining weight loss from medical therapies, incretin-containing anti-obesity medication regimens were effective for treating weight regain and facilitating healthier weight after bariatric surgery.
Chronic therapy is needed for weight maintenance because several neurohormonal changes occur owing to weight loss. Metabolic adaptation is the relative reduction in energy expenditure, below what would be expected, in people after weight loss. When this is combined with physiologic changes that increase appetite and decrease satiety, many people create a positive energy balance that results in weight regain. This has been observed in reality TV shows such as “The Biggest Loser”: It’s biology, not willpower.
Unfortunately, many people – including health care providers – don’t understand how these changes promote weight regain and patients are too often blamed when their weight goes back up after medications are stopped. This blame is greatly misinformed by weight-biased beliefs that people with obesity are lazy and lack self-control for weight loss or maintenance. Nobody would be surprised if someone’s blood pressure went up if their antihypertensive medications were stopped. Why do we think so differently when treating obesity?
The prevalence of obesity in the United States is over 40% and growing. We are fortunate to have new medications that on average lead to 15% or greater weight loss when combined with lifestyle modification.
However, these medications are expensive and the limited insurance coverage currently available may not improve. From a patient experience perspective, it’s distressing to have to discontinue treatments that have helped to achieve a healthier weight and then experience regain.
People need better access to evidence-based treatments for obesity, which include lifestyle interventions, anti-obesity medications, and bariatric procedures. Successful treatment of obesity should include a personalized, patient-centered approach that may require a combination of therapies, such as medications and surgery, for lasting weight control.
Dr. Almandoz is associate professor, department of internal medicine, division of endocrinology; medical director, weight wellness program, University of Texas Southwestern, Dallas. He disclosed ties with Novo Nordisk and Eli Lilly. Follow Dr. Almandoz on Twitter: @JaimeAlmandoz.
A version of this article originally appeared on Medscape.com.
Some of these medicines are approved for treating obesity (Wegovy), whereas others are approved for type 2 diabetes (Ozempic and Mounjaro). Tirzepatide (Mounjaro) has been fast-tracked for approval for weight loss by the U.S. Food and Drug Administration this year, and in the first of the series of studies looking at its effect on obesity, the SURMOUNT-1 trial, tirzepatide demonstrated a mean weight loss of around 22% in people without diabetes, spurring significant off-label use.
Our offices are full of patients who have taken these medications, with unprecedented improvements in their weight, cardiometabolic health, and quality of life. What happens when patients stop taking these medications? Or more importantly, why stop them?
Although these drugs are very effective for weight loss and treating diabetes, there can be adverse effects, primarily gastrointestinal, that limit treatment continuation. Nausea is the most common side effect and usually diminishes over time. Slow dose titration and dietary modification can minimize unwanted gastrointestinal side effects.
Drug-induced acute pancreatitis, a rare adverse event requiring patients to stop therapy, was seen in approximately 0.2% of people in clinical trials.
Medications effective but cost prohibitive?
Beyond adverse effects, patients may be forced to stop treatment because of medication cost, changes in insurance coverage, or issues with drug availability.
Two incretin therapies currently approved for treating obesity – liraglutide (Saxenda) and semaglutide (Wegovy) – cost around $1,400 per month. Insurance coverage and manufacturer discounts can make treatment affordable, but anti-obesity medicines aren’t covered by Medicare or by many employer-sponsored commercial plans.
Changes in employment or insurance coverage, or expiration of manufacturer copay cards, may require patients to stop or change therapies. The increased prescribing and overall expense of these drugs have prompted insurance plans and self-insured groups to consider whether providing coverage for these medications is sustainable.
Limited coverage has led to significant off-label prescribing of incretin therapies that aren’t approved for treating obesity (for instance, Ozempic and Mounjaro) and compounding pharmacies selling peptides that allegedly contain the active pharmaceutical ingredients. High demand for these medications has created significant supply shortages over the past year, causing many people to be without treatment for significant periods of time, as reported by this news organization.
Recently, I saw a patient who lost more than 30 pounds with semaglutide (Wegovy). She then changed employers and the medication was no longer covered. She gained back almost 10 pounds over 3 months and was prescribed tirzepatide (Mounjaro) off-label for weight loss by another provider, using a manufacturer discount card to make the medication affordable. The patient did well with the new regimen and lost about 20 pounds, but the pharmacy stopped filling the prescription when changes were made to the discount card. Afraid of regaining the weight, she came to see us as a new patient to discuss her options with her lack of coverage for anti-obesity medications.
Stopping equals weight regain
Obesity is a chronic disease like hypertension. It responds to treatment and when people stop taking these anti-obesity medications, this is generally associated with increased appetite and less satiety, and there is subsequent weight regain and a recurrence in excess weight-related complications.
The STEP-1 trial extension showed an initial mean body weight reduction of 17.3% with weekly semaglutide 2.4 mg over 1 year. On average, two-thirds of the weight lost was regained by participants within 1 year of stopping semaglutide and the study’s lifestyle intervention. Many of the improvements seen in cardiometabolic variables, like blood glucose and blood pressure, similarly reverted to baseline.
There are also 2-year data from the STEP-5 trial with semaglutide; 3-year data from the SCALE trial with liraglutide; and 5-year nonrandomized data with multiple agents that show durable, clinically significant weight loss from medical therapies for obesity.
These data together demonstrate that medications are effective for durable weight loss if they are continued. However, this is not how obesity is currently treated. Anti-obesity medications are prescribed to less than 3% of eligible people in the United States, and the average duration of therapy is less than 90 days. This treatment length isn’t sufficient to see the full benefits most medications offer and certainly doesn’t support long-term weight maintenance.
A recent study showed that, in addition to maintaining weight loss from medical therapies, incretin-containing anti-obesity medication regimens were effective for treating weight regain and facilitating healthier weight after bariatric surgery.
Chronic therapy is needed for weight maintenance because several neurohormonal changes occur owing to weight loss. Metabolic adaptation is the relative reduction in energy expenditure, below what would be expected, in people after weight loss. When this is combined with physiologic changes that increase appetite and decrease satiety, many people create a positive energy balance that results in weight regain. This has been observed in reality TV shows such as “The Biggest Loser”: It’s biology, not willpower.
Unfortunately, many people – including health care providers – don’t understand how these changes promote weight regain and patients are too often blamed when their weight goes back up after medications are stopped. This blame is greatly misinformed by weight-biased beliefs that people with obesity are lazy and lack self-control for weight loss or maintenance. Nobody would be surprised if someone’s blood pressure went up if their antihypertensive medications were stopped. Why do we think so differently when treating obesity?
The prevalence of obesity in the United States is over 40% and growing. We are fortunate to have new medications that on average lead to 15% or greater weight loss when combined with lifestyle modification.
However, these medications are expensive and the limited insurance coverage currently available may not improve. From a patient experience perspective, it’s distressing to have to discontinue treatments that have helped to achieve a healthier weight and then experience regain.
People need better access to evidence-based treatments for obesity, which include lifestyle interventions, anti-obesity medications, and bariatric procedures. Successful treatment of obesity should include a personalized, patient-centered approach that may require a combination of therapies, such as medications and surgery, for lasting weight control.
Dr. Almandoz is associate professor, department of internal medicine, division of endocrinology; medical director, weight wellness program, University of Texas Southwestern, Dallas. He disclosed ties with Novo Nordisk and Eli Lilly. Follow Dr. Almandoz on Twitter: @JaimeAlmandoz.
A version of this article originally appeared on Medscape.com.
Some of these medicines are approved for treating obesity (Wegovy), whereas others are approved for type 2 diabetes (Ozempic and Mounjaro). Tirzepatide (Mounjaro) has been fast-tracked for approval for weight loss by the U.S. Food and Drug Administration this year, and in the first of the series of studies looking at its effect on obesity, the SURMOUNT-1 trial, tirzepatide demonstrated a mean weight loss of around 22% in people without diabetes, spurring significant off-label use.
Our offices are full of patients who have taken these medications, with unprecedented improvements in their weight, cardiometabolic health, and quality of life. What happens when patients stop taking these medications? Or more importantly, why stop them?
Although these drugs are very effective for weight loss and treating diabetes, there can be adverse effects, primarily gastrointestinal, that limit treatment continuation. Nausea is the most common side effect and usually diminishes over time. Slow dose titration and dietary modification can minimize unwanted gastrointestinal side effects.
Drug-induced acute pancreatitis, a rare adverse event requiring patients to stop therapy, was seen in approximately 0.2% of people in clinical trials.
Medications effective but cost prohibitive?
Beyond adverse effects, patients may be forced to stop treatment because of medication cost, changes in insurance coverage, or issues with drug availability.
Two incretin therapies currently approved for treating obesity – liraglutide (Saxenda) and semaglutide (Wegovy) – cost around $1,400 per month. Insurance coverage and manufacturer discounts can make treatment affordable, but anti-obesity medicines aren’t covered by Medicare or by many employer-sponsored commercial plans.
Changes in employment or insurance coverage, or expiration of manufacturer copay cards, may require patients to stop or change therapies. The increased prescribing and overall expense of these drugs have prompted insurance plans and self-insured groups to consider whether providing coverage for these medications is sustainable.
Limited coverage has led to significant off-label prescribing of incretin therapies that aren’t approved for treating obesity (for instance, Ozempic and Mounjaro) and compounding pharmacies selling peptides that allegedly contain the active pharmaceutical ingredients. High demand for these medications has created significant supply shortages over the past year, causing many people to be without treatment for significant periods of time, as reported by this news organization.
Recently, I saw a patient who lost more than 30 pounds with semaglutide (Wegovy). She then changed employers and the medication was no longer covered. She gained back almost 10 pounds over 3 months and was prescribed tirzepatide (Mounjaro) off-label for weight loss by another provider, using a manufacturer discount card to make the medication affordable. The patient did well with the new regimen and lost about 20 pounds, but the pharmacy stopped filling the prescription when changes were made to the discount card. Afraid of regaining the weight, she came to see us as a new patient to discuss her options with her lack of coverage for anti-obesity medications.
Stopping equals weight regain
Obesity is a chronic disease like hypertension. It responds to treatment and when people stop taking these anti-obesity medications, this is generally associated with increased appetite and less satiety, and there is subsequent weight regain and a recurrence in excess weight-related complications.
The STEP-1 trial extension showed an initial mean body weight reduction of 17.3% with weekly semaglutide 2.4 mg over 1 year. On average, two-thirds of the weight lost was regained by participants within 1 year of stopping semaglutide and the study’s lifestyle intervention. Many of the improvements seen in cardiometabolic variables, like blood glucose and blood pressure, similarly reverted to baseline.
There are also 2-year data from the STEP-5 trial with semaglutide; 3-year data from the SCALE trial with liraglutide; and 5-year nonrandomized data with multiple agents that show durable, clinically significant weight loss from medical therapies for obesity.
These data together demonstrate that medications are effective for durable weight loss if they are continued. However, this is not how obesity is currently treated. Anti-obesity medications are prescribed to less than 3% of eligible people in the United States, and the average duration of therapy is less than 90 days. This treatment length isn’t sufficient to see the full benefits most medications offer and certainly doesn’t support long-term weight maintenance.
A recent study showed that, in addition to maintaining weight loss from medical therapies, incretin-containing anti-obesity medication regimens were effective for treating weight regain and facilitating healthier weight after bariatric surgery.
Chronic therapy is needed for weight maintenance because several neurohormonal changes occur owing to weight loss. Metabolic adaptation is the relative reduction in energy expenditure, below what would be expected, in people after weight loss. When this is combined with physiologic changes that increase appetite and decrease satiety, many people create a positive energy balance that results in weight regain. This has been observed in reality TV shows such as “The Biggest Loser”: It’s biology, not willpower.
Unfortunately, many people – including health care providers – don’t understand how these changes promote weight regain and patients are too often blamed when their weight goes back up after medications are stopped. This blame is greatly misinformed by weight-biased beliefs that people with obesity are lazy and lack self-control for weight loss or maintenance. Nobody would be surprised if someone’s blood pressure went up if their antihypertensive medications were stopped. Why do we think so differently when treating obesity?
The prevalence of obesity in the United States is over 40% and growing. We are fortunate to have new medications that on average lead to 15% or greater weight loss when combined with lifestyle modification.
However, these medications are expensive and the limited insurance coverage currently available may not improve. From a patient experience perspective, it’s distressing to have to discontinue treatments that have helped to achieve a healthier weight and then experience regain.
People need better access to evidence-based treatments for obesity, which include lifestyle interventions, anti-obesity medications, and bariatric procedures. Successful treatment of obesity should include a personalized, patient-centered approach that may require a combination of therapies, such as medications and surgery, for lasting weight control.
Dr. Almandoz is associate professor, department of internal medicine, division of endocrinology; medical director, weight wellness program, University of Texas Southwestern, Dallas. He disclosed ties with Novo Nordisk and Eli Lilly. Follow Dr. Almandoz on Twitter: @JaimeAlmandoz.
A version of this article originally appeared on Medscape.com.
Headache before the revolution: A clinician looks back
Headache treatment before the early 1990s was marked by decades of improvisation with mostly unapproved agents, followed by an explosion of scientific interest and new treatments developed specifically for migraine.
But this is largely thanks to the sea change that occurred 30 years ago.
In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, past president of the International Headache Society and clinical professor of neurology at UCLA’s David Geffen School of Medicine in Los Angeles, recalled what it was like to treat patients before and after triptan medications came onto the market.
After the first of these anti-migraine agents, sumatriptan, was approved by the Food and Drug Administration in late December 1992, headache specialists found themselves with a powerful, approved treatment that validated their commitment to solving the disorder, and helped put to rest a persistent but mistaken notion that migraine was a psychiatric condition affecting young women.
But in the 1970s and 1980s, “there wasn’t great science explaining the pathophysiology of common primary headaches like tension-type headache, cluster headache, and migraine,” Dr. Rapoport recalled. “There is often comorbid depression and anxiety with migraine, and sometimes more serious psychiatric disease, but it doesn’t mean migraine is caused by psychological issues. Now we see it clearly as a disease of the brain, but it took years of investigation to prove that.”
The early years
Dr. Rapoport’s journey with headache began in 1972, when he joined a private neurology practice in Stamford and Greenwich, Conn. Neurologists were frowned upon then for having too much interest in headache, he said. There was poor remuneration for doctors treating headache patients, who were hard to properly diagnose and effectively care for. Few medications could effectively stop a migraine attack or reliably reduce the frequency of headaches or the disability they caused.
On weekends Dr. Rapoport covered emergency departments and ICUs at three hospitals, where standard treatment for a migraine attack was injectable opiates. Not only did this treatment aggravate nausea, a common migraine symptom, “but it did not stop the migraine process.” Once the pain relief wore off, patients woke up with the same headache, Dr. Rapoport recalled. “The other drug that was available was ergotamine tartrate” – a fungal alkaloid used since medieval times to treat headache – “given sublingually. It helped the headache slightly but increased the nausea. DHE, or dihydroergotamine, was available only by injection and not used very much.”
DHE, a semi-synthetic molecule based on ergotamine, had FDA approval for migraine, but was complicated to administer. Like the opioids, it provoked vomiting when given intravenously, in patients already suffering migraine-induced nausea. But Dr. Rapoport, along with some of his colleagues, felt that there was a role for DHE for the most severe subtypes of patients, those with long histories of frequent migraines.
“We put people in the hospital and we gave them intravenous DHE. Eventually I got the idea to give it intramuscularly or subcutaneously in the emergency room or my office. When you give it that way, it doesn’t work as quickly but has fewer side effects.” Dr. Rapoport designed a cocktail by coadministering promethazine for nausea, and eventually added a steroid, dexamethasone. The triple shots worked on most patients experiencing severe daily or near-daily migraine attacks, Dr. Rapoport saw, and he began administering the drug combination at The New England Center for Headache in Stamford and Greenwich, Conn., which he opened with Dr. Fred D. Sheftell in 1979.
“The triple shots really worked,” Dr. Rapoport recalled. “There was no need to keep patients in the office or emergency room for intravenous therapy. The patients never called to complain or came back the next day,” he said, as often occurred with opioid treatment.
Dr. Rapoport had learned early in his residency, in the late 1960s, from Dr. David R. Coddon, a neurologist at Mount Sinai hospital in New York, that a tricyclic antidepressant, imipramine, could be helpful in some patients with frequent migraine attacks. As evidence trickled in that other antidepressants, beta-blockers, and antiepileptic drugs might have preventive properties, Dr. Rapoport and others prescribed them for certain patients. But of all the drugs in the headache specialists’ repertoire, few were approved for either treatment or prevention. “And this continued until the triptans,” Dr. Rapoport said.
The triptan era
Sumatriptan was developed by Glaxo for the acute treatment of migraine. The medication, first available only as self-administered subcutaneous injections, was originally designed to bind to vascular serotonin receptors to allow selective constriction of cranial vessels that dilate, causing pain, during a migraine attack. (Years later it was discovered that triptans also worked as anti-inflammatory agents that decreased the release of the neurotransmitter calcitonin gene-related peptide, or CGRP.)
Triptans “changed the world for migraine patients and for me,” Dr. Rapoport said. “I could now prescribe a medication that people could take at home to decrease or stop the migraine process in an hour or two.” The success of the triptans prompted pharmaceutical companies to search for new, more effective ways to treat migraine attacks, with better tolerability.
Seven different triptans were developed, some as injections or tablets and others as nasal sprays. “If one triptan didn’t work, we’d give a second and rarely a third,” Dr. Rapoport said. “We learned that if oral triptans did not work, the most likely issue was that it was not rapidly absorbed from the small intestine, as migraine patients have nausea, poor GI absorption, and slow transit times. This prompted the greater use of injections and nasal sprays.” Headache specialists began combining triptan treatment with nonsteroidal anti-inflammatory drugs, offering further relief for the acute care of migraine.
Medication overuse headache
The years between 1993 and 2000, which saw all the current triptan drugs come onto the market, was an exhilarating one for headache specialists. But even those who were thrilled by the possibilities of the triptans, like Dr. Rapoport, soon came to recognize their limitations, in terms of side effects and poor tolerability for some patients.
Specialists also noticed something unsettling about the triptans: that patients’ headaches seemed to recur within a day, or occur more frequently over time, with higher medication use.
Medication overuse headache (MOH) was known to occur when patients treated migraine too often with acute care medications, especially over-the-counter analgesics and prescription opioids and barbiturates. Dr. Rapoport began warning at conferences and in seminars that MOH seemed to occur with the triptans as well. “In the beginning other doctors didn’t think the triptans could cause MOH, but I observed that patients who were taking triptans daily or almost daily were having increased headache frequency and the triptans stopped being effective. If they didn’t take the drug they were overusing, they were going to get much worse, almost like a withdrawal.”
Today, all seven triptans are now generic, and they remain a mainstay of migraine treatment: “Almost all of my patients are using, or have used a triptan,” Dr. Rapoport said. Yet researchers came to recognize the need for treatments targeting different pathways, both for prevention and acute care.
The next revolution: CGRP and gepants
Studies in the early 2000s began to show a link between the release of one ubiquitous nervous system neurotransmitter, calcitonin gene-related peptide, or CGRP, and migraine. They also noticed that blocking meningeal inflammation could lead to improvement in headache. Two new drug classes emerged from this science: monoclonal antibodies against CGRP or its receptor that had to be given by injection, and oral CGRP receptor blockers that could be used both as a preventive or as an acute care medication.
In 2018 the first monoclonal antibody against the CGRP receptor, erenumab (Aimovig, marketed by Amgen), delivered by injection, was approved for migraine prevention. Three others followed, most given by autoinjector, and one by IV infusion in office or hospital settings. “Those drugs are great,” Dr. Rapoport said. “You take one shot a month or every 3 months, and your headaches drop by 50% or more with very few side effects. Some patients actually see their migraines disappear.”
The following year ubrogepant (Ubrelvy, marketed by AbbVie), the first of a novel class of oral CGRP receptor blockers known as “gepants,” was approved to treat acute migraine. The FDA soon approved another gepant, rimegepant (Nurtec, marketed by Pfizer), which received indications both for prevention and for stopping a migraine attack acutely.
Both classes of therapies – the antibodies and the gepants – are far costlier than the triptans, which are all generic, and may not be needed for every migraine patient. With the gepants, for example, insurers may restrict use to people who have not responded to triptans or for whom triptans are contraindicated or cause too many adverse events. But the CGRP-targeted therapies as a whole “have been every bit as revolutionary” as the triptans, Dr. Rapoport said. The treatments work quickly to resolve headache and disability and get the patient functioning within an hour or two, and there are fewer side effects.
In a review article published in CNS Drugs in 2021, Dr. Rapoport and his colleagues reported that the anti-CGRP treatment with gepants did not appear linked to medication overuse headache, as virtually all previous acute care medication classes did, and could be used in patients who had previously reported MOH. “I am confident that over the next few years, more people will be using them as insurance coverage will improve for patients living with migraine,” he said.
Headache treatment today
Migraine specialists and patients now have a staggering range of therapeutic options. Approved treatments now include prevention of migraine with onabotulinumtoxinA (Botox, marketed by the Allergan division of AbbVie) injections, which work alone and with other medicines; acute care treatment with ditans like lasmiditan (Reyvow, marketed by Lilly*), a category of acute care medicines that work like triptans but target different serotonin receptors. Five devices have been cleared for migraine and other types of headache by the FDA. These work alone or along with medication and can be used acutely or preventively. The devices “should be used more,” Dr. Rapoport said, but are not yet well covered by insurance.
Thirty years after the triptans, scientists and researchers continue to explore the pathophysiology of headache disorders, finding new pathways and identifying new potential targets.
“There are many parts of the brain and brain stem that are involved, as well as the thalamus and hypothalamus,” Dr. Rapoport said. “It’s interesting that the newer medications, and some of the older ones, work in the peripheral nervous system, outside the brain stem in the trigeminovascular system, to modulate the central nervous system. We also know that the CGRP system is involved with cellular second-order messengers. Stimulating and blocking this chain of reactions with newer drugs may become treatments in the future.”
Recent research has focused on a blood vessel dilating neurotransmitter, pituitary adenylate-cyclase-activating polypeptide, or PACAP-38, as a potential therapeutic target. Psychedelic medications such as psilocybin, strong pain medications such as ketamine, and even cannabinoids such as marijuana have all been investigated in migraine. Biofeedback therapies, mindfulness, and other behavioral interventions also have proved effective.
“I expect the next 2-5 years to bring us many important clinical trials on new types of pharmacological treatments,” Dr. Rapoport said. “This is a wonderful time to be a doctor or nurse treating patients living with migraine. When I started out treating headache, 51 years ago, we had only ergotamine tartrate. Today we have so many therapies and combinations of therapies that I hardly know where to start.”
Dr. Rapoport has served as a consultant to or speaker for AbbVie, Amgen, Biohaven, Cala Health, Lundbeck, Satsuma, and Teva, among others.
*Correction, 3/30/23: An earlier version of this article misstated the name of the company that markets Reyvow.
Headache treatment before the early 1990s was marked by decades of improvisation with mostly unapproved agents, followed by an explosion of scientific interest and new treatments developed specifically for migraine.
But this is largely thanks to the sea change that occurred 30 years ago.
In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, past president of the International Headache Society and clinical professor of neurology at UCLA’s David Geffen School of Medicine in Los Angeles, recalled what it was like to treat patients before and after triptan medications came onto the market.
After the first of these anti-migraine agents, sumatriptan, was approved by the Food and Drug Administration in late December 1992, headache specialists found themselves with a powerful, approved treatment that validated their commitment to solving the disorder, and helped put to rest a persistent but mistaken notion that migraine was a psychiatric condition affecting young women.
But in the 1970s and 1980s, “there wasn’t great science explaining the pathophysiology of common primary headaches like tension-type headache, cluster headache, and migraine,” Dr. Rapoport recalled. “There is often comorbid depression and anxiety with migraine, and sometimes more serious psychiatric disease, but it doesn’t mean migraine is caused by psychological issues. Now we see it clearly as a disease of the brain, but it took years of investigation to prove that.”
The early years
Dr. Rapoport’s journey with headache began in 1972, when he joined a private neurology practice in Stamford and Greenwich, Conn. Neurologists were frowned upon then for having too much interest in headache, he said. There was poor remuneration for doctors treating headache patients, who were hard to properly diagnose and effectively care for. Few medications could effectively stop a migraine attack or reliably reduce the frequency of headaches or the disability they caused.
On weekends Dr. Rapoport covered emergency departments and ICUs at three hospitals, where standard treatment for a migraine attack was injectable opiates. Not only did this treatment aggravate nausea, a common migraine symptom, “but it did not stop the migraine process.” Once the pain relief wore off, patients woke up with the same headache, Dr. Rapoport recalled. “The other drug that was available was ergotamine tartrate” – a fungal alkaloid used since medieval times to treat headache – “given sublingually. It helped the headache slightly but increased the nausea. DHE, or dihydroergotamine, was available only by injection and not used very much.”
DHE, a semi-synthetic molecule based on ergotamine, had FDA approval for migraine, but was complicated to administer. Like the opioids, it provoked vomiting when given intravenously, in patients already suffering migraine-induced nausea. But Dr. Rapoport, along with some of his colleagues, felt that there was a role for DHE for the most severe subtypes of patients, those with long histories of frequent migraines.
“We put people in the hospital and we gave them intravenous DHE. Eventually I got the idea to give it intramuscularly or subcutaneously in the emergency room or my office. When you give it that way, it doesn’t work as quickly but has fewer side effects.” Dr. Rapoport designed a cocktail by coadministering promethazine for nausea, and eventually added a steroid, dexamethasone. The triple shots worked on most patients experiencing severe daily or near-daily migraine attacks, Dr. Rapoport saw, and he began administering the drug combination at The New England Center for Headache in Stamford and Greenwich, Conn., which he opened with Dr. Fred D. Sheftell in 1979.
“The triple shots really worked,” Dr. Rapoport recalled. “There was no need to keep patients in the office or emergency room for intravenous therapy. The patients never called to complain or came back the next day,” he said, as often occurred with opioid treatment.
Dr. Rapoport had learned early in his residency, in the late 1960s, from Dr. David R. Coddon, a neurologist at Mount Sinai hospital in New York, that a tricyclic antidepressant, imipramine, could be helpful in some patients with frequent migraine attacks. As evidence trickled in that other antidepressants, beta-blockers, and antiepileptic drugs might have preventive properties, Dr. Rapoport and others prescribed them for certain patients. But of all the drugs in the headache specialists’ repertoire, few were approved for either treatment or prevention. “And this continued until the triptans,” Dr. Rapoport said.
The triptan era
Sumatriptan was developed by Glaxo for the acute treatment of migraine. The medication, first available only as self-administered subcutaneous injections, was originally designed to bind to vascular serotonin receptors to allow selective constriction of cranial vessels that dilate, causing pain, during a migraine attack. (Years later it was discovered that triptans also worked as anti-inflammatory agents that decreased the release of the neurotransmitter calcitonin gene-related peptide, or CGRP.)
Triptans “changed the world for migraine patients and for me,” Dr. Rapoport said. “I could now prescribe a medication that people could take at home to decrease or stop the migraine process in an hour or two.” The success of the triptans prompted pharmaceutical companies to search for new, more effective ways to treat migraine attacks, with better tolerability.
Seven different triptans were developed, some as injections or tablets and others as nasal sprays. “If one triptan didn’t work, we’d give a second and rarely a third,” Dr. Rapoport said. “We learned that if oral triptans did not work, the most likely issue was that it was not rapidly absorbed from the small intestine, as migraine patients have nausea, poor GI absorption, and slow transit times. This prompted the greater use of injections and nasal sprays.” Headache specialists began combining triptan treatment with nonsteroidal anti-inflammatory drugs, offering further relief for the acute care of migraine.
Medication overuse headache
The years between 1993 and 2000, which saw all the current triptan drugs come onto the market, was an exhilarating one for headache specialists. But even those who were thrilled by the possibilities of the triptans, like Dr. Rapoport, soon came to recognize their limitations, in terms of side effects and poor tolerability for some patients.
Specialists also noticed something unsettling about the triptans: that patients’ headaches seemed to recur within a day, or occur more frequently over time, with higher medication use.
Medication overuse headache (MOH) was known to occur when patients treated migraine too often with acute care medications, especially over-the-counter analgesics and prescription opioids and barbiturates. Dr. Rapoport began warning at conferences and in seminars that MOH seemed to occur with the triptans as well. “In the beginning other doctors didn’t think the triptans could cause MOH, but I observed that patients who were taking triptans daily or almost daily were having increased headache frequency and the triptans stopped being effective. If they didn’t take the drug they were overusing, they were going to get much worse, almost like a withdrawal.”
Today, all seven triptans are now generic, and they remain a mainstay of migraine treatment: “Almost all of my patients are using, or have used a triptan,” Dr. Rapoport said. Yet researchers came to recognize the need for treatments targeting different pathways, both for prevention and acute care.
The next revolution: CGRP and gepants
Studies in the early 2000s began to show a link between the release of one ubiquitous nervous system neurotransmitter, calcitonin gene-related peptide, or CGRP, and migraine. They also noticed that blocking meningeal inflammation could lead to improvement in headache. Two new drug classes emerged from this science: monoclonal antibodies against CGRP or its receptor that had to be given by injection, and oral CGRP receptor blockers that could be used both as a preventive or as an acute care medication.
In 2018 the first monoclonal antibody against the CGRP receptor, erenumab (Aimovig, marketed by Amgen), delivered by injection, was approved for migraine prevention. Three others followed, most given by autoinjector, and one by IV infusion in office or hospital settings. “Those drugs are great,” Dr. Rapoport said. “You take one shot a month or every 3 months, and your headaches drop by 50% or more with very few side effects. Some patients actually see their migraines disappear.”
The following year ubrogepant (Ubrelvy, marketed by AbbVie), the first of a novel class of oral CGRP receptor blockers known as “gepants,” was approved to treat acute migraine. The FDA soon approved another gepant, rimegepant (Nurtec, marketed by Pfizer), which received indications both for prevention and for stopping a migraine attack acutely.
Both classes of therapies – the antibodies and the gepants – are far costlier than the triptans, which are all generic, and may not be needed for every migraine patient. With the gepants, for example, insurers may restrict use to people who have not responded to triptans or for whom triptans are contraindicated or cause too many adverse events. But the CGRP-targeted therapies as a whole “have been every bit as revolutionary” as the triptans, Dr. Rapoport said. The treatments work quickly to resolve headache and disability and get the patient functioning within an hour or two, and there are fewer side effects.
In a review article published in CNS Drugs in 2021, Dr. Rapoport and his colleagues reported that the anti-CGRP treatment with gepants did not appear linked to medication overuse headache, as virtually all previous acute care medication classes did, and could be used in patients who had previously reported MOH. “I am confident that over the next few years, more people will be using them as insurance coverage will improve for patients living with migraine,” he said.
Headache treatment today
Migraine specialists and patients now have a staggering range of therapeutic options. Approved treatments now include prevention of migraine with onabotulinumtoxinA (Botox, marketed by the Allergan division of AbbVie) injections, which work alone and with other medicines; acute care treatment with ditans like lasmiditan (Reyvow, marketed by Lilly*), a category of acute care medicines that work like triptans but target different serotonin receptors. Five devices have been cleared for migraine and other types of headache by the FDA. These work alone or along with medication and can be used acutely or preventively. The devices “should be used more,” Dr. Rapoport said, but are not yet well covered by insurance.
Thirty years after the triptans, scientists and researchers continue to explore the pathophysiology of headache disorders, finding new pathways and identifying new potential targets.
“There are many parts of the brain and brain stem that are involved, as well as the thalamus and hypothalamus,” Dr. Rapoport said. “It’s interesting that the newer medications, and some of the older ones, work in the peripheral nervous system, outside the brain stem in the trigeminovascular system, to modulate the central nervous system. We also know that the CGRP system is involved with cellular second-order messengers. Stimulating and blocking this chain of reactions with newer drugs may become treatments in the future.”
Recent research has focused on a blood vessel dilating neurotransmitter, pituitary adenylate-cyclase-activating polypeptide, or PACAP-38, as a potential therapeutic target. Psychedelic medications such as psilocybin, strong pain medications such as ketamine, and even cannabinoids such as marijuana have all been investigated in migraine. Biofeedback therapies, mindfulness, and other behavioral interventions also have proved effective.
“I expect the next 2-5 years to bring us many important clinical trials on new types of pharmacological treatments,” Dr. Rapoport said. “This is a wonderful time to be a doctor or nurse treating patients living with migraine. When I started out treating headache, 51 years ago, we had only ergotamine tartrate. Today we have so many therapies and combinations of therapies that I hardly know where to start.”
Dr. Rapoport has served as a consultant to or speaker for AbbVie, Amgen, Biohaven, Cala Health, Lundbeck, Satsuma, and Teva, among others.
*Correction, 3/30/23: An earlier version of this article misstated the name of the company that markets Reyvow.
Headache treatment before the early 1990s was marked by decades of improvisation with mostly unapproved agents, followed by an explosion of scientific interest and new treatments developed specifically for migraine.
But this is largely thanks to the sea change that occurred 30 years ago.
In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, past president of the International Headache Society and clinical professor of neurology at UCLA’s David Geffen School of Medicine in Los Angeles, recalled what it was like to treat patients before and after triptan medications came onto the market.
After the first of these anti-migraine agents, sumatriptan, was approved by the Food and Drug Administration in late December 1992, headache specialists found themselves with a powerful, approved treatment that validated their commitment to solving the disorder, and helped put to rest a persistent but mistaken notion that migraine was a psychiatric condition affecting young women.
But in the 1970s and 1980s, “there wasn’t great science explaining the pathophysiology of common primary headaches like tension-type headache, cluster headache, and migraine,” Dr. Rapoport recalled. “There is often comorbid depression and anxiety with migraine, and sometimes more serious psychiatric disease, but it doesn’t mean migraine is caused by psychological issues. Now we see it clearly as a disease of the brain, but it took years of investigation to prove that.”
The early years
Dr. Rapoport’s journey with headache began in 1972, when he joined a private neurology practice in Stamford and Greenwich, Conn. Neurologists were frowned upon then for having too much interest in headache, he said. There was poor remuneration for doctors treating headache patients, who were hard to properly diagnose and effectively care for. Few medications could effectively stop a migraine attack or reliably reduce the frequency of headaches or the disability they caused.
On weekends Dr. Rapoport covered emergency departments and ICUs at three hospitals, where standard treatment for a migraine attack was injectable opiates. Not only did this treatment aggravate nausea, a common migraine symptom, “but it did not stop the migraine process.” Once the pain relief wore off, patients woke up with the same headache, Dr. Rapoport recalled. “The other drug that was available was ergotamine tartrate” – a fungal alkaloid used since medieval times to treat headache – “given sublingually. It helped the headache slightly but increased the nausea. DHE, or dihydroergotamine, was available only by injection and not used very much.”
DHE, a semi-synthetic molecule based on ergotamine, had FDA approval for migraine, but was complicated to administer. Like the opioids, it provoked vomiting when given intravenously, in patients already suffering migraine-induced nausea. But Dr. Rapoport, along with some of his colleagues, felt that there was a role for DHE for the most severe subtypes of patients, those with long histories of frequent migraines.
“We put people in the hospital and we gave them intravenous DHE. Eventually I got the idea to give it intramuscularly or subcutaneously in the emergency room or my office. When you give it that way, it doesn’t work as quickly but has fewer side effects.” Dr. Rapoport designed a cocktail by coadministering promethazine for nausea, and eventually added a steroid, dexamethasone. The triple shots worked on most patients experiencing severe daily or near-daily migraine attacks, Dr. Rapoport saw, and he began administering the drug combination at The New England Center for Headache in Stamford and Greenwich, Conn., which he opened with Dr. Fred D. Sheftell in 1979.
“The triple shots really worked,” Dr. Rapoport recalled. “There was no need to keep patients in the office or emergency room for intravenous therapy. The patients never called to complain or came back the next day,” he said, as often occurred with opioid treatment.
Dr. Rapoport had learned early in his residency, in the late 1960s, from Dr. David R. Coddon, a neurologist at Mount Sinai hospital in New York, that a tricyclic antidepressant, imipramine, could be helpful in some patients with frequent migraine attacks. As evidence trickled in that other antidepressants, beta-blockers, and antiepileptic drugs might have preventive properties, Dr. Rapoport and others prescribed them for certain patients. But of all the drugs in the headache specialists’ repertoire, few were approved for either treatment or prevention. “And this continued until the triptans,” Dr. Rapoport said.
The triptan era
Sumatriptan was developed by Glaxo for the acute treatment of migraine. The medication, first available only as self-administered subcutaneous injections, was originally designed to bind to vascular serotonin receptors to allow selective constriction of cranial vessels that dilate, causing pain, during a migraine attack. (Years later it was discovered that triptans also worked as anti-inflammatory agents that decreased the release of the neurotransmitter calcitonin gene-related peptide, or CGRP.)
Triptans “changed the world for migraine patients and for me,” Dr. Rapoport said. “I could now prescribe a medication that people could take at home to decrease or stop the migraine process in an hour or two.” The success of the triptans prompted pharmaceutical companies to search for new, more effective ways to treat migraine attacks, with better tolerability.
Seven different triptans were developed, some as injections or tablets and others as nasal sprays. “If one triptan didn’t work, we’d give a second and rarely a third,” Dr. Rapoport said. “We learned that if oral triptans did not work, the most likely issue was that it was not rapidly absorbed from the small intestine, as migraine patients have nausea, poor GI absorption, and slow transit times. This prompted the greater use of injections and nasal sprays.” Headache specialists began combining triptan treatment with nonsteroidal anti-inflammatory drugs, offering further relief for the acute care of migraine.
Medication overuse headache
The years between 1993 and 2000, which saw all the current triptan drugs come onto the market, was an exhilarating one for headache specialists. But even those who were thrilled by the possibilities of the triptans, like Dr. Rapoport, soon came to recognize their limitations, in terms of side effects and poor tolerability for some patients.
Specialists also noticed something unsettling about the triptans: that patients’ headaches seemed to recur within a day, or occur more frequently over time, with higher medication use.
Medication overuse headache (MOH) was known to occur when patients treated migraine too often with acute care medications, especially over-the-counter analgesics and prescription opioids and barbiturates. Dr. Rapoport began warning at conferences and in seminars that MOH seemed to occur with the triptans as well. “In the beginning other doctors didn’t think the triptans could cause MOH, but I observed that patients who were taking triptans daily or almost daily were having increased headache frequency and the triptans stopped being effective. If they didn’t take the drug they were overusing, they were going to get much worse, almost like a withdrawal.”
Today, all seven triptans are now generic, and they remain a mainstay of migraine treatment: “Almost all of my patients are using, or have used a triptan,” Dr. Rapoport said. Yet researchers came to recognize the need for treatments targeting different pathways, both for prevention and acute care.
The next revolution: CGRP and gepants
Studies in the early 2000s began to show a link between the release of one ubiquitous nervous system neurotransmitter, calcitonin gene-related peptide, or CGRP, and migraine. They also noticed that blocking meningeal inflammation could lead to improvement in headache. Two new drug classes emerged from this science: monoclonal antibodies against CGRP or its receptor that had to be given by injection, and oral CGRP receptor blockers that could be used both as a preventive or as an acute care medication.
In 2018 the first monoclonal antibody against the CGRP receptor, erenumab (Aimovig, marketed by Amgen), delivered by injection, was approved for migraine prevention. Three others followed, most given by autoinjector, and one by IV infusion in office or hospital settings. “Those drugs are great,” Dr. Rapoport said. “You take one shot a month or every 3 months, and your headaches drop by 50% or more with very few side effects. Some patients actually see their migraines disappear.”
The following year ubrogepant (Ubrelvy, marketed by AbbVie), the first of a novel class of oral CGRP receptor blockers known as “gepants,” was approved to treat acute migraine. The FDA soon approved another gepant, rimegepant (Nurtec, marketed by Pfizer), which received indications both for prevention and for stopping a migraine attack acutely.
Both classes of therapies – the antibodies and the gepants – are far costlier than the triptans, which are all generic, and may not be needed for every migraine patient. With the gepants, for example, insurers may restrict use to people who have not responded to triptans or for whom triptans are contraindicated or cause too many adverse events. But the CGRP-targeted therapies as a whole “have been every bit as revolutionary” as the triptans, Dr. Rapoport said. The treatments work quickly to resolve headache and disability and get the patient functioning within an hour or two, and there are fewer side effects.
In a review article published in CNS Drugs in 2021, Dr. Rapoport and his colleagues reported that the anti-CGRP treatment with gepants did not appear linked to medication overuse headache, as virtually all previous acute care medication classes did, and could be used in patients who had previously reported MOH. “I am confident that over the next few years, more people will be using them as insurance coverage will improve for patients living with migraine,” he said.
Headache treatment today
Migraine specialists and patients now have a staggering range of therapeutic options. Approved treatments now include prevention of migraine with onabotulinumtoxinA (Botox, marketed by the Allergan division of AbbVie) injections, which work alone and with other medicines; acute care treatment with ditans like lasmiditan (Reyvow, marketed by Lilly*), a category of acute care medicines that work like triptans but target different serotonin receptors. Five devices have been cleared for migraine and other types of headache by the FDA. These work alone or along with medication and can be used acutely or preventively. The devices “should be used more,” Dr. Rapoport said, but are not yet well covered by insurance.
Thirty years after the triptans, scientists and researchers continue to explore the pathophysiology of headache disorders, finding new pathways and identifying new potential targets.
“There are many parts of the brain and brain stem that are involved, as well as the thalamus and hypothalamus,” Dr. Rapoport said. “It’s interesting that the newer medications, and some of the older ones, work in the peripheral nervous system, outside the brain stem in the trigeminovascular system, to modulate the central nervous system. We also know that the CGRP system is involved with cellular second-order messengers. Stimulating and blocking this chain of reactions with newer drugs may become treatments in the future.”
Recent research has focused on a blood vessel dilating neurotransmitter, pituitary adenylate-cyclase-activating polypeptide, or PACAP-38, as a potential therapeutic target. Psychedelic medications such as psilocybin, strong pain medications such as ketamine, and even cannabinoids such as marijuana have all been investigated in migraine. Biofeedback therapies, mindfulness, and other behavioral interventions also have proved effective.
“I expect the next 2-5 years to bring us many important clinical trials on new types of pharmacological treatments,” Dr. Rapoport said. “This is a wonderful time to be a doctor or nurse treating patients living with migraine. When I started out treating headache, 51 years ago, we had only ergotamine tartrate. Today we have so many therapies and combinations of therapies that I hardly know where to start.”
Dr. Rapoport has served as a consultant to or speaker for AbbVie, Amgen, Biohaven, Cala Health, Lundbeck, Satsuma, and Teva, among others.
*Correction, 3/30/23: An earlier version of this article misstated the name of the company that markets Reyvow.
Dapagliflozin’s HFpEF benefit tied to lower filling pressure
NEW ORLEANS – Treatment of patients with heart failure with preserved ejection fraction (HFpEF) with the SGLT2 inhibitor dapagliflozin (Farxiga) for 24 weeks produced significant and beneficial reductions in left-heart filling pressures in a mechanistic, randomized clinical study.
The findings “provide new insight into the mechanisms underlying the favorable clinical effects of dapagliflozin in patients with HFpEF,” Barry A. Borlaug, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. “Elevations in left heart filling pressures at rest and during exercise are fundamental pathophysiologic features of HFpEF,” he noted.
Results from prior studies documented the benefit of dapagliflozin for improving clinical outcomes in patients with HFpEF in the DELIVER trial, and for the related sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in the EMPEROR-Preserved trial. The new findings presented by Dr. Borlaug provide evidence from a placebo-controlled, prospective study for one way by which these SGLT2 inhibitors exert this benefit in patients with HFpEF.
The results of his single-center study showed that, in patients with HFpEF who also exhibited “severe” elevations in pulmonary capillary wedge pressure (PCWP) during exercise, 24 weeks of treatment with dapagliflozin led to a significant reduction in PCWP during exercise. The treatment produced an average 6.1–mm Hg drop from baseline compared with control patients who received placebo. A similar pattern occurred when these patients were at rest, when dapagliflozin treatment linked with a significant average reduction in PCWP from baseline of 3.5 mm Hg compared with controls.
Improving a ‘specific and fundamental’ feature of HFpEF
“This fantastic study looked at one of the fundamental aspects of HFpEF,” said John R. Teerlink, MD, designated discussant for the study. “You’ve shown that dapagliflozin targets a specific and fundamental” manifestation of HFpEF by lowering PCWP, said Dr. Teerlink, director of Heart Failure at the San Francisco Veterans Affairs Medical Center.
However, Dr. Teerlink added, the study did not directly address the related question of what physiologic action of dapagliflozin produces this notable drop in PCWP.
“We’re just starting to look at that,” replied Dr. Borlaug, a cardiologist and professor at the Mayo Clinic in Rochester, Minn.
He reported finding an intriguing correlate in the current study linked to the cut in PCWP with dapagliflozin treatment. The SGLT2 inhibitor at a standard daily 10-mg dose produced an average 3.5-kg drop in body weight in the dapagliflozin-treated patients that significantly linked with the changes in PCWP both at rest and during exercise. Dapagliflozin-treated patients also showed a significant reduction from their baseline plasma volume compared with placebo-treated patients, but this “poorly correlated” with the dapagliflozin-linked cuts in PCWP, Dr. Borlaug said.
“I don’t think this means weight loss is the cause of the hemodynamic benefit, but maybe it’s an indicator. When patients [with HFpEF] lose weight, they are in a metabolic state that leads to good changes in hemodynamics,” he suggested. “My guess is that there is probably a combination of many different little things [caused by dapagliflozin treatment of patients with HFpEF] that together result in the 20%-25% relative improvement we see in filling pressure.”
An ‘obese, cardiometabolic’ HFpEF phenotype
The study enrolled patients with HFpEF and a left ventricular ejection fraction of at least 50%, a New York Heart Association functional class of 2 or 3, and a PCWP during exercise of at least 25 mm Hg. Of the 37 evaluable patients, about two-thirds of the patients were women, more than two-thirds were in functional class 3, about 70% were obese, and their average ejection fraction was about 62%. The study excluded patients with HFpEF who also had type 1 diabetes, cardiomyopathy, pericardial disease, or other causes of dyspnea or heart failure.
Dr. Teerlink asked about the generalizability of the findings, as the study cohort seemed to differ in certain respects from the patients enrolled in the DELIVER trial, and because of the many apparently distinct patient phenotypes that exist within the scope of HFpEF.
An “obese, cardiometabolic phenotype” predominated the study cohort, Dr. Borlaug said. “The patients we enrolled look like the HFpEF patients seen in U.S. clinics.” However, he added that “in reality, many [HFpEF phenotypes] coexist in one patient. It’s not that simple,” that every patient with HFpEF can be categorized into a single HFpEF phenotype.
The researchers monitored PCWP invasively with high-fidelity micromanometer catheters.
The study was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Borlaug has received research funding from AstraZeneca, as well as from Corvia, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax. Dr. Teerlink has had financial relationships with AstraZeneca, as well as with Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics.
NEW ORLEANS – Treatment of patients with heart failure with preserved ejection fraction (HFpEF) with the SGLT2 inhibitor dapagliflozin (Farxiga) for 24 weeks produced significant and beneficial reductions in left-heart filling pressures in a mechanistic, randomized clinical study.
The findings “provide new insight into the mechanisms underlying the favorable clinical effects of dapagliflozin in patients with HFpEF,” Barry A. Borlaug, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. “Elevations in left heart filling pressures at rest and during exercise are fundamental pathophysiologic features of HFpEF,” he noted.
Results from prior studies documented the benefit of dapagliflozin for improving clinical outcomes in patients with HFpEF in the DELIVER trial, and for the related sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in the EMPEROR-Preserved trial. The new findings presented by Dr. Borlaug provide evidence from a placebo-controlled, prospective study for one way by which these SGLT2 inhibitors exert this benefit in patients with HFpEF.
The results of his single-center study showed that, in patients with HFpEF who also exhibited “severe” elevations in pulmonary capillary wedge pressure (PCWP) during exercise, 24 weeks of treatment with dapagliflozin led to a significant reduction in PCWP during exercise. The treatment produced an average 6.1–mm Hg drop from baseline compared with control patients who received placebo. A similar pattern occurred when these patients were at rest, when dapagliflozin treatment linked with a significant average reduction in PCWP from baseline of 3.5 mm Hg compared with controls.
Improving a ‘specific and fundamental’ feature of HFpEF
“This fantastic study looked at one of the fundamental aspects of HFpEF,” said John R. Teerlink, MD, designated discussant for the study. “You’ve shown that dapagliflozin targets a specific and fundamental” manifestation of HFpEF by lowering PCWP, said Dr. Teerlink, director of Heart Failure at the San Francisco Veterans Affairs Medical Center.
However, Dr. Teerlink added, the study did not directly address the related question of what physiologic action of dapagliflozin produces this notable drop in PCWP.
“We’re just starting to look at that,” replied Dr. Borlaug, a cardiologist and professor at the Mayo Clinic in Rochester, Minn.
He reported finding an intriguing correlate in the current study linked to the cut in PCWP with dapagliflozin treatment. The SGLT2 inhibitor at a standard daily 10-mg dose produced an average 3.5-kg drop in body weight in the dapagliflozin-treated patients that significantly linked with the changes in PCWP both at rest and during exercise. Dapagliflozin-treated patients also showed a significant reduction from their baseline plasma volume compared with placebo-treated patients, but this “poorly correlated” with the dapagliflozin-linked cuts in PCWP, Dr. Borlaug said.
“I don’t think this means weight loss is the cause of the hemodynamic benefit, but maybe it’s an indicator. When patients [with HFpEF] lose weight, they are in a metabolic state that leads to good changes in hemodynamics,” he suggested. “My guess is that there is probably a combination of many different little things [caused by dapagliflozin treatment of patients with HFpEF] that together result in the 20%-25% relative improvement we see in filling pressure.”
An ‘obese, cardiometabolic’ HFpEF phenotype
The study enrolled patients with HFpEF and a left ventricular ejection fraction of at least 50%, a New York Heart Association functional class of 2 or 3, and a PCWP during exercise of at least 25 mm Hg. Of the 37 evaluable patients, about two-thirds of the patients were women, more than two-thirds were in functional class 3, about 70% were obese, and their average ejection fraction was about 62%. The study excluded patients with HFpEF who also had type 1 diabetes, cardiomyopathy, pericardial disease, or other causes of dyspnea or heart failure.
Dr. Teerlink asked about the generalizability of the findings, as the study cohort seemed to differ in certain respects from the patients enrolled in the DELIVER trial, and because of the many apparently distinct patient phenotypes that exist within the scope of HFpEF.
An “obese, cardiometabolic phenotype” predominated the study cohort, Dr. Borlaug said. “The patients we enrolled look like the HFpEF patients seen in U.S. clinics.” However, he added that “in reality, many [HFpEF phenotypes] coexist in one patient. It’s not that simple,” that every patient with HFpEF can be categorized into a single HFpEF phenotype.
The researchers monitored PCWP invasively with high-fidelity micromanometer catheters.
The study was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Borlaug has received research funding from AstraZeneca, as well as from Corvia, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax. Dr. Teerlink has had financial relationships with AstraZeneca, as well as with Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics.
NEW ORLEANS – Treatment of patients with heart failure with preserved ejection fraction (HFpEF) with the SGLT2 inhibitor dapagliflozin (Farxiga) for 24 weeks produced significant and beneficial reductions in left-heart filling pressures in a mechanistic, randomized clinical study.
The findings “provide new insight into the mechanisms underlying the favorable clinical effects of dapagliflozin in patients with HFpEF,” Barry A. Borlaug, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. “Elevations in left heart filling pressures at rest and during exercise are fundamental pathophysiologic features of HFpEF,” he noted.
Results from prior studies documented the benefit of dapagliflozin for improving clinical outcomes in patients with HFpEF in the DELIVER trial, and for the related sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in the EMPEROR-Preserved trial. The new findings presented by Dr. Borlaug provide evidence from a placebo-controlled, prospective study for one way by which these SGLT2 inhibitors exert this benefit in patients with HFpEF.
The results of his single-center study showed that, in patients with HFpEF who also exhibited “severe” elevations in pulmonary capillary wedge pressure (PCWP) during exercise, 24 weeks of treatment with dapagliflozin led to a significant reduction in PCWP during exercise. The treatment produced an average 6.1–mm Hg drop from baseline compared with control patients who received placebo. A similar pattern occurred when these patients were at rest, when dapagliflozin treatment linked with a significant average reduction in PCWP from baseline of 3.5 mm Hg compared with controls.
Improving a ‘specific and fundamental’ feature of HFpEF
“This fantastic study looked at one of the fundamental aspects of HFpEF,” said John R. Teerlink, MD, designated discussant for the study. “You’ve shown that dapagliflozin targets a specific and fundamental” manifestation of HFpEF by lowering PCWP, said Dr. Teerlink, director of Heart Failure at the San Francisco Veterans Affairs Medical Center.
However, Dr. Teerlink added, the study did not directly address the related question of what physiologic action of dapagliflozin produces this notable drop in PCWP.
“We’re just starting to look at that,” replied Dr. Borlaug, a cardiologist and professor at the Mayo Clinic in Rochester, Minn.
He reported finding an intriguing correlate in the current study linked to the cut in PCWP with dapagliflozin treatment. The SGLT2 inhibitor at a standard daily 10-mg dose produced an average 3.5-kg drop in body weight in the dapagliflozin-treated patients that significantly linked with the changes in PCWP both at rest and during exercise. Dapagliflozin-treated patients also showed a significant reduction from their baseline plasma volume compared with placebo-treated patients, but this “poorly correlated” with the dapagliflozin-linked cuts in PCWP, Dr. Borlaug said.
“I don’t think this means weight loss is the cause of the hemodynamic benefit, but maybe it’s an indicator. When patients [with HFpEF] lose weight, they are in a metabolic state that leads to good changes in hemodynamics,” he suggested. “My guess is that there is probably a combination of many different little things [caused by dapagliflozin treatment of patients with HFpEF] that together result in the 20%-25% relative improvement we see in filling pressure.”
An ‘obese, cardiometabolic’ HFpEF phenotype
The study enrolled patients with HFpEF and a left ventricular ejection fraction of at least 50%, a New York Heart Association functional class of 2 or 3, and a PCWP during exercise of at least 25 mm Hg. Of the 37 evaluable patients, about two-thirds of the patients were women, more than two-thirds were in functional class 3, about 70% were obese, and their average ejection fraction was about 62%. The study excluded patients with HFpEF who also had type 1 diabetes, cardiomyopathy, pericardial disease, or other causes of dyspnea or heart failure.
Dr. Teerlink asked about the generalizability of the findings, as the study cohort seemed to differ in certain respects from the patients enrolled in the DELIVER trial, and because of the many apparently distinct patient phenotypes that exist within the scope of HFpEF.
An “obese, cardiometabolic phenotype” predominated the study cohort, Dr. Borlaug said. “The patients we enrolled look like the HFpEF patients seen in U.S. clinics.” However, he added that “in reality, many [HFpEF phenotypes] coexist in one patient. It’s not that simple,” that every patient with HFpEF can be categorized into a single HFpEF phenotype.
The researchers monitored PCWP invasively with high-fidelity micromanometer catheters.
The study was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Borlaug has received research funding from AstraZeneca, as well as from Corvia, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax. Dr. Teerlink has had financial relationships with AstraZeneca, as well as with Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics.
AT ACC 2023
Even small changes in fitness tied to lower mortality risk
Even relatively small changes in cardiorespiratory fitness (CRF) are associated with “considerable” impact on clinical symptoms and mortality risk among individuals with and without cardiovascular disease, new observational data in United States veterans suggest.
“We had a few surprises,” Peter Kokkinos, PhD, Robert Wood Johnson Medical School, New Brunswick, N. J., and the VA Medical Center, Washington, told this news organization. “First, the mortality risk was greatly attenuated in those who were moderate- and high-fit at baseline, despite a decline in fitness over time. In fact, in those with no CVD, the risk was not significantly elevated even when CRF declined by at least one MET [metabolic equivalent of task] for the moderate-fit and two or more METs for the high-fit group.”
“Second,” he said, “Our findings suggest that the impact of CRF on human health is not ephemeral, but rather carries a certain protection over time. Third, the changes in CRF necessary to impact mortality risk are relatively small (> 1.0 METs). This has a substantial clinical and public health significance.”
The study was published online in the Journal of the American College of Cardiology.
CRF up, mortality risk down
Dr. Kokkinos and colleagues analyzed data from 93,060 U.S. veterans; of these, 95% were men (mean age, 61.4 years) and 5% were women (mean age, 57.1 years). Overall, 72% of participants were White; 19.8%, African American; 5.2%, Hispanic; 1.9%, Native American, Asian, or Hawaiian; and 1.2%, unknown.
Participants were assigned to age-specific fitness quartiles based on peak METs achieved on a baseline exercise treadmill test (ETT). Each CRF quartile was stratified based on CRF changes (increase, decrease, no change) on the final ETT, with at least two ETT assessments at least 1 year apart.
The mean follow-up was 5.8 years (663,522 person-years), during which 18,302 deaths (19.7%) occurred, for an average annual mortality rate of 27.6 events per 1,000 person-years.
CRF was unchanged in 25.1% of the cohort, increased in 29.3%, and decreased in 45.6%. The trend was similar for those with and without CVD.
Significant differences were seen in all variables across CRF categories. In general, body weight, body mass index, CVD risk factors, and overall disease burden were progressively more unfavorable for those in the lowest CRF categories.
Conversely, medication use was progressively higher among those in low CRF categories.
After adjustment, higher CRF was inversely related to mortality risk for the entire cohort, with and without CVD. Cumulative survival rates across CRF categories declined progressively with increased fitness.
For patients with CVD (hazard ratio, 1.11), other significant predictors of all-cause mortality for patients were age (HR, 1.07), body mass index (HR, 0.98), chronic kidney disease (HR, 1.85), smoking (HR, 1.57), type 2 diabetes (HR, 1.42), hypertension (HR, 1.39), and cancers (HR, 1.37).
Generally, changes in CRF of at least 1.0 MET were associated with inverse and proportionate changes in mortality risk, regardless of baseline CRF status. For example, they note, a CRF decline of > 2.0 METs was associated with a 74% increased mortality risk for low-fit individuals with CVD, and a 69% increase for those without CVD.
A second analysis was done after excluding patients whose CRF declined and who died within 2 years of their last ETT, to account for the possibility that higher mortality rates and CRF declines were consequences of underlying disease (reverse causality). The association between changes in CRF and mortality risk persisted and remained similar to that observed in the entire cohort.
The authors add, “It is noteworthy that CRF increased by at least 1 MET in approximately 29% of the participants in the current study and decreased in approximately 46% of participants. This finding underscores the need to promote physical activity to maintain or increase CRF levels in middle-aged and older individuals.”
“Our findings make a persuasive argument that CRF is a strong and independent determinant of all-cause mortality risk, independent of genetic factors,” Dr. Kokkinos said. “We know that CRF is determined to some degree by genetic factors. However, improvements in aerobic capacity or CRF over time are largely the outcomes of regular engagement in aerobic activities of adequate intensity and volume.”
“Conversely,” he said, “a decline in CRF is likely the result of sedentary behavior, the onset of a chronic condition, or aging.”
If genetics were the sole contributor to mortality risk, then changes in CRF would not influence mortality risk, he concluded.
CRF impact “woefully underestimated”
Barry A. Franklin, PhD, past chair of both the American Heart Association’s Council on Physical Activity and Metabolism and the National Advocacy Committee, said the study substantiates previous smaller studies and is a “seminal” work.
“CRF is woefully underestimated as an index of health outcomes and survival,” said Dr. Franklin, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Mich. “Moderate to vigorous physical activity should be regularly promoted by the medical community.”
Dr. Franklin’s recent review, published in Mayo Clinic Proceedings, provides evidence for other exercise benefits that clinicians may not be aware of, he noted. These include:
- Each 1 MET increase in CRF is generally associated with approximately 16% reduction in mortality.
- At any given risk factor profile or coronary calcium score, unfit people have 2-3 times the mortality as their fit counterparts.
- Fitness is inversely related to annual health care costs (each 1 MET increase in CRF is associated with approximately 6% lower annual health care costs).
- Physically active people hospitalized with acute coronary syndromes have better short-term outcomes (likely because of a phenomenon called ‘exercise preconditioning’).
- Fit people who undergo elective or emergent surgical procedures have better outcomes.
- Regular physical activity is a common characteristic in population subsets who routinely live into their 90s and to 100+.
Dr. Franklin had this advice for clinicians seeking to promote CRF increases of 1 MET or more among patients: “Sedentary people who embark on a walking program, who over time increase their walking speed to 3 mph or faster, invariably show at least a 1 MET increase in CRF during subsequent peak or symptom-limited treadmill testing.”
“Another general rule is that if an exercise program decreases heart rate at a given or fixed workload by about 10 beats per minute [bpm], the same treadmill workload that initially was accomplished at a heart rate of 120 bpm is now being accomplished at a heart rate of 110 bpm,” likely resulting in about a 1 MET increase in fitness.
“Accordingly,” he added, “a 20-bpm decrease would suggest a 2 MET increase in fitness!”
In a related editorial, Leonard A. Kaminsky, Ball State University, Muncie, Ind. and colleagues, write, “We agree with and believe the conclusion, reached by Kokkinos et al., bears repeating. We (again) call on both clinicians and public health professionals to adopt CRF as a key health indicator.”
“This should be done by coupling routine assessments of CRF with continued advocacy for promoting physical activity as an essential healthy lifestyle behavior,” they write.
No funding or relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
Even relatively small changes in cardiorespiratory fitness (CRF) are associated with “considerable” impact on clinical symptoms and mortality risk among individuals with and without cardiovascular disease, new observational data in United States veterans suggest.
“We had a few surprises,” Peter Kokkinos, PhD, Robert Wood Johnson Medical School, New Brunswick, N. J., and the VA Medical Center, Washington, told this news organization. “First, the mortality risk was greatly attenuated in those who were moderate- and high-fit at baseline, despite a decline in fitness over time. In fact, in those with no CVD, the risk was not significantly elevated even when CRF declined by at least one MET [metabolic equivalent of task] for the moderate-fit and two or more METs for the high-fit group.”
“Second,” he said, “Our findings suggest that the impact of CRF on human health is not ephemeral, but rather carries a certain protection over time. Third, the changes in CRF necessary to impact mortality risk are relatively small (> 1.0 METs). This has a substantial clinical and public health significance.”
The study was published online in the Journal of the American College of Cardiology.
CRF up, mortality risk down
Dr. Kokkinos and colleagues analyzed data from 93,060 U.S. veterans; of these, 95% were men (mean age, 61.4 years) and 5% were women (mean age, 57.1 years). Overall, 72% of participants were White; 19.8%, African American; 5.2%, Hispanic; 1.9%, Native American, Asian, or Hawaiian; and 1.2%, unknown.
Participants were assigned to age-specific fitness quartiles based on peak METs achieved on a baseline exercise treadmill test (ETT). Each CRF quartile was stratified based on CRF changes (increase, decrease, no change) on the final ETT, with at least two ETT assessments at least 1 year apart.
The mean follow-up was 5.8 years (663,522 person-years), during which 18,302 deaths (19.7%) occurred, for an average annual mortality rate of 27.6 events per 1,000 person-years.
CRF was unchanged in 25.1% of the cohort, increased in 29.3%, and decreased in 45.6%. The trend was similar for those with and without CVD.
Significant differences were seen in all variables across CRF categories. In general, body weight, body mass index, CVD risk factors, and overall disease burden were progressively more unfavorable for those in the lowest CRF categories.
Conversely, medication use was progressively higher among those in low CRF categories.
After adjustment, higher CRF was inversely related to mortality risk for the entire cohort, with and without CVD. Cumulative survival rates across CRF categories declined progressively with increased fitness.
For patients with CVD (hazard ratio, 1.11), other significant predictors of all-cause mortality for patients were age (HR, 1.07), body mass index (HR, 0.98), chronic kidney disease (HR, 1.85), smoking (HR, 1.57), type 2 diabetes (HR, 1.42), hypertension (HR, 1.39), and cancers (HR, 1.37).
Generally, changes in CRF of at least 1.0 MET were associated with inverse and proportionate changes in mortality risk, regardless of baseline CRF status. For example, they note, a CRF decline of > 2.0 METs was associated with a 74% increased mortality risk for low-fit individuals with CVD, and a 69% increase for those without CVD.
A second analysis was done after excluding patients whose CRF declined and who died within 2 years of their last ETT, to account for the possibility that higher mortality rates and CRF declines were consequences of underlying disease (reverse causality). The association between changes in CRF and mortality risk persisted and remained similar to that observed in the entire cohort.
The authors add, “It is noteworthy that CRF increased by at least 1 MET in approximately 29% of the participants in the current study and decreased in approximately 46% of participants. This finding underscores the need to promote physical activity to maintain or increase CRF levels in middle-aged and older individuals.”
“Our findings make a persuasive argument that CRF is a strong and independent determinant of all-cause mortality risk, independent of genetic factors,” Dr. Kokkinos said. “We know that CRF is determined to some degree by genetic factors. However, improvements in aerobic capacity or CRF over time are largely the outcomes of regular engagement in aerobic activities of adequate intensity and volume.”
“Conversely,” he said, “a decline in CRF is likely the result of sedentary behavior, the onset of a chronic condition, or aging.”
If genetics were the sole contributor to mortality risk, then changes in CRF would not influence mortality risk, he concluded.
CRF impact “woefully underestimated”
Barry A. Franklin, PhD, past chair of both the American Heart Association’s Council on Physical Activity and Metabolism and the National Advocacy Committee, said the study substantiates previous smaller studies and is a “seminal” work.
“CRF is woefully underestimated as an index of health outcomes and survival,” said Dr. Franklin, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Mich. “Moderate to vigorous physical activity should be regularly promoted by the medical community.”
Dr. Franklin’s recent review, published in Mayo Clinic Proceedings, provides evidence for other exercise benefits that clinicians may not be aware of, he noted. These include:
- Each 1 MET increase in CRF is generally associated with approximately 16% reduction in mortality.
- At any given risk factor profile or coronary calcium score, unfit people have 2-3 times the mortality as their fit counterparts.
- Fitness is inversely related to annual health care costs (each 1 MET increase in CRF is associated with approximately 6% lower annual health care costs).
- Physically active people hospitalized with acute coronary syndromes have better short-term outcomes (likely because of a phenomenon called ‘exercise preconditioning’).
- Fit people who undergo elective or emergent surgical procedures have better outcomes.
- Regular physical activity is a common characteristic in population subsets who routinely live into their 90s and to 100+.
Dr. Franklin had this advice for clinicians seeking to promote CRF increases of 1 MET or more among patients: “Sedentary people who embark on a walking program, who over time increase their walking speed to 3 mph or faster, invariably show at least a 1 MET increase in CRF during subsequent peak or symptom-limited treadmill testing.”
“Another general rule is that if an exercise program decreases heart rate at a given or fixed workload by about 10 beats per minute [bpm], the same treadmill workload that initially was accomplished at a heart rate of 120 bpm is now being accomplished at a heart rate of 110 bpm,” likely resulting in about a 1 MET increase in fitness.
“Accordingly,” he added, “a 20-bpm decrease would suggest a 2 MET increase in fitness!”
In a related editorial, Leonard A. Kaminsky, Ball State University, Muncie, Ind. and colleagues, write, “We agree with and believe the conclusion, reached by Kokkinos et al., bears repeating. We (again) call on both clinicians and public health professionals to adopt CRF as a key health indicator.”
“This should be done by coupling routine assessments of CRF with continued advocacy for promoting physical activity as an essential healthy lifestyle behavior,” they write.
No funding or relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
Even relatively small changes in cardiorespiratory fitness (CRF) are associated with “considerable” impact on clinical symptoms and mortality risk among individuals with and without cardiovascular disease, new observational data in United States veterans suggest.
“We had a few surprises,” Peter Kokkinos, PhD, Robert Wood Johnson Medical School, New Brunswick, N. J., and the VA Medical Center, Washington, told this news organization. “First, the mortality risk was greatly attenuated in those who were moderate- and high-fit at baseline, despite a decline in fitness over time. In fact, in those with no CVD, the risk was not significantly elevated even when CRF declined by at least one MET [metabolic equivalent of task] for the moderate-fit and two or more METs for the high-fit group.”
“Second,” he said, “Our findings suggest that the impact of CRF on human health is not ephemeral, but rather carries a certain protection over time. Third, the changes in CRF necessary to impact mortality risk are relatively small (> 1.0 METs). This has a substantial clinical and public health significance.”
The study was published online in the Journal of the American College of Cardiology.
CRF up, mortality risk down
Dr. Kokkinos and colleagues analyzed data from 93,060 U.S. veterans; of these, 95% were men (mean age, 61.4 years) and 5% were women (mean age, 57.1 years). Overall, 72% of participants were White; 19.8%, African American; 5.2%, Hispanic; 1.9%, Native American, Asian, or Hawaiian; and 1.2%, unknown.
Participants were assigned to age-specific fitness quartiles based on peak METs achieved on a baseline exercise treadmill test (ETT). Each CRF quartile was stratified based on CRF changes (increase, decrease, no change) on the final ETT, with at least two ETT assessments at least 1 year apart.
The mean follow-up was 5.8 years (663,522 person-years), during which 18,302 deaths (19.7%) occurred, for an average annual mortality rate of 27.6 events per 1,000 person-years.
CRF was unchanged in 25.1% of the cohort, increased in 29.3%, and decreased in 45.6%. The trend was similar for those with and without CVD.
Significant differences were seen in all variables across CRF categories. In general, body weight, body mass index, CVD risk factors, and overall disease burden were progressively more unfavorable for those in the lowest CRF categories.
Conversely, medication use was progressively higher among those in low CRF categories.
After adjustment, higher CRF was inversely related to mortality risk for the entire cohort, with and without CVD. Cumulative survival rates across CRF categories declined progressively with increased fitness.
For patients with CVD (hazard ratio, 1.11), other significant predictors of all-cause mortality for patients were age (HR, 1.07), body mass index (HR, 0.98), chronic kidney disease (HR, 1.85), smoking (HR, 1.57), type 2 diabetes (HR, 1.42), hypertension (HR, 1.39), and cancers (HR, 1.37).
Generally, changes in CRF of at least 1.0 MET were associated with inverse and proportionate changes in mortality risk, regardless of baseline CRF status. For example, they note, a CRF decline of > 2.0 METs was associated with a 74% increased mortality risk for low-fit individuals with CVD, and a 69% increase for those without CVD.
A second analysis was done after excluding patients whose CRF declined and who died within 2 years of their last ETT, to account for the possibility that higher mortality rates and CRF declines were consequences of underlying disease (reverse causality). The association between changes in CRF and mortality risk persisted and remained similar to that observed in the entire cohort.
The authors add, “It is noteworthy that CRF increased by at least 1 MET in approximately 29% of the participants in the current study and decreased in approximately 46% of participants. This finding underscores the need to promote physical activity to maintain or increase CRF levels in middle-aged and older individuals.”
“Our findings make a persuasive argument that CRF is a strong and independent determinant of all-cause mortality risk, independent of genetic factors,” Dr. Kokkinos said. “We know that CRF is determined to some degree by genetic factors. However, improvements in aerobic capacity or CRF over time are largely the outcomes of regular engagement in aerobic activities of adequate intensity and volume.”
“Conversely,” he said, “a decline in CRF is likely the result of sedentary behavior, the onset of a chronic condition, or aging.”
If genetics were the sole contributor to mortality risk, then changes in CRF would not influence mortality risk, he concluded.
CRF impact “woefully underestimated”
Barry A. Franklin, PhD, past chair of both the American Heart Association’s Council on Physical Activity and Metabolism and the National Advocacy Committee, said the study substantiates previous smaller studies and is a “seminal” work.
“CRF is woefully underestimated as an index of health outcomes and survival,” said Dr. Franklin, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Mich. “Moderate to vigorous physical activity should be regularly promoted by the medical community.”
Dr. Franklin’s recent review, published in Mayo Clinic Proceedings, provides evidence for other exercise benefits that clinicians may not be aware of, he noted. These include:
- Each 1 MET increase in CRF is generally associated with approximately 16% reduction in mortality.
- At any given risk factor profile or coronary calcium score, unfit people have 2-3 times the mortality as their fit counterparts.
- Fitness is inversely related to annual health care costs (each 1 MET increase in CRF is associated with approximately 6% lower annual health care costs).
- Physically active people hospitalized with acute coronary syndromes have better short-term outcomes (likely because of a phenomenon called ‘exercise preconditioning’).
- Fit people who undergo elective or emergent surgical procedures have better outcomes.
- Regular physical activity is a common characteristic in population subsets who routinely live into their 90s and to 100+.
Dr. Franklin had this advice for clinicians seeking to promote CRF increases of 1 MET or more among patients: “Sedentary people who embark on a walking program, who over time increase their walking speed to 3 mph or faster, invariably show at least a 1 MET increase in CRF during subsequent peak or symptom-limited treadmill testing.”
“Another general rule is that if an exercise program decreases heart rate at a given or fixed workload by about 10 beats per minute [bpm], the same treadmill workload that initially was accomplished at a heart rate of 120 bpm is now being accomplished at a heart rate of 110 bpm,” likely resulting in about a 1 MET increase in fitness.
“Accordingly,” he added, “a 20-bpm decrease would suggest a 2 MET increase in fitness!”
In a related editorial, Leonard A. Kaminsky, Ball State University, Muncie, Ind. and colleagues, write, “We agree with and believe the conclusion, reached by Kokkinos et al., bears repeating. We (again) call on both clinicians and public health professionals to adopt CRF as a key health indicator.”
“This should be done by coupling routine assessments of CRF with continued advocacy for promoting physical activity as an essential healthy lifestyle behavior,” they write.
No funding or relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Tooth loss and diabetes together hasten mental decline
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF DENTAL RESEARCH
Nurse makes millions selling her licensing exam study sheets
Ms. Beggs, 28, sells one-page study sheets or bundles of sheets, sometimes with colorful drawings, conversation bubbles and underlining, that boil down concepts for particular conditions into easy-to-understand language.
The biggest seller on Ms. Beggs’ online marketplace Etsy site, RNExplained, is a bundle of study guides covering eight core nursing classes. The notes range in price from $2 to $150. More than 70,000 customers have bought the $60 bundle, according to the website.
Ms. Beggs’ business developed in a “very unintentional” way when COVID hit with just months left in her nursing program at Mount Saint Mary’s University, Los Angeles, she told this news organization.
Classes had switched to Zoom, and she had no one to study with as she prepared to take her board exams.
“The best way I know how to study is to teach things out loud. But because I had nobody to teach out loud to, I would literally teach them to the wall,” Ms. Beggs said. “I would record myself so I could play it back and teach myself these topics that were hard for me to understand.”
Just for fun, she says, she posted them on TikTok and the responses started flowing in, with followers asking where she was selling the sheets. She now has more than 660,000 TikTok followers and 9 million likes.
Ms. Beggs said that every sheet highlights a condition, and she has made 308 of them.
Traditional classroom lessons typically teach one medical condition in 5-6 pages, Ms. Beggs said. “I go straight to the point.”
One reviewer on Ms. Beggs’ Etsy site appreciated the handwritten notes, calling them “simplified and concise.” Another commented: “Definitely helped me pass my last exam.”
Ms. Beggs says that her notes may seem simple, but each page represents comprehensive research.
“I have to go through not just one source of information to make sure my information is factual,” Ms. Beggs says. “What you teach in California might be a little different than what you teach in Florida. It’s very meticulous. The lab values will be a little different everywhere you go.”
She acknowledges her competition, noting that there are many other study guides for the NCLEX and nursing courses.
Nursing groups weigh in
Dawn Kappel, spokesperson for the National Council of State Boards of Nursing, which oversees NCLEX, said in an interview that “NCSBN has no issue with the current content of Stephanee Beggs’ business venture.”
For many students, the study guides will be helpful, especially for visual learners, said Carole Kenner, PhD, RN, dean and professor in the School of Nursing and Health Sciences at The College of New Jersey.
But for students “who are less confident in their knowledge, I would want to see a lot more in-depth explanation and rationale,” Dr. Kenner said.
“Since the NCLEX is moving to more cased-based scenarios, the next-gen unfolding cases, you really have to understand a lot of the rationale.”
The notes remind Dr. Kenner of traditional flash cards. “I don’t think it will work for all students, but even the fanciest of onsite review courses are useful to everyone,” she said.
‘Not cutting corners’
As an emergency nurse, Ms. Beggs said, “I have the experience as a nurse to show people that what you are learning will be seen in real life.”
“The way I teach my brand is not to take shortcuts. I love to teach to understand rather than teaching to memorize for an exam.”
She said she sees her guides as a supplement to learning, not a replacement.
“It’s not cutting corners,” she says. “I condense a medical condition that could take a very long time to understand and break it into layman’s terms.”
Ms. Beggs said when people hear about the $2 million, they often ask her whether she plans to give up her shifts in the emergency department for the more lucrative venture.
The answer is no, at least not yet.
“Aside from teaching, I genuinely love being at the bedside,” Ms. Beggs said. “I don’t foresee myself leaving that for good for as long as I can handle both.” She acknowledged, though, that her business now takes up most of her time.
“I love everything about both aspects, so it’s hard for me to choose.”
A version of this article first appeared on Medscape.com.
Ms. Beggs, 28, sells one-page study sheets or bundles of sheets, sometimes with colorful drawings, conversation bubbles and underlining, that boil down concepts for particular conditions into easy-to-understand language.
The biggest seller on Ms. Beggs’ online marketplace Etsy site, RNExplained, is a bundle of study guides covering eight core nursing classes. The notes range in price from $2 to $150. More than 70,000 customers have bought the $60 bundle, according to the website.
Ms. Beggs’ business developed in a “very unintentional” way when COVID hit with just months left in her nursing program at Mount Saint Mary’s University, Los Angeles, she told this news organization.
Classes had switched to Zoom, and she had no one to study with as she prepared to take her board exams.
“The best way I know how to study is to teach things out loud. But because I had nobody to teach out loud to, I would literally teach them to the wall,” Ms. Beggs said. “I would record myself so I could play it back and teach myself these topics that were hard for me to understand.”
Just for fun, she says, she posted them on TikTok and the responses started flowing in, with followers asking where she was selling the sheets. She now has more than 660,000 TikTok followers and 9 million likes.
Ms. Beggs said that every sheet highlights a condition, and she has made 308 of them.
Traditional classroom lessons typically teach one medical condition in 5-6 pages, Ms. Beggs said. “I go straight to the point.”
One reviewer on Ms. Beggs’ Etsy site appreciated the handwritten notes, calling them “simplified and concise.” Another commented: “Definitely helped me pass my last exam.”
Ms. Beggs says that her notes may seem simple, but each page represents comprehensive research.
“I have to go through not just one source of information to make sure my information is factual,” Ms. Beggs says. “What you teach in California might be a little different than what you teach in Florida. It’s very meticulous. The lab values will be a little different everywhere you go.”
She acknowledges her competition, noting that there are many other study guides for the NCLEX and nursing courses.
Nursing groups weigh in
Dawn Kappel, spokesperson for the National Council of State Boards of Nursing, which oversees NCLEX, said in an interview that “NCSBN has no issue with the current content of Stephanee Beggs’ business venture.”
For many students, the study guides will be helpful, especially for visual learners, said Carole Kenner, PhD, RN, dean and professor in the School of Nursing and Health Sciences at The College of New Jersey.
But for students “who are less confident in their knowledge, I would want to see a lot more in-depth explanation and rationale,” Dr. Kenner said.
“Since the NCLEX is moving to more cased-based scenarios, the next-gen unfolding cases, you really have to understand a lot of the rationale.”
The notes remind Dr. Kenner of traditional flash cards. “I don’t think it will work for all students, but even the fanciest of onsite review courses are useful to everyone,” she said.
‘Not cutting corners’
As an emergency nurse, Ms. Beggs said, “I have the experience as a nurse to show people that what you are learning will be seen in real life.”
“The way I teach my brand is not to take shortcuts. I love to teach to understand rather than teaching to memorize for an exam.”
She said she sees her guides as a supplement to learning, not a replacement.
“It’s not cutting corners,” she says. “I condense a medical condition that could take a very long time to understand and break it into layman’s terms.”
Ms. Beggs said when people hear about the $2 million, they often ask her whether she plans to give up her shifts in the emergency department for the more lucrative venture.
The answer is no, at least not yet.
“Aside from teaching, I genuinely love being at the bedside,” Ms. Beggs said. “I don’t foresee myself leaving that for good for as long as I can handle both.” She acknowledged, though, that her business now takes up most of her time.
“I love everything about both aspects, so it’s hard for me to choose.”
A version of this article first appeared on Medscape.com.
Ms. Beggs, 28, sells one-page study sheets or bundles of sheets, sometimes with colorful drawings, conversation bubbles and underlining, that boil down concepts for particular conditions into easy-to-understand language.
The biggest seller on Ms. Beggs’ online marketplace Etsy site, RNExplained, is a bundle of study guides covering eight core nursing classes. The notes range in price from $2 to $150. More than 70,000 customers have bought the $60 bundle, according to the website.
Ms. Beggs’ business developed in a “very unintentional” way when COVID hit with just months left in her nursing program at Mount Saint Mary’s University, Los Angeles, she told this news organization.
Classes had switched to Zoom, and she had no one to study with as she prepared to take her board exams.
“The best way I know how to study is to teach things out loud. But because I had nobody to teach out loud to, I would literally teach them to the wall,” Ms. Beggs said. “I would record myself so I could play it back and teach myself these topics that were hard for me to understand.”
Just for fun, she says, she posted them on TikTok and the responses started flowing in, with followers asking where she was selling the sheets. She now has more than 660,000 TikTok followers and 9 million likes.
Ms. Beggs said that every sheet highlights a condition, and she has made 308 of them.
Traditional classroom lessons typically teach one medical condition in 5-6 pages, Ms. Beggs said. “I go straight to the point.”
One reviewer on Ms. Beggs’ Etsy site appreciated the handwritten notes, calling them “simplified and concise.” Another commented: “Definitely helped me pass my last exam.”
Ms. Beggs says that her notes may seem simple, but each page represents comprehensive research.
“I have to go through not just one source of information to make sure my information is factual,” Ms. Beggs says. “What you teach in California might be a little different than what you teach in Florida. It’s very meticulous. The lab values will be a little different everywhere you go.”
She acknowledges her competition, noting that there are many other study guides for the NCLEX and nursing courses.
Nursing groups weigh in
Dawn Kappel, spokesperson for the National Council of State Boards of Nursing, which oversees NCLEX, said in an interview that “NCSBN has no issue with the current content of Stephanee Beggs’ business venture.”
For many students, the study guides will be helpful, especially for visual learners, said Carole Kenner, PhD, RN, dean and professor in the School of Nursing and Health Sciences at The College of New Jersey.
But for students “who are less confident in their knowledge, I would want to see a lot more in-depth explanation and rationale,” Dr. Kenner said.
“Since the NCLEX is moving to more cased-based scenarios, the next-gen unfolding cases, you really have to understand a lot of the rationale.”
The notes remind Dr. Kenner of traditional flash cards. “I don’t think it will work for all students, but even the fanciest of onsite review courses are useful to everyone,” she said.
‘Not cutting corners’
As an emergency nurse, Ms. Beggs said, “I have the experience as a nurse to show people that what you are learning will be seen in real life.”
“The way I teach my brand is not to take shortcuts. I love to teach to understand rather than teaching to memorize for an exam.”
She said she sees her guides as a supplement to learning, not a replacement.
“It’s not cutting corners,” she says. “I condense a medical condition that could take a very long time to understand and break it into layman’s terms.”
Ms. Beggs said when people hear about the $2 million, they often ask her whether she plans to give up her shifts in the emergency department for the more lucrative venture.
The answer is no, at least not yet.
“Aside from teaching, I genuinely love being at the bedside,” Ms. Beggs said. “I don’t foresee myself leaving that for good for as long as I can handle both.” She acknowledged, though, that her business now takes up most of her time.
“I love everything about both aspects, so it’s hard for me to choose.”
A version of this article first appeared on Medscape.com.
COVID can mimic prostate cancer symptoms
This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter painkillers are not helping, you’d think, “check for metastases,” right?
That patient was me in late January 2023.
As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.
With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.
To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6.
But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit.
The COVID effect
I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study2 of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.
Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.
That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
COVID-19 pain
What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies3 have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.
To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.
References
1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.
2. Cinislioglu AE et al. Urology. 2022;159:16-21.
3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.
Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.
A version of this article first appeared on Medscape.com.
This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter painkillers are not helping, you’d think, “check for metastases,” right?
That patient was me in late January 2023.
As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.
With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.
To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6.
But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit.
The COVID effect
I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study2 of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.
Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.
That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
COVID-19 pain
What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies3 have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.
To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.
References
1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.
2. Cinislioglu AE et al. Urology. 2022;159:16-21.
3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.
Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.
A version of this article first appeared on Medscape.com.
This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter painkillers are not helping, you’d think, “check for metastases,” right?
That patient was me in late January 2023.
As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.
With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.
To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6.
But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit.
The COVID effect
I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study2 of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.
Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.
That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
COVID-19 pain
What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies3 have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.
To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.
References
1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.
2. Cinislioglu AE et al. Urology. 2022;159:16-21.
3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.
Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.
A version of this article first appeared on Medscape.com.
California picks generic drug company Civica to produce low-cost insulin
Gov. Gavin Newsom on March 18 announced the selection of Utah-based generic drug manufacturer Civica to produce low-cost insulin for California, an unprecedented move that makes good on his promise to put state government in direct competition with the brand-name drug companies that dominate the market.
“People should not be forced to go into debt to get lifesaving prescriptions,” Gov. Newsom said. “Californians will have access to some of the most inexpensive insulin available, helping them save thousands of dollars each year.”
The contract, with an initial cost of $50 million that Gov. Newsom and his fellow Democratic lawmakers approved last year, calls for Civica to manufacture state-branded insulin and make the lifesaving drug available to any Californian who needs it, regardless of insurance coverage, by mail order and at local pharmacies. But insulin is just the beginning. Gov. Newsom said the state will also look to produce the opioid overdose reversal drug naloxone.
Allan Coukell, Civica’s senior vice president of public policy, said in an interview that the nonprofit drugmaker is also in talks with the Newsom administration to potentially produce other generic medications, but he declined to elaborate, saying the company is focused on making cheap insulin widely available first.
“We are very excited about this partnership with the state of California,” Mr. Coukell said. “We’re not looking to have 100% of the market, but we do want 100% of people to have access to fair insulin prices.”
As insulin costs for consumers have soared, Democratic lawmakers and activists have called on the industry to rein in prices. Just weeks after President Joe Biden attacked Big Pharma for jacking up insulin prices, the three drugmakers that control the insulin market – Eli Lilly, Novo Nordisk, and Sanofi – announced they would slash the list prices of some products.
Gov. Newsom, who has previously accused the pharmaceutical industry of gouging Californians with “sky-high prices,” argued that the launch of the state’s generic drug label, CalRx, will add competition and apply pressure on the industry. Administration officials declined to say when California’s insulin products would be available, but experts say it could be as soon as 2025. Mr. Coukell said the state-branded medication will still require approval from the Food and Drug Administration, which can take roughly 10 months.
The Pharmaceutical Research and Manufacturers of America, which lobbies on behalf of brand-name companies, blasted California’s move. Reid Porter, senior director of state public affairs for PhRMA, said Gov. Newsom just “wants to score political points.”
“If the governor wants to impact what patients pay for insulins and other medicines meaningfully, he should expand his focus to others in the system that often make patients pay more than they do for medicines,” Mr. Porter said, blaming pharmaceutical go-between companies, known as pharmacy benefit managers, that negotiate with manufacturers on behalf of insurers for rebates and discounts on drugs.
The Pharmaceutical Care Management Association, which represents pharmacy benefit managers argued in turn that it’s pharmaceutical companies that are to blame for high prices.
Drug pricing experts, however, say pharmacy benefit managers and drugmakers share the blame.
Gov. Newsom administration officials say that inflated insulin costs force some to pay as much as $300 per vial or $500 for a box of injectable pens, and that too many Californians with diabetes skip or ration their medication. Doing so can lead to blindness, amputations, and life-threatening conditions such as heart disease and kidney failure. Nearly 10% of California adults have diabetes.
Civica is developing three types of generic insulin, known as a biosimilar, which will be available both in vials and in injectable pens. They are expected to be interchangeable with brand-name products including Lantus, Humalog, and NovoLog. Mr. Coukell said the company would make the drug available for no more than $30 a vial, or $55 for five injectable pens.
Gov. Newsom said the state’s insulin will save many patients $2,000-$4,000 a year, though critical questions about how California would get the products into the hands of consumers remain unanswered, including how it would persuade pharmacies, insurers, and retailers to distribute the drugs.
In 2022, Gov. Newsom also secured $50 million in seed money to build a facility to manufacture insulin; Mr. Coukell said Civica is exploring building a plant in California.
California’s move, though never previously tried by a state government, could be blunted by recent industry decisions to lower insulin prices. In March, Lilly, Novo Nordisk, and Sanofi vowed to cut prices, with Lilly offering a vial at $25 per month, Novo Nordisk promising major reductions that would bring the price of a particular generic vial to $48, and Sanofi pegging one vial at $64.
The governor’s office said it will cost the state $30 per vial to manufacture and distribute insulin and it will be sold at that price. Doing so, the administration argued, “will prevent the egregious cost-shifting that happens in traditional pharmaceutical price games.”
Drug pricing experts said generic production in California could further lower costs for insulin, and benefit people with high-deductible health insurance plans or no insurance.
“This is an extraordinary move in the pharmaceutical industry, not just for insulin but potentially for all kinds of drugs,” said Robin Feldman, a professor at the University of California, San Francisco. “It’s a very difficult industry to disrupt, but California is poised to do just that.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Gov. Gavin Newsom on March 18 announced the selection of Utah-based generic drug manufacturer Civica to produce low-cost insulin for California, an unprecedented move that makes good on his promise to put state government in direct competition with the brand-name drug companies that dominate the market.
“People should not be forced to go into debt to get lifesaving prescriptions,” Gov. Newsom said. “Californians will have access to some of the most inexpensive insulin available, helping them save thousands of dollars each year.”
The contract, with an initial cost of $50 million that Gov. Newsom and his fellow Democratic lawmakers approved last year, calls for Civica to manufacture state-branded insulin and make the lifesaving drug available to any Californian who needs it, regardless of insurance coverage, by mail order and at local pharmacies. But insulin is just the beginning. Gov. Newsom said the state will also look to produce the opioid overdose reversal drug naloxone.
Allan Coukell, Civica’s senior vice president of public policy, said in an interview that the nonprofit drugmaker is also in talks with the Newsom administration to potentially produce other generic medications, but he declined to elaborate, saying the company is focused on making cheap insulin widely available first.
“We are very excited about this partnership with the state of California,” Mr. Coukell said. “We’re not looking to have 100% of the market, but we do want 100% of people to have access to fair insulin prices.”
As insulin costs for consumers have soared, Democratic lawmakers and activists have called on the industry to rein in prices. Just weeks after President Joe Biden attacked Big Pharma for jacking up insulin prices, the three drugmakers that control the insulin market – Eli Lilly, Novo Nordisk, and Sanofi – announced they would slash the list prices of some products.
Gov. Newsom, who has previously accused the pharmaceutical industry of gouging Californians with “sky-high prices,” argued that the launch of the state’s generic drug label, CalRx, will add competition and apply pressure on the industry. Administration officials declined to say when California’s insulin products would be available, but experts say it could be as soon as 2025. Mr. Coukell said the state-branded medication will still require approval from the Food and Drug Administration, which can take roughly 10 months.
The Pharmaceutical Research and Manufacturers of America, which lobbies on behalf of brand-name companies, blasted California’s move. Reid Porter, senior director of state public affairs for PhRMA, said Gov. Newsom just “wants to score political points.”
“If the governor wants to impact what patients pay for insulins and other medicines meaningfully, he should expand his focus to others in the system that often make patients pay more than they do for medicines,” Mr. Porter said, blaming pharmaceutical go-between companies, known as pharmacy benefit managers, that negotiate with manufacturers on behalf of insurers for rebates and discounts on drugs.
The Pharmaceutical Care Management Association, which represents pharmacy benefit managers argued in turn that it’s pharmaceutical companies that are to blame for high prices.
Drug pricing experts, however, say pharmacy benefit managers and drugmakers share the blame.
Gov. Newsom administration officials say that inflated insulin costs force some to pay as much as $300 per vial or $500 for a box of injectable pens, and that too many Californians with diabetes skip or ration their medication. Doing so can lead to blindness, amputations, and life-threatening conditions such as heart disease and kidney failure. Nearly 10% of California adults have diabetes.
Civica is developing three types of generic insulin, known as a biosimilar, which will be available both in vials and in injectable pens. They are expected to be interchangeable with brand-name products including Lantus, Humalog, and NovoLog. Mr. Coukell said the company would make the drug available for no more than $30 a vial, or $55 for five injectable pens.
Gov. Newsom said the state’s insulin will save many patients $2,000-$4,000 a year, though critical questions about how California would get the products into the hands of consumers remain unanswered, including how it would persuade pharmacies, insurers, and retailers to distribute the drugs.
In 2022, Gov. Newsom also secured $50 million in seed money to build a facility to manufacture insulin; Mr. Coukell said Civica is exploring building a plant in California.
California’s move, though never previously tried by a state government, could be blunted by recent industry decisions to lower insulin prices. In March, Lilly, Novo Nordisk, and Sanofi vowed to cut prices, with Lilly offering a vial at $25 per month, Novo Nordisk promising major reductions that would bring the price of a particular generic vial to $48, and Sanofi pegging one vial at $64.
The governor’s office said it will cost the state $30 per vial to manufacture and distribute insulin and it will be sold at that price. Doing so, the administration argued, “will prevent the egregious cost-shifting that happens in traditional pharmaceutical price games.”
Drug pricing experts said generic production in California could further lower costs for insulin, and benefit people with high-deductible health insurance plans or no insurance.
“This is an extraordinary move in the pharmaceutical industry, not just for insulin but potentially for all kinds of drugs,” said Robin Feldman, a professor at the University of California, San Francisco. “It’s a very difficult industry to disrupt, but California is poised to do just that.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Gov. Gavin Newsom on March 18 announced the selection of Utah-based generic drug manufacturer Civica to produce low-cost insulin for California, an unprecedented move that makes good on his promise to put state government in direct competition with the brand-name drug companies that dominate the market.
“People should not be forced to go into debt to get lifesaving prescriptions,” Gov. Newsom said. “Californians will have access to some of the most inexpensive insulin available, helping them save thousands of dollars each year.”
The contract, with an initial cost of $50 million that Gov. Newsom and his fellow Democratic lawmakers approved last year, calls for Civica to manufacture state-branded insulin and make the lifesaving drug available to any Californian who needs it, regardless of insurance coverage, by mail order and at local pharmacies. But insulin is just the beginning. Gov. Newsom said the state will also look to produce the opioid overdose reversal drug naloxone.
Allan Coukell, Civica’s senior vice president of public policy, said in an interview that the nonprofit drugmaker is also in talks with the Newsom administration to potentially produce other generic medications, but he declined to elaborate, saying the company is focused on making cheap insulin widely available first.
“We are very excited about this partnership with the state of California,” Mr. Coukell said. “We’re not looking to have 100% of the market, but we do want 100% of people to have access to fair insulin prices.”
As insulin costs for consumers have soared, Democratic lawmakers and activists have called on the industry to rein in prices. Just weeks after President Joe Biden attacked Big Pharma for jacking up insulin prices, the three drugmakers that control the insulin market – Eli Lilly, Novo Nordisk, and Sanofi – announced they would slash the list prices of some products.
Gov. Newsom, who has previously accused the pharmaceutical industry of gouging Californians with “sky-high prices,” argued that the launch of the state’s generic drug label, CalRx, will add competition and apply pressure on the industry. Administration officials declined to say when California’s insulin products would be available, but experts say it could be as soon as 2025. Mr. Coukell said the state-branded medication will still require approval from the Food and Drug Administration, which can take roughly 10 months.
The Pharmaceutical Research and Manufacturers of America, which lobbies on behalf of brand-name companies, blasted California’s move. Reid Porter, senior director of state public affairs for PhRMA, said Gov. Newsom just “wants to score political points.”
“If the governor wants to impact what patients pay for insulins and other medicines meaningfully, he should expand his focus to others in the system that often make patients pay more than they do for medicines,” Mr. Porter said, blaming pharmaceutical go-between companies, known as pharmacy benefit managers, that negotiate with manufacturers on behalf of insurers for rebates and discounts on drugs.
The Pharmaceutical Care Management Association, which represents pharmacy benefit managers argued in turn that it’s pharmaceutical companies that are to blame for high prices.
Drug pricing experts, however, say pharmacy benefit managers and drugmakers share the blame.
Gov. Newsom administration officials say that inflated insulin costs force some to pay as much as $300 per vial or $500 for a box of injectable pens, and that too many Californians with diabetes skip or ration their medication. Doing so can lead to blindness, amputations, and life-threatening conditions such as heart disease and kidney failure. Nearly 10% of California adults have diabetes.
Civica is developing three types of generic insulin, known as a biosimilar, which will be available both in vials and in injectable pens. They are expected to be interchangeable with brand-name products including Lantus, Humalog, and NovoLog. Mr. Coukell said the company would make the drug available for no more than $30 a vial, or $55 for five injectable pens.
Gov. Newsom said the state’s insulin will save many patients $2,000-$4,000 a year, though critical questions about how California would get the products into the hands of consumers remain unanswered, including how it would persuade pharmacies, insurers, and retailers to distribute the drugs.
In 2022, Gov. Newsom also secured $50 million in seed money to build a facility to manufacture insulin; Mr. Coukell said Civica is exploring building a plant in California.
California’s move, though never previously tried by a state government, could be blunted by recent industry decisions to lower insulin prices. In March, Lilly, Novo Nordisk, and Sanofi vowed to cut prices, with Lilly offering a vial at $25 per month, Novo Nordisk promising major reductions that would bring the price of a particular generic vial to $48, and Sanofi pegging one vial at $64.
The governor’s office said it will cost the state $30 per vial to manufacture and distribute insulin and it will be sold at that price. Doing so, the administration argued, “will prevent the egregious cost-shifting that happens in traditional pharmaceutical price games.”
Drug pricing experts said generic production in California could further lower costs for insulin, and benefit people with high-deductible health insurance plans or no insurance.
“This is an extraordinary move in the pharmaceutical industry, not just for insulin but potentially for all kinds of drugs,” said Robin Feldman, a professor at the University of California, San Francisco. “It’s a very difficult industry to disrupt, but California is poised to do just that.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.