As inclisiran, a first-in-class LDL-cholesterol lowering drug, enters the U.S. market following Food and Drug Administration approval in December 2021, several issues muddy how popular inclisiran will be in actual practice. That’s despite stellar phase 3 trial evidence for safety, tolerability, and a potent lipid-lowering effect.

The active ingredient of inclisiran (Leqvio) is a small interfering RNA (siRNA) molecule that shuts down production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein, an enzyme that’s made and functions primarily in the liver and degrades cellular receptors for LDL cholesterol. Inhibiting PCSK9 production means LDL-cholesterol receptors accumulate and boost the ability of liver cells to pull more LDL cholesterol out of blood.

PCSK9 inhibition is the most potent LDL-cholesterol lowering method now available, and it works well in patients who have maxed out LDL reduction by diet and statin treatment. The siRNA of inclisiran is tweaked to target the molecule to the surface of liver cells following subcutaneous injection. Other modifications of the siRNA give it stability that allows twice-a-year dosing, although patients receive a third injection during their first year to hasten a maximum treatment effect.

Inclisiran’s FDA approval relied on results from three pivotal trials that together enrolled 3,660 patients with either atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalents, or heterozygous familial hypercholesterolemia (HeFH), and LDL-cholesterol levels of at least 70 mg/dL in those with established ASCVD, or at least 100 mg/dL in other patients. (HeFH and ASCVD are the drug’s approved indications.) Pooled data from the three trials showed that inclisiran was safe and well tolerated during 18 months and produced an average LDL-cholesterol reduction after 510 days (1.4 years) of about 51% compared to baseline after correction for placebo effects (J Am Coll Cardiol. 2021 Mar 9;77 [9]:1182-93).

These data showed inclisiran was about as safe and effective for reducing LDL-cholesterol as agents from another class of PCSK9 inhibitors that rely on injected antibodies to inactivate PCSK9. Two agents from this class, alirocumab (Praluent) and evolocumab (Repatha), both came on the U.S. market in 2015. Although their performance in routine practice during the ensuing 6-plus years has been as safe and effective as what they showed in their respective registration trials, they have faced a rocky uptake road that’s been primarily hindered by the hefty price tag that both drugs carry.
 

Prior-authorization blues

When they first came out, evolocumab and alirocumab were burdened by annual drug costs of roughly $14,000, a fact that led to widespread prior-authorization and copay barriers set up by U.S. insurers. Although these barriers gradually lessened over time, in part aided by a substantial price cut for both drugs that led to annual drug costs more in the range of $6,000/year, they remain relatively pricey and are still not easy to start in patients because of prior-authorization requirements, said clinicians.

Recent penetration of the older PCSK9 inhibitors into eligible U.S. patients “is only about 1%-2%, based on the latest data,” said Michael H. Davidson, MD, a lipid specialist and director of Preventive Cardiology at the University of Chicago.

“We have these great, effective drugs, but they haven’t really made an impact over the past 5 years,” because of very limited uptake, a situation Dr. Davidson called “very disappointing,” during an interview.

Given this recent history, inclisiran, another expensive PCSK9 inhibitor, may face similar coverage pushback as it hits the U.S. market with a retail price, announced by its manufacturer Novartis, of $3,250/dose. This means that patients who start the drug and receive their initial dose, a second dose after 3 months, and then additional doses every 6 months, rack up a drug cost of close to $10,000 the first year on the drug and $6,500 each subsequent year.

This treatment schedule highlights the major logistical difference that distinguishes inclisiran from the antibody-based PCSK9 inhibitors, which are given by repeated subcutaneous injection every 2 or 4 weeks, usually with patients self-injecting the drugs at home. The less-frequent dosing schedule for inclisiran prompted the drug’s developers to schedule injections by a clinician in an office setting in the pivotal trials, which led to labeling for inclisiran that specifies administration only by a health care professional.
 

The ‘buy-and-bill’ coverage model

This difference in drug administration between inclisiran and the antibody-based PCSK9 inhibitors set up Novartis to promote insurance reimbursement for inclisiran using a “buy-and-bill” paradigm that was first developed for oncology drugs and which may provide a loophole around the prior-authorization roadblocks that hindered early uptake of the antibody-based PCSK9 inhibitors.

It’s also an approach that has made U.S. clinicians unsure how it will play out in practice. Infrequent inclisiran dosing may also boost patient compliance.

“Adherence is the greatest challenge in preventive cardiology, and thus inclisiran has the potential to be a game changer,” commented Christie M. Ballantyne, MD, professor and chief of cardiology at Baylor College of Medicine, Houston.

“Will it be easier for physicians to write a prescription and for patients to get the medication without a demanding and frustrating prior-authorization process?” he wondered during an interview. “I’m waiting to see how this unfolds, especially in systems where pharmacy is not fully integrated with the outpatient setting. In some ways, this is as big of an experiment as was development of the drug,” Dr. Ballantyne said.

Although the prior-authorization hoops for evolocumab and alirocumab have become easier to jump through, “most physicians don’t have the resources to handle it and don’t bother,” noted Dr. Davidson, and he’s concerned that infrastructure challenges will also hamper the buy-and-bill strategy for inclisiran.

He also expressed skepticism that the prior-authorization barrier will disappear. “Payers don’t want to open a large population to a very expensive drug without some gatekeeping,” he said, while acknowledging that in late January 2022 he did not yet have personal experience administering inclisiran or navigating its insurance reimbursement.
 

Boosting patient compliance

Dr. Davidson agreed that the prospect for enhanced patient compliance with inclisiran was intriguing and had already drawn the interest of some of his patients.

“There is a lot of appeal” to a treatment that’s only given once every 6 months, he said. “Compliance is a major issue, and this is less work for patients.”

“The biggest possible attraction of inclisiran is that it is given twice a year, but whether this plays out as anticipated in the real world need to be seen,” cautioned Vijay Nambi, MD, a cardiologist at the Michael E. DeBakey VA Hospital, Houston, and at Baylor College of Medicine who has written about inclisiran. He noted that while two doses a year is “on paper very attractive,” this scheme opens the door to missed or delayed appointments because of vacations, other patient travel, or events like a pandemic.

“The biggest pro for inclisiran is the dosing schedule,” said Chandni Bardolia, PharmD, a drug information specialist at Tabula Rasa Healthcare, Moorestown, N.J., who has analyzed and written about inclisiran and other lipid-lowering medications. “Twice yearly dosing following initiation will be a huge benefit to improve adherence and reduce the number of injections.”

However, inclisiran’s attractive dosing schedule as well as its safety and potent efficacy do not tell the whole story, she highlighted in an interview.

Inclisiran’s clinical evidence still cooking

“I see inclisiran as a last-line drug, mainly because the current alternatives have more safety and efficacy data,” Dr. Bardolia said.

Inclisiran’s “cost and the fact that there are other agents with clinical outcome data already available [alirocumab and evolocumab] means inclisiran is not a first-line agent after statins,” agreed Dr. Nambi.

The FDA based its inclisiran approval entirely on the drug’s demonstrated safety and LDL-lowering efficacy. The cardiovascular outcomes trial for inclisiran, ORION-4, with about 15,000 enrolled patients, started in 2018 and remains in progress with full results expected in 2026.

The lack of clinical outcomes data for inclisiran is a major limitation, said Neil J. Stone, MD, a cardiologist and professor at Northwestern University, Chicago, and vice chair of the panel that wrote the most recent cholesterol guideline for the American College of Cardiology and American Heart Association.

“My greatest concern is the lack of outcome trial data. That’s very important,” Dr. Stone said in an interview.

But others minimize this limitation given the overwhelming evidence that links lower levels of LDL-cholesterol to reduced clinical events.

Most clinicians “support lower LDL as a surrogate” for reduced clinical events, “just like blood pressure and hemoglobin A1c,” noted Dr. Davidson, although he conceded that a “substantial minority wants to wait to see inclisiran’s outcome benefits.”
 

It’s all about price

While opinions are mixed on the need for clinical outcomes data, experts are more uniform in seeing drug prices that run to several thousands per year as the main uptake issue.

“We need to look at the cost-efficacy with inclisiran, and we need benefit data to determine this,” said Dr. Stone.

“Outcomes data are central to characterizing value. I imagine that costs will impact adoption and dissemination” of inclisiran, commented Paul L. Hess, MD, a cardiologist at the Rocky Mountain Regional VA Medical Center, Denver.

Patient interest in less frequent dosing will be important for driving use, but “ultimately cost will be the most important driving factor,” for inclisiran uptake, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado School of Medicine, Aurora.

Dr. Davidson has ties to New Amsterdam Pharma and Amgen, which markets evolocumab (Repatha). Dr. Ballantyne is a consultant to numerous companies, including Amgen and Regeneron, which market alirocumab (Praluent). Dr. Nambi has been a site investigator for studies sponsored by Amgen, and by Merck, which markets the LDL-cholesterol drug ezetimibe (Zetia) and is developing an oral PCSK9 inhibitor (he said that the views he expressed are his own and don’t represent that of the department of Veterans Affairs or Baylor.) Dr. Bardolia had no disclosures beyond her employment at Tabula Rasa Healthcare. Dr. Stone, Dr. Hess, and Dr. Eckel had no relevant disclosures.


 

As inclisiran, a first-in-class LDL-cholesterol lowering drug, enters the U.S. market following Food and Drug Administration approval in December 2021, several issues muddy how popular inclisiran will be in actual practice. That’s despite stellar phase 3 trial evidence for safety, tolerability, and a potent lipid-lowering effect.

The active ingredient of inclisiran (Leqvio) is a small interfering RNA (siRNA) molecule that shuts down production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein, an enzyme that’s made and functions primarily in the liver and degrades cellular receptors for LDL cholesterol. Inhibiting PCSK9 production means LDL-cholesterol receptors accumulate and boost the ability of liver cells to pull more LDL cholesterol out of blood.

PCSK9 inhibition is the most potent LDL-cholesterol lowering method now available, and it works well in patients who have maxed out LDL reduction by diet and statin treatment. The siRNA of inclisiran is tweaked to target the molecule to the surface of liver cells following subcutaneous injection. Other modifications of the siRNA give it stability that allows twice-a-year dosing, although patients receive a third injection during their first year to hasten a maximum treatment effect.

Inclisiran’s FDA approval relied on results from three pivotal trials that together enrolled 3,660 patients with either atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalents, or heterozygous familial hypercholesterolemia (HeFH), and LDL-cholesterol levels of at least 70 mg/dL in those with established ASCVD, or at least 100 mg/dL in other patients. (HeFH and ASCVD are the drug’s approved indications.) Pooled data from the three trials showed that inclisiran was safe and well tolerated during 18 months and produced an average LDL-cholesterol reduction after 510 days (1.4 years) of about 51% compared to baseline after correction for placebo effects (J Am Coll Cardiol. 2021 Mar 9;77 [9]:1182-93).

These data showed inclisiran was about as safe and effective for reducing LDL-cholesterol as agents from another class of PCSK9 inhibitors that rely on injected antibodies to inactivate PCSK9. Two agents from this class, alirocumab (Praluent) and evolocumab (Repatha), both came on the U.S. market in 2015. Although their performance in routine practice during the ensuing 6-plus years has been as safe and effective as what they showed in their respective registration trials, they have faced a rocky uptake road that’s been primarily hindered by the hefty price tag that both drugs carry.
 

Prior-authorization blues

When they first came out, evolocumab and alirocumab were burdened by annual drug costs of roughly $14,000, a fact that led to widespread prior-authorization and copay barriers set up by U.S. insurers. Although these barriers gradually lessened over time, in part aided by a substantial price cut for both drugs that led to annual drug costs more in the range of $6,000/year, they remain relatively pricey and are still not easy to start in patients because of prior-authorization requirements, said clinicians.

Recent penetration of the older PCSK9 inhibitors into eligible U.S. patients “is only about 1%-2%, based on the latest data,” said Michael H. Davidson, MD, a lipid specialist and director of Preventive Cardiology at the University of Chicago.

“We have these great, effective drugs, but they haven’t really made an impact over the past 5 years,” because of very limited uptake, a situation Dr. Davidson called “very disappointing,” during an interview.

Given this recent history, inclisiran, another expensive PCSK9 inhibitor, may face similar coverage pushback as it hits the U.S. market with a retail price, announced by its manufacturer Novartis, of $3,250/dose. This means that patients who start the drug and receive their initial dose, a second dose after 3 months, and then additional doses every 6 months, rack up a drug cost of close to $10,000 the first year on the drug and $6,500 each subsequent year.

This treatment schedule highlights the major logistical difference that distinguishes inclisiran from the antibody-based PCSK9 inhibitors, which are given by repeated subcutaneous injection every 2 or 4 weeks, usually with patients self-injecting the drugs at home. The less-frequent dosing schedule for inclisiran prompted the drug’s developers to schedule injections by a clinician in an office setting in the pivotal trials, which led to labeling for inclisiran that specifies administration only by a health care professional.
 

The ‘buy-and-bill’ coverage model

This difference in drug administration between inclisiran and the antibody-based PCSK9 inhibitors set up Novartis to promote insurance reimbursement for inclisiran using a “buy-and-bill” paradigm that was first developed for oncology drugs and which may provide a loophole around the prior-authorization roadblocks that hindered early uptake of the antibody-based PCSK9 inhibitors.

It’s also an approach that has made U.S. clinicians unsure how it will play out in practice. Infrequent inclisiran dosing may also boost patient compliance.

“Adherence is the greatest challenge in preventive cardiology, and thus inclisiran has the potential to be a game changer,” commented Christie M. Ballantyne, MD, professor and chief of cardiology at Baylor College of Medicine, Houston.

“Will it be easier for physicians to write a prescription and for patients to get the medication without a demanding and frustrating prior-authorization process?” he wondered during an interview. “I’m waiting to see how this unfolds, especially in systems where pharmacy is not fully integrated with the outpatient setting. In some ways, this is as big of an experiment as was development of the drug,” Dr. Ballantyne said.

Although the prior-authorization hoops for evolocumab and alirocumab have become easier to jump through, “most physicians don’t have the resources to handle it and don’t bother,” noted Dr. Davidson, and he’s concerned that infrastructure challenges will also hamper the buy-and-bill strategy for inclisiran.

He also expressed skepticism that the prior-authorization barrier will disappear. “Payers don’t want to open a large population to a very expensive drug without some gatekeeping,” he said, while acknowledging that in late January 2022 he did not yet have personal experience administering inclisiran or navigating its insurance reimbursement.
 

Boosting patient compliance

Dr. Davidson agreed that the prospect for enhanced patient compliance with inclisiran was intriguing and had already drawn the interest of some of his patients.

“There is a lot of appeal” to a treatment that’s only given once every 6 months, he said. “Compliance is a major issue, and this is less work for patients.”

“The biggest possible attraction of inclisiran is that it is given twice a year, but whether this plays out as anticipated in the real world need to be seen,” cautioned Vijay Nambi, MD, a cardiologist at the Michael E. DeBakey VA Hospital, Houston, and at Baylor College of Medicine who has written about inclisiran. He noted that while two doses a year is “on paper very attractive,” this scheme opens the door to missed or delayed appointments because of vacations, other patient travel, or events like a pandemic.

“The biggest pro for inclisiran is the dosing schedule,” said Chandni Bardolia, PharmD, a drug information specialist at Tabula Rasa Healthcare, Moorestown, N.J., who has analyzed and written about inclisiran and other lipid-lowering medications. “Twice yearly dosing following initiation will be a huge benefit to improve adherence and reduce the number of injections.”

However, inclisiran’s attractive dosing schedule as well as its safety and potent efficacy do not tell the whole story, she highlighted in an interview.

Inclisiran’s clinical evidence still cooking

“I see inclisiran as a last-line drug, mainly because the current alternatives have more safety and efficacy data,” Dr. Bardolia said.

Inclisiran’s “cost and the fact that there are other agents with clinical outcome data already available [alirocumab and evolocumab] means inclisiran is not a first-line agent after statins,” agreed Dr. Nambi.

The FDA based its inclisiran approval entirely on the drug’s demonstrated safety and LDL-lowering efficacy. The cardiovascular outcomes trial for inclisiran, ORION-4, with about 15,000 enrolled patients, started in 2018 and remains in progress with full results expected in 2026.

The lack of clinical outcomes data for inclisiran is a major limitation, said Neil J. Stone, MD, a cardiologist and professor at Northwestern University, Chicago, and vice chair of the panel that wrote the most recent cholesterol guideline for the American College of Cardiology and American Heart Association.

“My greatest concern is the lack of outcome trial data. That’s very important,” Dr. Stone said in an interview.

But others minimize this limitation given the overwhelming evidence that links lower levels of LDL-cholesterol to reduced clinical events.

Most clinicians “support lower LDL as a surrogate” for reduced clinical events, “just like blood pressure and hemoglobin A1c,” noted Dr. Davidson, although he conceded that a “substantial minority wants to wait to see inclisiran’s outcome benefits.”
 

It’s all about price

While opinions are mixed on the need for clinical outcomes data, experts are more uniform in seeing drug prices that run to several thousands per year as the main uptake issue.

“We need to look at the cost-efficacy with inclisiran, and we need benefit data to determine this,” said Dr. Stone.

“Outcomes data are central to characterizing value. I imagine that costs will impact adoption and dissemination” of inclisiran, commented Paul L. Hess, MD, a cardiologist at the Rocky Mountain Regional VA Medical Center, Denver.

Patient interest in less frequent dosing will be important for driving use, but “ultimately cost will be the most important driving factor,” for inclisiran uptake, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado School of Medicine, Aurora.

Dr. Davidson has ties to New Amsterdam Pharma and Amgen, which markets evolocumab (Repatha). Dr. Ballantyne is a consultant to numerous companies, including Amgen and Regeneron, which market alirocumab (Praluent). Dr. Nambi has been a site investigator for studies sponsored by Amgen, and by Merck, which markets the LDL-cholesterol drug ezetimibe (Zetia) and is developing an oral PCSK9 inhibitor (he said that the views he expressed are his own and don’t represent that of the department of Veterans Affairs or Baylor.) Dr. Bardolia had no disclosures beyond her employment at Tabula Rasa Healthcare. Dr. Stone, Dr. Hess, and Dr. Eckel had no relevant disclosures.


 

As inclisiran, a first-in-class LDL-cholesterol lowering drug, enters the U.S. market following Food and Drug Administration approval in December 2021, several issues muddy how popular inclisiran will be in actual practice. That’s despite stellar phase 3 trial evidence for safety, tolerability, and a potent lipid-lowering effect.

The active ingredient of inclisiran (Leqvio) is a small interfering RNA (siRNA) molecule that shuts down production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein, an enzyme that’s made and functions primarily in the liver and degrades cellular receptors for LDL cholesterol. Inhibiting PCSK9 production means LDL-cholesterol receptors accumulate and boost the ability of liver cells to pull more LDL cholesterol out of blood.

PCSK9 inhibition is the most potent LDL-cholesterol lowering method now available, and it works well in patients who have maxed out LDL reduction by diet and statin treatment. The siRNA of inclisiran is tweaked to target the molecule to the surface of liver cells following subcutaneous injection. Other modifications of the siRNA give it stability that allows twice-a-year dosing, although patients receive a third injection during their first year to hasten a maximum treatment effect.

Inclisiran’s FDA approval relied on results from three pivotal trials that together enrolled 3,660 patients with either atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalents, or heterozygous familial hypercholesterolemia (HeFH), and LDL-cholesterol levels of at least 70 mg/dL in those with established ASCVD, or at least 100 mg/dL in other patients. (HeFH and ASCVD are the drug’s approved indications.) Pooled data from the three trials showed that inclisiran was safe and well tolerated during 18 months and produced an average LDL-cholesterol reduction after 510 days (1.4 years) of about 51% compared to baseline after correction for placebo effects (J Am Coll Cardiol. 2021 Mar 9;77 [9]:1182-93).

These data showed inclisiran was about as safe and effective for reducing LDL-cholesterol as agents from another class of PCSK9 inhibitors that rely on injected antibodies to inactivate PCSK9. Two agents from this class, alirocumab (Praluent) and evolocumab (Repatha), both came on the U.S. market in 2015. Although their performance in routine practice during the ensuing 6-plus years has been as safe and effective as what they showed in their respective registration trials, they have faced a rocky uptake road that’s been primarily hindered by the hefty price tag that both drugs carry.
 

Prior-authorization blues

When they first came out, evolocumab and alirocumab were burdened by annual drug costs of roughly $14,000, a fact that led to widespread prior-authorization and copay barriers set up by U.S. insurers. Although these barriers gradually lessened over time, in part aided by a substantial price cut for both drugs that led to annual drug costs more in the range of $6,000/year, they remain relatively pricey and are still not easy to start in patients because of prior-authorization requirements, said clinicians.

Recent penetration of the older PCSK9 inhibitors into eligible U.S. patients “is only about 1%-2%, based on the latest data,” said Michael H. Davidson, MD, a lipid specialist and director of Preventive Cardiology at the University of Chicago.

“We have these great, effective drugs, but they haven’t really made an impact over the past 5 years,” because of very limited uptake, a situation Dr. Davidson called “very disappointing,” during an interview.

Given this recent history, inclisiran, another expensive PCSK9 inhibitor, may face similar coverage pushback as it hits the U.S. market with a retail price, announced by its manufacturer Novartis, of $3,250/dose. This means that patients who start the drug and receive their initial dose, a second dose after 3 months, and then additional doses every 6 months, rack up a drug cost of close to $10,000 the first year on the drug and $6,500 each subsequent year.

This treatment schedule highlights the major logistical difference that distinguishes inclisiran from the antibody-based PCSK9 inhibitors, which are given by repeated subcutaneous injection every 2 or 4 weeks, usually with patients self-injecting the drugs at home. The less-frequent dosing schedule for inclisiran prompted the drug’s developers to schedule injections by a clinician in an office setting in the pivotal trials, which led to labeling for inclisiran that specifies administration only by a health care professional.
 

The ‘buy-and-bill’ coverage model

This difference in drug administration between inclisiran and the antibody-based PCSK9 inhibitors set up Novartis to promote insurance reimbursement for inclisiran using a “buy-and-bill” paradigm that was first developed for oncology drugs and which may provide a loophole around the prior-authorization roadblocks that hindered early uptake of the antibody-based PCSK9 inhibitors.

It’s also an approach that has made U.S. clinicians unsure how it will play out in practice. Infrequent inclisiran dosing may also boost patient compliance.

“Adherence is the greatest challenge in preventive cardiology, and thus inclisiran has the potential to be a game changer,” commented Christie M. Ballantyne, MD, professor and chief of cardiology at Baylor College of Medicine, Houston.

“Will it be easier for physicians to write a prescription and for patients to get the medication without a demanding and frustrating prior-authorization process?” he wondered during an interview. “I’m waiting to see how this unfolds, especially in systems where pharmacy is not fully integrated with the outpatient setting. In some ways, this is as big of an experiment as was development of the drug,” Dr. Ballantyne said.

Although the prior-authorization hoops for evolocumab and alirocumab have become easier to jump through, “most physicians don’t have the resources to handle it and don’t bother,” noted Dr. Davidson, and he’s concerned that infrastructure challenges will also hamper the buy-and-bill strategy for inclisiran.

He also expressed skepticism that the prior-authorization barrier will disappear. “Payers don’t want to open a large population to a very expensive drug without some gatekeeping,” he said, while acknowledging that in late January 2022 he did not yet have personal experience administering inclisiran or navigating its insurance reimbursement.
 

Boosting patient compliance

Dr. Davidson agreed that the prospect for enhanced patient compliance with inclisiran was intriguing and had already drawn the interest of some of his patients.

“There is a lot of appeal” to a treatment that’s only given once every 6 months, he said. “Compliance is a major issue, and this is less work for patients.”

“The biggest possible attraction of inclisiran is that it is given twice a year, but whether this plays out as anticipated in the real world need to be seen,” cautioned Vijay Nambi, MD, a cardiologist at the Michael E. DeBakey VA Hospital, Houston, and at Baylor College of Medicine who has written about inclisiran. He noted that while two doses a year is “on paper very attractive,” this scheme opens the door to missed or delayed appointments because of vacations, other patient travel, or events like a pandemic.

“The biggest pro for inclisiran is the dosing schedule,” said Chandni Bardolia, PharmD, a drug information specialist at Tabula Rasa Healthcare, Moorestown, N.J., who has analyzed and written about inclisiran and other lipid-lowering medications. “Twice yearly dosing following initiation will be a huge benefit to improve adherence and reduce the number of injections.”

However, inclisiran’s attractive dosing schedule as well as its safety and potent efficacy do not tell the whole story, she highlighted in an interview.

Inclisiran’s clinical evidence still cooking

“I see inclisiran as a last-line drug, mainly because the current alternatives have more safety and efficacy data,” Dr. Bardolia said.

Inclisiran’s “cost and the fact that there are other agents with clinical outcome data already available [alirocumab and evolocumab] means inclisiran is not a first-line agent after statins,” agreed Dr. Nambi.

The FDA based its inclisiran approval entirely on the drug’s demonstrated safety and LDL-lowering efficacy. The cardiovascular outcomes trial for inclisiran, ORION-4, with about 15,000 enrolled patients, started in 2018 and remains in progress with full results expected in 2026.

The lack of clinical outcomes data for inclisiran is a major limitation, said Neil J. Stone, MD, a cardiologist and professor at Northwestern University, Chicago, and vice chair of the panel that wrote the most recent cholesterol guideline for the American College of Cardiology and American Heart Association.

“My greatest concern is the lack of outcome trial data. That’s very important,” Dr. Stone said in an interview.

But others minimize this limitation given the overwhelming evidence that links lower levels of LDL-cholesterol to reduced clinical events.

Most clinicians “support lower LDL as a surrogate” for reduced clinical events, “just like blood pressure and hemoglobin A1c,” noted Dr. Davidson, although he conceded that a “substantial minority wants to wait to see inclisiran’s outcome benefits.”
 

It’s all about price

While opinions are mixed on the need for clinical outcomes data, experts are more uniform in seeing drug prices that run to several thousands per year as the main uptake issue.

“We need to look at the cost-efficacy with inclisiran, and we need benefit data to determine this,” said Dr. Stone.

“Outcomes data are central to characterizing value. I imagine that costs will impact adoption and dissemination” of inclisiran, commented Paul L. Hess, MD, a cardiologist at the Rocky Mountain Regional VA Medical Center, Denver.

Patient interest in less frequent dosing will be important for driving use, but “ultimately cost will be the most important driving factor,” for inclisiran uptake, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado School of Medicine, Aurora.

Dr. Davidson has ties to New Amsterdam Pharma and Amgen, which markets evolocumab (Repatha). Dr. Ballantyne is a consultant to numerous companies, including Amgen and Regeneron, which market alirocumab (Praluent). Dr. Nambi has been a site investigator for studies sponsored by Amgen, and by Merck, which markets the LDL-cholesterol drug ezetimibe (Zetia) and is developing an oral PCSK9 inhibitor (he said that the views he expressed are his own and don’t represent that of the department of Veterans Affairs or Baylor.) Dr. Bardolia had no disclosures beyond her employment at Tabula Rasa Healthcare. Dr. Stone, Dr. Hess, and Dr. Eckel had no relevant disclosures.


 

A deep molecular dive into COVID-19 patients found that the presence of autoantibodies in peripheral blood at initial diagnosis was the chief of four risk factors predicting if a patient would experience long COVID.

Other significant early predictors of prolonged COVID symptoms – which the researchers called postacute sequelae – were having type 2 diabetes, SARS-CoV-2 RNAemia, and Epstein-Barr virus (EBV) viremia, Yapeng Su, PhD, of the Institute for Systems Biology (ISB) in Seattle, and colleagues wrote in Cell.

Having EBV viremia suggested that latent EBV has been reactivated, the authors noted.

“The most important postacute sequelae [that is conditions that are consequences of a disease] of COVID is the presence of autoantibodies,” James R. Heath, PhD, president of ISB and a bioengineering professor at the University of Washington, Seattle, said in an interview. “It’s about two times more important than the others.”

Dr. Heath and coauthors said early detection of this and other variables could prompt earlier aggressive treatment in patients susceptible to long COVID and ward off lingering symptoms.

“These predictive measures of long COVID can also help to better inform patients of their possible disease course,” study coauthor Daniel G. Chen, an undergraduate researcher at ISB, said in an interview. “We were also able to partially resolve the immunological underpinnings of some postacute sequelae of COVID in a way that suggested potential therapies, and the timing of those therapies.”

For example, he continued, the use of antivirals very early in the infectious course may mitigate the later development of long COVID. “This will, of course, have to be explored in an appropriately designed clinical trial.

“We also identified biomarkers of certain types of long COVID, such as neurological sequelae. Those biomarkers can help define the condition, which is a first step towards developing treatments.”

Study findings

With COVID patients monitored for 2 or 3 months, the study findings of the international “multiomic profiling” analysis include:

• Subclinical patient autoantibodies that reduce anti–SARS-CoV-2 antibodies suggest there is immune dysregulation during COVID-19 infection.
• Reactivation of latent other viruses during initial infection may be contributing to long COVID.
• Gastrointestinal postacute sequelae of COVID presents with a unique postacute expansion of cytotoxic T cells.
• SARS-CoV-2–specific and cytomegalovirus-specific CD8+ T cells displayed unique dynamics during recovery from infection.

According to the authors, as many as 69% of COVID-19 patients suffer from long COVID – a range of new, recurrent, or ongoing problems 4 or more weeks following initial SARS-CoV-2 infection. These may include memory loss, gastrointestinal distress, fatigue, anosmia, and shortness of breath.

Long COVID has been associated with acute disease severity, and is suspected to be related to autoimmune factors and unresolved viral fragments, according to the paper.
 

Research methods

The international study did a deep and detailed dive into multiple molecular markers of long COVID. It enrolled 209 COVID-19 patients with varying degrees of disease severity and matched them to 457 healthy controls. The researchers’ goal was to identify discrete and quantifiable long COVID factors and guide possible preemptive treatment. 

Patients were assessed at three time points: at initial diagnosis, during the acute disease phase about a week later, and again 2 to 3 months post onset of symptoms after recovery from the acute phase of COVID. At the third assessment, some patients had lingering symptoms such as fatigue (52% ), cough (25%), and loss of taste or sense of smell (18%).

Blood draws were analyzed for autoantibodies and SARS-CoV-2–specific antibodies, global plasma proteomic and metabolomic profiles, and single-cell multiomic characterizations of peripheral blood mononuclear cells.

Each blood draw was paired with nasal-swab and plasma measurements of SARS-CoV-2 viral load and the data sets were integrated with electronic health records and self-reported patient symptoms to guide the interpretation of the molecular signatures of long COVID.
 

Author conclusions

The authors found an association between T2 hyperinflammation and long COVID–anticipating autoantibodies. This association further implies that hyperinflammation-controlling therapies in the acute stage of COVID may influence whether a patient experiences long COVID. “However, the detailed timing and context of these therapies matter, and, thus, future well-controlled studies will be needed to test these and other therapeutic implications,” Dr. Su and colleagues wrote.

Moreover, the negative correlations between anti–SARS-CoV-2 IgG and certain autoantibodies may suggest that patients with elevated autoantibody levels are more susceptible to breakthrough infections, the authors said.

“Many patients with high autoantibodies simultaneously have low protective antibodies that neutralize SARS-CoV-2, and that’s going to make them more susceptible to breakthrough infections,” Mr. Chen explained.*

“Detectability of most [long COVID-19 factors] at COVID diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests [long COVID] treatment strategies,” they wrote.

According to Mr. Chen, there are clear similarities in underlying immunobiology between patients with COVID autoantibodies and patients with systemic lupus erythematosus.

“These findings are also helping us frame our thinking around other chronic autoimmune conditions, such as postacute Lyme syndrome, for example,” said Dr. Heath.

The bottom line, said Mr. Chen, is that measuring early long COVID indicators may result in preventive treatments. “An example is the cortisol deficiency we see in certain long COVID patients. There are known treatments such as cortisol replacement therapy that should be explored for this group.”

Outside expert’s take on findings

Commenting on the study, Sherry Hsiang-Yi Chou, MD, who was not involved in the research, called the study a very important first step in understanding the path of this complex phenomenon and perhaps other conditions with long-term side effects.

“The researchers have done huge amount of innovative scientific work. They’ve shown the DNA signature of how our bodies respond to this disease,” said Dr. Chou, who is chief of the division of neurocritical care at Northwestern Medicine in Chicago.

“This type of research will help us scientifically understand and differentiate the various syndromes within long COVID. It will help identify who’s at risk for different aspects of this syndrome and lead to following them for longer periods in clinical trials,” she added.

The authors acknowledged that lengthier studies in larger cohorts were needed to see which patients will develop long-term chronic postacute sequelae of COVID.

This research was supported by the Wilke Family Foundation, the Parker Institute for Cancer Immunotherapy, Merck, and the Biomedical Advanced Research and Development Authority. Other support came from the National Institutes of Health, the Bill and Melinda Gates Foundation, Saint John’s Cancer Center, Fred Hutchinson Cancer Research Center, and the European Union’s Horizon 2020 research and innovation program. Dr. Heath is a cofounder of Pact Pharma. He and several coauthors disclosed various ties to multiple private-sector companies. Mr. Chen and Dr. Chou had no competing interests.

*Correction, 1/28: An earlier version of this story misidentified Daniel G. Chen, an undergraduate researcher at ISB.

A deep molecular dive into COVID-19 patients found that the presence of autoantibodies in peripheral blood at initial diagnosis was the chief of four risk factors predicting if a patient would experience long COVID.

Other significant early predictors of prolonged COVID symptoms – which the researchers called postacute sequelae – were having type 2 diabetes, SARS-CoV-2 RNAemia, and Epstein-Barr virus (EBV) viremia, Yapeng Su, PhD, of the Institute for Systems Biology (ISB) in Seattle, and colleagues wrote in Cell.

Having EBV viremia suggested that latent EBV has been reactivated, the authors noted.

“The most important postacute sequelae [that is conditions that are consequences of a disease] of COVID is the presence of autoantibodies,” James R. Heath, PhD, president of ISB and a bioengineering professor at the University of Washington, Seattle, said in an interview. “It’s about two times more important than the others.”

Dr. Heath and coauthors said early detection of this and other variables could prompt earlier aggressive treatment in patients susceptible to long COVID and ward off lingering symptoms.

“These predictive measures of long COVID can also help to better inform patients of their possible disease course,” study coauthor Daniel G. Chen, an undergraduate researcher at ISB, said in an interview. “We were also able to partially resolve the immunological underpinnings of some postacute sequelae of COVID in a way that suggested potential therapies, and the timing of those therapies.”

For example, he continued, the use of antivirals very early in the infectious course may mitigate the later development of long COVID. “This will, of course, have to be explored in an appropriately designed clinical trial.

“We also identified biomarkers of certain types of long COVID, such as neurological sequelae. Those biomarkers can help define the condition, which is a first step towards developing treatments.”

Study findings

With COVID patients monitored for 2 or 3 months, the study findings of the international “multiomic profiling” analysis include:

• Subclinical patient autoantibodies that reduce anti–SARS-CoV-2 antibodies suggest there is immune dysregulation during COVID-19 infection.
• Reactivation of latent other viruses during initial infection may be contributing to long COVID.
• Gastrointestinal postacute sequelae of COVID presents with a unique postacute expansion of cytotoxic T cells.
• SARS-CoV-2–specific and cytomegalovirus-specific CD8+ T cells displayed unique dynamics during recovery from infection.

According to the authors, as many as 69% of COVID-19 patients suffer from long COVID – a range of new, recurrent, or ongoing problems 4 or more weeks following initial SARS-CoV-2 infection. These may include memory loss, gastrointestinal distress, fatigue, anosmia, and shortness of breath.

Long COVID has been associated with acute disease severity, and is suspected to be related to autoimmune factors and unresolved viral fragments, according to the paper.
 

Research methods

The international study did a deep and detailed dive into multiple molecular markers of long COVID. It enrolled 209 COVID-19 patients with varying degrees of disease severity and matched them to 457 healthy controls. The researchers’ goal was to identify discrete and quantifiable long COVID factors and guide possible preemptive treatment. 

Patients were assessed at three time points: at initial diagnosis, during the acute disease phase about a week later, and again 2 to 3 months post onset of symptoms after recovery from the acute phase of COVID. At the third assessment, some patients had lingering symptoms such as fatigue (52% ), cough (25%), and loss of taste or sense of smell (18%).

Blood draws were analyzed for autoantibodies and SARS-CoV-2–specific antibodies, global plasma proteomic and metabolomic profiles, and single-cell multiomic characterizations of peripheral blood mononuclear cells.

Each blood draw was paired with nasal-swab and plasma measurements of SARS-CoV-2 viral load and the data sets were integrated with electronic health records and self-reported patient symptoms to guide the interpretation of the molecular signatures of long COVID.
 

Author conclusions

The authors found an association between T2 hyperinflammation and long COVID–anticipating autoantibodies. This association further implies that hyperinflammation-controlling therapies in the acute stage of COVID may influence whether a patient experiences long COVID. “However, the detailed timing and context of these therapies matter, and, thus, future well-controlled studies will be needed to test these and other therapeutic implications,” Dr. Su and colleagues wrote.

Moreover, the negative correlations between anti–SARS-CoV-2 IgG and certain autoantibodies may suggest that patients with elevated autoantibody levels are more susceptible to breakthrough infections, the authors said.

“Many patients with high autoantibodies simultaneously have low protective antibodies that neutralize SARS-CoV-2, and that’s going to make them more susceptible to breakthrough infections,” Mr. Chen explained.*

“Detectability of most [long COVID-19 factors] at COVID diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests [long COVID] treatment strategies,” they wrote.

According to Mr. Chen, there are clear similarities in underlying immunobiology between patients with COVID autoantibodies and patients with systemic lupus erythematosus.

“These findings are also helping us frame our thinking around other chronic autoimmune conditions, such as postacute Lyme syndrome, for example,” said Dr. Heath.

The bottom line, said Mr. Chen, is that measuring early long COVID indicators may result in preventive treatments. “An example is the cortisol deficiency we see in certain long COVID patients. There are known treatments such as cortisol replacement therapy that should be explored for this group.”

Outside expert’s take on findings

Commenting on the study, Sherry Hsiang-Yi Chou, MD, who was not involved in the research, called the study a very important first step in understanding the path of this complex phenomenon and perhaps other conditions with long-term side effects.

“The researchers have done huge amount of innovative scientific work. They’ve shown the DNA signature of how our bodies respond to this disease,” said Dr. Chou, who is chief of the division of neurocritical care at Northwestern Medicine in Chicago.

“This type of research will help us scientifically understand and differentiate the various syndromes within long COVID. It will help identify who’s at risk for different aspects of this syndrome and lead to following them for longer periods in clinical trials,” she added.

The authors acknowledged that lengthier studies in larger cohorts were needed to see which patients will develop long-term chronic postacute sequelae of COVID.

This research was supported by the Wilke Family Foundation, the Parker Institute for Cancer Immunotherapy, Merck, and the Biomedical Advanced Research and Development Authority. Other support came from the National Institutes of Health, the Bill and Melinda Gates Foundation, Saint John’s Cancer Center, Fred Hutchinson Cancer Research Center, and the European Union’s Horizon 2020 research and innovation program. Dr. Heath is a cofounder of Pact Pharma. He and several coauthors disclosed various ties to multiple private-sector companies. Mr. Chen and Dr. Chou had no competing interests.

*Correction, 1/28: An earlier version of this story misidentified Daniel G. Chen, an undergraduate researcher at ISB.

A deep molecular dive into COVID-19 patients found that the presence of autoantibodies in peripheral blood at initial diagnosis was the chief of four risk factors predicting if a patient would experience long COVID.

Other significant early predictors of prolonged COVID symptoms – which the researchers called postacute sequelae – were having type 2 diabetes, SARS-CoV-2 RNAemia, and Epstein-Barr virus (EBV) viremia, Yapeng Su, PhD, of the Institute for Systems Biology (ISB) in Seattle, and colleagues wrote in Cell.

Having EBV viremia suggested that latent EBV has been reactivated, the authors noted.

“The most important postacute sequelae [that is conditions that are consequences of a disease] of COVID is the presence of autoantibodies,” James R. Heath, PhD, president of ISB and a bioengineering professor at the University of Washington, Seattle, said in an interview. “It’s about two times more important than the others.”

Dr. Heath and coauthors said early detection of this and other variables could prompt earlier aggressive treatment in patients susceptible to long COVID and ward off lingering symptoms.

“These predictive measures of long COVID can also help to better inform patients of their possible disease course,” study coauthor Daniel G. Chen, an undergraduate researcher at ISB, said in an interview. “We were also able to partially resolve the immunological underpinnings of some postacute sequelae of COVID in a way that suggested potential therapies, and the timing of those therapies.”

For example, he continued, the use of antivirals very early in the infectious course may mitigate the later development of long COVID. “This will, of course, have to be explored in an appropriately designed clinical trial.

“We also identified biomarkers of certain types of long COVID, such as neurological sequelae. Those biomarkers can help define the condition, which is a first step towards developing treatments.”

Study findings

With COVID patients monitored for 2 or 3 months, the study findings of the international “multiomic profiling” analysis include:

• Subclinical patient autoantibodies that reduce anti–SARS-CoV-2 antibodies suggest there is immune dysregulation during COVID-19 infection.
• Reactivation of latent other viruses during initial infection may be contributing to long COVID.
• Gastrointestinal postacute sequelae of COVID presents with a unique postacute expansion of cytotoxic T cells.
• SARS-CoV-2–specific and cytomegalovirus-specific CD8+ T cells displayed unique dynamics during recovery from infection.

According to the authors, as many as 69% of COVID-19 patients suffer from long COVID – a range of new, recurrent, or ongoing problems 4 or more weeks following initial SARS-CoV-2 infection. These may include memory loss, gastrointestinal distress, fatigue, anosmia, and shortness of breath.

Long COVID has been associated with acute disease severity, and is suspected to be related to autoimmune factors and unresolved viral fragments, according to the paper.
 

Research methods

The international study did a deep and detailed dive into multiple molecular markers of long COVID. It enrolled 209 COVID-19 patients with varying degrees of disease severity and matched them to 457 healthy controls. The researchers’ goal was to identify discrete and quantifiable long COVID factors and guide possible preemptive treatment. 

Patients were assessed at three time points: at initial diagnosis, during the acute disease phase about a week later, and again 2 to 3 months post onset of symptoms after recovery from the acute phase of COVID. At the third assessment, some patients had lingering symptoms such as fatigue (52% ), cough (25%), and loss of taste or sense of smell (18%).

Blood draws were analyzed for autoantibodies and SARS-CoV-2–specific antibodies, global plasma proteomic and metabolomic profiles, and single-cell multiomic characterizations of peripheral blood mononuclear cells.

Each blood draw was paired with nasal-swab and plasma measurements of SARS-CoV-2 viral load and the data sets were integrated with electronic health records and self-reported patient symptoms to guide the interpretation of the molecular signatures of long COVID.
 

Author conclusions

The authors found an association between T2 hyperinflammation and long COVID–anticipating autoantibodies. This association further implies that hyperinflammation-controlling therapies in the acute stage of COVID may influence whether a patient experiences long COVID. “However, the detailed timing and context of these therapies matter, and, thus, future well-controlled studies will be needed to test these and other therapeutic implications,” Dr. Su and colleagues wrote.

Moreover, the negative correlations between anti–SARS-CoV-2 IgG and certain autoantibodies may suggest that patients with elevated autoantibody levels are more susceptible to breakthrough infections, the authors said.

“Many patients with high autoantibodies simultaneously have low protective antibodies that neutralize SARS-CoV-2, and that’s going to make them more susceptible to breakthrough infections,” Mr. Chen explained.*

“Detectability of most [long COVID-19 factors] at COVID diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests [long COVID] treatment strategies,” they wrote.

According to Mr. Chen, there are clear similarities in underlying immunobiology between patients with COVID autoantibodies and patients with systemic lupus erythematosus.

“These findings are also helping us frame our thinking around other chronic autoimmune conditions, such as postacute Lyme syndrome, for example,” said Dr. Heath.

The bottom line, said Mr. Chen, is that measuring early long COVID indicators may result in preventive treatments. “An example is the cortisol deficiency we see in certain long COVID patients. There are known treatments such as cortisol replacement therapy that should be explored for this group.”

Outside expert’s take on findings

Commenting on the study, Sherry Hsiang-Yi Chou, MD, who was not involved in the research, called the study a very important first step in understanding the path of this complex phenomenon and perhaps other conditions with long-term side effects.

“The researchers have done huge amount of innovative scientific work. They’ve shown the DNA signature of how our bodies respond to this disease,” said Dr. Chou, who is chief of the division of neurocritical care at Northwestern Medicine in Chicago.

“This type of research will help us scientifically understand and differentiate the various syndromes within long COVID. It will help identify who’s at risk for different aspects of this syndrome and lead to following them for longer periods in clinical trials,” she added.

The authors acknowledged that lengthier studies in larger cohorts were needed to see which patients will develop long-term chronic postacute sequelae of COVID.

This research was supported by the Wilke Family Foundation, the Parker Institute for Cancer Immunotherapy, Merck, and the Biomedical Advanced Research and Development Authority. Other support came from the National Institutes of Health, the Bill and Melinda Gates Foundation, Saint John’s Cancer Center, Fred Hutchinson Cancer Research Center, and the European Union’s Horizon 2020 research and innovation program. Dr. Heath is a cofounder of Pact Pharma. He and several coauthors disclosed various ties to multiple private-sector companies. Mr. Chen and Dr. Chou had no competing interests.

*Correction, 1/28: An earlier version of this story misidentified Daniel G. Chen, an undergraduate researcher at ISB.

After participating in the activity, PCPs should be able to:

• Assess a patient with possible signs and symptoms of opioid use disorder
• Identify criteria necessary to make a diagnosis of opioid use disorder
• Recognize factors that should be considered to tailor treatments for patients with opioid use disorder
• Select the best treatment option for patients with opioid use disorder

Click here to access this content now 

After participating in the activity, PCPs should be able to:

• Assess a patient with possible signs and symptoms of opioid use disorder
• Identify criteria necessary to make a diagnosis of opioid use disorder
• Recognize factors that should be considered to tailor treatments for patients with opioid use disorder
• Select the best treatment option for patients with opioid use disorder

Click here to access this content now 

After participating in the activity, PCPs should be able to:

• Assess a patient with possible signs and symptoms of opioid use disorder
• Identify criteria necessary to make a diagnosis of opioid use disorder
• Recognize factors that should be considered to tailor treatments for patients with opioid use disorder
• Select the best treatment option for patients with opioid use disorder

Click here to access this content now 

More steps per day, particularly at a higher intensity, may reduce the risk of type 2 diabetes in older women, based on a prospective cohort study.

The link between daily stepping and diabetes was not significantly modified by body mass index (BMI) or other common diabetes risk factors, suggesting that the relationship is highly generalizable, lead author Alexis C. Garduno, MPH, a PhD student at the University of California, San Diego, and colleagues reported.

“Physical activity is a key modifiable behavior for diabetes prevention and management,” the investigators wrote in Diabetes Care. “Many prevention studies have demonstrated that regular physical activity, along with improved diet, reduces the risk of diabetes in adults. ... To the best of our knowledge, there are few studies examining the association between objectively measured steps per day and incident diabetes in a community-based setting.”

To this end, the investigators analyzed data from 4,838 older, community-living women in the Objective Physical Activity and Cardiovascular Health Study. Upon enrollment, women were without physician-diagnosed diabetes and had a mean age of 78.9 years. For 1 week, participants wore ActiGraph GT3X+ accelerometers to measure steps per day, as well as step intensity, graded as light or moderate to vigorous.

The relationship between daily activity and diabetes was analyzed using three multivariate models: The first included race/ethnicity and age; the second also included family history of diabetes, education, physical functioning, self-rated health, smoking status, and alcohol consumption; and the third added BMI, “a potential mediator in the causal pathway between steps per day and diabetes,” the investigators wrote.

Participants took an average of 3,729 steps per day, divided roughly evenly between light and moderate to vigorous intensity.

After a median follow-up of 5.7 years, 8.1% of women developed diabetes. The least-adjusted model showed a 14% reduction in diabetes risk per 2,000 steps (hazard ratio, 0.86; 95% confidence interval, 0.80-0.92; P = .007), whereas the second model, adjusting for more confounding variables, showed a 12% reduction in diabetes risk per 2,000 steps (HR, 0.88; 95% CI, 0.78-1.00; P = .045).

The final model, which added BMI, showed a 10% reduction in risk, although it didn’t reach statistical significance (HR, 0.90; 95% CI, 0.80-1.02; P = .11). Furthermore, accelerated failure time models suggested that BMI did not significantly impact the link between steps and diabetes (proportion mediated, 17.7%;95% CI, –55.0 to 142.0; P = .09). Further analyses also found no significant interactions between BMI or other possible confounders.

“The steps per day–diabetes association was not modified by age, race/ethnicity, BMI, physical functioning, or family history of diabetes, which supports the generalizability of these findings to community-living older women,” the investigators wrote.

Increased stepping intensity also appeared to lower risk of diabetes. After adjusting for confounding variables, light stepping was not linked to reduced risk (HR, 0.97; 95% CI, 0.73-1.29; P = .83), whereas moderate to vigorous stepping reduced risk by 14% per 2,000 steps (HR, 0.86; 95% CI, 0.74-1.00; P = .04).

“This study provides evidence supporting an association between steps per day and lower incident diabetes,” the investigators concluded. “While further work is needed to identify whether there is a minimum number of steps per day that results in a clinically significant reduction of diabetes and to evaluate the role that step intensity plays in diabetes etiology for older adults, findings from this study suggest that moderate-vigorous–intensity steps may be more important than lower-intensity steps with respect to incident diabetes. Steps per day–based interventions are needed to advance diabetes prevention science in older adults.”

The study was supported by the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the Tobacco-Related Disease Research Program, and others. The investigators had no potential conflicts of interest.

More steps per day, particularly at a higher intensity, may reduce the risk of type 2 diabetes in older women, based on a prospective cohort study.

The link between daily stepping and diabetes was not significantly modified by body mass index (BMI) or other common diabetes risk factors, suggesting that the relationship is highly generalizable, lead author Alexis C. Garduno, MPH, a PhD student at the University of California, San Diego, and colleagues reported.

“Physical activity is a key modifiable behavior for diabetes prevention and management,” the investigators wrote in Diabetes Care. “Many prevention studies have demonstrated that regular physical activity, along with improved diet, reduces the risk of diabetes in adults. ... To the best of our knowledge, there are few studies examining the association between objectively measured steps per day and incident diabetes in a community-based setting.”

To this end, the investigators analyzed data from 4,838 older, community-living women in the Objective Physical Activity and Cardiovascular Health Study. Upon enrollment, women were without physician-diagnosed diabetes and had a mean age of 78.9 years. For 1 week, participants wore ActiGraph GT3X+ accelerometers to measure steps per day, as well as step intensity, graded as light or moderate to vigorous.

The relationship between daily activity and diabetes was analyzed using three multivariate models: The first included race/ethnicity and age; the second also included family history of diabetes, education, physical functioning, self-rated health, smoking status, and alcohol consumption; and the third added BMI, “a potential mediator in the causal pathway between steps per day and diabetes,” the investigators wrote.

Participants took an average of 3,729 steps per day, divided roughly evenly between light and moderate to vigorous intensity.

After a median follow-up of 5.7 years, 8.1% of women developed diabetes. The least-adjusted model showed a 14% reduction in diabetes risk per 2,000 steps (hazard ratio, 0.86; 95% confidence interval, 0.80-0.92; P = .007), whereas the second model, adjusting for more confounding variables, showed a 12% reduction in diabetes risk per 2,000 steps (HR, 0.88; 95% CI, 0.78-1.00; P = .045).

The final model, which added BMI, showed a 10% reduction in risk, although it didn’t reach statistical significance (HR, 0.90; 95% CI, 0.80-1.02; P = .11). Furthermore, accelerated failure time models suggested that BMI did not significantly impact the link between steps and diabetes (proportion mediated, 17.7%;95% CI, –55.0 to 142.0; P = .09). Further analyses also found no significant interactions between BMI or other possible confounders.

“The steps per day–diabetes association was not modified by age, race/ethnicity, BMI, physical functioning, or family history of diabetes, which supports the generalizability of these findings to community-living older women,” the investigators wrote.

Increased stepping intensity also appeared to lower risk of diabetes. After adjusting for confounding variables, light stepping was not linked to reduced risk (HR, 0.97; 95% CI, 0.73-1.29; P = .83), whereas moderate to vigorous stepping reduced risk by 14% per 2,000 steps (HR, 0.86; 95% CI, 0.74-1.00; P = .04).

“This study provides evidence supporting an association between steps per day and lower incident diabetes,” the investigators concluded. “While further work is needed to identify whether there is a minimum number of steps per day that results in a clinically significant reduction of diabetes and to evaluate the role that step intensity plays in diabetes etiology for older adults, findings from this study suggest that moderate-vigorous–intensity steps may be more important than lower-intensity steps with respect to incident diabetes. Steps per day–based interventions are needed to advance diabetes prevention science in older adults.”

The study was supported by the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the Tobacco-Related Disease Research Program, and others. The investigators had no potential conflicts of interest.

More steps per day, particularly at a higher intensity, may reduce the risk of type 2 diabetes in older women, based on a prospective cohort study.

The link between daily stepping and diabetes was not significantly modified by body mass index (BMI) or other common diabetes risk factors, suggesting that the relationship is highly generalizable, lead author Alexis C. Garduno, MPH, a PhD student at the University of California, San Diego, and colleagues reported.

“Physical activity is a key modifiable behavior for diabetes prevention and management,” the investigators wrote in Diabetes Care. “Many prevention studies have demonstrated that regular physical activity, along with improved diet, reduces the risk of diabetes in adults. ... To the best of our knowledge, there are few studies examining the association between objectively measured steps per day and incident diabetes in a community-based setting.”

To this end, the investigators analyzed data from 4,838 older, community-living women in the Objective Physical Activity and Cardiovascular Health Study. Upon enrollment, women were without physician-diagnosed diabetes and had a mean age of 78.9 years. For 1 week, participants wore ActiGraph GT3X+ accelerometers to measure steps per day, as well as step intensity, graded as light or moderate to vigorous.

The relationship between daily activity and diabetes was analyzed using three multivariate models: The first included race/ethnicity and age; the second also included family history of diabetes, education, physical functioning, self-rated health, smoking status, and alcohol consumption; and the third added BMI, “a potential mediator in the causal pathway between steps per day and diabetes,” the investigators wrote.

Participants took an average of 3,729 steps per day, divided roughly evenly between light and moderate to vigorous intensity.

After a median follow-up of 5.7 years, 8.1% of women developed diabetes. The least-adjusted model showed a 14% reduction in diabetes risk per 2,000 steps (hazard ratio, 0.86; 95% confidence interval, 0.80-0.92; P = .007), whereas the second model, adjusting for more confounding variables, showed a 12% reduction in diabetes risk per 2,000 steps (HR, 0.88; 95% CI, 0.78-1.00; P = .045).

The final model, which added BMI, showed a 10% reduction in risk, although it didn’t reach statistical significance (HR, 0.90; 95% CI, 0.80-1.02; P = .11). Furthermore, accelerated failure time models suggested that BMI did not significantly impact the link between steps and diabetes (proportion mediated, 17.7%;95% CI, –55.0 to 142.0; P = .09). Further analyses also found no significant interactions between BMI or other possible confounders.

“The steps per day–diabetes association was not modified by age, race/ethnicity, BMI, physical functioning, or family history of diabetes, which supports the generalizability of these findings to community-living older women,” the investigators wrote.

Increased stepping intensity also appeared to lower risk of diabetes. After adjusting for confounding variables, light stepping was not linked to reduced risk (HR, 0.97; 95% CI, 0.73-1.29; P = .83), whereas moderate to vigorous stepping reduced risk by 14% per 2,000 steps (HR, 0.86; 95% CI, 0.74-1.00; P = .04).

“This study provides evidence supporting an association between steps per day and lower incident diabetes,” the investigators concluded. “While further work is needed to identify whether there is a minimum number of steps per day that results in a clinically significant reduction of diabetes and to evaluate the role that step intensity plays in diabetes etiology for older adults, findings from this study suggest that moderate-vigorous–intensity steps may be more important than lower-intensity steps with respect to incident diabetes. Steps per day–based interventions are needed to advance diabetes prevention science in older adults.”

The study was supported by the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the Tobacco-Related Disease Research Program, and others. The investigators had no potential conflicts of interest.

A new statement from the U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for atrial fibrillation (AFib) in asymptomatic adults.

The guidance is similar to the task force’s 2018 statement on screening for AFib with electrocardiography in asymptomatic adults 65 years or older, but lowers the inclusion age to adults 50 years or older.

“This 2021 evidence review included searching for evidence on additional screening methods such as automated blood pressure cuffs, pulse oximeters, and consumer devices such as smartwatches and smartphone apps. However, even with this expanded scope, the USPSTF did not find evidence to recommend for or against screening for AF,” the task force states.

The prevalence of increases in age from less than 0.2% in adults younger than 55 years to about 10% in those 85 years or older, the group says. The prevalence is higher in men than in women, but it is uncertain if it differs by race and ethnicity.

Although AFib substantially increases the risk for stroke, the stroke risk associated with subclinical AFib, particularly that of shorter duration lasting less than 24 hours or of lower burden, as might be detected by some screening approaches, is “uncertain,” the task force adds.

The updated recommendations were published online in JAMA, along with a separate evidence report and editorial.

The task force reviewed 26 studies in 113,784 patients, including 12 new to the update.

Studies showed that systematic screening detected significantly more AFib than no screening or pulse palpation (absolute difference, 1.0%-4.8% over up to 12 months). In two of the trials, however, only 10.7% and 44.5% of participants actually received the screening test.

The review included three randomized trials of screening vs. no screening that reported on health outcomes, but only one, STROKESTOP, was powered for health outcomes. It found a significantly lower risk for the primary composite endpoint of ischemic or hemorrhagic stroke, system embolism, bleeding leading to hospitalization, and all-cause mortality with twice-daily intermittent single-lead ECG monitoring for 14 days, compared with no screening. However, there were no significant differences in any of the individual outcomes of the composite endpoint.

“Additionally, and probably the most important thing to appreciate for the STROKESTOP study is that it has several limitations,” task force member Gbenga Ogedegbe, MD, MPH, of New York University told this news organization. The intervention was not masked, and outcomes weren’t centrally adjudicated.

Further, “about 11% of patients in the trial had a history of transient ischemic attack (TIA), stroke, or embolism and the population that we’re looking at within the task force are people without symptoms or history of stroke or ischemic attack,” he said. “That’s the fundamental difference here. So those limitations make it difficult to say that STROKESTOP actually has benefit.”

Notably absent from the review was the recent LOOP study, which found no significant benefit on outcomes with continuous monitoring with an implantable loop recorder (ILR) over usual care in older adults.

While it “offers some context for this issue,” it was not eligible for inclusion because 25% of the population had a prior history of stroke, TIA, or embolism and “because this screening approach may not be feasible for primary care settings,” lead author of the Evidence Report Leila Kahwati, MD, MPH, from RTI International’s Social and Health Organizational Research and Evaluation Program and the University of North Carolina at Chapel Hill, explained in an email.

Treatment with warfarin (mean, 1.5 years) was associated with a lower risk for ischemic stroke (relative risk, 0.32) and all-cause mortality (relative risk, 0.68), while direct oral anticoagulants were associated with a lower incidence of stroke (adjusted odds ratio range, 0.32-0.44). Patients had an increased risk for major bleeding with both warfarin (pooled relative risk, 1.8) and direct-acting oral anticoagulants (odds ratio, 1.38-2.21), but confidence intervals did not exclude a null effect.

The USPSTF found no trials that reported on the benefits of anticoagulation therapy in screen-detected patients.

In an accompanying editorial Philip Greenland, MD, points out that the task force’s conclusion differs from the 2020 European Society of Cardiology AFib guideline, which endorses opportunistic screening for AFib by pulse palpation or ECG rhythm strip in patients 65 years or older (class I recommendation) and advises that clinicians consider systematic ECG screening to detect AFib in people 75 years or older, or those at high risk for stroke (class IIa).

To possibly resolve whether screening for AFib in asymptomatic patients is justified, “future trials may need to consider enrolling only higher risk patients and identifying those with AF of longer duration,” said Dr. Greenland, JAMA editor and professor of preventive medicine and medicine at Northwestern University, Chicago.

“One important point raised by the LOOP trial is whether there is a threshold for AF duration that is most strongly associated with stroke risk and therefore most likely to benefit from anticoagulation,” he writes. Indeed, the LOOP authors themselves questioned whether the trial’s short AFib duration of 6 minutes may have led to many low-risk patients being diagnosed and treated.

“Additionally, trials need to recognize the need for longer monitoring periods (preferably continuous), and perhaps novel wearables will allow long-term monitoring, with accurate interpretation of the ECG and long-term adherence,” Dr. Greenland said.

In a related editorial in JAMA Internal Medicine, John Mandrola, MD, Baptist Health Louisville, Ky., and Andrew Foy, MD, Pennsylvania State University, Hershey, point out that continuous ILR monitoring in the LOOP trial found threefold more AFib and led to 2.7-fold higher rates of oral anticoagulation use, compared with standard care. Yet, there was no statistically significant difference in stroke reduction, and the 20% relative reduction in thromboembolic complications in the screened group was offset by a 26% relative increase in major bleeding.

“Perhaps the most remarkable aspect of the AF screening trials is that as the tools for screening improve, from a single 12-lead ECG to 14-day recordings and then the always-on ILR, more AF is detected and more [oral anticoagulant] is used, yet there is little demonstrable improvement in outcomes,” Dr. Mandrola and Dr. Foy write.

The editorialists also point to the potential for rhythm monitoring to lead to misdiagnosis and downstream cascades of care. “If you assume a 2% AF prevalence, even a device with 98% specificity will misdiagnose approximately 2000 individuals for every million screened.”

Dr. Mandrola told this news organization that the “greatest value” of these reports on AF screening and the critical appraisal of them is as an exercise in thinking about the limits of screening for disease. As James Maxwell Glover Wilson and Gunner Jungner wrote in their 1968 textbook, “Principles and Practice of Screening for Disease”: “in theory, screening is an admirable method of combating disease … [but] in practice, there are snags.”

“It would be good for the public to understand these snags…because they also apply to cancer, coronary calcium testing, and vascular screening as well,” Dr. Mandrola said.

Asked whether it’s possible to put the genie back in the bottle now that every other patient in clinic may have an ECG on their wrist, Dr. Ogedegbe said, “if a patient has no history of stroke or TIA and is 50 years or older, really, monitoring with these devices for AFib, there’s no evidence for or against doing that. Ultimately, the clinician has got to use their clinical judgment in talking to these patients.”

A related editorial in JAMA Cardiology suggests that, to be effective, the movement toward consumer-based screening must first show that such an approach improves outcomes and must deal with the paradox that those at highest risk for AFib and AFib-related stroke may be the least likely to own these technologies unless supported by the healthcare system.

“In addition, appropriate care pathways for confirming the diagnosis and, if necessary, initiating appropriate treatment in individuals with positive findings will need to be established,” Rod Passman, MD, Northwestern University, and Ben Freedman, MBBS, PhD, University of Sydney, Australia, say. “It will also be critical to ensure that device costs and variable technological literacy do not create barriers to making screening accessible to all those at risk.”

Finally, in a related editorial in JAMA Network Open Matthew Kalscheur, MD, and Zachary D. Goldberger, MD, both from the University of Wisconsin-Madison, say the potential benefits of early AFib detection should extend beyond stroke prevention.

“Patients identified with AF likely would benefit from targeted management of modifiable risk factors that contribute to AF, including obesity, hypertension, alcohol use, sleep apnea, smoking, and diabetes,” they write.

All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. Dr. Ogedegbe has a study included in the Evidence-based Practice Center report for this topic. Dr. Kahwati reported no relevant financial conflicts of interest. Dr. Greenland reported receiving research grants from the National Institutes of Health and from the American Heart Association. Dr. Mandrola is a regular contributor to this news organization. Dr. Foy, Dr. Kalscheur, and Dr. Goldberger reported no relevant financial relationships.

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

A new statement from the U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for atrial fibrillation (AFib) in asymptomatic adults.

The guidance is similar to the task force’s 2018 statement on screening for AFib with electrocardiography in asymptomatic adults 65 years or older, but lowers the inclusion age to adults 50 years or older.

“This 2021 evidence review included searching for evidence on additional screening methods such as automated blood pressure cuffs, pulse oximeters, and consumer devices such as smartwatches and smartphone apps. However, even with this expanded scope, the USPSTF did not find evidence to recommend for or against screening for AF,” the task force states.

The prevalence of increases in age from less than 0.2% in adults younger than 55 years to about 10% in those 85 years or older, the group says. The prevalence is higher in men than in women, but it is uncertain if it differs by race and ethnicity.

Although AFib substantially increases the risk for stroke, the stroke risk associated with subclinical AFib, particularly that of shorter duration lasting less than 24 hours or of lower burden, as might be detected by some screening approaches, is “uncertain,” the task force adds.

The updated recommendations were published online in JAMA, along with a separate evidence report and editorial.

The task force reviewed 26 studies in 113,784 patients, including 12 new to the update.

Studies showed that systematic screening detected significantly more AFib than no screening or pulse palpation (absolute difference, 1.0%-4.8% over up to 12 months). In two of the trials, however, only 10.7% and 44.5% of participants actually received the screening test.

The review included three randomized trials of screening vs. no screening that reported on health outcomes, but only one, STROKESTOP, was powered for health outcomes. It found a significantly lower risk for the primary composite endpoint of ischemic or hemorrhagic stroke, system embolism, bleeding leading to hospitalization, and all-cause mortality with twice-daily intermittent single-lead ECG monitoring for 14 days, compared with no screening. However, there were no significant differences in any of the individual outcomes of the composite endpoint.

“Additionally, and probably the most important thing to appreciate for the STROKESTOP study is that it has several limitations,” task force member Gbenga Ogedegbe, MD, MPH, of New York University told this news organization. The intervention was not masked, and outcomes weren’t centrally adjudicated.

Further, “about 11% of patients in the trial had a history of transient ischemic attack (TIA), stroke, or embolism and the population that we’re looking at within the task force are people without symptoms or history of stroke or ischemic attack,” he said. “That’s the fundamental difference here. So those limitations make it difficult to say that STROKESTOP actually has benefit.”

Notably absent from the review was the recent LOOP study, which found no significant benefit on outcomes with continuous monitoring with an implantable loop recorder (ILR) over usual care in older adults.

While it “offers some context for this issue,” it was not eligible for inclusion because 25% of the population had a prior history of stroke, TIA, or embolism and “because this screening approach may not be feasible for primary care settings,” lead author of the Evidence Report Leila Kahwati, MD, MPH, from RTI International’s Social and Health Organizational Research and Evaluation Program and the University of North Carolina at Chapel Hill, explained in an email.

Treatment with warfarin (mean, 1.5 years) was associated with a lower risk for ischemic stroke (relative risk, 0.32) and all-cause mortality (relative risk, 0.68), while direct oral anticoagulants were associated with a lower incidence of stroke (adjusted odds ratio range, 0.32-0.44). Patients had an increased risk for major bleeding with both warfarin (pooled relative risk, 1.8) and direct-acting oral anticoagulants (odds ratio, 1.38-2.21), but confidence intervals did not exclude a null effect.

The USPSTF found no trials that reported on the benefits of anticoagulation therapy in screen-detected patients.

In an accompanying editorial Philip Greenland, MD, points out that the task force’s conclusion differs from the 2020 European Society of Cardiology AFib guideline, which endorses opportunistic screening for AFib by pulse palpation or ECG rhythm strip in patients 65 years or older (class I recommendation) and advises that clinicians consider systematic ECG screening to detect AFib in people 75 years or older, or those at high risk for stroke (class IIa).

To possibly resolve whether screening for AFib in asymptomatic patients is justified, “future trials may need to consider enrolling only higher risk patients and identifying those with AF of longer duration,” said Dr. Greenland, JAMA editor and professor of preventive medicine and medicine at Northwestern University, Chicago.

“One important point raised by the LOOP trial is whether there is a threshold for AF duration that is most strongly associated with stroke risk and therefore most likely to benefit from anticoagulation,” he writes. Indeed, the LOOP authors themselves questioned whether the trial’s short AFib duration of 6 minutes may have led to many low-risk patients being diagnosed and treated.

“Additionally, trials need to recognize the need for longer monitoring periods (preferably continuous), and perhaps novel wearables will allow long-term monitoring, with accurate interpretation of the ECG and long-term adherence,” Dr. Greenland said.

In a related editorial in JAMA Internal Medicine, John Mandrola, MD, Baptist Health Louisville, Ky., and Andrew Foy, MD, Pennsylvania State University, Hershey, point out that continuous ILR monitoring in the LOOP trial found threefold more AFib and led to 2.7-fold higher rates of oral anticoagulation use, compared with standard care. Yet, there was no statistically significant difference in stroke reduction, and the 20% relative reduction in thromboembolic complications in the screened group was offset by a 26% relative increase in major bleeding.

“Perhaps the most remarkable aspect of the AF screening trials is that as the tools for screening improve, from a single 12-lead ECG to 14-day recordings and then the always-on ILR, more AF is detected and more [oral anticoagulant] is used, yet there is little demonstrable improvement in outcomes,” Dr. Mandrola and Dr. Foy write.

The editorialists also point to the potential for rhythm monitoring to lead to misdiagnosis and downstream cascades of care. “If you assume a 2% AF prevalence, even a device with 98% specificity will misdiagnose approximately 2000 individuals for every million screened.”

Dr. Mandrola told this news organization that the “greatest value” of these reports on AF screening and the critical appraisal of them is as an exercise in thinking about the limits of screening for disease. As James Maxwell Glover Wilson and Gunner Jungner wrote in their 1968 textbook, “Principles and Practice of Screening for Disease”: “in theory, screening is an admirable method of combating disease … [but] in practice, there are snags.”

“It would be good for the public to understand these snags…because they also apply to cancer, coronary calcium testing, and vascular screening as well,” Dr. Mandrola said.

Asked whether it’s possible to put the genie back in the bottle now that every other patient in clinic may have an ECG on their wrist, Dr. Ogedegbe said, “if a patient has no history of stroke or TIA and is 50 years or older, really, monitoring with these devices for AFib, there’s no evidence for or against doing that. Ultimately, the clinician has got to use their clinical judgment in talking to these patients.”

A related editorial in JAMA Cardiology suggests that, to be effective, the movement toward consumer-based screening must first show that such an approach improves outcomes and must deal with the paradox that those at highest risk for AFib and AFib-related stroke may be the least likely to own these technologies unless supported by the healthcare system.

“In addition, appropriate care pathways for confirming the diagnosis and, if necessary, initiating appropriate treatment in individuals with positive findings will need to be established,” Rod Passman, MD, Northwestern University, and Ben Freedman, MBBS, PhD, University of Sydney, Australia, say. “It will also be critical to ensure that device costs and variable technological literacy do not create barriers to making screening accessible to all those at risk.”

Finally, in a related editorial in JAMA Network Open Matthew Kalscheur, MD, and Zachary D. Goldberger, MD, both from the University of Wisconsin-Madison, say the potential benefits of early AFib detection should extend beyond stroke prevention.

“Patients identified with AF likely would benefit from targeted management of modifiable risk factors that contribute to AF, including obesity, hypertension, alcohol use, sleep apnea, smoking, and diabetes,” they write.

All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. Dr. Ogedegbe has a study included in the Evidence-based Practice Center report for this topic. Dr. Kahwati reported no relevant financial conflicts of interest. Dr. Greenland reported receiving research grants from the National Institutes of Health and from the American Heart Association. Dr. Mandrola is a regular contributor to this news organization. Dr. Foy, Dr. Kalscheur, and Dr. Goldberger reported no relevant financial relationships.

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

A new statement from the U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for atrial fibrillation (AFib) in asymptomatic adults.

The guidance is similar to the task force’s 2018 statement on screening for AFib with electrocardiography in asymptomatic adults 65 years or older, but lowers the inclusion age to adults 50 years or older.

“This 2021 evidence review included searching for evidence on additional screening methods such as automated blood pressure cuffs, pulse oximeters, and consumer devices such as smartwatches and smartphone apps. However, even with this expanded scope, the USPSTF did not find evidence to recommend for or against screening for AF,” the task force states.

The prevalence of increases in age from less than 0.2% in adults younger than 55 years to about 10% in those 85 years or older, the group says. The prevalence is higher in men than in women, but it is uncertain if it differs by race and ethnicity.

Although AFib substantially increases the risk for stroke, the stroke risk associated with subclinical AFib, particularly that of shorter duration lasting less than 24 hours or of lower burden, as might be detected by some screening approaches, is “uncertain,” the task force adds.

The updated recommendations were published online in JAMA, along with a separate evidence report and editorial.

The task force reviewed 26 studies in 113,784 patients, including 12 new to the update.

Studies showed that systematic screening detected significantly more AFib than no screening or pulse palpation (absolute difference, 1.0%-4.8% over up to 12 months). In two of the trials, however, only 10.7% and 44.5% of participants actually received the screening test.

The review included three randomized trials of screening vs. no screening that reported on health outcomes, but only one, STROKESTOP, was powered for health outcomes. It found a significantly lower risk for the primary composite endpoint of ischemic or hemorrhagic stroke, system embolism, bleeding leading to hospitalization, and all-cause mortality with twice-daily intermittent single-lead ECG monitoring for 14 days, compared with no screening. However, there were no significant differences in any of the individual outcomes of the composite endpoint.

“Additionally, and probably the most important thing to appreciate for the STROKESTOP study is that it has several limitations,” task force member Gbenga Ogedegbe, MD, MPH, of New York University told this news organization. The intervention was not masked, and outcomes weren’t centrally adjudicated.

Further, “about 11% of patients in the trial had a history of transient ischemic attack (TIA), stroke, or embolism and the population that we’re looking at within the task force are people without symptoms or history of stroke or ischemic attack,” he said. “That’s the fundamental difference here. So those limitations make it difficult to say that STROKESTOP actually has benefit.”

Notably absent from the review was the recent LOOP study, which found no significant benefit on outcomes with continuous monitoring with an implantable loop recorder (ILR) over usual care in older adults.

While it “offers some context for this issue,” it was not eligible for inclusion because 25% of the population had a prior history of stroke, TIA, or embolism and “because this screening approach may not be feasible for primary care settings,” lead author of the Evidence Report Leila Kahwati, MD, MPH, from RTI International’s Social and Health Organizational Research and Evaluation Program and the University of North Carolina at Chapel Hill, explained in an email.

Treatment with warfarin (mean, 1.5 years) was associated with a lower risk for ischemic stroke (relative risk, 0.32) and all-cause mortality (relative risk, 0.68), while direct oral anticoagulants were associated with a lower incidence of stroke (adjusted odds ratio range, 0.32-0.44). Patients had an increased risk for major bleeding with both warfarin (pooled relative risk, 1.8) and direct-acting oral anticoagulants (odds ratio, 1.38-2.21), but confidence intervals did not exclude a null effect.

The USPSTF found no trials that reported on the benefits of anticoagulation therapy in screen-detected patients.

In an accompanying editorial Philip Greenland, MD, points out that the task force’s conclusion differs from the 2020 European Society of Cardiology AFib guideline, which endorses opportunistic screening for AFib by pulse palpation or ECG rhythm strip in patients 65 years or older (class I recommendation) and advises that clinicians consider systematic ECG screening to detect AFib in people 75 years or older, or those at high risk for stroke (class IIa).

To possibly resolve whether screening for AFib in asymptomatic patients is justified, “future trials may need to consider enrolling only higher risk patients and identifying those with AF of longer duration,” said Dr. Greenland, JAMA editor and professor of preventive medicine and medicine at Northwestern University, Chicago.

“One important point raised by the LOOP trial is whether there is a threshold for AF duration that is most strongly associated with stroke risk and therefore most likely to benefit from anticoagulation,” he writes. Indeed, the LOOP authors themselves questioned whether the trial’s short AFib duration of 6 minutes may have led to many low-risk patients being diagnosed and treated.

“Additionally, trials need to recognize the need for longer monitoring periods (preferably continuous), and perhaps novel wearables will allow long-term monitoring, with accurate interpretation of the ECG and long-term adherence,” Dr. Greenland said.

In a related editorial in JAMA Internal Medicine, John Mandrola, MD, Baptist Health Louisville, Ky., and Andrew Foy, MD, Pennsylvania State University, Hershey, point out that continuous ILR monitoring in the LOOP trial found threefold more AFib and led to 2.7-fold higher rates of oral anticoagulation use, compared with standard care. Yet, there was no statistically significant difference in stroke reduction, and the 20% relative reduction in thromboembolic complications in the screened group was offset by a 26% relative increase in major bleeding.

“Perhaps the most remarkable aspect of the AF screening trials is that as the tools for screening improve, from a single 12-lead ECG to 14-day recordings and then the always-on ILR, more AF is detected and more [oral anticoagulant] is used, yet there is little demonstrable improvement in outcomes,” Dr. Mandrola and Dr. Foy write.

The editorialists also point to the potential for rhythm monitoring to lead to misdiagnosis and downstream cascades of care. “If you assume a 2% AF prevalence, even a device with 98% specificity will misdiagnose approximately 2000 individuals for every million screened.”

Dr. Mandrola told this news organization that the “greatest value” of these reports on AF screening and the critical appraisal of them is as an exercise in thinking about the limits of screening for disease. As James Maxwell Glover Wilson and Gunner Jungner wrote in their 1968 textbook, “Principles and Practice of Screening for Disease”: “in theory, screening is an admirable method of combating disease … [but] in practice, there are snags.”

“It would be good for the public to understand these snags…because they also apply to cancer, coronary calcium testing, and vascular screening as well,” Dr. Mandrola said.

Asked whether it’s possible to put the genie back in the bottle now that every other patient in clinic may have an ECG on their wrist, Dr. Ogedegbe said, “if a patient has no history of stroke or TIA and is 50 years or older, really, monitoring with these devices for AFib, there’s no evidence for or against doing that. Ultimately, the clinician has got to use their clinical judgment in talking to these patients.”

A related editorial in JAMA Cardiology suggests that, to be effective, the movement toward consumer-based screening must first show that such an approach improves outcomes and must deal with the paradox that those at highest risk for AFib and AFib-related stroke may be the least likely to own these technologies unless supported by the healthcare system.

“In addition, appropriate care pathways for confirming the diagnosis and, if necessary, initiating appropriate treatment in individuals with positive findings will need to be established,” Rod Passman, MD, Northwestern University, and Ben Freedman, MBBS, PhD, University of Sydney, Australia, say. “It will also be critical to ensure that device costs and variable technological literacy do not create barriers to making screening accessible to all those at risk.”

Finally, in a related editorial in JAMA Network Open Matthew Kalscheur, MD, and Zachary D. Goldberger, MD, both from the University of Wisconsin-Madison, say the potential benefits of early AFib detection should extend beyond stroke prevention.

“Patients identified with AF likely would benefit from targeted management of modifiable risk factors that contribute to AF, including obesity, hypertension, alcohol use, sleep apnea, smoking, and diabetes,” they write.

All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. Dr. Ogedegbe has a study included in the Evidence-based Practice Center report for this topic. Dr. Kahwati reported no relevant financial conflicts of interest. Dr. Greenland reported receiving research grants from the National Institutes of Health and from the American Heart Association. Dr. Mandrola is a regular contributor to this news organization. Dr. Foy, Dr. Kalscheur, and Dr. Goldberger reported no relevant financial relationships.

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

Gender equality remains elusive for women in academic oncology, a survey of nearly 700 U.S. female oncologists suggests.

More than half of respondents in academic medicine said they believe their gender adversely affects their likelihood for promotion, and 1 in 5 said they were considering leaving academia in the next 5 years.

Given the percentage of female oncologists planning to exit academia, “gender inequality is at high risk of continuing if the culture is not addressed,” write the authors in their study, published online Dec. 30 in JAMA Network Open.

Although women currently outnumber men in U.S. medical schools – a shift that first occurred in 2019 – female representation in academic oncology dwindles at more senior levels. Women represent 45% of hematology and oncology residents, only about 36% of academic faculty, and an even smaller percentage of leadership positions in academic medicine. Women, for instance, occupy about 31% of the chair positions in medical oncology, 17.4% in radiation oncology, and 11% in surgical oncology.

A team of researchers led by Emily C. Merfeld, MD, of the University of Wisconsin Hospitals and Clinics, Madison, set out to understand the factors influencing female oncologists’ decisions to pursue academic versus nonacademic career paths.

Dr. Merfeld and colleagues analyzed survey responses from 667 female oncologists between August 1 and Oct. 31, 2020 – 422 (63.2%) in academic medicine and 245 (36.8%) in nonacademic practice.

Overall, 1 in 4 oncologists said their spouse or partner and family “extremely or moderately” affected their decision to pursue academic practice.

Almost 43% of academic oncologists perceived time spent with loved ones as the biggest sacrifice related to pursuing a career in academic medicine. Approximately the same percentage (41.6%) of nonacademic oncologists perceived the pressure to achieve academic promotion as the most significant sacrifice associated with academic oncology, whereas only 22.4% perceived less time with loved ones as the biggest sacrifice.

“Although work-life balance was a concern for academic oncologists and may be a factor in female oncologists leaving academia, survey data suggested that women in nonacademic practice faced similar challenges,” the authors write.

More specifically, women in academic oncology reported working 2 more hours on the weekends compared to women not in academic medicine; however, both groups worked a similar number of hours during the week.

On the hiring front, almost 24% of academic oncologists said their gender had a “negative or somewhat negative” impact on their ability to get a job, compared with 21% of nonacademic oncologists. Conversely, nearly 28% of academic oncologists said their gender had a “positive or somewhat positive” influence on whether they were hired compared with 41.2% of nonacademic oncologists.

Respondents, however, perceived that gender strongly influenced promotion opportunities. More than half of the respondents – 54.6% of academic oncologists and 50.6% of nonacademic oncologists – believed they were less likely to be promoted than their male colleagues.

This perception aligns with findings from prior studies, which “found women were less likely than men to be promoted to associate professor, full professor, or department chair positions,” the authors write.

Overall, most respondents in each group – 71.3% in academic medicine and 68.6% in nonacademic practice – said they would choose the same career path again. But almost 22% of those in academia said they were “likely or very likely” to leave academic oncology in the next 5 years. Of these women, 28.2% said they would switch to industry employment and 25% would move to community practice.

“Contrary to popular assumptions,” the researchers note, “a spouse or partner and/or family were not a major factor in female oncologists favoring nonacademic careers, because this factor was similarly important to both academic and nonacademic oncologists.”

However, they note, “the increased financial compensation in nonacademic oncology may play a large role in some women’s career decisions.”
 

Making headway on gender equality?

In 2013, oncologist Katherine Reeder-Hayes, MD, MBA, now an associate at the University of North Carolina, Chapel Hill, published a study on gender equality in oncology in which she concluded that despite “an increasingly significant presence in the oncology physician workforce” women remained “under-represented in leadership positions and at the senior levels of academic medicine.”

Since then, Dr. Reeder-Hayes says that she has seen progress but recognizes the need for more.

“To some extent, I think that representation is improving over time due to factors outside the workplace – women are entering medical school in large numbers and may have more supportive partners and more social support for pursuing a professional career in general, [compared with] a decade or two ago,” Dr. Reeder-Hayes told this news organization.

On a personal level, she noted, “I do see many midcareer women assuming key leadership roles in my own institution.” However, she added, “I think the translation of those good candidates into increased representation in leadership probably varies widely across different institutions.”

In a 2019 editorial, researchers highlighted this variation while calling attention to the “notable progress” made by the American Association for Cancer Research (AACR). Specifically, the editorialists reported that women represent 40% of AACR members, 45% of the AACR Board of Directors, and half of the last 10 association presidents.

Editorial coauthor Elizabeth Jaffee, MD, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and former AACR president, told this news organization that she attributes this progress to “concrete measures to ensure equality throughout the organization,” which include gender balance on nominating and program committees as well as research meetings and providing opportunities for mentoring, leadership training, and networking.

Despite this positive change, the COVID-19 pandemic threatens to widen the gender imbalance. In a recent article, Julie Silver, MD, an expert in gender equity in medicine, told this news organization that she anticipates trouble ahead.

“There are many indications that women are leaving medicine in disproportionately high numbers,” said Dr. Silver, associate chair and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”

In addition to salary and promotion disparities, the U.S. continues to suffer from “a chronic shortage of available, affordable, and high-quality childcare and a lack of federal-level policy initiatives or employer initiatives to broaden paid family leave and develop childcare infrastructure and workforce,” Dr. Reeder-Hayes said. Providing extended leave for new parents and on-site childcare could go a long way to improving this problem, she said.

However, Dr. Reeder-Hayes noted that perhaps the “leaky pipeline” problem in oncology highlights the fact that women “are making good decisions that reflect balanced life priorities, [and that] if we don’t structure job responsibilities, childcare, and pacing of promotion and tenure in ways that allow people to nurture other parts of their lives, employees will feel they’re being asked to sacrifice key things.”

In other words, she said, “it’s the workplace that needs to change if we’re going to convince [women], and many men with similar values, to stay.”

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

Gender equality remains elusive for women in academic oncology, a survey of nearly 700 U.S. female oncologists suggests.

More than half of respondents in academic medicine said they believe their gender adversely affects their likelihood for promotion, and 1 in 5 said they were considering leaving academia in the next 5 years.

Given the percentage of female oncologists planning to exit academia, “gender inequality is at high risk of continuing if the culture is not addressed,” write the authors in their study, published online Dec. 30 in JAMA Network Open.

Although women currently outnumber men in U.S. medical schools – a shift that first occurred in 2019 – female representation in academic oncology dwindles at more senior levels. Women represent 45% of hematology and oncology residents, only about 36% of academic faculty, and an even smaller percentage of leadership positions in academic medicine. Women, for instance, occupy about 31% of the chair positions in medical oncology, 17.4% in radiation oncology, and 11% in surgical oncology.

A team of researchers led by Emily C. Merfeld, MD, of the University of Wisconsin Hospitals and Clinics, Madison, set out to understand the factors influencing female oncologists’ decisions to pursue academic versus nonacademic career paths.

Dr. Merfeld and colleagues analyzed survey responses from 667 female oncologists between August 1 and Oct. 31, 2020 – 422 (63.2%) in academic medicine and 245 (36.8%) in nonacademic practice.

Overall, 1 in 4 oncologists said their spouse or partner and family “extremely or moderately” affected their decision to pursue academic practice.

Almost 43% of academic oncologists perceived time spent with loved ones as the biggest sacrifice related to pursuing a career in academic medicine. Approximately the same percentage (41.6%) of nonacademic oncologists perceived the pressure to achieve academic promotion as the most significant sacrifice associated with academic oncology, whereas only 22.4% perceived less time with loved ones as the biggest sacrifice.

“Although work-life balance was a concern for academic oncologists and may be a factor in female oncologists leaving academia, survey data suggested that women in nonacademic practice faced similar challenges,” the authors write.

More specifically, women in academic oncology reported working 2 more hours on the weekends compared to women not in academic medicine; however, both groups worked a similar number of hours during the week.

On the hiring front, almost 24% of academic oncologists said their gender had a “negative or somewhat negative” impact on their ability to get a job, compared with 21% of nonacademic oncologists. Conversely, nearly 28% of academic oncologists said their gender had a “positive or somewhat positive” influence on whether they were hired compared with 41.2% of nonacademic oncologists.

Respondents, however, perceived that gender strongly influenced promotion opportunities. More than half of the respondents – 54.6% of academic oncologists and 50.6% of nonacademic oncologists – believed they were less likely to be promoted than their male colleagues.

This perception aligns with findings from prior studies, which “found women were less likely than men to be promoted to associate professor, full professor, or department chair positions,” the authors write.

Overall, most respondents in each group – 71.3% in academic medicine and 68.6% in nonacademic practice – said they would choose the same career path again. But almost 22% of those in academia said they were “likely or very likely” to leave academic oncology in the next 5 years. Of these women, 28.2% said they would switch to industry employment and 25% would move to community practice.

“Contrary to popular assumptions,” the researchers note, “a spouse or partner and/or family were not a major factor in female oncologists favoring nonacademic careers, because this factor was similarly important to both academic and nonacademic oncologists.”

However, they note, “the increased financial compensation in nonacademic oncology may play a large role in some women’s career decisions.”
 

Making headway on gender equality?

In 2013, oncologist Katherine Reeder-Hayes, MD, MBA, now an associate at the University of North Carolina, Chapel Hill, published a study on gender equality in oncology in which she concluded that despite “an increasingly significant presence in the oncology physician workforce” women remained “under-represented in leadership positions and at the senior levels of academic medicine.”

Since then, Dr. Reeder-Hayes says that she has seen progress but recognizes the need for more.

“To some extent, I think that representation is improving over time due to factors outside the workplace – women are entering medical school in large numbers and may have more supportive partners and more social support for pursuing a professional career in general, [compared with] a decade or two ago,” Dr. Reeder-Hayes told this news organization.

On a personal level, she noted, “I do see many midcareer women assuming key leadership roles in my own institution.” However, she added, “I think the translation of those good candidates into increased representation in leadership probably varies widely across different institutions.”

In a 2019 editorial, researchers highlighted this variation while calling attention to the “notable progress” made by the American Association for Cancer Research (AACR). Specifically, the editorialists reported that women represent 40% of AACR members, 45% of the AACR Board of Directors, and half of the last 10 association presidents.

Editorial coauthor Elizabeth Jaffee, MD, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and former AACR president, told this news organization that she attributes this progress to “concrete measures to ensure equality throughout the organization,” which include gender balance on nominating and program committees as well as research meetings and providing opportunities for mentoring, leadership training, and networking.

Despite this positive change, the COVID-19 pandemic threatens to widen the gender imbalance. In a recent article, Julie Silver, MD, an expert in gender equity in medicine, told this news organization that she anticipates trouble ahead.

“There are many indications that women are leaving medicine in disproportionately high numbers,” said Dr. Silver, associate chair and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”

In addition to salary and promotion disparities, the U.S. continues to suffer from “a chronic shortage of available, affordable, and high-quality childcare and a lack of federal-level policy initiatives or employer initiatives to broaden paid family leave and develop childcare infrastructure and workforce,” Dr. Reeder-Hayes said. Providing extended leave for new parents and on-site childcare could go a long way to improving this problem, she said.

However, Dr. Reeder-Hayes noted that perhaps the “leaky pipeline” problem in oncology highlights the fact that women “are making good decisions that reflect balanced life priorities, [and that] if we don’t structure job responsibilities, childcare, and pacing of promotion and tenure in ways that allow people to nurture other parts of their lives, employees will feel they’re being asked to sacrifice key things.”

In other words, she said, “it’s the workplace that needs to change if we’re going to convince [women], and many men with similar values, to stay.”

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

Gender equality remains elusive for women in academic oncology, a survey of nearly 700 U.S. female oncologists suggests.

More than half of respondents in academic medicine said they believe their gender adversely affects their likelihood for promotion, and 1 in 5 said they were considering leaving academia in the next 5 years.

Given the percentage of female oncologists planning to exit academia, “gender inequality is at high risk of continuing if the culture is not addressed,” write the authors in their study, published online Dec. 30 in JAMA Network Open.

Although women currently outnumber men in U.S. medical schools – a shift that first occurred in 2019 – female representation in academic oncology dwindles at more senior levels. Women represent 45% of hematology and oncology residents, only about 36% of academic faculty, and an even smaller percentage of leadership positions in academic medicine. Women, for instance, occupy about 31% of the chair positions in medical oncology, 17.4% in radiation oncology, and 11% in surgical oncology.

A team of researchers led by Emily C. Merfeld, MD, of the University of Wisconsin Hospitals and Clinics, Madison, set out to understand the factors influencing female oncologists’ decisions to pursue academic versus nonacademic career paths.

Dr. Merfeld and colleagues analyzed survey responses from 667 female oncologists between August 1 and Oct. 31, 2020 – 422 (63.2%) in academic medicine and 245 (36.8%) in nonacademic practice.

Overall, 1 in 4 oncologists said their spouse or partner and family “extremely or moderately” affected their decision to pursue academic practice.

Almost 43% of academic oncologists perceived time spent with loved ones as the biggest sacrifice related to pursuing a career in academic medicine. Approximately the same percentage (41.6%) of nonacademic oncologists perceived the pressure to achieve academic promotion as the most significant sacrifice associated with academic oncology, whereas only 22.4% perceived less time with loved ones as the biggest sacrifice.

“Although work-life balance was a concern for academic oncologists and may be a factor in female oncologists leaving academia, survey data suggested that women in nonacademic practice faced similar challenges,” the authors write.

More specifically, women in academic oncology reported working 2 more hours on the weekends compared to women not in academic medicine; however, both groups worked a similar number of hours during the week.

On the hiring front, almost 24% of academic oncologists said their gender had a “negative or somewhat negative” impact on their ability to get a job, compared with 21% of nonacademic oncologists. Conversely, nearly 28% of academic oncologists said their gender had a “positive or somewhat positive” influence on whether they were hired compared with 41.2% of nonacademic oncologists.

Respondents, however, perceived that gender strongly influenced promotion opportunities. More than half of the respondents – 54.6% of academic oncologists and 50.6% of nonacademic oncologists – believed they were less likely to be promoted than their male colleagues.

This perception aligns with findings from prior studies, which “found women were less likely than men to be promoted to associate professor, full professor, or department chair positions,” the authors write.

Overall, most respondents in each group – 71.3% in academic medicine and 68.6% in nonacademic practice – said they would choose the same career path again. But almost 22% of those in academia said they were “likely or very likely” to leave academic oncology in the next 5 years. Of these women, 28.2% said they would switch to industry employment and 25% would move to community practice.

“Contrary to popular assumptions,” the researchers note, “a spouse or partner and/or family were not a major factor in female oncologists favoring nonacademic careers, because this factor was similarly important to both academic and nonacademic oncologists.”

However, they note, “the increased financial compensation in nonacademic oncology may play a large role in some women’s career decisions.”
 

Making headway on gender equality?

In 2013, oncologist Katherine Reeder-Hayes, MD, MBA, now an associate at the University of North Carolina, Chapel Hill, published a study on gender equality in oncology in which she concluded that despite “an increasingly significant presence in the oncology physician workforce” women remained “under-represented in leadership positions and at the senior levels of academic medicine.”

Since then, Dr. Reeder-Hayes says that she has seen progress but recognizes the need for more.

“To some extent, I think that representation is improving over time due to factors outside the workplace – women are entering medical school in large numbers and may have more supportive partners and more social support for pursuing a professional career in general, [compared with] a decade or two ago,” Dr. Reeder-Hayes told this news organization.

On a personal level, she noted, “I do see many midcareer women assuming key leadership roles in my own institution.” However, she added, “I think the translation of those good candidates into increased representation in leadership probably varies widely across different institutions.”

In a 2019 editorial, researchers highlighted this variation while calling attention to the “notable progress” made by the American Association for Cancer Research (AACR). Specifically, the editorialists reported that women represent 40% of AACR members, 45% of the AACR Board of Directors, and half of the last 10 association presidents.

Editorial coauthor Elizabeth Jaffee, MD, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and former AACR president, told this news organization that she attributes this progress to “concrete measures to ensure equality throughout the organization,” which include gender balance on nominating and program committees as well as research meetings and providing opportunities for mentoring, leadership training, and networking.

Despite this positive change, the COVID-19 pandemic threatens to widen the gender imbalance. In a recent article, Julie Silver, MD, an expert in gender equity in medicine, told this news organization that she anticipates trouble ahead.

“There are many indications that women are leaving medicine in disproportionately high numbers,” said Dr. Silver, associate chair and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”

In addition to salary and promotion disparities, the U.S. continues to suffer from “a chronic shortage of available, affordable, and high-quality childcare and a lack of federal-level policy initiatives or employer initiatives to broaden paid family leave and develop childcare infrastructure and workforce,” Dr. Reeder-Hayes said. Providing extended leave for new parents and on-site childcare could go a long way to improving this problem, she said.

However, Dr. Reeder-Hayes noted that perhaps the “leaky pipeline” problem in oncology highlights the fact that women “are making good decisions that reflect balanced life priorities, [and that] if we don’t structure job responsibilities, childcare, and pacing of promotion and tenure in ways that allow people to nurture other parts of their lives, employees will feel they’re being asked to sacrifice key things.”

In other words, she said, “it’s the workplace that needs to change if we’re going to convince [women], and many men with similar values, to stay.”

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

A proactive approach to therapeutic drug monitoring during maintenance therapy with infliximab in the treatment of inflammatory bowel diseases (IBDs) and other chronic immune-mediated inflammatory diseases significantly improves sustained disease control, compared with standard care, which was defined as no therapeutic drug monitoring, new research shows.

“This trial showed that therapeutic drug monitoring improved infliximab [maintenance] treatment by preventing disease flares without increasing drug consumption,” reported the authors of the study published in JAMA.

Infliximab and other tumor necrosis factor (TNF)–inhibitor drugs offer significant benefits in the treatment of IBDs and other chronic inflammatory diseases; however, up to 50% of patients become nonresponsive to the therapy within the first years of treatment, posing risks of disease worsening and possible organ damage.

To address the problem, therapeutic drug monitoring has been recommended, more so with IBD guidelines than rheumatoid arthritis; these have included measures such as dose adjustment or drug switching when there is evidence that disease control is not being maintained.

However, with low serum drug concentrations and the development of antidrug antibodies believed to be key indicators of a waning response, there is growing interest in a more proactive monitoring approach, involving scheduled assessments of serum and antibody levels, performed regardless of any signs of disease activity changes, and the provision of dosing adjustments, if needed.

In the earlier Norwegian Drug Monitoring (NORDRUM) A trial, first author Silje Watterdal Syversen, MD, PhD, of the division of rheumatology and research, Diakonhjemmet Hospital, Oslo, Norway, and colleagues evaluated the effects of the proactive drug monitoring approach during the initiation phase of infliximab treatment, but found no significant improvement in the study of 411 patients in terms of the primary outcome of remission rates.

For the current NORDRUM B trial, they sought to instead determine if benefits of the proactive therapeutic drug monitoring may be more apparent during the maintenance phase of infliximab treatment.

The trial involved 458 adults at 20 hospitals in Norway who had immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37), and who were undergoing maintenance therapy with infliximab.

The patients, who had a median of about 40 weeks’ prior infliximab therapy, were randomized 1:1 to receive either proactive therapeutic drug monitoring, consisting of scheduled monitoring of serum drug levels and antidrug antibodies and adjustments in dose and intervals as needed according to a trial algorithm (n = 228), or standard infliximab therapy, without the regular drug and antibody level monitoring (n = 230).

Over a 52-week follow-up, the primary outcome of sustained disease control without disease worsening was significantly higher in the proactive therapeutic drug monitoring group (73.6%; n = 167) versus standard care (55.9%; n = 127; P < .001). The risk of disease worsening was meanwhile significantly greater with standard care versus proactive drug monitoring (hazard ratio, 2.1).

Serum infliximab levels remained within the therapeutic range throughout the study period in 30% of patients receiving proactive therapeutic drug monitoring, compared with 17% in the standard care group, and low serum infliximab levels (≤2 mg/L) occurred at least once during the study period among 19% and 27% of the two groups, respectively.

Clinically significant levels of antidrug antibodies (≥50 mcg/L) occurred in 9.2% of the therapeutic drug monitoring patients and 15.0% of the standard care group.

About 55% of patients were also using concomitant immunosuppressive therapy, and the findings were consistent among those who did and did not use the drugs. There no significant differences in adverse events between the therapeutic drug-monitoring (60%) and standard care groups (63%).

Importantly, while the mean dose of infliximab during the trial was 4.8 mg/kg in both groups, an increase in dosage after disease worsening was more common in the standard therapy group (51%) than in the therapeutic drug monitoring group (31.6%), underscoring the improved dose control provided with the proactive therapeutic drug monitoring, the authors note.

The findings suggest “proactive therapeutic drug monitoring might be more important during maintenance therapy, a period during which low drug levels could be an important risk factor for therapeutic failure,” the authors conclude.

In commenting to this news organizatin, Dr. Syversen noted that, despite the variety of IMIDs, there were no significant differences with IBDs or other disorders.

“Our data show consistent findings across all diseases included,” she said.

Furthermore, “in the present study, and [prior research] using the same definition of disease worsening, IBD patients in general had a comparable flare rate as compared to inflammatory arthritis.”
 

Caveats include severe illness, potential cost challenges

Commenting on the research, Stephen B. Hanauer, MD, noted that a potential exception to the lack of benefit previously observed during treatment induction could be patients with severe illness.

“In patients with more severe disease and in particular with low albumin, [which is] more common in IBD than other immune-mediated inflammatory diseases, there is rapid metabolism and clearance of monoclonal antibodies early that limit efficacy of standard induction dosing,” said Dr. Hanauer, a professor of medicine and medical director of the Digestive Health Center at Northwestern University, Chicago. 

Northwestern University

Noting that the average duration of treatment in the study prior to randomization was nearly a year (about 40 weeks), he added that a key question is “How to initiate therapeutic drug monitoring earlier in course to further optimize induction and prevent loss of response in maintenance.”

Dr. Hanauer shared that, “in our practice, we use a combination of proactive and reactive therapeutic drug monitoring based on individual patients and their history with prior biologics.”
 

Findings may usher in ‘new era’ in immune-mediated inflammatory disease treatment

In an editorial published in JAMA with the study, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, both of Harvard Medical School in Boston, further commented that “maintaining disease control in nearly 3 of 4 patients represents a meaningful improvement over standard care.”

However, key challenges with the approach include the potential need for additional nurses and others to help monitor patients, and associated costs, which insurance providers may not always cover, they noted.

Another consideration is a lack of effective tools for monitoring measures including antidrug antibodies, they added, and “additional clinical trials within specific disease subgroups are needed.”

However, addressing such barriers “may help introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases,” the editorialists write.

Niels Vande Casteele, PharmD, PhD, an associate professor at the department of medicine, University of California, San Diego, and affiliate faculty, Skaggs School of Pharmacy & Pharmaceutical Sciences, commented that the study is “an important milestone in the field of therapeutic drug monitoring of biologics for immunoinflammatory diseases.”

“The ability of proactive therapeutic drug monitoring to achieve sustained disease control without increased drug consumption is [a] notable finding,” he said in an interview.

Noting a limitation, Dr. Casteele suggested the inclusion of more specific measures of disease activity could have provided clearer insights.

“In particular for gastrointestinal diseases, we know that symptoms do not correlate well with inflammatory disease activity,” he said. “As such, I would have preferred to see clinical symptoms being complemented with endoscopic and histologic finds to confirm disease activity.”

Ultimately, he said that the results suggest “proactive therapeutic drug monitoring is not required for all patients, but it is beneficial in some to achieve sustained disease control over a prolonged period of time.”

This study received funding by grants from the Norwegian Regional Health Authorities (interregional KLINBEFORSK grants) and the South-Eastern Norway Regional Health Authorities; study authors reported relationships with various pharmaceutical companies, including Pfizer, which makes infliximab. Dr. Wallace reported research support from Bristol Myers Squibb and Principia/Sanofi and consulting fees from Viela Bio, Zenas Biopharma, and MedPace. Dr. Sparks reported consultancy fees from AbbVie, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer. Dr. Hanauer is a consultant and lecturer for Abbvie, Janssen, and Takeda and consultant for Pfizer, Celltrion, Amgen, Samsung Bioepis. Dr. Casteele has received research grants and personal fees from R-Biopharm, Takeda and UCB; and personal fees from AcelaBio, Alimentiv, Celltrion, Prometheus, Procise DX, and Vividion for activities that were all outside of the reviewed study.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

A proactive approach to therapeutic drug monitoring during maintenance therapy with infliximab in the treatment of inflammatory bowel diseases (IBDs) and other chronic immune-mediated inflammatory diseases significantly improves sustained disease control, compared with standard care, which was defined as no therapeutic drug monitoring, new research shows.

“This trial showed that therapeutic drug monitoring improved infliximab [maintenance] treatment by preventing disease flares without increasing drug consumption,” reported the authors of the study published in JAMA.

Infliximab and other tumor necrosis factor (TNF)–inhibitor drugs offer significant benefits in the treatment of IBDs and other chronic inflammatory diseases; however, up to 50% of patients become nonresponsive to the therapy within the first years of treatment, posing risks of disease worsening and possible organ damage.

To address the problem, therapeutic drug monitoring has been recommended, more so with IBD guidelines than rheumatoid arthritis; these have included measures such as dose adjustment or drug switching when there is evidence that disease control is not being maintained.

However, with low serum drug concentrations and the development of antidrug antibodies believed to be key indicators of a waning response, there is growing interest in a more proactive monitoring approach, involving scheduled assessments of serum and antibody levels, performed regardless of any signs of disease activity changes, and the provision of dosing adjustments, if needed.

In the earlier Norwegian Drug Monitoring (NORDRUM) A trial, first author Silje Watterdal Syversen, MD, PhD, of the division of rheumatology and research, Diakonhjemmet Hospital, Oslo, Norway, and colleagues evaluated the effects of the proactive drug monitoring approach during the initiation phase of infliximab treatment, but found no significant improvement in the study of 411 patients in terms of the primary outcome of remission rates.

For the current NORDRUM B trial, they sought to instead determine if benefits of the proactive therapeutic drug monitoring may be more apparent during the maintenance phase of infliximab treatment.

The trial involved 458 adults at 20 hospitals in Norway who had immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37), and who were undergoing maintenance therapy with infliximab.

The patients, who had a median of about 40 weeks’ prior infliximab therapy, were randomized 1:1 to receive either proactive therapeutic drug monitoring, consisting of scheduled monitoring of serum drug levels and antidrug antibodies and adjustments in dose and intervals as needed according to a trial algorithm (n = 228), or standard infliximab therapy, without the regular drug and antibody level monitoring (n = 230).

Over a 52-week follow-up, the primary outcome of sustained disease control without disease worsening was significantly higher in the proactive therapeutic drug monitoring group (73.6%; n = 167) versus standard care (55.9%; n = 127; P < .001). The risk of disease worsening was meanwhile significantly greater with standard care versus proactive drug monitoring (hazard ratio, 2.1).

Serum infliximab levels remained within the therapeutic range throughout the study period in 30% of patients receiving proactive therapeutic drug monitoring, compared with 17% in the standard care group, and low serum infliximab levels (≤2 mg/L) occurred at least once during the study period among 19% and 27% of the two groups, respectively.

Clinically significant levels of antidrug antibodies (≥50 mcg/L) occurred in 9.2% of the therapeutic drug monitoring patients and 15.0% of the standard care group.

About 55% of patients were also using concomitant immunosuppressive therapy, and the findings were consistent among those who did and did not use the drugs. There no significant differences in adverse events between the therapeutic drug-monitoring (60%) and standard care groups (63%).

Importantly, while the mean dose of infliximab during the trial was 4.8 mg/kg in both groups, an increase in dosage after disease worsening was more common in the standard therapy group (51%) than in the therapeutic drug monitoring group (31.6%), underscoring the improved dose control provided with the proactive therapeutic drug monitoring, the authors note.

The findings suggest “proactive therapeutic drug monitoring might be more important during maintenance therapy, a period during which low drug levels could be an important risk factor for therapeutic failure,” the authors conclude.

In commenting to this news organizatin, Dr. Syversen noted that, despite the variety of IMIDs, there were no significant differences with IBDs or other disorders.

“Our data show consistent findings across all diseases included,” she said.

Furthermore, “in the present study, and [prior research] using the same definition of disease worsening, IBD patients in general had a comparable flare rate as compared to inflammatory arthritis.”
 

Caveats include severe illness, potential cost challenges

Commenting on the research, Stephen B. Hanauer, MD, noted that a potential exception to the lack of benefit previously observed during treatment induction could be patients with severe illness.

“In patients with more severe disease and in particular with low albumin, [which is] more common in IBD than other immune-mediated inflammatory diseases, there is rapid metabolism and clearance of monoclonal antibodies early that limit efficacy of standard induction dosing,” said Dr. Hanauer, a professor of medicine and medical director of the Digestive Health Center at Northwestern University, Chicago. 

Northwestern University

Noting that the average duration of treatment in the study prior to randomization was nearly a year (about 40 weeks), he added that a key question is “How to initiate therapeutic drug monitoring earlier in course to further optimize induction and prevent loss of response in maintenance.”

Dr. Hanauer shared that, “in our practice, we use a combination of proactive and reactive therapeutic drug monitoring based on individual patients and their history with prior biologics.”
 

Findings may usher in ‘new era’ in immune-mediated inflammatory disease treatment

In an editorial published in JAMA with the study, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, both of Harvard Medical School in Boston, further commented that “maintaining disease control in nearly 3 of 4 patients represents a meaningful improvement over standard care.”

However, key challenges with the approach include the potential need for additional nurses and others to help monitor patients, and associated costs, which insurance providers may not always cover, they noted.

Another consideration is a lack of effective tools for monitoring measures including antidrug antibodies, they added, and “additional clinical trials within specific disease subgroups are needed.”

However, addressing such barriers “may help introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases,” the editorialists write.

Niels Vande Casteele, PharmD, PhD, an associate professor at the department of medicine, University of California, San Diego, and affiliate faculty, Skaggs School of Pharmacy & Pharmaceutical Sciences, commented that the study is “an important milestone in the field of therapeutic drug monitoring of biologics for immunoinflammatory diseases.”

“The ability of proactive therapeutic drug monitoring to achieve sustained disease control without increased drug consumption is [a] notable finding,” he said in an interview.

Noting a limitation, Dr. Casteele suggested the inclusion of more specific measures of disease activity could have provided clearer insights.

“In particular for gastrointestinal diseases, we know that symptoms do not correlate well with inflammatory disease activity,” he said. “As such, I would have preferred to see clinical symptoms being complemented with endoscopic and histologic finds to confirm disease activity.”

Ultimately, he said that the results suggest “proactive therapeutic drug monitoring is not required for all patients, but it is beneficial in some to achieve sustained disease control over a prolonged period of time.”

This study received funding by grants from the Norwegian Regional Health Authorities (interregional KLINBEFORSK grants) and the South-Eastern Norway Regional Health Authorities; study authors reported relationships with various pharmaceutical companies, including Pfizer, which makes infliximab. Dr. Wallace reported research support from Bristol Myers Squibb and Principia/Sanofi and consulting fees from Viela Bio, Zenas Biopharma, and MedPace. Dr. Sparks reported consultancy fees from AbbVie, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer. Dr. Hanauer is a consultant and lecturer for Abbvie, Janssen, and Takeda and consultant for Pfizer, Celltrion, Amgen, Samsung Bioepis. Dr. Casteele has received research grants and personal fees from R-Biopharm, Takeda and UCB; and personal fees from AcelaBio, Alimentiv, Celltrion, Prometheus, Procise DX, and Vividion for activities that were all outside of the reviewed study.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

A proactive approach to therapeutic drug monitoring during maintenance therapy with infliximab in the treatment of inflammatory bowel diseases (IBDs) and other chronic immune-mediated inflammatory diseases significantly improves sustained disease control, compared with standard care, which was defined as no therapeutic drug monitoring, new research shows.

“This trial showed that therapeutic drug monitoring improved infliximab [maintenance] treatment by preventing disease flares without increasing drug consumption,” reported the authors of the study published in JAMA.

Infliximab and other tumor necrosis factor (TNF)–inhibitor drugs offer significant benefits in the treatment of IBDs and other chronic inflammatory diseases; however, up to 50% of patients become nonresponsive to the therapy within the first years of treatment, posing risks of disease worsening and possible organ damage.

To address the problem, therapeutic drug monitoring has been recommended, more so with IBD guidelines than rheumatoid arthritis; these have included measures such as dose adjustment or drug switching when there is evidence that disease control is not being maintained.

However, with low serum drug concentrations and the development of antidrug antibodies believed to be key indicators of a waning response, there is growing interest in a more proactive monitoring approach, involving scheduled assessments of serum and antibody levels, performed regardless of any signs of disease activity changes, and the provision of dosing adjustments, if needed.

In the earlier Norwegian Drug Monitoring (NORDRUM) A trial, first author Silje Watterdal Syversen, MD, PhD, of the division of rheumatology and research, Diakonhjemmet Hospital, Oslo, Norway, and colleagues evaluated the effects of the proactive drug monitoring approach during the initiation phase of infliximab treatment, but found no significant improvement in the study of 411 patients in terms of the primary outcome of remission rates.

For the current NORDRUM B trial, they sought to instead determine if benefits of the proactive therapeutic drug monitoring may be more apparent during the maintenance phase of infliximab treatment.

The trial involved 458 adults at 20 hospitals in Norway who had immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37), and who were undergoing maintenance therapy with infliximab.

The patients, who had a median of about 40 weeks’ prior infliximab therapy, were randomized 1:1 to receive either proactive therapeutic drug monitoring, consisting of scheduled monitoring of serum drug levels and antidrug antibodies and adjustments in dose and intervals as needed according to a trial algorithm (n = 228), or standard infliximab therapy, without the regular drug and antibody level monitoring (n = 230).

Over a 52-week follow-up, the primary outcome of sustained disease control without disease worsening was significantly higher in the proactive therapeutic drug monitoring group (73.6%; n = 167) versus standard care (55.9%; n = 127; P < .001). The risk of disease worsening was meanwhile significantly greater with standard care versus proactive drug monitoring (hazard ratio, 2.1).

Serum infliximab levels remained within the therapeutic range throughout the study period in 30% of patients receiving proactive therapeutic drug monitoring, compared with 17% in the standard care group, and low serum infliximab levels (≤2 mg/L) occurred at least once during the study period among 19% and 27% of the two groups, respectively.

Clinically significant levels of antidrug antibodies (≥50 mcg/L) occurred in 9.2% of the therapeutic drug monitoring patients and 15.0% of the standard care group.

About 55% of patients were also using concomitant immunosuppressive therapy, and the findings were consistent among those who did and did not use the drugs. There no significant differences in adverse events between the therapeutic drug-monitoring (60%) and standard care groups (63%).

Importantly, while the mean dose of infliximab during the trial was 4.8 mg/kg in both groups, an increase in dosage after disease worsening was more common in the standard therapy group (51%) than in the therapeutic drug monitoring group (31.6%), underscoring the improved dose control provided with the proactive therapeutic drug monitoring, the authors note.

The findings suggest “proactive therapeutic drug monitoring might be more important during maintenance therapy, a period during which low drug levels could be an important risk factor for therapeutic failure,” the authors conclude.

In commenting to this news organizatin, Dr. Syversen noted that, despite the variety of IMIDs, there were no significant differences with IBDs or other disorders.

“Our data show consistent findings across all diseases included,” she said.

Furthermore, “in the present study, and [prior research] using the same definition of disease worsening, IBD patients in general had a comparable flare rate as compared to inflammatory arthritis.”
 

Caveats include severe illness, potential cost challenges

Commenting on the research, Stephen B. Hanauer, MD, noted that a potential exception to the lack of benefit previously observed during treatment induction could be patients with severe illness.

“In patients with more severe disease and in particular with low albumin, [which is] more common in IBD than other immune-mediated inflammatory diseases, there is rapid metabolism and clearance of monoclonal antibodies early that limit efficacy of standard induction dosing,” said Dr. Hanauer, a professor of medicine and medical director of the Digestive Health Center at Northwestern University, Chicago. 

Northwestern University

Noting that the average duration of treatment in the study prior to randomization was nearly a year (about 40 weeks), he added that a key question is “How to initiate therapeutic drug monitoring earlier in course to further optimize induction and prevent loss of response in maintenance.”

Dr. Hanauer shared that, “in our practice, we use a combination of proactive and reactive therapeutic drug monitoring based on individual patients and their history with prior biologics.”
 

Findings may usher in ‘new era’ in immune-mediated inflammatory disease treatment

In an editorial published in JAMA with the study, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, both of Harvard Medical School in Boston, further commented that “maintaining disease control in nearly 3 of 4 patients represents a meaningful improvement over standard care.”

However, key challenges with the approach include the potential need for additional nurses and others to help monitor patients, and associated costs, which insurance providers may not always cover, they noted.

Another consideration is a lack of effective tools for monitoring measures including antidrug antibodies, they added, and “additional clinical trials within specific disease subgroups are needed.”

However, addressing such barriers “may help introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases,” the editorialists write.

Niels Vande Casteele, PharmD, PhD, an associate professor at the department of medicine, University of California, San Diego, and affiliate faculty, Skaggs School of Pharmacy & Pharmaceutical Sciences, commented that the study is “an important milestone in the field of therapeutic drug monitoring of biologics for immunoinflammatory diseases.”

“The ability of proactive therapeutic drug monitoring to achieve sustained disease control without increased drug consumption is [a] notable finding,” he said in an interview.

Noting a limitation, Dr. Casteele suggested the inclusion of more specific measures of disease activity could have provided clearer insights.

“In particular for gastrointestinal diseases, we know that symptoms do not correlate well with inflammatory disease activity,” he said. “As such, I would have preferred to see clinical symptoms being complemented with endoscopic and histologic finds to confirm disease activity.”

Ultimately, he said that the results suggest “proactive therapeutic drug monitoring is not required for all patients, but it is beneficial in some to achieve sustained disease control over a prolonged period of time.”

This study received funding by grants from the Norwegian Regional Health Authorities (interregional KLINBEFORSK grants) and the South-Eastern Norway Regional Health Authorities; study authors reported relationships with various pharmaceutical companies, including Pfizer, which makes infliximab. Dr. Wallace reported research support from Bristol Myers Squibb and Principia/Sanofi and consulting fees from Viela Bio, Zenas Biopharma, and MedPace. Dr. Sparks reported consultancy fees from AbbVie, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer. Dr. Hanauer is a consultant and lecturer for Abbvie, Janssen, and Takeda and consultant for Pfizer, Celltrion, Amgen, Samsung Bioepis. Dr. Casteele has received research grants and personal fees from R-Biopharm, Takeda and UCB; and personal fees from AcelaBio, Alimentiv, Celltrion, Prometheus, Procise DX, and Vividion for activities that were all outside of the reviewed study.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

An Alaska physician has been sentenced to 34 months in prison followed by 3 years of supervised release and fined $25,000 for illegally dispensing and distributing controlled substances to his patients.

According to court documents, between January 2014 and October 2019, family physician David Chisholm, MD, 64, of Wasilla, Alaska, wrote more than 20,000 prescriptions to approximately 350 patients for oxycodone, methadone, and hydrocodone, often prescribing the pills using variations of patients’ names in an attempt to avoid being red-flagged by payers.

When Walmart refused to continue filling the prescriptions, Dr. Chisholm told his staff to advise the patients to use other pharmacies. In addition, he often prescribed combinations of medications, such as concurrent opioids, benzodiazepines, sedatives, and carisoprodol, thus increasing the chances that his patients would become addicted to or overdose on the drugs. Chisholm, who pleaded guilty in June, acknowledged to federal officials that his prescriptions were a significant contributing factor to the overdose deaths of five of his patients during this time, according to a statement by the U.S. Attorney’s Office for the District of Alaska.

According to the Anchorage Daily News, Dr. Chisholm, who was not board certified in pain medicine, said his reason for prescribing the drugs was not to make money but to help patients suffering from chronic pain and because he enjoyed the challenge.

Dr. Chisholm’s attorney, Nick Oberheiden, told CNN his client “sacrificed his reputation as a patient advocate and his years of service to the Alaskan community” in overprescribing opioids. “He expressed his sincere remorse in open court and he accepts the consequences of his misconduct. He hopes that his case serves as a warning to other physicians facing the same dilemma when treating chronic pain.”

He surrendered his medical license in November 2020 before being formally charged in April 2021.
 

Texas hospital CEO, seven doctors settle kickback

A hospital executive and seven physicians have agreed to pay a total of $1.1 million to settle allegations that they violated the Anti-Kickback Statute and Stark Law. The eight have also agreed to cooperate in investigations and litigation involving other parties.

The Texas physicians involved in the settlement are internist Jaspaul Bhangoo, MD, of Denton; family physician Robert Megna, DO, of Ferris; cardiologist Baxter Montgomery, MD, of Houston; internist Murtaza Mussaji, DO, of Houston; family physician David Sneed, DO, of Austin; family physician Kevin Lewis, DO, of Houston; and family physician Angela Mosley-Nunnery, MD, of Kingwood.

Also settling was Richard DeFoore, former CEO of Jones County Regional Healthcare (dba Stamford Memorial Hospital).

The physicians were accused of accepting payments from organizations in exchange for ordering lab tests from True Health Diagnostics, Little River Healthcare, and Boston Heart. The payments to the physicians were disguised as investment returns but, according to the allegations, were in fact offered in exchange for the doctors’ referrals. Mr. DeFoore, the hospital executive involved in the settlement, allegedly oversaw a similar scheme that benefited the now-defunct Stamford Memorial.

“Paying kickbacks to physicians distorts the medical decision-making process, corrupts our health care system, and increases the cost of healthcare funded by the taxpayer,” Brit Featherston, U.S. attorney for the Eastern District of Texas, said in a statement announcing the agreement. “Laboratories, marketers, and physicians cannot immunize their conduct by attempting to disguise the kickbacks as some sort of investment arrangement.”
 

Practice administrative assistant sentenced for fraudulent prescriptions

An administrative assistant at an Illinois orthopedics office was sentenced to a year and a day in federal prison for writing fraudulent prescriptions for opioids.

Amanda Biesiada, 39, of Alsip, Ill., who worked as an administrative assistant at Hinsdale Orthopaedics in Westmont, Ill., was not a licensed physician and could not legally write the prescriptions unless instructed to do so and supervised by licensed doctors.

According to a statement by the U.S. Attorney’s Office for the Northern District of Illinois, the prescriptions for hydrocodone, oxycodone, and other controlled substances – 85 prescriptions in all from 2017 to 2019 – were made out to an acquaintance of Biesiada’s and written without the knowledge or approval of the providers in whose names she wrote them.

Federal officials said Ms. Biesiada attempted to conceal the fraudulent prescriptions by marking them “filed in error” in the practice’s prescription system.
 

Lab owner pleads guilty to $6.9 million testing fraud scheme

A Florida lab owner has pleaded guilty to conspiracy to defraud Medicare through false and fraudulent claims totaling more than $6.9 million.

According to court documents, Christopher Licata, 45, of Delray Beach, Fla., admitted to bribing patient brokers to refer orders for medically unnecessary genetic testing to his lab. The tests were then billed to Medicare.

Mr. Licata and the patient brokers entered sham agreements meant to disguise the true purpose of the payments, according to a statement from the Department of Justice. The 45-year-old owner of Boca Toxicology (dba Lab Dynamics) pleaded guilty to one count of conspiring to commit health care fraud.

The scheme began in 2018; however, once the pandemic began, Mr. Licata shifted strategies, playing on patients’ fears of COVID-19 to bundle inexpensive COVID tests with more expensive medically unnecessary tests. These tests included respiratory pathogen panels and genetic testing for cardiovascular disease, cancer, diabetes, Alzheimer’s disease, and other illnesses. In all, Mr. Licata’s laboratory submitted over $6.9 million in false and fraudulent claims to Medicare for these unnecessary tests, according to the DOJ statement.

The case is a part of the U.S. Attorney General’s COVID-19 Fraud Enforcement Task Force that was established to enhance the efforts of agencies and governments across the country to combat and prevent pandemic-related fraud.

Mr. Licata faces a maximum penalty of 10 years in prison. His sentencing is scheduled for March 24.

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

An Alaska physician has been sentenced to 34 months in prison followed by 3 years of supervised release and fined $25,000 for illegally dispensing and distributing controlled substances to his patients.

According to court documents, between January 2014 and October 2019, family physician David Chisholm, MD, 64, of Wasilla, Alaska, wrote more than 20,000 prescriptions to approximately 350 patients for oxycodone, methadone, and hydrocodone, often prescribing the pills using variations of patients’ names in an attempt to avoid being red-flagged by payers.

When Walmart refused to continue filling the prescriptions, Dr. Chisholm told his staff to advise the patients to use other pharmacies. In addition, he often prescribed combinations of medications, such as concurrent opioids, benzodiazepines, sedatives, and carisoprodol, thus increasing the chances that his patients would become addicted to or overdose on the drugs. Chisholm, who pleaded guilty in June, acknowledged to federal officials that his prescriptions were a significant contributing factor to the overdose deaths of five of his patients during this time, according to a statement by the U.S. Attorney’s Office for the District of Alaska.

According to the Anchorage Daily News, Dr. Chisholm, who was not board certified in pain medicine, said his reason for prescribing the drugs was not to make money but to help patients suffering from chronic pain and because he enjoyed the challenge.

Dr. Chisholm’s attorney, Nick Oberheiden, told CNN his client “sacrificed his reputation as a patient advocate and his years of service to the Alaskan community” in overprescribing opioids. “He expressed his sincere remorse in open court and he accepts the consequences of his misconduct. He hopes that his case serves as a warning to other physicians facing the same dilemma when treating chronic pain.”

He surrendered his medical license in November 2020 before being formally charged in April 2021.
 

Texas hospital CEO, seven doctors settle kickback

A hospital executive and seven physicians have agreed to pay a total of $1.1 million to settle allegations that they violated the Anti-Kickback Statute and Stark Law. The eight have also agreed to cooperate in investigations and litigation involving other parties.

The Texas physicians involved in the settlement are internist Jaspaul Bhangoo, MD, of Denton; family physician Robert Megna, DO, of Ferris; cardiologist Baxter Montgomery, MD, of Houston; internist Murtaza Mussaji, DO, of Houston; family physician David Sneed, DO, of Austin; family physician Kevin Lewis, DO, of Houston; and family physician Angela Mosley-Nunnery, MD, of Kingwood.

Also settling was Richard DeFoore, former CEO of Jones County Regional Healthcare (dba Stamford Memorial Hospital).

The physicians were accused of accepting payments from organizations in exchange for ordering lab tests from True Health Diagnostics, Little River Healthcare, and Boston Heart. The payments to the physicians were disguised as investment returns but, according to the allegations, were in fact offered in exchange for the doctors’ referrals. Mr. DeFoore, the hospital executive involved in the settlement, allegedly oversaw a similar scheme that benefited the now-defunct Stamford Memorial.

“Paying kickbacks to physicians distorts the medical decision-making process, corrupts our health care system, and increases the cost of healthcare funded by the taxpayer,” Brit Featherston, U.S. attorney for the Eastern District of Texas, said in a statement announcing the agreement. “Laboratories, marketers, and physicians cannot immunize their conduct by attempting to disguise the kickbacks as some sort of investment arrangement.”
 

Practice administrative assistant sentenced for fraudulent prescriptions

An administrative assistant at an Illinois orthopedics office was sentenced to a year and a day in federal prison for writing fraudulent prescriptions for opioids.

Amanda Biesiada, 39, of Alsip, Ill., who worked as an administrative assistant at Hinsdale Orthopaedics in Westmont, Ill., was not a licensed physician and could not legally write the prescriptions unless instructed to do so and supervised by licensed doctors.

According to a statement by the U.S. Attorney’s Office for the Northern District of Illinois, the prescriptions for hydrocodone, oxycodone, and other controlled substances – 85 prescriptions in all from 2017 to 2019 – were made out to an acquaintance of Biesiada’s and written without the knowledge or approval of the providers in whose names she wrote them.

Federal officials said Ms. Biesiada attempted to conceal the fraudulent prescriptions by marking them “filed in error” in the practice’s prescription system.
 

Lab owner pleads guilty to $6.9 million testing fraud scheme

A Florida lab owner has pleaded guilty to conspiracy to defraud Medicare through false and fraudulent claims totaling more than $6.9 million.

According to court documents, Christopher Licata, 45, of Delray Beach, Fla., admitted to bribing patient brokers to refer orders for medically unnecessary genetic testing to his lab. The tests were then billed to Medicare.

Mr. Licata and the patient brokers entered sham agreements meant to disguise the true purpose of the payments, according to a statement from the Department of Justice. The 45-year-old owner of Boca Toxicology (dba Lab Dynamics) pleaded guilty to one count of conspiring to commit health care fraud.

The scheme began in 2018; however, once the pandemic began, Mr. Licata shifted strategies, playing on patients’ fears of COVID-19 to bundle inexpensive COVID tests with more expensive medically unnecessary tests. These tests included respiratory pathogen panels and genetic testing for cardiovascular disease, cancer, diabetes, Alzheimer’s disease, and other illnesses. In all, Mr. Licata’s laboratory submitted over $6.9 million in false and fraudulent claims to Medicare for these unnecessary tests, according to the DOJ statement.

The case is a part of the U.S. Attorney General’s COVID-19 Fraud Enforcement Task Force that was established to enhance the efforts of agencies and governments across the country to combat and prevent pandemic-related fraud.

Mr. Licata faces a maximum penalty of 10 years in prison. His sentencing is scheduled for March 24.

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

An Alaska physician has been sentenced to 34 months in prison followed by 3 years of supervised release and fined $25,000 for illegally dispensing and distributing controlled substances to his patients.

According to court documents, between January 2014 and October 2019, family physician David Chisholm, MD, 64, of Wasilla, Alaska, wrote more than 20,000 prescriptions to approximately 350 patients for oxycodone, methadone, and hydrocodone, often prescribing the pills using variations of patients’ names in an attempt to avoid being red-flagged by payers.

When Walmart refused to continue filling the prescriptions, Dr. Chisholm told his staff to advise the patients to use other pharmacies. In addition, he often prescribed combinations of medications, such as concurrent opioids, benzodiazepines, sedatives, and carisoprodol, thus increasing the chances that his patients would become addicted to or overdose on the drugs. Chisholm, who pleaded guilty in June, acknowledged to federal officials that his prescriptions were a significant contributing factor to the overdose deaths of five of his patients during this time, according to a statement by the U.S. Attorney’s Office for the District of Alaska.

According to the Anchorage Daily News, Dr. Chisholm, who was not board certified in pain medicine, said his reason for prescribing the drugs was not to make money but to help patients suffering from chronic pain and because he enjoyed the challenge.

Dr. Chisholm’s attorney, Nick Oberheiden, told CNN his client “sacrificed his reputation as a patient advocate and his years of service to the Alaskan community” in overprescribing opioids. “He expressed his sincere remorse in open court and he accepts the consequences of his misconduct. He hopes that his case serves as a warning to other physicians facing the same dilemma when treating chronic pain.”

He surrendered his medical license in November 2020 before being formally charged in April 2021.
 

Texas hospital CEO, seven doctors settle kickback

A hospital executive and seven physicians have agreed to pay a total of $1.1 million to settle allegations that they violated the Anti-Kickback Statute and Stark Law. The eight have also agreed to cooperate in investigations and litigation involving other parties.

The Texas physicians involved in the settlement are internist Jaspaul Bhangoo, MD, of Denton; family physician Robert Megna, DO, of Ferris; cardiologist Baxter Montgomery, MD, of Houston; internist Murtaza Mussaji, DO, of Houston; family physician David Sneed, DO, of Austin; family physician Kevin Lewis, DO, of Houston; and family physician Angela Mosley-Nunnery, MD, of Kingwood.

Also settling was Richard DeFoore, former CEO of Jones County Regional Healthcare (dba Stamford Memorial Hospital).

The physicians were accused of accepting payments from organizations in exchange for ordering lab tests from True Health Diagnostics, Little River Healthcare, and Boston Heart. The payments to the physicians were disguised as investment returns but, according to the allegations, were in fact offered in exchange for the doctors’ referrals. Mr. DeFoore, the hospital executive involved in the settlement, allegedly oversaw a similar scheme that benefited the now-defunct Stamford Memorial.

“Paying kickbacks to physicians distorts the medical decision-making process, corrupts our health care system, and increases the cost of healthcare funded by the taxpayer,” Brit Featherston, U.S. attorney for the Eastern District of Texas, said in a statement announcing the agreement. “Laboratories, marketers, and physicians cannot immunize their conduct by attempting to disguise the kickbacks as some sort of investment arrangement.”
 

Practice administrative assistant sentenced for fraudulent prescriptions

An administrative assistant at an Illinois orthopedics office was sentenced to a year and a day in federal prison for writing fraudulent prescriptions for opioids.

Amanda Biesiada, 39, of Alsip, Ill., who worked as an administrative assistant at Hinsdale Orthopaedics in Westmont, Ill., was not a licensed physician and could not legally write the prescriptions unless instructed to do so and supervised by licensed doctors.

According to a statement by the U.S. Attorney’s Office for the Northern District of Illinois, the prescriptions for hydrocodone, oxycodone, and other controlled substances – 85 prescriptions in all from 2017 to 2019 – were made out to an acquaintance of Biesiada’s and written without the knowledge or approval of the providers in whose names she wrote them.

Federal officials said Ms. Biesiada attempted to conceal the fraudulent prescriptions by marking them “filed in error” in the practice’s prescription system.
 

Lab owner pleads guilty to $6.9 million testing fraud scheme

A Florida lab owner has pleaded guilty to conspiracy to defraud Medicare through false and fraudulent claims totaling more than $6.9 million.

According to court documents, Christopher Licata, 45, of Delray Beach, Fla., admitted to bribing patient brokers to refer orders for medically unnecessary genetic testing to his lab. The tests were then billed to Medicare.

Mr. Licata and the patient brokers entered sham agreements meant to disguise the true purpose of the payments, according to a statement from the Department of Justice. The 45-year-old owner of Boca Toxicology (dba Lab Dynamics) pleaded guilty to one count of conspiring to commit health care fraud.

The scheme began in 2018; however, once the pandemic began, Mr. Licata shifted strategies, playing on patients’ fears of COVID-19 to bundle inexpensive COVID tests with more expensive medically unnecessary tests. These tests included respiratory pathogen panels and genetic testing for cardiovascular disease, cancer, diabetes, Alzheimer’s disease, and other illnesses. In all, Mr. Licata’s laboratory submitted over $6.9 million in false and fraudulent claims to Medicare for these unnecessary tests, according to the DOJ statement.

The case is a part of the U.S. Attorney General’s COVID-19 Fraud Enforcement Task Force that was established to enhance the efforts of agencies and governments across the country to combat and prevent pandemic-related fraud.

Mr. Licata faces a maximum penalty of 10 years in prison. His sentencing is scheduled for March 24.

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

Dhaval Bhatt had been warned about hospital emergency departments.

“People always told me to avoid the ER in America unless you are really dying,” said Dr. Bhatt, an immigrant from India who got a PhD in pharmacology in the United States and is now a research scientist at Washington University, St. Louis.

But when Dr. Bhatt’s 2-year-old son burned his hand on the kitchen stove on a Wednesday morning in April, the family’s pediatrician directed them the next day to the local children’s hospital.

Dr. Bhatt was traveling. So, his wife, Mansi Bhatt, took their son to the hospital and was sent to the ED. A nurse practitioner took the toddler’s vitals and looked at the wound. She said a surgeon would inspect it more closely.

When the surgeon didn’t appear after more than an hour, Dr. Bhatt’s wife took her son home. The hospital told her to make a follow-up appointment with a doctor, which turned out to be unnecessary because the burn healed quickly.

Then the bill came.

The patient: Martand Bhatt, a toddler covered by a UnitedHealthcare insurance plan provided by the employer of his father, Dhaval Bhatt.

Medical service: An ED visit for a burn sustained when Martand touched an electric stove.

Total bill: $1,012. UnitedHealthcare’s negotiated rate was $858.92, all of which the Bhatts were responsible for because their plan had a $3,000 deductible.

Service provider: SSM Health Cardinal Glennon Children’s Hospital, one of 23 hospitals owned by SSM Health, a Catholic, nonprofit health system with more than $8 billion in annual revenue.

What gives: Many patients don’t understand that they can rack up huge bills almost as soon as they walk through the doors of an ED.

Unlike a restaurant or a mechanic who won’t charge if someone gets tired of waiting for a table or an inspection of a rattling engine, hospital emergency rooms almost invariably charge patients as soon as they check in.

And once they register, patients will be billed – often a lot – whether treatment was rendered or not.

Martand Bhatt received almost no medical service. A nurse practitioner looked over the toddler, listened to his heart and stomach, and looked in his nose, mouth and ears, according to provider notes prepared by the hospital and shared with KHN by Dr. Bhatt.

The nurse didn’t change the dressing on the wound or order any testing.

“My objection to this is that there was no care provided,” Dr. Bhatt wrote to Bill of the Month.

“My wife did not drive for 45 minutes to get to an ER and wait for an additional 1½ hours for someone to tell me that our child’s vitals – weight, height, temperature and blood pressure – were okay,” Dr. Bhatt continued. “We already knew that. ... It is absolutely ridiculous and unethical.”

When the Bhatts left the ED, Martand was “alert, active and well appearing,” according to the notes.

The nurse’s assessment of Martand cost $192, which was discounted by UnitedHealthcare to a negotiated rate of $38.92. The bulk of the Bhatts’ bill – $820 – was something called a facility fee.

Hospital officials defend these fees as necessary to keep the ED open 24 hours a day as a community asset.

SSM Health spokesperson Stephanie Zoller Mueller declined to discuss the details of Martand’s medical condition even though the Bhatts gave their permission for the hospital to do so.

In an email, Ms. Zoller Mueller said the charges were “appropriate” based on the “acuity of condition, discharge instructions, vital sign monitoring, traumatic wound care, [and] numerous assessments.”

She added: “A patient does not have to receive additional treatment – procedure, labs, x-rays, etc. – to validate an ED-level charge.”

But some patient advocates say these facility fees are applied much too widely and should be limited to patients who actually receive medical care.

“It’s just not appropriate for someone to be charged if they’re not provided treatment,” said Adam Fox, deputy director of the Colorado Consumer Health Initiative. “Patients aren’t availing themselves of a facility if they don’t get care.”

At the very least, hospitals could communicate more clearly to patients about the fees they may be charged for coming to an ED, said Maureen Hensley-Quinn, senior program director at the National Academy for State Health Policy.

“People should know that when they walk in to receive care, there is this fee that they will be assessed,” Ms. Hensley-Quinn said.

Hospitals could also post at the entrance to the ED standard fees for different levels of emergency care.

Dr. Bhatt’s fee still could have been lower if the hospital had classified his son’s injury as minor. But, again, the hospital billing process worked against the family and in favor of the hospital’s bottom line.

Emergency visits are usually classified for billing on a scale from 1 to 5. Level 1 is minor and routine; level 5 requires complex care for life-threatening conditions. And hospitals are increasingly using the highest-severity codes to classify emergency visits, research shows.

“There are financial incentives for billing at a higher severity,” said Aditi Sen, who directs policy and research at the nonprofit Health Care Cost Institute, which has studied ED coding.

Despite the lack of severity of Martand’s wound and the absence of medical care, his visit was classified as level 3, a moderate-severity problem.

Resolution: Incensed that he’d been charged so much, Dr. Bhatt made numerous attempts to get the hospital to reduce the charges. He also appealed to UnitedHealthcare to review the charges.

His efforts failed. In August, Dr. Bhatt received a letter from an SSM Health “patient advocate” informing him that the hospital would not adjust the bill and instructing him to contact patient billing to arrange for payment.

While Dr. Bhatt was trying to reach the patient advocate by phone, his bill was sent to Medicredit, a collection agency, which began sending him notices and calling him.

After KHN contacted SSM Health, Dr. Bhatt received a call from someone who worked on “patient financial experience” issues at the hospital.

The hospital agreed to forgive the $820 facility fee. Dr. Bhatt agreed to pay the remaining $38.92, the professional fee for the ED nurse’s work. Dr. Bhatt also received a notice from Medicredit that it would take no further action against him.

The takeaway: The Bhatts did what most parents would do when a pediatrician advises them to take their child to the hospital.

But EDs are among the most expensive places to get care in the U.S. health system.

If you have a relatively low-level issue, think twice before even registering at the front desk, the act that initiates the billing process. If your doctor doesn’t have same-day appointments or after-hours service, think about urgent care, which is often much cheaper if the center isn’t attached to a hospital.

And remember that if you go to a hospital ED with a relatively minor issue, chances are that you’ll have to wait, as the Bhatts did. Patients with more serious problems will be seen first.

Once you’re taken past the front desk, you will almost certainly be hit with a substantial facility fee even if you don’t receive care.

Appealing that fee to the hospital can occasionally be successful, but there are no guarantees. And, as Dr. Bhatt learned, don’t expect the health insurer to offer much help. Most insurers won’t challenge how a medical visit is coded except on extremely expensive medical claims that will cost them money.

In this case, Dr. Bhatt was on the hook for the whole fee because he had a high-deductible plan, so the insurer had little incentive to take up his cause.

For now, patients’ best hope, many advocates believe, is to publicize the high prices that hospitals charge for their services, inside and outside the ED.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Dhaval Bhatt had been warned about hospital emergency departments.

“People always told me to avoid the ER in America unless you are really dying,” said Dr. Bhatt, an immigrant from India who got a PhD in pharmacology in the United States and is now a research scientist at Washington University, St. Louis.

But when Dr. Bhatt’s 2-year-old son burned his hand on the kitchen stove on a Wednesday morning in April, the family’s pediatrician directed them the next day to the local children’s hospital.

Dr. Bhatt was traveling. So, his wife, Mansi Bhatt, took their son to the hospital and was sent to the ED. A nurse practitioner took the toddler’s vitals and looked at the wound. She said a surgeon would inspect it more closely.

When the surgeon didn’t appear after more than an hour, Dr. Bhatt’s wife took her son home. The hospital told her to make a follow-up appointment with a doctor, which turned out to be unnecessary because the burn healed quickly.

Then the bill came.

The patient: Martand Bhatt, a toddler covered by a UnitedHealthcare insurance plan provided by the employer of his father, Dhaval Bhatt.

Medical service: An ED visit for a burn sustained when Martand touched an electric stove.

Total bill: $1,012. UnitedHealthcare’s negotiated rate was $858.92, all of which the Bhatts were responsible for because their plan had a $3,000 deductible.

Service provider: SSM Health Cardinal Glennon Children’s Hospital, one of 23 hospitals owned by SSM Health, a Catholic, nonprofit health system with more than $8 billion in annual revenue.

What gives: Many patients don’t understand that they can rack up huge bills almost as soon as they walk through the doors of an ED.

Unlike a restaurant or a mechanic who won’t charge if someone gets tired of waiting for a table or an inspection of a rattling engine, hospital emergency rooms almost invariably charge patients as soon as they check in.

And once they register, patients will be billed – often a lot – whether treatment was rendered or not.

Martand Bhatt received almost no medical service. A nurse practitioner looked over the toddler, listened to his heart and stomach, and looked in his nose, mouth and ears, according to provider notes prepared by the hospital and shared with KHN by Dr. Bhatt.

The nurse didn’t change the dressing on the wound or order any testing.

“My objection to this is that there was no care provided,” Dr. Bhatt wrote to Bill of the Month.

“My wife did not drive for 45 minutes to get to an ER and wait for an additional 1½ hours for someone to tell me that our child’s vitals – weight, height, temperature and blood pressure – were okay,” Dr. Bhatt continued. “We already knew that. ... It is absolutely ridiculous and unethical.”

When the Bhatts left the ED, Martand was “alert, active and well appearing,” according to the notes.

The nurse’s assessment of Martand cost $192, which was discounted by UnitedHealthcare to a negotiated rate of $38.92. The bulk of the Bhatts’ bill – $820 – was something called a facility fee.

Hospital officials defend these fees as necessary to keep the ED open 24 hours a day as a community asset.

SSM Health spokesperson Stephanie Zoller Mueller declined to discuss the details of Martand’s medical condition even though the Bhatts gave their permission for the hospital to do so.

In an email, Ms. Zoller Mueller said the charges were “appropriate” based on the “acuity of condition, discharge instructions, vital sign monitoring, traumatic wound care, [and] numerous assessments.”

She added: “A patient does not have to receive additional treatment – procedure, labs, x-rays, etc. – to validate an ED-level charge.”

But some patient advocates say these facility fees are applied much too widely and should be limited to patients who actually receive medical care.

“It’s just not appropriate for someone to be charged if they’re not provided treatment,” said Adam Fox, deputy director of the Colorado Consumer Health Initiative. “Patients aren’t availing themselves of a facility if they don’t get care.”

At the very least, hospitals could communicate more clearly to patients about the fees they may be charged for coming to an ED, said Maureen Hensley-Quinn, senior program director at the National Academy for State Health Policy.

“People should know that when they walk in to receive care, there is this fee that they will be assessed,” Ms. Hensley-Quinn said.

Hospitals could also post at the entrance to the ED standard fees for different levels of emergency care.

Dr. Bhatt’s fee still could have been lower if the hospital had classified his son’s injury as minor. But, again, the hospital billing process worked against the family and in favor of the hospital’s bottom line.

Emergency visits are usually classified for billing on a scale from 1 to 5. Level 1 is minor and routine; level 5 requires complex care for life-threatening conditions. And hospitals are increasingly using the highest-severity codes to classify emergency visits, research shows.

“There are financial incentives for billing at a higher severity,” said Aditi Sen, who directs policy and research at the nonprofit Health Care Cost Institute, which has studied ED coding.

Despite the lack of severity of Martand’s wound and the absence of medical care, his visit was classified as level 3, a moderate-severity problem.

Resolution: Incensed that he’d been charged so much, Dr. Bhatt made numerous attempts to get the hospital to reduce the charges. He also appealed to UnitedHealthcare to review the charges.

His efforts failed. In August, Dr. Bhatt received a letter from an SSM Health “patient advocate” informing him that the hospital would not adjust the bill and instructing him to contact patient billing to arrange for payment.

While Dr. Bhatt was trying to reach the patient advocate by phone, his bill was sent to Medicredit, a collection agency, which began sending him notices and calling him.

After KHN contacted SSM Health, Dr. Bhatt received a call from someone who worked on “patient financial experience” issues at the hospital.

The hospital agreed to forgive the $820 facility fee. Dr. Bhatt agreed to pay the remaining $38.92, the professional fee for the ED nurse’s work. Dr. Bhatt also received a notice from Medicredit that it would take no further action against him.

The takeaway: The Bhatts did what most parents would do when a pediatrician advises them to take their child to the hospital.

But EDs are among the most expensive places to get care in the U.S. health system.

If you have a relatively low-level issue, think twice before even registering at the front desk, the act that initiates the billing process. If your doctor doesn’t have same-day appointments or after-hours service, think about urgent care, which is often much cheaper if the center isn’t attached to a hospital.

And remember that if you go to a hospital ED with a relatively minor issue, chances are that you’ll have to wait, as the Bhatts did. Patients with more serious problems will be seen first.

Once you’re taken past the front desk, you will almost certainly be hit with a substantial facility fee even if you don’t receive care.

Appealing that fee to the hospital can occasionally be successful, but there are no guarantees. And, as Dr. Bhatt learned, don’t expect the health insurer to offer much help. Most insurers won’t challenge how a medical visit is coded except on extremely expensive medical claims that will cost them money.

In this case, Dr. Bhatt was on the hook for the whole fee because he had a high-deductible plan, so the insurer had little incentive to take up his cause.

For now, patients’ best hope, many advocates believe, is to publicize the high prices that hospitals charge for their services, inside and outside the ED.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Dhaval Bhatt had been warned about hospital emergency departments.

“People always told me to avoid the ER in America unless you are really dying,” said Dr. Bhatt, an immigrant from India who got a PhD in pharmacology in the United States and is now a research scientist at Washington University, St. Louis.

But when Dr. Bhatt’s 2-year-old son burned his hand on the kitchen stove on a Wednesday morning in April, the family’s pediatrician directed them the next day to the local children’s hospital.

Dr. Bhatt was traveling. So, his wife, Mansi Bhatt, took their son to the hospital and was sent to the ED. A nurse practitioner took the toddler’s vitals and looked at the wound. She said a surgeon would inspect it more closely.

When the surgeon didn’t appear after more than an hour, Dr. Bhatt’s wife took her son home. The hospital told her to make a follow-up appointment with a doctor, which turned out to be unnecessary because the burn healed quickly.

Then the bill came.

The patient: Martand Bhatt, a toddler covered by a UnitedHealthcare insurance plan provided by the employer of his father, Dhaval Bhatt.

Medical service: An ED visit for a burn sustained when Martand touched an electric stove.

Total bill: $1,012. UnitedHealthcare’s negotiated rate was $858.92, all of which the Bhatts were responsible for because their plan had a $3,000 deductible.

Service provider: SSM Health Cardinal Glennon Children’s Hospital, one of 23 hospitals owned by SSM Health, a Catholic, nonprofit health system with more than $8 billion in annual revenue.

What gives: Many patients don’t understand that they can rack up huge bills almost as soon as they walk through the doors of an ED.

Unlike a restaurant or a mechanic who won’t charge if someone gets tired of waiting for a table or an inspection of a rattling engine, hospital emergency rooms almost invariably charge patients as soon as they check in.

And once they register, patients will be billed – often a lot – whether treatment was rendered or not.

Martand Bhatt received almost no medical service. A nurse practitioner looked over the toddler, listened to his heart and stomach, and looked in his nose, mouth and ears, according to provider notes prepared by the hospital and shared with KHN by Dr. Bhatt.

The nurse didn’t change the dressing on the wound or order any testing.

“My objection to this is that there was no care provided,” Dr. Bhatt wrote to Bill of the Month.

“My wife did not drive for 45 minutes to get to an ER and wait for an additional 1½ hours for someone to tell me that our child’s vitals – weight, height, temperature and blood pressure – were okay,” Dr. Bhatt continued. “We already knew that. ... It is absolutely ridiculous and unethical.”

When the Bhatts left the ED, Martand was “alert, active and well appearing,” according to the notes.

The nurse’s assessment of Martand cost $192, which was discounted by UnitedHealthcare to a negotiated rate of $38.92. The bulk of the Bhatts’ bill – $820 – was something called a facility fee.

Hospital officials defend these fees as necessary to keep the ED open 24 hours a day as a community asset.

SSM Health spokesperson Stephanie Zoller Mueller declined to discuss the details of Martand’s medical condition even though the Bhatts gave their permission for the hospital to do so.

In an email, Ms. Zoller Mueller said the charges were “appropriate” based on the “acuity of condition, discharge instructions, vital sign monitoring, traumatic wound care, [and] numerous assessments.”

She added: “A patient does not have to receive additional treatment – procedure, labs, x-rays, etc. – to validate an ED-level charge.”

But some patient advocates say these facility fees are applied much too widely and should be limited to patients who actually receive medical care.

“It’s just not appropriate for someone to be charged if they’re not provided treatment,” said Adam Fox, deputy director of the Colorado Consumer Health Initiative. “Patients aren’t availing themselves of a facility if they don’t get care.”

At the very least, hospitals could communicate more clearly to patients about the fees they may be charged for coming to an ED, said Maureen Hensley-Quinn, senior program director at the National Academy for State Health Policy.

“People should know that when they walk in to receive care, there is this fee that they will be assessed,” Ms. Hensley-Quinn said.

Hospitals could also post at the entrance to the ED standard fees for different levels of emergency care.

Dr. Bhatt’s fee still could have been lower if the hospital had classified his son’s injury as minor. But, again, the hospital billing process worked against the family and in favor of the hospital’s bottom line.

Emergency visits are usually classified for billing on a scale from 1 to 5. Level 1 is minor and routine; level 5 requires complex care for life-threatening conditions. And hospitals are increasingly using the highest-severity codes to classify emergency visits, research shows.

“There are financial incentives for billing at a higher severity,” said Aditi Sen, who directs policy and research at the nonprofit Health Care Cost Institute, which has studied ED coding.

Despite the lack of severity of Martand’s wound and the absence of medical care, his visit was classified as level 3, a moderate-severity problem.

Resolution: Incensed that he’d been charged so much, Dr. Bhatt made numerous attempts to get the hospital to reduce the charges. He also appealed to UnitedHealthcare to review the charges.

His efforts failed. In August, Dr. Bhatt received a letter from an SSM Health “patient advocate” informing him that the hospital would not adjust the bill and instructing him to contact patient billing to arrange for payment.

While Dr. Bhatt was trying to reach the patient advocate by phone, his bill was sent to Medicredit, a collection agency, which began sending him notices and calling him.

After KHN contacted SSM Health, Dr. Bhatt received a call from someone who worked on “patient financial experience” issues at the hospital.

The hospital agreed to forgive the $820 facility fee. Dr. Bhatt agreed to pay the remaining $38.92, the professional fee for the ED nurse’s work. Dr. Bhatt also received a notice from Medicredit that it would take no further action against him.

The takeaway: The Bhatts did what most parents would do when a pediatrician advises them to take their child to the hospital.

But EDs are among the most expensive places to get care in the U.S. health system.

If you have a relatively low-level issue, think twice before even registering at the front desk, the act that initiates the billing process. If your doctor doesn’t have same-day appointments or after-hours service, think about urgent care, which is often much cheaper if the center isn’t attached to a hospital.

And remember that if you go to a hospital ED with a relatively minor issue, chances are that you’ll have to wait, as the Bhatts did. Patients with more serious problems will be seen first.

Once you’re taken past the front desk, you will almost certainly be hit with a substantial facility fee even if you don’t receive care.

Appealing that fee to the hospital can occasionally be successful, but there are no guarantees. And, as Dr. Bhatt learned, don’t expect the health insurer to offer much help. Most insurers won’t challenge how a medical visit is coded except on extremely expensive medical claims that will cost them money.

In this case, Dr. Bhatt was on the hook for the whole fee because he had a high-deductible plan, so the insurer had little incentive to take up his cause.

For now, patients’ best hope, many advocates believe, is to publicize the high prices that hospitals charge for their services, inside and outside the ED.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.

Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.

The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.

The study was published online Jan. 11 in the American Journal of Psychiatry.
 

Target depression

Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.

“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.

Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.

To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.

All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.

Participants were randomly allocated to one of four groups:

1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy

2. three saline infusions plus psychological therapy

3. three ketamine infusions plus alcohol education

4. three saline infusions plus alcohol education

The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.

At 6-month follow-up, ketamine was associated with a significantly greater number of days abstinent from alcohol (mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.

The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).

There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
 

Growing evidence

These findings support some other studies that have also suggested a benefit of ketamine in AUD.

As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.

A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.

“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.

“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.

Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
 

An ‘Intriguing new therapy’

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”

“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.

“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.

The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.

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

Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.

Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.

The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.

The study was published online Jan. 11 in the American Journal of Psychiatry.
 

Target depression

Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.

“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.

Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.

To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.

All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.

Participants were randomly allocated to one of four groups:

1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy

2. three saline infusions plus psychological therapy

3. three ketamine infusions plus alcohol education

4. three saline infusions plus alcohol education

The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.

At 6-month follow-up, ketamine was associated with a significantly greater number of days abstinent from alcohol (mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.

The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).

There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
 

Growing evidence

These findings support some other studies that have also suggested a benefit of ketamine in AUD.

As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.

A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.

“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.

“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.

Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
 

An ‘Intriguing new therapy’

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”

“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.

“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.

The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.

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

Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.

Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.

The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.

The study was published online Jan. 11 in the American Journal of Psychiatry.
 

Target depression

Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.

“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.

Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.

To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.

All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.

Participants were randomly allocated to one of four groups:

1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy

2. three saline infusions plus psychological therapy

3. three ketamine infusions plus alcohol education

4. three saline infusions plus alcohol education

The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.

At 6-month follow-up, ketamine was associated with a significantly greater number of days abstinent from alcohol (mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.

The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).

There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
 

Growing evidence

These findings support some other studies that have also suggested a benefit of ketamine in AUD.

As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.

A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.

“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.

“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.

Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
 

An ‘Intriguing new therapy’

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”

“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.

“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.

The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.

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