Pharmacology

Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.

Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.

Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.

The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.

Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.

“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.

Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”

The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.

Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.

When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.

Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.

“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”

“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”

For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.

For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.

“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”

Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.

“We need more information on what drives this in older adults,” she said.

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

Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.

Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.

Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.

The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.

Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.

“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.

Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”

The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.

Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.

When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.

Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.

“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”

“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”

For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.

For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.

“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”

Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.

“We need more information on what drives this in older adults,” she said.

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

Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.

Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.

Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.

The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.

Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.

“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.

Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”

The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.

Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.

When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.

Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.

“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”

“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”

For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.

For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.

“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”

Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.

“We need more information on what drives this in older adults,” she said.

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

Can’t sleep? When slumber doesn’t come naturally, some are turning to melatonin, an over-the-counter sleep aid that often is mistaken for a supplement. This powerful hormone plays an important role in human biology, and specialists are questioning whether increasing levels could be doing more harm than good.

A new investigation launched by the American Academy of Sleep Medicine is looking into the safety of melatonin. And while the health advisory checking the evidence is underway, the academy is recommending that melatonin not be used for insomnia in adults or children.

But what is insomnia, and how is it different from a few bad nights of sleep? Insomnia disturbs sleep at least three times a week for more than 3 months, often causing people to feel tired during the day as well.

Production of melatonin (dubbed the “vampire hormone”) begins at night, when it starts getting dark outside. Melatonin release is scheduled by the small but mighty pineal gland at the back of the head. Melatonin signals to the body that it’s time to sleep. And as the sun rises and light shines, melatonin levels decline again to help the body wake.

Sometimes packaged in gummy bear fruit flavors, melatonin can have an alluring appeal to sleep-deprived parents looking for relief for themselves and their children.

Muhammad Adeel Rishi, MD, vice chair of the public safety committee for the American Academy of Sleep Medicine, said he has a doctor colleague who started taking melatonin to help him during the pandemic when he was having trouble falling asleep at night. His doctor friend started giving the hormone to his own children, who were also having sleep issues.

But Dr. Rishi said there are important reasons to not use melatonin for insomnia until more information is available.

Melatonin affects sleep, but this hormone also influences other functions in the body. “It has an impact on body temperature, blood sugar, and even the tone of blood vessels,” Dr. Rishi said.

And because melatonin is available over the counter in the United States, it hasn’t been approved as a medicine under the Food and Drug Administration. A previous study of melatonin products, for instance, flagged problems with inconsistent doses, which make it hard for people to know exactly how much they are getting and prompted calls for more FDA oversight.
 

Imprecise doses

While melatonin doses typically range from 1 to 5 milligrams, bottles examined have been off target with much more or less hormone in the product than listed on the label.

Researchers from the University of Guelph (Ont.), tested 30 commercially available formulas and found the melatonin content varied from the ingredients labeled on the bottles by more than 10%. In addition to melatonin, the researchers found other substances in the bottles too: In about a quarter of the products, they also identified serotonin.
 

Impurities

While melatonin plays a role in setting the body’s biological clock and the sleep and wake cycle, serotonin is also at work. Occurring naturally in our bodies, serotonin is involved in mood and helps with deep REM sleep. But adding serotonin in unknown amounts could be unhealthy.

Dr. Rishi said it can be dangerous to use a product as a medication when doses can be so off and there are unknown byproducts in it.

Serotonin can influence the heart, blood vessels, and brain, so it’s not something Dr. Rishi wants to see people taking without paying attention. People taking medication for mood disorders could be especially affected by the serotonin in their sleep aid, he warns.

For anyone taking melatonin, Dr. Rishi recommended they check the bottle to see whether they are using a product with a USP-verified check mark, which indicates that the product meets the standards of the U.S. Pharmacopeia Convention.

The risk of impurities is a good reason for kids to not be given the hormone, but another worry is whether melatonin interferes with puberty in children – which is also a question researchers at the Children’s Hospital of Eastern Ontario in Ottawa are asking.
 

Disrupting puberty

While short-term melatonin use is considered safe, the researchers reported, concerns that long-term use might delay children’s sexual maturation require more study. One theory is that nightly melatonin use might interrupt the decline of natural hormone levels and interfere with the start of puberty.

Researchers from the Children’s Hospital of Michigan in Detroit also reported an uptick in accidental ingestion of melatonin in children. Kids got their hands on melatonin and swallowed too many capsules more often than other pill-related mishaps during the pandemic.

Dr. Rishi said more research is needed to assess the safe use of melatonin in children. He points out that the hormone can treat circadian rhythm disorders in adults.

While specialists weigh the benefits and risks of melatonin use and where it is safest to try, Dr. Rishi said the hormone does have a role in medicine.

Melatonin will probably need to be regulated by the FDA as a medication – especially for children – Dr. Rishi pointed out. And what place, if any, it will have for managing chronic insomnia is “a big question mark.”

Results of the investigation by the American Academy of Sleep Medicine will be published on its sleepeducation.org website in a few months.

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

Can’t sleep? When slumber doesn’t come naturally, some are turning to melatonin, an over-the-counter sleep aid that often is mistaken for a supplement. This powerful hormone plays an important role in human biology, and specialists are questioning whether increasing levels could be doing more harm than good.

A new investigation launched by the American Academy of Sleep Medicine is looking into the safety of melatonin. And while the health advisory checking the evidence is underway, the academy is recommending that melatonin not be used for insomnia in adults or children.

But what is insomnia, and how is it different from a few bad nights of sleep? Insomnia disturbs sleep at least three times a week for more than 3 months, often causing people to feel tired during the day as well.

Production of melatonin (dubbed the “vampire hormone”) begins at night, when it starts getting dark outside. Melatonin release is scheduled by the small but mighty pineal gland at the back of the head. Melatonin signals to the body that it’s time to sleep. And as the sun rises and light shines, melatonin levels decline again to help the body wake.

Sometimes packaged in gummy bear fruit flavors, melatonin can have an alluring appeal to sleep-deprived parents looking for relief for themselves and their children.

Muhammad Adeel Rishi, MD, vice chair of the public safety committee for the American Academy of Sleep Medicine, said he has a doctor colleague who started taking melatonin to help him during the pandemic when he was having trouble falling asleep at night. His doctor friend started giving the hormone to his own children, who were also having sleep issues.

But Dr. Rishi said there are important reasons to not use melatonin for insomnia until more information is available.

Melatonin affects sleep, but this hormone also influences other functions in the body. “It has an impact on body temperature, blood sugar, and even the tone of blood vessels,” Dr. Rishi said.

And because melatonin is available over the counter in the United States, it hasn’t been approved as a medicine under the Food and Drug Administration. A previous study of melatonin products, for instance, flagged problems with inconsistent doses, which make it hard for people to know exactly how much they are getting and prompted calls for more FDA oversight.
 

Imprecise doses

While melatonin doses typically range from 1 to 5 milligrams, bottles examined have been off target with much more or less hormone in the product than listed on the label.

Researchers from the University of Guelph (Ont.), tested 30 commercially available formulas and found the melatonin content varied from the ingredients labeled on the bottles by more than 10%. In addition to melatonin, the researchers found other substances in the bottles too: In about a quarter of the products, they also identified serotonin.
 

Impurities

While melatonin plays a role in setting the body’s biological clock and the sleep and wake cycle, serotonin is also at work. Occurring naturally in our bodies, serotonin is involved in mood and helps with deep REM sleep. But adding serotonin in unknown amounts could be unhealthy.

Dr. Rishi said it can be dangerous to use a product as a medication when doses can be so off and there are unknown byproducts in it.

Serotonin can influence the heart, blood vessels, and brain, so it’s not something Dr. Rishi wants to see people taking without paying attention. People taking medication for mood disorders could be especially affected by the serotonin in their sleep aid, he warns.

For anyone taking melatonin, Dr. Rishi recommended they check the bottle to see whether they are using a product with a USP-verified check mark, which indicates that the product meets the standards of the U.S. Pharmacopeia Convention.

The risk of impurities is a good reason for kids to not be given the hormone, but another worry is whether melatonin interferes with puberty in children – which is also a question researchers at the Children’s Hospital of Eastern Ontario in Ottawa are asking.
 

Disrupting puberty

While short-term melatonin use is considered safe, the researchers reported, concerns that long-term use might delay children’s sexual maturation require more study. One theory is that nightly melatonin use might interrupt the decline of natural hormone levels and interfere with the start of puberty.

Researchers from the Children’s Hospital of Michigan in Detroit also reported an uptick in accidental ingestion of melatonin in children. Kids got their hands on melatonin and swallowed too many capsules more often than other pill-related mishaps during the pandemic.

Dr. Rishi said more research is needed to assess the safe use of melatonin in children. He points out that the hormone can treat circadian rhythm disorders in adults.

While specialists weigh the benefits and risks of melatonin use and where it is safest to try, Dr. Rishi said the hormone does have a role in medicine.

Melatonin will probably need to be regulated by the FDA as a medication – especially for children – Dr. Rishi pointed out. And what place, if any, it will have for managing chronic insomnia is “a big question mark.”

Results of the investigation by the American Academy of Sleep Medicine will be published on its sleepeducation.org website in a few months.

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

Can’t sleep? When slumber doesn’t come naturally, some are turning to melatonin, an over-the-counter sleep aid that often is mistaken for a supplement. This powerful hormone plays an important role in human biology, and specialists are questioning whether increasing levels could be doing more harm than good.

A new investigation launched by the American Academy of Sleep Medicine is looking into the safety of melatonin. And while the health advisory checking the evidence is underway, the academy is recommending that melatonin not be used for insomnia in adults or children.

But what is insomnia, and how is it different from a few bad nights of sleep? Insomnia disturbs sleep at least three times a week for more than 3 months, often causing people to feel tired during the day as well.

Production of melatonin (dubbed the “vampire hormone”) begins at night, when it starts getting dark outside. Melatonin release is scheduled by the small but mighty pineal gland at the back of the head. Melatonin signals to the body that it’s time to sleep. And as the sun rises and light shines, melatonin levels decline again to help the body wake.

Sometimes packaged in gummy bear fruit flavors, melatonin can have an alluring appeal to sleep-deprived parents looking for relief for themselves and their children.

Muhammad Adeel Rishi, MD, vice chair of the public safety committee for the American Academy of Sleep Medicine, said he has a doctor colleague who started taking melatonin to help him during the pandemic when he was having trouble falling asleep at night. His doctor friend started giving the hormone to his own children, who were also having sleep issues.

But Dr. Rishi said there are important reasons to not use melatonin for insomnia until more information is available.

Melatonin affects sleep, but this hormone also influences other functions in the body. “It has an impact on body temperature, blood sugar, and even the tone of blood vessels,” Dr. Rishi said.

And because melatonin is available over the counter in the United States, it hasn’t been approved as a medicine under the Food and Drug Administration. A previous study of melatonin products, for instance, flagged problems with inconsistent doses, which make it hard for people to know exactly how much they are getting and prompted calls for more FDA oversight.
 

Imprecise doses

While melatonin doses typically range from 1 to 5 milligrams, bottles examined have been off target with much more or less hormone in the product than listed on the label.

Researchers from the University of Guelph (Ont.), tested 30 commercially available formulas and found the melatonin content varied from the ingredients labeled on the bottles by more than 10%. In addition to melatonin, the researchers found other substances in the bottles too: In about a quarter of the products, they also identified serotonin.
 

Impurities

While melatonin plays a role in setting the body’s biological clock and the sleep and wake cycle, serotonin is also at work. Occurring naturally in our bodies, serotonin is involved in mood and helps with deep REM sleep. But adding serotonin in unknown amounts could be unhealthy.

Dr. Rishi said it can be dangerous to use a product as a medication when doses can be so off and there are unknown byproducts in it.

Serotonin can influence the heart, blood vessels, and brain, so it’s not something Dr. Rishi wants to see people taking without paying attention. People taking medication for mood disorders could be especially affected by the serotonin in their sleep aid, he warns.

For anyone taking melatonin, Dr. Rishi recommended they check the bottle to see whether they are using a product with a USP-verified check mark, which indicates that the product meets the standards of the U.S. Pharmacopeia Convention.

The risk of impurities is a good reason for kids to not be given the hormone, but another worry is whether melatonin interferes with puberty in children – which is also a question researchers at the Children’s Hospital of Eastern Ontario in Ottawa are asking.
 

Disrupting puberty

While short-term melatonin use is considered safe, the researchers reported, concerns that long-term use might delay children’s sexual maturation require more study. One theory is that nightly melatonin use might interrupt the decline of natural hormone levels and interfere with the start of puberty.

Researchers from the Children’s Hospital of Michigan in Detroit also reported an uptick in accidental ingestion of melatonin in children. Kids got their hands on melatonin and swallowed too many capsules more often than other pill-related mishaps during the pandemic.

Dr. Rishi said more research is needed to assess the safe use of melatonin in children. He points out that the hormone can treat circadian rhythm disorders in adults.

While specialists weigh the benefits and risks of melatonin use and where it is safest to try, Dr. Rishi said the hormone does have a role in medicine.

Melatonin will probably need to be regulated by the FDA as a medication – especially for children – Dr. Rishi pointed out. And what place, if any, it will have for managing chronic insomnia is “a big question mark.”

Results of the investigation by the American Academy of Sleep Medicine will be published on its sleepeducation.org website in a few months.

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

Sips of pickle juice may be all it takes to lessen the severity of muscle cramps in adults with cirrhosis, according to results of the PICCLES randomized controlled trial.

In the trial, patients with cirrhotic cramps who sipped pickle brine at the onset of a muscle cramp saw a significant decrease in cramp severity relative to peers who sipped tap water when the cramp hit.

“The acid (vinegar) in the brine triggers a nerve reflex to stop the cramp when it hits the throat. This is why only a sip is needed,” lead investigator Elliot Tapper, MD, division of gastroenterology and hepatology, University of Michigan, Ann Arbor, told this news organization. The study was published online April 13 in American Journal of Gastroenterology.
 

Common and bothersome

Cramps are common in adults with cirrhosis, irrespective of disease severity. They can sometimes last for hours, and treatment options are limited.

In a prior study, 1 tablespoon of pickle juice rapidly stopped experimentally induced cramps.

“This is something that athletes use, and kidney doctors often recommend to their patients, so it is nothing unique to cirrhosis,” Dr. Tapper said.

The PICCLES trial involved 74 adults (mean age, 56.6 years) with at least 4 muscle cramps in the prior month. In the cohort, 54% were men, and 41% had ascites.

The median cramp frequency was 11-12 per month, with an average cramp severity of more than 4 out of 10 on the Visual Analog Scale (VAS) for cramps. 

Some patients were receiving medications for their cramps at baseline, such as magnesium, potassium, baclofen, vitamin E, taurine, and gabapentin/pregabalin.

Thirty-eight patients were randomly allocated to sip pickle juice and 36 to sip tap water at the onset of a muscle cramp.

The proportion of cramps treated was similar in the pickle juice and tap water groups (77% and 72%). More patients in the pickle juice group said their cramps were aborted by the intervention (69% vs. 40%).

The primary outcome was the change in cramp severity at 28-days VAS for cramps. Cramps were assessed 10 times over 28 days using interactive text messages.

Pickle juice was associated with a larger average reduction in cramp severity than tap water (–2.25 points vs. –0.36 on the VAS-cramps), a difference that was statistically significant (P = .03).

There were no significant changes in the proportion of days with cramp severity of more than 5 on the VAS, or on sleep quality or health-related quality of life. 

Because pickle juice contains sodium, the researchers also assessed weight change as a safety outcome. They found no significant differences in weight change between the two groups overall or in the subset with ascites.

Pickle juice is a “safe option that can stop painful cramps,” Dr. Tapper said in an interview, but was “disheartened” that it did not improve quality of life.

Dr. Tapper encourages patients with cramps to ask their doctor about pickle juice and doctors to ask their patients about muscle cramps.

“Awareness of a patient’s cramps is often lacking. Asking about cramps is not routine but could be the most important advance relating to this study,” he said.

While sips of pickle juice are “unlikely to cause harm,” Dr. Tapper said, he is “a little nervous about advising patients to address their complex needs alone. [Doctors] are there to think through the root causes and help make adjustments that could prevent the cramps in the first place,” he said.
 

Outside experts weigh in

This news organization reached out to several outside experts for their perspective on the study.

Nancy Reau, MD, professor of internal medicine, associate director of solid organ transplantation, and section chief of hepatology. Rush University Medical Center, Chicago, noted that interventions to manage and prevent muscle cramps are “important, as cramping is common in cirrhosis and strongly affects quality of life.”

Dr. Reau cautioned that while pickle juice “sounds benign, it does have a lot of salt. Despite the salt content, this study didn’t show any difference between patients with and without ascites.

“However, cramping is more common in our patients with sarcopenia and those on diuretics for fluid management and it would be easy to see how this might impact fluid management,” Dr. Reau noted.

“Given that it is the acid (not the salt) in the pickle juice, there might be low salt alternatives,” Dr. Reau said.

Echoing Dr. Reau, Ankur Shah, MD, division of kidney disease and hypertension, Brown University, Providence, R.I., noted that “overuse of pickle juice could place patients at risk of developing high blood pressure and fluid overload, and pickle juice should be included in the sodium restriction guidance given to patients with high blood pressure and heart failure.”

In this study, however, the individual dose consumed was low, Dr. Shah noted.

He said the study “elegantly provides evidence to support the practice of sipping pickle juice for cramping.”

The authors should be “applauded for studying a simple solution with the most rigorous of methodologies, a randomized controlled trial,” Dr. Shah added.  

“This simple treatment may be helpful to patients far beyond those with just cirrhosis, and expect future studies to explore this treatment in other populations,” Dr. Shah said in an interview.

Paul Martin, MD, chief of the division of digestive health and liver diseases and Mandel Chair in Gastroenterology, University of Miami, noted that, while muscle cramps can have a major impact on quality of life, “in terms of some of the other complications of cirrhosis that health care providers are dealing with, they may seem relatively innocuous, but obviously patients have a slightly different interpretation because of the effect cramps can have on sleep and so on.

“There have been a variety of home remedies to treat muscle cramps, but this study is intriguing as it suggests that pickle juice, which is freely available, helps mitigate the severity of the cramps. However, it’s unclear whether it prevents cramps,” Dr. Martin said in an interview.

Given that the study is getting traction on Twitter, Dr. Martin encouraged health care providers to be aware of the study and prepared to answer questions from patients.

The study had no specific funding. Dr. Tapper has served as a consultant to Novartis, Axcella, and Allergan, has served on advisory boards for Mallinckrodt, Bausch Health, Kaleido, and Novo Nordisk, and has received unrestricted research grants from Gilead and Valeant. Dr. Reau, Dr. Shah, and Dr. Martin have disclosed no relevant financial relationships.

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

Sips of pickle juice may be all it takes to lessen the severity of muscle cramps in adults with cirrhosis, according to results of the PICCLES randomized controlled trial.

In the trial, patients with cirrhotic cramps who sipped pickle brine at the onset of a muscle cramp saw a significant decrease in cramp severity relative to peers who sipped tap water when the cramp hit.

“The acid (vinegar) in the brine triggers a nerve reflex to stop the cramp when it hits the throat. This is why only a sip is needed,” lead investigator Elliot Tapper, MD, division of gastroenterology and hepatology, University of Michigan, Ann Arbor, told this news organization. The study was published online April 13 in American Journal of Gastroenterology.
 

Common and bothersome

Cramps are common in adults with cirrhosis, irrespective of disease severity. They can sometimes last for hours, and treatment options are limited.

In a prior study, 1 tablespoon of pickle juice rapidly stopped experimentally induced cramps.

“This is something that athletes use, and kidney doctors often recommend to their patients, so it is nothing unique to cirrhosis,” Dr. Tapper said.

The PICCLES trial involved 74 adults (mean age, 56.6 years) with at least 4 muscle cramps in the prior month. In the cohort, 54% were men, and 41% had ascites.

The median cramp frequency was 11-12 per month, with an average cramp severity of more than 4 out of 10 on the Visual Analog Scale (VAS) for cramps. 

Some patients were receiving medications for their cramps at baseline, such as magnesium, potassium, baclofen, vitamin E, taurine, and gabapentin/pregabalin.

Thirty-eight patients were randomly allocated to sip pickle juice and 36 to sip tap water at the onset of a muscle cramp.

The proportion of cramps treated was similar in the pickle juice and tap water groups (77% and 72%). More patients in the pickle juice group said their cramps were aborted by the intervention (69% vs. 40%).

The primary outcome was the change in cramp severity at 28-days VAS for cramps. Cramps were assessed 10 times over 28 days using interactive text messages.

Pickle juice was associated with a larger average reduction in cramp severity than tap water (–2.25 points vs. –0.36 on the VAS-cramps), a difference that was statistically significant (P = .03).

There were no significant changes in the proportion of days with cramp severity of more than 5 on the VAS, or on sleep quality or health-related quality of life. 

Because pickle juice contains sodium, the researchers also assessed weight change as a safety outcome. They found no significant differences in weight change between the two groups overall or in the subset with ascites.

Pickle juice is a “safe option that can stop painful cramps,” Dr. Tapper said in an interview, but was “disheartened” that it did not improve quality of life.

Dr. Tapper encourages patients with cramps to ask their doctor about pickle juice and doctors to ask their patients about muscle cramps.

“Awareness of a patient’s cramps is often lacking. Asking about cramps is not routine but could be the most important advance relating to this study,” he said.

While sips of pickle juice are “unlikely to cause harm,” Dr. Tapper said, he is “a little nervous about advising patients to address their complex needs alone. [Doctors] are there to think through the root causes and help make adjustments that could prevent the cramps in the first place,” he said.
 

Outside experts weigh in

This news organization reached out to several outside experts for their perspective on the study.

Nancy Reau, MD, professor of internal medicine, associate director of solid organ transplantation, and section chief of hepatology. Rush University Medical Center, Chicago, noted that interventions to manage and prevent muscle cramps are “important, as cramping is common in cirrhosis and strongly affects quality of life.”

Dr. Reau cautioned that while pickle juice “sounds benign, it does have a lot of salt. Despite the salt content, this study didn’t show any difference between patients with and without ascites.

“However, cramping is more common in our patients with sarcopenia and those on diuretics for fluid management and it would be easy to see how this might impact fluid management,” Dr. Reau noted.

“Given that it is the acid (not the salt) in the pickle juice, there might be low salt alternatives,” Dr. Reau said.

Echoing Dr. Reau, Ankur Shah, MD, division of kidney disease and hypertension, Brown University, Providence, R.I., noted that “overuse of pickle juice could place patients at risk of developing high blood pressure and fluid overload, and pickle juice should be included in the sodium restriction guidance given to patients with high blood pressure and heart failure.”

In this study, however, the individual dose consumed was low, Dr. Shah noted.

He said the study “elegantly provides evidence to support the practice of sipping pickle juice for cramping.”

The authors should be “applauded for studying a simple solution with the most rigorous of methodologies, a randomized controlled trial,” Dr. Shah added.  

“This simple treatment may be helpful to patients far beyond those with just cirrhosis, and expect future studies to explore this treatment in other populations,” Dr. Shah said in an interview.

Paul Martin, MD, chief of the division of digestive health and liver diseases and Mandel Chair in Gastroenterology, University of Miami, noted that, while muscle cramps can have a major impact on quality of life, “in terms of some of the other complications of cirrhosis that health care providers are dealing with, they may seem relatively innocuous, but obviously patients have a slightly different interpretation because of the effect cramps can have on sleep and so on.

“There have been a variety of home remedies to treat muscle cramps, but this study is intriguing as it suggests that pickle juice, which is freely available, helps mitigate the severity of the cramps. However, it’s unclear whether it prevents cramps,” Dr. Martin said in an interview.

Given that the study is getting traction on Twitter, Dr. Martin encouraged health care providers to be aware of the study and prepared to answer questions from patients.

The study had no specific funding. Dr. Tapper has served as a consultant to Novartis, Axcella, and Allergan, has served on advisory boards for Mallinckrodt, Bausch Health, Kaleido, and Novo Nordisk, and has received unrestricted research grants from Gilead and Valeant. Dr. Reau, Dr. Shah, and Dr. Martin have disclosed no relevant financial relationships.

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

Sips of pickle juice may be all it takes to lessen the severity of muscle cramps in adults with cirrhosis, according to results of the PICCLES randomized controlled trial.

In the trial, patients with cirrhotic cramps who sipped pickle brine at the onset of a muscle cramp saw a significant decrease in cramp severity relative to peers who sipped tap water when the cramp hit.

“The acid (vinegar) in the brine triggers a nerve reflex to stop the cramp when it hits the throat. This is why only a sip is needed,” lead investigator Elliot Tapper, MD, division of gastroenterology and hepatology, University of Michigan, Ann Arbor, told this news organization. The study was published online April 13 in American Journal of Gastroenterology.
 

Common and bothersome

Cramps are common in adults with cirrhosis, irrespective of disease severity. They can sometimes last for hours, and treatment options are limited.

In a prior study, 1 tablespoon of pickle juice rapidly stopped experimentally induced cramps.

“This is something that athletes use, and kidney doctors often recommend to their patients, so it is nothing unique to cirrhosis,” Dr. Tapper said.

The PICCLES trial involved 74 adults (mean age, 56.6 years) with at least 4 muscle cramps in the prior month. In the cohort, 54% were men, and 41% had ascites.

The median cramp frequency was 11-12 per month, with an average cramp severity of more than 4 out of 10 on the Visual Analog Scale (VAS) for cramps. 

Some patients were receiving medications for their cramps at baseline, such as magnesium, potassium, baclofen, vitamin E, taurine, and gabapentin/pregabalin.

Thirty-eight patients were randomly allocated to sip pickle juice and 36 to sip tap water at the onset of a muscle cramp.

The proportion of cramps treated was similar in the pickle juice and tap water groups (77% and 72%). More patients in the pickle juice group said their cramps were aborted by the intervention (69% vs. 40%).

The primary outcome was the change in cramp severity at 28-days VAS for cramps. Cramps were assessed 10 times over 28 days using interactive text messages.

Pickle juice was associated with a larger average reduction in cramp severity than tap water (–2.25 points vs. –0.36 on the VAS-cramps), a difference that was statistically significant (P = .03).

There were no significant changes in the proportion of days with cramp severity of more than 5 on the VAS, or on sleep quality or health-related quality of life. 

Because pickle juice contains sodium, the researchers also assessed weight change as a safety outcome. They found no significant differences in weight change between the two groups overall or in the subset with ascites.

Pickle juice is a “safe option that can stop painful cramps,” Dr. Tapper said in an interview, but was “disheartened” that it did not improve quality of life.

Dr. Tapper encourages patients with cramps to ask their doctor about pickle juice and doctors to ask their patients about muscle cramps.

“Awareness of a patient’s cramps is often lacking. Asking about cramps is not routine but could be the most important advance relating to this study,” he said.

While sips of pickle juice are “unlikely to cause harm,” Dr. Tapper said, he is “a little nervous about advising patients to address their complex needs alone. [Doctors] are there to think through the root causes and help make adjustments that could prevent the cramps in the first place,” he said.
 

Outside experts weigh in

This news organization reached out to several outside experts for their perspective on the study.

Nancy Reau, MD, professor of internal medicine, associate director of solid organ transplantation, and section chief of hepatology. Rush University Medical Center, Chicago, noted that interventions to manage and prevent muscle cramps are “important, as cramping is common in cirrhosis and strongly affects quality of life.”

Dr. Reau cautioned that while pickle juice “sounds benign, it does have a lot of salt. Despite the salt content, this study didn’t show any difference between patients with and without ascites.

“However, cramping is more common in our patients with sarcopenia and those on diuretics for fluid management and it would be easy to see how this might impact fluid management,” Dr. Reau noted.

“Given that it is the acid (not the salt) in the pickle juice, there might be low salt alternatives,” Dr. Reau said.

Echoing Dr. Reau, Ankur Shah, MD, division of kidney disease and hypertension, Brown University, Providence, R.I., noted that “overuse of pickle juice could place patients at risk of developing high blood pressure and fluid overload, and pickle juice should be included in the sodium restriction guidance given to patients with high blood pressure and heart failure.”

In this study, however, the individual dose consumed was low, Dr. Shah noted.

He said the study “elegantly provides evidence to support the practice of sipping pickle juice for cramping.”

The authors should be “applauded for studying a simple solution with the most rigorous of methodologies, a randomized controlled trial,” Dr. Shah added.  

“This simple treatment may be helpful to patients far beyond those with just cirrhosis, and expect future studies to explore this treatment in other populations,” Dr. Shah said in an interview.

Paul Martin, MD, chief of the division of digestive health and liver diseases and Mandel Chair in Gastroenterology, University of Miami, noted that, while muscle cramps can have a major impact on quality of life, “in terms of some of the other complications of cirrhosis that health care providers are dealing with, they may seem relatively innocuous, but obviously patients have a slightly different interpretation because of the effect cramps can have on sleep and so on.

“There have been a variety of home remedies to treat muscle cramps, but this study is intriguing as it suggests that pickle juice, which is freely available, helps mitigate the severity of the cramps. However, it’s unclear whether it prevents cramps,” Dr. Martin said in an interview.

Given that the study is getting traction on Twitter, Dr. Martin encouraged health care providers to be aware of the study and prepared to answer questions from patients.

The study had no specific funding. Dr. Tapper has served as a consultant to Novartis, Axcella, and Allergan, has served on advisory boards for Mallinckrodt, Bausch Health, Kaleido, and Novo Nordisk, and has received unrestricted research grants from Gilead and Valeant. Dr. Reau, Dr. Shah, and Dr. Martin have disclosed no relevant financial relationships.

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

New research suggests that chemotherapy treatments for recurrent high-grade gliomas indicated by an assay-guided tool called ChemoID can boost median survival, compared with physician choice.

The randomized, phase 3 trial results were presented at the annual meeting of the American Association for Cancer Research.

Over a median follow-up of 9 months, median overall survival in the ChemoID group was 12.5 months (95% confidence interval, 10.2-14.7), compared with 9 months (95% CI, 4.2-13.8) in the group whose treatments were chosen by physicians (P = .010).

“While the prognosis is very dismal, we’re still providing a 3.5-month benefit in the guided arm versus physician choice,” said study coauthor Jagan Valluri, PhD, professor of cellular biology and integrative medicine at Marshall University, Huntington, W. Va.

As Dr. Valluri noted, patients with recurrent high-grade gliomas typically have failed radiation and are left with poor prognoses. Fewer than one in four patients respond to chemotherapy at this point, he said, and the response is inconsistent from patient to patient.

“We developed ChemoID since cancer is very unique,” he said, “and any kind of chemotherapy should be tailored to each individual patient on a case-by-case basis.”

The ChemoID tool, a proprietary assay, tests the response of patient cells to various chemotherapy treatments. A test costs $3,500, and some insurers cover it, Dr. Valluri said.

For the new study, researchers randomly assigned 50 patients with grade III/IV recurrent glioma to be treated with chemotherapy chosen by physicians or chemotherapy recommended by the ChemoID tool.

Risk of death in the ChemoID group was lower than in the physician-guided group (hazard ratio, 0.44; 95% CI, 0.24-0.81; P = .008), and median progression-free survival was higher in the ChemoID group (10.1 months vs. 3.5 months; 95% CI, 4.8-15.4 vs. 1.9-5.1; HR, 0.25; 95% CI, 0.14-0.44; P < .001).

“We want the treating physician to have actionable tools in front of them before they treat the patient,” Dr. Valluri said. “We want this assay to become mainstream and part of the standard care workup.”

The study is funded by Cordgenics, where Dr. Valluri serves as chief operating officer.

New research suggests that chemotherapy treatments for recurrent high-grade gliomas indicated by an assay-guided tool called ChemoID can boost median survival, compared with physician choice.

The randomized, phase 3 trial results were presented at the annual meeting of the American Association for Cancer Research.

Over a median follow-up of 9 months, median overall survival in the ChemoID group was 12.5 months (95% confidence interval, 10.2-14.7), compared with 9 months (95% CI, 4.2-13.8) in the group whose treatments were chosen by physicians (P = .010).

“While the prognosis is very dismal, we’re still providing a 3.5-month benefit in the guided arm versus physician choice,” said study coauthor Jagan Valluri, PhD, professor of cellular biology and integrative medicine at Marshall University, Huntington, W. Va.

As Dr. Valluri noted, patients with recurrent high-grade gliomas typically have failed radiation and are left with poor prognoses. Fewer than one in four patients respond to chemotherapy at this point, he said, and the response is inconsistent from patient to patient.

“We developed ChemoID since cancer is very unique,” he said, “and any kind of chemotherapy should be tailored to each individual patient on a case-by-case basis.”

The ChemoID tool, a proprietary assay, tests the response of patient cells to various chemotherapy treatments. A test costs $3,500, and some insurers cover it, Dr. Valluri said.

For the new study, researchers randomly assigned 50 patients with grade III/IV recurrent glioma to be treated with chemotherapy chosen by physicians or chemotherapy recommended by the ChemoID tool.

Risk of death in the ChemoID group was lower than in the physician-guided group (hazard ratio, 0.44; 95% CI, 0.24-0.81; P = .008), and median progression-free survival was higher in the ChemoID group (10.1 months vs. 3.5 months; 95% CI, 4.8-15.4 vs. 1.9-5.1; HR, 0.25; 95% CI, 0.14-0.44; P < .001).

“We want the treating physician to have actionable tools in front of them before they treat the patient,” Dr. Valluri said. “We want this assay to become mainstream and part of the standard care workup.”

The study is funded by Cordgenics, where Dr. Valluri serves as chief operating officer.

New research suggests that chemotherapy treatments for recurrent high-grade gliomas indicated by an assay-guided tool called ChemoID can boost median survival, compared with physician choice.

The randomized, phase 3 trial results were presented at the annual meeting of the American Association for Cancer Research.

Over a median follow-up of 9 months, median overall survival in the ChemoID group was 12.5 months (95% confidence interval, 10.2-14.7), compared with 9 months (95% CI, 4.2-13.8) in the group whose treatments were chosen by physicians (P = .010).

“While the prognosis is very dismal, we’re still providing a 3.5-month benefit in the guided arm versus physician choice,” said study coauthor Jagan Valluri, PhD, professor of cellular biology and integrative medicine at Marshall University, Huntington, W. Va.

As Dr. Valluri noted, patients with recurrent high-grade gliomas typically have failed radiation and are left with poor prognoses. Fewer than one in four patients respond to chemotherapy at this point, he said, and the response is inconsistent from patient to patient.

“We developed ChemoID since cancer is very unique,” he said, “and any kind of chemotherapy should be tailored to each individual patient on a case-by-case basis.”

The ChemoID tool, a proprietary assay, tests the response of patient cells to various chemotherapy treatments. A test costs $3,500, and some insurers cover it, Dr. Valluri said.

For the new study, researchers randomly assigned 50 patients with grade III/IV recurrent glioma to be treated with chemotherapy chosen by physicians or chemotherapy recommended by the ChemoID tool.

Risk of death in the ChemoID group was lower than in the physician-guided group (hazard ratio, 0.44; 95% CI, 0.24-0.81; P = .008), and median progression-free survival was higher in the ChemoID group (10.1 months vs. 3.5 months; 95% CI, 4.8-15.4 vs. 1.9-5.1; HR, 0.25; 95% CI, 0.14-0.44; P < .001).

“We want the treating physician to have actionable tools in front of them before they treat the patient,” Dr. Valluri said. “We want this assay to become mainstream and part of the standard care workup.”

The study is funded by Cordgenics, where Dr. Valluri serves as chief operating officer.

The addition of aspirin to standard guideline management for blood pressure did not reduce the risk of cardiovascular events among adults with hypertension and controlled systolic blood pressure in a study.

The benefits of aspirin use for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) have been questioned in light of data showing neutral outcomes in low-risk patients and concerns about increased bleeding risk and mortality in healthy older adults, wrote Rita Del Pinto, MD, of University of L’Aquila (Italy) and colleagues in JAMA Network Open.

In the study, Dr. Del Pinto and colleagues conducted a post hoc analysis of data from more than 2,500 participants in SPRINT (Systolic Blood Pressure Intervention Trial), a multicenter, randomized trial conducted from 2010 to 2013.

The goal of SPRINT was to compare intensive and standard blood pressure–lowering strategies for hypertension patients. The primary outcome of the current study was risk of a first cardiovascular event, which included adjudicated myocardial infarction, non–myocardial infarction acute coronary syndrome, stroke, acute heart failure, and CVD death.“There has been considerable improvement in the management of cardiovascular risk factors since the first reports on aspirin use for cardiovascular prevention,” Dr. Del Pinto said in an interview.

“As for hypertension, not only have more effective antihypertensive medications become available, but also evidence has recently emerged in support of a downwards redefinition of blood pressure targets during treatment,” she said. “In this context, in an era when great attention is paid to the personalization of treatment, no specific studies had addressed the association of aspirin use as a primary prevention strategy in a cohort of relatively old, high-risk individuals with treated systolic blood pressure steadily below the recommended target,” she added.

The researchers assessed whether aspirin use in addition to standard blood pressure management (a target of less than 140 mm Hg) decreased risk and improved survival.

The study population included 2,664 adult patients; 29.3% were women, and 24.5% were aged 75 years and older. Half of the patients (1,332) received aspirin and 1,332 did not.

In a multivariate analysis, 42 cardiovascular events occurred in the aspirin group, compared with 20 events in those not exposed to aspirin (hazard ratio, 2.30). The findings were consistent in subgroup analyses of younger individuals, current and former smokers, and patients on statins.

An additional subgroup analysis of individuals randomized to standard care or intensive care in the SPRINT study showed no significant difference in primary outcome rates between individuals who received aspirin and those who did not. The rates for aspirin use vs. non–aspirin use were 5.85% vs. 3.60% in the standard treatment group and 4.66% vs. 2.56% in the intensive treatment group.

The study findings were limited by several factors, including the post hoc design, short follow-up period, and lack of data on the initiation of aspirin and bleeding events, the researchers wrote. However, the results suggest that modern management of hypertension may have redefined the potential benefits of aspirin in patients with hypertension, they concluded.

Findings confirm value of preventive care

“The study was conducted as a post-hoc analysis on an experimental cohort, which must be considered when interpreting the results,” Dr. Del Pinto said.

Despite the limitations, the study findings affirm that effective treatment of major cardiovascular risk factors, such as hypertension, with proven drugs is “a mainstay of the primary prevention of ASCVD,” she emphasized.

As for additional research, “Testing our findings in a dedicated setting with sufficiently long follow-up, where aspirin dose and indication, as well as any possible bleeding event, are reported could expand the clinical meaning of our observations,” said Dr. Del Pinto. “Also, the clinical impact of aspirin, even in combination with novel cardiovascular drugs such as direct oral anticoagulants, in populations exposed to combinations of risk factors, deserves further investigation.”

Data support shared decision-making

“While recent evidence has not shown a benefit of aspirin in the primary prevention of ASCVD in several populations, the subpopulation of patients with hypertension as an ASCVD risk factor is also of interest to the clinician,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview. “The lack of benefit of aspirin in this study, despite its limitations, was surprising, and I would be eager to see how the role of aspirin in ASCVD prevention would continue to evolve in conjunction with improvement in other therapies for modification of risk factors.”

“The decision to continue aspirin in this subgroup of patients should warrant a discussion with patients and a reexamination of risks and benefits until further data are available,” Dr. Pal emphasized. 

Larger studies with long-term follow-ups would be required to further clarify the role of aspirin in primary prevention of ASCVD in patients with hypertension without diabetes or chronic kidney disease, he added.

Data were supplied courtesy of BioLINCC. The study received no outside funding. The researchers and Dr. Pal had no financial conflicts to disclose.

The addition of aspirin to standard guideline management for blood pressure did not reduce the risk of cardiovascular events among adults with hypertension and controlled systolic blood pressure in a study.

The benefits of aspirin use for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) have been questioned in light of data showing neutral outcomes in low-risk patients and concerns about increased bleeding risk and mortality in healthy older adults, wrote Rita Del Pinto, MD, of University of L’Aquila (Italy) and colleagues in JAMA Network Open.

In the study, Dr. Del Pinto and colleagues conducted a post hoc analysis of data from more than 2,500 participants in SPRINT (Systolic Blood Pressure Intervention Trial), a multicenter, randomized trial conducted from 2010 to 2013.

The goal of SPRINT was to compare intensive and standard blood pressure–lowering strategies for hypertension patients. The primary outcome of the current study was risk of a first cardiovascular event, which included adjudicated myocardial infarction, non–myocardial infarction acute coronary syndrome, stroke, acute heart failure, and CVD death.“There has been considerable improvement in the management of cardiovascular risk factors since the first reports on aspirin use for cardiovascular prevention,” Dr. Del Pinto said in an interview.

“As for hypertension, not only have more effective antihypertensive medications become available, but also evidence has recently emerged in support of a downwards redefinition of blood pressure targets during treatment,” she said. “In this context, in an era when great attention is paid to the personalization of treatment, no specific studies had addressed the association of aspirin use as a primary prevention strategy in a cohort of relatively old, high-risk individuals with treated systolic blood pressure steadily below the recommended target,” she added.

The researchers assessed whether aspirin use in addition to standard blood pressure management (a target of less than 140 mm Hg) decreased risk and improved survival.

The study population included 2,664 adult patients; 29.3% were women, and 24.5% were aged 75 years and older. Half of the patients (1,332) received aspirin and 1,332 did not.

In a multivariate analysis, 42 cardiovascular events occurred in the aspirin group, compared with 20 events in those not exposed to aspirin (hazard ratio, 2.30). The findings were consistent in subgroup analyses of younger individuals, current and former smokers, and patients on statins.

An additional subgroup analysis of individuals randomized to standard care or intensive care in the SPRINT study showed no significant difference in primary outcome rates between individuals who received aspirin and those who did not. The rates for aspirin use vs. non–aspirin use were 5.85% vs. 3.60% in the standard treatment group and 4.66% vs. 2.56% in the intensive treatment group.

The study findings were limited by several factors, including the post hoc design, short follow-up period, and lack of data on the initiation of aspirin and bleeding events, the researchers wrote. However, the results suggest that modern management of hypertension may have redefined the potential benefits of aspirin in patients with hypertension, they concluded.

Findings confirm value of preventive care

“The study was conducted as a post-hoc analysis on an experimental cohort, which must be considered when interpreting the results,” Dr. Del Pinto said.

Despite the limitations, the study findings affirm that effective treatment of major cardiovascular risk factors, such as hypertension, with proven drugs is “a mainstay of the primary prevention of ASCVD,” she emphasized.

As for additional research, “Testing our findings in a dedicated setting with sufficiently long follow-up, where aspirin dose and indication, as well as any possible bleeding event, are reported could expand the clinical meaning of our observations,” said Dr. Del Pinto. “Also, the clinical impact of aspirin, even in combination with novel cardiovascular drugs such as direct oral anticoagulants, in populations exposed to combinations of risk factors, deserves further investigation.”

Data support shared decision-making

“While recent evidence has not shown a benefit of aspirin in the primary prevention of ASCVD in several populations, the subpopulation of patients with hypertension as an ASCVD risk factor is also of interest to the clinician,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview. “The lack of benefit of aspirin in this study, despite its limitations, was surprising, and I would be eager to see how the role of aspirin in ASCVD prevention would continue to evolve in conjunction with improvement in other therapies for modification of risk factors.”

“The decision to continue aspirin in this subgroup of patients should warrant a discussion with patients and a reexamination of risks and benefits until further data are available,” Dr. Pal emphasized. 

Larger studies with long-term follow-ups would be required to further clarify the role of aspirin in primary prevention of ASCVD in patients with hypertension without diabetes or chronic kidney disease, he added.

Data were supplied courtesy of BioLINCC. The study received no outside funding. The researchers and Dr. Pal had no financial conflicts to disclose.

The addition of aspirin to standard guideline management for blood pressure did not reduce the risk of cardiovascular events among adults with hypertension and controlled systolic blood pressure in a study.

The benefits of aspirin use for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) have been questioned in light of data showing neutral outcomes in low-risk patients and concerns about increased bleeding risk and mortality in healthy older adults, wrote Rita Del Pinto, MD, of University of L’Aquila (Italy) and colleagues in JAMA Network Open.

In the study, Dr. Del Pinto and colleagues conducted a post hoc analysis of data from more than 2,500 participants in SPRINT (Systolic Blood Pressure Intervention Trial), a multicenter, randomized trial conducted from 2010 to 2013.

The goal of SPRINT was to compare intensive and standard blood pressure–lowering strategies for hypertension patients. The primary outcome of the current study was risk of a first cardiovascular event, which included adjudicated myocardial infarction, non–myocardial infarction acute coronary syndrome, stroke, acute heart failure, and CVD death.“There has been considerable improvement in the management of cardiovascular risk factors since the first reports on aspirin use for cardiovascular prevention,” Dr. Del Pinto said in an interview.

“As for hypertension, not only have more effective antihypertensive medications become available, but also evidence has recently emerged in support of a downwards redefinition of blood pressure targets during treatment,” she said. “In this context, in an era when great attention is paid to the personalization of treatment, no specific studies had addressed the association of aspirin use as a primary prevention strategy in a cohort of relatively old, high-risk individuals with treated systolic blood pressure steadily below the recommended target,” she added.

The researchers assessed whether aspirin use in addition to standard blood pressure management (a target of less than 140 mm Hg) decreased risk and improved survival.

The study population included 2,664 adult patients; 29.3% were women, and 24.5% were aged 75 years and older. Half of the patients (1,332) received aspirin and 1,332 did not.

In a multivariate analysis, 42 cardiovascular events occurred in the aspirin group, compared with 20 events in those not exposed to aspirin (hazard ratio, 2.30). The findings were consistent in subgroup analyses of younger individuals, current and former smokers, and patients on statins.

An additional subgroup analysis of individuals randomized to standard care or intensive care in the SPRINT study showed no significant difference in primary outcome rates between individuals who received aspirin and those who did not. The rates for aspirin use vs. non–aspirin use were 5.85% vs. 3.60% in the standard treatment group and 4.66% vs. 2.56% in the intensive treatment group.

The study findings were limited by several factors, including the post hoc design, short follow-up period, and lack of data on the initiation of aspirin and bleeding events, the researchers wrote. However, the results suggest that modern management of hypertension may have redefined the potential benefits of aspirin in patients with hypertension, they concluded.

Findings confirm value of preventive care

“The study was conducted as a post-hoc analysis on an experimental cohort, which must be considered when interpreting the results,” Dr. Del Pinto said.

Despite the limitations, the study findings affirm that effective treatment of major cardiovascular risk factors, such as hypertension, with proven drugs is “a mainstay of the primary prevention of ASCVD,” she emphasized.

As for additional research, “Testing our findings in a dedicated setting with sufficiently long follow-up, where aspirin dose and indication, as well as any possible bleeding event, are reported could expand the clinical meaning of our observations,” said Dr. Del Pinto. “Also, the clinical impact of aspirin, even in combination with novel cardiovascular drugs such as direct oral anticoagulants, in populations exposed to combinations of risk factors, deserves further investigation.”

Data support shared decision-making

“While recent evidence has not shown a benefit of aspirin in the primary prevention of ASCVD in several populations, the subpopulation of patients with hypertension as an ASCVD risk factor is also of interest to the clinician,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview. “The lack of benefit of aspirin in this study, despite its limitations, was surprising, and I would be eager to see how the role of aspirin in ASCVD prevention would continue to evolve in conjunction with improvement in other therapies for modification of risk factors.”

“The decision to continue aspirin in this subgroup of patients should warrant a discussion with patients and a reexamination of risks and benefits until further data are available,” Dr. Pal emphasized. 

Larger studies with long-term follow-ups would be required to further clarify the role of aspirin in primary prevention of ASCVD in patients with hypertension without diabetes or chronic kidney disease, he added.

Data were supplied courtesy of BioLINCC. The study received no outside funding. The researchers and Dr. Pal had no financial conflicts to disclose.

WASHINGTON – Patients with type 2 diabetes and established atherosclerotic cardiovascular disease treated with both an sodium-glucose transporter 2 inhibitor and a glucagonlike peptide–1 receptor agonist had a significant 80% cut in their rate of all-cause death during 1-year follow-up, compared with matched patients treated with an agent from either class alone in an observational, retrospective study of more than 15,000 people in the U.S. Veterans Affairs health system.

For the study’s primary endpoint, the combined rate of all-cause death, nonfatal MI, or nonfatal stroke, combined treatment with both an agent from the sodium-glucose transporter 2 (SGLT2) inhibitor class and from the glucagonlike peptide–1 receptor agonist (GLP-1 RA) class linked with a significant, roughly 50% cut in events during 1-year follow-up, compared with patients treated with an agent from just one of these two classes, Persio D. Lopez, MD, reported at the annual scientific sessions of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

This improvement in the combined endpoint outcome resulted entirely from reduced all-cause mortality. Dual treatment showed no significant association with the incidence of nonfatal MIs or strokes, compared with monotherapy, with rates that were nearly identical regardless of whether patients took one of the agents or both, said Dr. Lopez, a cardiologist at Mount Sinai Morningside and the James J. Peters VA Medical Center, both in New York.
 

Combining classes for hard-to-control diabetes

“We’re not sure what drives combined use” of agents from both drug classes in these types of patients, admitted Dr. Lopez during his talk. “Our hypothesis is that dual treatment is used in patients with harder-to-control diabetes.”

Salim S. Virani, MD, PhD, who practices in the VA system but was not involved with the study, agreed that this is the likely explanation for most instances of high-risk VA patients with diabetes who receive agents from both classes.

Mitchel L. Zoler/MDedge News

“I have a few patients” on both classes, usually “patients with higher starting A1c levels who need greater glycemic control,” said Dr. Virani, professor of medicine at Baylor College of Medicine and a cardiologist at the Michael E. DeBakey VA Medical Center, both in Houston.

U.S. use of either drug class, let alone both, in patients with type 2 diabetes is still struggling to gain traction in U.S. practice and remains limited to a minority of these patients, a prescribing pattern reflected in recent VA data. Analysis of more than half a million patients in the VA system with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) who received treatment at any of 130 VA medical centers throughout 2020 showed that 11% had received an SGLT2 inhibitor, and 8% a GLP-1 RA.

The most frequently used antidiabetes drug classes in these patients were insulin in 36%, biguanides in 47%, and sulfonylureas in 22%.

These data also showed a striking level of variability among the 130 VA centers, with some of the sites prescribing either an SGLT2 inhibitor or a GLP-1 RA to as few as about 3% each of these patients, while other centers had a roughly 10-fold higher prescription rate for each of about 25%-30% of their patients with type 2 diabetes and ASCVD.

Despite the overall modest level of use of both classes in these types of patients as recently as 2020, no barriers exist at the VA to prescribing an agent from one or both classes “if you provide a good reason” for a patient to receive the drugs, Dr. Virani said in an interview. He also predicted that use of both classes in these patients, including combination treatment, will likely soon expand.
 

‘A lot of interest’ in combining an SGLT2 inhibitor and a GLP-1 RA

“There will be a lot of interest in combing the two classes. It makes intuitive sense [to treat with both classes] because most patients with diabetes need more than one drug” for glycemic control, he noted. “Why not use two classes that each reduce a patient’s risk” for adverse outcomes involving ASCVD, heart failure, and renal dysfunction, added Dr. Virani.

The study run by Dr. Lopez and his associates used data collected in the National VA Database and included 121,156 patients with both type 2 diabetes and established ASCVD. Using propensity-score matching the researchers compiled three subgroups that each included 5,277 matched patients. One subgroup had patients prescribed an SGLT2 inhibitor, a second subgroup included patients on a GLP-1 RA, and a third subgroup had patients on agents from both classes. Patient matching relied on age, sex, left ventricular ejection fraction, hemoglobin A1c level, systolic blood pressure, and the presence of coronary artery disease or peripheral artery disease.

Patients included in the analysis averaged about 67 years of age; 97% were men, their average body mass index was about 34 kg/m², their average A1c was about 7.9%, their average estimated glomerular filtration rate was about 55-66 mL/min per 1.73 m², and their average left ventricular ejection fraction was about 55%. The database provided a median follow-up of 902 days (about 2.5 years). The prespecified primary endpoint focused on events that occurred during the first year of follow-up, but the investigators also ran a 3-year follow-up analysis on a post hoc basis.

The most common SGLT2 inhibitor received by these patients was empagliflozin (Jardiance), used on virtually everyone who received an agent from this class. In contrast, the GLP-1 RA drugs that patients received split more widely. The most prescribed agent was liraglutide (Victoza), followed by semaglutide (Ozempic), and dulaglutide (Trulicity), with fewer than 5% receiving exenatide (Bydureon, Byetta).

Regarding other treatments, about 97% of all patients received a statin, about 94% were on a renin-angiotensin system inhibitor, about 90% were on metformin, and roughly 75% were on insulin, aspirin, and a beta-blocker, with smaller numbers on other types of agents.

For the study’s primary endpoint, the 1-year incidence of combined ASCVD events including all-cause death, patients on agents from both classes had a significant 46% reduced rate compared with those on an SGLT2 inhibitor only, and a significant 49% reduced rate, compared with those on a GLP-1 RA only. These between-group separations broadened slightly during 3-year follow-up. Dr. Lopez did not report results of a direct comparison between patients on just an SGLT2 inhibitor and those on just a GLP-1 RA.

For the endpoint of all-cause death, those on combined treatment had a 1-year rate that was 83% below the rate among patients on only an SGLT2 inhibitor, and 81% below the rate among patients who received a GLP-1 RA but not the other class.

Dr. Lopez cautioned that selection bias could have influenced the outcomes of patients who received both classes rather than one or the other, and he also highlighted that the analysis relied on administrative data rather than information gleaned from more detailed medical records or prospectively collected findings and was limited by only including a very small number of women.

“Our results need to be validated in prospective studies,” he declared.

Dr. Lopez and Dr. Virani had no commercial disclosures.

WASHINGTON – Patients with type 2 diabetes and established atherosclerotic cardiovascular disease treated with both an sodium-glucose transporter 2 inhibitor and a glucagonlike peptide–1 receptor agonist had a significant 80% cut in their rate of all-cause death during 1-year follow-up, compared with matched patients treated with an agent from either class alone in an observational, retrospective study of more than 15,000 people in the U.S. Veterans Affairs health system.

For the study’s primary endpoint, the combined rate of all-cause death, nonfatal MI, or nonfatal stroke, combined treatment with both an agent from the sodium-glucose transporter 2 (SGLT2) inhibitor class and from the glucagonlike peptide–1 receptor agonist (GLP-1 RA) class linked with a significant, roughly 50% cut in events during 1-year follow-up, compared with patients treated with an agent from just one of these two classes, Persio D. Lopez, MD, reported at the annual scientific sessions of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

This improvement in the combined endpoint outcome resulted entirely from reduced all-cause mortality. Dual treatment showed no significant association with the incidence of nonfatal MIs or strokes, compared with monotherapy, with rates that were nearly identical regardless of whether patients took one of the agents or both, said Dr. Lopez, a cardiologist at Mount Sinai Morningside and the James J. Peters VA Medical Center, both in New York.
 

Combining classes for hard-to-control diabetes

“We’re not sure what drives combined use” of agents from both drug classes in these types of patients, admitted Dr. Lopez during his talk. “Our hypothesis is that dual treatment is used in patients with harder-to-control diabetes.”

Salim S. Virani, MD, PhD, who practices in the VA system but was not involved with the study, agreed that this is the likely explanation for most instances of high-risk VA patients with diabetes who receive agents from both classes.

Mitchel L. Zoler/MDedge News

“I have a few patients” on both classes, usually “patients with higher starting A1c levels who need greater glycemic control,” said Dr. Virani, professor of medicine at Baylor College of Medicine and a cardiologist at the Michael E. DeBakey VA Medical Center, both in Houston.

U.S. use of either drug class, let alone both, in patients with type 2 diabetes is still struggling to gain traction in U.S. practice and remains limited to a minority of these patients, a prescribing pattern reflected in recent VA data. Analysis of more than half a million patients in the VA system with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) who received treatment at any of 130 VA medical centers throughout 2020 showed that 11% had received an SGLT2 inhibitor, and 8% a GLP-1 RA.

The most frequently used antidiabetes drug classes in these patients were insulin in 36%, biguanides in 47%, and sulfonylureas in 22%.

These data also showed a striking level of variability among the 130 VA centers, with some of the sites prescribing either an SGLT2 inhibitor or a GLP-1 RA to as few as about 3% each of these patients, while other centers had a roughly 10-fold higher prescription rate for each of about 25%-30% of their patients with type 2 diabetes and ASCVD.

Despite the overall modest level of use of both classes in these types of patients as recently as 2020, no barriers exist at the VA to prescribing an agent from one or both classes “if you provide a good reason” for a patient to receive the drugs, Dr. Virani said in an interview. He also predicted that use of both classes in these patients, including combination treatment, will likely soon expand.
 

‘A lot of interest’ in combining an SGLT2 inhibitor and a GLP-1 RA

“There will be a lot of interest in combing the two classes. It makes intuitive sense [to treat with both classes] because most patients with diabetes need more than one drug” for glycemic control, he noted. “Why not use two classes that each reduce a patient’s risk” for adverse outcomes involving ASCVD, heart failure, and renal dysfunction, added Dr. Virani.

The study run by Dr. Lopez and his associates used data collected in the National VA Database and included 121,156 patients with both type 2 diabetes and established ASCVD. Using propensity-score matching the researchers compiled three subgroups that each included 5,277 matched patients. One subgroup had patients prescribed an SGLT2 inhibitor, a second subgroup included patients on a GLP-1 RA, and a third subgroup had patients on agents from both classes. Patient matching relied on age, sex, left ventricular ejection fraction, hemoglobin A1c level, systolic blood pressure, and the presence of coronary artery disease or peripheral artery disease.

Patients included in the analysis averaged about 67 years of age; 97% were men, their average body mass index was about 34 kg/m², their average A1c was about 7.9%, their average estimated glomerular filtration rate was about 55-66 mL/min per 1.73 m², and their average left ventricular ejection fraction was about 55%. The database provided a median follow-up of 902 days (about 2.5 years). The prespecified primary endpoint focused on events that occurred during the first year of follow-up, but the investigators also ran a 3-year follow-up analysis on a post hoc basis.

The most common SGLT2 inhibitor received by these patients was empagliflozin (Jardiance), used on virtually everyone who received an agent from this class. In contrast, the GLP-1 RA drugs that patients received split more widely. The most prescribed agent was liraglutide (Victoza), followed by semaglutide (Ozempic), and dulaglutide (Trulicity), with fewer than 5% receiving exenatide (Bydureon, Byetta).

Regarding other treatments, about 97% of all patients received a statin, about 94% were on a renin-angiotensin system inhibitor, about 90% were on metformin, and roughly 75% were on insulin, aspirin, and a beta-blocker, with smaller numbers on other types of agents.

For the study’s primary endpoint, the 1-year incidence of combined ASCVD events including all-cause death, patients on agents from both classes had a significant 46% reduced rate compared with those on an SGLT2 inhibitor only, and a significant 49% reduced rate, compared with those on a GLP-1 RA only. These between-group separations broadened slightly during 3-year follow-up. Dr. Lopez did not report results of a direct comparison between patients on just an SGLT2 inhibitor and those on just a GLP-1 RA.

For the endpoint of all-cause death, those on combined treatment had a 1-year rate that was 83% below the rate among patients on only an SGLT2 inhibitor, and 81% below the rate among patients who received a GLP-1 RA but not the other class.

Dr. Lopez cautioned that selection bias could have influenced the outcomes of patients who received both classes rather than one or the other, and he also highlighted that the analysis relied on administrative data rather than information gleaned from more detailed medical records or prospectively collected findings and was limited by only including a very small number of women.

“Our results need to be validated in prospective studies,” he declared.

Dr. Lopez and Dr. Virani had no commercial disclosures.

WASHINGTON – Patients with type 2 diabetes and established atherosclerotic cardiovascular disease treated with both an sodium-glucose transporter 2 inhibitor and a glucagonlike peptide–1 receptor agonist had a significant 80% cut in their rate of all-cause death during 1-year follow-up, compared with matched patients treated with an agent from either class alone in an observational, retrospective study of more than 15,000 people in the U.S. Veterans Affairs health system.

For the study’s primary endpoint, the combined rate of all-cause death, nonfatal MI, or nonfatal stroke, combined treatment with both an agent from the sodium-glucose transporter 2 (SGLT2) inhibitor class and from the glucagonlike peptide–1 receptor agonist (GLP-1 RA) class linked with a significant, roughly 50% cut in events during 1-year follow-up, compared with patients treated with an agent from just one of these two classes, Persio D. Lopez, MD, reported at the annual scientific sessions of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

This improvement in the combined endpoint outcome resulted entirely from reduced all-cause mortality. Dual treatment showed no significant association with the incidence of nonfatal MIs or strokes, compared with monotherapy, with rates that were nearly identical regardless of whether patients took one of the agents or both, said Dr. Lopez, a cardiologist at Mount Sinai Morningside and the James J. Peters VA Medical Center, both in New York.
 

Combining classes for hard-to-control diabetes

“We’re not sure what drives combined use” of agents from both drug classes in these types of patients, admitted Dr. Lopez during his talk. “Our hypothesis is that dual treatment is used in patients with harder-to-control diabetes.”

Salim S. Virani, MD, PhD, who practices in the VA system but was not involved with the study, agreed that this is the likely explanation for most instances of high-risk VA patients with diabetes who receive agents from both classes.

Mitchel L. Zoler/MDedge News

“I have a few patients” on both classes, usually “patients with higher starting A1c levels who need greater glycemic control,” said Dr. Virani, professor of medicine at Baylor College of Medicine and a cardiologist at the Michael E. DeBakey VA Medical Center, both in Houston.

U.S. use of either drug class, let alone both, in patients with type 2 diabetes is still struggling to gain traction in U.S. practice and remains limited to a minority of these patients, a prescribing pattern reflected in recent VA data. Analysis of more than half a million patients in the VA system with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) who received treatment at any of 130 VA medical centers throughout 2020 showed that 11% had received an SGLT2 inhibitor, and 8% a GLP-1 RA.

The most frequently used antidiabetes drug classes in these patients were insulin in 36%, biguanides in 47%, and sulfonylureas in 22%.

These data also showed a striking level of variability among the 130 VA centers, with some of the sites prescribing either an SGLT2 inhibitor or a GLP-1 RA to as few as about 3% each of these patients, while other centers had a roughly 10-fold higher prescription rate for each of about 25%-30% of their patients with type 2 diabetes and ASCVD.

Despite the overall modest level of use of both classes in these types of patients as recently as 2020, no barriers exist at the VA to prescribing an agent from one or both classes “if you provide a good reason” for a patient to receive the drugs, Dr. Virani said in an interview. He also predicted that use of both classes in these patients, including combination treatment, will likely soon expand.
 

‘A lot of interest’ in combining an SGLT2 inhibitor and a GLP-1 RA

“There will be a lot of interest in combing the two classes. It makes intuitive sense [to treat with both classes] because most patients with diabetes need more than one drug” for glycemic control, he noted. “Why not use two classes that each reduce a patient’s risk” for adverse outcomes involving ASCVD, heart failure, and renal dysfunction, added Dr. Virani.

The study run by Dr. Lopez and his associates used data collected in the National VA Database and included 121,156 patients with both type 2 diabetes and established ASCVD. Using propensity-score matching the researchers compiled three subgroups that each included 5,277 matched patients. One subgroup had patients prescribed an SGLT2 inhibitor, a second subgroup included patients on a GLP-1 RA, and a third subgroup had patients on agents from both classes. Patient matching relied on age, sex, left ventricular ejection fraction, hemoglobin A1c level, systolic blood pressure, and the presence of coronary artery disease or peripheral artery disease.

Patients included in the analysis averaged about 67 years of age; 97% were men, their average body mass index was about 34 kg/m², their average A1c was about 7.9%, their average estimated glomerular filtration rate was about 55-66 mL/min per 1.73 m², and their average left ventricular ejection fraction was about 55%. The database provided a median follow-up of 902 days (about 2.5 years). The prespecified primary endpoint focused on events that occurred during the first year of follow-up, but the investigators also ran a 3-year follow-up analysis on a post hoc basis.

The most common SGLT2 inhibitor received by these patients was empagliflozin (Jardiance), used on virtually everyone who received an agent from this class. In contrast, the GLP-1 RA drugs that patients received split more widely. The most prescribed agent was liraglutide (Victoza), followed by semaglutide (Ozempic), and dulaglutide (Trulicity), with fewer than 5% receiving exenatide (Bydureon, Byetta).

Regarding other treatments, about 97% of all patients received a statin, about 94% were on a renin-angiotensin system inhibitor, about 90% were on metformin, and roughly 75% were on insulin, aspirin, and a beta-blocker, with smaller numbers on other types of agents.

For the study’s primary endpoint, the 1-year incidence of combined ASCVD events including all-cause death, patients on agents from both classes had a significant 46% reduced rate compared with those on an SGLT2 inhibitor only, and a significant 49% reduced rate, compared with those on a GLP-1 RA only. These between-group separations broadened slightly during 3-year follow-up. Dr. Lopez did not report results of a direct comparison between patients on just an SGLT2 inhibitor and those on just a GLP-1 RA.

For the endpoint of all-cause death, those on combined treatment had a 1-year rate that was 83% below the rate among patients on only an SGLT2 inhibitor, and 81% below the rate among patients who received a GLP-1 RA but not the other class.

Dr. Lopez cautioned that selection bias could have influenced the outcomes of patients who received both classes rather than one or the other, and he also highlighted that the analysis relied on administrative data rather than information gleaned from more detailed medical records or prospectively collected findings and was limited by only including a very small number of women.

“Our results need to be validated in prospective studies,” he declared.

Dr. Lopez and Dr. Virani had no commercial disclosures.

Since the start of the pandemic, supply-chain problems have permeated just about every industry sector. While most of the media attention has focused on toilet paper and retail shipment delays, a darker, more sinister supply chain disruption has been unfolding, one that entails a sophisticated criminal enterprise that has been operating at scale to distribute and profit from counterfeit HIV drugs.

Recently, news has emerged – most notably in the Wall Street Journal – with reports of a Justice Department investigation into what appears to be a national drug trafficking network comprising more than 70 distributors and marketers.

The details read like a best-selling crime novel.

Since last year, authorities have seized 85,247 bottles of counterfeit HIV drugs, both Biktarvy (bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg tablets) and Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg tablets). Law enforcement has conducted raids at 17 locations in eight states. Doctored supply chain papers have provided cover for the fake medicines and the individuals behind them.

But unlike the inconvenience of sparse toilet paper, this crime poses life-threatening risks to millions of patients with HIV who rely on Biktarvy to suppress the virus or Descovy to prevent infection from it. Even worse, some patients have been exposed to over-the-counter painkillers or the antipsychotic drug quetiapine fumarate masquerading as HIV drugs in legitimate but repurposed bottles.

Gilead Sciences (Foster City, Calif.), which manufactures both Biktarvy and Descovy, declined to comment when contacted, instead referring this news organization to previous press statements.
 

Falsified HIV medications, illicit purchases over 2 Years

On Aug. 5, 2021, Gilead first warned the public that it had become aware of tampered and counterfeit Biktarvy and Descovy tablets. In coordination with the Food and Drug Administration, it alerted pharmacies to “investigate the potential for counterfeit or tampered Gilead medication sold by [unauthorized] distributors that may be within their recent supply.”

On Jan. 19, 2022, Gilead issued a second statement outlining ongoing actions in coordination with U.S. marshals and local law enforcement to remove these illegal medications from circulation and prevent further distribution.

The timing of the most recent announcement was not accidental. The day before, a federal judge serving the U.S. District Court for the Eastern District of New York unsealed documents detailing the company’s lawsuit against dozens of individuals and entities who they alleged had engaged in a highly coordinated effort to defraud pharmacies and consumers. The suit followed two prior Gilead filings that ultimately resulted in court-issued ex parte seizure orders (orders that allow a court to seize property without the property owner’s consent) and the recovery of more than 1,000 bottles containing questionable Gilead medications.

The lawsuit centered on Cambridge, Mass.–based wholesale pharmaceutical distributor Safe Chain Solutions and its two cofounders. The document is peppered with terms such as “shifting series of fly-by-night corporate entities,” “gray market” distributors, a “dedicated sales force,” and “shell entities,” along with accusations that the defendants were believed to have made purchases of gold bullion, jewelry, and other luxury items for conversion into cash.

In a curious twist of fate, this sinister effort appeared to have been first revealed not by a pharmacist but by a patient who had returned a bottle of Biktarvy with “foreign medication inside” to the California pharmacy that dispensed it.

“Specifically with HIV medications, there’s no point in which the pharmacy is actually opening the bottle, breaking the seal, and counting out pills to put into a smaller prescription bottle,” Emily Heil, PharmD, BCIDP, AAHIVP, associate professor of infectious diseases in the department of pharmacy practice and science at the University of Maryland School of Pharmacy, Baltimore, told this news organization.

“But that’s also why pharmacies work with these centralized groups of distributors that maintain a chain of command and fidelity with drug manufacturers so that we don’t run into these situations,” she said.

This is the link in the chain where that tightly coordinated and highly regulated process was broken.

Although Gilead and Safe Chain Solutions were informed of the incident as early as August 2020, the distributor repeatedly refused to identify the supplier and the pedigree (the record demonstrating the chain of all sales or transfers of a specific drug, going back to the manufacturer, as required by the FDA’s Drug Supply Chain Security Act in 2013).

Later that year, Janssen Pharmaceutical Companies of Johnson & Johnson issued a media statement saying that they had been alerted to the distribution of counterfeit Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) to three pharmacies in the United States.

A spokesperson for the FDA declined to comment on the ongoing investigation when contacted by this news organization and instead wrote in an email that the agency “will continue to use all available tools to ensure consumers and patients have access to a safe and effective medical product supply.”
 

Old dog, new tricks

This is not the first time that HIV drugs have been targeted for criminal benefit. An analysis published in September 2014 in JAMA highlighted a federal investigation that year into a $32 million dollar scheme to defraud Medicare’s Part D program for HIV drugs and divert them for resale on the black market.

What’s more, prior research and news reports highlight the attractiveness of HIV drug diversion both for the buyer and the seller – not only because of the cost of the drugs themselves but also because of institutional or systemic deficiencies that exclude certain individuals from obtaining treatment through federal initiatives such as the Ryan White/AIDS Drug Assistance program.

In its most recent statement, Gilead reinforced that this practice remains alive and well.

On the buyer side, the company stated, many of the counterfeits originated from suppliers who purchased Gilead HIV medication from individuals after it was first dispensed to them. Unfortunately, the exploitation of individuals with low incomes who experience homelessness or substance use/abuse echoes a pattern whereby HIV patients sell medications to cover personal needs or are forced to buy them on the black market to keep up with their treatment regimens.

On the supply side, Gilead explained that individuals’ medications “are unlawfully resold ... on the secondary market by way of counterfeit supply chain documentation, concealing and fraudulently misrepresenting its origin. All of these counterfeits were sold as though they were legitimate Gilead products.”

But counterfeit pedigrees make it impossible to verify where the products came from, how they have been handled and stored, and what pills are in the bottles – all of which can have dire consequences for patients who ingest them.

The ramifications can be devastating.

“With HIV meds specifically, the worst case scenario would be if the medication is not actually the medication they’re supposed to be on,” said Dr. Heil, reinforcing that the increased safety net provided with viral suppression and against transmission is lost.

Dr. Heil pointed to another significant risk: resistance.

“In a situation like this, where maybe it’s not the full strength of the medication, maybe it’s expired and lost potency or was not stored correctly or is not even the accurate medication, changing those drug level exposures potentially puts the patient at risk for developing resistance to their regimen without them knowing.”

Yet another risk was posed by the replacement of HIV drugs with other medications, such as quetiapine, which increased the risk for life-threatening and irreversible side effects. The lawsuit included a story of a patient who unknowingly took quetiapine after receiving a counterfeit bottle of Biktarvy and could not speak or walk afterward.

Where this tale will ultimately end is unclear. There’s no telling what other activities or bad actors the Justice Department investigation will uncover as it works to unravel the counterfeit network’s activities and deal with its aftermath.

Regardless, clinicians are encouraged to inform HIV patients about the risks associated with counterfeit medications, how to determine whether the drugs they’ve been dispensed are authentic, and to report any product they believe to be counterfeit or to have been tampered with to their doctors, pharmacies, and to Gilead or other drug manufacturers.

“It’s okay to ask questions of your pharmacy about where they get their medications from,” noted Dr. Heil. “If patients have access to an independent pharmacy, it’s a great way for them to have a relationship with their pharmacist.

“We went into this profession to be able to have those conversations with patients,” Dr. Heil said.

The FDA recommends that patients receiving these medications who believe that their drugs may be counterfeit or who experience any adverse effects report the event to FDA’s MedWatch Safety Information and Adverse Event Reporting Program (1-800-FDA-1088 or www.fda.gov/medwatch).

Dr. Heil reported having no relevant financial relationships.

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

Since the start of the pandemic, supply-chain problems have permeated just about every industry sector. While most of the media attention has focused on toilet paper and retail shipment delays, a darker, more sinister supply chain disruption has been unfolding, one that entails a sophisticated criminal enterprise that has been operating at scale to distribute and profit from counterfeit HIV drugs.

Recently, news has emerged – most notably in the Wall Street Journal – with reports of a Justice Department investigation into what appears to be a national drug trafficking network comprising more than 70 distributors and marketers.

The details read like a best-selling crime novel.

Since last year, authorities have seized 85,247 bottles of counterfeit HIV drugs, both Biktarvy (bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg tablets) and Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg tablets). Law enforcement has conducted raids at 17 locations in eight states. Doctored supply chain papers have provided cover for the fake medicines and the individuals behind them.

But unlike the inconvenience of sparse toilet paper, this crime poses life-threatening risks to millions of patients with HIV who rely on Biktarvy to suppress the virus or Descovy to prevent infection from it. Even worse, some patients have been exposed to over-the-counter painkillers or the antipsychotic drug quetiapine fumarate masquerading as HIV drugs in legitimate but repurposed bottles.

Gilead Sciences (Foster City, Calif.), which manufactures both Biktarvy and Descovy, declined to comment when contacted, instead referring this news organization to previous press statements.
 

Falsified HIV medications, illicit purchases over 2 Years

On Aug. 5, 2021, Gilead first warned the public that it had become aware of tampered and counterfeit Biktarvy and Descovy tablets. In coordination with the Food and Drug Administration, it alerted pharmacies to “investigate the potential for counterfeit or tampered Gilead medication sold by [unauthorized] distributors that may be within their recent supply.”

On Jan. 19, 2022, Gilead issued a second statement outlining ongoing actions in coordination with U.S. marshals and local law enforcement to remove these illegal medications from circulation and prevent further distribution.

The timing of the most recent announcement was not accidental. The day before, a federal judge serving the U.S. District Court for the Eastern District of New York unsealed documents detailing the company’s lawsuit against dozens of individuals and entities who they alleged had engaged in a highly coordinated effort to defraud pharmacies and consumers. The suit followed two prior Gilead filings that ultimately resulted in court-issued ex parte seizure orders (orders that allow a court to seize property without the property owner’s consent) and the recovery of more than 1,000 bottles containing questionable Gilead medications.

The lawsuit centered on Cambridge, Mass.–based wholesale pharmaceutical distributor Safe Chain Solutions and its two cofounders. The document is peppered with terms such as “shifting series of fly-by-night corporate entities,” “gray market” distributors, a “dedicated sales force,” and “shell entities,” along with accusations that the defendants were believed to have made purchases of gold bullion, jewelry, and other luxury items for conversion into cash.

In a curious twist of fate, this sinister effort appeared to have been first revealed not by a pharmacist but by a patient who had returned a bottle of Biktarvy with “foreign medication inside” to the California pharmacy that dispensed it.

“Specifically with HIV medications, there’s no point in which the pharmacy is actually opening the bottle, breaking the seal, and counting out pills to put into a smaller prescription bottle,” Emily Heil, PharmD, BCIDP, AAHIVP, associate professor of infectious diseases in the department of pharmacy practice and science at the University of Maryland School of Pharmacy, Baltimore, told this news organization.

“But that’s also why pharmacies work with these centralized groups of distributors that maintain a chain of command and fidelity with drug manufacturers so that we don’t run into these situations,” she said.

This is the link in the chain where that tightly coordinated and highly regulated process was broken.

Although Gilead and Safe Chain Solutions were informed of the incident as early as August 2020, the distributor repeatedly refused to identify the supplier and the pedigree (the record demonstrating the chain of all sales or transfers of a specific drug, going back to the manufacturer, as required by the FDA’s Drug Supply Chain Security Act in 2013).

Later that year, Janssen Pharmaceutical Companies of Johnson & Johnson issued a media statement saying that they had been alerted to the distribution of counterfeit Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) to three pharmacies in the United States.

A spokesperson for the FDA declined to comment on the ongoing investigation when contacted by this news organization and instead wrote in an email that the agency “will continue to use all available tools to ensure consumers and patients have access to a safe and effective medical product supply.”
 

Old dog, new tricks

This is not the first time that HIV drugs have been targeted for criminal benefit. An analysis published in September 2014 in JAMA highlighted a federal investigation that year into a $32 million dollar scheme to defraud Medicare’s Part D program for HIV drugs and divert them for resale on the black market.

What’s more, prior research and news reports highlight the attractiveness of HIV drug diversion both for the buyer and the seller – not only because of the cost of the drugs themselves but also because of institutional or systemic deficiencies that exclude certain individuals from obtaining treatment through federal initiatives such as the Ryan White/AIDS Drug Assistance program.

In its most recent statement, Gilead reinforced that this practice remains alive and well.

On the buyer side, the company stated, many of the counterfeits originated from suppliers who purchased Gilead HIV medication from individuals after it was first dispensed to them. Unfortunately, the exploitation of individuals with low incomes who experience homelessness or substance use/abuse echoes a pattern whereby HIV patients sell medications to cover personal needs or are forced to buy them on the black market to keep up with their treatment regimens.

On the supply side, Gilead explained that individuals’ medications “are unlawfully resold ... on the secondary market by way of counterfeit supply chain documentation, concealing and fraudulently misrepresenting its origin. All of these counterfeits were sold as though they were legitimate Gilead products.”

But counterfeit pedigrees make it impossible to verify where the products came from, how they have been handled and stored, and what pills are in the bottles – all of which can have dire consequences for patients who ingest them.

The ramifications can be devastating.

“With HIV meds specifically, the worst case scenario would be if the medication is not actually the medication they’re supposed to be on,” said Dr. Heil, reinforcing that the increased safety net provided with viral suppression and against transmission is lost.

Dr. Heil pointed to another significant risk: resistance.

“In a situation like this, where maybe it’s not the full strength of the medication, maybe it’s expired and lost potency or was not stored correctly or is not even the accurate medication, changing those drug level exposures potentially puts the patient at risk for developing resistance to their regimen without them knowing.”

Yet another risk was posed by the replacement of HIV drugs with other medications, such as quetiapine, which increased the risk for life-threatening and irreversible side effects. The lawsuit included a story of a patient who unknowingly took quetiapine after receiving a counterfeit bottle of Biktarvy and could not speak or walk afterward.

Where this tale will ultimately end is unclear. There’s no telling what other activities or bad actors the Justice Department investigation will uncover as it works to unravel the counterfeit network’s activities and deal with its aftermath.

Regardless, clinicians are encouraged to inform HIV patients about the risks associated with counterfeit medications, how to determine whether the drugs they’ve been dispensed are authentic, and to report any product they believe to be counterfeit or to have been tampered with to their doctors, pharmacies, and to Gilead or other drug manufacturers.

“It’s okay to ask questions of your pharmacy about where they get their medications from,” noted Dr. Heil. “If patients have access to an independent pharmacy, it’s a great way for them to have a relationship with their pharmacist.

“We went into this profession to be able to have those conversations with patients,” Dr. Heil said.

The FDA recommends that patients receiving these medications who believe that their drugs may be counterfeit or who experience any adverse effects report the event to FDA’s MedWatch Safety Information and Adverse Event Reporting Program (1-800-FDA-1088 or www.fda.gov/medwatch).

Dr. Heil reported having no relevant financial relationships.

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

Since the start of the pandemic, supply-chain problems have permeated just about every industry sector. While most of the media attention has focused on toilet paper and retail shipment delays, a darker, more sinister supply chain disruption has been unfolding, one that entails a sophisticated criminal enterprise that has been operating at scale to distribute and profit from counterfeit HIV drugs.

Recently, news has emerged – most notably in the Wall Street Journal – with reports of a Justice Department investigation into what appears to be a national drug trafficking network comprising more than 70 distributors and marketers.

The details read like a best-selling crime novel.

Since last year, authorities have seized 85,247 bottles of counterfeit HIV drugs, both Biktarvy (bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg tablets) and Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg tablets). Law enforcement has conducted raids at 17 locations in eight states. Doctored supply chain papers have provided cover for the fake medicines and the individuals behind them.

But unlike the inconvenience of sparse toilet paper, this crime poses life-threatening risks to millions of patients with HIV who rely on Biktarvy to suppress the virus or Descovy to prevent infection from it. Even worse, some patients have been exposed to over-the-counter painkillers or the antipsychotic drug quetiapine fumarate masquerading as HIV drugs in legitimate but repurposed bottles.

Gilead Sciences (Foster City, Calif.), which manufactures both Biktarvy and Descovy, declined to comment when contacted, instead referring this news organization to previous press statements.
 

Falsified HIV medications, illicit purchases over 2 Years

On Aug. 5, 2021, Gilead first warned the public that it had become aware of tampered and counterfeit Biktarvy and Descovy tablets. In coordination with the Food and Drug Administration, it alerted pharmacies to “investigate the potential for counterfeit or tampered Gilead medication sold by [unauthorized] distributors that may be within their recent supply.”

On Jan. 19, 2022, Gilead issued a second statement outlining ongoing actions in coordination with U.S. marshals and local law enforcement to remove these illegal medications from circulation and prevent further distribution.

The timing of the most recent announcement was not accidental. The day before, a federal judge serving the U.S. District Court for the Eastern District of New York unsealed documents detailing the company’s lawsuit against dozens of individuals and entities who they alleged had engaged in a highly coordinated effort to defraud pharmacies and consumers. The suit followed two prior Gilead filings that ultimately resulted in court-issued ex parte seizure orders (orders that allow a court to seize property without the property owner’s consent) and the recovery of more than 1,000 bottles containing questionable Gilead medications.

The lawsuit centered on Cambridge, Mass.–based wholesale pharmaceutical distributor Safe Chain Solutions and its two cofounders. The document is peppered with terms such as “shifting series of fly-by-night corporate entities,” “gray market” distributors, a “dedicated sales force,” and “shell entities,” along with accusations that the defendants were believed to have made purchases of gold bullion, jewelry, and other luxury items for conversion into cash.

In a curious twist of fate, this sinister effort appeared to have been first revealed not by a pharmacist but by a patient who had returned a bottle of Biktarvy with “foreign medication inside” to the California pharmacy that dispensed it.

“Specifically with HIV medications, there’s no point in which the pharmacy is actually opening the bottle, breaking the seal, and counting out pills to put into a smaller prescription bottle,” Emily Heil, PharmD, BCIDP, AAHIVP, associate professor of infectious diseases in the department of pharmacy practice and science at the University of Maryland School of Pharmacy, Baltimore, told this news organization.

“But that’s also why pharmacies work with these centralized groups of distributors that maintain a chain of command and fidelity with drug manufacturers so that we don’t run into these situations,” she said.

This is the link in the chain where that tightly coordinated and highly regulated process was broken.

Although Gilead and Safe Chain Solutions were informed of the incident as early as August 2020, the distributor repeatedly refused to identify the supplier and the pedigree (the record demonstrating the chain of all sales or transfers of a specific drug, going back to the manufacturer, as required by the FDA’s Drug Supply Chain Security Act in 2013).

Later that year, Janssen Pharmaceutical Companies of Johnson & Johnson issued a media statement saying that they had been alerted to the distribution of counterfeit Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) to three pharmacies in the United States.

A spokesperson for the FDA declined to comment on the ongoing investigation when contacted by this news organization and instead wrote in an email that the agency “will continue to use all available tools to ensure consumers and patients have access to a safe and effective medical product supply.”
 

Old dog, new tricks

This is not the first time that HIV drugs have been targeted for criminal benefit. An analysis published in September 2014 in JAMA highlighted a federal investigation that year into a $32 million dollar scheme to defraud Medicare’s Part D program for HIV drugs and divert them for resale on the black market.

What’s more, prior research and news reports highlight the attractiveness of HIV drug diversion both for the buyer and the seller – not only because of the cost of the drugs themselves but also because of institutional or systemic deficiencies that exclude certain individuals from obtaining treatment through federal initiatives such as the Ryan White/AIDS Drug Assistance program.

In its most recent statement, Gilead reinforced that this practice remains alive and well.

On the buyer side, the company stated, many of the counterfeits originated from suppliers who purchased Gilead HIV medication from individuals after it was first dispensed to them. Unfortunately, the exploitation of individuals with low incomes who experience homelessness or substance use/abuse echoes a pattern whereby HIV patients sell medications to cover personal needs or are forced to buy them on the black market to keep up with their treatment regimens.

On the supply side, Gilead explained that individuals’ medications “are unlawfully resold ... on the secondary market by way of counterfeit supply chain documentation, concealing and fraudulently misrepresenting its origin. All of these counterfeits were sold as though they were legitimate Gilead products.”

But counterfeit pedigrees make it impossible to verify where the products came from, how they have been handled and stored, and what pills are in the bottles – all of which can have dire consequences for patients who ingest them.

The ramifications can be devastating.

“With HIV meds specifically, the worst case scenario would be if the medication is not actually the medication they’re supposed to be on,” said Dr. Heil, reinforcing that the increased safety net provided with viral suppression and against transmission is lost.

Dr. Heil pointed to another significant risk: resistance.

“In a situation like this, where maybe it’s not the full strength of the medication, maybe it’s expired and lost potency or was not stored correctly or is not even the accurate medication, changing those drug level exposures potentially puts the patient at risk for developing resistance to their regimen without them knowing.”

Yet another risk was posed by the replacement of HIV drugs with other medications, such as quetiapine, which increased the risk for life-threatening and irreversible side effects. The lawsuit included a story of a patient who unknowingly took quetiapine after receiving a counterfeit bottle of Biktarvy and could not speak or walk afterward.

Where this tale will ultimately end is unclear. There’s no telling what other activities or bad actors the Justice Department investigation will uncover as it works to unravel the counterfeit network’s activities and deal with its aftermath.

Regardless, clinicians are encouraged to inform HIV patients about the risks associated with counterfeit medications, how to determine whether the drugs they’ve been dispensed are authentic, and to report any product they believe to be counterfeit or to have been tampered with to their doctors, pharmacies, and to Gilead or other drug manufacturers.

“It’s okay to ask questions of your pharmacy about where they get their medications from,” noted Dr. Heil. “If patients have access to an independent pharmacy, it’s a great way for them to have a relationship with their pharmacist.

“We went into this profession to be able to have those conversations with patients,” Dr. Heil said.

The FDA recommends that patients receiving these medications who believe that their drugs may be counterfeit or who experience any adverse effects report the event to FDA’s MedWatch Safety Information and Adverse Event Reporting Program (1-800-FDA-1088 or www.fda.gov/medwatch).

Dr. Heil reported having no relevant financial relationships.

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

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

The Food and Drug Administration has approved dexmedetomidine (Igalmi, BioXcel Therapeutics) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.

This is the first FDA-approved, orally dissolving, self-administered sublingual treatment for this indication. With a demonstrated onset of action as early as 20 minutes, it shows a high response rate in patients at both 120-mcg and 180-mcg doses.

Olivier Le Moal/Getty Images

An estimated 7.3 million individuals in the United States are diagnosed with schizophrenia or bipolar disorders, and up to one-quarter of them experience episodes of agitation that can occur 10-17 times annually. These episodes represent a significant burden for patients, caregivers, and the health care system.

“There are large numbers of patients who experience agitation associated with schizophrenia and bipolar disorders, and this condition has been a long-standing challenge for health care professionals to treat,” said John Krystal, MD, the Robert L. McNeil Jr. Professor of Translational Research and chair of the department of psychiatry at Yale University, New Haven, Conn.

“The approval of Igalmi, a self-administered film with a desirable onset of action, represents a milestone moment. It provides health care teams with an innovative tool to help control agitation. As clinicians, we welcome this much-needed new oral treatment option,” he added.

“Igalmi is the first new acute treatment for schizophrenia or bipolar disorder–associated agitation in nearly a decade and represents a differentiated approach to helping patients manage this difficult and debilitating symptom,” said Vimal Mehta, PhD, CEO of BioXcel Therapeutics.

The FDA approval of Igalmi is based on data from two pivotal randomized, double-blinded, placebo-controlled, parallel-group, phase 3 trials that evaluated Igalmi for the acute treatment of agitation associated with schizophrenia (SERENITY I) or bipolar I or II disorder (SERENITY II).

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were somnolence, paresthesia or oral hypoesthesia, dizziness, dry mouth, hypotension, and orthostatic hypotension. All adverse drug reactions were mild to moderate in severity. While Igalmi was not associated with any treatment-related serious adverse effects in phase 3 studies, it may cause notable side effects, including hypotension, orthostatic hypotension, bradycardia, QT interval prolongation, and somnolence.

As previously reported by this news organization, data from the phase 3 SERENITY II trial that evaluated Igalmi in bipolar disorders were published in JAMA.

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

The Food and Drug Administration has approved dexmedetomidine (Igalmi, BioXcel Therapeutics) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.

This is the first FDA-approved, orally dissolving, self-administered sublingual treatment for this indication. With a demonstrated onset of action as early as 20 minutes, it shows a high response rate in patients at both 120-mcg and 180-mcg doses.

Olivier Le Moal/Getty Images

An estimated 7.3 million individuals in the United States are diagnosed with schizophrenia or bipolar disorders, and up to one-quarter of them experience episodes of agitation that can occur 10-17 times annually. These episodes represent a significant burden for patients, caregivers, and the health care system.

“There are large numbers of patients who experience agitation associated with schizophrenia and bipolar disorders, and this condition has been a long-standing challenge for health care professionals to treat,” said John Krystal, MD, the Robert L. McNeil Jr. Professor of Translational Research and chair of the department of psychiatry at Yale University, New Haven, Conn.

“The approval of Igalmi, a self-administered film with a desirable onset of action, represents a milestone moment. It provides health care teams with an innovative tool to help control agitation. As clinicians, we welcome this much-needed new oral treatment option,” he added.

“Igalmi is the first new acute treatment for schizophrenia or bipolar disorder–associated agitation in nearly a decade and represents a differentiated approach to helping patients manage this difficult and debilitating symptom,” said Vimal Mehta, PhD, CEO of BioXcel Therapeutics.

The FDA approval of Igalmi is based on data from two pivotal randomized, double-blinded, placebo-controlled, parallel-group, phase 3 trials that evaluated Igalmi for the acute treatment of agitation associated with schizophrenia (SERENITY I) or bipolar I or II disorder (SERENITY II).

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were somnolence, paresthesia or oral hypoesthesia, dizziness, dry mouth, hypotension, and orthostatic hypotension. All adverse drug reactions were mild to moderate in severity. While Igalmi was not associated with any treatment-related serious adverse effects in phase 3 studies, it may cause notable side effects, including hypotension, orthostatic hypotension, bradycardia, QT interval prolongation, and somnolence.

As previously reported by this news organization, data from the phase 3 SERENITY II trial that evaluated Igalmi in bipolar disorders were published in JAMA.

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

The Food and Drug Administration has approved dexmedetomidine (Igalmi, BioXcel Therapeutics) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.

This is the first FDA-approved, orally dissolving, self-administered sublingual treatment for this indication. With a demonstrated onset of action as early as 20 minutes, it shows a high response rate in patients at both 120-mcg and 180-mcg doses.

Olivier Le Moal/Getty Images

An estimated 7.3 million individuals in the United States are diagnosed with schizophrenia or bipolar disorders, and up to one-quarter of them experience episodes of agitation that can occur 10-17 times annually. These episodes represent a significant burden for patients, caregivers, and the health care system.

“There are large numbers of patients who experience agitation associated with schizophrenia and bipolar disorders, and this condition has been a long-standing challenge for health care professionals to treat,” said John Krystal, MD, the Robert L. McNeil Jr. Professor of Translational Research and chair of the department of psychiatry at Yale University, New Haven, Conn.

“The approval of Igalmi, a self-administered film with a desirable onset of action, represents a milestone moment. It provides health care teams with an innovative tool to help control agitation. As clinicians, we welcome this much-needed new oral treatment option,” he added.

“Igalmi is the first new acute treatment for schizophrenia or bipolar disorder–associated agitation in nearly a decade and represents a differentiated approach to helping patients manage this difficult and debilitating symptom,” said Vimal Mehta, PhD, CEO of BioXcel Therapeutics.

The FDA approval of Igalmi is based on data from two pivotal randomized, double-blinded, placebo-controlled, parallel-group, phase 3 trials that evaluated Igalmi for the acute treatment of agitation associated with schizophrenia (SERENITY I) or bipolar I or II disorder (SERENITY II).

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were somnolence, paresthesia or oral hypoesthesia, dizziness, dry mouth, hypotension, and orthostatic hypotension. All adverse drug reactions were mild to moderate in severity. While Igalmi was not associated with any treatment-related serious adverse effects in phase 3 studies, it may cause notable side effects, including hypotension, orthostatic hypotension, bradycardia, QT interval prolongation, and somnolence.

As previously reported by this news organization, data from the phase 3 SERENITY II trial that evaluated Igalmi in bipolar disorders were published in JAMA.

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

Sepsis is life-threatening organ dysfunction caused by dysregulated host response to an infection that can progress to shock. Sepsis is a major cause of death in the United States, with > 1 million people developing sepsis and > 250,000 people dying from sepsis annually.¹ The Surviving Sepsis Campaign (SSC) guidelines recommend treating sepsis as an emergency with timely administration of fluids and antibiotics, as administering antibiotics within the first hour has been found to reduce mortality and disease progression. In addition, empiric antibiotic regimens should be chosen to target the most probable pathogens and dosing should be optimized. To achieve this, the SSC guidelines recommend that hospitals develop quality improvement (QI) programs developed by a multidisciplinary group to improve sepsis recognition and response using a protocolized approach.²

There are several studies describing efforts to improve the sepsis response at facilities, some of which have evaluated the addition of a pharmacist into the sepsis response, particularly in the emergency department (ED). Some studies found improved selection and decreased time to antibiotic administration with the addition of an ED pharmacist.^3-7 Despite this, ED pharmacists are not present in all hospitals, with a 2015 national survey reporting the presence of an ED pharmacist in 68.7% of respondents at 187 facilities. Even facilities with ED pharmacists often have limited hours of coverage, with at least 8 hours of coverage in 49.4% of facilities with an ED pharmacist and no weekend coverage at 34.8% of these facilities.⁸

While many hospitals do not routinely employ ED pharmacists, most hospitals have clinical staff pharmacists (CSPs), and many inpatient hospital pharmacies are staffed with CSPs 24 hours per day, 7 days per week. A 2017 survey conducted by the American Society of Health-System Pharmacists (ASHP) found 43% of all hospital pharmacy departments were staffed by a CSP around the clock, with the prevalence increasing to 56.7 to 100% in hospitals with > 100 beds.⁹ As a result, CSPs may be a useful resource to assist with the management of patients with sepsis in hospitals without an ED pharmacist.

Methods

Lexington VAHCS is a 94-bed hospital that provides services to veterans, including an ED, inpatient medical services, surgical services, acute mental health, progressive care, and intensive care units. This facility has 1 antimicrobial stewardship clinical pharmacy specialist, 2 critical care clinical pharmacy specialists, and 16 full-time CSPs with 24-hour CSP coverage. The annual ED volume at the time of this study was approximately 21,000 patients.

Consistent with the SSC guideline recommendation to develop multidisciplinary QI initiatives on sepsis recognition and response, an Interdisciplinary Sepsis Committee (ISC) was created in 2018 comprised of ED, pulmonary, critical care, and infectious diseases licensed independent practitioners (LIPs), ED nurses, and pharmacists. The ISC developed a comprehensive set of sepsis tools that included a sepsis screening tool used by ED triage nurses to provide early detection of sepsis and an updated electronic order set to decrease time to appropriate treatment. This order set included automatic orders for blood cultures and serum lactate, the initiation of IV crystalloids, as well as a Sepsis Alert order placed by ED LIPs which alerted CSPs to a patient with sepsis in the ED.

To ensure a protocol-based approach by the CSPs responding to the sepsis alert, an antibiotic algorithm and vancomycin dosing nomogram were developed by the ISC based on current guideline recommendations and the local antibiogram. These were subsequently approved by ED practitioners, the pharmacy and therapeutics committee, and the critical care committee. The antibiotic algorithm prompts CSPs to perform a chart review to identify β-lactam allergies, evaluate the severity of the allergy and which agents the patient has tolerated in the past, as well as determine whether the patient has a history of extended spectrum β-lactamase (ESBL)–producing organisms from previous cultures. A decision tree then guides CSPs toward the selection of 1 of 5 empiric antibiotic regimens to cover all likely pathogens. The medication orders are then entered by the CSPs as a telephone order from the ED LIP per protocol. Unless patients had a true vancomycin allergy, all patients received vancomycin as the empiric gram-positive backbone of the regimen. The vancomycin dosing nomogram was created to ensure an appropriate and consistent vancomycin weight-based loading dose was administered.

Results

Between December 3, 2018 and May 31, 2020, 160 sepsis alerts were ordered by ED practitioners. Of the 160 patients, 157 were included in the final data analysis. Two patients were excluded due to vancomycin allergy, and 1 patient because the physician ordered antibiotics prior to pharmacist order entry. The population was largely composed of male patients (98%) with a median age of 72 years (Table 2).

Of 157 sepsis alerts, the antibiotic selection algorithm was used appropriately in 154 (98%) instances (Table 3). Chart reviews were performed in instances of antimicrobial selection different from the algorithm. Of the 3 patients who received antibiotics not consistent with the algorithm, 1 patient without a history of ESBL-producing organisms in their culture history received meropenem instead of piperacillin/tazobactam. Another patient without a penicillin allergy received cefepime (plus metronidazole ordered separately from the ED practitioner) instead of piperacillin/tazobactam, and the third patient received piperacillin/tazobactam instead of meropenem despite a culture history of ESBL-producing organisms. Vancomycin dose was appropriate according to the weight-based nomogram in 147 cases (94%). The median time to administration of first dose antibiotics was 39 minutes after the sepsis alert order was placed and 96 minutes after initial ED presentation.

Discussion

This study found extremely high rates of accuracy among CSPs for both the antibiotic selection algorithm (98%) and the vancomycin dosing nomogram (94%). Moreover, analysis of the 3 patients who received antibiotics that were inconsistent with the algorithm revealed that 2 of these patients arguably still received adequate empiric coverage, increasing the percentage of patients receiving appropriate empiric antibiotics to 99.4%. Similarly, chart review of 10 patients who received vancomycin doses that deviated from the nomogram revealed that in at least 3 cases, patients were likely given correct vancomycin doses based on the patient’s last known weight. However, when actual current weights were recorded soon after admission, the updated weights rendered the initial vancomycin loading dose incorrect when this analysis was performed. Thus, the adherence to the vancomycin dosing nomogram is higher than it appears.

Median time to antibiotic administration from the sepsis alert was 39 minutes—well within SSC recommendations (60 minutes).² Previous internal analyses at Lexington VAHCS demonstrated the mean time to first dose of antibiotics in the ED has been 39 minutes since about 2015. Thus, this initiative did not necessarily make this process quicker; however it did remove 1 responsibility from LIPs so that they could focus their efforts on other components of sepsis management.

Further studies are needed to evaluate the effects of this initiative on other aspects of the sepsis bundle, such as volume of fluid administered and appropriateness of laboratory tests. It was noted that while the time to first-dose antibiotic administration was < 1 hour from order placement, the median time from ED presentation to antibiotic administration was 96 minutes. This suggests that another focus of the sepsis workgroup should be on speeding recognition of sepsis, triggering the sepsis alert even sooner, and evaluating the feasibility of storing first doses of antibiotics in the automatic dispensing cabinets in the ED.

Limitations

This descriptive study evaluating CSPs’ ability to accurately use the newly developed antibiotic selection algorithm and vancomycin dosing nomogram had no control group for outcome comparison. This study was not designed to evaluate clinical outcomes, such as mortality, so the impact of these interventions need to be further studied. In addition, as veterans receive most of their care at our facility, with their allergies and previous cultures readily available in our electronic health record, this process may not be feasible at other facilities where patients' care is divided among multiple facilities/systems.

Moreover, as the veteran population studied was predominately male patients aged > 60 years, implementation at other hospitals may require the dosing nomograms and treatment algorithms to be adapted for a broader population, such as children and pregnant women. In particular, the ISC chose to implement an algorithm that did not differentiate between suspected source of infections and included anti-Pseudomonal coverage in all regimens based on the most encountered diseases among our veteran population and our local antibiogram; implementation at other facilities would require a thoughtful evaluation of the most appropriate site-specific regimen. Finally, many of the CSPs at our facility are board certified and/or residency trained, so more staff development may be required prior to implementation at other facilities, depending on the experience and comfort level of the CSPs.

Strengths

This study describes an example of a protocolized and multidisciplinary approach to improve sepsis recognition and standardize the response, consistent with SSC guideline recommendations. To the best of our knowledge, this is the first study to demonstrate the incorporation of CSPs into the interdisciplinary sepsis response. This allows for CSPs to practice at the top of their license and contributes to their professional development. Although it was not formally assessed, anecdotally CSPs reported that this process presented a negligible addition to their workload (< 5 minutes was the most reported time requirement), and they expressed satisfaction with their involvement in the sepsis response. Overall, this presents a possible solution to improve the sepsis response in hospitals without a dedicated ED pharmacist.

Conclusions

This study describes the successful incorporation of CSPs into the sepsis response in the ED. As CSPs are more likely than ED pharmacists to be present at a facility, they are arguably an underused resource whose clinical skills can be used to optimize the treatment of patients with sepsis.

Sepsis is life-threatening organ dysfunction caused by dysregulated host response to an infection that can progress to shock. Sepsis is a major cause of death in the United States, with > 1 million people developing sepsis and > 250,000 people dying from sepsis annually.¹ The Surviving Sepsis Campaign (SSC) guidelines recommend treating sepsis as an emergency with timely administration of fluids and antibiotics, as administering antibiotics within the first hour has been found to reduce mortality and disease progression. In addition, empiric antibiotic regimens should be chosen to target the most probable pathogens and dosing should be optimized. To achieve this, the SSC guidelines recommend that hospitals develop quality improvement (QI) programs developed by a multidisciplinary group to improve sepsis recognition and response using a protocolized approach.²

There are several studies describing efforts to improve the sepsis response at facilities, some of which have evaluated the addition of a pharmacist into the sepsis response, particularly in the emergency department (ED). Some studies found improved selection and decreased time to antibiotic administration with the addition of an ED pharmacist.^3-7 Despite this, ED pharmacists are not present in all hospitals, with a 2015 national survey reporting the presence of an ED pharmacist in 68.7% of respondents at 187 facilities. Even facilities with ED pharmacists often have limited hours of coverage, with at least 8 hours of coverage in 49.4% of facilities with an ED pharmacist and no weekend coverage at 34.8% of these facilities.⁸

While many hospitals do not routinely employ ED pharmacists, most hospitals have clinical staff pharmacists (CSPs), and many inpatient hospital pharmacies are staffed with CSPs 24 hours per day, 7 days per week. A 2017 survey conducted by the American Society of Health-System Pharmacists (ASHP) found 43% of all hospital pharmacy departments were staffed by a CSP around the clock, with the prevalence increasing to 56.7 to 100% in hospitals with > 100 beds.⁹ As a result, CSPs may be a useful resource to assist with the management of patients with sepsis in hospitals without an ED pharmacist.

Methods

Lexington VAHCS is a 94-bed hospital that provides services to veterans, including an ED, inpatient medical services, surgical services, acute mental health, progressive care, and intensive care units. This facility has 1 antimicrobial stewardship clinical pharmacy specialist, 2 critical care clinical pharmacy specialists, and 16 full-time CSPs with 24-hour CSP coverage. The annual ED volume at the time of this study was approximately 21,000 patients.

Consistent with the SSC guideline recommendation to develop multidisciplinary QI initiatives on sepsis recognition and response, an Interdisciplinary Sepsis Committee (ISC) was created in 2018 comprised of ED, pulmonary, critical care, and infectious diseases licensed independent practitioners (LIPs), ED nurses, and pharmacists. The ISC developed a comprehensive set of sepsis tools that included a sepsis screening tool used by ED triage nurses to provide early detection of sepsis and an updated electronic order set to decrease time to appropriate treatment. This order set included automatic orders for blood cultures and serum lactate, the initiation of IV crystalloids, as well as a Sepsis Alert order placed by ED LIPs which alerted CSPs to a patient with sepsis in the ED.

To ensure a protocol-based approach by the CSPs responding to the sepsis alert, an antibiotic algorithm and vancomycin dosing nomogram were developed by the ISC based on current guideline recommendations and the local antibiogram. These were subsequently approved by ED practitioners, the pharmacy and therapeutics committee, and the critical care committee. The antibiotic algorithm prompts CSPs to perform a chart review to identify β-lactam allergies, evaluate the severity of the allergy and which agents the patient has tolerated in the past, as well as determine whether the patient has a history of extended spectrum β-lactamase (ESBL)–producing organisms from previous cultures. A decision tree then guides CSPs toward the selection of 1 of 5 empiric antibiotic regimens to cover all likely pathogens. The medication orders are then entered by the CSPs as a telephone order from the ED LIP per protocol. Unless patients had a true vancomycin allergy, all patients received vancomycin as the empiric gram-positive backbone of the regimen. The vancomycin dosing nomogram was created to ensure an appropriate and consistent vancomycin weight-based loading dose was administered.

Results

Between December 3, 2018 and May 31, 2020, 160 sepsis alerts were ordered by ED practitioners. Of the 160 patients, 157 were included in the final data analysis. Two patients were excluded due to vancomycin allergy, and 1 patient because the physician ordered antibiotics prior to pharmacist order entry. The population was largely composed of male patients (98%) with a median age of 72 years (Table 2).

Of 157 sepsis alerts, the antibiotic selection algorithm was used appropriately in 154 (98%) instances (Table 3). Chart reviews were performed in instances of antimicrobial selection different from the algorithm. Of the 3 patients who received antibiotics not consistent with the algorithm, 1 patient without a history of ESBL-producing organisms in their culture history received meropenem instead of piperacillin/tazobactam. Another patient without a penicillin allergy received cefepime (plus metronidazole ordered separately from the ED practitioner) instead of piperacillin/tazobactam, and the third patient received piperacillin/tazobactam instead of meropenem despite a culture history of ESBL-producing organisms. Vancomycin dose was appropriate according to the weight-based nomogram in 147 cases (94%). The median time to administration of first dose antibiotics was 39 minutes after the sepsis alert order was placed and 96 minutes after initial ED presentation.

Discussion

This study found extremely high rates of accuracy among CSPs for both the antibiotic selection algorithm (98%) and the vancomycin dosing nomogram (94%). Moreover, analysis of the 3 patients who received antibiotics that were inconsistent with the algorithm revealed that 2 of these patients arguably still received adequate empiric coverage, increasing the percentage of patients receiving appropriate empiric antibiotics to 99.4%. Similarly, chart review of 10 patients who received vancomycin doses that deviated from the nomogram revealed that in at least 3 cases, patients were likely given correct vancomycin doses based on the patient’s last known weight. However, when actual current weights were recorded soon after admission, the updated weights rendered the initial vancomycin loading dose incorrect when this analysis was performed. Thus, the adherence to the vancomycin dosing nomogram is higher than it appears.

Median time to antibiotic administration from the sepsis alert was 39 minutes—well within SSC recommendations (60 minutes).² Previous internal analyses at Lexington VAHCS demonstrated the mean time to first dose of antibiotics in the ED has been 39 minutes since about 2015. Thus, this initiative did not necessarily make this process quicker; however it did remove 1 responsibility from LIPs so that they could focus their efforts on other components of sepsis management.

Further studies are needed to evaluate the effects of this initiative on other aspects of the sepsis bundle, such as volume of fluid administered and appropriateness of laboratory tests. It was noted that while the time to first-dose antibiotic administration was < 1 hour from order placement, the median time from ED presentation to antibiotic administration was 96 minutes. This suggests that another focus of the sepsis workgroup should be on speeding recognition of sepsis, triggering the sepsis alert even sooner, and evaluating the feasibility of storing first doses of antibiotics in the automatic dispensing cabinets in the ED.

Limitations

This descriptive study evaluating CSPs’ ability to accurately use the newly developed antibiotic selection algorithm and vancomycin dosing nomogram had no control group for outcome comparison. This study was not designed to evaluate clinical outcomes, such as mortality, so the impact of these interventions need to be further studied. In addition, as veterans receive most of their care at our facility, with their allergies and previous cultures readily available in our electronic health record, this process may not be feasible at other facilities where patients' care is divided among multiple facilities/systems.

Moreover, as the veteran population studied was predominately male patients aged > 60 years, implementation at other hospitals may require the dosing nomograms and treatment algorithms to be adapted for a broader population, such as children and pregnant women. In particular, the ISC chose to implement an algorithm that did not differentiate between suspected source of infections and included anti-Pseudomonal coverage in all regimens based on the most encountered diseases among our veteran population and our local antibiogram; implementation at other facilities would require a thoughtful evaluation of the most appropriate site-specific regimen. Finally, many of the CSPs at our facility are board certified and/or residency trained, so more staff development may be required prior to implementation at other facilities, depending on the experience and comfort level of the CSPs.

Strengths

This study describes an example of a protocolized and multidisciplinary approach to improve sepsis recognition and standardize the response, consistent with SSC guideline recommendations. To the best of our knowledge, this is the first study to demonstrate the incorporation of CSPs into the interdisciplinary sepsis response. This allows for CSPs to practice at the top of their license and contributes to their professional development. Although it was not formally assessed, anecdotally CSPs reported that this process presented a negligible addition to their workload (< 5 minutes was the most reported time requirement), and they expressed satisfaction with their involvement in the sepsis response. Overall, this presents a possible solution to improve the sepsis response in hospitals without a dedicated ED pharmacist.

Conclusions

This study describes the successful incorporation of CSPs into the sepsis response in the ED. As CSPs are more likely than ED pharmacists to be present at a facility, they are arguably an underused resource whose clinical skills can be used to optimize the treatment of patients with sepsis.

Sepsis is life-threatening organ dysfunction caused by dysregulated host response to an infection that can progress to shock. Sepsis is a major cause of death in the United States, with > 1 million people developing sepsis and > 250,000 people dying from sepsis annually.¹ The Surviving Sepsis Campaign (SSC) guidelines recommend treating sepsis as an emergency with timely administration of fluids and antibiotics, as administering antibiotics within the first hour has been found to reduce mortality and disease progression. In addition, empiric antibiotic regimens should be chosen to target the most probable pathogens and dosing should be optimized. To achieve this, the SSC guidelines recommend that hospitals develop quality improvement (QI) programs developed by a multidisciplinary group to improve sepsis recognition and response using a protocolized approach.²

There are several studies describing efforts to improve the sepsis response at facilities, some of which have evaluated the addition of a pharmacist into the sepsis response, particularly in the emergency department (ED). Some studies found improved selection and decreased time to antibiotic administration with the addition of an ED pharmacist.^3-7 Despite this, ED pharmacists are not present in all hospitals, with a 2015 national survey reporting the presence of an ED pharmacist in 68.7% of respondents at 187 facilities. Even facilities with ED pharmacists often have limited hours of coverage, with at least 8 hours of coverage in 49.4% of facilities with an ED pharmacist and no weekend coverage at 34.8% of these facilities.⁸

While many hospitals do not routinely employ ED pharmacists, most hospitals have clinical staff pharmacists (CSPs), and many inpatient hospital pharmacies are staffed with CSPs 24 hours per day, 7 days per week. A 2017 survey conducted by the American Society of Health-System Pharmacists (ASHP) found 43% of all hospital pharmacy departments were staffed by a CSP around the clock, with the prevalence increasing to 56.7 to 100% in hospitals with > 100 beds.⁹ As a result, CSPs may be a useful resource to assist with the management of patients with sepsis in hospitals without an ED pharmacist.

Methods

Lexington VAHCS is a 94-bed hospital that provides services to veterans, including an ED, inpatient medical services, surgical services, acute mental health, progressive care, and intensive care units. This facility has 1 antimicrobial stewardship clinical pharmacy specialist, 2 critical care clinical pharmacy specialists, and 16 full-time CSPs with 24-hour CSP coverage. The annual ED volume at the time of this study was approximately 21,000 patients.

Consistent with the SSC guideline recommendation to develop multidisciplinary QI initiatives on sepsis recognition and response, an Interdisciplinary Sepsis Committee (ISC) was created in 2018 comprised of ED, pulmonary, critical care, and infectious diseases licensed independent practitioners (LIPs), ED nurses, and pharmacists. The ISC developed a comprehensive set of sepsis tools that included a sepsis screening tool used by ED triage nurses to provide early detection of sepsis and an updated electronic order set to decrease time to appropriate treatment. This order set included automatic orders for blood cultures and serum lactate, the initiation of IV crystalloids, as well as a Sepsis Alert order placed by ED LIPs which alerted CSPs to a patient with sepsis in the ED.

To ensure a protocol-based approach by the CSPs responding to the sepsis alert, an antibiotic algorithm and vancomycin dosing nomogram were developed by the ISC based on current guideline recommendations and the local antibiogram. These were subsequently approved by ED practitioners, the pharmacy and therapeutics committee, and the critical care committee. The antibiotic algorithm prompts CSPs to perform a chart review to identify β-lactam allergies, evaluate the severity of the allergy and which agents the patient has tolerated in the past, as well as determine whether the patient has a history of extended spectrum β-lactamase (ESBL)–producing organisms from previous cultures. A decision tree then guides CSPs toward the selection of 1 of 5 empiric antibiotic regimens to cover all likely pathogens. The medication orders are then entered by the CSPs as a telephone order from the ED LIP per protocol. Unless patients had a true vancomycin allergy, all patients received vancomycin as the empiric gram-positive backbone of the regimen. The vancomycin dosing nomogram was created to ensure an appropriate and consistent vancomycin weight-based loading dose was administered.

Results

Between December 3, 2018 and May 31, 2020, 160 sepsis alerts were ordered by ED practitioners. Of the 160 patients, 157 were included in the final data analysis. Two patients were excluded due to vancomycin allergy, and 1 patient because the physician ordered antibiotics prior to pharmacist order entry. The population was largely composed of male patients (98%) with a median age of 72 years (Table 2).

Of 157 sepsis alerts, the antibiotic selection algorithm was used appropriately in 154 (98%) instances (Table 3). Chart reviews were performed in instances of antimicrobial selection different from the algorithm. Of the 3 patients who received antibiotics not consistent with the algorithm, 1 patient without a history of ESBL-producing organisms in their culture history received meropenem instead of piperacillin/tazobactam. Another patient without a penicillin allergy received cefepime (plus metronidazole ordered separately from the ED practitioner) instead of piperacillin/tazobactam, and the third patient received piperacillin/tazobactam instead of meropenem despite a culture history of ESBL-producing organisms. Vancomycin dose was appropriate according to the weight-based nomogram in 147 cases (94%). The median time to administration of first dose antibiotics was 39 minutes after the sepsis alert order was placed and 96 minutes after initial ED presentation.

Discussion

This study found extremely high rates of accuracy among CSPs for both the antibiotic selection algorithm (98%) and the vancomycin dosing nomogram (94%). Moreover, analysis of the 3 patients who received antibiotics that were inconsistent with the algorithm revealed that 2 of these patients arguably still received adequate empiric coverage, increasing the percentage of patients receiving appropriate empiric antibiotics to 99.4%. Similarly, chart review of 10 patients who received vancomycin doses that deviated from the nomogram revealed that in at least 3 cases, patients were likely given correct vancomycin doses based on the patient’s last known weight. However, when actual current weights were recorded soon after admission, the updated weights rendered the initial vancomycin loading dose incorrect when this analysis was performed. Thus, the adherence to the vancomycin dosing nomogram is higher than it appears.

Median time to antibiotic administration from the sepsis alert was 39 minutes—well within SSC recommendations (60 minutes).² Previous internal analyses at Lexington VAHCS demonstrated the mean time to first dose of antibiotics in the ED has been 39 minutes since about 2015. Thus, this initiative did not necessarily make this process quicker; however it did remove 1 responsibility from LIPs so that they could focus their efforts on other components of sepsis management.

Further studies are needed to evaluate the effects of this initiative on other aspects of the sepsis bundle, such as volume of fluid administered and appropriateness of laboratory tests. It was noted that while the time to first-dose antibiotic administration was < 1 hour from order placement, the median time from ED presentation to antibiotic administration was 96 minutes. This suggests that another focus of the sepsis workgroup should be on speeding recognition of sepsis, triggering the sepsis alert even sooner, and evaluating the feasibility of storing first doses of antibiotics in the automatic dispensing cabinets in the ED.

Limitations

This descriptive study evaluating CSPs’ ability to accurately use the newly developed antibiotic selection algorithm and vancomycin dosing nomogram had no control group for outcome comparison. This study was not designed to evaluate clinical outcomes, such as mortality, so the impact of these interventions need to be further studied. In addition, as veterans receive most of their care at our facility, with their allergies and previous cultures readily available in our electronic health record, this process may not be feasible at other facilities where patients' care is divided among multiple facilities/systems.

Moreover, as the veteran population studied was predominately male patients aged > 60 years, implementation at other hospitals may require the dosing nomograms and treatment algorithms to be adapted for a broader population, such as children and pregnant women. In particular, the ISC chose to implement an algorithm that did not differentiate between suspected source of infections and included anti-Pseudomonal coverage in all regimens based on the most encountered diseases among our veteran population and our local antibiogram; implementation at other facilities would require a thoughtful evaluation of the most appropriate site-specific regimen. Finally, many of the CSPs at our facility are board certified and/or residency trained, so more staff development may be required prior to implementation at other facilities, depending on the experience and comfort level of the CSPs.

Strengths

This study describes an example of a protocolized and multidisciplinary approach to improve sepsis recognition and standardize the response, consistent with SSC guideline recommendations. To the best of our knowledge, this is the first study to demonstrate the incorporation of CSPs into the interdisciplinary sepsis response. This allows for CSPs to practice at the top of their license and contributes to their professional development. Although it was not formally assessed, anecdotally CSPs reported that this process presented a negligible addition to their workload (< 5 minutes was the most reported time requirement), and they expressed satisfaction with their involvement in the sepsis response. Overall, this presents a possible solution to improve the sepsis response in hospitals without a dedicated ED pharmacist.

Conclusions

This study describes the successful incorporation of CSPs into the sepsis response in the ED. As CSPs are more likely than ED pharmacists to be present at a facility, they are arguably an underused resource whose clinical skills can be used to optimize the treatment of patients with sepsis.