Clinician Reviews

PHILADELPHIA – Treatment with aprocitentan, a novel agent currently under Food and Drug Administration review for lowering blood pressure in people with treatment-resistant hypertension, showed efficacy and safety in people with stage 3 or 4 chronic kidney disease (CKD). The results come from a prespecified subgroup analysis of data collected in the drug’s pivotal trial, PRECISION.

The findings provide support for potentially using aprocitentan, if approved for U.S. marketing in 2024, in patients with blood pressure that remains elevated despite treatment with three established antihypertensive drug classes and with stage 3 CKD with an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m². This is a key group of patients because “chronic kidney disease is the most common comorbidity in patients with resistant hypertension,” said George Bakris, MD, who presented the subgroup analysis at Kidney Week 2023, organized by the American Society of Nephrology.

Mtchel L. Zoler/MDedge News

The CKD subgroup analysis showed “good evidence for safety and evidence in stage 3 CKD,” a subgroup of 141 patients among the total 730 enrolled in PRECISION, said Dr. Bakris. Professor and director of the Comprehensive Hypertension Center at the University of Chicago, he acknowledged that while the results also showed a signal for safety and efficacy in the 21 enrolled patients with stage 4 hypertension, 15-29 mL/min per 1.73m², this number of stage 4 patients was too small to allow definitive conclusions.

Nephrologist Nishigandha Pradhan, MD, who cochaired the session with this report, agreed. “Resistant hypertension is a particularly intractable problem in patients with CKD, and the risk is greatest with stage 4 CKD. If studies could show that aprocitentan is safe in people with stage 4 CKD, that would be a big plus, but we need more data,” commented Dr. Pradhan in an interview.
 

Incremental blood pressure reductions

The parallel-group, phase 3 PRECISION trial investigated the safety and short-term antihypertensive effect of aprocitentan in patients with resistant hypertension. The study’s primary efficacy endpoint was blood pressure reduction from baseline in 730 randomized people with persistent systolic hypertension despite treatment with three established antihypertensive agents including a diuretic. The study ran during June 2018–April 2022 at 191 sites in 22 countries.

The primary outcome after 4 weeks on treatment was a least-square mean reduction in office-measured systolic blood pressure, compared with placebo, of 3.8 mm Hg with a 12.5-mg daily oral dose of aprocitentan and 3.7 mm Hg with a 25-mg daily oral dose. Both significant differences were first reported in 2022. Twenty-four–hour ambulatory systolic blood pressures after 4 weeks of treatment fell by an average of 4.2 mm Hg on the lower dose compared with placebo and by an average of 5.9 mm Hg on the higher daily dose, compared with placebo.

Consistent blood pressure reductions occurred in the CKD subgroups. Among people with stage 3 CKD, daytime ambulatory blood pressure at 4 weeks fell by about 10 mm Hg on both the 12.5-mg daily and 25-mg daily doses, compared with placebo.

Among the small number of people with stage 4 CKD, the incremental nighttime systolic blood pressure on aprocitentan, compared with placebo, was even greater, with about a 15–mm Hg incremental reduction on 12.5 mg daily and about a 17–mm Hg incremental reduction on the higher dose.

“This is the first evidence for a change in nocturnal blood pressure in people with stage 4 CKD [and treatment-resistant hypertension], but it was just 21 patients so not yet a big deal,” Dr. Bakris noted.
 

Increased rates of fluid retention

Although aprocitentan was generally well tolerated, the most common adverse effect was edema or fluid retention, mainly during the first 4 weeks of treatment. In the full PRECISION cohort, this adverse event occurred in 2.1% of people treated with placebo, 9.1% of those on the 12.5-mg daily dose, and in 18.4% of those on the higher dose during the initial 4-week phase of treatment.

Among all stage 3 and 4 CKD patients on aprocitentan, edema or fluid retention occurred in 21% during the first 4 weeks, and in 27% during an additional 32 weeks of treatment with 25 mg aprocitentan daily. A majority of these patients started a diuretic to address their excess fluid, with only two discontinuing aprocitentan treatment.

“Fluid retention is an issue with aprocitentan,” Dr. Bakris acknowledged. But he also highlighted than only 6 of the 162 patients with CKD required hospitalization for heart failure during the study, and one of these cases had placebo treatment. Among the five with acute heart failure while on aprocitentan, none had to stop their treatment, and two had a clear prior history of heart failure.

The companies developing aprocitentan, Janssen and Idorsia, used the PRECISION results as the centerpiece in filing for a new drug approval to the FDA, with a March 2024 goal for the FDA‘s decision. Dr. Bakris called the application “a solid case for approval.” But he added that approval will likely require that all treatment candidates first undergo testing of their heart function or fluid volume, such as a measure of their blood level of N-terminal pro-B-type natriuretic peptide, with treatment withheld when the level is too high.

The upside of aprocitentan compared with current drug options for treating resistant hypertension is that it has not appeared to cause any increase in blood potassium levels, which is an issue with the current top agent for resistant hypertension, spironolactone.

“The problem with spironolactone is the risk for hyperkalemia, which keeps us looking for something with lower risk,” commented Dr. Pradhan, a nephrologist with University Hospitals in Cleveland. Hyperkalemia is an even greater risk for people with CKD. Although the PRECISION trial identified the issue of fluid retention with aprocitentan, titrating an effective dose of a loop diuretic for treated patients may effectively blunt the edema risk, Dr. Pradhan said.

Endothelin has a potent vasoconstrictive effect and is “implicated in the pathogenesis of hypertension,” Dr. Bakris explained. Aprocitentan antagonizes both the endothelin A and B receptors. The subgroup analyses also showed that in people with CKD, treatment with aprocitentan led to roughly a halving of the baseline level of urine albumin-to-creatinine ratio, a small and stable decrease in estimated glomerular filtration rate, and a modest and stable increase in blood levels of N-terminal pro-B-type natriuretic hormone.

The PRECISION trial was sponsored by Janssen Pharmaceuticals and Idorsia Pharmaceuticals, the companies jointly developing aprocitentan. Dr. Bakris has been a consultant to Janssen, and also a consultant to or honoraria recipient of Alnylam, AstraZeneca, Bayer, Dia Medica Therapeutics, Ionis, inREGEN, KBP Biosciences, Merck, Novo Nordisk, and Quantum Genomics. Dr. Pradhan had no disclosures.

PHILADELPHIA – Treatment with aprocitentan, a novel agent currently under Food and Drug Administration review for lowering blood pressure in people with treatment-resistant hypertension, showed efficacy and safety in people with stage 3 or 4 chronic kidney disease (CKD). The results come from a prespecified subgroup analysis of data collected in the drug’s pivotal trial, PRECISION.

The findings provide support for potentially using aprocitentan, if approved for U.S. marketing in 2024, in patients with blood pressure that remains elevated despite treatment with three established antihypertensive drug classes and with stage 3 CKD with an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m². This is a key group of patients because “chronic kidney disease is the most common comorbidity in patients with resistant hypertension,” said George Bakris, MD, who presented the subgroup analysis at Kidney Week 2023, organized by the American Society of Nephrology.

Mtchel L. Zoler/MDedge News

The CKD subgroup analysis showed “good evidence for safety and evidence in stage 3 CKD,” a subgroup of 141 patients among the total 730 enrolled in PRECISION, said Dr. Bakris. Professor and director of the Comprehensive Hypertension Center at the University of Chicago, he acknowledged that while the results also showed a signal for safety and efficacy in the 21 enrolled patients with stage 4 hypertension, 15-29 mL/min per 1.73m², this number of stage 4 patients was too small to allow definitive conclusions.

Nephrologist Nishigandha Pradhan, MD, who cochaired the session with this report, agreed. “Resistant hypertension is a particularly intractable problem in patients with CKD, and the risk is greatest with stage 4 CKD. If studies could show that aprocitentan is safe in people with stage 4 CKD, that would be a big plus, but we need more data,” commented Dr. Pradhan in an interview.
 

Incremental blood pressure reductions

The parallel-group, phase 3 PRECISION trial investigated the safety and short-term antihypertensive effect of aprocitentan in patients with resistant hypertension. The study’s primary efficacy endpoint was blood pressure reduction from baseline in 730 randomized people with persistent systolic hypertension despite treatment with three established antihypertensive agents including a diuretic. The study ran during June 2018–April 2022 at 191 sites in 22 countries.

The primary outcome after 4 weeks on treatment was a least-square mean reduction in office-measured systolic blood pressure, compared with placebo, of 3.8 mm Hg with a 12.5-mg daily oral dose of aprocitentan and 3.7 mm Hg with a 25-mg daily oral dose. Both significant differences were first reported in 2022. Twenty-four–hour ambulatory systolic blood pressures after 4 weeks of treatment fell by an average of 4.2 mm Hg on the lower dose compared with placebo and by an average of 5.9 mm Hg on the higher daily dose, compared with placebo.

Consistent blood pressure reductions occurred in the CKD subgroups. Among people with stage 3 CKD, daytime ambulatory blood pressure at 4 weeks fell by about 10 mm Hg on both the 12.5-mg daily and 25-mg daily doses, compared with placebo.

Among the small number of people with stage 4 CKD, the incremental nighttime systolic blood pressure on aprocitentan, compared with placebo, was even greater, with about a 15–mm Hg incremental reduction on 12.5 mg daily and about a 17–mm Hg incremental reduction on the higher dose.

“This is the first evidence for a change in nocturnal blood pressure in people with stage 4 CKD [and treatment-resistant hypertension], but it was just 21 patients so not yet a big deal,” Dr. Bakris noted.
 

Increased rates of fluid retention

Although aprocitentan was generally well tolerated, the most common adverse effect was edema or fluid retention, mainly during the first 4 weeks of treatment. In the full PRECISION cohort, this adverse event occurred in 2.1% of people treated with placebo, 9.1% of those on the 12.5-mg daily dose, and in 18.4% of those on the higher dose during the initial 4-week phase of treatment.

Among all stage 3 and 4 CKD patients on aprocitentan, edema or fluid retention occurred in 21% during the first 4 weeks, and in 27% during an additional 32 weeks of treatment with 25 mg aprocitentan daily. A majority of these patients started a diuretic to address their excess fluid, with only two discontinuing aprocitentan treatment.

“Fluid retention is an issue with aprocitentan,” Dr. Bakris acknowledged. But he also highlighted than only 6 of the 162 patients with CKD required hospitalization for heart failure during the study, and one of these cases had placebo treatment. Among the five with acute heart failure while on aprocitentan, none had to stop their treatment, and two had a clear prior history of heart failure.

The companies developing aprocitentan, Janssen and Idorsia, used the PRECISION results as the centerpiece in filing for a new drug approval to the FDA, with a March 2024 goal for the FDA‘s decision. Dr. Bakris called the application “a solid case for approval.” But he added that approval will likely require that all treatment candidates first undergo testing of their heart function or fluid volume, such as a measure of their blood level of N-terminal pro-B-type natriuretic peptide, with treatment withheld when the level is too high.

The upside of aprocitentan compared with current drug options for treating resistant hypertension is that it has not appeared to cause any increase in blood potassium levels, which is an issue with the current top agent for resistant hypertension, spironolactone.

“The problem with spironolactone is the risk for hyperkalemia, which keeps us looking for something with lower risk,” commented Dr. Pradhan, a nephrologist with University Hospitals in Cleveland. Hyperkalemia is an even greater risk for people with CKD. Although the PRECISION trial identified the issue of fluid retention with aprocitentan, titrating an effective dose of a loop diuretic for treated patients may effectively blunt the edema risk, Dr. Pradhan said.

Endothelin has a potent vasoconstrictive effect and is “implicated in the pathogenesis of hypertension,” Dr. Bakris explained. Aprocitentan antagonizes both the endothelin A and B receptors. The subgroup analyses also showed that in people with CKD, treatment with aprocitentan led to roughly a halving of the baseline level of urine albumin-to-creatinine ratio, a small and stable decrease in estimated glomerular filtration rate, and a modest and stable increase in blood levels of N-terminal pro-B-type natriuretic hormone.

The PRECISION trial was sponsored by Janssen Pharmaceuticals and Idorsia Pharmaceuticals, the companies jointly developing aprocitentan. Dr. Bakris has been a consultant to Janssen, and also a consultant to or honoraria recipient of Alnylam, AstraZeneca, Bayer, Dia Medica Therapeutics, Ionis, inREGEN, KBP Biosciences, Merck, Novo Nordisk, and Quantum Genomics. Dr. Pradhan had no disclosures.

PHILADELPHIA – Treatment with aprocitentan, a novel agent currently under Food and Drug Administration review for lowering blood pressure in people with treatment-resistant hypertension, showed efficacy and safety in people with stage 3 or 4 chronic kidney disease (CKD). The results come from a prespecified subgroup analysis of data collected in the drug’s pivotal trial, PRECISION.

The findings provide support for potentially using aprocitentan, if approved for U.S. marketing in 2024, in patients with blood pressure that remains elevated despite treatment with three established antihypertensive drug classes and with stage 3 CKD with an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m². This is a key group of patients because “chronic kidney disease is the most common comorbidity in patients with resistant hypertension,” said George Bakris, MD, who presented the subgroup analysis at Kidney Week 2023, organized by the American Society of Nephrology.

Mtchel L. Zoler/MDedge News

The CKD subgroup analysis showed “good evidence for safety and evidence in stage 3 CKD,” a subgroup of 141 patients among the total 730 enrolled in PRECISION, said Dr. Bakris. Professor and director of the Comprehensive Hypertension Center at the University of Chicago, he acknowledged that while the results also showed a signal for safety and efficacy in the 21 enrolled patients with stage 4 hypertension, 15-29 mL/min per 1.73m², this number of stage 4 patients was too small to allow definitive conclusions.

Nephrologist Nishigandha Pradhan, MD, who cochaired the session with this report, agreed. “Resistant hypertension is a particularly intractable problem in patients with CKD, and the risk is greatest with stage 4 CKD. If studies could show that aprocitentan is safe in people with stage 4 CKD, that would be a big plus, but we need more data,” commented Dr. Pradhan in an interview.
 

Incremental blood pressure reductions

The parallel-group, phase 3 PRECISION trial investigated the safety and short-term antihypertensive effect of aprocitentan in patients with resistant hypertension. The study’s primary efficacy endpoint was blood pressure reduction from baseline in 730 randomized people with persistent systolic hypertension despite treatment with three established antihypertensive agents including a diuretic. The study ran during June 2018–April 2022 at 191 sites in 22 countries.

The primary outcome after 4 weeks on treatment was a least-square mean reduction in office-measured systolic blood pressure, compared with placebo, of 3.8 mm Hg with a 12.5-mg daily oral dose of aprocitentan and 3.7 mm Hg with a 25-mg daily oral dose. Both significant differences were first reported in 2022. Twenty-four–hour ambulatory systolic blood pressures after 4 weeks of treatment fell by an average of 4.2 mm Hg on the lower dose compared with placebo and by an average of 5.9 mm Hg on the higher daily dose, compared with placebo.

Consistent blood pressure reductions occurred in the CKD subgroups. Among people with stage 3 CKD, daytime ambulatory blood pressure at 4 weeks fell by about 10 mm Hg on both the 12.5-mg daily and 25-mg daily doses, compared with placebo.

Among the small number of people with stage 4 CKD, the incremental nighttime systolic blood pressure on aprocitentan, compared with placebo, was even greater, with about a 15–mm Hg incremental reduction on 12.5 mg daily and about a 17–mm Hg incremental reduction on the higher dose.

“This is the first evidence for a change in nocturnal blood pressure in people with stage 4 CKD [and treatment-resistant hypertension], but it was just 21 patients so not yet a big deal,” Dr. Bakris noted.
 

Increased rates of fluid retention

Although aprocitentan was generally well tolerated, the most common adverse effect was edema or fluid retention, mainly during the first 4 weeks of treatment. In the full PRECISION cohort, this adverse event occurred in 2.1% of people treated with placebo, 9.1% of those on the 12.5-mg daily dose, and in 18.4% of those on the higher dose during the initial 4-week phase of treatment.

Among all stage 3 and 4 CKD patients on aprocitentan, edema or fluid retention occurred in 21% during the first 4 weeks, and in 27% during an additional 32 weeks of treatment with 25 mg aprocitentan daily. A majority of these patients started a diuretic to address their excess fluid, with only two discontinuing aprocitentan treatment.

“Fluid retention is an issue with aprocitentan,” Dr. Bakris acknowledged. But he also highlighted than only 6 of the 162 patients with CKD required hospitalization for heart failure during the study, and one of these cases had placebo treatment. Among the five with acute heart failure while on aprocitentan, none had to stop their treatment, and two had a clear prior history of heart failure.

The companies developing aprocitentan, Janssen and Idorsia, used the PRECISION results as the centerpiece in filing for a new drug approval to the FDA, with a March 2024 goal for the FDA‘s decision. Dr. Bakris called the application “a solid case for approval.” But he added that approval will likely require that all treatment candidates first undergo testing of their heart function or fluid volume, such as a measure of their blood level of N-terminal pro-B-type natriuretic peptide, with treatment withheld when the level is too high.

The upside of aprocitentan compared with current drug options for treating resistant hypertension is that it has not appeared to cause any increase in blood potassium levels, which is an issue with the current top agent for resistant hypertension, spironolactone.

“The problem with spironolactone is the risk for hyperkalemia, which keeps us looking for something with lower risk,” commented Dr. Pradhan, a nephrologist with University Hospitals in Cleveland. Hyperkalemia is an even greater risk for people with CKD. Although the PRECISION trial identified the issue of fluid retention with aprocitentan, titrating an effective dose of a loop diuretic for treated patients may effectively blunt the edema risk, Dr. Pradhan said.

Endothelin has a potent vasoconstrictive effect and is “implicated in the pathogenesis of hypertension,” Dr. Bakris explained. Aprocitentan antagonizes both the endothelin A and B receptors. The subgroup analyses also showed that in people with CKD, treatment with aprocitentan led to roughly a halving of the baseline level of urine albumin-to-creatinine ratio, a small and stable decrease in estimated glomerular filtration rate, and a modest and stable increase in blood levels of N-terminal pro-B-type natriuretic hormone.

The PRECISION trial was sponsored by Janssen Pharmaceuticals and Idorsia Pharmaceuticals, the companies jointly developing aprocitentan. Dr. Bakris has been a consultant to Janssen, and also a consultant to or honoraria recipient of Alnylam, AstraZeneca, Bayer, Dia Medica Therapeutics, Ionis, inREGEN, KBP Biosciences, Merck, Novo Nordisk, and Quantum Genomics. Dr. Pradhan had no disclosures.

Regularly using marijuana can significantly increase a person’s risk of heart attack, heart failure, and stroke, according to a pair of new studies that will be presented at a major upcoming medical conference.

People who use marijuana daily have a 34% increased risk of heart failure, compared with people who don’t use the drug, according to one of the new studies.

The new findings leverage health data from 157,000 people in the National Institutes of Health “All of Us” research program. Researchers analyzed whether marijuana users were more likely to experience heart failure than nonusers over the course of nearly 4 years. The results indicated that coronary artery disease was behind marijuana users’ increased risk. (Coronary artery disease is the buildup of plaque on the walls of the arteries that supply blood to the heart.)

The research was conducted by a team at Medstar Health, a large Maryland health care system that operates 10 hospitals plus hundreds of clinics. The findings will be presented at the American Heart Association’s Scientific Sessions 2023 in Philadelphia.

“Our results should encourage more researchers to study the use of marijuana to better understand its health implications, especially on cardiovascular risk,” said researcher Yakubu Bene-Alhasan, MD, MPH, a doctor at Medstar Health in Baltimore. “We want to provide the population with high-quality information on marijuana use and to help inform policy decisions at the state level, to educate patients, and to guide health care professionals.”

About one in five people in the United States use marijuana, according to the Centers for Disease Control and Prevention. The majority of U.S. states allow marijuana to be used legally for medical purposes, and more than 20 states have legalized recreational marijuana, a tracker from the National Conference of State Legislatures shows. 

A second study that will be presented at the conference shows that older people with any combination of type 2 diabetes, high blood pressure, and high cholesterol who use marijuana have an increased risk for a major heart or brain event, compared with people who never used the drug. 

The researchers analyzed data for more than 28,000 people age 65 and older who had health conditions that put them at risk for heart problems and whose medical records showed they were marijuana users but not tobacco users. The results showed at least a 20% increased risk of heart attack, stroke, cardiac arrest, or arrhythmia (irregular heartbeat). 

The findings are significant because medical professionals have long said that research on the long-term health effects of using marijuana are limited. 

“The latest research about cannabis use indicates that smoking and inhaling cannabis increases concentrations of blood carboxyhemoglobin (carbon monoxide, a poisonous gas), tar (partly burned combustible matter) similar to the effects of inhaling a tobacco cigarette, both of which have been linked to heart muscle disease, chest pain, heart rhythm disturbances, heart attacks and other serious conditions,” said Robert L. Page II, PharmD, MSPH, chair of the volunteer writing group for the 2020 American Heart Association Scientific Statement: Medical Marijuana, Recreational Cannabis, and Cardiovascular Health, in a statement. “Together with the results of these two research studies, the cardiovascular risks of cannabis use are becoming clearer and should be carefully considered and monitored by health care professionals and the public.”

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

Regularly using marijuana can significantly increase a person’s risk of heart attack, heart failure, and stroke, according to a pair of new studies that will be presented at a major upcoming medical conference.

People who use marijuana daily have a 34% increased risk of heart failure, compared with people who don’t use the drug, according to one of the new studies.

The new findings leverage health data from 157,000 people in the National Institutes of Health “All of Us” research program. Researchers analyzed whether marijuana users were more likely to experience heart failure than nonusers over the course of nearly 4 years. The results indicated that coronary artery disease was behind marijuana users’ increased risk. (Coronary artery disease is the buildup of plaque on the walls of the arteries that supply blood to the heart.)

The research was conducted by a team at Medstar Health, a large Maryland health care system that operates 10 hospitals plus hundreds of clinics. The findings will be presented at the American Heart Association’s Scientific Sessions 2023 in Philadelphia.

“Our results should encourage more researchers to study the use of marijuana to better understand its health implications, especially on cardiovascular risk,” said researcher Yakubu Bene-Alhasan, MD, MPH, a doctor at Medstar Health in Baltimore. “We want to provide the population with high-quality information on marijuana use and to help inform policy decisions at the state level, to educate patients, and to guide health care professionals.”

About one in five people in the United States use marijuana, according to the Centers for Disease Control and Prevention. The majority of U.S. states allow marijuana to be used legally for medical purposes, and more than 20 states have legalized recreational marijuana, a tracker from the National Conference of State Legislatures shows. 

A second study that will be presented at the conference shows that older people with any combination of type 2 diabetes, high blood pressure, and high cholesterol who use marijuana have an increased risk for a major heart or brain event, compared with people who never used the drug. 

The researchers analyzed data for more than 28,000 people age 65 and older who had health conditions that put them at risk for heart problems and whose medical records showed they were marijuana users but not tobacco users. The results showed at least a 20% increased risk of heart attack, stroke, cardiac arrest, or arrhythmia (irregular heartbeat). 

The findings are significant because medical professionals have long said that research on the long-term health effects of using marijuana are limited. 

“The latest research about cannabis use indicates that smoking and inhaling cannabis increases concentrations of blood carboxyhemoglobin (carbon monoxide, a poisonous gas), tar (partly burned combustible matter) similar to the effects of inhaling a tobacco cigarette, both of which have been linked to heart muscle disease, chest pain, heart rhythm disturbances, heart attacks and other serious conditions,” said Robert L. Page II, PharmD, MSPH, chair of the volunteer writing group for the 2020 American Heart Association Scientific Statement: Medical Marijuana, Recreational Cannabis, and Cardiovascular Health, in a statement. “Together with the results of these two research studies, the cardiovascular risks of cannabis use are becoming clearer and should be carefully considered and monitored by health care professionals and the public.”

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

Regularly using marijuana can significantly increase a person’s risk of heart attack, heart failure, and stroke, according to a pair of new studies that will be presented at a major upcoming medical conference.

People who use marijuana daily have a 34% increased risk of heart failure, compared with people who don’t use the drug, according to one of the new studies.

The new findings leverage health data from 157,000 people in the National Institutes of Health “All of Us” research program. Researchers analyzed whether marijuana users were more likely to experience heart failure than nonusers over the course of nearly 4 years. The results indicated that coronary artery disease was behind marijuana users’ increased risk. (Coronary artery disease is the buildup of plaque on the walls of the arteries that supply blood to the heart.)

The research was conducted by a team at Medstar Health, a large Maryland health care system that operates 10 hospitals plus hundreds of clinics. The findings will be presented at the American Heart Association’s Scientific Sessions 2023 in Philadelphia.

“Our results should encourage more researchers to study the use of marijuana to better understand its health implications, especially on cardiovascular risk,” said researcher Yakubu Bene-Alhasan, MD, MPH, a doctor at Medstar Health in Baltimore. “We want to provide the population with high-quality information on marijuana use and to help inform policy decisions at the state level, to educate patients, and to guide health care professionals.”

About one in five people in the United States use marijuana, according to the Centers for Disease Control and Prevention. The majority of U.S. states allow marijuana to be used legally for medical purposes, and more than 20 states have legalized recreational marijuana, a tracker from the National Conference of State Legislatures shows. 

A second study that will be presented at the conference shows that older people with any combination of type 2 diabetes, high blood pressure, and high cholesterol who use marijuana have an increased risk for a major heart or brain event, compared with people who never used the drug. 

The researchers analyzed data for more than 28,000 people age 65 and older who had health conditions that put them at risk for heart problems and whose medical records showed they were marijuana users but not tobacco users. The results showed at least a 20% increased risk of heart attack, stroke, cardiac arrest, or arrhythmia (irregular heartbeat). 

The findings are significant because medical professionals have long said that research on the long-term health effects of using marijuana are limited. 

“The latest research about cannabis use indicates that smoking and inhaling cannabis increases concentrations of blood carboxyhemoglobin (carbon monoxide, a poisonous gas), tar (partly burned combustible matter) similar to the effects of inhaling a tobacco cigarette, both of which have been linked to heart muscle disease, chest pain, heart rhythm disturbances, heart attacks and other serious conditions,” said Robert L. Page II, PharmD, MSPH, chair of the volunteer writing group for the 2020 American Heart Association Scientific Statement: Medical Marijuana, Recreational Cannabis, and Cardiovascular Health, in a statement. “Together with the results of these two research studies, the cardiovascular risks of cannabis use are becoming clearer and should be carefully considered and monitored by health care professionals and the public.”

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

People infected multiple times with COVID-19 are more likely to develop long COVID, and most never fully recover from the condition. Those are two of the most striking findings of a comprehensive new research study of 138,000 veterans.

Lead researcher Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, spoke with this news organization about his team’s findings, what we know – and don’t – about long COVID, and what it means for physicians treating patients with the condition.

Excerpts of the interview follow.

Your research concluded that for those infected early in the pandemic, some long COVID symptoms declined over 2 years, but some did not. You have also concluded that long COVID is a chronic disease. Why?

We’ve been in this journey a little bit more than three and a half years. Some patients do experience some recovery. But that’s not the norm. Most people do not really fully recover. The health trajectory for people with long COVID is really very heterogeneous. There is no one-size-fits-all. There’s really no one line that I could give you that could cover all your patients. But it is very, very, very clear that a bunch of them experienced long COVID for sure; that’s really happening.

It happened in the pre-Delta era and in the Delta era, and with Omicron subvariants, even now. There are people who think, “This is a nothing-burger anymore,” or “It’s not an issue anymore.” It’s still happening with the current variants. Vaccines do reduce risk for long COVID, but do not completely eliminate the risk for long COVID.

You work with patients with long COVID in the clinic and also analyze data from thousands more. If long COVID does not go away, what should doctors look for in everyday practice that will help them recognize and help patients with long COVID?

Long COVID is not uncommon. We see it in the clinic in large numbers. Whatever clinic you’re running – if you’re running a cardiology clinic, or a nephrology clinic, or diabetes, or primary care – probably some of your people have it. You may not know about it. They may not tell you about it. You may not recognize it.

Not all long COVID is the same, and that’s really what makes it complex and makes it really hard to deal with in the clinic. But that’s the reality that we’re all dealing with. And it’s multisystemic; it’s not like it affects the heart only, the brain only, or the autonomic nervous system only. It does not behave in the same way in different individuals – they may have different manifestations, various health trajectories, and different outcomes. It’s important for doctors to get up to speed on long COVID as a multisystem illness.

Management at this point is really managing the symptoms. We don’t have a treatment for it; we don’t have a cure for it.

Some patients experience what you’ve described as partial recovery. What does that look like?

Some individuals do experience some recovery over time, but for most individuals, the recovery is long and arduous. Long COVID can last with them for many years. Some people may come back to the clinic and say, “I’m doing better,” but if you really flesh it out and dig deeper, they didn’t do better; they adjusted to a new baseline. They used to walk the dog three to four blocks, and now they walk the dog only half a block. They used to do an activity with their partner every Saturday or Sunday, and now they do half of that.

If you’re a physician, a primary care provider, or any other provider who is dealing with a patient with long COVID, know that this is really happening. It can happen even in vaccinated individuals. The presentation is heterogeneous. Some people may present to you with and say. “Well, before I had COVID I was mentally sharp and now having I’m having difficulty with memory, etc.” It can sometimes present as fatigue or postexertional malaise.

In some instances, it can present as sleep problems. It can present as what we call postural orthostatic tachycardia syndrome (POTS). Those people get a significant increase in heart rate with postural changes.

What the most important thing we can we learn from the emergence of long COVID?

This whole thing taught us that infections can cause chronic disease. That’s really the No. 1 lesson that I take from this pandemic – that infections can cause chronic disease.

Looking at only acute illness from COVID is really only looking at the tip of the iceberg. Beneath that tip of the iceberg lies this hidden toll of disease that we don’t really talk about that much.

This pandemic shone a very, very good light on the idea that there is really an intimate connection between infections and chronic disease. It was really hardwired into our medical training as doctors that most infections, when people get over the hump of the acute phase of the disease, it’s all behind them. I think long COVID has humbled us in many, many ways, but chief among those is the realization – the stark realization – that infections can cause chronic disease.

That’s really going back to your [first] question: What does it mean that some people are not recovering? They actually have chronic illness. I’m hoping that we will find a treatment, that we’ll start finding things that would help them get back to baseline. But at this point in time, what we’re dealing with is people with chronic illness or chronic disease that may continue to affect them for many years to come in the absence of a treatment or a cure.

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

People infected multiple times with COVID-19 are more likely to develop long COVID, and most never fully recover from the condition. Those are two of the most striking findings of a comprehensive new research study of 138,000 veterans.

Lead researcher Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, spoke with this news organization about his team’s findings, what we know – and don’t – about long COVID, and what it means for physicians treating patients with the condition.

Excerpts of the interview follow.

Your research concluded that for those infected early in the pandemic, some long COVID symptoms declined over 2 years, but some did not. You have also concluded that long COVID is a chronic disease. Why?

We’ve been in this journey a little bit more than three and a half years. Some patients do experience some recovery. But that’s not the norm. Most people do not really fully recover. The health trajectory for people with long COVID is really very heterogeneous. There is no one-size-fits-all. There’s really no one line that I could give you that could cover all your patients. But it is very, very, very clear that a bunch of them experienced long COVID for sure; that’s really happening.

It happened in the pre-Delta era and in the Delta era, and with Omicron subvariants, even now. There are people who think, “This is a nothing-burger anymore,” or “It’s not an issue anymore.” It’s still happening with the current variants. Vaccines do reduce risk for long COVID, but do not completely eliminate the risk for long COVID.

You work with patients with long COVID in the clinic and also analyze data from thousands more. If long COVID does not go away, what should doctors look for in everyday practice that will help them recognize and help patients with long COVID?

Long COVID is not uncommon. We see it in the clinic in large numbers. Whatever clinic you’re running – if you’re running a cardiology clinic, or a nephrology clinic, or diabetes, or primary care – probably some of your people have it. You may not know about it. They may not tell you about it. You may not recognize it.

Not all long COVID is the same, and that’s really what makes it complex and makes it really hard to deal with in the clinic. But that’s the reality that we’re all dealing with. And it’s multisystemic; it’s not like it affects the heart only, the brain only, or the autonomic nervous system only. It does not behave in the same way in different individuals – they may have different manifestations, various health trajectories, and different outcomes. It’s important for doctors to get up to speed on long COVID as a multisystem illness.

Management at this point is really managing the symptoms. We don’t have a treatment for it; we don’t have a cure for it.

Some patients experience what you’ve described as partial recovery. What does that look like?

Some individuals do experience some recovery over time, but for most individuals, the recovery is long and arduous. Long COVID can last with them for many years. Some people may come back to the clinic and say, “I’m doing better,” but if you really flesh it out and dig deeper, they didn’t do better; they adjusted to a new baseline. They used to walk the dog three to four blocks, and now they walk the dog only half a block. They used to do an activity with their partner every Saturday or Sunday, and now they do half of that.

If you’re a physician, a primary care provider, or any other provider who is dealing with a patient with long COVID, know that this is really happening. It can happen even in vaccinated individuals. The presentation is heterogeneous. Some people may present to you with and say. “Well, before I had COVID I was mentally sharp and now having I’m having difficulty with memory, etc.” It can sometimes present as fatigue or postexertional malaise.

In some instances, it can present as sleep problems. It can present as what we call postural orthostatic tachycardia syndrome (POTS). Those people get a significant increase in heart rate with postural changes.

What the most important thing we can we learn from the emergence of long COVID?

This whole thing taught us that infections can cause chronic disease. That’s really the No. 1 lesson that I take from this pandemic – that infections can cause chronic disease.

Looking at only acute illness from COVID is really only looking at the tip of the iceberg. Beneath that tip of the iceberg lies this hidden toll of disease that we don’t really talk about that much.

This pandemic shone a very, very good light on the idea that there is really an intimate connection between infections and chronic disease. It was really hardwired into our medical training as doctors that most infections, when people get over the hump of the acute phase of the disease, it’s all behind them. I think long COVID has humbled us in many, many ways, but chief among those is the realization – the stark realization – that infections can cause chronic disease.

That’s really going back to your [first] question: What does it mean that some people are not recovering? They actually have chronic illness. I’m hoping that we will find a treatment, that we’ll start finding things that would help them get back to baseline. But at this point in time, what we’re dealing with is people with chronic illness or chronic disease that may continue to affect them for many years to come in the absence of a treatment or a cure.

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

People infected multiple times with COVID-19 are more likely to develop long COVID, and most never fully recover from the condition. Those are two of the most striking findings of a comprehensive new research study of 138,000 veterans.

Lead researcher Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, spoke with this news organization about his team’s findings, what we know – and don’t – about long COVID, and what it means for physicians treating patients with the condition.

Excerpts of the interview follow.

Your research concluded that for those infected early in the pandemic, some long COVID symptoms declined over 2 years, but some did not. You have also concluded that long COVID is a chronic disease. Why?

We’ve been in this journey a little bit more than three and a half years. Some patients do experience some recovery. But that’s not the norm. Most people do not really fully recover. The health trajectory for people with long COVID is really very heterogeneous. There is no one-size-fits-all. There’s really no one line that I could give you that could cover all your patients. But it is very, very, very clear that a bunch of them experienced long COVID for sure; that’s really happening.

It happened in the pre-Delta era and in the Delta era, and with Omicron subvariants, even now. There are people who think, “This is a nothing-burger anymore,” or “It’s not an issue anymore.” It’s still happening with the current variants. Vaccines do reduce risk for long COVID, but do not completely eliminate the risk for long COVID.

You work with patients with long COVID in the clinic and also analyze data from thousands more. If long COVID does not go away, what should doctors look for in everyday practice that will help them recognize and help patients with long COVID?

Long COVID is not uncommon. We see it in the clinic in large numbers. Whatever clinic you’re running – if you’re running a cardiology clinic, or a nephrology clinic, or diabetes, or primary care – probably some of your people have it. You may not know about it. They may not tell you about it. You may not recognize it.

Not all long COVID is the same, and that’s really what makes it complex and makes it really hard to deal with in the clinic. But that’s the reality that we’re all dealing with. And it’s multisystemic; it’s not like it affects the heart only, the brain only, or the autonomic nervous system only. It does not behave in the same way in different individuals – they may have different manifestations, various health trajectories, and different outcomes. It’s important for doctors to get up to speed on long COVID as a multisystem illness.

Management at this point is really managing the symptoms. We don’t have a treatment for it; we don’t have a cure for it.

Some patients experience what you’ve described as partial recovery. What does that look like?

Some individuals do experience some recovery over time, but for most individuals, the recovery is long and arduous. Long COVID can last with them for many years. Some people may come back to the clinic and say, “I’m doing better,” but if you really flesh it out and dig deeper, they didn’t do better; they adjusted to a new baseline. They used to walk the dog three to four blocks, and now they walk the dog only half a block. They used to do an activity with their partner every Saturday or Sunday, and now they do half of that.

If you’re a physician, a primary care provider, or any other provider who is dealing with a patient with long COVID, know that this is really happening. It can happen even in vaccinated individuals. The presentation is heterogeneous. Some people may present to you with and say. “Well, before I had COVID I was mentally sharp and now having I’m having difficulty with memory, etc.” It can sometimes present as fatigue or postexertional malaise.

In some instances, it can present as sleep problems. It can present as what we call postural orthostatic tachycardia syndrome (POTS). Those people get a significant increase in heart rate with postural changes.

What the most important thing we can we learn from the emergence of long COVID?

This whole thing taught us that infections can cause chronic disease. That’s really the No. 1 lesson that I take from this pandemic – that infections can cause chronic disease.

Looking at only acute illness from COVID is really only looking at the tip of the iceberg. Beneath that tip of the iceberg lies this hidden toll of disease that we don’t really talk about that much.

This pandemic shone a very, very good light on the idea that there is really an intimate connection between infections and chronic disease. It was really hardwired into our medical training as doctors that most infections, when people get over the hump of the acute phase of the disease, it’s all behind them. I think long COVID has humbled us in many, many ways, but chief among those is the realization – the stark realization – that infections can cause chronic disease.

That’s really going back to your [first] question: What does it mean that some people are not recovering? They actually have chronic illness. I’m hoping that we will find a treatment, that we’ll start finding things that would help them get back to baseline. But at this point in time, what we’re dealing with is people with chronic illness or chronic disease that may continue to affect them for many years to come in the absence of a treatment or a cure.

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

PHILADELPHIA – An electronic medical record alert to primary care physicians that their adult patients with type 2 diabetes were due for an albuminuria and renal-function check boosted screening for chronic kidney disease (CKD) by roughly half compared with the preintervention rate in a single U.S. academic health system.

“Screening rates for CKD more rapidly improved after implementation” of the EMR alert, said Maggy M. Spolnik, MD, at Kidney Week 2023, organized by the American Society of Nephrology.

“There was an immediate and ongoing effect over a year,” said Dr. Spolnik, a nephrologist at Indiana University in Indianapolis.

Mitchel L. Zoler/MDedge News

However, CKD screening rates in the primary care setting remain a challenge. In the study, the EMR alert produced a urine albumin-to-creatinine ratio (UACR) screening rate of about 26% of patient encounters, she reported. While this was significantly above the roughly 17% rate that had persisted for months before the intervention, it still fell short of the universal annual screening for adults with type 2 diabetes not previously diagnosed with CKD recommended by medical groups such as the American Diabetes Association and the Kidney Disease: Improving Global Outcomes organization. The U.S. Preventive Services Task Force’s assessment in 2012 concluded inadequate information existed at that time to make recommendations about CKD screening, but the group is now revisiting the issue.
 

‘Albuminuria is an earlier marker’ than eGFR

“Primary care physicians need to regularly monitor albuminuria in adults with type 2 diabetes,” commented Karen A. Griffin, MD, a nephrologist and professor at Loyola University in Maywood, Ill. “By the time you diagnose CKD based on reduced estimated glomerular filtration rate (eGFR), a patient has already lost more than half their renal function. Albuminuria is an earlier marker of a problem,” Dr. Griffin said in an interview.

Mitchel L. Zoler/MDedge News

Primary care physicians have been slow to adopt at least annual checks on both eGFR and the urinary albumin-to-creatinine ratio (UACR) in their adult patients with type 2 diabetes. Dr. Spolnik cited reasons such as the brief 15-minute consultation that primary care physicians have when seeing a patient, and an often confusing ordering menu that gives a UACR test various other names such as tests for microalbuminuria or macroalbuminuria.

To simplify ordering, the EMR prompt assessed in Dr. Spolnik’s study called the test “kidney screening” that automatically bundled an order for both eGFR calculation with UACR measurement. Another limitation is that UACR measurement requires a urine sample, which patients often find inconvenient to provide at the time of their examination.

The study run by Dr. Spolnik involved 10,744 adults with type 2 diabetes without an existing diagnosis of CKD seen in an outpatient, primary care visit to the UVA Health system centered in Charlottesville, Va. during April 2021–April 2022. A total of 23,419 encounters served as usual-care controls. The intervention period with active EMR alerts for kidney screening included 10,204 similar patients seen during April 2022–April 2023 in a total of 20,358 encounters. The patients averaged about 61-62 years old, and about 45% were men.
 

Bundling alerts into a single pop-up

The primary care clinicians who received the prompts were generally receptive to them, but they asked the researchers to bundle the UACR and eGFR measurement prompts along with any other alerts they received in the EMR into a single on-screen pop-up.

Dr. Spolnik acknowledged the need for further research and refinement to the prompt. For example, she wants to assess prompts for patients identified as having CKD that would promote best-practice management, including lifestyle and medical interventions. She also envisions expanding the prompts to also include other, related disorders such as hypertension.

But she and her colleagues were convinced enough by the results that they have not only continued the program at UVA Health but they also expanded it, starting in October 2023, to the academic primary care practice at Indiana University.

If the Indiana University trial confirms the efficacy seen in Virginia, the next step might be inclusion by Epic of the CKD screening alert as a routine option in the EMR software it distributes to its U.S. clients, Dr. Spolnik said in an interview.

Dr. Spolnik and Dr. Griffin had no disclosures.

PHILADELPHIA – An electronic medical record alert to primary care physicians that their adult patients with type 2 diabetes were due for an albuminuria and renal-function check boosted screening for chronic kidney disease (CKD) by roughly half compared with the preintervention rate in a single U.S. academic health system.

“Screening rates for CKD more rapidly improved after implementation” of the EMR alert, said Maggy M. Spolnik, MD, at Kidney Week 2023, organized by the American Society of Nephrology.

“There was an immediate and ongoing effect over a year,” said Dr. Spolnik, a nephrologist at Indiana University in Indianapolis.

Mitchel L. Zoler/MDedge News

However, CKD screening rates in the primary care setting remain a challenge. In the study, the EMR alert produced a urine albumin-to-creatinine ratio (UACR) screening rate of about 26% of patient encounters, she reported. While this was significantly above the roughly 17% rate that had persisted for months before the intervention, it still fell short of the universal annual screening for adults with type 2 diabetes not previously diagnosed with CKD recommended by medical groups such as the American Diabetes Association and the Kidney Disease: Improving Global Outcomes organization. The U.S. Preventive Services Task Force’s assessment in 2012 concluded inadequate information existed at that time to make recommendations about CKD screening, but the group is now revisiting the issue.
 

‘Albuminuria is an earlier marker’ than eGFR

“Primary care physicians need to regularly monitor albuminuria in adults with type 2 diabetes,” commented Karen A. Griffin, MD, a nephrologist and professor at Loyola University in Maywood, Ill. “By the time you diagnose CKD based on reduced estimated glomerular filtration rate (eGFR), a patient has already lost more than half their renal function. Albuminuria is an earlier marker of a problem,” Dr. Griffin said in an interview.

Mitchel L. Zoler/MDedge News

Primary care physicians have been slow to adopt at least annual checks on both eGFR and the urinary albumin-to-creatinine ratio (UACR) in their adult patients with type 2 diabetes. Dr. Spolnik cited reasons such as the brief 15-minute consultation that primary care physicians have when seeing a patient, and an often confusing ordering menu that gives a UACR test various other names such as tests for microalbuminuria or macroalbuminuria.

To simplify ordering, the EMR prompt assessed in Dr. Spolnik’s study called the test “kidney screening” that automatically bundled an order for both eGFR calculation with UACR measurement. Another limitation is that UACR measurement requires a urine sample, which patients often find inconvenient to provide at the time of their examination.

The study run by Dr. Spolnik involved 10,744 adults with type 2 diabetes without an existing diagnosis of CKD seen in an outpatient, primary care visit to the UVA Health system centered in Charlottesville, Va. during April 2021–April 2022. A total of 23,419 encounters served as usual-care controls. The intervention period with active EMR alerts for kidney screening included 10,204 similar patients seen during April 2022–April 2023 in a total of 20,358 encounters. The patients averaged about 61-62 years old, and about 45% were men.
 

Bundling alerts into a single pop-up

The primary care clinicians who received the prompts were generally receptive to them, but they asked the researchers to bundle the UACR and eGFR measurement prompts along with any other alerts they received in the EMR into a single on-screen pop-up.

Dr. Spolnik acknowledged the need for further research and refinement to the prompt. For example, she wants to assess prompts for patients identified as having CKD that would promote best-practice management, including lifestyle and medical interventions. She also envisions expanding the prompts to also include other, related disorders such as hypertension.

But she and her colleagues were convinced enough by the results that they have not only continued the program at UVA Health but they also expanded it, starting in October 2023, to the academic primary care practice at Indiana University.

If the Indiana University trial confirms the efficacy seen in Virginia, the next step might be inclusion by Epic of the CKD screening alert as a routine option in the EMR software it distributes to its U.S. clients, Dr. Spolnik said in an interview.

Dr. Spolnik and Dr. Griffin had no disclosures.

PHILADELPHIA – An electronic medical record alert to primary care physicians that their adult patients with type 2 diabetes were due for an albuminuria and renal-function check boosted screening for chronic kidney disease (CKD) by roughly half compared with the preintervention rate in a single U.S. academic health system.

“Screening rates for CKD more rapidly improved after implementation” of the EMR alert, said Maggy M. Spolnik, MD, at Kidney Week 2023, organized by the American Society of Nephrology.

“There was an immediate and ongoing effect over a year,” said Dr. Spolnik, a nephrologist at Indiana University in Indianapolis.

Mitchel L. Zoler/MDedge News

However, CKD screening rates in the primary care setting remain a challenge. In the study, the EMR alert produced a urine albumin-to-creatinine ratio (UACR) screening rate of about 26% of patient encounters, she reported. While this was significantly above the roughly 17% rate that had persisted for months before the intervention, it still fell short of the universal annual screening for adults with type 2 diabetes not previously diagnosed with CKD recommended by medical groups such as the American Diabetes Association and the Kidney Disease: Improving Global Outcomes organization. The U.S. Preventive Services Task Force’s assessment in 2012 concluded inadequate information existed at that time to make recommendations about CKD screening, but the group is now revisiting the issue.
 

‘Albuminuria is an earlier marker’ than eGFR

“Primary care physicians need to regularly monitor albuminuria in adults with type 2 diabetes,” commented Karen A. Griffin, MD, a nephrologist and professor at Loyola University in Maywood, Ill. “By the time you diagnose CKD based on reduced estimated glomerular filtration rate (eGFR), a patient has already lost more than half their renal function. Albuminuria is an earlier marker of a problem,” Dr. Griffin said in an interview.

Mitchel L. Zoler/MDedge News

Primary care physicians have been slow to adopt at least annual checks on both eGFR and the urinary albumin-to-creatinine ratio (UACR) in their adult patients with type 2 diabetes. Dr. Spolnik cited reasons such as the brief 15-minute consultation that primary care physicians have when seeing a patient, and an often confusing ordering menu that gives a UACR test various other names such as tests for microalbuminuria or macroalbuminuria.

To simplify ordering, the EMR prompt assessed in Dr. Spolnik’s study called the test “kidney screening” that automatically bundled an order for both eGFR calculation with UACR measurement. Another limitation is that UACR measurement requires a urine sample, which patients often find inconvenient to provide at the time of their examination.

The study run by Dr. Spolnik involved 10,744 adults with type 2 diabetes without an existing diagnosis of CKD seen in an outpatient, primary care visit to the UVA Health system centered in Charlottesville, Va. during April 2021–April 2022. A total of 23,419 encounters served as usual-care controls. The intervention period with active EMR alerts for kidney screening included 10,204 similar patients seen during April 2022–April 2023 in a total of 20,358 encounters. The patients averaged about 61-62 years old, and about 45% were men.
 

Bundling alerts into a single pop-up

The primary care clinicians who received the prompts were generally receptive to them, but they asked the researchers to bundle the UACR and eGFR measurement prompts along with any other alerts they received in the EMR into a single on-screen pop-up.

Dr. Spolnik acknowledged the need for further research and refinement to the prompt. For example, she wants to assess prompts for patients identified as having CKD that would promote best-practice management, including lifestyle and medical interventions. She also envisions expanding the prompts to also include other, related disorders such as hypertension.

But she and her colleagues were convinced enough by the results that they have not only continued the program at UVA Health but they also expanded it, starting in October 2023, to the academic primary care practice at Indiana University.

If the Indiana University trial confirms the efficacy seen in Virginia, the next step might be inclusion by Epic of the CKD screening alert as a routine option in the EMR software it distributes to its U.S. clients, Dr. Spolnik said in an interview.

Dr. Spolnik and Dr. Griffin had no disclosures.

TOPLINE:

The prevalence of elevated LDL cholesterol (LDL-C) has declined over the past 2 decades, but 1 in 17 Americans still have a level of 160-189 mg/dL, and 1 in 48 have a level of at least 190 mg/dL, new research shows. Among people with the higher LDL-C level, one in four are both unaware and untreated, the authors report.

METHODOLOGY:

• Using data on 23,667 adult participants in the National Health and Nutrition Examination Survey conducted from 1999 to 2020, researchers identified 1,851 (7.8%) with an LDL-C level of 160-189 mg/dL and 669 (2.8%) with an LDL-C level of at least 190 mg/dL.
• Individuals were classified as “unaware” if they had never had their LDL-C measured or had never been informed of having elevated LDL-C and as “untreated” if their medications didn’t include a statin, ezetimibe, a bile acid sequestrant, or a proprotein convertase subtilisin/kexin type 9 inhibitor.
• The authors compared the prevalence of “unaware” and “untreated” by age, sex, race and ethnicity, educational attainment, poverty index, and insurance status.

TAKEAWAY:

• During the study period, the age-adjusted prevalence of an LDL-C level of 160-189 mg/dL declined from 12.4% (95% confidence interval, 10.0%-15.3%), representing 21.5 million U.S. adults, to 6.1% (95% CI, 4.8%-7.6%), representing 14.0 million adults (P < .001).
• The age-adjusted prevalence of an LDL-C level of at least 190 mg/dL declined from 3.8% (95% CI, 2.8%-5.2%), representing 6.6 million adults, to 2.1% (95% CI, 1.4%-3.0%), representing 4.8 million adults (P = .001).
• Among those with an LDL-C level of 160-189 mg/dL, the proportion of who were unaware and untreated declined from 52.1% to 42.7%, and among those with an LDL-C level of at least 190 mg/dL, it declined from 40.8% to 26.8%.
• Being unaware and untreated was more common in younger adults, men, racial and ethnic minority groups, those with lower educational attainment, those with lower income, and those without health insurance.

IN PRACTICE:

The lack of awareness and treatment of high LDL-C uncovered by the study “may be due to difficulties accessing primary care, low rates of screening in primary care, lack of consensus on screening recommendations, insufficient emphasis on LDL-C as a quality measure, and hesitance to treat asymptomatic individuals,” the authors concluded.

SOURCE:

The research was led by Ahmed Sayed, MBBS, faculty of medicine, Ain Shams University, Cairo, Egypt. It was published online in JAMA Cardiology.

LIMITATIONS:

The analysis was limited by a small number of participants with LDL-C levels of at least 190 mg/dL, possible nonresponse bias, and dependency on participant recall of whether LDL-C was previously measured. The inclusion of pregnant women may have influenced LDL-C levels.

DISCLOSURES:

Dr. Sayed has no relevant conflict of interest. The disclosures of the other authors are listed in the original publication.

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

TOPLINE:

The prevalence of elevated LDL cholesterol (LDL-C) has declined over the past 2 decades, but 1 in 17 Americans still have a level of 160-189 mg/dL, and 1 in 48 have a level of at least 190 mg/dL, new research shows. Among people with the higher LDL-C level, one in four are both unaware and untreated, the authors report.

METHODOLOGY:

• Using data on 23,667 adult participants in the National Health and Nutrition Examination Survey conducted from 1999 to 2020, researchers identified 1,851 (7.8%) with an LDL-C level of 160-189 mg/dL and 669 (2.8%) with an LDL-C level of at least 190 mg/dL.
• Individuals were classified as “unaware” if they had never had their LDL-C measured or had never been informed of having elevated LDL-C and as “untreated” if their medications didn’t include a statin, ezetimibe, a bile acid sequestrant, or a proprotein convertase subtilisin/kexin type 9 inhibitor.
• The authors compared the prevalence of “unaware” and “untreated” by age, sex, race and ethnicity, educational attainment, poverty index, and insurance status.

TAKEAWAY:

• During the study period, the age-adjusted prevalence of an LDL-C level of 160-189 mg/dL declined from 12.4% (95% confidence interval, 10.0%-15.3%), representing 21.5 million U.S. adults, to 6.1% (95% CI, 4.8%-7.6%), representing 14.0 million adults (P < .001).
• The age-adjusted prevalence of an LDL-C level of at least 190 mg/dL declined from 3.8% (95% CI, 2.8%-5.2%), representing 6.6 million adults, to 2.1% (95% CI, 1.4%-3.0%), representing 4.8 million adults (P = .001).
• Among those with an LDL-C level of 160-189 mg/dL, the proportion of who were unaware and untreated declined from 52.1% to 42.7%, and among those with an LDL-C level of at least 190 mg/dL, it declined from 40.8% to 26.8%.
• Being unaware and untreated was more common in younger adults, men, racial and ethnic minority groups, those with lower educational attainment, those with lower income, and those without health insurance.

IN PRACTICE:

The lack of awareness and treatment of high LDL-C uncovered by the study “may be due to difficulties accessing primary care, low rates of screening in primary care, lack of consensus on screening recommendations, insufficient emphasis on LDL-C as a quality measure, and hesitance to treat asymptomatic individuals,” the authors concluded.

SOURCE:

The research was led by Ahmed Sayed, MBBS, faculty of medicine, Ain Shams University, Cairo, Egypt. It was published online in JAMA Cardiology.

LIMITATIONS:

The analysis was limited by a small number of participants with LDL-C levels of at least 190 mg/dL, possible nonresponse bias, and dependency on participant recall of whether LDL-C was previously measured. The inclusion of pregnant women may have influenced LDL-C levels.

DISCLOSURES:

Dr. Sayed has no relevant conflict of interest. The disclosures of the other authors are listed in the original publication.

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

TOPLINE:

The prevalence of elevated LDL cholesterol (LDL-C) has declined over the past 2 decades, but 1 in 17 Americans still have a level of 160-189 mg/dL, and 1 in 48 have a level of at least 190 mg/dL, new research shows. Among people with the higher LDL-C level, one in four are both unaware and untreated, the authors report.

METHODOLOGY:

• Using data on 23,667 adult participants in the National Health and Nutrition Examination Survey conducted from 1999 to 2020, researchers identified 1,851 (7.8%) with an LDL-C level of 160-189 mg/dL and 669 (2.8%) with an LDL-C level of at least 190 mg/dL.
• Individuals were classified as “unaware” if they had never had their LDL-C measured or had never been informed of having elevated LDL-C and as “untreated” if their medications didn’t include a statin, ezetimibe, a bile acid sequestrant, or a proprotein convertase subtilisin/kexin type 9 inhibitor.
• The authors compared the prevalence of “unaware” and “untreated” by age, sex, race and ethnicity, educational attainment, poverty index, and insurance status.

TAKEAWAY:

• During the study period, the age-adjusted prevalence of an LDL-C level of 160-189 mg/dL declined from 12.4% (95% confidence interval, 10.0%-15.3%), representing 21.5 million U.S. adults, to 6.1% (95% CI, 4.8%-7.6%), representing 14.0 million adults (P < .001).
• The age-adjusted prevalence of an LDL-C level of at least 190 mg/dL declined from 3.8% (95% CI, 2.8%-5.2%), representing 6.6 million adults, to 2.1% (95% CI, 1.4%-3.0%), representing 4.8 million adults (P = .001).
• Among those with an LDL-C level of 160-189 mg/dL, the proportion of who were unaware and untreated declined from 52.1% to 42.7%, and among those with an LDL-C level of at least 190 mg/dL, it declined from 40.8% to 26.8%.
• Being unaware and untreated was more common in younger adults, men, racial and ethnic minority groups, those with lower educational attainment, those with lower income, and those without health insurance.

IN PRACTICE:

The lack of awareness and treatment of high LDL-C uncovered by the study “may be due to difficulties accessing primary care, low rates of screening in primary care, lack of consensus on screening recommendations, insufficient emphasis on LDL-C as a quality measure, and hesitance to treat asymptomatic individuals,” the authors concluded.

SOURCE:

The research was led by Ahmed Sayed, MBBS, faculty of medicine, Ain Shams University, Cairo, Egypt. It was published online in JAMA Cardiology.

LIMITATIONS:

The analysis was limited by a small number of participants with LDL-C levels of at least 190 mg/dL, possible nonresponse bias, and dependency on participant recall of whether LDL-C was previously measured. The inclusion of pregnant women may have influenced LDL-C levels.

DISCLOSURES:

Dr. Sayed has no relevant conflict of interest. The disclosures of the other authors are listed in the original publication.

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

GLASGOW – An interactive digital decision tool that individualizes menopause care received praise from primary care clinicians in the United Kingdom, who said it could improve patient care and streamline office visits.

The tool, called Wellspring, helps clarify menopause guidelines from the U.K.’s National Institute for Health and Care Excellence while fostering shared decision-making with evidence-based data.  

“Access to hormone replacement therapy [HRT], as well as decision-making around treatment for menopausal symptoms, is often complicated by concerns around its safety, and there is still a knowledge and a confidence gap among health care professionals causing reluctance to prescribe HRT,”  said Aini Kamal, MSc, from University College London. Ms. Kamal presented results of a survey about the tool at the annual meeting of the Royal College of General Practitioners.

For the study, Ms. Kamal, Daniel Reisel, MBBS, PhD, a gynecologist at UCL, and colleagues evaluated Wellspring with doctors, nurses, and pharmacists.

“Ensuring that women receive education around symptoms, so that they are empowered, is a key part of optimizing their care and sharing decision-making,” Dr. Reisel said in an interview. He added that U.K. primary care had seen an increase in cases of women presenting with symptoms associated with the perimenopause and menopause at a time when U.K. Members of Parliament are debating whether to make it mandatory for all women to have menopause check-up in their early 40s.

The online survey was completed by 280 participants, and respondents were primarily GPs with several years of relevant prescribing practice. Of those, 93% found information from national guidelines to be accurately presented in the tool, and 97% said they would recommend this decision aid to other health care professionals, Ms. Kamal reported.

Nearly all participants said they could see themselves using the tool with patients in the clinic or as an adjunct to virtual sessions. “This [finding] was particularly important because it demonstrates the clinical potential this tool has,” she said.

 

One consult, too many problems

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said primary care appointments are often time-pressured and follow a “’one problem-one consultation’” policy. As such, women are often thinking ‘Do I go with my joint pains, or my palpitations, tinnitus, or what?’ If a patient presents with tinnitus, a doctor might focus on the potential of an inner ear problem rather than a hormone deficiency, but I do know that if the woman is perimenopausal or menopausal, we often look to replace the missing hormones, and then if the tinnitus doesn’t improve we can revisit the ear problem.” 

Dr. Newson noted that 17% of women in her clinics have had more than six GP visits in the year before she sees them, but in the year following, this figure drops to 1%. Acknowledging that a menopause consultation for a GP is time-consuming, Dr. Newson pointed out that taking time initially with the patient “means it will reduce the number of future consultations quickly, but more importantly, we also know that taking HRT reduces long-term risk of serious diseases, including heart disease and osteoporosis.”

The digital tool can be used by both doctors and patients to help women work through their symptoms and equip them with knowledge so their GP visits are more productive.

“When we see women who are empowered with knowledge [about menopause symptoms], then the consultations are quicker and essentially place the patient central to the discussion,” Dr. Newson said.

Ed Russell-Smith, MBChB, a GP in Scotland who moderated the session, said the tool “lays out a nicely structured approach and provides modern treatment options and resources for patients.”

However, he added “we also need to remember there are potential harms to be done from HRT too. It’s vitally important that while patients might see HRT as a panacea, doctors need to balance this with the risks involved for each individual. As a tool, I think Wellspring can help us in this respect to apply general principles to that patient and individualize treatment.”

Dr. Reisel, Dr. Newson, Ms. Kamal, and Dr. Russell-Smith disclosed no relevant financial relationships. The Wellspring Decision Aid was supported by UCL’s Institute for Women’s Health. The Newson Health clinic is fully private, but research is done via the nonprofit arm, which is supported by the clinic. There is no pharma involvement.

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

GLASGOW – An interactive digital decision tool that individualizes menopause care received praise from primary care clinicians in the United Kingdom, who said it could improve patient care and streamline office visits.

The tool, called Wellspring, helps clarify menopause guidelines from the U.K.’s National Institute for Health and Care Excellence while fostering shared decision-making with evidence-based data.  

“Access to hormone replacement therapy [HRT], as well as decision-making around treatment for menopausal symptoms, is often complicated by concerns around its safety, and there is still a knowledge and a confidence gap among health care professionals causing reluctance to prescribe HRT,”  said Aini Kamal, MSc, from University College London. Ms. Kamal presented results of a survey about the tool at the annual meeting of the Royal College of General Practitioners.

For the study, Ms. Kamal, Daniel Reisel, MBBS, PhD, a gynecologist at UCL, and colleagues evaluated Wellspring with doctors, nurses, and pharmacists.

“Ensuring that women receive education around symptoms, so that they are empowered, is a key part of optimizing their care and sharing decision-making,” Dr. Reisel said in an interview. He added that U.K. primary care had seen an increase in cases of women presenting with symptoms associated with the perimenopause and menopause at a time when U.K. Members of Parliament are debating whether to make it mandatory for all women to have menopause check-up in their early 40s.

The online survey was completed by 280 participants, and respondents were primarily GPs with several years of relevant prescribing practice. Of those, 93% found information from national guidelines to be accurately presented in the tool, and 97% said they would recommend this decision aid to other health care professionals, Ms. Kamal reported.

Nearly all participants said they could see themselves using the tool with patients in the clinic or as an adjunct to virtual sessions. “This [finding] was particularly important because it demonstrates the clinical potential this tool has,” she said.

 

One consult, too many problems

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said primary care appointments are often time-pressured and follow a “’one problem-one consultation’” policy. As such, women are often thinking ‘Do I go with my joint pains, or my palpitations, tinnitus, or what?’ If a patient presents with tinnitus, a doctor might focus on the potential of an inner ear problem rather than a hormone deficiency, but I do know that if the woman is perimenopausal or menopausal, we often look to replace the missing hormones, and then if the tinnitus doesn’t improve we can revisit the ear problem.” 

Dr. Newson noted that 17% of women in her clinics have had more than six GP visits in the year before she sees them, but in the year following, this figure drops to 1%. Acknowledging that a menopause consultation for a GP is time-consuming, Dr. Newson pointed out that taking time initially with the patient “means it will reduce the number of future consultations quickly, but more importantly, we also know that taking HRT reduces long-term risk of serious diseases, including heart disease and osteoporosis.”

The digital tool can be used by both doctors and patients to help women work through their symptoms and equip them with knowledge so their GP visits are more productive.

“When we see women who are empowered with knowledge [about menopause symptoms], then the consultations are quicker and essentially place the patient central to the discussion,” Dr. Newson said.

Ed Russell-Smith, MBChB, a GP in Scotland who moderated the session, said the tool “lays out a nicely structured approach and provides modern treatment options and resources for patients.”

However, he added “we also need to remember there are potential harms to be done from HRT too. It’s vitally important that while patients might see HRT as a panacea, doctors need to balance this with the risks involved for each individual. As a tool, I think Wellspring can help us in this respect to apply general principles to that patient and individualize treatment.”

Dr. Reisel, Dr. Newson, Ms. Kamal, and Dr. Russell-Smith disclosed no relevant financial relationships. The Wellspring Decision Aid was supported by UCL’s Institute for Women’s Health. The Newson Health clinic is fully private, but research is done via the nonprofit arm, which is supported by the clinic. There is no pharma involvement.

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

GLASGOW – An interactive digital decision tool that individualizes menopause care received praise from primary care clinicians in the United Kingdom, who said it could improve patient care and streamline office visits.

The tool, called Wellspring, helps clarify menopause guidelines from the U.K.’s National Institute for Health and Care Excellence while fostering shared decision-making with evidence-based data.  

“Access to hormone replacement therapy [HRT], as well as decision-making around treatment for menopausal symptoms, is often complicated by concerns around its safety, and there is still a knowledge and a confidence gap among health care professionals causing reluctance to prescribe HRT,”  said Aini Kamal, MSc, from University College London. Ms. Kamal presented results of a survey about the tool at the annual meeting of the Royal College of General Practitioners.

For the study, Ms. Kamal, Daniel Reisel, MBBS, PhD, a gynecologist at UCL, and colleagues evaluated Wellspring with doctors, nurses, and pharmacists.

“Ensuring that women receive education around symptoms, so that they are empowered, is a key part of optimizing their care and sharing decision-making,” Dr. Reisel said in an interview. He added that U.K. primary care had seen an increase in cases of women presenting with symptoms associated with the perimenopause and menopause at a time when U.K. Members of Parliament are debating whether to make it mandatory for all women to have menopause check-up in their early 40s.

The online survey was completed by 280 participants, and respondents were primarily GPs with several years of relevant prescribing practice. Of those, 93% found information from national guidelines to be accurately presented in the tool, and 97% said they would recommend this decision aid to other health care professionals, Ms. Kamal reported.

Nearly all participants said they could see themselves using the tool with patients in the clinic or as an adjunct to virtual sessions. “This [finding] was particularly important because it demonstrates the clinical potential this tool has,” she said.

 

One consult, too many problems

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said primary care appointments are often time-pressured and follow a “’one problem-one consultation’” policy. As such, women are often thinking ‘Do I go with my joint pains, or my palpitations, tinnitus, or what?’ If a patient presents with tinnitus, a doctor might focus on the potential of an inner ear problem rather than a hormone deficiency, but I do know that if the woman is perimenopausal or menopausal, we often look to replace the missing hormones, and then if the tinnitus doesn’t improve we can revisit the ear problem.” 

Dr. Newson noted that 17% of women in her clinics have had more than six GP visits in the year before she sees them, but in the year following, this figure drops to 1%. Acknowledging that a menopause consultation for a GP is time-consuming, Dr. Newson pointed out that taking time initially with the patient “means it will reduce the number of future consultations quickly, but more importantly, we also know that taking HRT reduces long-term risk of serious diseases, including heart disease and osteoporosis.”

The digital tool can be used by both doctors and patients to help women work through their symptoms and equip them with knowledge so their GP visits are more productive.

“When we see women who are empowered with knowledge [about menopause symptoms], then the consultations are quicker and essentially place the patient central to the discussion,” Dr. Newson said.

Ed Russell-Smith, MBChB, a GP in Scotland who moderated the session, said the tool “lays out a nicely structured approach and provides modern treatment options and resources for patients.”

However, he added “we also need to remember there are potential harms to be done from HRT too. It’s vitally important that while patients might see HRT as a panacea, doctors need to balance this with the risks involved for each individual. As a tool, I think Wellspring can help us in this respect to apply general principles to that patient and individualize treatment.”

Dr. Reisel, Dr. Newson, Ms. Kamal, and Dr. Russell-Smith disclosed no relevant financial relationships. The Wellspring Decision Aid was supported by UCL’s Institute for Women’s Health. The Newson Health clinic is fully private, but research is done via the nonprofit arm, which is supported by the clinic. There is no pharma involvement.

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

The 10 best-selling liver health supplements on Amazon bring in an estimated $2.5 million each month. But none of them contain ingredients recommended by major groups of doctors who treat liver issues in the United States or Europe.

Like many supplements, popular online liver products are unregulated, meaning they do not have to meet the same safety and effectiveness standards as prescription medications. 

Sales of liver supplements are growing, particularly in the last few years, said Ahmed Eltelbany, MD, MPH, a first-year gastrointestinal fellow at the University of New Mexico. One reason could be increased alcohol use during the COVID-19 pandemic.

Some manufacturers make bold claims on Amazon, said Dr. Eltelbany, author of a study that looked into the supplements. “The most recurrent claims were that their supplements maintain normal liver function, are scientifically formulated, and – my personal favorite – are a highly effective liver detox formulation developed according to the latest scientific findings.”

While these claims might sound reassuring and scientifically grounded to an average consumer, he said, most of them are not backed up by rigorous clinical research.
 

Does natural mean safe?

Many supplements are marketed as “liver cleansing,” for “liver detox,” or for “liver support,” Dr. Eltelbany said as he presented the study results at the annual meeting of the American College of Gastroenterology. 

“People take these supplements because they believe they’re natural and therefore they’re safe,” said Paul Y. Kwo, MD, who moderated a session on the study at the meeting, when asked to comment. “As I tell every patient in clinic, a great white shark is natural, a scorpion is natural, and so is a hurricane. So just because they’re natural doesn’t mean they’re safe.”

At the same time, “it’s not that every supplement is bad for you. Nonetheless, there’s just a dizzying array of these out there” said Dr. Kwo, a professor of medicine at Stanford Medicine in Redwood, Calif.

“We have to be very cautious,” he said. For example, some people might believe that “if a little bit of a supplement is good, a tremendous amount must be really good.” The antioxidant turmeric, for example, has a pretty good safety record, he said. But this past year, some liver toxicity concerns arose about preparations with “very, very high concentrations” of turmeric. 
 

The top 10 sellers

Dr. Eltelbany and colleagues studied prices for 1-month supplies, monthly sales, and revenue for the top 10 liver supplements sold on Amazon on June 3, 2023:

Ranking by sales:

• 1. Liver Cleanse Detox & Repair Formula – Herbal Liver Supplement with Milk Thistle, Dandelion Root, Organic Turmeric and Artichoke Extract for Liver Health – Silymarin Milk Thistle Detox Capsules
• 2. Ancestral Supplements Grass Fed Beef Liver Capsules. Supports Energy Production, Detoxification, Digestion, Immunity and Full Body Wellness, Non-GMO, Freeze Dried Liver Health Supplement, 180 Capsules
• 3. Bronson Milk Thistle 1,000 mg Silymarin Marianum & Dandelion Root Liver Health Support, 120 Capsules
• 4. PUREHEALTH RESEARCH Liver Supplement – Herbal Liver Cleanse Detox & Repair with Milk Thistle, Artichoke Extract, Dandelion Root, Turmeric, Berberine to Healthy Liver Renew with 11 Natural Nutrients
• 5. TUDCA Bile Salts Liver Support Supplement, 500-mg Servings, Liver and Gallbladder Cleanse Supplement (60 Capsules 250 mg) Genuine Bile Acid. TUDCA Strong Bitter Taste by Double Wood
• 6. 28-in-1 Liver Cleanse Detox & Repair Fatty Liver Formula, Milk Thistle Silymarin, Artichoke Extract, Dandelion & Apple Cider Vinegar – Liver Health Supplement Support Pills – Vegan Capsules
• 7. Vita-Liver Liver Health Supplement – Support Liver Cleanse & Detox – Liquid Delivery for Absorption – Milk Thistle, Artichoke, Chanca Piedra, Dandelion & More
• 8. Liver Supplement with Milk Thistle, Liver Detox Formula, Artichoke and Turmeric. Supports Liver Health Defense & Liver Renew. Liver Cleanse Detox & Repair for Fatty Liver Support. 60 Capsules
• 9. Liver Cleanse Detox & Repair. Milk Thistle Extract with Silymarin 80%, Artichoke Extract, Dandelion Root, Chicory, 25+ Herbs – Premium Liver Health Formula, Liver Support Detox Health Formula – Liver Support Detox Cleanse Supplement
• 10. Arazo Nutrition Liver Cleanse Detox & Repair Formula – Milk Thistle Herbal Support Supplement: Silymarin, Beet, Artichoke, Dandelion, Chicory Root

The investigators found a total of 65 unique ingredients. “Most of these ingredients have historical uses linked to liver health. But our research revealed that strong scientific evidence supporting the efficacy of any of these supplements is currently lacking,” Dr. Eltelbany said. They started the study by creating a new account on Amazon to make sure the search would not be influenced by prior shopping or purchases. They next searched for supplements using the keywords “liver” and “cleanse.” To figure out sales numbers, they used the AMZScout proprietary analytics software that Amazon sellers use to track sales. 
 

Reviewing the reviews

The researchers discovered an average 11,526 reviews for each supplement product. The average rating was 4.42 stars out of 5. 

Using Fakespot.com, proprietary Amazon customer review software that analyzes the timing and language of reviews, they found that only 65% of product reviews were genuine. 

“We felt it was crucial to vet the authenticity of customer feedback,” Dr. Eltelbany said.
 

Few other options?

Liver disease remains a persistent and significant global health burden. Despite advances in many areas of gastroenterology, there remains no curative treatment for liver cirrhosis, Dr. Eltelbany said. 

The primary option for people with end-stage liver disease is a liver transplant. “However, given the scarcity of donors and the vast number of patients in need, many individuals, unfortunately, do not get a timely transplant,” he said. “This void of treatment options and the desperation to find relief often drives patients towards alternative therapies.”

Also, online shopping has made getting these supplements “as simple as a click away. But what’s more concerning is the trust placed in these products by our patients,” Dr. Eltelbany said.

“There’s a strong need for rigorous scientific investigation into the actual health benefits of any liver detox supplements,” he said. “Above all, patient education remains paramount, warning them of potential risks and unknowns of these supplements.”

A version of this article appeared on WebMD.com.

The 10 best-selling liver health supplements on Amazon bring in an estimated $2.5 million each month. But none of them contain ingredients recommended by major groups of doctors who treat liver issues in the United States or Europe.

Like many supplements, popular online liver products are unregulated, meaning they do not have to meet the same safety and effectiveness standards as prescription medications. 

Sales of liver supplements are growing, particularly in the last few years, said Ahmed Eltelbany, MD, MPH, a first-year gastrointestinal fellow at the University of New Mexico. One reason could be increased alcohol use during the COVID-19 pandemic.

Some manufacturers make bold claims on Amazon, said Dr. Eltelbany, author of a study that looked into the supplements. “The most recurrent claims were that their supplements maintain normal liver function, are scientifically formulated, and – my personal favorite – are a highly effective liver detox formulation developed according to the latest scientific findings.”

While these claims might sound reassuring and scientifically grounded to an average consumer, he said, most of them are not backed up by rigorous clinical research.
 

Does natural mean safe?

Many supplements are marketed as “liver cleansing,” for “liver detox,” or for “liver support,” Dr. Eltelbany said as he presented the study results at the annual meeting of the American College of Gastroenterology. 

“People take these supplements because they believe they’re natural and therefore they’re safe,” said Paul Y. Kwo, MD, who moderated a session on the study at the meeting, when asked to comment. “As I tell every patient in clinic, a great white shark is natural, a scorpion is natural, and so is a hurricane. So just because they’re natural doesn’t mean they’re safe.”

At the same time, “it’s not that every supplement is bad for you. Nonetheless, there’s just a dizzying array of these out there” said Dr. Kwo, a professor of medicine at Stanford Medicine in Redwood, Calif.

“We have to be very cautious,” he said. For example, some people might believe that “if a little bit of a supplement is good, a tremendous amount must be really good.” The antioxidant turmeric, for example, has a pretty good safety record, he said. But this past year, some liver toxicity concerns arose about preparations with “very, very high concentrations” of turmeric. 
 

The top 10 sellers

Dr. Eltelbany and colleagues studied prices for 1-month supplies, monthly sales, and revenue for the top 10 liver supplements sold on Amazon on June 3, 2023:

Ranking by sales:

• 1. Liver Cleanse Detox & Repair Formula – Herbal Liver Supplement with Milk Thistle, Dandelion Root, Organic Turmeric and Artichoke Extract for Liver Health – Silymarin Milk Thistle Detox Capsules
• 2. Ancestral Supplements Grass Fed Beef Liver Capsules. Supports Energy Production, Detoxification, Digestion, Immunity and Full Body Wellness, Non-GMO, Freeze Dried Liver Health Supplement, 180 Capsules
• 3. Bronson Milk Thistle 1,000 mg Silymarin Marianum & Dandelion Root Liver Health Support, 120 Capsules
• 4. PUREHEALTH RESEARCH Liver Supplement – Herbal Liver Cleanse Detox & Repair with Milk Thistle, Artichoke Extract, Dandelion Root, Turmeric, Berberine to Healthy Liver Renew with 11 Natural Nutrients
• 5. TUDCA Bile Salts Liver Support Supplement, 500-mg Servings, Liver and Gallbladder Cleanse Supplement (60 Capsules 250 mg) Genuine Bile Acid. TUDCA Strong Bitter Taste by Double Wood
• 6. 28-in-1 Liver Cleanse Detox & Repair Fatty Liver Formula, Milk Thistle Silymarin, Artichoke Extract, Dandelion & Apple Cider Vinegar – Liver Health Supplement Support Pills – Vegan Capsules
• 7. Vita-Liver Liver Health Supplement – Support Liver Cleanse & Detox – Liquid Delivery for Absorption – Milk Thistle, Artichoke, Chanca Piedra, Dandelion & More
• 8. Liver Supplement with Milk Thistle, Liver Detox Formula, Artichoke and Turmeric. Supports Liver Health Defense & Liver Renew. Liver Cleanse Detox & Repair for Fatty Liver Support. 60 Capsules
• 9. Liver Cleanse Detox & Repair. Milk Thistle Extract with Silymarin 80%, Artichoke Extract, Dandelion Root, Chicory, 25+ Herbs – Premium Liver Health Formula, Liver Support Detox Health Formula – Liver Support Detox Cleanse Supplement
• 10. Arazo Nutrition Liver Cleanse Detox & Repair Formula – Milk Thistle Herbal Support Supplement: Silymarin, Beet, Artichoke, Dandelion, Chicory Root

The investigators found a total of 65 unique ingredients. “Most of these ingredients have historical uses linked to liver health. But our research revealed that strong scientific evidence supporting the efficacy of any of these supplements is currently lacking,” Dr. Eltelbany said. They started the study by creating a new account on Amazon to make sure the search would not be influenced by prior shopping or purchases. They next searched for supplements using the keywords “liver” and “cleanse.” To figure out sales numbers, they used the AMZScout proprietary analytics software that Amazon sellers use to track sales. 
 

Reviewing the reviews

The researchers discovered an average 11,526 reviews for each supplement product. The average rating was 4.42 stars out of 5. 

Using Fakespot.com, proprietary Amazon customer review software that analyzes the timing and language of reviews, they found that only 65% of product reviews were genuine. 

“We felt it was crucial to vet the authenticity of customer feedback,” Dr. Eltelbany said.
 

Few other options?

Liver disease remains a persistent and significant global health burden. Despite advances in many areas of gastroenterology, there remains no curative treatment for liver cirrhosis, Dr. Eltelbany said. 

The primary option for people with end-stage liver disease is a liver transplant. “However, given the scarcity of donors and the vast number of patients in need, many individuals, unfortunately, do not get a timely transplant,” he said. “This void of treatment options and the desperation to find relief often drives patients towards alternative therapies.”

Also, online shopping has made getting these supplements “as simple as a click away. But what’s more concerning is the trust placed in these products by our patients,” Dr. Eltelbany said.

“There’s a strong need for rigorous scientific investigation into the actual health benefits of any liver detox supplements,” he said. “Above all, patient education remains paramount, warning them of potential risks and unknowns of these supplements.”

A version of this article appeared on WebMD.com.

The 10 best-selling liver health supplements on Amazon bring in an estimated $2.5 million each month. But none of them contain ingredients recommended by major groups of doctors who treat liver issues in the United States or Europe.

Like many supplements, popular online liver products are unregulated, meaning they do not have to meet the same safety and effectiveness standards as prescription medications. 

Sales of liver supplements are growing, particularly in the last few years, said Ahmed Eltelbany, MD, MPH, a first-year gastrointestinal fellow at the University of New Mexico. One reason could be increased alcohol use during the COVID-19 pandemic.

Some manufacturers make bold claims on Amazon, said Dr. Eltelbany, author of a study that looked into the supplements. “The most recurrent claims were that their supplements maintain normal liver function, are scientifically formulated, and – my personal favorite – are a highly effective liver detox formulation developed according to the latest scientific findings.”

While these claims might sound reassuring and scientifically grounded to an average consumer, he said, most of them are not backed up by rigorous clinical research.
 

Does natural mean safe?

Many supplements are marketed as “liver cleansing,” for “liver detox,” or for “liver support,” Dr. Eltelbany said as he presented the study results at the annual meeting of the American College of Gastroenterology. 

“People take these supplements because they believe they’re natural and therefore they’re safe,” said Paul Y. Kwo, MD, who moderated a session on the study at the meeting, when asked to comment. “As I tell every patient in clinic, a great white shark is natural, a scorpion is natural, and so is a hurricane. So just because they’re natural doesn’t mean they’re safe.”

At the same time, “it’s not that every supplement is bad for you. Nonetheless, there’s just a dizzying array of these out there” said Dr. Kwo, a professor of medicine at Stanford Medicine in Redwood, Calif.

“We have to be very cautious,” he said. For example, some people might believe that “if a little bit of a supplement is good, a tremendous amount must be really good.” The antioxidant turmeric, for example, has a pretty good safety record, he said. But this past year, some liver toxicity concerns arose about preparations with “very, very high concentrations” of turmeric. 
 

The top 10 sellers

Dr. Eltelbany and colleagues studied prices for 1-month supplies, monthly sales, and revenue for the top 10 liver supplements sold on Amazon on June 3, 2023:

Ranking by sales:

• 1. Liver Cleanse Detox & Repair Formula – Herbal Liver Supplement with Milk Thistle, Dandelion Root, Organic Turmeric and Artichoke Extract for Liver Health – Silymarin Milk Thistle Detox Capsules
• 2. Ancestral Supplements Grass Fed Beef Liver Capsules. Supports Energy Production, Detoxification, Digestion, Immunity and Full Body Wellness, Non-GMO, Freeze Dried Liver Health Supplement, 180 Capsules
• 3. Bronson Milk Thistle 1,000 mg Silymarin Marianum & Dandelion Root Liver Health Support, 120 Capsules
• 4. PUREHEALTH RESEARCH Liver Supplement – Herbal Liver Cleanse Detox & Repair with Milk Thistle, Artichoke Extract, Dandelion Root, Turmeric, Berberine to Healthy Liver Renew with 11 Natural Nutrients
• 5. TUDCA Bile Salts Liver Support Supplement, 500-mg Servings, Liver and Gallbladder Cleanse Supplement (60 Capsules 250 mg) Genuine Bile Acid. TUDCA Strong Bitter Taste by Double Wood
• 6. 28-in-1 Liver Cleanse Detox & Repair Fatty Liver Formula, Milk Thistle Silymarin, Artichoke Extract, Dandelion & Apple Cider Vinegar – Liver Health Supplement Support Pills – Vegan Capsules
• 7. Vita-Liver Liver Health Supplement – Support Liver Cleanse & Detox – Liquid Delivery for Absorption – Milk Thistle, Artichoke, Chanca Piedra, Dandelion & More
• 8. Liver Supplement with Milk Thistle, Liver Detox Formula, Artichoke and Turmeric. Supports Liver Health Defense & Liver Renew. Liver Cleanse Detox & Repair for Fatty Liver Support. 60 Capsules
• 9. Liver Cleanse Detox & Repair. Milk Thistle Extract with Silymarin 80%, Artichoke Extract, Dandelion Root, Chicory, 25+ Herbs – Premium Liver Health Formula, Liver Support Detox Health Formula – Liver Support Detox Cleanse Supplement
• 10. Arazo Nutrition Liver Cleanse Detox & Repair Formula – Milk Thistle Herbal Support Supplement: Silymarin, Beet, Artichoke, Dandelion, Chicory Root

The investigators found a total of 65 unique ingredients. “Most of these ingredients have historical uses linked to liver health. But our research revealed that strong scientific evidence supporting the efficacy of any of these supplements is currently lacking,” Dr. Eltelbany said. They started the study by creating a new account on Amazon to make sure the search would not be influenced by prior shopping or purchases. They next searched for supplements using the keywords “liver” and “cleanse.” To figure out sales numbers, they used the AMZScout proprietary analytics software that Amazon sellers use to track sales. 
 

Reviewing the reviews

The researchers discovered an average 11,526 reviews for each supplement product. The average rating was 4.42 stars out of 5. 

Using Fakespot.com, proprietary Amazon customer review software that analyzes the timing and language of reviews, they found that only 65% of product reviews were genuine. 

“We felt it was crucial to vet the authenticity of customer feedback,” Dr. Eltelbany said.
 

Few other options?

Liver disease remains a persistent and significant global health burden. Despite advances in many areas of gastroenterology, there remains no curative treatment for liver cirrhosis, Dr. Eltelbany said. 

The primary option for people with end-stage liver disease is a liver transplant. “However, given the scarcity of donors and the vast number of patients in need, many individuals, unfortunately, do not get a timely transplant,” he said. “This void of treatment options and the desperation to find relief often drives patients towards alternative therapies.”

Also, online shopping has made getting these supplements “as simple as a click away. But what’s more concerning is the trust placed in these products by our patients,” Dr. Eltelbany said.

“There’s a strong need for rigorous scientific investigation into the actual health benefits of any liver detox supplements,” he said. “Above all, patient education remains paramount, warning them of potential risks and unknowns of these supplements.”

A version of this article appeared on WebMD.com.

A pair of new studies published about long COVID have shed more light on the sometimes-disabling condition that affects millions of people in the United States. 

Scientists worldwide have been working to understand the wide-ranging condition, from risk factors to causes to potential treatments. 

In the first study, 31 adults underwent lumbar puncture and blood draws to look for changes in their immune systems and also to look for changes in the nerve cells that could affect transmission of signals to the brain.

Among the participants, 25 people had neurocognitive symptoms of long COVID, such as memory loss or attention problems. Six participants had fully recovered from COVID, and 17 people had never had COVID. 

Those who had COVID were diagnosed between March 2020 and May 2021. Their fluid samples were drawn at least three months after their first symptoms.

The results were published in the Journal of Infectious Diseases. Study results showed that long COVID does not appear to be linked to the SARS-CoV-2 virus invading the brain or causing active brain damage.

According to a summary of the study from the University of Gothenburg (Sweden), where the researchers work, “there were no significant differences between the groups when analyzing blood and cerebrospinal fluid for immune activation or brain injury markers. The findings thus suggest that post-COVID condition is not the result of ongoing infection, immune activation, or brain damage.”

In the second study, Norwegian researchers compared the likelihood of having 17 different long COVID symptoms based on whether a person had been infected with COVID. The analysis included 53,846 people who were diagnosed with COVID between February 2020 and February 2021, as well as more than 485,000 people who were not infected. Most people had not been vaccinated against COVID-19 during the time of the study.

The results were published in the journal BMC Infectious Diseases. Study results showed that people who had COVID were more than twice as likely to experience shortness of breath or fatigue. They were also more likely to experience memory loss or headache compared to people who never had COVID. Researchers only looked at symptoms that occurred at least three months after a COVID diagnosis.

They also found that hospitalization increased the risk for experiencing long COVID symptoms of shortness of breath, fatigue, and memory loss.

The authors noted that a limitation of their study was that, often, not all symptoms reported during a visit with a general practice medical provider are recorded in Norway, which could have affected the results.

A version of this article appeared on Medscape.com.

A pair of new studies published about long COVID have shed more light on the sometimes-disabling condition that affects millions of people in the United States. 

Scientists worldwide have been working to understand the wide-ranging condition, from risk factors to causes to potential treatments. 

In the first study, 31 adults underwent lumbar puncture and blood draws to look for changes in their immune systems and also to look for changes in the nerve cells that could affect transmission of signals to the brain.

Among the participants, 25 people had neurocognitive symptoms of long COVID, such as memory loss or attention problems. Six participants had fully recovered from COVID, and 17 people had never had COVID. 

Those who had COVID were diagnosed between March 2020 and May 2021. Their fluid samples were drawn at least three months after their first symptoms.

The results were published in the Journal of Infectious Diseases. Study results showed that long COVID does not appear to be linked to the SARS-CoV-2 virus invading the brain or causing active brain damage.

According to a summary of the study from the University of Gothenburg (Sweden), where the researchers work, “there were no significant differences between the groups when analyzing blood and cerebrospinal fluid for immune activation or brain injury markers. The findings thus suggest that post-COVID condition is not the result of ongoing infection, immune activation, or brain damage.”

In the second study, Norwegian researchers compared the likelihood of having 17 different long COVID symptoms based on whether a person had been infected with COVID. The analysis included 53,846 people who were diagnosed with COVID between February 2020 and February 2021, as well as more than 485,000 people who were not infected. Most people had not been vaccinated against COVID-19 during the time of the study.

The results were published in the journal BMC Infectious Diseases. Study results showed that people who had COVID were more than twice as likely to experience shortness of breath or fatigue. They were also more likely to experience memory loss or headache compared to people who never had COVID. Researchers only looked at symptoms that occurred at least three months after a COVID diagnosis.

They also found that hospitalization increased the risk for experiencing long COVID symptoms of shortness of breath, fatigue, and memory loss.

The authors noted that a limitation of their study was that, often, not all symptoms reported during a visit with a general practice medical provider are recorded in Norway, which could have affected the results.

A version of this article appeared on Medscape.com.

A pair of new studies published about long COVID have shed more light on the sometimes-disabling condition that affects millions of people in the United States. 

Scientists worldwide have been working to understand the wide-ranging condition, from risk factors to causes to potential treatments. 

In the first study, 31 adults underwent lumbar puncture and blood draws to look for changes in their immune systems and also to look for changes in the nerve cells that could affect transmission of signals to the brain.

Among the participants, 25 people had neurocognitive symptoms of long COVID, such as memory loss or attention problems. Six participants had fully recovered from COVID, and 17 people had never had COVID. 

Those who had COVID were diagnosed between March 2020 and May 2021. Their fluid samples were drawn at least three months after their first symptoms.

The results were published in the Journal of Infectious Diseases. Study results showed that long COVID does not appear to be linked to the SARS-CoV-2 virus invading the brain or causing active brain damage.

According to a summary of the study from the University of Gothenburg (Sweden), where the researchers work, “there were no significant differences between the groups when analyzing blood and cerebrospinal fluid for immune activation or brain injury markers. The findings thus suggest that post-COVID condition is not the result of ongoing infection, immune activation, or brain damage.”

In the second study, Norwegian researchers compared the likelihood of having 17 different long COVID symptoms based on whether a person had been infected with COVID. The analysis included 53,846 people who were diagnosed with COVID between February 2020 and February 2021, as well as more than 485,000 people who were not infected. Most people had not been vaccinated against COVID-19 during the time of the study.

The results were published in the journal BMC Infectious Diseases. Study results showed that people who had COVID were more than twice as likely to experience shortness of breath or fatigue. They were also more likely to experience memory loss or headache compared to people who never had COVID. Researchers only looked at symptoms that occurred at least three months after a COVID diagnosis.

They also found that hospitalization increased the risk for experiencing long COVID symptoms of shortness of breath, fatigue, and memory loss.

The authors noted that a limitation of their study was that, often, not all symptoms reported during a visit with a general practice medical provider are recorded in Norway, which could have affected the results.

A version of this article appeared on Medscape.com.

TOPLINE:

Atrial fibrillation (AF) is associated with a 45% increased risk of mild cognitive impairment (MCI), an outcome that’s linked to cardiovascular risk factors and multi-comorbidity, results of a new study suggest.

METHODOLOGY:

• From over 4.3 million people in the UK primary electronic health record (EHR) database, researchers identified 233,833 (5.4%) with AF (mean age, 74.2 years) and randomly selected one age- and sex-matched control person without AF for each AF case patient.
• The primary outcome was incidence of mild cognitive impairment (MCI).
• The authors adjusted for age, sex, year at study entry, socioeconomic status, smoking, and a number of comorbid conditions.
• During a median of 5.3 years of follow-up, there were 4,269 incident MCI cases among both AF and non-AF patients.

TAKEAWAY:

• Individuals with AF had a higher risk of MCI than that of those without AF (adjusted hazard ratio [aHR], 1.45; 95% confidence interval [CI], 1.35-1.56).
• Besides AF, older age (risk ratio [RR], 1.08) and history of depression (RR, 1.44) were associated with greater risk of MCI, as were female sex, greater socioeconomic deprivation, stroke, and multimorbidity, including, for example, diabetes, hypercholesterolemia, and peripheral artery disease (all P < .001).
• Individuals with AF who received oral anticoagulants or amiodarone were not at increased risk of MCI, as was the case for those treated with digoxin.
• Individuals with AF and MCI were at greater risk of dementia (aHR, 1.25; 95% CI, 1.09-1.42). Sex, smoking, chronic kidney disease, and multi-comorbidity were among factors linked to elevated dementia risk.

IN PRACTICE:

The findings emphasize the association of multi-comorbidity and cardiovascular risk factors with development of MCI and progression to dementia in AF patients, the authors wrote. They noted that the data suggest combining anticoagulation and symptom and comorbidity management may prevent cognitive deterioration.

SOURCE:

The study was conducted by Sheng-Chia Chung, PhD, Institute of Health informatics Research, University College London, and colleagues. It was published online Oct. 25, 2023, as a research letter in the Journal of the American College of Cardiology (JACC): Advances. 

LIMITATIONS:

The EHR dataset may have lacked granularity and detail, and some risk factors or comorbidities may not have been measured. While those with AF receiving digoxin or amiodarone treatment had no higher risk of MCI than their non-AF peers, the study’s observational design and very wide confidence intervals for these subgroups prevent making solid inferences about causality or a potential protective role of these drugs.

DISCLOSURES:

Dr. Chung is supported by the National Institute of Health and Care Research (NIHR) Author Rui Providencia, MD, PhD, of the Institute of Health informatics Research, University College London, is supported by the University College London British Heart Foundation and NIHR. All other authors report no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Atrial fibrillation (AF) is associated with a 45% increased risk of mild cognitive impairment (MCI), an outcome that’s linked to cardiovascular risk factors and multi-comorbidity, results of a new study suggest.

METHODOLOGY:

• From over 4.3 million people in the UK primary electronic health record (EHR) database, researchers identified 233,833 (5.4%) with AF (mean age, 74.2 years) and randomly selected one age- and sex-matched control person without AF for each AF case patient.
• The primary outcome was incidence of mild cognitive impairment (MCI).
• The authors adjusted for age, sex, year at study entry, socioeconomic status, smoking, and a number of comorbid conditions.
• During a median of 5.3 years of follow-up, there were 4,269 incident MCI cases among both AF and non-AF patients.

TAKEAWAY:

• Individuals with AF had a higher risk of MCI than that of those without AF (adjusted hazard ratio [aHR], 1.45; 95% confidence interval [CI], 1.35-1.56).
• Besides AF, older age (risk ratio [RR], 1.08) and history of depression (RR, 1.44) were associated with greater risk of MCI, as were female sex, greater socioeconomic deprivation, stroke, and multimorbidity, including, for example, diabetes, hypercholesterolemia, and peripheral artery disease (all P < .001).
• Individuals with AF who received oral anticoagulants or amiodarone were not at increased risk of MCI, as was the case for those treated with digoxin.
• Individuals with AF and MCI were at greater risk of dementia (aHR, 1.25; 95% CI, 1.09-1.42). Sex, smoking, chronic kidney disease, and multi-comorbidity were among factors linked to elevated dementia risk.

IN PRACTICE:

The findings emphasize the association of multi-comorbidity and cardiovascular risk factors with development of MCI and progression to dementia in AF patients, the authors wrote. They noted that the data suggest combining anticoagulation and symptom and comorbidity management may prevent cognitive deterioration.

SOURCE:

The study was conducted by Sheng-Chia Chung, PhD, Institute of Health informatics Research, University College London, and colleagues. It was published online Oct. 25, 2023, as a research letter in the Journal of the American College of Cardiology (JACC): Advances. 

LIMITATIONS:

The EHR dataset may have lacked granularity and detail, and some risk factors or comorbidities may not have been measured. While those with AF receiving digoxin or amiodarone treatment had no higher risk of MCI than their non-AF peers, the study’s observational design and very wide confidence intervals for these subgroups prevent making solid inferences about causality or a potential protective role of these drugs.

DISCLOSURES:

Dr. Chung is supported by the National Institute of Health and Care Research (NIHR) Author Rui Providencia, MD, PhD, of the Institute of Health informatics Research, University College London, is supported by the University College London British Heart Foundation and NIHR. All other authors report no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Atrial fibrillation (AF) is associated with a 45% increased risk of mild cognitive impairment (MCI), an outcome that’s linked to cardiovascular risk factors and multi-comorbidity, results of a new study suggest.

METHODOLOGY:

• From over 4.3 million people in the UK primary electronic health record (EHR) database, researchers identified 233,833 (5.4%) with AF (mean age, 74.2 years) and randomly selected one age- and sex-matched control person without AF for each AF case patient.
• The primary outcome was incidence of mild cognitive impairment (MCI).
• The authors adjusted for age, sex, year at study entry, socioeconomic status, smoking, and a number of comorbid conditions.
• During a median of 5.3 years of follow-up, there were 4,269 incident MCI cases among both AF and non-AF patients.

TAKEAWAY:

• Individuals with AF had a higher risk of MCI than that of those without AF (adjusted hazard ratio [aHR], 1.45; 95% confidence interval [CI], 1.35-1.56).
• Besides AF, older age (risk ratio [RR], 1.08) and history of depression (RR, 1.44) were associated with greater risk of MCI, as were female sex, greater socioeconomic deprivation, stroke, and multimorbidity, including, for example, diabetes, hypercholesterolemia, and peripheral artery disease (all P < .001).
• Individuals with AF who received oral anticoagulants or amiodarone were not at increased risk of MCI, as was the case for those treated with digoxin.
• Individuals with AF and MCI were at greater risk of dementia (aHR, 1.25; 95% CI, 1.09-1.42). Sex, smoking, chronic kidney disease, and multi-comorbidity were among factors linked to elevated dementia risk.

IN PRACTICE:

The findings emphasize the association of multi-comorbidity and cardiovascular risk factors with development of MCI and progression to dementia in AF patients, the authors wrote. They noted that the data suggest combining anticoagulation and symptom and comorbidity management may prevent cognitive deterioration.

SOURCE:

The study was conducted by Sheng-Chia Chung, PhD, Institute of Health informatics Research, University College London, and colleagues. It was published online Oct. 25, 2023, as a research letter in the Journal of the American College of Cardiology (JACC): Advances. 

LIMITATIONS:

The EHR dataset may have lacked granularity and detail, and some risk factors or comorbidities may not have been measured. While those with AF receiving digoxin or amiodarone treatment had no higher risk of MCI than their non-AF peers, the study’s observational design and very wide confidence intervals for these subgroups prevent making solid inferences about causality or a potential protective role of these drugs.

DISCLOSURES:

Dr. Chung is supported by the National Institute of Health and Care Research (NIHR) Author Rui Providencia, MD, PhD, of the Institute of Health informatics Research, University College London, is supported by the University College London British Heart Foundation and NIHR. All other authors report no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

For some patients with atopic dermatitis (AD), dupilumab treatment can cause a benign reversible lymphoid reaction (LR) that mimics mycosis fungoides (MF) but differs histologically, according to a study published in JAMA Dermatology

The potential for such reactions requires diagnosing AD carefully, monitoring patients on dupilumab for new and unusual symptoms, and thoroughly working up suspicious LRs, according to an accompanying editorial and experts interviewed for this article.

“Dupilumab has become such an important first-line systemic medication for our patients with moderate to severe atopic dermatitis. It’s important for us to understand everything we can about its use in the real world – both good and bad,”Raj Chovatiya, MD, PhD, MSCI, assistant professor of dermatology at Northwestern University, Chicago, said in an interview. He was uninvolved with either publication.

Robert Sidbury, MD, MPH, added that, although the affected patient group was small, studying lymphoid reactions associated with dupilumab is important because of the risk for diagnostic misadventure that these reactions carry. He is a professor of pediatrics and division head of dermatology at Seattle Children’s Hospital and the University of Washington, Seattle.

“AD and MF are easily confused for one another at baseline,” explained Dr. Sidbury, who was not involved with the study or editorial. “Dupilumab is known to make AD better and theoretically could help MF via its effect on interleukin (IL)–13, yet case reports of exacerbation and/or unmasking of MF are out there.”

For the study, researchers retrospectively examined records of 530 patients with AD treated with dupilumab at the University Medical Center Utrecht (the Netherlands). Reviewing pretreatment biopsies revealed that among 14 (2.6%) patients who developed clinical suspicion of cutaneous T-cell lymphoma (CTCL) while on treatment, three actually had preexisting MF.

All 14 patients with LR initially responded to dupilumab then developed worsening symptoms at a median of 4 months. Patients reported that the worsening lesions looked and felt different than did previous lesions, with symptoms including burning/pain and an appearance of generalized erythematous maculopapular plaques, sometimes with severe lichenification, on the lower trunk and upper thighs.

The 14 patients’ posttreatment biopsies showed an atypical lymphoid infiltrate with lichenoid or perivascular distribution and intraepithelial T-cell lymphocytes. Whereas patients with MF had hyperconvoluted cerebriform lymphocytes aligned in the epidermal basal layer at the dermoepidermal junction, the 11 with LR had similar-looking lesions dispersed throughout the upper epidermis.

Immunohistochemically, both groups had a dysregulated (mostly increased) CD4:CD8 ratio. CD30 overexpression, usually absent in early-stage MF, affected only patients with LR and one patient with advanced MF. In addition, patients with LR maintained pan–T-cell antigens (CD2, CD3, and CD5), whereas those with MF did not. The 11 patients with LR experienced biopsy-confirmed resolution once they discontinued dupilumab.

It is reassuring that the LRs resolved after dupilumab discontinuation, writes the author of the accompanying editorial, Joan Guitart, MD, chief of dermatopathology at Northwestern University. Nevertheless, he added, such patients deserve “a comprehensive workup including skin biopsy with T-cell receptor clonality assay, blood cell counts with flow cytometry analysis, serum lactate dehydrogenase, and documentation of possible adenopathy, followed with imaging studies and/or local biopsies in cases with abnormal results.”

The possibility that these LRs may represent a first step toward lymphoma requires dermatologists to remain vigilant in ruling out MF, Dr. Guitart wrote, particularly in atypical presentations such as adult-onset AD, cases lacking a history of AD, and cases involving erythrodermic and other uncharacteristic presentations such as plaques, nodules, or spared flexural sites.

For dermatopathologists, Dr. Guitart recommended a cautious approach that resists overdiagnosing MF and acknowledging that insufficient evidence exists to report such reactions as benign. The fact that one study patient had both MF and LR raises concerns that the LR may not always be reversible, Dr. Guitart added.

Clinicians and patients must consider the possibility of dupilumab-induced LR as part of the shared decision-making process and risk-benefit calculus, Dr. Sidbury said. In cases involving unexpected responses or atypical presentations, he added, clinicians must have a low threshold for stopping dupilumab.

For patients who must discontinue dupilumab because of LR, the list of treatment options is growing. “While more investigation is required to understand the role of newer IL-13–blocking biologics and JAK inhibitors among patients experiencing lymphoid reactions,” said Dr. Chovatiya, “traditional atopic dermatitis therapies like narrowband UVB phototherapy and the oral immunosuppressant methotrexate may be reassuring in this population.” Conversely, cyclosporine has been associated with progression of MF.

Also reassuring, said Dr. Sidbury and Dr. Chovatiya, is the rarity of LR overall. Dr. Sidbury said, “The numbers of patients in whom LR or onset/exacerbation of MF occurs is extraordinarily low when compared to those helped immeasurably by dupilumab.”

Dr. Sidbury added that the study and accompanying editorial also will alert clinicians to the potential for newer AD biologics that target solely IL-13 and not IL-4/13, as dupilumab does. “If the deregulated response leading to LR and potentially MF in the affected few is driven by IL-4 inhibition,” he said, “drugs such as tralokinumab (Adbry), lebrikizumab (once approved), and perhaps other newer options might calm AD without causing LRs.”

(Lebrikizumab is not yet approved. In an Oct. 2 press release, Eli Lilly and Company, developer of lebrikizumab, said that it would address issues the U.S. Food and Drug Administration had raised about a third-party manufacturing facility that arose during evaluation of the lebrikizumab biologic license application.)

Study limitations include the fact that most patients who experienced LR had already undergone skin biopsies before dupilumab treatment, which suggests that they had a more atypical AD presentation from the start. The authors add that their having treated all study patients in a tertiary referral hospital indicates a hard-to-treat AD subpopulation.

Study authors reported relationships with several biologic drug manufacturers including Sanofi and Regeneron (dupilumab), LEO Pharma (tralokinumab), and Eli Lilly (lebrikizumab). However, none of these companies provided support for the study.

Dr. Sidbury has been an investigator for Regeneron, Pfizer, and Galderma and a consultant for LEO Pharma and Eli Lilly. Dr. Chovatiya has served as an advisor, consultant, speaker, and investigator for Sanofi and Regeneron. Dr. Guitart reported no conflicts of interest.

A version of this article appeared on Medscape.com.

For some patients with atopic dermatitis (AD), dupilumab treatment can cause a benign reversible lymphoid reaction (LR) that mimics mycosis fungoides (MF) but differs histologically, according to a study published in JAMA Dermatology

The potential for such reactions requires diagnosing AD carefully, monitoring patients on dupilumab for new and unusual symptoms, and thoroughly working up suspicious LRs, according to an accompanying editorial and experts interviewed for this article.

“Dupilumab has become such an important first-line systemic medication for our patients with moderate to severe atopic dermatitis. It’s important for us to understand everything we can about its use in the real world – both good and bad,”Raj Chovatiya, MD, PhD, MSCI, assistant professor of dermatology at Northwestern University, Chicago, said in an interview. He was uninvolved with either publication.

Robert Sidbury, MD, MPH, added that, although the affected patient group was small, studying lymphoid reactions associated with dupilumab is important because of the risk for diagnostic misadventure that these reactions carry. He is a professor of pediatrics and division head of dermatology at Seattle Children’s Hospital and the University of Washington, Seattle.

“AD and MF are easily confused for one another at baseline,” explained Dr. Sidbury, who was not involved with the study or editorial. “Dupilumab is known to make AD better and theoretically could help MF via its effect on interleukin (IL)–13, yet case reports of exacerbation and/or unmasking of MF are out there.”

For the study, researchers retrospectively examined records of 530 patients with AD treated with dupilumab at the University Medical Center Utrecht (the Netherlands). Reviewing pretreatment biopsies revealed that among 14 (2.6%) patients who developed clinical suspicion of cutaneous T-cell lymphoma (CTCL) while on treatment, three actually had preexisting MF.

All 14 patients with LR initially responded to dupilumab then developed worsening symptoms at a median of 4 months. Patients reported that the worsening lesions looked and felt different than did previous lesions, with symptoms including burning/pain and an appearance of generalized erythematous maculopapular plaques, sometimes with severe lichenification, on the lower trunk and upper thighs.

The 14 patients’ posttreatment biopsies showed an atypical lymphoid infiltrate with lichenoid or perivascular distribution and intraepithelial T-cell lymphocytes. Whereas patients with MF had hyperconvoluted cerebriform lymphocytes aligned in the epidermal basal layer at the dermoepidermal junction, the 11 with LR had similar-looking lesions dispersed throughout the upper epidermis.

Immunohistochemically, both groups had a dysregulated (mostly increased) CD4:CD8 ratio. CD30 overexpression, usually absent in early-stage MF, affected only patients with LR and one patient with advanced MF. In addition, patients with LR maintained pan–T-cell antigens (CD2, CD3, and CD5), whereas those with MF did not. The 11 patients with LR experienced biopsy-confirmed resolution once they discontinued dupilumab.

It is reassuring that the LRs resolved after dupilumab discontinuation, writes the author of the accompanying editorial, Joan Guitart, MD, chief of dermatopathology at Northwestern University. Nevertheless, he added, such patients deserve “a comprehensive workup including skin biopsy with T-cell receptor clonality assay, blood cell counts with flow cytometry analysis, serum lactate dehydrogenase, and documentation of possible adenopathy, followed with imaging studies and/or local biopsies in cases with abnormal results.”

The possibility that these LRs may represent a first step toward lymphoma requires dermatologists to remain vigilant in ruling out MF, Dr. Guitart wrote, particularly in atypical presentations such as adult-onset AD, cases lacking a history of AD, and cases involving erythrodermic and other uncharacteristic presentations such as plaques, nodules, or spared flexural sites.

For dermatopathologists, Dr. Guitart recommended a cautious approach that resists overdiagnosing MF and acknowledging that insufficient evidence exists to report such reactions as benign. The fact that one study patient had both MF and LR raises concerns that the LR may not always be reversible, Dr. Guitart added.

Clinicians and patients must consider the possibility of dupilumab-induced LR as part of the shared decision-making process and risk-benefit calculus, Dr. Sidbury said. In cases involving unexpected responses or atypical presentations, he added, clinicians must have a low threshold for stopping dupilumab.

For patients who must discontinue dupilumab because of LR, the list of treatment options is growing. “While more investigation is required to understand the role of newer IL-13–blocking biologics and JAK inhibitors among patients experiencing lymphoid reactions,” said Dr. Chovatiya, “traditional atopic dermatitis therapies like narrowband UVB phototherapy and the oral immunosuppressant methotrexate may be reassuring in this population.” Conversely, cyclosporine has been associated with progression of MF.

Also reassuring, said Dr. Sidbury and Dr. Chovatiya, is the rarity of LR overall. Dr. Sidbury said, “The numbers of patients in whom LR or onset/exacerbation of MF occurs is extraordinarily low when compared to those helped immeasurably by dupilumab.”

Dr. Sidbury added that the study and accompanying editorial also will alert clinicians to the potential for newer AD biologics that target solely IL-13 and not IL-4/13, as dupilumab does. “If the deregulated response leading to LR and potentially MF in the affected few is driven by IL-4 inhibition,” he said, “drugs such as tralokinumab (Adbry), lebrikizumab (once approved), and perhaps other newer options might calm AD without causing LRs.”

(Lebrikizumab is not yet approved. In an Oct. 2 press release, Eli Lilly and Company, developer of lebrikizumab, said that it would address issues the U.S. Food and Drug Administration had raised about a third-party manufacturing facility that arose during evaluation of the lebrikizumab biologic license application.)

Study limitations include the fact that most patients who experienced LR had already undergone skin biopsies before dupilumab treatment, which suggests that they had a more atypical AD presentation from the start. The authors add that their having treated all study patients in a tertiary referral hospital indicates a hard-to-treat AD subpopulation.

Study authors reported relationships with several biologic drug manufacturers including Sanofi and Regeneron (dupilumab), LEO Pharma (tralokinumab), and Eli Lilly (lebrikizumab). However, none of these companies provided support for the study.

Dr. Sidbury has been an investigator for Regeneron, Pfizer, and Galderma and a consultant for LEO Pharma and Eli Lilly. Dr. Chovatiya has served as an advisor, consultant, speaker, and investigator for Sanofi and Regeneron. Dr. Guitart reported no conflicts of interest.

A version of this article appeared on Medscape.com.

For some patients with atopic dermatitis (AD), dupilumab treatment can cause a benign reversible lymphoid reaction (LR) that mimics mycosis fungoides (MF) but differs histologically, according to a study published in JAMA Dermatology

The potential for such reactions requires diagnosing AD carefully, monitoring patients on dupilumab for new and unusual symptoms, and thoroughly working up suspicious LRs, according to an accompanying editorial and experts interviewed for this article.

“Dupilumab has become such an important first-line systemic medication for our patients with moderate to severe atopic dermatitis. It’s important for us to understand everything we can about its use in the real world – both good and bad,”Raj Chovatiya, MD, PhD, MSCI, assistant professor of dermatology at Northwestern University, Chicago, said in an interview. He was uninvolved with either publication.

Robert Sidbury, MD, MPH, added that, although the affected patient group was small, studying lymphoid reactions associated with dupilumab is important because of the risk for diagnostic misadventure that these reactions carry. He is a professor of pediatrics and division head of dermatology at Seattle Children’s Hospital and the University of Washington, Seattle.

“AD and MF are easily confused for one another at baseline,” explained Dr. Sidbury, who was not involved with the study or editorial. “Dupilumab is known to make AD better and theoretically could help MF via its effect on interleukin (IL)–13, yet case reports of exacerbation and/or unmasking of MF are out there.”

For the study, researchers retrospectively examined records of 530 patients with AD treated with dupilumab at the University Medical Center Utrecht (the Netherlands). Reviewing pretreatment biopsies revealed that among 14 (2.6%) patients who developed clinical suspicion of cutaneous T-cell lymphoma (CTCL) while on treatment, three actually had preexisting MF.

All 14 patients with LR initially responded to dupilumab then developed worsening symptoms at a median of 4 months. Patients reported that the worsening lesions looked and felt different than did previous lesions, with symptoms including burning/pain and an appearance of generalized erythematous maculopapular plaques, sometimes with severe lichenification, on the lower trunk and upper thighs.

The 14 patients’ posttreatment biopsies showed an atypical lymphoid infiltrate with lichenoid or perivascular distribution and intraepithelial T-cell lymphocytes. Whereas patients with MF had hyperconvoluted cerebriform lymphocytes aligned in the epidermal basal layer at the dermoepidermal junction, the 11 with LR had similar-looking lesions dispersed throughout the upper epidermis.

Immunohistochemically, both groups had a dysregulated (mostly increased) CD4:CD8 ratio. CD30 overexpression, usually absent in early-stage MF, affected only patients with LR and one patient with advanced MF. In addition, patients with LR maintained pan–T-cell antigens (CD2, CD3, and CD5), whereas those with MF did not. The 11 patients with LR experienced biopsy-confirmed resolution once they discontinued dupilumab.

It is reassuring that the LRs resolved after dupilumab discontinuation, writes the author of the accompanying editorial, Joan Guitart, MD, chief of dermatopathology at Northwestern University. Nevertheless, he added, such patients deserve “a comprehensive workup including skin biopsy with T-cell receptor clonality assay, blood cell counts with flow cytometry analysis, serum lactate dehydrogenase, and documentation of possible adenopathy, followed with imaging studies and/or local biopsies in cases with abnormal results.”

The possibility that these LRs may represent a first step toward lymphoma requires dermatologists to remain vigilant in ruling out MF, Dr. Guitart wrote, particularly in atypical presentations such as adult-onset AD, cases lacking a history of AD, and cases involving erythrodermic and other uncharacteristic presentations such as plaques, nodules, or spared flexural sites.

For dermatopathologists, Dr. Guitart recommended a cautious approach that resists overdiagnosing MF and acknowledging that insufficient evidence exists to report such reactions as benign. The fact that one study patient had both MF and LR raises concerns that the LR may not always be reversible, Dr. Guitart added.

Clinicians and patients must consider the possibility of dupilumab-induced LR as part of the shared decision-making process and risk-benefit calculus, Dr. Sidbury said. In cases involving unexpected responses or atypical presentations, he added, clinicians must have a low threshold for stopping dupilumab.

For patients who must discontinue dupilumab because of LR, the list of treatment options is growing. “While more investigation is required to understand the role of newer IL-13–blocking biologics and JAK inhibitors among patients experiencing lymphoid reactions,” said Dr. Chovatiya, “traditional atopic dermatitis therapies like narrowband UVB phototherapy and the oral immunosuppressant methotrexate may be reassuring in this population.” Conversely, cyclosporine has been associated with progression of MF.

Also reassuring, said Dr. Sidbury and Dr. Chovatiya, is the rarity of LR overall. Dr. Sidbury said, “The numbers of patients in whom LR or onset/exacerbation of MF occurs is extraordinarily low when compared to those helped immeasurably by dupilumab.”

Dr. Sidbury added that the study and accompanying editorial also will alert clinicians to the potential for newer AD biologics that target solely IL-13 and not IL-4/13, as dupilumab does. “If the deregulated response leading to LR and potentially MF in the affected few is driven by IL-4 inhibition,” he said, “drugs such as tralokinumab (Adbry), lebrikizumab (once approved), and perhaps other newer options might calm AD without causing LRs.”

(Lebrikizumab is not yet approved. In an Oct. 2 press release, Eli Lilly and Company, developer of lebrikizumab, said that it would address issues the U.S. Food and Drug Administration had raised about a third-party manufacturing facility that arose during evaluation of the lebrikizumab biologic license application.)

Study limitations include the fact that most patients who experienced LR had already undergone skin biopsies before dupilumab treatment, which suggests that they had a more atypical AD presentation from the start. The authors add that their having treated all study patients in a tertiary referral hospital indicates a hard-to-treat AD subpopulation.

Study authors reported relationships with several biologic drug manufacturers including Sanofi and Regeneron (dupilumab), LEO Pharma (tralokinumab), and Eli Lilly (lebrikizumab). However, none of these companies provided support for the study.

Dr. Sidbury has been an investigator for Regeneron, Pfizer, and Galderma and a consultant for LEO Pharma and Eli Lilly. Dr. Chovatiya has served as an advisor, consultant, speaker, and investigator for Sanofi and Regeneron. Dr. Guitart reported no conflicts of interest.

A version of this article appeared on Medscape.com.