Emily Willingham

A mainstay of treatment for prostate cancer is to deprive it of androgens, the hormones that make it grow. The testes are the main source of these hormones, so treatment can consist of either surgical removal of these organs or use of drugs to block their hormone production.

Over time, some prostate cancers become resistant to these treatments and begin to expand again. As with many cancers that show these behaviors, finding exactly what makes them resistant can be tricky.

A culprit may be bacteria that live in the gut. Researchers found that in castrated mice and in people having androgen deprivation therapy, some of these gut bacteria start producing androgens that are easily taken into the bloodstream. According to these new findings,published in the journal Science, the androgens seem to support the growth of prostate cancer and its resistance to treatment.

This study is the first to show that bacteria can produce testosterone, although the investigators are not yet sure what triggers them to start doing that. Androgen deprivation treatment may also lead to more of these hormone-producing microbes in the gut, the results suggest. Fecal bacterial of people with treatment-resistant prostate cancer also showed a link to lower life expectancy.

Fecal transplants from mice with treatment-resistant prostate cancer could trigger resistance in animals with disease susceptible to these hormones. When these mice received fecal transplants from humans with resistant cancer, the effect was the same: a shift to treatment resistance.

But the converse also was true: Fecal transplants from mice or humans with hormone-susceptible cancer contributed to limiting tumor growth.

The findings may suggest new therapeutic targets: the microbes living in the gut. In mouse studies, the researchers found that when they wiped out these bacteria, the cancer was much slower to progress to treatment resistance. Authors of a commentary accompanying the study say there are other places to look for bacteria that might be making these hormones, too, including the urinary tract or even in the tumor itself.

A version of this article first appeared on WebMD.com.

A mainstay of treatment for prostate cancer is to deprive it of androgens, the hormones that make it grow. The testes are the main source of these hormones, so treatment can consist of either surgical removal of these organs or use of drugs to block their hormone production.

Over time, some prostate cancers become resistant to these treatments and begin to expand again. As with many cancers that show these behaviors, finding exactly what makes them resistant can be tricky.

A culprit may be bacteria that live in the gut. Researchers found that in castrated mice and in people having androgen deprivation therapy, some of these gut bacteria start producing androgens that are easily taken into the bloodstream. According to these new findings,published in the journal Science, the androgens seem to support the growth of prostate cancer and its resistance to treatment.

This study is the first to show that bacteria can produce testosterone, although the investigators are not yet sure what triggers them to start doing that. Androgen deprivation treatment may also lead to more of these hormone-producing microbes in the gut, the results suggest. Fecal bacterial of people with treatment-resistant prostate cancer also showed a link to lower life expectancy.

Fecal transplants from mice with treatment-resistant prostate cancer could trigger resistance in animals with disease susceptible to these hormones. When these mice received fecal transplants from humans with resistant cancer, the effect was the same: a shift to treatment resistance.

But the converse also was true: Fecal transplants from mice or humans with hormone-susceptible cancer contributed to limiting tumor growth.

The findings may suggest new therapeutic targets: the microbes living in the gut. In mouse studies, the researchers found that when they wiped out these bacteria, the cancer was much slower to progress to treatment resistance. Authors of a commentary accompanying the study say there are other places to look for bacteria that might be making these hormones, too, including the urinary tract or even in the tumor itself.

A version of this article first appeared on WebMD.com.

A mainstay of treatment for prostate cancer is to deprive it of androgens, the hormones that make it grow. The testes are the main source of these hormones, so treatment can consist of either surgical removal of these organs or use of drugs to block their hormone production.

Over time, some prostate cancers become resistant to these treatments and begin to expand again. As with many cancers that show these behaviors, finding exactly what makes them resistant can be tricky.

A culprit may be bacteria that live in the gut. Researchers found that in castrated mice and in people having androgen deprivation therapy, some of these gut bacteria start producing androgens that are easily taken into the bloodstream. According to these new findings,published in the journal Science, the androgens seem to support the growth of prostate cancer and its resistance to treatment.

This study is the first to show that bacteria can produce testosterone, although the investigators are not yet sure what triggers them to start doing that. Androgen deprivation treatment may also lead to more of these hormone-producing microbes in the gut, the results suggest. Fecal bacterial of people with treatment-resistant prostate cancer also showed a link to lower life expectancy.

Fecal transplants from mice with treatment-resistant prostate cancer could trigger resistance in animals with disease susceptible to these hormones. When these mice received fecal transplants from humans with resistant cancer, the effect was the same: a shift to treatment resistance.

But the converse also was true: Fecal transplants from mice or humans with hormone-susceptible cancer contributed to limiting tumor growth.

The findings may suggest new therapeutic targets: the microbes living in the gut. In mouse studies, the researchers found that when they wiped out these bacteria, the cancer was much slower to progress to treatment resistance. Authors of a commentary accompanying the study say there are other places to look for bacteria that might be making these hormones, too, including the urinary tract or even in the tumor itself.

A version of this article first appeared on WebMD.com.

Two new cases of a mysterious virus have been reported by the Alaska Department of Health and Social Services. Both people were diagnosed after receiving urgent care in a Fairbanks-area clinic. One was a child with a sore on the left elbow, along with fever and swollen lymph nodes. And the other was an unrelated middle-aged woman with a pox mark on her leg, swollen lymph nodes, and joint pain. In both cases, symptoms improved within 3 weeks.

This isn’t the first time the so-called Alaskapox virus has been detected in the region. In 2015, a woman living near Fairbanks turned up at her doctor’s office with a single reddened pox-like mark on her upper arm and a feeling of fatigue.

Sampling of the pox mark showed that it was caused by a previously unidentified virus of the same family as smallpox and cowpox.

Five years later, another woman showed up with similar signs and symptoms, and her pox also proved to be the result of what public health experts started calling the Alaskapox virus.

In both cases, the women recovered completely.
 

Smallpox-like illness

Public health sleuths figured out that in three of the four cases, the patients lived in a home with a cat or cats, and one of these cats was known to hunt small animals.

Experts already knew that cats mingling in cow pastures and sickened by cattle virus had helped cowpox make the leap from bovines to humans. And just as in the case of cowpox, they suspected that cats might again be spreading this new virus to people, too.

All four of the infected people lived in sparsely populated areas amid forests. Officials laid animal traps where some of the affected people lived and identified the virus in several species of small wild animals.

The animals that turned up most often with Alaskapox were small mouse-like voles. The rodents with rounded muzzles are known for burrowing in the region. And scientists suspect the Alaskapox virus makes its way from these wild animals to humans through their pet cats or possibly by direct exposure outdoors.

None of the four people identified so far with Alaskapox knew each other or interacted, so officials also suspect that there are more cases going unrecognized, possibly because the symptoms are mild or nonexistent.

There are no documented cases of person-to-person transmission of Alaskapox, according to public health officials monitoring the small number of cases. But other pox viruses can spread by direct contact with skin lesions, so clinicians are recommending that people cover wounds with bandages. Three of the people with Alaskapox mistook their lesions at first for a bite from a spider or insect.

A version of this article first appeared on WebMD.com.

Two new cases of a mysterious virus have been reported by the Alaska Department of Health and Social Services. Both people were diagnosed after receiving urgent care in a Fairbanks-area clinic. One was a child with a sore on the left elbow, along with fever and swollen lymph nodes. And the other was an unrelated middle-aged woman with a pox mark on her leg, swollen lymph nodes, and joint pain. In both cases, symptoms improved within 3 weeks.

This isn’t the first time the so-called Alaskapox virus has been detected in the region. In 2015, a woman living near Fairbanks turned up at her doctor’s office with a single reddened pox-like mark on her upper arm and a feeling of fatigue.

Sampling of the pox mark showed that it was caused by a previously unidentified virus of the same family as smallpox and cowpox.

Five years later, another woman showed up with similar signs and symptoms, and her pox also proved to be the result of what public health experts started calling the Alaskapox virus.

In both cases, the women recovered completely.
 

Smallpox-like illness

Public health sleuths figured out that in three of the four cases, the patients lived in a home with a cat or cats, and one of these cats was known to hunt small animals.

Experts already knew that cats mingling in cow pastures and sickened by cattle virus had helped cowpox make the leap from bovines to humans. And just as in the case of cowpox, they suspected that cats might again be spreading this new virus to people, too.

All four of the infected people lived in sparsely populated areas amid forests. Officials laid animal traps where some of the affected people lived and identified the virus in several species of small wild animals.

The animals that turned up most often with Alaskapox were small mouse-like voles. The rodents with rounded muzzles are known for burrowing in the region. And scientists suspect the Alaskapox virus makes its way from these wild animals to humans through their pet cats or possibly by direct exposure outdoors.

None of the four people identified so far with Alaskapox knew each other or interacted, so officials also suspect that there are more cases going unrecognized, possibly because the symptoms are mild or nonexistent.

There are no documented cases of person-to-person transmission of Alaskapox, according to public health officials monitoring the small number of cases. But other pox viruses can spread by direct contact with skin lesions, so clinicians are recommending that people cover wounds with bandages. Three of the people with Alaskapox mistook their lesions at first for a bite from a spider or insect.

A version of this article first appeared on WebMD.com.

Two new cases of a mysterious virus have been reported by the Alaska Department of Health and Social Services. Both people were diagnosed after receiving urgent care in a Fairbanks-area clinic. One was a child with a sore on the left elbow, along with fever and swollen lymph nodes. And the other was an unrelated middle-aged woman with a pox mark on her leg, swollen lymph nodes, and joint pain. In both cases, symptoms improved within 3 weeks.

This isn’t the first time the so-called Alaskapox virus has been detected in the region. In 2015, a woman living near Fairbanks turned up at her doctor’s office with a single reddened pox-like mark on her upper arm and a feeling of fatigue.

Sampling of the pox mark showed that it was caused by a previously unidentified virus of the same family as smallpox and cowpox.

Five years later, another woman showed up with similar signs and symptoms, and her pox also proved to be the result of what public health experts started calling the Alaskapox virus.

In both cases, the women recovered completely.
 

Smallpox-like illness

Public health sleuths figured out that in three of the four cases, the patients lived in a home with a cat or cats, and one of these cats was known to hunt small animals.

Experts already knew that cats mingling in cow pastures and sickened by cattle virus had helped cowpox make the leap from bovines to humans. And just as in the case of cowpox, they suspected that cats might again be spreading this new virus to people, too.

All four of the infected people lived in sparsely populated areas amid forests. Officials laid animal traps where some of the affected people lived and identified the virus in several species of small wild animals.

The animals that turned up most often with Alaskapox were small mouse-like voles. The rodents with rounded muzzles are known for burrowing in the region. And scientists suspect the Alaskapox virus makes its way from these wild animals to humans through their pet cats or possibly by direct exposure outdoors.

None of the four people identified so far with Alaskapox knew each other or interacted, so officials also suspect that there are more cases going unrecognized, possibly because the symptoms are mild or nonexistent.

There are no documented cases of person-to-person transmission of Alaskapox, according to public health officials monitoring the small number of cases. But other pox viruses can spread by direct contact with skin lesions, so clinicians are recommending that people cover wounds with bandages. Three of the people with Alaskapox mistook their lesions at first for a bite from a spider or insect.

A version of this article first appeared on WebMD.com.

Cobra the dog has been hard at work at the Miami International Airport, sniffing masks proffered by American Airlines employees making their way through a security checkpoint. If she identifies a specific scent, she’ll let her handler know simply by sitting down. When this good girl sits, that means Cobra has detected an olfactory signal of the coronavirus, the virus that causes COVID-19.

Cobra, a Belgian Malinois, is one of two canines – her partner is One Betta, a Dutch shepherd – working this checkpoint at Miami International. They are part of a pilot program with the Global Forensic and Justice Center at Florida International University, using the detection dogs as a quick screen for people who have COVID-19.

Their detection rate is high, at more than 98%, and the program has been such a success that it’s being extended for another month at the airport.

If these two dogs continue to accurately detect COVID-19, they and other canines with similar training could be deployed to other places with lots of people coming and going at once, including other airports or even schools. In fact, COVID-sniffing dogs are in use in some university classrooms already.

But building up a big brigade of live animals as disease detectors involves some thorny issues, including where the animals retire once their careers are complete.

“When COVID first arose, we said let’s see if we can train these two dogs on either the virus or the odor of COVID-19,” says Kenneth Furton, PhD, a professor of chemistry and biochemistry, provost, and executive vice president at Florida International University.

His team had completed a study with what he calls “medical detector dogs,” animals that might be able to detect the odor of someone having a seizure. That led them to see how well the animals could detect other kinds of disorders.

Training a dog to sniff out specific odors starts with getting them to understand the task in general. Dr. Furton says that the animals first are trained to grasp that their job is to detect one odor among many. Once the dogs grasp that, they can be trained on just about any specific odor.

In fact, in addition to detecting seizures, dogs reportedly have been able to identify diabetes and even some cancers, such as ovarian cancer.

Dr. Furton says he’s not aware of any previous use of dogs to screen for infectious disease. That may simply be because nothing recently has struck with the global ferocity of COVID, driving humans to turn to their best friends for help.

Cobra and One Betta got their start learning to identify the presence of laurel wilt, a fungus that attacks avocado trees and kills them, costing Florida growers millions. With that expertise under their collars, the two dogs need only a few weeks to get good at detecting other smells assigned to them.
 

Training the dogs, safely

To train Cobra and One Betta on COVID-19 odors, Dr. Furton’s team first acquired mask samples from people hospitalized with COVID and people who did not have the disease. In battling the viruses, people produce certain chemicals that they exhale every time they breathe. When Dr. Furton and his colleagues compared the exhaled components trapped in the masks, they found differences between masks from people with COVID and those without.

Having confirmed that exhalations can be COVID-specific, the research team trained four dogs – Cobra, One Betta, Hubble, and Max – to detect masks from people with COVID among an assortment of mask choices. Before this step, though, the researchers made sure that any trace of active virus was destroyed by ultraviolet light so that the dogs would not be infected.

Each time the dogs accurately selected a mask from a COVID patient, their reward was access to a favorite toy: A red ball to chew on. Although all four dogs performed very well, yes, they did, Cobra and One Betta showed the most accuracy, outperforming their training colleagues. From their training scores, Cobra ranked first, with 99.45% accuracy. Despite her name, says Dr. Furton, One Betta was “not one better,” coming in second at 98.1%, which is still quite high.

Both dogs are good at their airport screening duties. If one of them sits after sniffing a mask at the checkpoint, the next step is for the mask owner to be tested.

From Aug. 23 to Sept. 8, the two canines screened 1,093 people during 8 working days, alerting on only one case, according to Greg Chin, communications director for the Miami-Dade Aviation Department. That person had tested positive for COVID 2 weeks earlier and was returning to work after quarantine, and their rapid test after the dog alerted was negative.

Dr. Furton says that there are some reports of dogs also alerting before tests can show a positive result, suggesting the dogs’ odor detection can be more precise. They hope to expand their study to see how tight the window of dog-based detection is.

For now, the detector dogs are doing so well that the program has been extended for 30 more days, Mr. Chin says.

As promising as this seems, using dogs for screening carries some logistical and ethical tangles. Training a canine army to deploy for high-volume detection points means that once the work is done, a whole lot of dogs will need a safe place to retire. In addition, the initial training takes several months, says Dr. Furton, whereas if a device were developed for screening, manufacturing could likely be ramped up quickly to meet demand.

The dogs might not need to retire right away, though.

“We envision that they could be redeployed to another type of detection for another infectious disease” if the need arises, Dr. Furton says. But in the end, when working with dogs, he says, there is “a moral connection that you don’t have to deal with using instruments.”

Although the pilot screening at Miami International is the first airport test, the dogs have also done this work in other venues, including at a state emergency operations center in Florida and in some university classrooms, says Dr. Furton.

A version of this article first appeared on WebMD.com.

Cobra the dog has been hard at work at the Miami International Airport, sniffing masks proffered by American Airlines employees making their way through a security checkpoint. If she identifies a specific scent, she’ll let her handler know simply by sitting down. When this good girl sits, that means Cobra has detected an olfactory signal of the coronavirus, the virus that causes COVID-19.

Cobra, a Belgian Malinois, is one of two canines – her partner is One Betta, a Dutch shepherd – working this checkpoint at Miami International. They are part of a pilot program with the Global Forensic and Justice Center at Florida International University, using the detection dogs as a quick screen for people who have COVID-19.

Their detection rate is high, at more than 98%, and the program has been such a success that it’s being extended for another month at the airport.

If these two dogs continue to accurately detect COVID-19, they and other canines with similar training could be deployed to other places with lots of people coming and going at once, including other airports or even schools. In fact, COVID-sniffing dogs are in use in some university classrooms already.

But building up a big brigade of live animals as disease detectors involves some thorny issues, including where the animals retire once their careers are complete.

“When COVID first arose, we said let’s see if we can train these two dogs on either the virus or the odor of COVID-19,” says Kenneth Furton, PhD, a professor of chemistry and biochemistry, provost, and executive vice president at Florida International University.

His team had completed a study with what he calls “medical detector dogs,” animals that might be able to detect the odor of someone having a seizure. That led them to see how well the animals could detect other kinds of disorders.

Training a dog to sniff out specific odors starts with getting them to understand the task in general. Dr. Furton says that the animals first are trained to grasp that their job is to detect one odor among many. Once the dogs grasp that, they can be trained on just about any specific odor.

In fact, in addition to detecting seizures, dogs reportedly have been able to identify diabetes and even some cancers, such as ovarian cancer.

Dr. Furton says he’s not aware of any previous use of dogs to screen for infectious disease. That may simply be because nothing recently has struck with the global ferocity of COVID, driving humans to turn to their best friends for help.

Cobra and One Betta got their start learning to identify the presence of laurel wilt, a fungus that attacks avocado trees and kills them, costing Florida growers millions. With that expertise under their collars, the two dogs need only a few weeks to get good at detecting other smells assigned to them.
 

Training the dogs, safely

To train Cobra and One Betta on COVID-19 odors, Dr. Furton’s team first acquired mask samples from people hospitalized with COVID and people who did not have the disease. In battling the viruses, people produce certain chemicals that they exhale every time they breathe. When Dr. Furton and his colleagues compared the exhaled components trapped in the masks, they found differences between masks from people with COVID and those without.

Having confirmed that exhalations can be COVID-specific, the research team trained four dogs – Cobra, One Betta, Hubble, and Max – to detect masks from people with COVID among an assortment of mask choices. Before this step, though, the researchers made sure that any trace of active virus was destroyed by ultraviolet light so that the dogs would not be infected.

Each time the dogs accurately selected a mask from a COVID patient, their reward was access to a favorite toy: A red ball to chew on. Although all four dogs performed very well, yes, they did, Cobra and One Betta showed the most accuracy, outperforming their training colleagues. From their training scores, Cobra ranked first, with 99.45% accuracy. Despite her name, says Dr. Furton, One Betta was “not one better,” coming in second at 98.1%, which is still quite high.

Both dogs are good at their airport screening duties. If one of them sits after sniffing a mask at the checkpoint, the next step is for the mask owner to be tested.

From Aug. 23 to Sept. 8, the two canines screened 1,093 people during 8 working days, alerting on only one case, according to Greg Chin, communications director for the Miami-Dade Aviation Department. That person had tested positive for COVID 2 weeks earlier and was returning to work after quarantine, and their rapid test after the dog alerted was negative.

Dr. Furton says that there are some reports of dogs also alerting before tests can show a positive result, suggesting the dogs’ odor detection can be more precise. They hope to expand their study to see how tight the window of dog-based detection is.

For now, the detector dogs are doing so well that the program has been extended for 30 more days, Mr. Chin says.

As promising as this seems, using dogs for screening carries some logistical and ethical tangles. Training a canine army to deploy for high-volume detection points means that once the work is done, a whole lot of dogs will need a safe place to retire. In addition, the initial training takes several months, says Dr. Furton, whereas if a device were developed for screening, manufacturing could likely be ramped up quickly to meet demand.

The dogs might not need to retire right away, though.

“We envision that they could be redeployed to another type of detection for another infectious disease” if the need arises, Dr. Furton says. But in the end, when working with dogs, he says, there is “a moral connection that you don’t have to deal with using instruments.”

Although the pilot screening at Miami International is the first airport test, the dogs have also done this work in other venues, including at a state emergency operations center in Florida and in some university classrooms, says Dr. Furton.

A version of this article first appeared on WebMD.com.

Cobra the dog has been hard at work at the Miami International Airport, sniffing masks proffered by American Airlines employees making their way through a security checkpoint. If she identifies a specific scent, she’ll let her handler know simply by sitting down. When this good girl sits, that means Cobra has detected an olfactory signal of the coronavirus, the virus that causes COVID-19.

Cobra, a Belgian Malinois, is one of two canines – her partner is One Betta, a Dutch shepherd – working this checkpoint at Miami International. They are part of a pilot program with the Global Forensic and Justice Center at Florida International University, using the detection dogs as a quick screen for people who have COVID-19.

Their detection rate is high, at more than 98%, and the program has been such a success that it’s being extended for another month at the airport.

If these two dogs continue to accurately detect COVID-19, they and other canines with similar training could be deployed to other places with lots of people coming and going at once, including other airports or even schools. In fact, COVID-sniffing dogs are in use in some university classrooms already.

But building up a big brigade of live animals as disease detectors involves some thorny issues, including where the animals retire once their careers are complete.

“When COVID first arose, we said let’s see if we can train these two dogs on either the virus or the odor of COVID-19,” says Kenneth Furton, PhD, a professor of chemistry and biochemistry, provost, and executive vice president at Florida International University.

His team had completed a study with what he calls “medical detector dogs,” animals that might be able to detect the odor of someone having a seizure. That led them to see how well the animals could detect other kinds of disorders.

Training a dog to sniff out specific odors starts with getting them to understand the task in general. Dr. Furton says that the animals first are trained to grasp that their job is to detect one odor among many. Once the dogs grasp that, they can be trained on just about any specific odor.

In fact, in addition to detecting seizures, dogs reportedly have been able to identify diabetes and even some cancers, such as ovarian cancer.

Dr. Furton says he’s not aware of any previous use of dogs to screen for infectious disease. That may simply be because nothing recently has struck with the global ferocity of COVID, driving humans to turn to their best friends for help.

Cobra and One Betta got their start learning to identify the presence of laurel wilt, a fungus that attacks avocado trees and kills them, costing Florida growers millions. With that expertise under their collars, the two dogs need only a few weeks to get good at detecting other smells assigned to them.
 

Training the dogs, safely

To train Cobra and One Betta on COVID-19 odors, Dr. Furton’s team first acquired mask samples from people hospitalized with COVID and people who did not have the disease. In battling the viruses, people produce certain chemicals that they exhale every time they breathe. When Dr. Furton and his colleagues compared the exhaled components trapped in the masks, they found differences between masks from people with COVID and those without.

Having confirmed that exhalations can be COVID-specific, the research team trained four dogs – Cobra, One Betta, Hubble, and Max – to detect masks from people with COVID among an assortment of mask choices. Before this step, though, the researchers made sure that any trace of active virus was destroyed by ultraviolet light so that the dogs would not be infected.

Each time the dogs accurately selected a mask from a COVID patient, their reward was access to a favorite toy: A red ball to chew on. Although all four dogs performed very well, yes, they did, Cobra and One Betta showed the most accuracy, outperforming their training colleagues. From their training scores, Cobra ranked first, with 99.45% accuracy. Despite her name, says Dr. Furton, One Betta was “not one better,” coming in second at 98.1%, which is still quite high.

Both dogs are good at their airport screening duties. If one of them sits after sniffing a mask at the checkpoint, the next step is for the mask owner to be tested.

From Aug. 23 to Sept. 8, the two canines screened 1,093 people during 8 working days, alerting on only one case, according to Greg Chin, communications director for the Miami-Dade Aviation Department. That person had tested positive for COVID 2 weeks earlier and was returning to work after quarantine, and their rapid test after the dog alerted was negative.

Dr. Furton says that there are some reports of dogs also alerting before tests can show a positive result, suggesting the dogs’ odor detection can be more precise. They hope to expand their study to see how tight the window of dog-based detection is.

For now, the detector dogs are doing so well that the program has been extended for 30 more days, Mr. Chin says.

As promising as this seems, using dogs for screening carries some logistical and ethical tangles. Training a canine army to deploy for high-volume detection points means that once the work is done, a whole lot of dogs will need a safe place to retire. In addition, the initial training takes several months, says Dr. Furton, whereas if a device were developed for screening, manufacturing could likely be ramped up quickly to meet demand.

The dogs might not need to retire right away, though.

“We envision that they could be redeployed to another type of detection for another infectious disease” if the need arises, Dr. Furton says. But in the end, when working with dogs, he says, there is “a moral connection that you don’t have to deal with using instruments.”

Although the pilot screening at Miami International is the first airport test, the dogs have also done this work in other venues, including at a state emergency operations center in Florida and in some university classrooms, says Dr. Furton.

A version of this article first appeared on WebMD.com.

Opioid-related drug overdose deaths in the United States exploded to an estimated record high of 69,031 people in 2020, topping the 49,860 deaths logged in 2019, according to a new report from the Centers for Disease Control and Prevention. Most of the deaths involved synthetic opioids such as fentanyl.

President Joe Biden has pledged more than $10 billion to expand access to prevention, treatment, and recovery services. The money is important as people receiving treatment for opioid use disorder have a high risk for relapse, and that means a high risk for opioid overdose.

Now, researchers are studying a possible bridge to successful recovery: A vaccine that could blunt the drugs’ ability to cause harm.

The first such vaccines are now entering clinical trials, raising hopes of adding another tool to the antiaddiction armamentarium. But even if the vaccines prove safe and effective, their success could generate some new problems to solve.

An advantage of vaccines is that their effects can last for several months, said trial investigator Sandra Comer, PhD, professor of neurobiology and psychiatry at Columbia University Irving Medical Center, New York. Dropout rates for existing medical therapies for opioid use disorder are as high as 50% at 6 months, and a vaccine could protect people from overdose and give them time to re-enter treatment.

“It serves as a bit of a safety net,” she said.

The first vaccine to enter a trial targets oxycodone. Volunteers are being recruited who have a diagnosis of opioid use disorder but are not being medically treated and are still using opioids. A third of them will receive a placebo vaccine, a third will receive a low-dose injection of vaccine, and the other third will receive a high-dose vaccine.
 

A shot against oxycodone

Researchers are primarily tracking the safety of the shot, but they’re also looking at whether vaccination prevents the euphoria that opioids usually produce. They expect to enroll 24 people initially but expand to 45 if results look promising.

In response to the shot, the body produces antibodies, proteins that tag oxycodone and keep it from reaching the brain. If the drug can’t reach brain cells, it can’t produce euphoria. And more important for lifesaving effects, it can’t block the brain’s signals to the body to breathe. The vaccine has already performed well in animal studies.

Previous trials of vaccines for cocaine and nicotine failed. Those vaccines made it to the last clinical trial stage, but didn’t prove effective overall. So this time, investigators plan to track antibody levels in participants, examining blood samples for signs of a good immune response to the vaccine.

But even though earlier cocaine and nicotine vaccines didn’t work for everybody, there were some people they seemed to help. This is why investigators involved in opioid vaccine trials want to track immune responses, said Marco Pravetoni, PhD, associate professor of pharmacology and medicine at the University of Minnesota, Minneapolis, whose team will be assessing the blood samples. Ultimately, a doctor might even be able to use this information to tailor vaccine selection to a specific person.

Dr. Pravetoni also said that oxycodone is one of three vaccine targets – the other two are heroin and fentanyl – that researchers hope to combine into a single shot. Recipients might need to have one shot a month for the first 3 to 4 months and then receive annual boosters.
 

Stopping the pain

The vaccines also raise some issues that need attention, said Cody Wenthur, PharmD, PhD, assistant professor of pharmacy at the University of Wisconsin–Madison, who is not involved in the vaccine trials.

“If you’re vaccinated against oxycodone, you might not have access to adequate pain control if you get into a car accident, for example,” he said.

Clinicians could use other opioids for pain management, but limiting the opioids that the vaccine targets is a “double-edged sword,” said Dr. Wenthur, because vaccinated people could just switch their opioid of choice to one that a vaccine does not inhibit.

Although these issues need to be addressed, vaccines, if successful, will have an important role. Dr. Wenthur noted a survey of pharmacists and pharmacy students that he and his group conducted showing that respondents “overwhelmingly” viewed a potential vaccine as helpful.

If the vaccines do become available, their application could extend beyond people who have opioid use disorder, said Dr. Pravetoni. He mentioned the 2002 incident when terrorists took over a theater in Moscow and Russian special forces are thought to have used an aerosolized form of fentanyl to incapacitate everyone in the room. More than 100 of the hostages died, and the episode raised the specter of opioids being used in chemical attacks.

Dr. Pravetoni said vaccination could offer protection for first responders, law enforcement or other people whose professions place them at risk for inhalation, either accidentally or through such attacks.

These or other real-world applications for people at risk for exposure are several years away. Dr. Pravetoni said it took 10 years to get to this phase and estimates that, in about 5 years, a vaccine that targets multiple opioid drugs might enter the first clinical trial.

A version of this article first appeared on WebMD.com.

Opioid-related drug overdose deaths in the United States exploded to an estimated record high of 69,031 people in 2020, topping the 49,860 deaths logged in 2019, according to a new report from the Centers for Disease Control and Prevention. Most of the deaths involved synthetic opioids such as fentanyl.

President Joe Biden has pledged more than $10 billion to expand access to prevention, treatment, and recovery services. The money is important as people receiving treatment for opioid use disorder have a high risk for relapse, and that means a high risk for opioid overdose.

Now, researchers are studying a possible bridge to successful recovery: A vaccine that could blunt the drugs’ ability to cause harm.

The first such vaccines are now entering clinical trials, raising hopes of adding another tool to the antiaddiction armamentarium. But even if the vaccines prove safe and effective, their success could generate some new problems to solve.

An advantage of vaccines is that their effects can last for several months, said trial investigator Sandra Comer, PhD, professor of neurobiology and psychiatry at Columbia University Irving Medical Center, New York. Dropout rates for existing medical therapies for opioid use disorder are as high as 50% at 6 months, and a vaccine could protect people from overdose and give them time to re-enter treatment.

“It serves as a bit of a safety net,” she said.

The first vaccine to enter a trial targets oxycodone. Volunteers are being recruited who have a diagnosis of opioid use disorder but are not being medically treated and are still using opioids. A third of them will receive a placebo vaccine, a third will receive a low-dose injection of vaccine, and the other third will receive a high-dose vaccine.
 

A shot against oxycodone

Researchers are primarily tracking the safety of the shot, but they’re also looking at whether vaccination prevents the euphoria that opioids usually produce. They expect to enroll 24 people initially but expand to 45 if results look promising.

In response to the shot, the body produces antibodies, proteins that tag oxycodone and keep it from reaching the brain. If the drug can’t reach brain cells, it can’t produce euphoria. And more important for lifesaving effects, it can’t block the brain’s signals to the body to breathe. The vaccine has already performed well in animal studies.

Previous trials of vaccines for cocaine and nicotine failed. Those vaccines made it to the last clinical trial stage, but didn’t prove effective overall. So this time, investigators plan to track antibody levels in participants, examining blood samples for signs of a good immune response to the vaccine.

But even though earlier cocaine and nicotine vaccines didn’t work for everybody, there were some people they seemed to help. This is why investigators involved in opioid vaccine trials want to track immune responses, said Marco Pravetoni, PhD, associate professor of pharmacology and medicine at the University of Minnesota, Minneapolis, whose team will be assessing the blood samples. Ultimately, a doctor might even be able to use this information to tailor vaccine selection to a specific person.

Dr. Pravetoni also said that oxycodone is one of three vaccine targets – the other two are heroin and fentanyl – that researchers hope to combine into a single shot. Recipients might need to have one shot a month for the first 3 to 4 months and then receive annual boosters.
 

Stopping the pain

The vaccines also raise some issues that need attention, said Cody Wenthur, PharmD, PhD, assistant professor of pharmacy at the University of Wisconsin–Madison, who is not involved in the vaccine trials.

“If you’re vaccinated against oxycodone, you might not have access to adequate pain control if you get into a car accident, for example,” he said.

Clinicians could use other opioids for pain management, but limiting the opioids that the vaccine targets is a “double-edged sword,” said Dr. Wenthur, because vaccinated people could just switch their opioid of choice to one that a vaccine does not inhibit.

Although these issues need to be addressed, vaccines, if successful, will have an important role. Dr. Wenthur noted a survey of pharmacists and pharmacy students that he and his group conducted showing that respondents “overwhelmingly” viewed a potential vaccine as helpful.

If the vaccines do become available, their application could extend beyond people who have opioid use disorder, said Dr. Pravetoni. He mentioned the 2002 incident when terrorists took over a theater in Moscow and Russian special forces are thought to have used an aerosolized form of fentanyl to incapacitate everyone in the room. More than 100 of the hostages died, and the episode raised the specter of opioids being used in chemical attacks.

Dr. Pravetoni said vaccination could offer protection for first responders, law enforcement or other people whose professions place them at risk for inhalation, either accidentally or through such attacks.

These or other real-world applications for people at risk for exposure are several years away. Dr. Pravetoni said it took 10 years to get to this phase and estimates that, in about 5 years, a vaccine that targets multiple opioid drugs might enter the first clinical trial.

A version of this article first appeared on WebMD.com.

Opioid-related drug overdose deaths in the United States exploded to an estimated record high of 69,031 people in 2020, topping the 49,860 deaths logged in 2019, according to a new report from the Centers for Disease Control and Prevention. Most of the deaths involved synthetic opioids such as fentanyl.

President Joe Biden has pledged more than $10 billion to expand access to prevention, treatment, and recovery services. The money is important as people receiving treatment for opioid use disorder have a high risk for relapse, and that means a high risk for opioid overdose.

Now, researchers are studying a possible bridge to successful recovery: A vaccine that could blunt the drugs’ ability to cause harm.

The first such vaccines are now entering clinical trials, raising hopes of adding another tool to the antiaddiction armamentarium. But even if the vaccines prove safe and effective, their success could generate some new problems to solve.

An advantage of vaccines is that their effects can last for several months, said trial investigator Sandra Comer, PhD, professor of neurobiology and psychiatry at Columbia University Irving Medical Center, New York. Dropout rates for existing medical therapies for opioid use disorder are as high as 50% at 6 months, and a vaccine could protect people from overdose and give them time to re-enter treatment.

“It serves as a bit of a safety net,” she said.

The first vaccine to enter a trial targets oxycodone. Volunteers are being recruited who have a diagnosis of opioid use disorder but are not being medically treated and are still using opioids. A third of them will receive a placebo vaccine, a third will receive a low-dose injection of vaccine, and the other third will receive a high-dose vaccine.
 

A shot against oxycodone

Researchers are primarily tracking the safety of the shot, but they’re also looking at whether vaccination prevents the euphoria that opioids usually produce. They expect to enroll 24 people initially but expand to 45 if results look promising.

In response to the shot, the body produces antibodies, proteins that tag oxycodone and keep it from reaching the brain. If the drug can’t reach brain cells, it can’t produce euphoria. And more important for lifesaving effects, it can’t block the brain’s signals to the body to breathe. The vaccine has already performed well in animal studies.

Previous trials of vaccines for cocaine and nicotine failed. Those vaccines made it to the last clinical trial stage, but didn’t prove effective overall. So this time, investigators plan to track antibody levels in participants, examining blood samples for signs of a good immune response to the vaccine.

But even though earlier cocaine and nicotine vaccines didn’t work for everybody, there were some people they seemed to help. This is why investigators involved in opioid vaccine trials want to track immune responses, said Marco Pravetoni, PhD, associate professor of pharmacology and medicine at the University of Minnesota, Minneapolis, whose team will be assessing the blood samples. Ultimately, a doctor might even be able to use this information to tailor vaccine selection to a specific person.

Dr. Pravetoni also said that oxycodone is one of three vaccine targets – the other two are heroin and fentanyl – that researchers hope to combine into a single shot. Recipients might need to have one shot a month for the first 3 to 4 months and then receive annual boosters.
 

Stopping the pain

The vaccines also raise some issues that need attention, said Cody Wenthur, PharmD, PhD, assistant professor of pharmacy at the University of Wisconsin–Madison, who is not involved in the vaccine trials.

“If you’re vaccinated against oxycodone, you might not have access to adequate pain control if you get into a car accident, for example,” he said.

Clinicians could use other opioids for pain management, but limiting the opioids that the vaccine targets is a “double-edged sword,” said Dr. Wenthur, because vaccinated people could just switch their opioid of choice to one that a vaccine does not inhibit.

Although these issues need to be addressed, vaccines, if successful, will have an important role. Dr. Wenthur noted a survey of pharmacists and pharmacy students that he and his group conducted showing that respondents “overwhelmingly” viewed a potential vaccine as helpful.

If the vaccines do become available, their application could extend beyond people who have opioid use disorder, said Dr. Pravetoni. He mentioned the 2002 incident when terrorists took over a theater in Moscow and Russian special forces are thought to have used an aerosolized form of fentanyl to incapacitate everyone in the room. More than 100 of the hostages died, and the episode raised the specter of opioids being used in chemical attacks.

Dr. Pravetoni said vaccination could offer protection for first responders, law enforcement or other people whose professions place them at risk for inhalation, either accidentally or through such attacks.

These or other real-world applications for people at risk for exposure are several years away. Dr. Pravetoni said it took 10 years to get to this phase and estimates that, in about 5 years, a vaccine that targets multiple opioid drugs might enter the first clinical trial.

A version of this article first appeared on WebMD.com.

With two sets of Clostridioides difficile recommendations being published within a month of each other, clinicians may find themselves trying to reconcile some of the conflicts between the two guidelines.

The first set, published June 1 by the American College of Gastroenterology, focuses on fecal microbiota transplantation (FMT) and the antibiotic vancomycin. The second, published June 24 by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America, drives a shift in treatment for initial episodes and short-term recurrence from vancomycin to fidaxomicin and, in some cases, adding on the monoclonal antibody bezlotoxumab, both made by Merck.

The updates are timely because researchers are now recognizing that C. difficile can colonize people without causing symptoms, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, said in an interview. He was not involved in writing either set of guidelines. “C. diff infection was a hospital-type infection, but we’re now seeing it in up to approximately 35%-50% of patients coming from the community, so it’s a big concern.”

Although the guidelines agree on which treatments are effective, the recommendations give the options a different emphasis.

Infectious disease specialist Stuart Johnson, MD, professor of medicine at Loyola University Medical Center in Maywood, Ill., and a physician researcher at Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill., is the first author in the IDSA/SHEA guidelines. He told this news organization that one reason the two sets of recommendations may diverge in emphasis for initial and recurrent C. difficile is that “everyone has a different way of looking at things.” Compared with infectious disease specialists like him, he said, gastroenterologists “for the most part see the world a little different and have their own bent on things.” 

The differences between the two guidelines relate to the first-line therapy for people with an initial or recurrent C. difficile episode. For an initial episode, the IDSA/SHEA authors conditionally recommend fidaxomicin as first preferred choice over vancomycin, with a moderate certainty of evidence. They noted that implementing this recommendation depends on “available resources,” a reference to the higher cost and difficulty of access associated with fidaxomicin.

Gastroenterologist Monika Fischer, MD, an associate professor of medicine at Indiana University, Indianapolis, is one of the authors of the ACG guidelines. She told this news organization that the cost difference between fidaxomicin and vancomycin is considerable and finds the choice to foreground fidaxomicin puzzling. “They did not reference any new data compared to those we have published.” Their recommendation may make sense in terms of efficacy, but real-world demands require attention to cost and reimbursement. “They themselves state this in their recommendations,” she noted. 

Dr. Fischer cited a ballpark of about $100 for a course of vancomycin, compared with about $3,000 for a course of fidaxomicin. The IDSA/SHEA guidelines do cite vancomycin as an acceptable alternative. According to Dr. Fischer, the ACG guidelines authors discussed fidaxomicin and concluded that there just wasn’t enough evidence to justify favoring this antibiotic over vancomycin, given the cost-benefit imbalance. The ACG guidelines call for a standard course of oral vancomycin for a first, nonsevere C. difficile episode, listing oral fidaxomicin or oral metronidazole as alternatives.

For a recurrence, the IDSA/SHEA authors also favor fidaxomicin in a conditional recommendation over a standard course of vancomycin. For multiple recurrences, a tapered and pulsed vancomycin regimen, vancomycin followed by rifaximin, or FMT are also options.

Dr. David Johnson said that these recommendations favoring fidaxomicin are “surprising,” and that lower costs of vancomycin outweigh the benefit of fidaxomicin, given more-or-less comparable data on cure rates.

In contrast, the ACG guidelines recommend that an initial recurrence be treated with a tapering dose of vancomycin, and call for FMT for patients who are eligible and who experience a second or more C. difficile recurrences after a round of pulsed vancomycin.

Dr. Stuart Johnson said that FMT carries its own special set of issues. “If you don’t have a donor program set up, you have to rely on a stool bank,” noting that one widely used stool bank “basically had to stop making the product because of the coronavirus.” Costs for FMT products have doubled in recent years, and because Food and Drug Administration approval of the therapy is lacking, insurance does not cover it.

Dr. David Johnson also said that he is not “terribly happy” about the ACG recommendation for vancomycin prophylaxis. “It may help, but it also can have off-target effects against colonic bacterial flora, so we would not agree with that recommendation.”

The IDSA/SHEA authors also conditionally recommend bezlotoxumab, on very low certainty of evidence, as a cotherapy with standard of care antibiotics for recurrence prevention in patients with an episode in the last 6 months, particularly for patients at high recurrence risk “where logistics is not an issue.” The FDA has warned that this monoclonal antibody should be used with great care in patients with heart failure and only when benefits outweigh risks.

The ACG guidelines conditionally recommend considering bezlotoxumab to prevent recurrence in patients with specific risk factors, including age over 65 years and severe presentation. The IDSA/SHEA guidelines expand this population to anyone with a recurrence within 6 months, Dr. Fischer pointed out.

The antibody treatment “does offer another 10% absolute reduction in recurrent C. diff disease,” said Dr. Stuart Johnson, which is a “helpful option and primarily for people who have had recurrent C. diff already.” In general, he said, for both drugs, “access is still something we have to work with.”

In a commentary on the ACG guidelines, Dr. David Johnson wrote that there is good evidence that bezlotoxumab prevents relapse, especially in patients with specific risk factors. The hitch is the $4,500 price tag for a 1,000-mg vial, with a recommended dose of 10 mg/kg.

Dr. Stuart Johnson agreed that the costs of the fidaxomicin and bezlotoxumab are important considerations. In addition, there are logistical issues with using the antibody because most hospitals don’t offer infusions, which pushes patients to infusion centers.

Regardless, he added, “we’re happy that we have new options.”

Dr. Fischer, Dr. Stuart Johnson, and Dr. David Johnson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

With two sets of Clostridioides difficile recommendations being published within a month of each other, clinicians may find themselves trying to reconcile some of the conflicts between the two guidelines.

The first set, published June 1 by the American College of Gastroenterology, focuses on fecal microbiota transplantation (FMT) and the antibiotic vancomycin. The second, published June 24 by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America, drives a shift in treatment for initial episodes and short-term recurrence from vancomycin to fidaxomicin and, in some cases, adding on the monoclonal antibody bezlotoxumab, both made by Merck.

The updates are timely because researchers are now recognizing that C. difficile can colonize people without causing symptoms, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, said in an interview. He was not involved in writing either set of guidelines. “C. diff infection was a hospital-type infection, but we’re now seeing it in up to approximately 35%-50% of patients coming from the community, so it’s a big concern.”

Although the guidelines agree on which treatments are effective, the recommendations give the options a different emphasis.

Infectious disease specialist Stuart Johnson, MD, professor of medicine at Loyola University Medical Center in Maywood, Ill., and a physician researcher at Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill., is the first author in the IDSA/SHEA guidelines. He told this news organization that one reason the two sets of recommendations may diverge in emphasis for initial and recurrent C. difficile is that “everyone has a different way of looking at things.” Compared with infectious disease specialists like him, he said, gastroenterologists “for the most part see the world a little different and have their own bent on things.” 

The differences between the two guidelines relate to the first-line therapy for people with an initial or recurrent C. difficile episode. For an initial episode, the IDSA/SHEA authors conditionally recommend fidaxomicin as first preferred choice over vancomycin, with a moderate certainty of evidence. They noted that implementing this recommendation depends on “available resources,” a reference to the higher cost and difficulty of access associated with fidaxomicin.

Gastroenterologist Monika Fischer, MD, an associate professor of medicine at Indiana University, Indianapolis, is one of the authors of the ACG guidelines. She told this news organization that the cost difference between fidaxomicin and vancomycin is considerable and finds the choice to foreground fidaxomicin puzzling. “They did not reference any new data compared to those we have published.” Their recommendation may make sense in terms of efficacy, but real-world demands require attention to cost and reimbursement. “They themselves state this in their recommendations,” she noted. 

Dr. Fischer cited a ballpark of about $100 for a course of vancomycin, compared with about $3,000 for a course of fidaxomicin. The IDSA/SHEA guidelines do cite vancomycin as an acceptable alternative. According to Dr. Fischer, the ACG guidelines authors discussed fidaxomicin and concluded that there just wasn’t enough evidence to justify favoring this antibiotic over vancomycin, given the cost-benefit imbalance. The ACG guidelines call for a standard course of oral vancomycin for a first, nonsevere C. difficile episode, listing oral fidaxomicin or oral metronidazole as alternatives.

For a recurrence, the IDSA/SHEA authors also favor fidaxomicin in a conditional recommendation over a standard course of vancomycin. For multiple recurrences, a tapered and pulsed vancomycin regimen, vancomycin followed by rifaximin, or FMT are also options.

Dr. David Johnson said that these recommendations favoring fidaxomicin are “surprising,” and that lower costs of vancomycin outweigh the benefit of fidaxomicin, given more-or-less comparable data on cure rates.

In contrast, the ACG guidelines recommend that an initial recurrence be treated with a tapering dose of vancomycin, and call for FMT for patients who are eligible and who experience a second or more C. difficile recurrences after a round of pulsed vancomycin.

Dr. Stuart Johnson said that FMT carries its own special set of issues. “If you don’t have a donor program set up, you have to rely on a stool bank,” noting that one widely used stool bank “basically had to stop making the product because of the coronavirus.” Costs for FMT products have doubled in recent years, and because Food and Drug Administration approval of the therapy is lacking, insurance does not cover it.

Dr. David Johnson also said that he is not “terribly happy” about the ACG recommendation for vancomycin prophylaxis. “It may help, but it also can have off-target effects against colonic bacterial flora, so we would not agree with that recommendation.”

The IDSA/SHEA authors also conditionally recommend bezlotoxumab, on very low certainty of evidence, as a cotherapy with standard of care antibiotics for recurrence prevention in patients with an episode in the last 6 months, particularly for patients at high recurrence risk “where logistics is not an issue.” The FDA has warned that this monoclonal antibody should be used with great care in patients with heart failure and only when benefits outweigh risks.

The ACG guidelines conditionally recommend considering bezlotoxumab to prevent recurrence in patients with specific risk factors, including age over 65 years and severe presentation. The IDSA/SHEA guidelines expand this population to anyone with a recurrence within 6 months, Dr. Fischer pointed out.

The antibody treatment “does offer another 10% absolute reduction in recurrent C. diff disease,” said Dr. Stuart Johnson, which is a “helpful option and primarily for people who have had recurrent C. diff already.” In general, he said, for both drugs, “access is still something we have to work with.”

In a commentary on the ACG guidelines, Dr. David Johnson wrote that there is good evidence that bezlotoxumab prevents relapse, especially in patients with specific risk factors. The hitch is the $4,500 price tag for a 1,000-mg vial, with a recommended dose of 10 mg/kg.

Dr. Stuart Johnson agreed that the costs of the fidaxomicin and bezlotoxumab are important considerations. In addition, there are logistical issues with using the antibody because most hospitals don’t offer infusions, which pushes patients to infusion centers.

Regardless, he added, “we’re happy that we have new options.”

Dr. Fischer, Dr. Stuart Johnson, and Dr. David Johnson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

With two sets of Clostridioides difficile recommendations being published within a month of each other, clinicians may find themselves trying to reconcile some of the conflicts between the two guidelines.

The first set, published June 1 by the American College of Gastroenterology, focuses on fecal microbiota transplantation (FMT) and the antibiotic vancomycin. The second, published June 24 by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America, drives a shift in treatment for initial episodes and short-term recurrence from vancomycin to fidaxomicin and, in some cases, adding on the monoclonal antibody bezlotoxumab, both made by Merck.

The updates are timely because researchers are now recognizing that C. difficile can colonize people without causing symptoms, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, said in an interview. He was not involved in writing either set of guidelines. “C. diff infection was a hospital-type infection, but we’re now seeing it in up to approximately 35%-50% of patients coming from the community, so it’s a big concern.”

Although the guidelines agree on which treatments are effective, the recommendations give the options a different emphasis.

Infectious disease specialist Stuart Johnson, MD, professor of medicine at Loyola University Medical Center in Maywood, Ill., and a physician researcher at Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill., is the first author in the IDSA/SHEA guidelines. He told this news organization that one reason the two sets of recommendations may diverge in emphasis for initial and recurrent C. difficile is that “everyone has a different way of looking at things.” Compared with infectious disease specialists like him, he said, gastroenterologists “for the most part see the world a little different and have their own bent on things.” 

The differences between the two guidelines relate to the first-line therapy for people with an initial or recurrent C. difficile episode. For an initial episode, the IDSA/SHEA authors conditionally recommend fidaxomicin as first preferred choice over vancomycin, with a moderate certainty of evidence. They noted that implementing this recommendation depends on “available resources,” a reference to the higher cost and difficulty of access associated with fidaxomicin.

Gastroenterologist Monika Fischer, MD, an associate professor of medicine at Indiana University, Indianapolis, is one of the authors of the ACG guidelines. She told this news organization that the cost difference between fidaxomicin and vancomycin is considerable and finds the choice to foreground fidaxomicin puzzling. “They did not reference any new data compared to those we have published.” Their recommendation may make sense in terms of efficacy, but real-world demands require attention to cost and reimbursement. “They themselves state this in their recommendations,” she noted. 

Dr. Fischer cited a ballpark of about $100 for a course of vancomycin, compared with about $3,000 for a course of fidaxomicin. The IDSA/SHEA guidelines do cite vancomycin as an acceptable alternative. According to Dr. Fischer, the ACG guidelines authors discussed fidaxomicin and concluded that there just wasn’t enough evidence to justify favoring this antibiotic over vancomycin, given the cost-benefit imbalance. The ACG guidelines call for a standard course of oral vancomycin for a first, nonsevere C. difficile episode, listing oral fidaxomicin or oral metronidazole as alternatives.

For a recurrence, the IDSA/SHEA authors also favor fidaxomicin in a conditional recommendation over a standard course of vancomycin. For multiple recurrences, a tapered and pulsed vancomycin regimen, vancomycin followed by rifaximin, or FMT are also options.

Dr. David Johnson said that these recommendations favoring fidaxomicin are “surprising,” and that lower costs of vancomycin outweigh the benefit of fidaxomicin, given more-or-less comparable data on cure rates.

In contrast, the ACG guidelines recommend that an initial recurrence be treated with a tapering dose of vancomycin, and call for FMT for patients who are eligible and who experience a second or more C. difficile recurrences after a round of pulsed vancomycin.

Dr. Stuart Johnson said that FMT carries its own special set of issues. “If you don’t have a donor program set up, you have to rely on a stool bank,” noting that one widely used stool bank “basically had to stop making the product because of the coronavirus.” Costs for FMT products have doubled in recent years, and because Food and Drug Administration approval of the therapy is lacking, insurance does not cover it.

Dr. David Johnson also said that he is not “terribly happy” about the ACG recommendation for vancomycin prophylaxis. “It may help, but it also can have off-target effects against colonic bacterial flora, so we would not agree with that recommendation.”

The IDSA/SHEA authors also conditionally recommend bezlotoxumab, on very low certainty of evidence, as a cotherapy with standard of care antibiotics for recurrence prevention in patients with an episode in the last 6 months, particularly for patients at high recurrence risk “where logistics is not an issue.” The FDA has warned that this monoclonal antibody should be used with great care in patients with heart failure and only when benefits outweigh risks.

The ACG guidelines conditionally recommend considering bezlotoxumab to prevent recurrence in patients with specific risk factors, including age over 65 years and severe presentation. The IDSA/SHEA guidelines expand this population to anyone with a recurrence within 6 months, Dr. Fischer pointed out.

The antibody treatment “does offer another 10% absolute reduction in recurrent C. diff disease,” said Dr. Stuart Johnson, which is a “helpful option and primarily for people who have had recurrent C. diff already.” In general, he said, for both drugs, “access is still something we have to work with.”

In a commentary on the ACG guidelines, Dr. David Johnson wrote that there is good evidence that bezlotoxumab prevents relapse, especially in patients with specific risk factors. The hitch is the $4,500 price tag for a 1,000-mg vial, with a recommended dose of 10 mg/kg.

Dr. Stuart Johnson agreed that the costs of the fidaxomicin and bezlotoxumab are important considerations. In addition, there are logistical issues with using the antibody because most hospitals don’t offer infusions, which pushes patients to infusion centers.

Regardless, he added, “we’re happy that we have new options.”

Dr. Fischer, Dr. Stuart Johnson, and Dr. David Johnson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Practicing the meditative, rhythmic flow of tai chi works just as well as aerobic exercise and strength training for achieving some health benefits such as reducing waist size and improving cholesterol, new findings suggest.

Willie B. Thomas/iStockphoto

Results of a randomized controlled trial published online May 31 in Annals of Internal Medicine show that people who have a tough time with some kinds of aerobic exercise may gain similar benefits from tai chi.

The study is “very impressive,” said Bavani Nadeswaran, MD, of the University of California Irvine’s Susan Samueli Integrative Health Institute, who was not involved in the study.

Many people have arthritis or back pain, “and aerobic exercise can be hard on them,” she said. “The good thing about exercises like tai chi and yoga is that they are low-impact.” That means that people who can’t run or get access to a pool for swimming have a viable alternative.

The study included nearly 550 adults ages 50 and up in Hong Kong who were randomly assigned to engage in tai chi, aerobic exercise with strength training, or no exercise program for 12 weeks. All had waistlines greater than 35.4 inches for men and 31.5 inches for women.

The tai chi program involved three 1-hour weekly sessions of the practice, led by an instructor. Those who took part in the aerobic exercise group engaged three times each week in an exercise program of brisk tai chi and strength training, also led by an instructor.

The researchers measured changes in waistline size, cholesterol levels, and weight for about 9 months. Those who didn’t exercise had little change in their average waistline. Compared to the group that didn’t exercise, the average waistline of people in the two exercise groups declined more: by 0.7 inches more with tai chi, and 0.5 inches more with brisk walking and strength training.

Both exercise groups also had greater drops in body weight and triglyceride (a type of fat found in the blood) levels, and larger increases in high-density lipoprotein cholesterol, the “good” cholesterol, compared to the no-exercise group. All of these improvements lasted about 9 months with tai chi. But improvements in cholesterol levels did not last as long in those in the brisk-walking program.

The researchers also looked at the effects on blood pressure and blood sugar, but they found no differences between the groups.

The findings don’t necessarily mean that people with larger waistlines should dispense with their current exercise programs and turn to tai chi, said study author Parco Siu, PhD, head of the Division of Kinesiology at the University of Hong Kong’s School of Public Health. They show that tai chi is a good option if a person prefers it.

“This is good news for middle-aged and older adults who may be averse to conventional exercise,” he said in an email. But “certainly it is no problem for people to keep regularly participating in conventional exercise.”

Tai chi may also be a good choice for people without larger waistlines because practicing this form of exercise is a way to follow advice from the World Health Organization on physical activity, said Dr. Siu, though the study did not address this question.

Dr. Siu and the other researchers noted several limits to the study, including that all the people who took part were in China, so how the practice would affect people in different regions is not clear. Also, almost a third of those who began the study dropped out before it ended, and they tended to have a higher body weight than those who remained to the end. The authors said this high dropout rate could mean that some people had negative experiences during their exercise programs.

Next steps, said Dr. Siu, include further assessing how tai chi affects things such as blood sugar and blood pressure. Other, early-stage studies also show tai chi having some positive effects on mood and cognition, he said, pointing to a need for more research.

UC Irvine’s Dr. Nadeswaran agreed. The work opens the door, she said, to taking a long-term look at how practicing tai chi might affect a person’s risk of dying from heart disease or another cause. Her team’s work involves evaluating tai chi’s effects on several conditions, including metabolic syndrome and even the aftermath of COVID-19.

While researchers pursue these questions, tai chi is accessible in many ways. Dr. Siu noted the availability of classes in this “meditation in motion” practice at community centers and fitness clubs. For people who can’t yet rejoin activities in the real world, Dr. Nadeswaran said virtual tai chi classes also are available.
 

A version of this article first appeared on WebMD.com.

Practicing the meditative, rhythmic flow of tai chi works just as well as aerobic exercise and strength training for achieving some health benefits such as reducing waist size and improving cholesterol, new findings suggest.

Willie B. Thomas/iStockphoto

Results of a randomized controlled trial published online May 31 in Annals of Internal Medicine show that people who have a tough time with some kinds of aerobic exercise may gain similar benefits from tai chi.

The study is “very impressive,” said Bavani Nadeswaran, MD, of the University of California Irvine’s Susan Samueli Integrative Health Institute, who was not involved in the study.

Many people have arthritis or back pain, “and aerobic exercise can be hard on them,” she said. “The good thing about exercises like tai chi and yoga is that they are low-impact.” That means that people who can’t run or get access to a pool for swimming have a viable alternative.

The study included nearly 550 adults ages 50 and up in Hong Kong who were randomly assigned to engage in tai chi, aerobic exercise with strength training, or no exercise program for 12 weeks. All had waistlines greater than 35.4 inches for men and 31.5 inches for women.

The tai chi program involved three 1-hour weekly sessions of the practice, led by an instructor. Those who took part in the aerobic exercise group engaged three times each week in an exercise program of brisk tai chi and strength training, also led by an instructor.

The researchers measured changes in waistline size, cholesterol levels, and weight for about 9 months. Those who didn’t exercise had little change in their average waistline. Compared to the group that didn’t exercise, the average waistline of people in the two exercise groups declined more: by 0.7 inches more with tai chi, and 0.5 inches more with brisk walking and strength training.

Both exercise groups also had greater drops in body weight and triglyceride (a type of fat found in the blood) levels, and larger increases in high-density lipoprotein cholesterol, the “good” cholesterol, compared to the no-exercise group. All of these improvements lasted about 9 months with tai chi. But improvements in cholesterol levels did not last as long in those in the brisk-walking program.

The researchers also looked at the effects on blood pressure and blood sugar, but they found no differences between the groups.

The findings don’t necessarily mean that people with larger waistlines should dispense with their current exercise programs and turn to tai chi, said study author Parco Siu, PhD, head of the Division of Kinesiology at the University of Hong Kong’s School of Public Health. They show that tai chi is a good option if a person prefers it.

“This is good news for middle-aged and older adults who may be averse to conventional exercise,” he said in an email. But “certainly it is no problem for people to keep regularly participating in conventional exercise.”

Tai chi may also be a good choice for people without larger waistlines because practicing this form of exercise is a way to follow advice from the World Health Organization on physical activity, said Dr. Siu, though the study did not address this question.

Dr. Siu and the other researchers noted several limits to the study, including that all the people who took part were in China, so how the practice would affect people in different regions is not clear. Also, almost a third of those who began the study dropped out before it ended, and they tended to have a higher body weight than those who remained to the end. The authors said this high dropout rate could mean that some people had negative experiences during their exercise programs.

Next steps, said Dr. Siu, include further assessing how tai chi affects things such as blood sugar and blood pressure. Other, early-stage studies also show tai chi having some positive effects on mood and cognition, he said, pointing to a need for more research.

UC Irvine’s Dr. Nadeswaran agreed. The work opens the door, she said, to taking a long-term look at how practicing tai chi might affect a person’s risk of dying from heart disease or another cause. Her team’s work involves evaluating tai chi’s effects on several conditions, including metabolic syndrome and even the aftermath of COVID-19.

While researchers pursue these questions, tai chi is accessible in many ways. Dr. Siu noted the availability of classes in this “meditation in motion” practice at community centers and fitness clubs. For people who can’t yet rejoin activities in the real world, Dr. Nadeswaran said virtual tai chi classes also are available.
 

A version of this article first appeared on WebMD.com.

Practicing the meditative, rhythmic flow of tai chi works just as well as aerobic exercise and strength training for achieving some health benefits such as reducing waist size and improving cholesterol, new findings suggest.

Willie B. Thomas/iStockphoto

Results of a randomized controlled trial published online May 31 in Annals of Internal Medicine show that people who have a tough time with some kinds of aerobic exercise may gain similar benefits from tai chi.

The study is “very impressive,” said Bavani Nadeswaran, MD, of the University of California Irvine’s Susan Samueli Integrative Health Institute, who was not involved in the study.

Many people have arthritis or back pain, “and aerobic exercise can be hard on them,” she said. “The good thing about exercises like tai chi and yoga is that they are low-impact.” That means that people who can’t run or get access to a pool for swimming have a viable alternative.

The study included nearly 550 adults ages 50 and up in Hong Kong who were randomly assigned to engage in tai chi, aerobic exercise with strength training, or no exercise program for 12 weeks. All had waistlines greater than 35.4 inches for men and 31.5 inches for women.

The tai chi program involved three 1-hour weekly sessions of the practice, led by an instructor. Those who took part in the aerobic exercise group engaged three times each week in an exercise program of brisk tai chi and strength training, also led by an instructor.

The researchers measured changes in waistline size, cholesterol levels, and weight for about 9 months. Those who didn’t exercise had little change in their average waistline. Compared to the group that didn’t exercise, the average waistline of people in the two exercise groups declined more: by 0.7 inches more with tai chi, and 0.5 inches more with brisk walking and strength training.

Both exercise groups also had greater drops in body weight and triglyceride (a type of fat found in the blood) levels, and larger increases in high-density lipoprotein cholesterol, the “good” cholesterol, compared to the no-exercise group. All of these improvements lasted about 9 months with tai chi. But improvements in cholesterol levels did not last as long in those in the brisk-walking program.

The researchers also looked at the effects on blood pressure and blood sugar, but they found no differences between the groups.

The findings don’t necessarily mean that people with larger waistlines should dispense with their current exercise programs and turn to tai chi, said study author Parco Siu, PhD, head of the Division of Kinesiology at the University of Hong Kong’s School of Public Health. They show that tai chi is a good option if a person prefers it.

“This is good news for middle-aged and older adults who may be averse to conventional exercise,” he said in an email. But “certainly it is no problem for people to keep regularly participating in conventional exercise.”

Tai chi may also be a good choice for people without larger waistlines because practicing this form of exercise is a way to follow advice from the World Health Organization on physical activity, said Dr. Siu, though the study did not address this question.

Dr. Siu and the other researchers noted several limits to the study, including that all the people who took part were in China, so how the practice would affect people in different regions is not clear. Also, almost a third of those who began the study dropped out before it ended, and they tended to have a higher body weight than those who remained to the end. The authors said this high dropout rate could mean that some people had negative experiences during their exercise programs.

Next steps, said Dr. Siu, include further assessing how tai chi affects things such as blood sugar and blood pressure. Other, early-stage studies also show tai chi having some positive effects on mood and cognition, he said, pointing to a need for more research.

UC Irvine’s Dr. Nadeswaran agreed. The work opens the door, she said, to taking a long-term look at how practicing tai chi might affect a person’s risk of dying from heart disease or another cause. Her team’s work involves evaluating tai chi’s effects on several conditions, including metabolic syndrome and even the aftermath of COVID-19.

While researchers pursue these questions, tai chi is accessible in many ways. Dr. Siu noted the availability of classes in this “meditation in motion” practice at community centers and fitness clubs. For people who can’t yet rejoin activities in the real world, Dr. Nadeswaran said virtual tai chi classes also are available.
 

A version of this article first appeared on WebMD.com.

Researchers have worked at record-breaking speed to not only identify and characterize the novel coronavirus, but also to develop potential vaccines; it is a race that another trio of scientists, awarded the 2020 Nobel Prize in Medicine, know well after their own decades-long marathon to crack the code of hepatitis C.

The RNA virus vexed researchers like Harvey J. Alter, MD; Michael Houghton, PhD; and Charles M. Rice, PhD, for years. Unlike today’s parallel sequencing and polymerase chain reaction, screening at the time was tedious and painstaking. But they were all in for some big highs, some dead-ends, and a little inspiration by way of author Lewis Carroll.

“Our undertaking was a success,” Dr. Alter said in an interview, “because everyone got on board.” Investigators, the Food and Drug Administration, and blood banks all worked together. It was a national effort, he added.

The Laureates will share the $1 million prize that recognizes their achievement. This is the second time that scientists who have devoted their time to the pursuit of viral hepatitis have been honored.

Two main types of infectious hepatitis were identified in the 1940s. The first, hepatitis A, is transmitted by polluted water or food and generally has little long-term effect on the patient. The second, transmitted through blood and other bodily fluids, is a much more serious threat.

In the 1960s, Baruch Blumberg, MD, ascertained that blood-borne hepatitis was caused by an insidious virus – hepatitis B – which silently causes liver complications in otherwise healthy people years after infection. Dr. Blumberg’s discovery led to the development of diagnostic tests and an effective vaccine; he was awarded the Nobel Prize in Physiology or Medicine in 1976.

At that time, Dr. Alter was working at the National Institutes of Health in Bethesda, Md., studying the occurrence of hepatitis in patients who had received blood transfusions. Globally, blood-borne hepatitis was causing more than a million deaths each year.

When screening began in 1969 to prevent people with hepatitis A or hepatitis B from donating blood, many recipients were spared from developing liver inflammation after transfusion. However, some people were still getting sick and researchers began to suspect that something dubbed “non-A, non-B” was lurking in donated blood.

As scientists were tracking it down in the micro world, public health officials and others tried to block the presumed virus in the macro world. In the United States, this meant changing blood-donation practices. When it became clear that as many as one in five transfusion recipients developed hepatitis, probably as the result of a virus, the blood donation system switched from being a paid enterprise to a volunteer activity.

It was anticipated that this would eliminate one source of the virus – users of street drugs – and it did; rates of transmission after transfusion dropped by half. By the 1980s, researchers had figured out that donors carrying the mysterious pathogen often had elevated levels of antibodies to the hepatitis B virus or elevated levels of ALT. Blood banks then began testing prospective donors and cut the incidence of non-A, non-B hepatitis by another half.

When Dr. Alter and his team got to work studying chimpanzees, they were able to confirm that the non-A, non-B agent was transmittable by blood transfusion. But the next step proved insurmountable. “People knew what the virus would look like if we found it, but we couldn’t find it,” Dr. Alter said.

“Then Chiron came along and cloned it,” he recounts.

The tiny start-up company was housed in a few rented rooms in an abandoned plant in Emeryville, Calif. This is where Nobel Laureate Dr. Houghton and coworkers Qui-Lim Choo, PhD, and George Kuo, PhD, spent 7 years chasing the mystery pathogen. When every traditional method to pin it down failed, the team tried some nontraditional approaches.

They found success when they painstakingly cloned genomic fragments from the blood of an infected chimpanzee and then screened this library using serum isolated from affected patients. The hope was that antibodies in the serum samples would stick to the viral genetic material and create a signpost indicating its presence.

This “fishing expedition” was disappointing at first, said Dr. Choo, now vice president of research at Nansha Biologics Limited in Hong Kong. “We didn’t catch any fish.”

He likened the pursuit, which took place under growing pressure from upper management, to that in “The Imitation Game,” the film that depicted Alan Turing’s effort to decrypt German intelligence messages for the British government during World War II.

The effort wasn’t working out and the team was down. So to keep spirits up, Dr. Kuo shared a snippet of the Lewis Carroll poem “The Hunting of the Snark.” It just happened to encapsulate the frustrations of their pursuit while also encouraging perseverance: “For the Snark’s a peculiar creature, that won’t / Be caught in a commonplace way. / Do all that you know, and try all that you don’t: / Not a chance must be wasted today!”

Those words motivated the team to keep going, to try different approaches and, ultimately, to find the hepatitis C virus, said Dr. Kuo, now retired.

During the tedious process of screening millions of clones, Dr. Choo spotted a single likely area on one of the plates that his “gut feeling” told him would contain the viral material. And it did. The pathogen – RNA packed in a lipid coat – was a member of the Flaviviridae family.

In 1989, the team reported that they’d identified a new flavivirus associated with posttransfusion hepatitis, and published their findings in Science. Later that year, an antibody test for it was described in Science by the team, which included Dr. Alter.

The success was a “fantastic feeling,” mused Dr. Houghton, now a virologist at the University of Alberta, Edmonton. “I’ve often said that, from 1989 to 1991, I was high just on the discovery.” After that, “researchers and the pharmaceutical industry did a great job coming up with really effective antivirals.”

“Mike, with his team, took 7 years to get this tiny little piece of viral genome, which reacted with convalescent patient serum, and used that to build up the sequence. That’s where I come into it,” said Dr. Rice, professor of virology at Rockefeller University, New York, and the third scientist in the Nobel Prize–winning trio.

The next step was to confirm that this was causing the hepatitis in patients who received blood transfusions. Over the course of several years, Dr. Rice and colleagues at the Washington University, St. Louis, engineered a version of the virus that retained its replicating capacity and injected it into chimpanzees. The animals developed hepatitis, confirming that this flavivirus was indeed the cause. More than 8 years after the virus was identified, scientists had proof of its infectiousness.

“We finally knew the structure of the viral genome,” said Dr. Rice. “We showed that the sequence was sufficient to initiate infection and cause disease.”

Those findings, published in 1997 in Science, were the key final step in the search for a molecular target for therapies and, maybe someday, a vaccine.

For the first time in history, hepatitis C can now be cured, raising hopes that the virus will be eradicated from the world population. But obstacles remain as the World Health Organization works toward its goal of eliminating hepatitis C–related disease by 2030.

Rates have actually risen in the United States as the opioid epidemic has taken hold because the virus is common in people who use street drugs and are at increased risk for behaviors that lead to transmission.

The prevalence of chronic hepatitis C now hovers around 1%. In 2019, it affected an estimated 3.8 million Americans, and more than 39,000 people died of hepatitis C–related causes. Of all deaths from liver cancer in 2019, 39% were attributable to hepatitis C.

This “silent killer” can take years to develop, which dampens the sense of immediacy to help, said Jean-Michel Piedagnel, director of the Drugs for Neglected Diseases nonprofit initiative.

People infected with hepatitis C are often part of marginalized groups. There isn’t typically a common demographic factor to unite them in advocacy.

And even though treatment can cost as little as $200 in countries where generic drugs are available, money can still be an issue, Mr. Piedagnel pointed out.

The COVID-19 response shows how quickly health systems can evolve in a crisis and adapt. “If there is political will, means can be found, said Cary James, CEO at the World Hepatitis Alliance.

The incredible speed of vaccine development for SARS-CoV-2 has impressed the Nobel Laureates, who have yet to see a vaccine for hepatitis C.

Dr. Houghton said he hopes this momentum will perpetuate new emergency filings for hepatitis C vaccines.

If even a tiny fraction of the money that’s gone into COVID-19 were used, Dr. Rice pointed out, “we’d have a hep C vaccine by now.”

A version of this article first appeared on Medscape.com

Researchers have worked at record-breaking speed to not only identify and characterize the novel coronavirus, but also to develop potential vaccines; it is a race that another trio of scientists, awarded the 2020 Nobel Prize in Medicine, know well after their own decades-long marathon to crack the code of hepatitis C.

The RNA virus vexed researchers like Harvey J. Alter, MD; Michael Houghton, PhD; and Charles M. Rice, PhD, for years. Unlike today’s parallel sequencing and polymerase chain reaction, screening at the time was tedious and painstaking. But they were all in for some big highs, some dead-ends, and a little inspiration by way of author Lewis Carroll.

“Our undertaking was a success,” Dr. Alter said in an interview, “because everyone got on board.” Investigators, the Food and Drug Administration, and blood banks all worked together. It was a national effort, he added.

The Laureates will share the $1 million prize that recognizes their achievement. This is the second time that scientists who have devoted their time to the pursuit of viral hepatitis have been honored.

Two main types of infectious hepatitis were identified in the 1940s. The first, hepatitis A, is transmitted by polluted water or food and generally has little long-term effect on the patient. The second, transmitted through blood and other bodily fluids, is a much more serious threat.

In the 1960s, Baruch Blumberg, MD, ascertained that blood-borne hepatitis was caused by an insidious virus – hepatitis B – which silently causes liver complications in otherwise healthy people years after infection. Dr. Blumberg’s discovery led to the development of diagnostic tests and an effective vaccine; he was awarded the Nobel Prize in Physiology or Medicine in 1976.

At that time, Dr. Alter was working at the National Institutes of Health in Bethesda, Md., studying the occurrence of hepatitis in patients who had received blood transfusions. Globally, blood-borne hepatitis was causing more than a million deaths each year.

When screening began in 1969 to prevent people with hepatitis A or hepatitis B from donating blood, many recipients were spared from developing liver inflammation after transfusion. However, some people were still getting sick and researchers began to suspect that something dubbed “non-A, non-B” was lurking in donated blood.

As scientists were tracking it down in the micro world, public health officials and others tried to block the presumed virus in the macro world. In the United States, this meant changing blood-donation practices. When it became clear that as many as one in five transfusion recipients developed hepatitis, probably as the result of a virus, the blood donation system switched from being a paid enterprise to a volunteer activity.

It was anticipated that this would eliminate one source of the virus – users of street drugs – and it did; rates of transmission after transfusion dropped by half. By the 1980s, researchers had figured out that donors carrying the mysterious pathogen often had elevated levels of antibodies to the hepatitis B virus or elevated levels of ALT. Blood banks then began testing prospective donors and cut the incidence of non-A, non-B hepatitis by another half.

When Dr. Alter and his team got to work studying chimpanzees, they were able to confirm that the non-A, non-B agent was transmittable by blood transfusion. But the next step proved insurmountable. “People knew what the virus would look like if we found it, but we couldn’t find it,” Dr. Alter said.

“Then Chiron came along and cloned it,” he recounts.

The tiny start-up company was housed in a few rented rooms in an abandoned plant in Emeryville, Calif. This is where Nobel Laureate Dr. Houghton and coworkers Qui-Lim Choo, PhD, and George Kuo, PhD, spent 7 years chasing the mystery pathogen. When every traditional method to pin it down failed, the team tried some nontraditional approaches.

They found success when they painstakingly cloned genomic fragments from the blood of an infected chimpanzee and then screened this library using serum isolated from affected patients. The hope was that antibodies in the serum samples would stick to the viral genetic material and create a signpost indicating its presence.

This “fishing expedition” was disappointing at first, said Dr. Choo, now vice president of research at Nansha Biologics Limited in Hong Kong. “We didn’t catch any fish.”

He likened the pursuit, which took place under growing pressure from upper management, to that in “The Imitation Game,” the film that depicted Alan Turing’s effort to decrypt German intelligence messages for the British government during World War II.

The effort wasn’t working out and the team was down. So to keep spirits up, Dr. Kuo shared a snippet of the Lewis Carroll poem “The Hunting of the Snark.” It just happened to encapsulate the frustrations of their pursuit while also encouraging perseverance: “For the Snark’s a peculiar creature, that won’t / Be caught in a commonplace way. / Do all that you know, and try all that you don’t: / Not a chance must be wasted today!”

Those words motivated the team to keep going, to try different approaches and, ultimately, to find the hepatitis C virus, said Dr. Kuo, now retired.

During the tedious process of screening millions of clones, Dr. Choo spotted a single likely area on one of the plates that his “gut feeling” told him would contain the viral material. And it did. The pathogen – RNA packed in a lipid coat – was a member of the Flaviviridae family.

In 1989, the team reported that they’d identified a new flavivirus associated with posttransfusion hepatitis, and published their findings in Science. Later that year, an antibody test for it was described in Science by the team, which included Dr. Alter.

The success was a “fantastic feeling,” mused Dr. Houghton, now a virologist at the University of Alberta, Edmonton. “I’ve often said that, from 1989 to 1991, I was high just on the discovery.” After that, “researchers and the pharmaceutical industry did a great job coming up with really effective antivirals.”

“Mike, with his team, took 7 years to get this tiny little piece of viral genome, which reacted with convalescent patient serum, and used that to build up the sequence. That’s where I come into it,” said Dr. Rice, professor of virology at Rockefeller University, New York, and the third scientist in the Nobel Prize–winning trio.

The next step was to confirm that this was causing the hepatitis in patients who received blood transfusions. Over the course of several years, Dr. Rice and colleagues at the Washington University, St. Louis, engineered a version of the virus that retained its replicating capacity and injected it into chimpanzees. The animals developed hepatitis, confirming that this flavivirus was indeed the cause. More than 8 years after the virus was identified, scientists had proof of its infectiousness.

“We finally knew the structure of the viral genome,” said Dr. Rice. “We showed that the sequence was sufficient to initiate infection and cause disease.”

Those findings, published in 1997 in Science, were the key final step in the search for a molecular target for therapies and, maybe someday, a vaccine.

For the first time in history, hepatitis C can now be cured, raising hopes that the virus will be eradicated from the world population. But obstacles remain as the World Health Organization works toward its goal of eliminating hepatitis C–related disease by 2030.

Rates have actually risen in the United States as the opioid epidemic has taken hold because the virus is common in people who use street drugs and are at increased risk for behaviors that lead to transmission.

The prevalence of chronic hepatitis C now hovers around 1%. In 2019, it affected an estimated 3.8 million Americans, and more than 39,000 people died of hepatitis C–related causes. Of all deaths from liver cancer in 2019, 39% were attributable to hepatitis C.

This “silent killer” can take years to develop, which dampens the sense of immediacy to help, said Jean-Michel Piedagnel, director of the Drugs for Neglected Diseases nonprofit initiative.

People infected with hepatitis C are often part of marginalized groups. There isn’t typically a common demographic factor to unite them in advocacy.

And even though treatment can cost as little as $200 in countries where generic drugs are available, money can still be an issue, Mr. Piedagnel pointed out.

The COVID-19 response shows how quickly health systems can evolve in a crisis and adapt. “If there is political will, means can be found, said Cary James, CEO at the World Hepatitis Alliance.

The incredible speed of vaccine development for SARS-CoV-2 has impressed the Nobel Laureates, who have yet to see a vaccine for hepatitis C.

Dr. Houghton said he hopes this momentum will perpetuate new emergency filings for hepatitis C vaccines.

If even a tiny fraction of the money that’s gone into COVID-19 were used, Dr. Rice pointed out, “we’d have a hep C vaccine by now.”

A version of this article first appeared on Medscape.com

Researchers have worked at record-breaking speed to not only identify and characterize the novel coronavirus, but also to develop potential vaccines; it is a race that another trio of scientists, awarded the 2020 Nobel Prize in Medicine, know well after their own decades-long marathon to crack the code of hepatitis C.

The RNA virus vexed researchers like Harvey J. Alter, MD; Michael Houghton, PhD; and Charles M. Rice, PhD, for years. Unlike today’s parallel sequencing and polymerase chain reaction, screening at the time was tedious and painstaking. But they were all in for some big highs, some dead-ends, and a little inspiration by way of author Lewis Carroll.

“Our undertaking was a success,” Dr. Alter said in an interview, “because everyone got on board.” Investigators, the Food and Drug Administration, and blood banks all worked together. It was a national effort, he added.

The Laureates will share the $1 million prize that recognizes their achievement. This is the second time that scientists who have devoted their time to the pursuit of viral hepatitis have been honored.

Two main types of infectious hepatitis were identified in the 1940s. The first, hepatitis A, is transmitted by polluted water or food and generally has little long-term effect on the patient. The second, transmitted through blood and other bodily fluids, is a much more serious threat.

In the 1960s, Baruch Blumberg, MD, ascertained that blood-borne hepatitis was caused by an insidious virus – hepatitis B – which silently causes liver complications in otherwise healthy people years after infection. Dr. Blumberg’s discovery led to the development of diagnostic tests and an effective vaccine; he was awarded the Nobel Prize in Physiology or Medicine in 1976.

At that time, Dr. Alter was working at the National Institutes of Health in Bethesda, Md., studying the occurrence of hepatitis in patients who had received blood transfusions. Globally, blood-borne hepatitis was causing more than a million deaths each year.

When screening began in 1969 to prevent people with hepatitis A or hepatitis B from donating blood, many recipients were spared from developing liver inflammation after transfusion. However, some people were still getting sick and researchers began to suspect that something dubbed “non-A, non-B” was lurking in donated blood.

As scientists were tracking it down in the micro world, public health officials and others tried to block the presumed virus in the macro world. In the United States, this meant changing blood-donation practices. When it became clear that as many as one in five transfusion recipients developed hepatitis, probably as the result of a virus, the blood donation system switched from being a paid enterprise to a volunteer activity.

It was anticipated that this would eliminate one source of the virus – users of street drugs – and it did; rates of transmission after transfusion dropped by half. By the 1980s, researchers had figured out that donors carrying the mysterious pathogen often had elevated levels of antibodies to the hepatitis B virus or elevated levels of ALT. Blood banks then began testing prospective donors and cut the incidence of non-A, non-B hepatitis by another half.

When Dr. Alter and his team got to work studying chimpanzees, they were able to confirm that the non-A, non-B agent was transmittable by blood transfusion. But the next step proved insurmountable. “People knew what the virus would look like if we found it, but we couldn’t find it,” Dr. Alter said.

“Then Chiron came along and cloned it,” he recounts.

The tiny start-up company was housed in a few rented rooms in an abandoned plant in Emeryville, Calif. This is where Nobel Laureate Dr. Houghton and coworkers Qui-Lim Choo, PhD, and George Kuo, PhD, spent 7 years chasing the mystery pathogen. When every traditional method to pin it down failed, the team tried some nontraditional approaches.

They found success when they painstakingly cloned genomic fragments from the blood of an infected chimpanzee and then screened this library using serum isolated from affected patients. The hope was that antibodies in the serum samples would stick to the viral genetic material and create a signpost indicating its presence.

This “fishing expedition” was disappointing at first, said Dr. Choo, now vice president of research at Nansha Biologics Limited in Hong Kong. “We didn’t catch any fish.”

He likened the pursuit, which took place under growing pressure from upper management, to that in “The Imitation Game,” the film that depicted Alan Turing’s effort to decrypt German intelligence messages for the British government during World War II.

The effort wasn’t working out and the team was down. So to keep spirits up, Dr. Kuo shared a snippet of the Lewis Carroll poem “The Hunting of the Snark.” It just happened to encapsulate the frustrations of their pursuit while also encouraging perseverance: “For the Snark’s a peculiar creature, that won’t / Be caught in a commonplace way. / Do all that you know, and try all that you don’t: / Not a chance must be wasted today!”

Those words motivated the team to keep going, to try different approaches and, ultimately, to find the hepatitis C virus, said Dr. Kuo, now retired.

During the tedious process of screening millions of clones, Dr. Choo spotted a single likely area on one of the plates that his “gut feeling” told him would contain the viral material. And it did. The pathogen – RNA packed in a lipid coat – was a member of the Flaviviridae family.

In 1989, the team reported that they’d identified a new flavivirus associated with posttransfusion hepatitis, and published their findings in Science. Later that year, an antibody test for it was described in Science by the team, which included Dr. Alter.

The success was a “fantastic feeling,” mused Dr. Houghton, now a virologist at the University of Alberta, Edmonton. “I’ve often said that, from 1989 to 1991, I was high just on the discovery.” After that, “researchers and the pharmaceutical industry did a great job coming up with really effective antivirals.”

“Mike, with his team, took 7 years to get this tiny little piece of viral genome, which reacted with convalescent patient serum, and used that to build up the sequence. That’s where I come into it,” said Dr. Rice, professor of virology at Rockefeller University, New York, and the third scientist in the Nobel Prize–winning trio.

The next step was to confirm that this was causing the hepatitis in patients who received blood transfusions. Over the course of several years, Dr. Rice and colleagues at the Washington University, St. Louis, engineered a version of the virus that retained its replicating capacity and injected it into chimpanzees. The animals developed hepatitis, confirming that this flavivirus was indeed the cause. More than 8 years after the virus was identified, scientists had proof of its infectiousness.

“We finally knew the structure of the viral genome,” said Dr. Rice. “We showed that the sequence was sufficient to initiate infection and cause disease.”

Those findings, published in 1997 in Science, were the key final step in the search for a molecular target for therapies and, maybe someday, a vaccine.

For the first time in history, hepatitis C can now be cured, raising hopes that the virus will be eradicated from the world population. But obstacles remain as the World Health Organization works toward its goal of eliminating hepatitis C–related disease by 2030.

Rates have actually risen in the United States as the opioid epidemic has taken hold because the virus is common in people who use street drugs and are at increased risk for behaviors that lead to transmission.

The prevalence of chronic hepatitis C now hovers around 1%. In 2019, it affected an estimated 3.8 million Americans, and more than 39,000 people died of hepatitis C–related causes. Of all deaths from liver cancer in 2019, 39% were attributable to hepatitis C.

This “silent killer” can take years to develop, which dampens the sense of immediacy to help, said Jean-Michel Piedagnel, director of the Drugs for Neglected Diseases nonprofit initiative.

People infected with hepatitis C are often part of marginalized groups. There isn’t typically a common demographic factor to unite them in advocacy.

And even though treatment can cost as little as $200 in countries where generic drugs are available, money can still be an issue, Mr. Piedagnel pointed out.

The COVID-19 response shows how quickly health systems can evolve in a crisis and adapt. “If there is political will, means can be found, said Cary James, CEO at the World Hepatitis Alliance.

The incredible speed of vaccine development for SARS-CoV-2 has impressed the Nobel Laureates, who have yet to see a vaccine for hepatitis C.

Dr. Houghton said he hopes this momentum will perpetuate new emergency filings for hepatitis C vaccines.

If even a tiny fraction of the money that’s gone into COVID-19 were used, Dr. Rice pointed out, “we’d have a hep C vaccine by now.”

A version of this article first appeared on Medscape.com

There is a link between liver injury and a tendency toward excessive clotting in patients with COVID-19, and the organ’s own blood vessels could be responsible, new research shows.

The effect of IL-6 on the liver sinusoidal endothelial cells lining the liver blood vessels creates a prothrombotic environment that includes the release of factor VIII, said investigator Matthew McConnell, MD, from the Yale University, New Haven, Conn.

Dr. McConnell presented the results at the virtual annual meeting of the American Association for the Study of Liver Diseases.

These associations offer insights into why COVID-19 patients with underlying liver disease can experience “devastating complications” related to improper blood vessel function in the organ, he added.

For their study, Dr. McConnell and colleagues analyzed data on ALT and hypercoagulability from 68 adults treated at the Yale–New Haven Hospital. The liver and coagulation tests were administered within 5 days of each other.

The team set the ALT cutoff for liver injury at three times the upper limit of normal. Patients with two or more parameters indicating excessive clotting were considered to have a hypercoagulable profile, which Dr. McConnell called “a signature clinical finding of COVID-19 infection.”

Patients with high levels of ALT also experienced elevations in clotting-related factors, such as fibrinogen levels and the activity of factor VIII and factor II. Furthermore, liver injury was significantly associated with hypercoagulability (P < .05).

Because COVID-19 is linked to the proinflammatory IL-6, the investigators examined how this cytokine and its receptor affect human liver sinusoidal cells. Cells exposed to IL-6 and its receptor pumped out factor VIII at levels that were significantly higher than in unexposed cells (P < .01). Exposed cells also produced significantly more von Willebrand factor (P < .05), another prothrombotic molecule, and showed increased expression of genes that induce the expression of factor VIII.There is utility in the findings beyond COVID-19, said Dr. McConnell. They provide “insights into complications of critical illness, in general, in the liver blood vessels” of patients with underlying liver disease.

Dr. McConnell has no conflicts.

For the latest clinical guidance, education, research, and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

A version of this article originally appeared on Medscape.com.

There is a link between liver injury and a tendency toward excessive clotting in patients with COVID-19, and the organ’s own blood vessels could be responsible, new research shows.

The effect of IL-6 on the liver sinusoidal endothelial cells lining the liver blood vessels creates a prothrombotic environment that includes the release of factor VIII, said investigator Matthew McConnell, MD, from the Yale University, New Haven, Conn.

Dr. McConnell presented the results at the virtual annual meeting of the American Association for the Study of Liver Diseases.

These associations offer insights into why COVID-19 patients with underlying liver disease can experience “devastating complications” related to improper blood vessel function in the organ, he added.

For their study, Dr. McConnell and colleagues analyzed data on ALT and hypercoagulability from 68 adults treated at the Yale–New Haven Hospital. The liver and coagulation tests were administered within 5 days of each other.

The team set the ALT cutoff for liver injury at three times the upper limit of normal. Patients with two or more parameters indicating excessive clotting were considered to have a hypercoagulable profile, which Dr. McConnell called “a signature clinical finding of COVID-19 infection.”

Patients with high levels of ALT also experienced elevations in clotting-related factors, such as fibrinogen levels and the activity of factor VIII and factor II. Furthermore, liver injury was significantly associated with hypercoagulability (P < .05).

Because COVID-19 is linked to the proinflammatory IL-6, the investigators examined how this cytokine and its receptor affect human liver sinusoidal cells. Cells exposed to IL-6 and its receptor pumped out factor VIII at levels that were significantly higher than in unexposed cells (P < .01). Exposed cells also produced significantly more von Willebrand factor (P < .05), another prothrombotic molecule, and showed increased expression of genes that induce the expression of factor VIII.There is utility in the findings beyond COVID-19, said Dr. McConnell. They provide “insights into complications of critical illness, in general, in the liver blood vessels” of patients with underlying liver disease.

Dr. McConnell has no conflicts.

For the latest clinical guidance, education, research, and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

A version of this article originally appeared on Medscape.com.

There is a link between liver injury and a tendency toward excessive clotting in patients with COVID-19, and the organ’s own blood vessels could be responsible, new research shows.

The effect of IL-6 on the liver sinusoidal endothelial cells lining the liver blood vessels creates a prothrombotic environment that includes the release of factor VIII, said investigator Matthew McConnell, MD, from the Yale University, New Haven, Conn.

Dr. McConnell presented the results at the virtual annual meeting of the American Association for the Study of Liver Diseases.

These associations offer insights into why COVID-19 patients with underlying liver disease can experience “devastating complications” related to improper blood vessel function in the organ, he added.

For their study, Dr. McConnell and colleagues analyzed data on ALT and hypercoagulability from 68 adults treated at the Yale–New Haven Hospital. The liver and coagulation tests were administered within 5 days of each other.

The team set the ALT cutoff for liver injury at three times the upper limit of normal. Patients with two or more parameters indicating excessive clotting were considered to have a hypercoagulable profile, which Dr. McConnell called “a signature clinical finding of COVID-19 infection.”

Patients with high levels of ALT also experienced elevations in clotting-related factors, such as fibrinogen levels and the activity of factor VIII and factor II. Furthermore, liver injury was significantly associated with hypercoagulability (P < .05).

Because COVID-19 is linked to the proinflammatory IL-6, the investigators examined how this cytokine and its receptor affect human liver sinusoidal cells. Cells exposed to IL-6 and its receptor pumped out factor VIII at levels that were significantly higher than in unexposed cells (P < .01). Exposed cells also produced significantly more von Willebrand factor (P < .05), another prothrombotic molecule, and showed increased expression of genes that induce the expression of factor VIII.There is utility in the findings beyond COVID-19, said Dr. McConnell. They provide “insights into complications of critical illness, in general, in the liver blood vessels” of patients with underlying liver disease.

Dr. McConnell has no conflicts.

For the latest clinical guidance, education, research, and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

A version of this article originally appeared on Medscape.com.

With U.S. approval of one coronavirus vaccine likely imminent and approval of a second one expected soon after, physicians will likely be deluged with questions. Public attitudes about the vaccines vary by demographics, with a recent poll showing that men and older adults are more likely to choose vaccination, and women and people of color evincing more wariness.

Although the reasons for reluctance may vary, questions from patient will likely be similar. Some are related to the “warp speed” language about the vaccines. Other concerns arise from the fact that the platform – mRNA – has not been used in human vaccines before. And as with any vaccine, there are rumors and false claims making the rounds on social media.

In anticipation of the most common questions physicians may encounter, two experts, Krutika Kuppalli, MD, assistant professor of medicine in the division of infectious diseases at the Medical University of South Carolina, Charleston, and Angela Rasmussen, PhD, virologist and nonresident affiliate at Georgetown University’s Center for Global Health Science and Security, Washington, talked in an interview about what clinicians can expect and what evidence-based – as well as compassionate – answers might look like.
 

Q: Will this vaccine give me COVID-19?

“There is not an intact virus in there,” Dr. Rasmussen said. The mRNA-based vaccines cannot cause COVID-19 because they don’t use any part of the coronavirus itself. Instead, the Moderna and Pfizer vaccines contain manufactured mRNA molecules that carry the instructions for building the virus’ spike protein. After vaccine administration, the recipient’s own cells take up this mRNA, use it to build this bit of protein, and display it on their surfaces. The foreign protein flag triggers the immune system response.

The mRNA does not enter the cell nucleus or interact with the recipient’s DNA. And because it’s so fragile, it degrades quite quickly. To keep that from happening before cell entry, the mRNAs are cushioned in protective fats.

Q: Was this vaccine made too quickly?

“People have been working on this platform for 30 years, so it’s not that this is brand new,” Dr. Kuppalli said.

Researchers began working on mRNA vaccines in the 1990s. Technological developments in the last decade have meant that their use has become feasible, and they have been tested in animals against many viral diseases. The mRNA vaccines are attractive because they’re expected to be safe and easily manufactured from common materials. That’s what we’ve seen in the COVID-19 pandemic, the  Centers for Disease Control and Prevention says on its website. Design of the spike protein mRNA component began as soon as the viral genome became available in January.

Usually, rolling out a vaccine takes years, so less than a year under a program called Operation Warp Speed can seem like moving too fast, Dr. Rasmussen acknowledged. “The name has given people the impression that by going at warp speed, we’re cutting all the corners. [But] the reality is that Operation Warp Speed is mostly for manufacturing and distribution.”

What underlies the speed is a restructuring of the normal vaccine development process, Dr. Kuppalli said. The same phases of development – animal testing, a small initial human phase, a second for safety testing, a third large phase for efficacy – were all conducted as for any vaccine. But in this case, some phases were completed in parallel, rather than sequentially. This approach has proved so successful that there is already talk about making it the model for developing future vaccines.

Two other factors contributed to the speed, said Dr. Kuppalli and Dr. Rasmussen. First, gearing up production can slow a rollout, but with these vaccines, companies ramped up production even before anyone knew if the vaccines would work – the “warp speed” part. The second factor has been the large number of cases, making exposures more likely and thus accelerating the results of the efficacy trials. “There is so much COVID being transmitted everywhere in the United States that it did not take long to hit the threshold of events to read out phase 3,” Dr. Rasmussen said.

Q: This vaccine has never been used in humans. How do we know it’s safe?

The Pfizer phase 3 trial included more than 43,000 people, and Moderna’s had more than 30,000. The first humans received mRNA-based COVID-19 vaccines in March. The most common adverse events emerge right after a vaccination, Dr. Kuppalli said.

As with any vaccine that gains approval, monitoring will continue.

UK health officials have reported that two health care workers vaccinated in the initial rollout of the Pfizer vaccine had what seems to have been a severe allergic response. Both recipients had a history of anaphylactic allergic responses and carried EpiPens, and both recovered. During the trial, allergic reaction rates were 0.63% in the vaccine group and 0.51% in the placebo group.

As a result of the two reactions, UK regulators are now recommending that patients with a history of severe allergies not receive the vaccine at the current time.

Q: What are the likely side effects?

So far, the most common side effects are pain at the injection site and an achy, flu-like feeling, Dr. Kuppalli said. More severe reactions have been reported, but were not common in the trials.

Dr. Rasmussen noted that the common side effects are a good sign, and signal that the recipient is generating “a robust immune response.”

“Everybody I’ve talked to who’s had the response has said they would go through it again,” Dr. Kruppalli said. “I definitely plan on lining up and being one of the first people to get the vaccine.”

Q: I already had COVID-19 or had a positive antibody test. Do I still need to get the vaccine?

Dr. Rasmussen said that there are “too many unknowns” to say if a history of COVID-19 would make a difference. “We don’t know how long neutralizing antibodies last” after infection, she said. “What we know is that the vaccine tends to produce antibody titers towards the higher end of the spectrum,” suggesting better immunity with vaccination than after natural infection.

Q: Can patients of color feel safe getting the vaccine?

“People of color might be understandably reluctant to take a vaccine that was developed in a way that appears to be faster [than past development],” said Dr. Rasmussen. She said physicians should acknowledge and understand the history that has led them to feel that way, “everything from Tuskegee to Henrietta Lacks to today.”

Empathy is key, and “providers should meet patients where they are and not condescend to them.”

Dr. Kuppalli agreed. “Clinicians really need to work on trying to strip away their biases.”

Thus far there are no safety signals that differ by race or ethnicity, according to the companies. The Pfizer phase 3 trial enrolled just over 9% Black participants, 0.5% Native American/Alaska Native, 0.2% Native Hawaiian/Pacific Islander, 2.3% multiracial participants, and 28% Hispanic/Latinx. For its part, Moderna says that approximately 37% of participants in its phase 3 trial come from communities of color.

Q: What about children and pregnant women?

Although the trials included participants from many different age groups and backgrounds, children and pregnant or lactating women were not among them. Pfizer gained approval in October to include participants as young as age 12 years, and a Moderna spokesperson said in an interview that the company planned pediatric inclusion at the end of 2020, pending approval.

“Unfortunately, we don’t have data on pregnant and lactating women,” Dr. Kuppalli said. She said she hopes that public health organizations such as the CDC will address that in the coming weeks. Dr. Rasmussen called the lack of data in pregnant women and children “a big oversight.”

Dr. Rasmussen has disclosed no relevant financial relationships. Dr. Kuppalli is a consultant with GlaxoSmithKline.

A version of this article originally appeared on Medscape.com.

With U.S. approval of one coronavirus vaccine likely imminent and approval of a second one expected soon after, physicians will likely be deluged with questions. Public attitudes about the vaccines vary by demographics, with a recent poll showing that men and older adults are more likely to choose vaccination, and women and people of color evincing more wariness.

Although the reasons for reluctance may vary, questions from patient will likely be similar. Some are related to the “warp speed” language about the vaccines. Other concerns arise from the fact that the platform – mRNA – has not been used in human vaccines before. And as with any vaccine, there are rumors and false claims making the rounds on social media.

In anticipation of the most common questions physicians may encounter, two experts, Krutika Kuppalli, MD, assistant professor of medicine in the division of infectious diseases at the Medical University of South Carolina, Charleston, and Angela Rasmussen, PhD, virologist and nonresident affiliate at Georgetown University’s Center for Global Health Science and Security, Washington, talked in an interview about what clinicians can expect and what evidence-based – as well as compassionate – answers might look like.
 

Q: Will this vaccine give me COVID-19?

“There is not an intact virus in there,” Dr. Rasmussen said. The mRNA-based vaccines cannot cause COVID-19 because they don’t use any part of the coronavirus itself. Instead, the Moderna and Pfizer vaccines contain manufactured mRNA molecules that carry the instructions for building the virus’ spike protein. After vaccine administration, the recipient’s own cells take up this mRNA, use it to build this bit of protein, and display it on their surfaces. The foreign protein flag triggers the immune system response.

The mRNA does not enter the cell nucleus or interact with the recipient’s DNA. And because it’s so fragile, it degrades quite quickly. To keep that from happening before cell entry, the mRNAs are cushioned in protective fats.

Q: Was this vaccine made too quickly?

“People have been working on this platform for 30 years, so it’s not that this is brand new,” Dr. Kuppalli said.

Researchers began working on mRNA vaccines in the 1990s. Technological developments in the last decade have meant that their use has become feasible, and they have been tested in animals against many viral diseases. The mRNA vaccines are attractive because they’re expected to be safe and easily manufactured from common materials. That’s what we’ve seen in the COVID-19 pandemic, the  Centers for Disease Control and Prevention says on its website. Design of the spike protein mRNA component began as soon as the viral genome became available in January.

Usually, rolling out a vaccine takes years, so less than a year under a program called Operation Warp Speed can seem like moving too fast, Dr. Rasmussen acknowledged. “The name has given people the impression that by going at warp speed, we’re cutting all the corners. [But] the reality is that Operation Warp Speed is mostly for manufacturing and distribution.”

What underlies the speed is a restructuring of the normal vaccine development process, Dr. Kuppalli said. The same phases of development – animal testing, a small initial human phase, a second for safety testing, a third large phase for efficacy – were all conducted as for any vaccine. But in this case, some phases were completed in parallel, rather than sequentially. This approach has proved so successful that there is already talk about making it the model for developing future vaccines.

Two other factors contributed to the speed, said Dr. Kuppalli and Dr. Rasmussen. First, gearing up production can slow a rollout, but with these vaccines, companies ramped up production even before anyone knew if the vaccines would work – the “warp speed” part. The second factor has been the large number of cases, making exposures more likely and thus accelerating the results of the efficacy trials. “There is so much COVID being transmitted everywhere in the United States that it did not take long to hit the threshold of events to read out phase 3,” Dr. Rasmussen said.

Q: This vaccine has never been used in humans. How do we know it’s safe?

The Pfizer phase 3 trial included more than 43,000 people, and Moderna’s had more than 30,000. The first humans received mRNA-based COVID-19 vaccines in March. The most common adverse events emerge right after a vaccination, Dr. Kuppalli said.

As with any vaccine that gains approval, monitoring will continue.

UK health officials have reported that two health care workers vaccinated in the initial rollout of the Pfizer vaccine had what seems to have been a severe allergic response. Both recipients had a history of anaphylactic allergic responses and carried EpiPens, and both recovered. During the trial, allergic reaction rates were 0.63% in the vaccine group and 0.51% in the placebo group.

As a result of the two reactions, UK regulators are now recommending that patients with a history of severe allergies not receive the vaccine at the current time.

Q: What are the likely side effects?

So far, the most common side effects are pain at the injection site and an achy, flu-like feeling, Dr. Kuppalli said. More severe reactions have been reported, but were not common in the trials.

Dr. Rasmussen noted that the common side effects are a good sign, and signal that the recipient is generating “a robust immune response.”

“Everybody I’ve talked to who’s had the response has said they would go through it again,” Dr. Kruppalli said. “I definitely plan on lining up and being one of the first people to get the vaccine.”

Q: I already had COVID-19 or had a positive antibody test. Do I still need to get the vaccine?

Dr. Rasmussen said that there are “too many unknowns” to say if a history of COVID-19 would make a difference. “We don’t know how long neutralizing antibodies last” after infection, she said. “What we know is that the vaccine tends to produce antibody titers towards the higher end of the spectrum,” suggesting better immunity with vaccination than after natural infection.

Q: Can patients of color feel safe getting the vaccine?

“People of color might be understandably reluctant to take a vaccine that was developed in a way that appears to be faster [than past development],” said Dr. Rasmussen. She said physicians should acknowledge and understand the history that has led them to feel that way, “everything from Tuskegee to Henrietta Lacks to today.”

Empathy is key, and “providers should meet patients where they are and not condescend to them.”

Dr. Kuppalli agreed. “Clinicians really need to work on trying to strip away their biases.”

Thus far there are no safety signals that differ by race or ethnicity, according to the companies. The Pfizer phase 3 trial enrolled just over 9% Black participants, 0.5% Native American/Alaska Native, 0.2% Native Hawaiian/Pacific Islander, 2.3% multiracial participants, and 28% Hispanic/Latinx. For its part, Moderna says that approximately 37% of participants in its phase 3 trial come from communities of color.

Q: What about children and pregnant women?

Although the trials included participants from many different age groups and backgrounds, children and pregnant or lactating women were not among them. Pfizer gained approval in October to include participants as young as age 12 years, and a Moderna spokesperson said in an interview that the company planned pediatric inclusion at the end of 2020, pending approval.

“Unfortunately, we don’t have data on pregnant and lactating women,” Dr. Kuppalli said. She said she hopes that public health organizations such as the CDC will address that in the coming weeks. Dr. Rasmussen called the lack of data in pregnant women and children “a big oversight.”

Dr. Rasmussen has disclosed no relevant financial relationships. Dr. Kuppalli is a consultant with GlaxoSmithKline.

A version of this article originally appeared on Medscape.com.

With U.S. approval of one coronavirus vaccine likely imminent and approval of a second one expected soon after, physicians will likely be deluged with questions. Public attitudes about the vaccines vary by demographics, with a recent poll showing that men and older adults are more likely to choose vaccination, and women and people of color evincing more wariness.

Although the reasons for reluctance may vary, questions from patient will likely be similar. Some are related to the “warp speed” language about the vaccines. Other concerns arise from the fact that the platform – mRNA – has not been used in human vaccines before. And as with any vaccine, there are rumors and false claims making the rounds on social media.

In anticipation of the most common questions physicians may encounter, two experts, Krutika Kuppalli, MD, assistant professor of medicine in the division of infectious diseases at the Medical University of South Carolina, Charleston, and Angela Rasmussen, PhD, virologist and nonresident affiliate at Georgetown University’s Center for Global Health Science and Security, Washington, talked in an interview about what clinicians can expect and what evidence-based – as well as compassionate – answers might look like.
 

Q: Will this vaccine give me COVID-19?

“There is not an intact virus in there,” Dr. Rasmussen said. The mRNA-based vaccines cannot cause COVID-19 because they don’t use any part of the coronavirus itself. Instead, the Moderna and Pfizer vaccines contain manufactured mRNA molecules that carry the instructions for building the virus’ spike protein. After vaccine administration, the recipient’s own cells take up this mRNA, use it to build this bit of protein, and display it on their surfaces. The foreign protein flag triggers the immune system response.

The mRNA does not enter the cell nucleus or interact with the recipient’s DNA. And because it’s so fragile, it degrades quite quickly. To keep that from happening before cell entry, the mRNAs are cushioned in protective fats.

Q: Was this vaccine made too quickly?

“People have been working on this platform for 30 years, so it’s not that this is brand new,” Dr. Kuppalli said.

Researchers began working on mRNA vaccines in the 1990s. Technological developments in the last decade have meant that their use has become feasible, and they have been tested in animals against many viral diseases. The mRNA vaccines are attractive because they’re expected to be safe and easily manufactured from common materials. That’s what we’ve seen in the COVID-19 pandemic, the  Centers for Disease Control and Prevention says on its website. Design of the spike protein mRNA component began as soon as the viral genome became available in January.

Usually, rolling out a vaccine takes years, so less than a year under a program called Operation Warp Speed can seem like moving too fast, Dr. Rasmussen acknowledged. “The name has given people the impression that by going at warp speed, we’re cutting all the corners. [But] the reality is that Operation Warp Speed is mostly for manufacturing and distribution.”

What underlies the speed is a restructuring of the normal vaccine development process, Dr. Kuppalli said. The same phases of development – animal testing, a small initial human phase, a second for safety testing, a third large phase for efficacy – were all conducted as for any vaccine. But in this case, some phases were completed in parallel, rather than sequentially. This approach has proved so successful that there is already talk about making it the model for developing future vaccines.

Two other factors contributed to the speed, said Dr. Kuppalli and Dr. Rasmussen. First, gearing up production can slow a rollout, but with these vaccines, companies ramped up production even before anyone knew if the vaccines would work – the “warp speed” part. The second factor has been the large number of cases, making exposures more likely and thus accelerating the results of the efficacy trials. “There is so much COVID being transmitted everywhere in the United States that it did not take long to hit the threshold of events to read out phase 3,” Dr. Rasmussen said.

Q: This vaccine has never been used in humans. How do we know it’s safe?

The Pfizer phase 3 trial included more than 43,000 people, and Moderna’s had more than 30,000. The first humans received mRNA-based COVID-19 vaccines in March. The most common adverse events emerge right after a vaccination, Dr. Kuppalli said.

As with any vaccine that gains approval, monitoring will continue.

UK health officials have reported that two health care workers vaccinated in the initial rollout of the Pfizer vaccine had what seems to have been a severe allergic response. Both recipients had a history of anaphylactic allergic responses and carried EpiPens, and both recovered. During the trial, allergic reaction rates were 0.63% in the vaccine group and 0.51% in the placebo group.

As a result of the two reactions, UK regulators are now recommending that patients with a history of severe allergies not receive the vaccine at the current time.

Q: What are the likely side effects?

So far, the most common side effects are pain at the injection site and an achy, flu-like feeling, Dr. Kuppalli said. More severe reactions have been reported, but were not common in the trials.

Dr. Rasmussen noted that the common side effects are a good sign, and signal that the recipient is generating “a robust immune response.”

“Everybody I’ve talked to who’s had the response has said they would go through it again,” Dr. Kruppalli said. “I definitely plan on lining up and being one of the first people to get the vaccine.”

Q: I already had COVID-19 or had a positive antibody test. Do I still need to get the vaccine?

Dr. Rasmussen said that there are “too many unknowns” to say if a history of COVID-19 would make a difference. “We don’t know how long neutralizing antibodies last” after infection, she said. “What we know is that the vaccine tends to produce antibody titers towards the higher end of the spectrum,” suggesting better immunity with vaccination than after natural infection.

Q: Can patients of color feel safe getting the vaccine?

“People of color might be understandably reluctant to take a vaccine that was developed in a way that appears to be faster [than past development],” said Dr. Rasmussen. She said physicians should acknowledge and understand the history that has led them to feel that way, “everything from Tuskegee to Henrietta Lacks to today.”

Empathy is key, and “providers should meet patients where they are and not condescend to them.”

Dr. Kuppalli agreed. “Clinicians really need to work on trying to strip away their biases.”

Thus far there are no safety signals that differ by race or ethnicity, according to the companies. The Pfizer phase 3 trial enrolled just over 9% Black participants, 0.5% Native American/Alaska Native, 0.2% Native Hawaiian/Pacific Islander, 2.3% multiracial participants, and 28% Hispanic/Latinx. For its part, Moderna says that approximately 37% of participants in its phase 3 trial come from communities of color.

Q: What about children and pregnant women?

Although the trials included participants from many different age groups and backgrounds, children and pregnant or lactating women were not among them. Pfizer gained approval in October to include participants as young as age 12 years, and a Moderna spokesperson said in an interview that the company planned pediatric inclusion at the end of 2020, pending approval.

“Unfortunately, we don’t have data on pregnant and lactating women,” Dr. Kuppalli said. She said she hopes that public health organizations such as the CDC will address that in the coming weeks. Dr. Rasmussen called the lack of data in pregnant women and children “a big oversight.”

Dr. Rasmussen has disclosed no relevant financial relationships. Dr. Kuppalli is a consultant with GlaxoSmithKline.

A version of this article originally appeared on Medscape.com.

For patients with chronic hepatitis B, the protective effects of aspirin against hepatocellular carcinoma (HCC) can vary with cirrhosis status and statin treatment, a pair of new studies finds.

One study showed that, although aspirin is linked to a reduction in risk for HCC in these patients, comedication with statins could explain some of that effect. The other showed that cirrhosis dampens the risk-reduction benefit of aspirin.

Currently, there is a link between a reduction in HCC risk and aspirin or statins in patients with chronic hepatitis B, said investigator Won-Mook Choi, MD, PhD, from the University of Ulsan College of Medicine, in Seoul, Republic of Korea.

In one of their analyses, Choi and his colleagues teased out the contribution of each drug and found that the decrease in HCC risk conferred by statins is similar whether or not patients also take aspirin.

“Only statins showed consistent and significant dose-dependent reductions in the risk of HCC, regardless of study design,” said Choi, who presented the findings at The Liver Meeting 2020.

The second study, which looked at the association between aspirin and the risk for HCC in patients with and without cirrhosis, was presented by Heejoon Jang, MD, from the Seoul National University College of Medicine.

Aspirin was shown to be associated with a reduced risk for HCC, but cirrhosis “had a substantial effect on this association,” erasing the benefit of aspirin, Jang reported.
 

Statins and aspirin

Statins and aspirin are more likely to be prescribed together for patients with chronic hepatitis B but no cirrhosis, said Choi. For that reason, he and his colleagues analyzed data from the Korean National Health Insurance Service database from 2005 to 2015.

In their nested case-control analysis, 17,150 patients with HCC were matched for sex, age, and other factors to 817,675 patients without HCC. All participants had chronic hepatitis B without cirrhosis and had never received antiviral treatment.

The team also analyzed the incidence of HCC in two historic cohorts of patients with chronic hepatitis B but no cirrhosis, one consisting of 673,107 people who took aspirin and the other with 588,045 who took statins.

The nested case-control analysis showed an 11% risk reduction with aspirin use (adjusted odds ratio [OR], 0.89; 95% CI, 0.85 - 0.94) and a 61% risk reduction with statin use (adjusted OR, 0.39; 95% CI, 0.36 - 0.40). There was a dose-response effect with statins, but not with aspirin.

The historic cohort analysis showed a 33% reduction in the risk for HCC with aspirin (adjusted hazard ratio [HR], 0.67; 95% CI, 0.63 - 0.72) and a 67% reduction with statins (adjusted HR, 0.33; 95% CI, 0.30 - 0.37). However, stratified analyses by drug showed a statin benefit with or without aspirin (P < .001 for both), but no aspirin benefit without statins.
 

Cirrhosis and aspirin

To assess the interaction between cirrhosis and aspirin, Jang and his colleagues identified 329,635 patients with chronic hepatitis B in the Korean National Health Insurance Service database.

A total of 20,200 had taken aspirin for at least 90 consecutive days, and the rest had never received antiplatelet therapy. Treated and untreated patients were matched for several factors, and HCC incidence was assessed after a median follow-up of 6.7 years.

Among the 2,697 patients who developed HCC during follow-up, the cumulative incidence of HCC was significantly lower for those who took aspirin than for those who did not (P < .001). There was a 15% reduction in the risk for HCC in the aspirin group (adjusted HR, 0.85; 95% CI, 0.78 - 0.92).

However, in patients with cirrhosis, the benefit of aspirin disappeared. Patients without cirrhosis still had a 13% reduction in risk for HCC (adjusted HR, 0.87: 95% CI, 0.79 - 0.95). This group also had a slightly elevated risk for major bleeding (adjusted HR, 1.1; 95% CI, 1.03 - 1.28).

The findings from these two studies add to a growing body of literature that shows the promise of statins and aspirin, which are both readily available and relatively safe, said Amit Singal, MD, from the UT Southwestern Medical Center in Dallas, who was not involved with either study.

“The studies are relatively simple but really do tackle an area of immense need in the field,” he said. Short of having higher-quality data, however, statins and aspirin aren’t quite ready to become bespoke chemotherapies in the clinic, he added, although the results show promise for future randomized trials.

The subgroup analyses that looked at cirrhosis and the interplay of aspirin and statins can help with the planning of such trials, which “is really important for trial design,” Singal noted.

He also pointed to studies that, unlike these results, have found a benefit of aspirin in patients with cirrhosis, underscoring the need for randomized trials. However, “each study does provide a data point that can help to inform those trials,” he said.

Choi and Jang have disclosed no relevant financial relationships. Singal is a consultant for Genentech, Bayer, Eisai, Exelixis, Bristol-Myers Squibb, Roche, Glycotest, FujiFilm, GRAIL, and Exact Sciences, primarily in relation to HCC treatment and screening, not chemoprevention.

This article first appeared on Medscape.com.

For patients with chronic hepatitis B, the protective effects of aspirin against hepatocellular carcinoma (HCC) can vary with cirrhosis status and statin treatment, a pair of new studies finds.

One study showed that, although aspirin is linked to a reduction in risk for HCC in these patients, comedication with statins could explain some of that effect. The other showed that cirrhosis dampens the risk-reduction benefit of aspirin.

Currently, there is a link between a reduction in HCC risk and aspirin or statins in patients with chronic hepatitis B, said investigator Won-Mook Choi, MD, PhD, from the University of Ulsan College of Medicine, in Seoul, Republic of Korea.

In one of their analyses, Choi and his colleagues teased out the contribution of each drug and found that the decrease in HCC risk conferred by statins is similar whether or not patients also take aspirin.

“Only statins showed consistent and significant dose-dependent reductions in the risk of HCC, regardless of study design,” said Choi, who presented the findings at The Liver Meeting 2020.

The second study, which looked at the association between aspirin and the risk for HCC in patients with and without cirrhosis, was presented by Heejoon Jang, MD, from the Seoul National University College of Medicine.

Aspirin was shown to be associated with a reduced risk for HCC, but cirrhosis “had a substantial effect on this association,” erasing the benefit of aspirin, Jang reported.
 

Statins and aspirin

Statins and aspirin are more likely to be prescribed together for patients with chronic hepatitis B but no cirrhosis, said Choi. For that reason, he and his colleagues analyzed data from the Korean National Health Insurance Service database from 2005 to 2015.

In their nested case-control analysis, 17,150 patients with HCC were matched for sex, age, and other factors to 817,675 patients without HCC. All participants had chronic hepatitis B without cirrhosis and had never received antiviral treatment.

The team also analyzed the incidence of HCC in two historic cohorts of patients with chronic hepatitis B but no cirrhosis, one consisting of 673,107 people who took aspirin and the other with 588,045 who took statins.

The nested case-control analysis showed an 11% risk reduction with aspirin use (adjusted odds ratio [OR], 0.89; 95% CI, 0.85 - 0.94) and a 61% risk reduction with statin use (adjusted OR, 0.39; 95% CI, 0.36 - 0.40). There was a dose-response effect with statins, but not with aspirin.

The historic cohort analysis showed a 33% reduction in the risk for HCC with aspirin (adjusted hazard ratio [HR], 0.67; 95% CI, 0.63 - 0.72) and a 67% reduction with statins (adjusted HR, 0.33; 95% CI, 0.30 - 0.37). However, stratified analyses by drug showed a statin benefit with or without aspirin (P < .001 for both), but no aspirin benefit without statins.
 

Cirrhosis and aspirin

To assess the interaction between cirrhosis and aspirin, Jang and his colleagues identified 329,635 patients with chronic hepatitis B in the Korean National Health Insurance Service database.

A total of 20,200 had taken aspirin for at least 90 consecutive days, and the rest had never received antiplatelet therapy. Treated and untreated patients were matched for several factors, and HCC incidence was assessed after a median follow-up of 6.7 years.

Among the 2,697 patients who developed HCC during follow-up, the cumulative incidence of HCC was significantly lower for those who took aspirin than for those who did not (P < .001). There was a 15% reduction in the risk for HCC in the aspirin group (adjusted HR, 0.85; 95% CI, 0.78 - 0.92).

However, in patients with cirrhosis, the benefit of aspirin disappeared. Patients without cirrhosis still had a 13% reduction in risk for HCC (adjusted HR, 0.87: 95% CI, 0.79 - 0.95). This group also had a slightly elevated risk for major bleeding (adjusted HR, 1.1; 95% CI, 1.03 - 1.28).

The findings from these two studies add to a growing body of literature that shows the promise of statins and aspirin, which are both readily available and relatively safe, said Amit Singal, MD, from the UT Southwestern Medical Center in Dallas, who was not involved with either study.

“The studies are relatively simple but really do tackle an area of immense need in the field,” he said. Short of having higher-quality data, however, statins and aspirin aren’t quite ready to become bespoke chemotherapies in the clinic, he added, although the results show promise for future randomized trials.

The subgroup analyses that looked at cirrhosis and the interplay of aspirin and statins can help with the planning of such trials, which “is really important for trial design,” Singal noted.

He also pointed to studies that, unlike these results, have found a benefit of aspirin in patients with cirrhosis, underscoring the need for randomized trials. However, “each study does provide a data point that can help to inform those trials,” he said.

Choi and Jang have disclosed no relevant financial relationships. Singal is a consultant for Genentech, Bayer, Eisai, Exelixis, Bristol-Myers Squibb, Roche, Glycotest, FujiFilm, GRAIL, and Exact Sciences, primarily in relation to HCC treatment and screening, not chemoprevention.

This article first appeared on Medscape.com.

For patients with chronic hepatitis B, the protective effects of aspirin against hepatocellular carcinoma (HCC) can vary with cirrhosis status and statin treatment, a pair of new studies finds.

One study showed that, although aspirin is linked to a reduction in risk for HCC in these patients, comedication with statins could explain some of that effect. The other showed that cirrhosis dampens the risk-reduction benefit of aspirin.

Currently, there is a link between a reduction in HCC risk and aspirin or statins in patients with chronic hepatitis B, said investigator Won-Mook Choi, MD, PhD, from the University of Ulsan College of Medicine, in Seoul, Republic of Korea.

In one of their analyses, Choi and his colleagues teased out the contribution of each drug and found that the decrease in HCC risk conferred by statins is similar whether or not patients also take aspirin.

“Only statins showed consistent and significant dose-dependent reductions in the risk of HCC, regardless of study design,” said Choi, who presented the findings at The Liver Meeting 2020.

The second study, which looked at the association between aspirin and the risk for HCC in patients with and without cirrhosis, was presented by Heejoon Jang, MD, from the Seoul National University College of Medicine.

Aspirin was shown to be associated with a reduced risk for HCC, but cirrhosis “had a substantial effect on this association,” erasing the benefit of aspirin, Jang reported.
 

Statins and aspirin

Statins and aspirin are more likely to be prescribed together for patients with chronic hepatitis B but no cirrhosis, said Choi. For that reason, he and his colleagues analyzed data from the Korean National Health Insurance Service database from 2005 to 2015.

In their nested case-control analysis, 17,150 patients with HCC were matched for sex, age, and other factors to 817,675 patients without HCC. All participants had chronic hepatitis B without cirrhosis and had never received antiviral treatment.

The team also analyzed the incidence of HCC in two historic cohorts of patients with chronic hepatitis B but no cirrhosis, one consisting of 673,107 people who took aspirin and the other with 588,045 who took statins.

The nested case-control analysis showed an 11% risk reduction with aspirin use (adjusted odds ratio [OR], 0.89; 95% CI, 0.85 - 0.94) and a 61% risk reduction with statin use (adjusted OR, 0.39; 95% CI, 0.36 - 0.40). There was a dose-response effect with statins, but not with aspirin.

The historic cohort analysis showed a 33% reduction in the risk for HCC with aspirin (adjusted hazard ratio [HR], 0.67; 95% CI, 0.63 - 0.72) and a 67% reduction with statins (adjusted HR, 0.33; 95% CI, 0.30 - 0.37). However, stratified analyses by drug showed a statin benefit with or without aspirin (P < .001 for both), but no aspirin benefit without statins.
 

Cirrhosis and aspirin

To assess the interaction between cirrhosis and aspirin, Jang and his colleagues identified 329,635 patients with chronic hepatitis B in the Korean National Health Insurance Service database.

A total of 20,200 had taken aspirin for at least 90 consecutive days, and the rest had never received antiplatelet therapy. Treated and untreated patients were matched for several factors, and HCC incidence was assessed after a median follow-up of 6.7 years.

Among the 2,697 patients who developed HCC during follow-up, the cumulative incidence of HCC was significantly lower for those who took aspirin than for those who did not (P < .001). There was a 15% reduction in the risk for HCC in the aspirin group (adjusted HR, 0.85; 95% CI, 0.78 - 0.92).

However, in patients with cirrhosis, the benefit of aspirin disappeared. Patients without cirrhosis still had a 13% reduction in risk for HCC (adjusted HR, 0.87: 95% CI, 0.79 - 0.95). This group also had a slightly elevated risk for major bleeding (adjusted HR, 1.1; 95% CI, 1.03 - 1.28).

The findings from these two studies add to a growing body of literature that shows the promise of statins and aspirin, which are both readily available and relatively safe, said Amit Singal, MD, from the UT Southwestern Medical Center in Dallas, who was not involved with either study.

“The studies are relatively simple but really do tackle an area of immense need in the field,” he said. Short of having higher-quality data, however, statins and aspirin aren’t quite ready to become bespoke chemotherapies in the clinic, he added, although the results show promise for future randomized trials.

The subgroup analyses that looked at cirrhosis and the interplay of aspirin and statins can help with the planning of such trials, which “is really important for trial design,” Singal noted.

He also pointed to studies that, unlike these results, have found a benefit of aspirin in patients with cirrhosis, underscoring the need for randomized trials. However, “each study does provide a data point that can help to inform those trials,” he said.

Choi and Jang have disclosed no relevant financial relationships. Singal is a consultant for Genentech, Bayer, Eisai, Exelixis, Bristol-Myers Squibb, Roche, Glycotest, FujiFilm, GRAIL, and Exact Sciences, primarily in relation to HCC treatment and screening, not chemoprevention.

This article first appeared on Medscape.com.