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Orally dissolving buprenorphine tied to severe tooth decay, FDA warns
Orally dissolving medications containing buprenorphine are linked to severe dental problems, including total tooth loss, the U.S. Food and Drug Administration warns in a safety communication.
The oral side effects of these medications, which are used to treat opioid use disorder (OUD) and pain, include cavities/tooth decay, including rampant caries; dental abscesses/infection; tooth erosion; fillings falling out; and, in some cases, total tooth loss.
Multiple cases have been reported even in patients with no history of dental problems.
The FDA is adding a warning about the risk of dental problems to the prescribing information and the patient medication guide for all buprenorphine-containing medicines dissolved in the mouth.
The FDA emphasizes, however, that buprenorphine remains “an important treatment option for OUD and pain, and the benefits of these medicines clearly outweigh the risks.”
More than 300 reported cases
Buprenorphine was approved in 2002 as a sublingual tablet, and in 2015 as a film to be placed inside the cheek to treat pain. Both delivery methods have been associated with dental problems.
Since buprenorphine was approved, the FDA has identified 305 cases of dental problems associated with orally dissolving buprenorphine, including 131 classified as serious.
There may be other cases, the FDA says, as this represents only cases reported to the FDA or published in the medical literature.
, but those as young as 18 years old were also affected.
Most cases occurred in patients using the medicines for OUD; however, 28 cases of dental problems occurred in patients using it to treat pain.
In 26 cases, patients had no prior history of dental problems. Some dental problems developed as soon as 2 weeks after treatment began; the median time to diagnosis was about 2 years after starting treatment.
Among all 305 cases reported, 113 involved two or more teeth.
The most common treatment for the dental problems was tooth extraction/removal, which was reported in 71 cases. Other cases required root canals, dental surgery, and other procedures such as crowns and implants.
Recommendations
The FDA says health care providers should counsel patients that severe and extensive tooth decay, tooth loss, and tooth fracture have been reported with the use of transmucosal buprenorphine-containing medicines and emphasize the importance of visiting their dentist to closely monitor their teeth.
Patients should be counseled to continue taking buprenorphine medications as prescribed and not stop suddenly without first talking to their health care provider, as this could lead to serious consequences, including relapse, misuse or abuse of other opioids, overdose, and death.
Patients are also being advised to take extra steps to help lessen the risk of serious dental problems.
Patients should also be educated on strategies to maintain or improve oral health while taking transmucosal buprenorphine medicines.
Counsel them that after the medicine is completely dissolved, the patient should take a large sip of water, swish it gently around the teeth and gums, swallow, and wait at least 1 hour before brushing their teeth, as the FDA advises. This will allow time for the mouth to gradually return to oral homeostasis and avoid any mechanical damage that may occur due to brushing.
The FDA also advises that patients tell their provider about any history of tooth problems, including cavities, and schedule a dentist visit soon after starting the medicine.
Dental problems related to transmucosal buprenorphine-containing medicines should be reported to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Orally dissolving medications containing buprenorphine are linked to severe dental problems, including total tooth loss, the U.S. Food and Drug Administration warns in a safety communication.
The oral side effects of these medications, which are used to treat opioid use disorder (OUD) and pain, include cavities/tooth decay, including rampant caries; dental abscesses/infection; tooth erosion; fillings falling out; and, in some cases, total tooth loss.
Multiple cases have been reported even in patients with no history of dental problems.
The FDA is adding a warning about the risk of dental problems to the prescribing information and the patient medication guide for all buprenorphine-containing medicines dissolved in the mouth.
The FDA emphasizes, however, that buprenorphine remains “an important treatment option for OUD and pain, and the benefits of these medicines clearly outweigh the risks.”
More than 300 reported cases
Buprenorphine was approved in 2002 as a sublingual tablet, and in 2015 as a film to be placed inside the cheek to treat pain. Both delivery methods have been associated with dental problems.
Since buprenorphine was approved, the FDA has identified 305 cases of dental problems associated with orally dissolving buprenorphine, including 131 classified as serious.
There may be other cases, the FDA says, as this represents only cases reported to the FDA or published in the medical literature.
, but those as young as 18 years old were also affected.
Most cases occurred in patients using the medicines for OUD; however, 28 cases of dental problems occurred in patients using it to treat pain.
In 26 cases, patients had no prior history of dental problems. Some dental problems developed as soon as 2 weeks after treatment began; the median time to diagnosis was about 2 years after starting treatment.
Among all 305 cases reported, 113 involved two or more teeth.
The most common treatment for the dental problems was tooth extraction/removal, which was reported in 71 cases. Other cases required root canals, dental surgery, and other procedures such as crowns and implants.
Recommendations
The FDA says health care providers should counsel patients that severe and extensive tooth decay, tooth loss, and tooth fracture have been reported with the use of transmucosal buprenorphine-containing medicines and emphasize the importance of visiting their dentist to closely monitor their teeth.
Patients should be counseled to continue taking buprenorphine medications as prescribed and not stop suddenly without first talking to their health care provider, as this could lead to serious consequences, including relapse, misuse or abuse of other opioids, overdose, and death.
Patients are also being advised to take extra steps to help lessen the risk of serious dental problems.
Patients should also be educated on strategies to maintain or improve oral health while taking transmucosal buprenorphine medicines.
Counsel them that after the medicine is completely dissolved, the patient should take a large sip of water, swish it gently around the teeth and gums, swallow, and wait at least 1 hour before brushing their teeth, as the FDA advises. This will allow time for the mouth to gradually return to oral homeostasis and avoid any mechanical damage that may occur due to brushing.
The FDA also advises that patients tell their provider about any history of tooth problems, including cavities, and schedule a dentist visit soon after starting the medicine.
Dental problems related to transmucosal buprenorphine-containing medicines should be reported to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Orally dissolving medications containing buprenorphine are linked to severe dental problems, including total tooth loss, the U.S. Food and Drug Administration warns in a safety communication.
The oral side effects of these medications, which are used to treat opioid use disorder (OUD) and pain, include cavities/tooth decay, including rampant caries; dental abscesses/infection; tooth erosion; fillings falling out; and, in some cases, total tooth loss.
Multiple cases have been reported even in patients with no history of dental problems.
The FDA is adding a warning about the risk of dental problems to the prescribing information and the patient medication guide for all buprenorphine-containing medicines dissolved in the mouth.
The FDA emphasizes, however, that buprenorphine remains “an important treatment option for OUD and pain, and the benefits of these medicines clearly outweigh the risks.”
More than 300 reported cases
Buprenorphine was approved in 2002 as a sublingual tablet, and in 2015 as a film to be placed inside the cheek to treat pain. Both delivery methods have been associated with dental problems.
Since buprenorphine was approved, the FDA has identified 305 cases of dental problems associated with orally dissolving buprenorphine, including 131 classified as serious.
There may be other cases, the FDA says, as this represents only cases reported to the FDA or published in the medical literature.
, but those as young as 18 years old were also affected.
Most cases occurred in patients using the medicines for OUD; however, 28 cases of dental problems occurred in patients using it to treat pain.
In 26 cases, patients had no prior history of dental problems. Some dental problems developed as soon as 2 weeks after treatment began; the median time to diagnosis was about 2 years after starting treatment.
Among all 305 cases reported, 113 involved two or more teeth.
The most common treatment for the dental problems was tooth extraction/removal, which was reported in 71 cases. Other cases required root canals, dental surgery, and other procedures such as crowns and implants.
Recommendations
The FDA says health care providers should counsel patients that severe and extensive tooth decay, tooth loss, and tooth fracture have been reported with the use of transmucosal buprenorphine-containing medicines and emphasize the importance of visiting their dentist to closely monitor their teeth.
Patients should be counseled to continue taking buprenorphine medications as prescribed and not stop suddenly without first talking to their health care provider, as this could lead to serious consequences, including relapse, misuse or abuse of other opioids, overdose, and death.
Patients are also being advised to take extra steps to help lessen the risk of serious dental problems.
Patients should also be educated on strategies to maintain or improve oral health while taking transmucosal buprenorphine medicines.
Counsel them that after the medicine is completely dissolved, the patient should take a large sip of water, swish it gently around the teeth and gums, swallow, and wait at least 1 hour before brushing their teeth, as the FDA advises. This will allow time for the mouth to gradually return to oral homeostasis and avoid any mechanical damage that may occur due to brushing.
The FDA also advises that patients tell their provider about any history of tooth problems, including cavities, and schedule a dentist visit soon after starting the medicine.
Dental problems related to transmucosal buprenorphine-containing medicines should be reported to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Quebec plans to fine unvaccinated adults
The amount hasn’t been decided yet, but it will be “significant” and more than $100. More details will be released at a later date, The Associated Press reported.
“Those who refuse to get their first doses in the coming weeks will have to pay a new health contribution,” Premier Francois Legault said during a news conference.
Not getting vaccinated burdens the health care system, and not all residents should pay for it, he said. About 10% of adults in Quebec are unvaccinated, but they represent about 50% of intensive care patients.
“I think it’s reasonable a majority of the population is asking that there be consequences,” he said. “It’s a question of fairness for the 90% of the population that have made some sacrifices. We owe them.”
The fine will apply to those who don’t qualify for a medical exemption, Mr. Legault said.
Provinces across Canada have reported a surge in COVID-19 cases due to the Omicron variant, with Quebec being one of the hardest-hit, according to Reuters. The province is regularly recording the highest daily case count across the country.
Quebec also has announced a 10 p.m. to 5 a.m. curfew, the AP reported. Starting Jan. 18, liquor and cannabis stores in the province will require proof of vaccination, and shopping malls and hair salons could soon require them as well.
About a quarter of all Canadians live in Quebec, according to CNN. The province was one of the first in Canada to require proof of vaccination for residents to eat in restaurants, go to the gym, or attend sporting events.
Some European countries have announced fees for unvaccinated residents, the AP reported, but Quebec is the first in Canada to announce a financial penalty for those who don’t get a shot.
In Greece, people older than 60 have until Jan. 16 to receive the first dose, or they will be fined 100 euros for every month they remain unvaccinated, the AP reported.
Austria will impose fines up to 3,600 euros for those who don’t follow the vaccine mandate for ages 14 and older, which is slated to start in February.
In Italy, residents who are 50 and older are required to be vaccinated. In mid-February, those who are unvaccinated could be fined up to 1,600 euros if they enter their workplaces, the AP reported.
A version of this article first appeared on WebMD.com.
The amount hasn’t been decided yet, but it will be “significant” and more than $100. More details will be released at a later date, The Associated Press reported.
“Those who refuse to get their first doses in the coming weeks will have to pay a new health contribution,” Premier Francois Legault said during a news conference.
Not getting vaccinated burdens the health care system, and not all residents should pay for it, he said. About 10% of adults in Quebec are unvaccinated, but they represent about 50% of intensive care patients.
“I think it’s reasonable a majority of the population is asking that there be consequences,” he said. “It’s a question of fairness for the 90% of the population that have made some sacrifices. We owe them.”
The fine will apply to those who don’t qualify for a medical exemption, Mr. Legault said.
Provinces across Canada have reported a surge in COVID-19 cases due to the Omicron variant, with Quebec being one of the hardest-hit, according to Reuters. The province is regularly recording the highest daily case count across the country.
Quebec also has announced a 10 p.m. to 5 a.m. curfew, the AP reported. Starting Jan. 18, liquor and cannabis stores in the province will require proof of vaccination, and shopping malls and hair salons could soon require them as well.
About a quarter of all Canadians live in Quebec, according to CNN. The province was one of the first in Canada to require proof of vaccination for residents to eat in restaurants, go to the gym, or attend sporting events.
Some European countries have announced fees for unvaccinated residents, the AP reported, but Quebec is the first in Canada to announce a financial penalty for those who don’t get a shot.
In Greece, people older than 60 have until Jan. 16 to receive the first dose, or they will be fined 100 euros for every month they remain unvaccinated, the AP reported.
Austria will impose fines up to 3,600 euros for those who don’t follow the vaccine mandate for ages 14 and older, which is slated to start in February.
In Italy, residents who are 50 and older are required to be vaccinated. In mid-February, those who are unvaccinated could be fined up to 1,600 euros if they enter their workplaces, the AP reported.
A version of this article first appeared on WebMD.com.
The amount hasn’t been decided yet, but it will be “significant” and more than $100. More details will be released at a later date, The Associated Press reported.
“Those who refuse to get their first doses in the coming weeks will have to pay a new health contribution,” Premier Francois Legault said during a news conference.
Not getting vaccinated burdens the health care system, and not all residents should pay for it, he said. About 10% of adults in Quebec are unvaccinated, but they represent about 50% of intensive care patients.
“I think it’s reasonable a majority of the population is asking that there be consequences,” he said. “It’s a question of fairness for the 90% of the population that have made some sacrifices. We owe them.”
The fine will apply to those who don’t qualify for a medical exemption, Mr. Legault said.
Provinces across Canada have reported a surge in COVID-19 cases due to the Omicron variant, with Quebec being one of the hardest-hit, according to Reuters. The province is regularly recording the highest daily case count across the country.
Quebec also has announced a 10 p.m. to 5 a.m. curfew, the AP reported. Starting Jan. 18, liquor and cannabis stores in the province will require proof of vaccination, and shopping malls and hair salons could soon require them as well.
About a quarter of all Canadians live in Quebec, according to CNN. The province was one of the first in Canada to require proof of vaccination for residents to eat in restaurants, go to the gym, or attend sporting events.
Some European countries have announced fees for unvaccinated residents, the AP reported, but Quebec is the first in Canada to announce a financial penalty for those who don’t get a shot.
In Greece, people older than 60 have until Jan. 16 to receive the first dose, or they will be fined 100 euros for every month they remain unvaccinated, the AP reported.
Austria will impose fines up to 3,600 euros for those who don’t follow the vaccine mandate for ages 14 and older, which is slated to start in February.
In Italy, residents who are 50 and older are required to be vaccinated. In mid-February, those who are unvaccinated could be fined up to 1,600 euros if they enter their workplaces, the AP reported.
A version of this article first appeared on WebMD.com.
CDC to update mask recommendations as Omicron spreads
Director Rochelle Walensky, MD, said on Jan. 12.
“We are preparing an update to the info on our mask website to best reflect the options that are available to people and the different levels of protection different masks provide, and we want to provide Americans the best and most updated information to choose what mask is going to be right for them,” she said at a White House news briefing.
While the higher-quality masks provide better protection, they can be uncomfortable to wear, expensive, and harder to find. That’s why Dr. Walensky added an important caveat.
“Any mask is better than no mask, and we do encourage all Americans to wear a well-fitting mask to protect themselves and prevent the spread of COVID-19. That recommendation is not going to change,” she said.
“Most importantly, the best mask that you wear is the one you will wear and the one you can keep on all day long and tolerate in public indoor settings.”
Meanwhile, the World Health Organization was more focused on vaccines.
WHO officials stressed on Jan. 12 that global vaccine distribution is first priority in defeating the highly contagious Omicron variant, as well as other variants that may evolve.
The WHO’s Technical Advisory Group on COVID-19 Vaccine Composition – a group of experts assessing how COVID-19 vaccines perform against Omicron and other emerging variants – says there is an “urgent need” for broader access to vaccines, along with reviewing and updating current vaccines as needed to ensure protection.
The WHO also disputed the idea that COVID-19 could become endemic in one largely vaccinated nation, while the rest of the world remains unprotected.
“It is up to us how this pandemic unfolds,” Maria Van Kerkhove, PhD, the WHO’s technical lead on COVID-19 response, said at a news briefing.
The WHO has a goal of vaccinating 70% of the population of every country by the middle of the year.
But right now, 90 countries have yet to reach 40% vaccination rates, and 36 of those countries have less than 10% of their populations vaccinated, according to WHO Director General Tedros Adhanom Ghebreyesus, PhD.
A staggering 85% of the African population has not received a first dose.
But progress is being made, Dr. Ghebreyesus said at the briefing.
The WHO said there were over 15 million COVID-19 cases reported last week – the most ever in a single week – and this is likely an underestimate.
The Omicron variant, first identified in South Africa 2 months ago and now found on all seven continents, is “rapidly replacing Delta in almost all countries,” Dr. Ghebreyesus said.
Dr. Walensky said this week’s U.S. daily average COVID-19 case count was 751,000, an increase of 47% from last week. The average daily hospital admissions this week is 19,800, an increase of 33%. Deaths are up 40%, reaching 1,600 per day.
But she also reported new data that supports other research showing Omicron may produce less severe disease. Kaiser Permanente Southern California released a study on Jan. 11 showing that, compared with Delta infections, Omicron was associated with a 53% reduction in hospitalizations, a 74% reduction in intensive care unit admissions, and a 91% lower risk of death.
In the study, no patients with Omicron required mechanical ventilation. The strain now accounts for 98% of cases nationwide.
But Dr. Walensky warned the lower disease severity is not enough to make up for the sheer number of cases that continue to overwhelm hospital systems.
“While we are seeing early evidence that Omicron is less severe than Delta and that those infected are less likely to require hospitalization, it’s important to note that Omicron continues to be much more transmissible than Delta,” she said. “The sudden rise in cases due to Omicron is resulting in unprecedented daily case counts, sickness, absenteeism, and strains on our health care system.”
A version of this article first appeared on WebMD.com.
Director Rochelle Walensky, MD, said on Jan. 12.
“We are preparing an update to the info on our mask website to best reflect the options that are available to people and the different levels of protection different masks provide, and we want to provide Americans the best and most updated information to choose what mask is going to be right for them,” she said at a White House news briefing.
While the higher-quality masks provide better protection, they can be uncomfortable to wear, expensive, and harder to find. That’s why Dr. Walensky added an important caveat.
“Any mask is better than no mask, and we do encourage all Americans to wear a well-fitting mask to protect themselves and prevent the spread of COVID-19. That recommendation is not going to change,” she said.
“Most importantly, the best mask that you wear is the one you will wear and the one you can keep on all day long and tolerate in public indoor settings.”
Meanwhile, the World Health Organization was more focused on vaccines.
WHO officials stressed on Jan. 12 that global vaccine distribution is first priority in defeating the highly contagious Omicron variant, as well as other variants that may evolve.
The WHO’s Technical Advisory Group on COVID-19 Vaccine Composition – a group of experts assessing how COVID-19 vaccines perform against Omicron and other emerging variants – says there is an “urgent need” for broader access to vaccines, along with reviewing and updating current vaccines as needed to ensure protection.
The WHO also disputed the idea that COVID-19 could become endemic in one largely vaccinated nation, while the rest of the world remains unprotected.
“It is up to us how this pandemic unfolds,” Maria Van Kerkhove, PhD, the WHO’s technical lead on COVID-19 response, said at a news briefing.
The WHO has a goal of vaccinating 70% of the population of every country by the middle of the year.
But right now, 90 countries have yet to reach 40% vaccination rates, and 36 of those countries have less than 10% of their populations vaccinated, according to WHO Director General Tedros Adhanom Ghebreyesus, PhD.
A staggering 85% of the African population has not received a first dose.
But progress is being made, Dr. Ghebreyesus said at the briefing.
The WHO said there were over 15 million COVID-19 cases reported last week – the most ever in a single week – and this is likely an underestimate.
The Omicron variant, first identified in South Africa 2 months ago and now found on all seven continents, is “rapidly replacing Delta in almost all countries,” Dr. Ghebreyesus said.
Dr. Walensky said this week’s U.S. daily average COVID-19 case count was 751,000, an increase of 47% from last week. The average daily hospital admissions this week is 19,800, an increase of 33%. Deaths are up 40%, reaching 1,600 per day.
But she also reported new data that supports other research showing Omicron may produce less severe disease. Kaiser Permanente Southern California released a study on Jan. 11 showing that, compared with Delta infections, Omicron was associated with a 53% reduction in hospitalizations, a 74% reduction in intensive care unit admissions, and a 91% lower risk of death.
In the study, no patients with Omicron required mechanical ventilation. The strain now accounts for 98% of cases nationwide.
But Dr. Walensky warned the lower disease severity is not enough to make up for the sheer number of cases that continue to overwhelm hospital systems.
“While we are seeing early evidence that Omicron is less severe than Delta and that those infected are less likely to require hospitalization, it’s important to note that Omicron continues to be much more transmissible than Delta,” she said. “The sudden rise in cases due to Omicron is resulting in unprecedented daily case counts, sickness, absenteeism, and strains on our health care system.”
A version of this article first appeared on WebMD.com.
Director Rochelle Walensky, MD, said on Jan. 12.
“We are preparing an update to the info on our mask website to best reflect the options that are available to people and the different levels of protection different masks provide, and we want to provide Americans the best and most updated information to choose what mask is going to be right for them,” she said at a White House news briefing.
While the higher-quality masks provide better protection, they can be uncomfortable to wear, expensive, and harder to find. That’s why Dr. Walensky added an important caveat.
“Any mask is better than no mask, and we do encourage all Americans to wear a well-fitting mask to protect themselves and prevent the spread of COVID-19. That recommendation is not going to change,” she said.
“Most importantly, the best mask that you wear is the one you will wear and the one you can keep on all day long and tolerate in public indoor settings.”
Meanwhile, the World Health Organization was more focused on vaccines.
WHO officials stressed on Jan. 12 that global vaccine distribution is first priority in defeating the highly contagious Omicron variant, as well as other variants that may evolve.
The WHO’s Technical Advisory Group on COVID-19 Vaccine Composition – a group of experts assessing how COVID-19 vaccines perform against Omicron and other emerging variants – says there is an “urgent need” for broader access to vaccines, along with reviewing and updating current vaccines as needed to ensure protection.
The WHO also disputed the idea that COVID-19 could become endemic in one largely vaccinated nation, while the rest of the world remains unprotected.
“It is up to us how this pandemic unfolds,” Maria Van Kerkhove, PhD, the WHO’s technical lead on COVID-19 response, said at a news briefing.
The WHO has a goal of vaccinating 70% of the population of every country by the middle of the year.
But right now, 90 countries have yet to reach 40% vaccination rates, and 36 of those countries have less than 10% of their populations vaccinated, according to WHO Director General Tedros Adhanom Ghebreyesus, PhD.
A staggering 85% of the African population has not received a first dose.
But progress is being made, Dr. Ghebreyesus said at the briefing.
The WHO said there were over 15 million COVID-19 cases reported last week – the most ever in a single week – and this is likely an underestimate.
The Omicron variant, first identified in South Africa 2 months ago and now found on all seven continents, is “rapidly replacing Delta in almost all countries,” Dr. Ghebreyesus said.
Dr. Walensky said this week’s U.S. daily average COVID-19 case count was 751,000, an increase of 47% from last week. The average daily hospital admissions this week is 19,800, an increase of 33%. Deaths are up 40%, reaching 1,600 per day.
But she also reported new data that supports other research showing Omicron may produce less severe disease. Kaiser Permanente Southern California released a study on Jan. 11 showing that, compared with Delta infections, Omicron was associated with a 53% reduction in hospitalizations, a 74% reduction in intensive care unit admissions, and a 91% lower risk of death.
In the study, no patients with Omicron required mechanical ventilation. The strain now accounts for 98% of cases nationwide.
But Dr. Walensky warned the lower disease severity is not enough to make up for the sheer number of cases that continue to overwhelm hospital systems.
“While we are seeing early evidence that Omicron is less severe than Delta and that those infected are less likely to require hospitalization, it’s important to note that Omicron continues to be much more transmissible than Delta,” she said. “The sudden rise in cases due to Omicron is resulting in unprecedented daily case counts, sickness, absenteeism, and strains on our health care system.”
A version of this article first appeared on WebMD.com.
Urine for a new vaccine alternative
Urine for a new vaccine alternative
Yep, you read that right: Another vaccine alternative. Urine sounds disgusting, but you’ve got to admit, it’s resourceful at least.
Christopher Key, the leader of a group of antivaxxers known as the “Vaccine Police,” is now claiming that you should do “urine therapy,” when means drinking your own pee to ward off COVID-19. According to My. Key, “tons and tons of research” shows the benefits of drinking urine to fight COVID-19, the Guardian reported.
He doesn’t seem like the best source of information, especially since he’s been arrested in the past for refusing to wear a mask in a store. Not wanting to wear a mask in a store doesn’t seem like much, but he also believes that those who administer the COVID-19 vaccine should be “executed” and he tried to impersonate a law official toattempt to arrest a Democratic governor for vaccine mandates.
The overwhelming amount of COVID-19 misinformation has been stressful, yet sometimes laugh-worthy. Urine is not the first “cure” and probably won’t be the last. If you heard something works in a sketchy group on Facebook, it’s probably safe to assume that it absolutely does not. Please don’t recycle your urine.
Vaccine or beer? You must now choose
As the COVID-19 pandemic drags on toward its third year, the large subset of the population who refuse to get vaccinated has proved nearly intractable. Governments have tried numerous incentives to boost vaccination rates, ranging from free beer to million dollar lotteries. Needless to say, beyond their ability to generate LOTME stories, these incentives have been less than effective.
As the frankly unfairly contagious Omicron variant makes it way through the world, our friends in the Great White North have decided enough is enough. If the carrot doesn’t work, the people of Quebec are going to get the stick. Starting on Jan. 18, vaccination cards will be required to enter stores that sell alcohol or cannabis, better known as the things that have gotten us all through this pandemic.
And you know what? Cutting off the booze supply seems to be working. Christian Dubé, Quebec’s health minister, said that the number of vaccination appointments had quadrupled in the new year, rising from 1,500 per day to 6,000 per day, according to the CTV News report. Now, those aren’t massive numbers, but this is big empty Canada we’re talking about, and the unvaccinated make up about 10% of Quebec’s population, so 6,000 a day is quite impressive.
Mr. Dubé added that additional nonessential businesses could be added to the restriction list in the coming weeks, but we’re not sure it’ll be necessary. Those middle-aged soccer moms will do anything to secure their daily merlot. Also, alcohol and cannabis nonessential? The LOTME staff is appalled and offended at this insinuation.
All I need is the polyester that I breathe
When you do laundry, you’re probably thinking more of how to get that ketchup stain out of your white shirt than the effect it has on the environment. Well, research shows it actually has some significance.
That significance comes in the form of microfibers, which are released from natural fabrics such as cotton and from synthetic fabrics such as polyester, which are also considered to be microplastics.
The microfibers that get released in the water when we wash clothes are filtered out eventually, but the dryer is the real culprit, according to a study in Environmental Science & Technology Letters. We’re talking a discharge of up to 120 million microfiber fragments directly into the air annually from just one dryer!
Dryers, they found, emitted between 1.4-40 times more microfibers than did washing machines in previous studies. And polyester fabrics produced more fragments when load sizes increased, while fragment production from cotton fabrics remained constant.
Recent findings suggest that inhaling these microfibers can cause lung inflammation, increase cancer risk, and induce asthma attacks. The authors of the current study suggested additional filtration should be done on dryer vents to reduce the amount of pollutants emitted into the air.
Who would have thought just drying your sheets could be such a dangerous act?
It’s always in the last place you look
At least a million times every morning in this country, a million children yell something like this as they get ready for school: “Mom, have you seen my ...?”
Well, thanks to Defector.com, now we know what Mom should yell back: “Look in your weird cousin Mortimer!”
We will explain ... again.
When they’re not dealing with COVID-19, the folks who work in emergency departments spend a lot of their time removing things that are stuck in people’s bodily orifices. The U.S. Consumer Product Safety Commission even keeps track of them.
So if you’re looking for the number 8 button from the TV remote, or maybe a bullet, check Mortimer’s nose. Maybe you’re missing a lollipop, a hairpin, or some espresso beans. Mortimer’s friend Beulah might have put them in her ear.
Has an earbud gone missing? Another friend of Mortimer’s went to the ED with something stuck in his throat and said that he had a “pill in one hand and his earbud in the other hand, got distracted and took the earbud instead.” Yes, that is an actual quote (via Defector) from the CPSC database.
What about that old saying that someone’s lost his marbles? Well, the ED found one of Mortimer’s marbles ... in his penis. Also a spork, and a bread twist tie, and a chopstick. No, not all at the same time. As for Beulah, a barbell and a Spider-Man action figure somehow found their way – not at the same time, thank goodness – into her vagina.
And have you ever heard someone say that they’re “not going to stand for this”? Mortimer has, so he sat down ... on a light bulb, and a rolling pin, and a billiard ball. Yup, the ED had to remove these items from his rectum.
But not all at the same time, thank goodness.
Urine for a new vaccine alternative
Yep, you read that right: Another vaccine alternative. Urine sounds disgusting, but you’ve got to admit, it’s resourceful at least.
Christopher Key, the leader of a group of antivaxxers known as the “Vaccine Police,” is now claiming that you should do “urine therapy,” when means drinking your own pee to ward off COVID-19. According to My. Key, “tons and tons of research” shows the benefits of drinking urine to fight COVID-19, the Guardian reported.
He doesn’t seem like the best source of information, especially since he’s been arrested in the past for refusing to wear a mask in a store. Not wanting to wear a mask in a store doesn’t seem like much, but he also believes that those who administer the COVID-19 vaccine should be “executed” and he tried to impersonate a law official toattempt to arrest a Democratic governor for vaccine mandates.
The overwhelming amount of COVID-19 misinformation has been stressful, yet sometimes laugh-worthy. Urine is not the first “cure” and probably won’t be the last. If you heard something works in a sketchy group on Facebook, it’s probably safe to assume that it absolutely does not. Please don’t recycle your urine.
Vaccine or beer? You must now choose
As the COVID-19 pandemic drags on toward its third year, the large subset of the population who refuse to get vaccinated has proved nearly intractable. Governments have tried numerous incentives to boost vaccination rates, ranging from free beer to million dollar lotteries. Needless to say, beyond their ability to generate LOTME stories, these incentives have been less than effective.
As the frankly unfairly contagious Omicron variant makes it way through the world, our friends in the Great White North have decided enough is enough. If the carrot doesn’t work, the people of Quebec are going to get the stick. Starting on Jan. 18, vaccination cards will be required to enter stores that sell alcohol or cannabis, better known as the things that have gotten us all through this pandemic.
And you know what? Cutting off the booze supply seems to be working. Christian Dubé, Quebec’s health minister, said that the number of vaccination appointments had quadrupled in the new year, rising from 1,500 per day to 6,000 per day, according to the CTV News report. Now, those aren’t massive numbers, but this is big empty Canada we’re talking about, and the unvaccinated make up about 10% of Quebec’s population, so 6,000 a day is quite impressive.
Mr. Dubé added that additional nonessential businesses could be added to the restriction list in the coming weeks, but we’re not sure it’ll be necessary. Those middle-aged soccer moms will do anything to secure their daily merlot. Also, alcohol and cannabis nonessential? The LOTME staff is appalled and offended at this insinuation.
All I need is the polyester that I breathe
When you do laundry, you’re probably thinking more of how to get that ketchup stain out of your white shirt than the effect it has on the environment. Well, research shows it actually has some significance.
That significance comes in the form of microfibers, which are released from natural fabrics such as cotton and from synthetic fabrics such as polyester, which are also considered to be microplastics.
The microfibers that get released in the water when we wash clothes are filtered out eventually, but the dryer is the real culprit, according to a study in Environmental Science & Technology Letters. We’re talking a discharge of up to 120 million microfiber fragments directly into the air annually from just one dryer!
Dryers, they found, emitted between 1.4-40 times more microfibers than did washing machines in previous studies. And polyester fabrics produced more fragments when load sizes increased, while fragment production from cotton fabrics remained constant.
Recent findings suggest that inhaling these microfibers can cause lung inflammation, increase cancer risk, and induce asthma attacks. The authors of the current study suggested additional filtration should be done on dryer vents to reduce the amount of pollutants emitted into the air.
Who would have thought just drying your sheets could be such a dangerous act?
It’s always in the last place you look
At least a million times every morning in this country, a million children yell something like this as they get ready for school: “Mom, have you seen my ...?”
Well, thanks to Defector.com, now we know what Mom should yell back: “Look in your weird cousin Mortimer!”
We will explain ... again.
When they’re not dealing with COVID-19, the folks who work in emergency departments spend a lot of their time removing things that are stuck in people’s bodily orifices. The U.S. Consumer Product Safety Commission even keeps track of them.
So if you’re looking for the number 8 button from the TV remote, or maybe a bullet, check Mortimer’s nose. Maybe you’re missing a lollipop, a hairpin, or some espresso beans. Mortimer’s friend Beulah might have put them in her ear.
Has an earbud gone missing? Another friend of Mortimer’s went to the ED with something stuck in his throat and said that he had a “pill in one hand and his earbud in the other hand, got distracted and took the earbud instead.” Yes, that is an actual quote (via Defector) from the CPSC database.
What about that old saying that someone’s lost his marbles? Well, the ED found one of Mortimer’s marbles ... in his penis. Also a spork, and a bread twist tie, and a chopstick. No, not all at the same time. As for Beulah, a barbell and a Spider-Man action figure somehow found their way – not at the same time, thank goodness – into her vagina.
And have you ever heard someone say that they’re “not going to stand for this”? Mortimer has, so he sat down ... on a light bulb, and a rolling pin, and a billiard ball. Yup, the ED had to remove these items from his rectum.
But not all at the same time, thank goodness.
Urine for a new vaccine alternative
Yep, you read that right: Another vaccine alternative. Urine sounds disgusting, but you’ve got to admit, it’s resourceful at least.
Christopher Key, the leader of a group of antivaxxers known as the “Vaccine Police,” is now claiming that you should do “urine therapy,” when means drinking your own pee to ward off COVID-19. According to My. Key, “tons and tons of research” shows the benefits of drinking urine to fight COVID-19, the Guardian reported.
He doesn’t seem like the best source of information, especially since he’s been arrested in the past for refusing to wear a mask in a store. Not wanting to wear a mask in a store doesn’t seem like much, but he also believes that those who administer the COVID-19 vaccine should be “executed” and he tried to impersonate a law official toattempt to arrest a Democratic governor for vaccine mandates.
The overwhelming amount of COVID-19 misinformation has been stressful, yet sometimes laugh-worthy. Urine is not the first “cure” and probably won’t be the last. If you heard something works in a sketchy group on Facebook, it’s probably safe to assume that it absolutely does not. Please don’t recycle your urine.
Vaccine or beer? You must now choose
As the COVID-19 pandemic drags on toward its third year, the large subset of the population who refuse to get vaccinated has proved nearly intractable. Governments have tried numerous incentives to boost vaccination rates, ranging from free beer to million dollar lotteries. Needless to say, beyond their ability to generate LOTME stories, these incentives have been less than effective.
As the frankly unfairly contagious Omicron variant makes it way through the world, our friends in the Great White North have decided enough is enough. If the carrot doesn’t work, the people of Quebec are going to get the stick. Starting on Jan. 18, vaccination cards will be required to enter stores that sell alcohol or cannabis, better known as the things that have gotten us all through this pandemic.
And you know what? Cutting off the booze supply seems to be working. Christian Dubé, Quebec’s health minister, said that the number of vaccination appointments had quadrupled in the new year, rising from 1,500 per day to 6,000 per day, according to the CTV News report. Now, those aren’t massive numbers, but this is big empty Canada we’re talking about, and the unvaccinated make up about 10% of Quebec’s population, so 6,000 a day is quite impressive.
Mr. Dubé added that additional nonessential businesses could be added to the restriction list in the coming weeks, but we’re not sure it’ll be necessary. Those middle-aged soccer moms will do anything to secure their daily merlot. Also, alcohol and cannabis nonessential? The LOTME staff is appalled and offended at this insinuation.
All I need is the polyester that I breathe
When you do laundry, you’re probably thinking more of how to get that ketchup stain out of your white shirt than the effect it has on the environment. Well, research shows it actually has some significance.
That significance comes in the form of microfibers, which are released from natural fabrics such as cotton and from synthetic fabrics such as polyester, which are also considered to be microplastics.
The microfibers that get released in the water when we wash clothes are filtered out eventually, but the dryer is the real culprit, according to a study in Environmental Science & Technology Letters. We’re talking a discharge of up to 120 million microfiber fragments directly into the air annually from just one dryer!
Dryers, they found, emitted between 1.4-40 times more microfibers than did washing machines in previous studies. And polyester fabrics produced more fragments when load sizes increased, while fragment production from cotton fabrics remained constant.
Recent findings suggest that inhaling these microfibers can cause lung inflammation, increase cancer risk, and induce asthma attacks. The authors of the current study suggested additional filtration should be done on dryer vents to reduce the amount of pollutants emitted into the air.
Who would have thought just drying your sheets could be such a dangerous act?
It’s always in the last place you look
At least a million times every morning in this country, a million children yell something like this as they get ready for school: “Mom, have you seen my ...?”
Well, thanks to Defector.com, now we know what Mom should yell back: “Look in your weird cousin Mortimer!”
We will explain ... again.
When they’re not dealing with COVID-19, the folks who work in emergency departments spend a lot of their time removing things that are stuck in people’s bodily orifices. The U.S. Consumer Product Safety Commission even keeps track of them.
So if you’re looking for the number 8 button from the TV remote, or maybe a bullet, check Mortimer’s nose. Maybe you’re missing a lollipop, a hairpin, or some espresso beans. Mortimer’s friend Beulah might have put them in her ear.
Has an earbud gone missing? Another friend of Mortimer’s went to the ED with something stuck in his throat and said that he had a “pill in one hand and his earbud in the other hand, got distracted and took the earbud instead.” Yes, that is an actual quote (via Defector) from the CPSC database.
What about that old saying that someone’s lost his marbles? Well, the ED found one of Mortimer’s marbles ... in his penis. Also a spork, and a bread twist tie, and a chopstick. No, not all at the same time. As for Beulah, a barbell and a Spider-Man action figure somehow found their way – not at the same time, thank goodness – into her vagina.
And have you ever heard someone say that they’re “not going to stand for this”? Mortimer has, so he sat down ... on a light bulb, and a rolling pin, and a billiard ball. Yup, the ED had to remove these items from his rectum.
But not all at the same time, thank goodness.
Common cold could protect against COVID-19, study says
, according to a small study published Jan. 10 in Nature Communications.
Previous studies have shown that T cells created from other coronaviruses can recognize SARS-CoV-2, the virus that causes COVID-19. In the new study, researchers at Imperial College London found that the presence of these T cells at the time of COVID-19 exposure could reduce the chance of getting infected.
The findings could provide a blueprint for a second-generation, universal vaccine to prevent infection from COVID-19 variants, including Omicron and ones that crop up later.
“Being exposed to SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why,” Rhia Kundu, PhD, the lead study author from Imperial’s National Heart and Lung Institute, said in a statement.
People with higher levels of T cells from the common cold were less likely to become infected with COVID-19, the researchers found.
“While this is an important discovery, it is only one form of protection, and I would stress that no one should rely on this alone,” Dr. Kundu said. “Instead, the best way to protect yourself against COVID-19 is to be fully vaccinated, including getting your booster dose.”
For the study, Dr. Kundu and colleagues analyzed blood samples from 52 people who lived with someone with confirmed COVID-19 in September 2020. Among the 26 people who didn’t contract COVID-19, there were “significantly higher levels” of preexisting T cells from common cold coronaviruses, as compared with the 26 people who did become infected.
The T cells researched in the study are considered “cross-reactive” and can recognize the proteins of SARS-CoV-2. They offer protection by targeting proteins inside the SARS-CoV-2 virus, rather than the spike proteins on the surface that allow the virus to invade cells.
The current COVID-19 vaccines target the spike proteins, which are more likely to mutate than internal proteins, the researchers wrote. The Omicron variant, for instance, has numerous mutations on spike proteins that may allow it to evade vaccines.
The data suggest that the next step of COVID-19 vaccine development could focus on internal proteins, the researchers said, which could provide lasting protection because T-cell responses persist longer than antibody responses that fade within a few months of vaccination.
“New vaccines that include these conserved, internal proteins would therefore induce broadly protective T-cell responses that should protect against current and future SARS-CoV-2 variants,” Ajit Lalvani, MD, the senior study author and director of Imperial’s respiratory infections health protection research unit, said in the statement.
But more research is needed, the authors said, noting that the study had a small sample size and lacked ethnic diversity, which puts limits on the research.
A version of this article first appeared on WebMD.com
, according to a small study published Jan. 10 in Nature Communications.
Previous studies have shown that T cells created from other coronaviruses can recognize SARS-CoV-2, the virus that causes COVID-19. In the new study, researchers at Imperial College London found that the presence of these T cells at the time of COVID-19 exposure could reduce the chance of getting infected.
The findings could provide a blueprint for a second-generation, universal vaccine to prevent infection from COVID-19 variants, including Omicron and ones that crop up later.
“Being exposed to SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why,” Rhia Kundu, PhD, the lead study author from Imperial’s National Heart and Lung Institute, said in a statement.
People with higher levels of T cells from the common cold were less likely to become infected with COVID-19, the researchers found.
“While this is an important discovery, it is only one form of protection, and I would stress that no one should rely on this alone,” Dr. Kundu said. “Instead, the best way to protect yourself against COVID-19 is to be fully vaccinated, including getting your booster dose.”
For the study, Dr. Kundu and colleagues analyzed blood samples from 52 people who lived with someone with confirmed COVID-19 in September 2020. Among the 26 people who didn’t contract COVID-19, there were “significantly higher levels” of preexisting T cells from common cold coronaviruses, as compared with the 26 people who did become infected.
The T cells researched in the study are considered “cross-reactive” and can recognize the proteins of SARS-CoV-2. They offer protection by targeting proteins inside the SARS-CoV-2 virus, rather than the spike proteins on the surface that allow the virus to invade cells.
The current COVID-19 vaccines target the spike proteins, which are more likely to mutate than internal proteins, the researchers wrote. The Omicron variant, for instance, has numerous mutations on spike proteins that may allow it to evade vaccines.
The data suggest that the next step of COVID-19 vaccine development could focus on internal proteins, the researchers said, which could provide lasting protection because T-cell responses persist longer than antibody responses that fade within a few months of vaccination.
“New vaccines that include these conserved, internal proteins would therefore induce broadly protective T-cell responses that should protect against current and future SARS-CoV-2 variants,” Ajit Lalvani, MD, the senior study author and director of Imperial’s respiratory infections health protection research unit, said in the statement.
But more research is needed, the authors said, noting that the study had a small sample size and lacked ethnic diversity, which puts limits on the research.
A version of this article first appeared on WebMD.com
, according to a small study published Jan. 10 in Nature Communications.
Previous studies have shown that T cells created from other coronaviruses can recognize SARS-CoV-2, the virus that causes COVID-19. In the new study, researchers at Imperial College London found that the presence of these T cells at the time of COVID-19 exposure could reduce the chance of getting infected.
The findings could provide a blueprint for a second-generation, universal vaccine to prevent infection from COVID-19 variants, including Omicron and ones that crop up later.
“Being exposed to SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why,” Rhia Kundu, PhD, the lead study author from Imperial’s National Heart and Lung Institute, said in a statement.
People with higher levels of T cells from the common cold were less likely to become infected with COVID-19, the researchers found.
“While this is an important discovery, it is only one form of protection, and I would stress that no one should rely on this alone,” Dr. Kundu said. “Instead, the best way to protect yourself against COVID-19 is to be fully vaccinated, including getting your booster dose.”
For the study, Dr. Kundu and colleagues analyzed blood samples from 52 people who lived with someone with confirmed COVID-19 in September 2020. Among the 26 people who didn’t contract COVID-19, there were “significantly higher levels” of preexisting T cells from common cold coronaviruses, as compared with the 26 people who did become infected.
The T cells researched in the study are considered “cross-reactive” and can recognize the proteins of SARS-CoV-2. They offer protection by targeting proteins inside the SARS-CoV-2 virus, rather than the spike proteins on the surface that allow the virus to invade cells.
The current COVID-19 vaccines target the spike proteins, which are more likely to mutate than internal proteins, the researchers wrote. The Omicron variant, for instance, has numerous mutations on spike proteins that may allow it to evade vaccines.
The data suggest that the next step of COVID-19 vaccine development could focus on internal proteins, the researchers said, which could provide lasting protection because T-cell responses persist longer than antibody responses that fade within a few months of vaccination.
“New vaccines that include these conserved, internal proteins would therefore induce broadly protective T-cell responses that should protect against current and future SARS-CoV-2 variants,” Ajit Lalvani, MD, the senior study author and director of Imperial’s respiratory infections health protection research unit, said in the statement.
But more research is needed, the authors said, noting that the study had a small sample size and lacked ethnic diversity, which puts limits on the research.
A version of this article first appeared on WebMD.com
Physicians react: Should docs lose their licenses for spreading false COVID information?
Doctors providing “fraudulent” COVID-19 information became a hot-button issue for physicians responding to Medscape’s recent article, "Shouldn’t Doctors Who Spread False COVID-19 Information Lose Their Licenses?”
COVID-19 safety recommendations are set by mainstream medical organizations as new information becomes available, but some doctors consistently oppose advice from the Centers for Disease Control and Prevention and other medical authorities. These physicians often promote off-label, unapproved use of medications for COVID-19 and/or contradict mainstream safety guidelines such as vaccines, masks, and social distancing.
Some medical organizations are concerned that these doctors are hampering efforts to control the highly contagious coronavirus and are, at worst, placing lives in danger with their contrarian views that can spread like wildfire on social media sites. Their words are often used by those who refuse to be vaccinated or wear masks.
State licensing boards have mostly refused to discipline these doctors for making false and/or misleading claims, but as the virus spreads, there are calls to take action against them. However, others worry that such actions would violate free speech and critical thought.
Yes, those doctors are doing wrong
Several physicians took a strong stand against their fellow doctors who are spreading misinformation about COVID-19.
One doctor endorsed the idea of removing licenses for spreading misinformation and called for criminal prosecution: “It should certainly be grounds for cancellation of all licensing (after appropriate examination to rule out acute psychotic episodes, dementia, tumor, etc.) and very likely [include] a charge of manslaughter.”
Another health care provider said, “A person who does not accept science should not, of course, be allowed to practice medicine. One who argues publicly that vaccines and masks don’t work should be prosecuted for crimes ranging from reckless endangerment to attempted murder.”
One reader framed COVID-19 misinformers in stark terms: “These men and women are medical prostitutes. Their medical and surgical colleges [should] have a panel to track in-court testimony and the disinformation they spread ...”
“This is malpractice of the worst kind,” said a clinician. “Public health officials and science are quite clear on [the] best practices for safety during a pandemic, which is killing millions. This is a standard of care.”
“Medical Boards should suspend licenses and give the physician a chance to testify [about] the scientific basis for his comments,” added a health care provider. “Boards involve themselves in all kinds of perceived disciplinary infractions. We are in the midst of a lethal pandemic. I would think that would take precedence over many other issues?”
“I do believe that physicians have the responsibility to speak the truth and have scientifically displayed minds,” said a reader. “Not [to] promulgate misleading, false, and/or unverified information.”
“Any physician, who holds a license, should abide [by] government and state regulation,” asserted a doctor. “He should be disciplined by the board for spreading medical/public misinformation since he is creating potential harm to the population.”
One specialist insisted that “state boards do not do enough to restrict/limit the practice of physicians touting questionable therapies.”
“Any doctor who spreads false information about Covid is hurting our country, our individuals, and our economy and leading to needless deaths,” asserted a physician. “However, there are uncertainties, and where those exist, physicians [should] simply say ‘it is unknown.’”
No, those physicians have a right to speak their beliefs
However, many physicians worried that science and controversial thought were being muzzled.
“Absolutely no,” a doctor stated. “Who judges what is misinformation in this age where debate is canceled? Science advances with challenge, and it’s not about an authority dictating the allowable opinion.”
Another clinician claimed the “truth is very difficult to discern from less-than-truth in a country running on a profit-oriented economic ideology.”
One specialist warned that if disinformation doctors are held responsible, then “that means a lot of doctors” will be “gone” because “almost anything that is written or said about COVID can be contested.”
Another physician warned his colleagues about suppressing new ideas: “To condemn what we didn’t try, or purposefully ignore a different approach because [it] doesn’t agree with our opinion is suppression of information.”
Some doctors insisted the issue extended beyond medicine and into Constitutional freedoms. They also expressed their mistrust in the government to regulate physicians.
“There is a First Amendment in this country,” said one reader. “What you think is false may not be so. The people can listen to whoever they want to and make their own medical decisions. We do not need one iota more of politicizing medicine. Having an MD or DO does not mean you relinquish your First Amendment rights.”
“One of the fundamental problems with a system that allows government to ‘license’ physicians, or any other profession, is that politics inevitably turn to cronyism, and big businesses and wealthy people start controlling the government,” argued a doctor.
One clinician suggested enforcement against health food, drug company commercials, and talk shows: “What about all the [misinformation] at the health food stores and the like. Doctors of natural-whatever? Those info-commercials on tv. How many faxes do I get to ‘approve’ because ‘patients request’ braces and pain-treating expensive compounds advertised on TV? We tolerate those ... What about Dr. Oz and the docs on talk shows claiming BS?”
And the debate goes even further
Some physicians questioned the very notion of claiming “truth.”
“Nobody should be certain that they have the ‘absolute truth,’” said one reader. “In fact, the best clinical insights exceed so-called knowledge by at least one step.”
“Who can determine exactly what is truth?” asked another clinician. “For sure, the ‘Federal Government,’ who ‘is here to help you,’ is not qualified to make such determinations, and who are you to make such a suggestion as to remove someone’s license because they disagree with you? Give me a break!”
Another physician echoed that sentiment: “What’s true and false is often and certainly currently debatable. There are well-qualified physicians (with credentials such as the development of mRNA technology), virologists, and biostatisticians that have valid thoughts on this but do not necessarily agree with the drug company-sponsored journals and news channels (most of them). Their voices should be heard, and they should not lose their licenses. They are doing their work in good conscience.”
One reader commented that he wanted his “freedom of speech,” and offered this defiant advice: “You can take this license and shove it.”
Finally, a physician noted that the political climate has influenced medical directives: “If someone in a leadership role knowingly, and with intent, spread false information, that is wrong. However, during this global pandemic the active and the politics have combined. Red state no mandate, blue state mandate – what does that tell you about American leadership?”
A version of this article first appeared on Medscape.com.
Doctors providing “fraudulent” COVID-19 information became a hot-button issue for physicians responding to Medscape’s recent article, "Shouldn’t Doctors Who Spread False COVID-19 Information Lose Their Licenses?”
COVID-19 safety recommendations are set by mainstream medical organizations as new information becomes available, but some doctors consistently oppose advice from the Centers for Disease Control and Prevention and other medical authorities. These physicians often promote off-label, unapproved use of medications for COVID-19 and/or contradict mainstream safety guidelines such as vaccines, masks, and social distancing.
Some medical organizations are concerned that these doctors are hampering efforts to control the highly contagious coronavirus and are, at worst, placing lives in danger with their contrarian views that can spread like wildfire on social media sites. Their words are often used by those who refuse to be vaccinated or wear masks.
State licensing boards have mostly refused to discipline these doctors for making false and/or misleading claims, but as the virus spreads, there are calls to take action against them. However, others worry that such actions would violate free speech and critical thought.
Yes, those doctors are doing wrong
Several physicians took a strong stand against their fellow doctors who are spreading misinformation about COVID-19.
One doctor endorsed the idea of removing licenses for spreading misinformation and called for criminal prosecution: “It should certainly be grounds for cancellation of all licensing (after appropriate examination to rule out acute psychotic episodes, dementia, tumor, etc.) and very likely [include] a charge of manslaughter.”
Another health care provider said, “A person who does not accept science should not, of course, be allowed to practice medicine. One who argues publicly that vaccines and masks don’t work should be prosecuted for crimes ranging from reckless endangerment to attempted murder.”
One reader framed COVID-19 misinformers in stark terms: “These men and women are medical prostitutes. Their medical and surgical colleges [should] have a panel to track in-court testimony and the disinformation they spread ...”
“This is malpractice of the worst kind,” said a clinician. “Public health officials and science are quite clear on [the] best practices for safety during a pandemic, which is killing millions. This is a standard of care.”
“Medical Boards should suspend licenses and give the physician a chance to testify [about] the scientific basis for his comments,” added a health care provider. “Boards involve themselves in all kinds of perceived disciplinary infractions. We are in the midst of a lethal pandemic. I would think that would take precedence over many other issues?”
“I do believe that physicians have the responsibility to speak the truth and have scientifically displayed minds,” said a reader. “Not [to] promulgate misleading, false, and/or unverified information.”
“Any physician, who holds a license, should abide [by] government and state regulation,” asserted a doctor. “He should be disciplined by the board for spreading medical/public misinformation since he is creating potential harm to the population.”
One specialist insisted that “state boards do not do enough to restrict/limit the practice of physicians touting questionable therapies.”
“Any doctor who spreads false information about Covid is hurting our country, our individuals, and our economy and leading to needless deaths,” asserted a physician. “However, there are uncertainties, and where those exist, physicians [should] simply say ‘it is unknown.’”
No, those physicians have a right to speak their beliefs
However, many physicians worried that science and controversial thought were being muzzled.
“Absolutely no,” a doctor stated. “Who judges what is misinformation in this age where debate is canceled? Science advances with challenge, and it’s not about an authority dictating the allowable opinion.”
Another clinician claimed the “truth is very difficult to discern from less-than-truth in a country running on a profit-oriented economic ideology.”
One specialist warned that if disinformation doctors are held responsible, then “that means a lot of doctors” will be “gone” because “almost anything that is written or said about COVID can be contested.”
Another physician warned his colleagues about suppressing new ideas: “To condemn what we didn’t try, or purposefully ignore a different approach because [it] doesn’t agree with our opinion is suppression of information.”
Some doctors insisted the issue extended beyond medicine and into Constitutional freedoms. They also expressed their mistrust in the government to regulate physicians.
“There is a First Amendment in this country,” said one reader. “What you think is false may not be so. The people can listen to whoever they want to and make their own medical decisions. We do not need one iota more of politicizing medicine. Having an MD or DO does not mean you relinquish your First Amendment rights.”
“One of the fundamental problems with a system that allows government to ‘license’ physicians, or any other profession, is that politics inevitably turn to cronyism, and big businesses and wealthy people start controlling the government,” argued a doctor.
One clinician suggested enforcement against health food, drug company commercials, and talk shows: “What about all the [misinformation] at the health food stores and the like. Doctors of natural-whatever? Those info-commercials on tv. How many faxes do I get to ‘approve’ because ‘patients request’ braces and pain-treating expensive compounds advertised on TV? We tolerate those ... What about Dr. Oz and the docs on talk shows claiming BS?”
And the debate goes even further
Some physicians questioned the very notion of claiming “truth.”
“Nobody should be certain that they have the ‘absolute truth,’” said one reader. “In fact, the best clinical insights exceed so-called knowledge by at least one step.”
“Who can determine exactly what is truth?” asked another clinician. “For sure, the ‘Federal Government,’ who ‘is here to help you,’ is not qualified to make such determinations, and who are you to make such a suggestion as to remove someone’s license because they disagree with you? Give me a break!”
Another physician echoed that sentiment: “What’s true and false is often and certainly currently debatable. There are well-qualified physicians (with credentials such as the development of mRNA technology), virologists, and biostatisticians that have valid thoughts on this but do not necessarily agree with the drug company-sponsored journals and news channels (most of them). Their voices should be heard, and they should not lose their licenses. They are doing their work in good conscience.”
One reader commented that he wanted his “freedom of speech,” and offered this defiant advice: “You can take this license and shove it.”
Finally, a physician noted that the political climate has influenced medical directives: “If someone in a leadership role knowingly, and with intent, spread false information, that is wrong. However, during this global pandemic the active and the politics have combined. Red state no mandate, blue state mandate – what does that tell you about American leadership?”
A version of this article first appeared on Medscape.com.
Doctors providing “fraudulent” COVID-19 information became a hot-button issue for physicians responding to Medscape’s recent article, "Shouldn’t Doctors Who Spread False COVID-19 Information Lose Their Licenses?”
COVID-19 safety recommendations are set by mainstream medical organizations as new information becomes available, but some doctors consistently oppose advice from the Centers for Disease Control and Prevention and other medical authorities. These physicians often promote off-label, unapproved use of medications for COVID-19 and/or contradict mainstream safety guidelines such as vaccines, masks, and social distancing.
Some medical organizations are concerned that these doctors are hampering efforts to control the highly contagious coronavirus and are, at worst, placing lives in danger with their contrarian views that can spread like wildfire on social media sites. Their words are often used by those who refuse to be vaccinated or wear masks.
State licensing boards have mostly refused to discipline these doctors for making false and/or misleading claims, but as the virus spreads, there are calls to take action against them. However, others worry that such actions would violate free speech and critical thought.
Yes, those doctors are doing wrong
Several physicians took a strong stand against their fellow doctors who are spreading misinformation about COVID-19.
One doctor endorsed the idea of removing licenses for spreading misinformation and called for criminal prosecution: “It should certainly be grounds for cancellation of all licensing (after appropriate examination to rule out acute psychotic episodes, dementia, tumor, etc.) and very likely [include] a charge of manslaughter.”
Another health care provider said, “A person who does not accept science should not, of course, be allowed to practice medicine. One who argues publicly that vaccines and masks don’t work should be prosecuted for crimes ranging from reckless endangerment to attempted murder.”
One reader framed COVID-19 misinformers in stark terms: “These men and women are medical prostitutes. Their medical and surgical colleges [should] have a panel to track in-court testimony and the disinformation they spread ...”
“This is malpractice of the worst kind,” said a clinician. “Public health officials and science are quite clear on [the] best practices for safety during a pandemic, which is killing millions. This is a standard of care.”
“Medical Boards should suspend licenses and give the physician a chance to testify [about] the scientific basis for his comments,” added a health care provider. “Boards involve themselves in all kinds of perceived disciplinary infractions. We are in the midst of a lethal pandemic. I would think that would take precedence over many other issues?”
“I do believe that physicians have the responsibility to speak the truth and have scientifically displayed minds,” said a reader. “Not [to] promulgate misleading, false, and/or unverified information.”
“Any physician, who holds a license, should abide [by] government and state regulation,” asserted a doctor. “He should be disciplined by the board for spreading medical/public misinformation since he is creating potential harm to the population.”
One specialist insisted that “state boards do not do enough to restrict/limit the practice of physicians touting questionable therapies.”
“Any doctor who spreads false information about Covid is hurting our country, our individuals, and our economy and leading to needless deaths,” asserted a physician. “However, there are uncertainties, and where those exist, physicians [should] simply say ‘it is unknown.’”
No, those physicians have a right to speak their beliefs
However, many physicians worried that science and controversial thought were being muzzled.
“Absolutely no,” a doctor stated. “Who judges what is misinformation in this age where debate is canceled? Science advances with challenge, and it’s not about an authority dictating the allowable opinion.”
Another clinician claimed the “truth is very difficult to discern from less-than-truth in a country running on a profit-oriented economic ideology.”
One specialist warned that if disinformation doctors are held responsible, then “that means a lot of doctors” will be “gone” because “almost anything that is written or said about COVID can be contested.”
Another physician warned his colleagues about suppressing new ideas: “To condemn what we didn’t try, or purposefully ignore a different approach because [it] doesn’t agree with our opinion is suppression of information.”
Some doctors insisted the issue extended beyond medicine and into Constitutional freedoms. They also expressed their mistrust in the government to regulate physicians.
“There is a First Amendment in this country,” said one reader. “What you think is false may not be so. The people can listen to whoever they want to and make their own medical decisions. We do not need one iota more of politicizing medicine. Having an MD or DO does not mean you relinquish your First Amendment rights.”
“One of the fundamental problems with a system that allows government to ‘license’ physicians, or any other profession, is that politics inevitably turn to cronyism, and big businesses and wealthy people start controlling the government,” argued a doctor.
One clinician suggested enforcement against health food, drug company commercials, and talk shows: “What about all the [misinformation] at the health food stores and the like. Doctors of natural-whatever? Those info-commercials on tv. How many faxes do I get to ‘approve’ because ‘patients request’ braces and pain-treating expensive compounds advertised on TV? We tolerate those ... What about Dr. Oz and the docs on talk shows claiming BS?”
And the debate goes even further
Some physicians questioned the very notion of claiming “truth.”
“Nobody should be certain that they have the ‘absolute truth,’” said one reader. “In fact, the best clinical insights exceed so-called knowledge by at least one step.”
“Who can determine exactly what is truth?” asked another clinician. “For sure, the ‘Federal Government,’ who ‘is here to help you,’ is not qualified to make such determinations, and who are you to make such a suggestion as to remove someone’s license because they disagree with you? Give me a break!”
Another physician echoed that sentiment: “What’s true and false is often and certainly currently debatable. There are well-qualified physicians (with credentials such as the development of mRNA technology), virologists, and biostatisticians that have valid thoughts on this but do not necessarily agree with the drug company-sponsored journals and news channels (most of them). Their voices should be heard, and they should not lose their licenses. They are doing their work in good conscience.”
One reader commented that he wanted his “freedom of speech,” and offered this defiant advice: “You can take this license and shove it.”
Finally, a physician noted that the political climate has influenced medical directives: “If someone in a leadership role knowingly, and with intent, spread false information, that is wrong. However, during this global pandemic the active and the politics have combined. Red state no mandate, blue state mandate – what does that tell you about American leadership?”
A version of this article first appeared on Medscape.com.
U.S. reports record-breaking 1.35 million new COVID cases in a day
The United States reported 1.35 million new COVID-19 cases on Jan. 10, logging the highest daily total for any country in the world during the pandemic.
The United States set the previous record of 1 million cases on Jan. 3. (A large number of cases are reported on Mondays, since many states don’t provide updates over the weekend, according to Reuters.)
Still, the 7-day average for new cases has surpassed 700,000, tripling in 2 weeks as the contagious Omicron variant continues to spread across the country.
The daily record of new cases came a day after the United States crossed the grim milestone of 60 million COVID-19 cases during the pandemic, according to the latest data from Johns Hopkins University. More than 11 million new cases were reported in the past 28 days, with 5 million reported since Jan. 2.
Globally, more than 310 million cases have been reported, resulting in nearly 5.5 million COVID-19 deaths. Almost 40 million cases have been confirmed worldwide during the past month, with the United States accounting for 28% of those.
Texas became the second state to report more than 5 million cases since the pandemic began, behind California’s total of 6 million cases. Florida has reported more than 4.6 million, while New York has reported more than 4.1 million.
The United States has also hit an all-time high for hospitalizations, with nearly 146,000 COVID-19 patients in hospitals across the country, according to the latest data from the U.S. Department of Health and Human Services. The previous record was 142,000 hospitalizations in January 2021.
Jan. 11’s hospitalizations are more than twice as many as 2 weeks ago, according to CNN. About 78% of inpatient beds are in use nationwide, and 21% are being used for COVID-19 patients.
Deaths are averaging about 1,700 per day, Reuters reported, which is up from 1,400 in recent days but not much higher than earlier this winter. The peak average was 3,400 daily deaths in mid-January 2021.
The surging numbers of cases and hospitalizations across the country are straining hospitals. On Jan. 10, Virginia Gov. Ralph Northam declared a state of emergency after the number of intensive care unit hospitalizations more than doubled since Dec. 1, CNN reported. The order allows hospitals to expand bed capacity, use telehealth options, and be more flexible with staffing.
Texas is hiring at least 2,700 medical staff to help with the surge, CNN reported, and Kentucky has mobilized the National Guard to provide support.
“Omicron continues to burn through the commonwealth, growing at levels we have never seen before. Omicron is significantly more contagious than even the Delta variant,” Kentucky Gov. Andy Beshear said during a news briefing Jan. 10.
Kentucky reported its highest weekly total of cases last week and has its highest rate of positive tests, at 26%. Mr. Beshear said the state is down to 134 available adult ICU beds.
“If it spreads at the rate we are seeing, it is certainly going to fill up our hospitals,” he said.
A version of this article first appeared on WebMD.com.
The United States reported 1.35 million new COVID-19 cases on Jan. 10, logging the highest daily total for any country in the world during the pandemic.
The United States set the previous record of 1 million cases on Jan. 3. (A large number of cases are reported on Mondays, since many states don’t provide updates over the weekend, according to Reuters.)
Still, the 7-day average for new cases has surpassed 700,000, tripling in 2 weeks as the contagious Omicron variant continues to spread across the country.
The daily record of new cases came a day after the United States crossed the grim milestone of 60 million COVID-19 cases during the pandemic, according to the latest data from Johns Hopkins University. More than 11 million new cases were reported in the past 28 days, with 5 million reported since Jan. 2.
Globally, more than 310 million cases have been reported, resulting in nearly 5.5 million COVID-19 deaths. Almost 40 million cases have been confirmed worldwide during the past month, with the United States accounting for 28% of those.
Texas became the second state to report more than 5 million cases since the pandemic began, behind California’s total of 6 million cases. Florida has reported more than 4.6 million, while New York has reported more than 4.1 million.
The United States has also hit an all-time high for hospitalizations, with nearly 146,000 COVID-19 patients in hospitals across the country, according to the latest data from the U.S. Department of Health and Human Services. The previous record was 142,000 hospitalizations in January 2021.
Jan. 11’s hospitalizations are more than twice as many as 2 weeks ago, according to CNN. About 78% of inpatient beds are in use nationwide, and 21% are being used for COVID-19 patients.
Deaths are averaging about 1,700 per day, Reuters reported, which is up from 1,400 in recent days but not much higher than earlier this winter. The peak average was 3,400 daily deaths in mid-January 2021.
The surging numbers of cases and hospitalizations across the country are straining hospitals. On Jan. 10, Virginia Gov. Ralph Northam declared a state of emergency after the number of intensive care unit hospitalizations more than doubled since Dec. 1, CNN reported. The order allows hospitals to expand bed capacity, use telehealth options, and be more flexible with staffing.
Texas is hiring at least 2,700 medical staff to help with the surge, CNN reported, and Kentucky has mobilized the National Guard to provide support.
“Omicron continues to burn through the commonwealth, growing at levels we have never seen before. Omicron is significantly more contagious than even the Delta variant,” Kentucky Gov. Andy Beshear said during a news briefing Jan. 10.
Kentucky reported its highest weekly total of cases last week and has its highest rate of positive tests, at 26%. Mr. Beshear said the state is down to 134 available adult ICU beds.
“If it spreads at the rate we are seeing, it is certainly going to fill up our hospitals,” he said.
A version of this article first appeared on WebMD.com.
The United States reported 1.35 million new COVID-19 cases on Jan. 10, logging the highest daily total for any country in the world during the pandemic.
The United States set the previous record of 1 million cases on Jan. 3. (A large number of cases are reported on Mondays, since many states don’t provide updates over the weekend, according to Reuters.)
Still, the 7-day average for new cases has surpassed 700,000, tripling in 2 weeks as the contagious Omicron variant continues to spread across the country.
The daily record of new cases came a day after the United States crossed the grim milestone of 60 million COVID-19 cases during the pandemic, according to the latest data from Johns Hopkins University. More than 11 million new cases were reported in the past 28 days, with 5 million reported since Jan. 2.
Globally, more than 310 million cases have been reported, resulting in nearly 5.5 million COVID-19 deaths. Almost 40 million cases have been confirmed worldwide during the past month, with the United States accounting for 28% of those.
Texas became the second state to report more than 5 million cases since the pandemic began, behind California’s total of 6 million cases. Florida has reported more than 4.6 million, while New York has reported more than 4.1 million.
The United States has also hit an all-time high for hospitalizations, with nearly 146,000 COVID-19 patients in hospitals across the country, according to the latest data from the U.S. Department of Health and Human Services. The previous record was 142,000 hospitalizations in January 2021.
Jan. 11’s hospitalizations are more than twice as many as 2 weeks ago, according to CNN. About 78% of inpatient beds are in use nationwide, and 21% are being used for COVID-19 patients.
Deaths are averaging about 1,700 per day, Reuters reported, which is up from 1,400 in recent days but not much higher than earlier this winter. The peak average was 3,400 daily deaths in mid-January 2021.
The surging numbers of cases and hospitalizations across the country are straining hospitals. On Jan. 10, Virginia Gov. Ralph Northam declared a state of emergency after the number of intensive care unit hospitalizations more than doubled since Dec. 1, CNN reported. The order allows hospitals to expand bed capacity, use telehealth options, and be more flexible with staffing.
Texas is hiring at least 2,700 medical staff to help with the surge, CNN reported, and Kentucky has mobilized the National Guard to provide support.
“Omicron continues to burn through the commonwealth, growing at levels we have never seen before. Omicron is significantly more contagious than even the Delta variant,” Kentucky Gov. Andy Beshear said during a news briefing Jan. 10.
Kentucky reported its highest weekly total of cases last week and has its highest rate of positive tests, at 26%. Mr. Beshear said the state is down to 134 available adult ICU beds.
“If it spreads at the rate we are seeing, it is certainly going to fill up our hospitals,” he said.
A version of this article first appeared on WebMD.com.
Super-low uric acid may not be best for erosive gout
Lowering the serum urate target to less than 0.20 mmol/L (<3.6 mg/dL) for patients with erosive gout does not achieve better gout outcomes and leads to more medication use and subsequent side effects, according to findings from a 2-year, double-blind, randomized, controlled trial.
Nicola Dalbeth, MD, of the bone and joint research group, department of medicine, faculty of medical and health sciences at University of Auckland (New Zealand), and coauthors noted that intensive serum urate lowering is difficult to achieve with oral urate-lowering therapy (ULT) and their findings suggest lower is not always better.
Their data, published in Arthritis & Rheumatology, suggest the less-intensive standard target of less than 0.30 mmol/L (<5.4 mg/dL), currently recommended by rheumatology guidelines, is sufficient.
The more intensive target leads to a high medication burden and does not improve bone erosion score in erosive gout, the authors found.
Rheumatologist Angelo Gaffo, MD, associate professor of medicine at the University of Alabama at Birmingham, who was not part of the study, said erosion scores are the best way to test outcomes and this study provides support for current gout treatment approaches.
“It is reassuring that the approach of treating to target is a good approach,” Dr. Gaffo said. “The very, very low targets were not better than the [standard target].”
The trial included 104 participants with erosive gout on oral ULT who were randomized either to a serum urate target of less than 0.20 mmol/L or less than 0.30 mmol/L.
Ninety participants completed the study: 44 (85%) in the intensive target group and 46 (88%) in the standard target group. All were included in the primary intention-to-treat analysis. Participants were mostly men with an average age of 61. Average period of disease was 19 years and about half had a gout flare in the 3 months before enrollment in the study.
Fewer in intensive group hit target
The researchers found that serum urate at year 2 was significantly lower in the intensive target group, compared with the level in the standard target group (P = .002), but fewer participants in the intensive group hit their target, compared with those in the standard group (62% vs. 83%; P < .05).
The intensive group also required more medication. Participants in that group needed higher doses of the first-line treatment allopurinol (mean, 746 mg/day vs. 496 mg/day; P < .001). They also used more combination therapy (P = .0004).
Bone erosion scores were slightly better in both groups over 2 years, but there was no between-group difference (P = .20).
Rates of adverse and serious adverse events were similar between the groups.
The authors noted that a previous study has shown that escalating doses of allopurinol to achieve a target lower than 0.36 mmol/L (6.48 mg/dL) can reduce progression of bone erosion in gout.
“However, improved erosion scores were not observed in this study,” the authors noted.
The authors said that emerging data on intensive serum urate lowering “may lead to erosion healing in gout,” particularly with pegloticase (Krystexxa), a treatment that leads to profound reductions in serum urate.
They highlighted a small longitudinal study of patients treated with pegloticase in whom researchers observed the filling in of bone erosions over a year.
Pegloticase not available outside United States
However, the authors explained, use of pegloticase is unlikely to be widespread for erosive gout because of its lack of availability outside the United States and the need for infusions every 2 weeks. Therefore, more feasible strategies are needed.
Guidelines suggest the serum urate target of less than 0.30 mmol/L (5.4 mg/dL) for people with severe gout, including those with chronic arthropathy.
Managing gout is a long-term process
Herbert S.B. Baraf, MD, a rheumatologist in a large group practice in the Washington, D.C., area and clinical professor of medicine at George Washington University, Washington, who was not part of this study, said he would not come to the conclusion that some cynics might draw that there’s no point in trying to continually lower uric acid.
“Managing gout is a long-term proposition, and the long-term benefit of continuous uric acid lowering continue to accumulate over a period of time,” Dr. Baraf said.
He agreed with Dr. Dalbeth and colleagues that trying to get serum uric acid to less than 0.20 mmol/L is very difficult to achieve with oral drugs.
He said: “The study was not able to show a change in erosions because the amount of uric acid lowering wasn’t profound enough over a short enough period of time to show that, but over a longer period of time it might well show that.”
He said oral therapies work more slowly than enzyme-based therapies, such as pegloticase, but agreed there are barriers to using pegloticase.
“A drug like pegloticase costs about $26,000 per infusion every 2 weeks for a 6-month period. It’s not practical, and we tend to use it for people who are severely functionally impaired,” said Dr. Baraf.
It would still be a goal to keep the arthritis from progressing by using oral therapies, he said.
“I wouldn’t denigrate the fact that oral therapies are effective in decreasing flares over time, decreasing tophaceous deposits and probably – over a longer period of time allowing bone to heal. But 2 years is not enough time to show that.” He said showing benefit on erosions may take 5-10 years instead.
The study authors noted that the trial’s results “are not relevant to those without erosive disease, and to health care systems without access to a broad range of urate-lowering agents.”
Dr. Dalbeth reports personal fees (all less than $10,000) from AstraZeneca, Dyve BioSciences, Selecta, Arthrosi, Horizon, AbbVie, JW Pharmaceuticals, and PK Med outside the submitted work. The other authors have no disclosures. Dr. Gaffo reported no relevant financial relationships. Dr. Baraf has been an investigator/consultant and speaker for Horizon Therapeutics, maker of pegloticase; is an investigator and a consultant to Selecta Biosciences; and has been an investigator, speaker, and consultant for Takeda.
Lowering the serum urate target to less than 0.20 mmol/L (<3.6 mg/dL) for patients with erosive gout does not achieve better gout outcomes and leads to more medication use and subsequent side effects, according to findings from a 2-year, double-blind, randomized, controlled trial.
Nicola Dalbeth, MD, of the bone and joint research group, department of medicine, faculty of medical and health sciences at University of Auckland (New Zealand), and coauthors noted that intensive serum urate lowering is difficult to achieve with oral urate-lowering therapy (ULT) and their findings suggest lower is not always better.
Their data, published in Arthritis & Rheumatology, suggest the less-intensive standard target of less than 0.30 mmol/L (<5.4 mg/dL), currently recommended by rheumatology guidelines, is sufficient.
The more intensive target leads to a high medication burden and does not improve bone erosion score in erosive gout, the authors found.
Rheumatologist Angelo Gaffo, MD, associate professor of medicine at the University of Alabama at Birmingham, who was not part of the study, said erosion scores are the best way to test outcomes and this study provides support for current gout treatment approaches.
“It is reassuring that the approach of treating to target is a good approach,” Dr. Gaffo said. “The very, very low targets were not better than the [standard target].”
The trial included 104 participants with erosive gout on oral ULT who were randomized either to a serum urate target of less than 0.20 mmol/L or less than 0.30 mmol/L.
Ninety participants completed the study: 44 (85%) in the intensive target group and 46 (88%) in the standard target group. All were included in the primary intention-to-treat analysis. Participants were mostly men with an average age of 61. Average period of disease was 19 years and about half had a gout flare in the 3 months before enrollment in the study.
Fewer in intensive group hit target
The researchers found that serum urate at year 2 was significantly lower in the intensive target group, compared with the level in the standard target group (P = .002), but fewer participants in the intensive group hit their target, compared with those in the standard group (62% vs. 83%; P < .05).
The intensive group also required more medication. Participants in that group needed higher doses of the first-line treatment allopurinol (mean, 746 mg/day vs. 496 mg/day; P < .001). They also used more combination therapy (P = .0004).
Bone erosion scores were slightly better in both groups over 2 years, but there was no between-group difference (P = .20).
Rates of adverse and serious adverse events were similar between the groups.
The authors noted that a previous study has shown that escalating doses of allopurinol to achieve a target lower than 0.36 mmol/L (6.48 mg/dL) can reduce progression of bone erosion in gout.
“However, improved erosion scores were not observed in this study,” the authors noted.
The authors said that emerging data on intensive serum urate lowering “may lead to erosion healing in gout,” particularly with pegloticase (Krystexxa), a treatment that leads to profound reductions in serum urate.
They highlighted a small longitudinal study of patients treated with pegloticase in whom researchers observed the filling in of bone erosions over a year.
Pegloticase not available outside United States
However, the authors explained, use of pegloticase is unlikely to be widespread for erosive gout because of its lack of availability outside the United States and the need for infusions every 2 weeks. Therefore, more feasible strategies are needed.
Guidelines suggest the serum urate target of less than 0.30 mmol/L (5.4 mg/dL) for people with severe gout, including those with chronic arthropathy.
Managing gout is a long-term process
Herbert S.B. Baraf, MD, a rheumatologist in a large group practice in the Washington, D.C., area and clinical professor of medicine at George Washington University, Washington, who was not part of this study, said he would not come to the conclusion that some cynics might draw that there’s no point in trying to continually lower uric acid.
“Managing gout is a long-term proposition, and the long-term benefit of continuous uric acid lowering continue to accumulate over a period of time,” Dr. Baraf said.
He agreed with Dr. Dalbeth and colleagues that trying to get serum uric acid to less than 0.20 mmol/L is very difficult to achieve with oral drugs.
He said: “The study was not able to show a change in erosions because the amount of uric acid lowering wasn’t profound enough over a short enough period of time to show that, but over a longer period of time it might well show that.”
He said oral therapies work more slowly than enzyme-based therapies, such as pegloticase, but agreed there are barriers to using pegloticase.
“A drug like pegloticase costs about $26,000 per infusion every 2 weeks for a 6-month period. It’s not practical, and we tend to use it for people who are severely functionally impaired,” said Dr. Baraf.
It would still be a goal to keep the arthritis from progressing by using oral therapies, he said.
“I wouldn’t denigrate the fact that oral therapies are effective in decreasing flares over time, decreasing tophaceous deposits and probably – over a longer period of time allowing bone to heal. But 2 years is not enough time to show that.” He said showing benefit on erosions may take 5-10 years instead.
The study authors noted that the trial’s results “are not relevant to those without erosive disease, and to health care systems without access to a broad range of urate-lowering agents.”
Dr. Dalbeth reports personal fees (all less than $10,000) from AstraZeneca, Dyve BioSciences, Selecta, Arthrosi, Horizon, AbbVie, JW Pharmaceuticals, and PK Med outside the submitted work. The other authors have no disclosures. Dr. Gaffo reported no relevant financial relationships. Dr. Baraf has been an investigator/consultant and speaker for Horizon Therapeutics, maker of pegloticase; is an investigator and a consultant to Selecta Biosciences; and has been an investigator, speaker, and consultant for Takeda.
Lowering the serum urate target to less than 0.20 mmol/L (<3.6 mg/dL) for patients with erosive gout does not achieve better gout outcomes and leads to more medication use and subsequent side effects, according to findings from a 2-year, double-blind, randomized, controlled trial.
Nicola Dalbeth, MD, of the bone and joint research group, department of medicine, faculty of medical and health sciences at University of Auckland (New Zealand), and coauthors noted that intensive serum urate lowering is difficult to achieve with oral urate-lowering therapy (ULT) and their findings suggest lower is not always better.
Their data, published in Arthritis & Rheumatology, suggest the less-intensive standard target of less than 0.30 mmol/L (<5.4 mg/dL), currently recommended by rheumatology guidelines, is sufficient.
The more intensive target leads to a high medication burden and does not improve bone erosion score in erosive gout, the authors found.
Rheumatologist Angelo Gaffo, MD, associate professor of medicine at the University of Alabama at Birmingham, who was not part of the study, said erosion scores are the best way to test outcomes and this study provides support for current gout treatment approaches.
“It is reassuring that the approach of treating to target is a good approach,” Dr. Gaffo said. “The very, very low targets were not better than the [standard target].”
The trial included 104 participants with erosive gout on oral ULT who were randomized either to a serum urate target of less than 0.20 mmol/L or less than 0.30 mmol/L.
Ninety participants completed the study: 44 (85%) in the intensive target group and 46 (88%) in the standard target group. All were included in the primary intention-to-treat analysis. Participants were mostly men with an average age of 61. Average period of disease was 19 years and about half had a gout flare in the 3 months before enrollment in the study.
Fewer in intensive group hit target
The researchers found that serum urate at year 2 was significantly lower in the intensive target group, compared with the level in the standard target group (P = .002), but fewer participants in the intensive group hit their target, compared with those in the standard group (62% vs. 83%; P < .05).
The intensive group also required more medication. Participants in that group needed higher doses of the first-line treatment allopurinol (mean, 746 mg/day vs. 496 mg/day; P < .001). They also used more combination therapy (P = .0004).
Bone erosion scores were slightly better in both groups over 2 years, but there was no between-group difference (P = .20).
Rates of adverse and serious adverse events were similar between the groups.
The authors noted that a previous study has shown that escalating doses of allopurinol to achieve a target lower than 0.36 mmol/L (6.48 mg/dL) can reduce progression of bone erosion in gout.
“However, improved erosion scores were not observed in this study,” the authors noted.
The authors said that emerging data on intensive serum urate lowering “may lead to erosion healing in gout,” particularly with pegloticase (Krystexxa), a treatment that leads to profound reductions in serum urate.
They highlighted a small longitudinal study of patients treated with pegloticase in whom researchers observed the filling in of bone erosions over a year.
Pegloticase not available outside United States
However, the authors explained, use of pegloticase is unlikely to be widespread for erosive gout because of its lack of availability outside the United States and the need for infusions every 2 weeks. Therefore, more feasible strategies are needed.
Guidelines suggest the serum urate target of less than 0.30 mmol/L (5.4 mg/dL) for people with severe gout, including those with chronic arthropathy.
Managing gout is a long-term process
Herbert S.B. Baraf, MD, a rheumatologist in a large group practice in the Washington, D.C., area and clinical professor of medicine at George Washington University, Washington, who was not part of this study, said he would not come to the conclusion that some cynics might draw that there’s no point in trying to continually lower uric acid.
“Managing gout is a long-term proposition, and the long-term benefit of continuous uric acid lowering continue to accumulate over a period of time,” Dr. Baraf said.
He agreed with Dr. Dalbeth and colleagues that trying to get serum uric acid to less than 0.20 mmol/L is very difficult to achieve with oral drugs.
He said: “The study was not able to show a change in erosions because the amount of uric acid lowering wasn’t profound enough over a short enough period of time to show that, but over a longer period of time it might well show that.”
He said oral therapies work more slowly than enzyme-based therapies, such as pegloticase, but agreed there are barriers to using pegloticase.
“A drug like pegloticase costs about $26,000 per infusion every 2 weeks for a 6-month period. It’s not practical, and we tend to use it for people who are severely functionally impaired,” said Dr. Baraf.
It would still be a goal to keep the arthritis from progressing by using oral therapies, he said.
“I wouldn’t denigrate the fact that oral therapies are effective in decreasing flares over time, decreasing tophaceous deposits and probably – over a longer period of time allowing bone to heal. But 2 years is not enough time to show that.” He said showing benefit on erosions may take 5-10 years instead.
The study authors noted that the trial’s results “are not relevant to those without erosive disease, and to health care systems without access to a broad range of urate-lowering agents.”
Dr. Dalbeth reports personal fees (all less than $10,000) from AstraZeneca, Dyve BioSciences, Selecta, Arthrosi, Horizon, AbbVie, JW Pharmaceuticals, and PK Med outside the submitted work. The other authors have no disclosures. Dr. Gaffo reported no relevant financial relationships. Dr. Baraf has been an investigator/consultant and speaker for Horizon Therapeutics, maker of pegloticase; is an investigator and a consultant to Selecta Biosciences; and has been an investigator, speaker, and consultant for Takeda.
FROM ARTHRITIS & RHEUMATOLOGY
Proactive infliximab monitoring found best for sustaining control of inflammatory diseases
A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.
The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.
TDM is ‘not the holy grail,’ and that’s OK
“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.
“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”
For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.
“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”
As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.
“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
Study details
To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.
The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.
Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.
A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.
Removing barriers to TDM
It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.
“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.
Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.
For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”
The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”
The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.
A version of this article first appeared on Medscape.com.
A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.
The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.
TDM is ‘not the holy grail,’ and that’s OK
“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.
“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”
For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.
“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”
As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.
“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
Study details
To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.
The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.
Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.
A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.
Removing barriers to TDM
It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.
“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.
Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.
For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”
The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”
The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.
A version of this article first appeared on Medscape.com.
A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.
The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.
TDM is ‘not the holy grail,’ and that’s OK
“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.
“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”
For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.
“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”
As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.
“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
Study details
To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.
The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.
Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.
A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.
Removing barriers to TDM
It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.
“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.
Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.
For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”
The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”
The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.
A version of this article first appeared on Medscape.com.
FROM JAMA
COVID-vaccine myocarditis: Rare, mild, and usually in young men
The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”
The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.
That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
Unlikely, brief, and ‘benign’
“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.
In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”
Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.
And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.
Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.
And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.
In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
Males of a certain age
Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.
The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.
In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.
In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”
Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.
In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
Sex hormones may be key
The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.
Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.
“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”
“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”
Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.
Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”
Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”
In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.
Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”
Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
Modulation of immune responses
Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.
“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.
But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”
“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.
Prospects for younger children
Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?
Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.
It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”
A version of this article first appeared on Medscape.com.
The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”
The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.
That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
Unlikely, brief, and ‘benign’
“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.
In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”
Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.
And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.
Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.
And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.
In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
Males of a certain age
Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.
The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.
In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.
In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”
Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.
In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
Sex hormones may be key
The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.
Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.
“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”
“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”
Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.
Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”
Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”
In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.
Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”
Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
Modulation of immune responses
Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.
“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.
But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”
“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.
Prospects for younger children
Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?
Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.
It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”
A version of this article first appeared on Medscape.com.
The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”
The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.
That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
Unlikely, brief, and ‘benign’
“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.
In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”
Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.
And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.
Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.
And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.
In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
Males of a certain age
Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.
The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.
In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.
In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”
Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.
In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
Sex hormones may be key
The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.
Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.
“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”
“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”
Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.
Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”
Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”
In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.
Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”
Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
Modulation of immune responses
Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.
“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.
But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”
“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.
Prospects for younger children
Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?
Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.
It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”
A version of this article first appeared on Medscape.com.