MDedge Endocrinology

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

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

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

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

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

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

The amount of medical knowledge is said to double every 73 days, making it much tougher for physicians to identify innovative findings and newer guidelines for helping patients. Yet not keeping up with the latest information can put doctors at risk. 

“Most doctors are feeling lost about keeping up to date,” said John P.A. Ioannidis, MD, professor of medicine at Stanford (Calif.) University School of Medicine. “The vast majority of new studies are either wrong or not useful, but physicians cannot sort out which are those studies.”

The sheer number of new studies may even force some doctors to retreat from areas where they have not kept up, said Stephen A. Martin, MD, professor of family medicine and community health at the University of Massachusetts, Worcester. “When doctors don’t feel they can stay current, they may refer more cases to specialists or narrow their focus,” he said.
 

Some specialties have a greater challenge than others

Dr. Martin said the deluge of studies heavily impacts generalists because they have a wider field of information to keep up with. However, certain specialties like oncology are particularly flooded with new findings.

Specialties with the greatest number of published studies are reportedly oncology, cardiology, and neurology. A 2021 study found that the number of articles with the word “stroke” in them increased five times from 2000 to 2020. And investigative treatments targeting cancer nearly quadrupled just between 2010 and 2020.

What’s more, physicians spend a great deal of time sifting through studies that are ultimately useless. In a survey of internists by Univadis, which is part of WebMD/Medscape, 82% said that fewer than half of the studies they read actually had an impact on how they practice medicine.

“You often have to dig into an article and learn more about a finding before you now whether it’s useful,” Dr. Martin said. “And in the end, relatively few new findings are truly novel ones that are useful for patient care.”
 

So what can a physician do? First, find out what you don’t know

Looking for new findings needs to be carried out systematically, according to William B. Cutrer, MD, MEd, a pediatric intensivist who is associate dean for undergraduate medical education at Vanderbilt University School of Medicine, Nashville, Tenn.

“Before you start, you have to know what you don’t know, and that’s often not so easy,” he said. “You may get a spark about what you don’t know in an encounter with a patient or colleague or through patient outcomes data,” he said. 

Dr. Martin, on the other hand, advocates a broad approach that involves finding out at least a little about everything in one’s field. “If you have a good base, you’re not starting from zero when you encounter a new clinical situation,” he said.

“The idea is that you don’t need to memorize most things, but you do need to know how to access them,” Dr. Martin said. “I memorize the things I do all the time, such as dosing or indicated testing, but I look up things that I don’t see that often and ones that have some complexity.”
 

Updating the old ways

For generations, doctors have stayed current by going to meetings, conversing with colleagues, and reading journals, but many physicians have updated these methods through various resources on the internet.

For example, meetings went virtual during the pandemic, and now that face-to-face meetings are back, many of them retain a virtual option, said Kevin Campbell, MD, a cardiologist at Health First Medical Group, Melbourne, Fla. “I typically go to one or two conferences a year, but I also learn a lot digitally,” he said. 

As to journal reading, “assessing an article is an essential skill,” Dr. Cutrer said. “It’s important to quickly decide whether a journal article is worth reading or not. One answer to this problem is to consult summaries of important articles. But summaries are sometimes unhelpful, and it is hard to know which articles are significant. Therefore, doctors have been reaching out to others who can research the articles for them.”   

For many years, some physicians have pooled their resources in journal clubs. “You get a chance to cross-cultivate your skills with others,” Dr. Ioannidis said. “But you need someone who is well informed and dedicated to run the journal club, using evidence-based principles.”

Dr. Cutrer said physicians like to cast their net wide because they are understandably wary of changing their practice based on one study. “Unless there is one large study that is really well designed, doctors will need two or more findings to be convinced,” he said. This requires having the ability to match studies across many journals.
 

Using research summaries

In the past two decades, physicians have gained access to countless summaries of journal articles prepared by armies of clinical experts working for review services such as the New England Journal of Medicine’s “Journal Watch,” Annals of Internal Medicine’s “In the Clinic,” and BMJ’s “State of the Arts.”

In addition to summarizing findings from a wide variety of journals in plain language, reviewers may compare them to similar studies and assess the validity of the finding by assigning a level of evidence.

Some commercial ventures provide similar services. Betsy Jones, executive vice president of clinical decisions at EBSCO, said the DynaMed service is now available through an app on the physician’s smartphone or through the electronic health record.

Physicians like this approach. Many specialists have noted that reading full-length articles was not an efficient use of their time, while even more said that reviews are efficient.
 

Exchanging information online

Physicians are increasingly keeping current by using the internet, especially on social media, Dr. Cutrer said. “Young doctors in particular are more likely to keep up digitally,” he said.

Internet-based information has become so widespread that disparities in health care from region to region have somewhat abated, according to Stuart J. Fischer, MD, an orthopedic surgeon at Summit Orthopaedics and Sports Medicine, New Jersey. “One positive outcome of this plethora of information today is that geographic disparities in clinical practice are not as great as they used to be,” he said.  

Rather than chatting up colleagues in the hallway, many physicians have come to rely on internet-based discussion boards. 
 

Blogs, podcasts, and Twitter

Blogs and podcasts, often focused on a specialty, can be a great way for physicians to keep up, said UMass Chan professor Dr. Martin. “Podcasts in particular have enhanced the ability to stay current,” he said. “You want to find someone you trust.”

Internal medicine podcasts include Annals on Call, where doctors discuss articles in the Annals of Internal Medicine, and the Curbsiders, where two internists interview a guest expert.

Orthopedic surgeons can visit podcasts like Nailed it, Orthobullets, the Ortho Show, and Inside Orthopedics. Neurologists can consult Brainwaves, Neurology Podcast, Practical Neurology Podcast, and Clinical Neurology with KD. And pediatricians can drop in on Talking Pediatrics, The Cribsiders, and PedsCases.

Meanwhile, Twitter has become a particularly effective way to broadcast new findings, speeding up the transition from the bench to the bedside, said Dr. Campbell, the Florida cardiologist. 

“I visit cardio-specific resources on Twitter,” he said. “They can be real-time video chats or posted messages. They spur discussion like a journal club. Colleagues present cases and drop in and out of the discussion.”

Others are not as enthusiastic. Although Stanford’s Dr. Ioannidis is in the heart of the Silicon Valley, he is leery of some of the new digital methods. “I don’t use Twitter,” he says. “You just add more people to the process, which could only make things more confusing. I want to be able to think a lot about it.”
 

Cutting-edge knowledge at the point of care

Consulting the literature often takes place at the point of care, when a particular patient requires treatment. This can be done by using clinical decision support (CDS) and by using clinical practice guidelines (CPGs), which are typically developed by panels of doctors at specialty societies.

“It used to be that the doctor was expected to know everything,” said Ms. Jones at DynaMed. “Today there is no way to keep up with it all. Doctors often need a quick memory jog.”

Ms. Jones said the CDS result always requires the doctor’s interpretation. “It is up to the doctor to decide whether a new finding is the best choice for his or her patient,” she said.

Dr. Martin recommends going easy on point-of-care resources. “They can be used for showing a patient a differential diagnosis list or checking the cost of a procedure, but they are harder to use for novel developments that require time and context to evaluate their impact,” he said.

CPGs, meanwhile, have a high profile in the research world. In a 2018 study, Dr. Ioannidis found that 8 of the 15 most-cited articles were CPGs, disease definitions, or disease statistics.

Dr. Fischer said CPGs are typically based on thorough reviews of the literature, but they do involve experts’ interpretation of the science. “It can be difficult to obtain specific answers to some medical questions, especially for problems with complex treatments or variations,” he said.

As a result, Dr. Fischer said doctors have to use their judgment in applying CPGs to a specific patient. “For example, the orthopedic surgeon would normally recommend a total hip replacement for patients with a bad hip, but it might not be appropriate for an overweight patient.”
 

Stay skeptical

There are many novel ways for physicians to keep current, including summaries of articles, discussion boards, blogs, podcasts, Twitter, clinical decision support, and clinical practice guidelines.

Even with all these new services, though, doctors need to retain a healthy amount of skepticism about new research findings, Dr. Ioannidis said. “Ask yourself questions such as: Does it deal with a real problem? Am I getting the real information? Is it relevant to real patients? Is it offering good value for money?”

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

The amount of medical knowledge is said to double every 73 days, making it much tougher for physicians to identify innovative findings and newer guidelines for helping patients. Yet not keeping up with the latest information can put doctors at risk. 

“Most doctors are feeling lost about keeping up to date,” said John P.A. Ioannidis, MD, professor of medicine at Stanford (Calif.) University School of Medicine. “The vast majority of new studies are either wrong or not useful, but physicians cannot sort out which are those studies.”

The sheer number of new studies may even force some doctors to retreat from areas where they have not kept up, said Stephen A. Martin, MD, professor of family medicine and community health at the University of Massachusetts, Worcester. “When doctors don’t feel they can stay current, they may refer more cases to specialists or narrow their focus,” he said.
 

Some specialties have a greater challenge than others

Dr. Martin said the deluge of studies heavily impacts generalists because they have a wider field of information to keep up with. However, certain specialties like oncology are particularly flooded with new findings.

Specialties with the greatest number of published studies are reportedly oncology, cardiology, and neurology. A 2021 study found that the number of articles with the word “stroke” in them increased five times from 2000 to 2020. And investigative treatments targeting cancer nearly quadrupled just between 2010 and 2020.

What’s more, physicians spend a great deal of time sifting through studies that are ultimately useless. In a survey of internists by Univadis, which is part of WebMD/Medscape, 82% said that fewer than half of the studies they read actually had an impact on how they practice medicine.

“You often have to dig into an article and learn more about a finding before you now whether it’s useful,” Dr. Martin said. “And in the end, relatively few new findings are truly novel ones that are useful for patient care.”
 

So what can a physician do? First, find out what you don’t know

Looking for new findings needs to be carried out systematically, according to William B. Cutrer, MD, MEd, a pediatric intensivist who is associate dean for undergraduate medical education at Vanderbilt University School of Medicine, Nashville, Tenn.

“Before you start, you have to know what you don’t know, and that’s often not so easy,” he said. “You may get a spark about what you don’t know in an encounter with a patient or colleague or through patient outcomes data,” he said. 

Dr. Martin, on the other hand, advocates a broad approach that involves finding out at least a little about everything in one’s field. “If you have a good base, you’re not starting from zero when you encounter a new clinical situation,” he said.

“The idea is that you don’t need to memorize most things, but you do need to know how to access them,” Dr. Martin said. “I memorize the things I do all the time, such as dosing or indicated testing, but I look up things that I don’t see that often and ones that have some complexity.”
 

Updating the old ways

For generations, doctors have stayed current by going to meetings, conversing with colleagues, and reading journals, but many physicians have updated these methods through various resources on the internet.

For example, meetings went virtual during the pandemic, and now that face-to-face meetings are back, many of them retain a virtual option, said Kevin Campbell, MD, a cardiologist at Health First Medical Group, Melbourne, Fla. “I typically go to one or two conferences a year, but I also learn a lot digitally,” he said. 

As to journal reading, “assessing an article is an essential skill,” Dr. Cutrer said. “It’s important to quickly decide whether a journal article is worth reading or not. One answer to this problem is to consult summaries of important articles. But summaries are sometimes unhelpful, and it is hard to know which articles are significant. Therefore, doctors have been reaching out to others who can research the articles for them.”   

For many years, some physicians have pooled their resources in journal clubs. “You get a chance to cross-cultivate your skills with others,” Dr. Ioannidis said. “But you need someone who is well informed and dedicated to run the journal club, using evidence-based principles.”

Dr. Cutrer said physicians like to cast their net wide because they are understandably wary of changing their practice based on one study. “Unless there is one large study that is really well designed, doctors will need two or more findings to be convinced,” he said. This requires having the ability to match studies across many journals.
 

Using research summaries

In the past two decades, physicians have gained access to countless summaries of journal articles prepared by armies of clinical experts working for review services such as the New England Journal of Medicine’s “Journal Watch,” Annals of Internal Medicine’s “In the Clinic,” and BMJ’s “State of the Arts.”

In addition to summarizing findings from a wide variety of journals in plain language, reviewers may compare them to similar studies and assess the validity of the finding by assigning a level of evidence.

Some commercial ventures provide similar services. Betsy Jones, executive vice president of clinical decisions at EBSCO, said the DynaMed service is now available through an app on the physician’s smartphone or through the electronic health record.

Physicians like this approach. Many specialists have noted that reading full-length articles was not an efficient use of their time, while even more said that reviews are efficient.
 

Exchanging information online

Physicians are increasingly keeping current by using the internet, especially on social media, Dr. Cutrer said. “Young doctors in particular are more likely to keep up digitally,” he said.

Internet-based information has become so widespread that disparities in health care from region to region have somewhat abated, according to Stuart J. Fischer, MD, an orthopedic surgeon at Summit Orthopaedics and Sports Medicine, New Jersey. “One positive outcome of this plethora of information today is that geographic disparities in clinical practice are not as great as they used to be,” he said.  

Rather than chatting up colleagues in the hallway, many physicians have come to rely on internet-based discussion boards. 
 

Blogs, podcasts, and Twitter

Blogs and podcasts, often focused on a specialty, can be a great way for physicians to keep up, said UMass Chan professor Dr. Martin. “Podcasts in particular have enhanced the ability to stay current,” he said. “You want to find someone you trust.”

Internal medicine podcasts include Annals on Call, where doctors discuss articles in the Annals of Internal Medicine, and the Curbsiders, where two internists interview a guest expert.

Orthopedic surgeons can visit podcasts like Nailed it, Orthobullets, the Ortho Show, and Inside Orthopedics. Neurologists can consult Brainwaves, Neurology Podcast, Practical Neurology Podcast, and Clinical Neurology with KD. And pediatricians can drop in on Talking Pediatrics, The Cribsiders, and PedsCases.

Meanwhile, Twitter has become a particularly effective way to broadcast new findings, speeding up the transition from the bench to the bedside, said Dr. Campbell, the Florida cardiologist. 

“I visit cardio-specific resources on Twitter,” he said. “They can be real-time video chats or posted messages. They spur discussion like a journal club. Colleagues present cases and drop in and out of the discussion.”

Others are not as enthusiastic. Although Stanford’s Dr. Ioannidis is in the heart of the Silicon Valley, he is leery of some of the new digital methods. “I don’t use Twitter,” he says. “You just add more people to the process, which could only make things more confusing. I want to be able to think a lot about it.”
 

Cutting-edge knowledge at the point of care

Consulting the literature often takes place at the point of care, when a particular patient requires treatment. This can be done by using clinical decision support (CDS) and by using clinical practice guidelines (CPGs), which are typically developed by panels of doctors at specialty societies.

“It used to be that the doctor was expected to know everything,” said Ms. Jones at DynaMed. “Today there is no way to keep up with it all. Doctors often need a quick memory jog.”

Ms. Jones said the CDS result always requires the doctor’s interpretation. “It is up to the doctor to decide whether a new finding is the best choice for his or her patient,” she said.

Dr. Martin recommends going easy on point-of-care resources. “They can be used for showing a patient a differential diagnosis list or checking the cost of a procedure, but they are harder to use for novel developments that require time and context to evaluate their impact,” he said.

CPGs, meanwhile, have a high profile in the research world. In a 2018 study, Dr. Ioannidis found that 8 of the 15 most-cited articles were CPGs, disease definitions, or disease statistics.

Dr. Fischer said CPGs are typically based on thorough reviews of the literature, but they do involve experts’ interpretation of the science. “It can be difficult to obtain specific answers to some medical questions, especially for problems with complex treatments or variations,” he said.

As a result, Dr. Fischer said doctors have to use their judgment in applying CPGs to a specific patient. “For example, the orthopedic surgeon would normally recommend a total hip replacement for patients with a bad hip, but it might not be appropriate for an overweight patient.”
 

Stay skeptical

There are many novel ways for physicians to keep current, including summaries of articles, discussion boards, blogs, podcasts, Twitter, clinical decision support, and clinical practice guidelines.

Even with all these new services, though, doctors need to retain a healthy amount of skepticism about new research findings, Dr. Ioannidis said. “Ask yourself questions such as: Does it deal with a real problem? Am I getting the real information? Is it relevant to real patients? Is it offering good value for money?”

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

The amount of medical knowledge is said to double every 73 days, making it much tougher for physicians to identify innovative findings and newer guidelines for helping patients. Yet not keeping up with the latest information can put doctors at risk. 

“Most doctors are feeling lost about keeping up to date,” said John P.A. Ioannidis, MD, professor of medicine at Stanford (Calif.) University School of Medicine. “The vast majority of new studies are either wrong or not useful, but physicians cannot sort out which are those studies.”

The sheer number of new studies may even force some doctors to retreat from areas where they have not kept up, said Stephen A. Martin, MD, professor of family medicine and community health at the University of Massachusetts, Worcester. “When doctors don’t feel they can stay current, they may refer more cases to specialists or narrow their focus,” he said.
 

Some specialties have a greater challenge than others

Dr. Martin said the deluge of studies heavily impacts generalists because they have a wider field of information to keep up with. However, certain specialties like oncology are particularly flooded with new findings.

Specialties with the greatest number of published studies are reportedly oncology, cardiology, and neurology. A 2021 study found that the number of articles with the word “stroke” in them increased five times from 2000 to 2020. And investigative treatments targeting cancer nearly quadrupled just between 2010 and 2020.

What’s more, physicians spend a great deal of time sifting through studies that are ultimately useless. In a survey of internists by Univadis, which is part of WebMD/Medscape, 82% said that fewer than half of the studies they read actually had an impact on how they practice medicine.

“You often have to dig into an article and learn more about a finding before you now whether it’s useful,” Dr. Martin said. “And in the end, relatively few new findings are truly novel ones that are useful for patient care.”
 

So what can a physician do? First, find out what you don’t know

Looking for new findings needs to be carried out systematically, according to William B. Cutrer, MD, MEd, a pediatric intensivist who is associate dean for undergraduate medical education at Vanderbilt University School of Medicine, Nashville, Tenn.

“Before you start, you have to know what you don’t know, and that’s often not so easy,” he said. “You may get a spark about what you don’t know in an encounter with a patient or colleague or through patient outcomes data,” he said. 

Dr. Martin, on the other hand, advocates a broad approach that involves finding out at least a little about everything in one’s field. “If you have a good base, you’re not starting from zero when you encounter a new clinical situation,” he said.

“The idea is that you don’t need to memorize most things, but you do need to know how to access them,” Dr. Martin said. “I memorize the things I do all the time, such as dosing or indicated testing, but I look up things that I don’t see that often and ones that have some complexity.”
 

Updating the old ways

For generations, doctors have stayed current by going to meetings, conversing with colleagues, and reading journals, but many physicians have updated these methods through various resources on the internet.

For example, meetings went virtual during the pandemic, and now that face-to-face meetings are back, many of them retain a virtual option, said Kevin Campbell, MD, a cardiologist at Health First Medical Group, Melbourne, Fla. “I typically go to one or two conferences a year, but I also learn a lot digitally,” he said. 

As to journal reading, “assessing an article is an essential skill,” Dr. Cutrer said. “It’s important to quickly decide whether a journal article is worth reading or not. One answer to this problem is to consult summaries of important articles. But summaries are sometimes unhelpful, and it is hard to know which articles are significant. Therefore, doctors have been reaching out to others who can research the articles for them.”   

For many years, some physicians have pooled their resources in journal clubs. “You get a chance to cross-cultivate your skills with others,” Dr. Ioannidis said. “But you need someone who is well informed and dedicated to run the journal club, using evidence-based principles.”

Dr. Cutrer said physicians like to cast their net wide because they are understandably wary of changing their practice based on one study. “Unless there is one large study that is really well designed, doctors will need two or more findings to be convinced,” he said. This requires having the ability to match studies across many journals.
 

Using research summaries

In the past two decades, physicians have gained access to countless summaries of journal articles prepared by armies of clinical experts working for review services such as the New England Journal of Medicine’s “Journal Watch,” Annals of Internal Medicine’s “In the Clinic,” and BMJ’s “State of the Arts.”

In addition to summarizing findings from a wide variety of journals in plain language, reviewers may compare them to similar studies and assess the validity of the finding by assigning a level of evidence.

Some commercial ventures provide similar services. Betsy Jones, executive vice president of clinical decisions at EBSCO, said the DynaMed service is now available through an app on the physician’s smartphone or through the electronic health record.

Physicians like this approach. Many specialists have noted that reading full-length articles was not an efficient use of their time, while even more said that reviews are efficient.
 

Exchanging information online

Physicians are increasingly keeping current by using the internet, especially on social media, Dr. Cutrer said. “Young doctors in particular are more likely to keep up digitally,” he said.

Internet-based information has become so widespread that disparities in health care from region to region have somewhat abated, according to Stuart J. Fischer, MD, an orthopedic surgeon at Summit Orthopaedics and Sports Medicine, New Jersey. “One positive outcome of this plethora of information today is that geographic disparities in clinical practice are not as great as they used to be,” he said.  

Rather than chatting up colleagues in the hallway, many physicians have come to rely on internet-based discussion boards. 
 

Blogs, podcasts, and Twitter

Blogs and podcasts, often focused on a specialty, can be a great way for physicians to keep up, said UMass Chan professor Dr. Martin. “Podcasts in particular have enhanced the ability to stay current,” he said. “You want to find someone you trust.”

Internal medicine podcasts include Annals on Call, where doctors discuss articles in the Annals of Internal Medicine, and the Curbsiders, where two internists interview a guest expert.

Orthopedic surgeons can visit podcasts like Nailed it, Orthobullets, the Ortho Show, and Inside Orthopedics. Neurologists can consult Brainwaves, Neurology Podcast, Practical Neurology Podcast, and Clinical Neurology with KD. And pediatricians can drop in on Talking Pediatrics, The Cribsiders, and PedsCases.

Meanwhile, Twitter has become a particularly effective way to broadcast new findings, speeding up the transition from the bench to the bedside, said Dr. Campbell, the Florida cardiologist. 

“I visit cardio-specific resources on Twitter,” he said. “They can be real-time video chats or posted messages. They spur discussion like a journal club. Colleagues present cases and drop in and out of the discussion.”

Others are not as enthusiastic. Although Stanford’s Dr. Ioannidis is in the heart of the Silicon Valley, he is leery of some of the new digital methods. “I don’t use Twitter,” he says. “You just add more people to the process, which could only make things more confusing. I want to be able to think a lot about it.”
 

Cutting-edge knowledge at the point of care

Consulting the literature often takes place at the point of care, when a particular patient requires treatment. This can be done by using clinical decision support (CDS) and by using clinical practice guidelines (CPGs), which are typically developed by panels of doctors at specialty societies.

“It used to be that the doctor was expected to know everything,” said Ms. Jones at DynaMed. “Today there is no way to keep up with it all. Doctors often need a quick memory jog.”

Ms. Jones said the CDS result always requires the doctor’s interpretation. “It is up to the doctor to decide whether a new finding is the best choice for his or her patient,” she said.

Dr. Martin recommends going easy on point-of-care resources. “They can be used for showing a patient a differential diagnosis list or checking the cost of a procedure, but they are harder to use for novel developments that require time and context to evaluate their impact,” he said.

CPGs, meanwhile, have a high profile in the research world. In a 2018 study, Dr. Ioannidis found that 8 of the 15 most-cited articles were CPGs, disease definitions, or disease statistics.

Dr. Fischer said CPGs are typically based on thorough reviews of the literature, but they do involve experts’ interpretation of the science. “It can be difficult to obtain specific answers to some medical questions, especially for problems with complex treatments or variations,” he said.

As a result, Dr. Fischer said doctors have to use their judgment in applying CPGs to a specific patient. “For example, the orthopedic surgeon would normally recommend a total hip replacement for patients with a bad hip, but it might not be appropriate for an overweight patient.”
 

Stay skeptical

There are many novel ways for physicians to keep current, including summaries of articles, discussion boards, blogs, podcasts, Twitter, clinical decision support, and clinical practice guidelines.

Even with all these new services, though, doctors need to retain a healthy amount of skepticism about new research findings, Dr. Ioannidis said. “Ask yourself questions such as: Does it deal with a real problem? Am I getting the real information? Is it relevant to real patients? Is it offering good value for money?”

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

Technologies that allow people to monitor blood sugar and automate the administration of insulin have radically transformed the lives of patients – and children in particular – with type 1 diabetes. But the devices often come with a cost: Insulin pumps and continuous glucose monitors can irritate the skin at the points of contact, causing some people to stop using their pumps or monitors altogether.

Regular use of lipid-rich skin creams can reduce eczema in children who use insulin pumps and continuous glucose monitors to manage type 1 diabetes, Danish researchers reported last month. The article is currently undergoing peer review at The Lancet Diabetes and Endocrinology, and the authors said they hope their approach will deter more children from abandoning diabetes technology.

“A simple thing can actually change a lot,” said Anna Korsgaard Berg, MD, a pediatrician who specializes in diabetes care at Copenhagen University Hospital’s Steno Diabetes Center in Herlev, Denmark, and a coauthor of the new study. “Not all skin reactions can be solved by the skin care program, but it can help improve the issue.”

More than 1.5 million children and adolescents worldwide live with type 1 diabetes, a condition that requires continuous insulin infusion. Insulin pumps meet this need in many wealthier countries, and are often used in combination with sensors that measure a child’s glucose level. Both the American Diabetes Association and the International Society for Adolescent and Pediatric Diabetes recommend insulin pumps and continuous glucose monitors as core treatment tools.

Dr. Berg and colleagues, who have previously shown that as many as 90% of children who use these devices experience some kind of skin reaction, want to minimize the rate of such discomfort in hopes that fewer children stop using the devices. According to a 2014 study, 18% of people with type 1 diabetes who stopped using continuous glucose monitors did so because of skin irritation.
 

Lather on that lipid-rich lotion

Dr. Berg and colleagues studied 170 children and adolescents with type 1 diabetes (average age, 11 years) who use insulin pumps, continuous glucose monitors, or both. From March 2020 to July 2021, 112 children (55 girls) employed a skin care program developed for the study, while the other 58 (34 girls) did not receive any skin care advice.

The skin care group received instructions about how to gently insert and remove their insulin pumps or glucose monitors, to minimize skin damage. They also were told to avoid disinfectants such as alcohol, which can irritate skin. The children in this group used a cream containing 70% lipids to help rehydrate their skin, applying the salve each day a device was not inserted into their skin.

Eczema can be a real problem for kids who use insulin pumps and continuous glucose monitors to manage type 1 diabetes. Researchers found that regular use of lipid-rich skin creams can reduce its incidence.

Although insulin pumps and glucose monitors are kept in place for longer periods of time than they once were, Dr. Berg and colleagues noted, users do periodically remove them when bathing or when undergoing medical tests that involve x-rays. On days when the devices were not in place for a period of time, children in the skin care group were encouraged to follow the protocol.
 

Study results

One-third of children in the skin care group developed eczema or experienced a wound, compared with almost half of the children in the control group, according to the researchers. The absolute difference in developing eczema or wounds between the two groups was 12.9 % (95% confidence interval, –28.7% to 2.9%).

Children in the skin care group were much less likely to develop wounds, the researchers found, when they focused only on wounds and not eczema (odds ratio, 0.29, 95% CI, 0.12-0.68).

Dr. Berg said she would like to explore whether other techniques, such as a combination of patches, adhesives, or other lotions, yield even better results.

“Anything that can help people use technology more consistently is better for both quality of life and diabetes outcomes,” said Priya Prahalad, MD, a specialist in pediatric endocrinology and diabetes at Stanford Medicine Children’s Health in Palo Alto and Sunnyvale, Calif. 

Dr. Prahalad, who was not involved in the Danish study, said that although the sample sizes in the trial were relatively small, the data are “headed in the right direction.”

Pediatricians already recommend using moisturizing creams at the sites where pumps or glucose monitors are inserted into the skin, she noted. But the new study simply employed an especially moisturizing cream to mitigate skin damage.

Although one reason for skin irritation may be the repeated insertion and removal of devices, Dr. Berg and Dr. Prahalad stressed that the medical devices themselves may contain allergy-causing components. Device makers are not required to disclose what’s inside the boxes.

“I do not understand why the full content of a device is not by law mandatory to declare, when declaration by law is mandatory for many other products and drugs but not for medical devices,” Dr. Berg said.

Dr. Berg reports receiving lipid cream from Teva Pharmaceuticals and research support from Medtronic. Dr. Prahalad reports no relevant financial relationships.

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

Technologies that allow people to monitor blood sugar and automate the administration of insulin have radically transformed the lives of patients – and children in particular – with type 1 diabetes. But the devices often come with a cost: Insulin pumps and continuous glucose monitors can irritate the skin at the points of contact, causing some people to stop using their pumps or monitors altogether.

Regular use of lipid-rich skin creams can reduce eczema in children who use insulin pumps and continuous glucose monitors to manage type 1 diabetes, Danish researchers reported last month. The article is currently undergoing peer review at The Lancet Diabetes and Endocrinology, and the authors said they hope their approach will deter more children from abandoning diabetes technology.

“A simple thing can actually change a lot,” said Anna Korsgaard Berg, MD, a pediatrician who specializes in diabetes care at Copenhagen University Hospital’s Steno Diabetes Center in Herlev, Denmark, and a coauthor of the new study. “Not all skin reactions can be solved by the skin care program, but it can help improve the issue.”

More than 1.5 million children and adolescents worldwide live with type 1 diabetes, a condition that requires continuous insulin infusion. Insulin pumps meet this need in many wealthier countries, and are often used in combination with sensors that measure a child’s glucose level. Both the American Diabetes Association and the International Society for Adolescent and Pediatric Diabetes recommend insulin pumps and continuous glucose monitors as core treatment tools.

Dr. Berg and colleagues, who have previously shown that as many as 90% of children who use these devices experience some kind of skin reaction, want to minimize the rate of such discomfort in hopes that fewer children stop using the devices. According to a 2014 study, 18% of people with type 1 diabetes who stopped using continuous glucose monitors did so because of skin irritation.
 

Lather on that lipid-rich lotion

Dr. Berg and colleagues studied 170 children and adolescents with type 1 diabetes (average age, 11 years) who use insulin pumps, continuous glucose monitors, or both. From March 2020 to July 2021, 112 children (55 girls) employed a skin care program developed for the study, while the other 58 (34 girls) did not receive any skin care advice.

The skin care group received instructions about how to gently insert and remove their insulin pumps or glucose monitors, to minimize skin damage. They also were told to avoid disinfectants such as alcohol, which can irritate skin. The children in this group used a cream containing 70% lipids to help rehydrate their skin, applying the salve each day a device was not inserted into their skin.

Eczema can be a real problem for kids who use insulin pumps and continuous glucose monitors to manage type 1 diabetes. Researchers found that regular use of lipid-rich skin creams can reduce its incidence.

Although insulin pumps and glucose monitors are kept in place for longer periods of time than they once were, Dr. Berg and colleagues noted, users do periodically remove them when bathing or when undergoing medical tests that involve x-rays. On days when the devices were not in place for a period of time, children in the skin care group were encouraged to follow the protocol.
 

Study results

One-third of children in the skin care group developed eczema or experienced a wound, compared with almost half of the children in the control group, according to the researchers. The absolute difference in developing eczema or wounds between the two groups was 12.9 % (95% confidence interval, –28.7% to 2.9%).

Children in the skin care group were much less likely to develop wounds, the researchers found, when they focused only on wounds and not eczema (odds ratio, 0.29, 95% CI, 0.12-0.68).

Dr. Berg said she would like to explore whether other techniques, such as a combination of patches, adhesives, or other lotions, yield even better results.

“Anything that can help people use technology more consistently is better for both quality of life and diabetes outcomes,” said Priya Prahalad, MD, a specialist in pediatric endocrinology and diabetes at Stanford Medicine Children’s Health in Palo Alto and Sunnyvale, Calif. 

Dr. Prahalad, who was not involved in the Danish study, said that although the sample sizes in the trial were relatively small, the data are “headed in the right direction.”

Pediatricians already recommend using moisturizing creams at the sites where pumps or glucose monitors are inserted into the skin, she noted. But the new study simply employed an especially moisturizing cream to mitigate skin damage.

Although one reason for skin irritation may be the repeated insertion and removal of devices, Dr. Berg and Dr. Prahalad stressed that the medical devices themselves may contain allergy-causing components. Device makers are not required to disclose what’s inside the boxes.

“I do not understand why the full content of a device is not by law mandatory to declare, when declaration by law is mandatory for many other products and drugs but not for medical devices,” Dr. Berg said.

Dr. Berg reports receiving lipid cream from Teva Pharmaceuticals and research support from Medtronic. Dr. Prahalad reports no relevant financial relationships.

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

Technologies that allow people to monitor blood sugar and automate the administration of insulin have radically transformed the lives of patients – and children in particular – with type 1 diabetes. But the devices often come with a cost: Insulin pumps and continuous glucose monitors can irritate the skin at the points of contact, causing some people to stop using their pumps or monitors altogether.

Regular use of lipid-rich skin creams can reduce eczema in children who use insulin pumps and continuous glucose monitors to manage type 1 diabetes, Danish researchers reported last month. The article is currently undergoing peer review at The Lancet Diabetes and Endocrinology, and the authors said they hope their approach will deter more children from abandoning diabetes technology.

“A simple thing can actually change a lot,” said Anna Korsgaard Berg, MD, a pediatrician who specializes in diabetes care at Copenhagen University Hospital’s Steno Diabetes Center in Herlev, Denmark, and a coauthor of the new study. “Not all skin reactions can be solved by the skin care program, but it can help improve the issue.”

More than 1.5 million children and adolescents worldwide live with type 1 diabetes, a condition that requires continuous insulin infusion. Insulin pumps meet this need in many wealthier countries, and are often used in combination with sensors that measure a child’s glucose level. Both the American Diabetes Association and the International Society for Adolescent and Pediatric Diabetes recommend insulin pumps and continuous glucose monitors as core treatment tools.

Dr. Berg and colleagues, who have previously shown that as many as 90% of children who use these devices experience some kind of skin reaction, want to minimize the rate of such discomfort in hopes that fewer children stop using the devices. According to a 2014 study, 18% of people with type 1 diabetes who stopped using continuous glucose monitors did so because of skin irritation.
 

Lather on that lipid-rich lotion

Dr. Berg and colleagues studied 170 children and adolescents with type 1 diabetes (average age, 11 years) who use insulin pumps, continuous glucose monitors, or both. From March 2020 to July 2021, 112 children (55 girls) employed a skin care program developed for the study, while the other 58 (34 girls) did not receive any skin care advice.

The skin care group received instructions about how to gently insert and remove their insulin pumps or glucose monitors, to minimize skin damage. They also were told to avoid disinfectants such as alcohol, which can irritate skin. The children in this group used a cream containing 70% lipids to help rehydrate their skin, applying the salve each day a device was not inserted into their skin.

Eczema can be a real problem for kids who use insulin pumps and continuous glucose monitors to manage type 1 diabetes. Researchers found that regular use of lipid-rich skin creams can reduce its incidence.

Although insulin pumps and glucose monitors are kept in place for longer periods of time than they once were, Dr. Berg and colleagues noted, users do periodically remove them when bathing or when undergoing medical tests that involve x-rays. On days when the devices were not in place for a period of time, children in the skin care group were encouraged to follow the protocol.
 

Study results

One-third of children in the skin care group developed eczema or experienced a wound, compared with almost half of the children in the control group, according to the researchers. The absolute difference in developing eczema or wounds between the two groups was 12.9 % (95% confidence interval, –28.7% to 2.9%).

Children in the skin care group were much less likely to develop wounds, the researchers found, when they focused only on wounds and not eczema (odds ratio, 0.29, 95% CI, 0.12-0.68).

Dr. Berg said she would like to explore whether other techniques, such as a combination of patches, adhesives, or other lotions, yield even better results.

“Anything that can help people use technology more consistently is better for both quality of life and diabetes outcomes,” said Priya Prahalad, MD, a specialist in pediatric endocrinology and diabetes at Stanford Medicine Children’s Health in Palo Alto and Sunnyvale, Calif. 

Dr. Prahalad, who was not involved in the Danish study, said that although the sample sizes in the trial were relatively small, the data are “headed in the right direction.”

Pediatricians already recommend using moisturizing creams at the sites where pumps or glucose monitors are inserted into the skin, she noted. But the new study simply employed an especially moisturizing cream to mitigate skin damage.

Although one reason for skin irritation may be the repeated insertion and removal of devices, Dr. Berg and Dr. Prahalad stressed that the medical devices themselves may contain allergy-causing components. Device makers are not required to disclose what’s inside the boxes.

“I do not understand why the full content of a device is not by law mandatory to declare, when declaration by law is mandatory for many other products and drugs but not for medical devices,” Dr. Berg said.

Dr. Berg reports receiving lipid cream from Teva Pharmaceuticals and research support from Medtronic. Dr. Prahalad reports no relevant financial relationships.

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

Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.

“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.

American Heart Association

The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.

The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.

Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.

Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.

Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.

The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).

In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).

Kei Uesugi/Stone/Getty Images

Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.

However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.

Small steps may get patients started

Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.

“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.

“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.

More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”

Study fills research gap for older adults

“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.

“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.

“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.

Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.

The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.

Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.

“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.

American Heart Association

The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.

The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.

Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.

Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.

Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.

The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).

In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).

Kei Uesugi/Stone/Getty Images

Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.

However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.

Small steps may get patients started

Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.

“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.

“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.

More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”

Study fills research gap for older adults

“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.

“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.

“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.

Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.

The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.

Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.

“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.

American Heart Association

The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.

The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.

Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.

Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.

Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.

The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).

In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).

Kei Uesugi/Stone/Getty Images

Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.

However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.

Small steps may get patients started

Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.

“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.

“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.

More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”

Study fills research gap for older adults

“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.

“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.

“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.

Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.

The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.

Eli Lilly will cut prices for most of its insulins in the United States by 70% and cap out-of-pocket costs for insulin at $35 per month, the company announced on March 1.

“Lilly is taking these actions to make it easier to access Lilly insulin and help Americans who may have difficulty navigating a complex healthcare system that may keep them from getting affordable insulin,” the company said in a statement.

iStock/ThinkStock

The $35 price cap is effective immediately at participating retail pharmacies for people with commercial insurance. Those without insurance can go to InsulinAffordability.com and download the Lilly Insulin Value Program savings card to receive Lilly insulins for $35 per month.

The company says it will cut the list price of its nonbranded Insulin Lispro Injection 100 units/mL to $25 a vial, effective May 1, 2023. The list price of the branded Humalog (insulin lispro injection) 100 units/mL will be cut by 70%, effective in the fourth quarter of 2023.

Lilly is among the three main companies that manufacture insulin, along with Novo Nordisk and Sanofi, that have come under fire over the cost of insulin in the US. Studies have shown that up to 25% of people with type 1 diabetes ration insulin because of costs, putting their health and often their lives in jeopardy.

Prices in the United States are around 10 times higher than in other countries. California is the latest state to say it plans to sue these big three companies over the high price of insulin and has announced plans to make its own cheaper versions.

Asked at a telephone press briefing if the lawsuit prompted the company’s move, Lilly chair and CEO David A. Ricks said: “Of course there are complaints against the industry and the company. We see those as completely unfounded. However, we can probably all agree that patients should have a consistent and lower-cost experience at the pharmacy counter, and that’s what today’s announcement is about. We’re doing this completely voluntarily because it’s time and it’s the right thing to do.”

On hearing the company announcement, Laura Nally, MD, a pediatric endocrinologist living with type 1 diabetes, @drnallypants, tweeted: “YES. After years of advocacy, the list price of Lispro/Humalog is now similar to what it was in the late 1990s. Cheers to all the #pwd [people with diabetes] who have advocated through #insulin4all! But we still have work to do to improve access to other diabetes medications & supplies.”

#insulin4all is a worldwide campaign to ensure that people with type 1 diabetes have access to affordable insulin and other supplies needed to manage the condition, such as glucose strips. It is supported, among others, by the advocacy group T1International.

Also giving his reaction to the Lilly announcement, Chuck Henderson, CEO of the American Diabetes Association, said: “We applaud Eli Lilly for taking the important step to limit cost-sharing for its insulin, and we encourage other insulin manufacturers to do the same.

“While we have been able to help achieve significant progress on the issue of insulin affordability, including Medicare’s new out-of-pocket cost cap on insulin, state copay caps, and patient assistance developments from insulin manufacturers, we know that our work is not done,” he added.

“ADA will work to ensure that Eli Lilly’s patient assistance program is benefiting patients as intended and continue the fight so that everyone who needs insulin has access.”

And Endocrine Society chief medical officer Robert Lash, MD, said: “Lilly’s move to apply a $35/month cap for people with private insurance will be a significant improvement for adults and children with diabetes who use Lilly’s products.

“We encourage all insulin manufacturers to join in the effort to reduce out-of-pocket costs for people who need insulin.”

Lilly will also launch a new insulin biosimilar, Rezvoglar (insulin glargine-aglr) injection, which is similar to and interchangeable with insulin glargine (Lantus). The cost will by $92 for a five pack of KwikPens, a 78% discount, compared with the cost of Lantus, beginning April 1, 2023.

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

Eli Lilly will cut prices for most of its insulins in the United States by 70% and cap out-of-pocket costs for insulin at $35 per month, the company announced on March 1.

“Lilly is taking these actions to make it easier to access Lilly insulin and help Americans who may have difficulty navigating a complex healthcare system that may keep them from getting affordable insulin,” the company said in a statement.

iStock/ThinkStock

The $35 price cap is effective immediately at participating retail pharmacies for people with commercial insurance. Those without insurance can go to InsulinAffordability.com and download the Lilly Insulin Value Program savings card to receive Lilly insulins for $35 per month.

The company says it will cut the list price of its nonbranded Insulin Lispro Injection 100 units/mL to $25 a vial, effective May 1, 2023. The list price of the branded Humalog (insulin lispro injection) 100 units/mL will be cut by 70%, effective in the fourth quarter of 2023.

Lilly is among the three main companies that manufacture insulin, along with Novo Nordisk and Sanofi, that have come under fire over the cost of insulin in the US. Studies have shown that up to 25% of people with type 1 diabetes ration insulin because of costs, putting their health and often their lives in jeopardy.

Prices in the United States are around 10 times higher than in other countries. California is the latest state to say it plans to sue these big three companies over the high price of insulin and has announced plans to make its own cheaper versions.

Asked at a telephone press briefing if the lawsuit prompted the company’s move, Lilly chair and CEO David A. Ricks said: “Of course there are complaints against the industry and the company. We see those as completely unfounded. However, we can probably all agree that patients should have a consistent and lower-cost experience at the pharmacy counter, and that’s what today’s announcement is about. We’re doing this completely voluntarily because it’s time and it’s the right thing to do.”

On hearing the company announcement, Laura Nally, MD, a pediatric endocrinologist living with type 1 diabetes, @drnallypants, tweeted: “YES. After years of advocacy, the list price of Lispro/Humalog is now similar to what it was in the late 1990s. Cheers to all the #pwd [people with diabetes] who have advocated through #insulin4all! But we still have work to do to improve access to other diabetes medications & supplies.”

#insulin4all is a worldwide campaign to ensure that people with type 1 diabetes have access to affordable insulin and other supplies needed to manage the condition, such as glucose strips. It is supported, among others, by the advocacy group T1International.

Also giving his reaction to the Lilly announcement, Chuck Henderson, CEO of the American Diabetes Association, said: “We applaud Eli Lilly for taking the important step to limit cost-sharing for its insulin, and we encourage other insulin manufacturers to do the same.

“While we have been able to help achieve significant progress on the issue of insulin affordability, including Medicare’s new out-of-pocket cost cap on insulin, state copay caps, and patient assistance developments from insulin manufacturers, we know that our work is not done,” he added.

“ADA will work to ensure that Eli Lilly’s patient assistance program is benefiting patients as intended and continue the fight so that everyone who needs insulin has access.”

And Endocrine Society chief medical officer Robert Lash, MD, said: “Lilly’s move to apply a $35/month cap for people with private insurance will be a significant improvement for adults and children with diabetes who use Lilly’s products.

“We encourage all insulin manufacturers to join in the effort to reduce out-of-pocket costs for people who need insulin.”

Lilly will also launch a new insulin biosimilar, Rezvoglar (insulin glargine-aglr) injection, which is similar to and interchangeable with insulin glargine (Lantus). The cost will by $92 for a five pack of KwikPens, a 78% discount, compared with the cost of Lantus, beginning April 1, 2023.

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

Eli Lilly will cut prices for most of its insulins in the United States by 70% and cap out-of-pocket costs for insulin at $35 per month, the company announced on March 1.

“Lilly is taking these actions to make it easier to access Lilly insulin and help Americans who may have difficulty navigating a complex healthcare system that may keep them from getting affordable insulin,” the company said in a statement.

iStock/ThinkStock

The $35 price cap is effective immediately at participating retail pharmacies for people with commercial insurance. Those without insurance can go to InsulinAffordability.com and download the Lilly Insulin Value Program savings card to receive Lilly insulins for $35 per month.

The company says it will cut the list price of its nonbranded Insulin Lispro Injection 100 units/mL to $25 a vial, effective May 1, 2023. The list price of the branded Humalog (insulin lispro injection) 100 units/mL will be cut by 70%, effective in the fourth quarter of 2023.

Lilly is among the three main companies that manufacture insulin, along with Novo Nordisk and Sanofi, that have come under fire over the cost of insulin in the US. Studies have shown that up to 25% of people with type 1 diabetes ration insulin because of costs, putting their health and often their lives in jeopardy.

Prices in the United States are around 10 times higher than in other countries. California is the latest state to say it plans to sue these big three companies over the high price of insulin and has announced plans to make its own cheaper versions.

Asked at a telephone press briefing if the lawsuit prompted the company’s move, Lilly chair and CEO David A. Ricks said: “Of course there are complaints against the industry and the company. We see those as completely unfounded. However, we can probably all agree that patients should have a consistent and lower-cost experience at the pharmacy counter, and that’s what today’s announcement is about. We’re doing this completely voluntarily because it’s time and it’s the right thing to do.”

On hearing the company announcement, Laura Nally, MD, a pediatric endocrinologist living with type 1 diabetes, @drnallypants, tweeted: “YES. After years of advocacy, the list price of Lispro/Humalog is now similar to what it was in the late 1990s. Cheers to all the #pwd [people with diabetes] who have advocated through #insulin4all! But we still have work to do to improve access to other diabetes medications & supplies.”

#insulin4all is a worldwide campaign to ensure that people with type 1 diabetes have access to affordable insulin and other supplies needed to manage the condition, such as glucose strips. It is supported, among others, by the advocacy group T1International.

Also giving his reaction to the Lilly announcement, Chuck Henderson, CEO of the American Diabetes Association, said: “We applaud Eli Lilly for taking the important step to limit cost-sharing for its insulin, and we encourage other insulin manufacturers to do the same.

“While we have been able to help achieve significant progress on the issue of insulin affordability, including Medicare’s new out-of-pocket cost cap on insulin, state copay caps, and patient assistance developments from insulin manufacturers, we know that our work is not done,” he added.

“ADA will work to ensure that Eli Lilly’s patient assistance program is benefiting patients as intended and continue the fight so that everyone who needs insulin has access.”

And Endocrine Society chief medical officer Robert Lash, MD, said: “Lilly’s move to apply a $35/month cap for people with private insurance will be a significant improvement for adults and children with diabetes who use Lilly’s products.

“We encourage all insulin manufacturers to join in the effort to reduce out-of-pocket costs for people who need insulin.”

Lilly will also launch a new insulin biosimilar, Rezvoglar (insulin glargine-aglr) injection, which is similar to and interchangeable with insulin glargine (Lantus). The cost will by $92 for a five pack of KwikPens, a 78% discount, compared with the cost of Lantus, beginning April 1, 2023.

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

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

Surgeon goes the extra half mile for his patient

Sorry medical profession, but it’s Adam Bodzin’s world now. When a donor liver got stuck in the middle of the Philadelphia Half Marathon’s 30,000 participants, Dr. Bodzin, the transplant team’s lead surgeon, took matters into his own hands. And by hands, of course, we mean feet.

Pixnio

Still wearing his hospital scrubs, Dr. Bodzin ran more than half a mile to where the van carrying the liver was stranded, according to the Philadelphia Inquirer. Fortunately, he was able to hitch a ride in a police car for the return trip and didn’t have to run back through the crowd carrying his somewhat unusual package. By package, of course, we mean human liver.

It’s been 3 months since the surgery/marathon and it’s still not clear why the driver had such trouble getting through – he had been trying for more than an hour and half by the time Dr. Bodzin reached him – but the surgery half of the big event was deemed a success and the patient has recovered.

Rick Hasz, president and chief executive officer of the Gift of Life Donor Program, which coordinates organ donation for transplants in the Philadelphia region, told the newspaper that “Dr. Bodzin’s quick action demonstrated his commitment to honoring the selfless generosity of all donors and their families and gives hope to everyone waiting for a second chance at life.”

Should Dr. Bodzin consider a step up from the transplant team to another group that’s fighting for the common good? The recipient of the liver in question seems to think so. “I guess he has a cape on under that white jacket,” 66-year-old Charles Rowe told Fox29. You already know where we’re going with this, right?

Avengers … Assemble.
 

Your spleen’s due for its 5,000-mile oil change

The human body is an incredible biological machine, capable of performing a countless array of tasks automatically and essentially without flaw, but there’s always room for improvement. After all, there are animals that can regrow entire missing limbs or live for up to 500 years. It would be nice if we could get some of that going.

Sigmund/Unsplash

Rather than any of that cool stuff, a recent survey of 2,000 average Americans revealed that our ambitions for improving the human body are a bit more mundane. The big thing that would make our lives better and easier, according to three-fourths of Americans, would be a built-in “check engine” light in our bodies. Come on guys, starfish can literally be cut in half and not only survive, but become two starfish. Mantis shrimp can punch with a force thousands of times their own weight. If we could punch like they could, we could literally break steel with our fists. Wouldn’t we rather have that?

Apparently not. Fine, we’ll stick with the check engine light.

Maybe it isn’t a huge surprise that we’d like the extra help in figuring out what our body needs. According to the survey, more than 60% of Americans struggle to identify when their body is trying to tell them something important, and only one-third actively checked in with their health every day. Considering about 40% said they feel tired for much of the day and nearly half reported not having a meal with fruits or vegetables in the past 3 days, perhaps a gentle reminder wouldn’t be the worst thing in the world.

So, if we did have a built-in check engine light, what would we use it for? A majority said they’d like to be reminded to drink a glass of water, with 45% saying they wanted to know when to take a nap. Feeling thirsty or tired isn’t quite enough, it seems.

Of course, the technology certainly exists to make the human check engine light a reality. An implanted microchip could absolutely tell us to drink a glass of water, but that would put our health in the hands of tech companies, and you just know Meta and Elon Muskrat wouldn’t pass up the chance for monetization. “Oh, sorry, we could have notified the hospital that you were about to have a heart attack, but you didn’t pay your life subscription this month.”
 

Sext offenders show more than their, well, you know

As we have become more and more attached to our phones, especially post pandemic, it’s no surprise that sexting – sending sexually explicit images and messages with those phones – has become a fairly common way for people to sexually communicate. And with dating apps just another venture in the dating landscape, regardless of age, sexting is an easy avenue to incite a mood without being physically present.

©agmit/istockphoto.com

A recent study, though, has linked sexting with anxiety, sleep issues, depression, and compulsive sexual behaviors. Yikes.

Although the researchers noted that sexting was primarily reciprocal (sending and receiving), “over 50% of adults report sending a sext, while women are up to four times more likely than men to report having received nonconsensual sexts,” said Brenda K. Wiederhold, PhD, editor-in-chief of Cyberpsychology, Behavior, and Social Networking, which published the study, in which Dr. Wiederhold was not involved.

Among the 2,160 U.S. college students who were involved, participants who had only sent sexts reported more anxiety, depression, and sleep problems than other groups (no sexting, received only, reciprocal). There was also a possible connection between sexting, marijuana use, and compulsive sexual behavior, the investigators said in a written statement.

Considering the study population, these data are perhaps not that surprising. For young adults, to receive or send an elusive nude is as common as it once was to give someone flowers. Not that the two things elicit the same reactions. “Many individuals reveal they enjoy consensual sexting and feel it empowers them and builds self-confidence,” Dr. Wiederhold added.

Receiving a nonconsensual sext, though, is definitely going to result in feeling violated and super awkward. Senders beware: Don’t be surprised if you’re ghosted after that.

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

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

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

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

Lille, France – The American College of Physicians has just updated its guidelines for osteoporosis treatment. Bernard Cortet, MD, PhD, chairperson of the Osteoporosis Research and Information Group and head of the rheumatology department at Lille (France) University Hospital, has agreed to compare the new U.S. guidelines to the 2018 French recommendations written under the aegis of the French Society for Rheumatology and GRIO. Dr. Cortet participated in drafting the French recommendations.

Question: The ACP “strongly” recommends initial pharmacologic treatment with bisphosphonate antiresorptive drugs (alendronate, ibandronate, risedronate, zoledronate) in postmenopausal females diagnosed with primary osteoporosis. Isn’t this what the SFR–GRIO have been recommending for many years?

Answer: The ACP reinforces its stance by arguing that in postmenopausal females with primary osteoporosis, bisphosphonates have the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Our French recommendations specify the choice of drug based on the type of fracture in women and on their bone mineral density (BMD). However, bisphosphonates are definitely given pride of place. When treatment for osteoporosis needs to be started, most of the time, a bisphosphonate is the treatment of choice.

Nevertheless, as also highlighted by the ACP, a more “aggressive” approach must be considered for more severe cases.

In the case of a severe fracture, the French recommendations indicate that all treatments can be prescribed. However, zoledronic acid should be favored as first-line treatment for a hip fracture. In other cases – with or without a nonsevere fracture – the therapeutic indication depends on the BMD values, and in difficult cases, on tools such as FRAX [the Fracture Risk Assessment Tool].

Our guidance strongly recommends opting for an injection in other contexts, such as significant decrease in bone density, presence of comorbidities, poor treatment compliance, brain function disorders, and polymedication.

Q. But it’s not really as simple as prescribing a bisphosphonate, is it?

A. You’re right, many people find the idea of taking bisphosphonates worrying because of associated jaw problems – osteonecrosis of the jaw – or atypical femoral fractures, based on what they’ve read on the Internet, where these serious adverse events are on display front and center with no mention of how often they actually happen and, often, failing to mention how effective bisphosphonates truly are.

These complications are real, but fortunately rare, especially during the first 5 years of treatment. To put this into context, for bisphosphonates, there’s one case of osteonecrosis of the jaw for every 10,000. And for denosumab, there are five cases for every 10,000. For atypical fractures, there’s one case for every 30,000 to 50,000.

Q. The U.S. guidelines also recommend that clinicians use a RANK ligand inhibitor – denosumab, also an antiresorptive drug – as second-line medical treatment. This is to reduce the risk of fractures in postmenopausal women diagnosed with primary osteoporosis and presenting with contraindications or side effects of bisphosphonates. Do you support the use of denosumab as second-line treatment?

A. French legislation classifies it as a second-line treatment, after bisphosphonates. However, there are arguments in favor of prescribing it as first-line treatment in some contexts. If denosumab is to be prescribed – via a twice-yearly subcutaneous injection – full compliance must be observed. If a patient is to stop taking denosumab, an opinion from a medical professional is required before treatment can be discontinued, and then treatment with bisphosphonates must be prescribed.

Q. The ACP recommends that clinicians use either a sclerostin inhibitor – romosozumab – or recombinant human parathyroid hormone – teriparatide – two anabolic agents, followed by a bisphosphonate, with the aim of reducing the risk of fractures. This is only used in women with primary osteoporosis who are at a very high risk of fracture. As romosozumab is not available in France, it’s not really worth discussing its use. Does this strategy seem advisable to you, though?

A. The main issue is what is understood by “women at a very high risk of fracture.” There’s no consensus on the definition of what constitutes a woman at a very high risk of fracture, but we can assume that it involves the combination of low BMD and at least one severe fracture.

The role of anabolic bone treatment, as [the ACP] has defined it, seems logical to me, because in cases of severe osteoporosis with fracture, the risk of recurrence is very high in the next 2-3 years. In a study comparing risedronate and teriparatide in cases of severe osteoporosis, teriparatide was more effective in reducing the recurrence of vertebral fractures.

The favorable opinion of the French National Authority for Health in relation to medical coverage for romosozumab in the treatment of severe postmenopausal osteoporosis in women under the age of 75 years with a history of severe fractures, a T-score less than –2.5, and no previous history of coronary artery disease dates to 2021. This is because medical coverage for this specific group was not listed in the marketing authorization (MA) description for this drug.

But the review by the Economic Committee for Health Products failed to reach a consensus regarding the price. Today, in theory, romosozumab can be dispensed in France by hospital pharmacies, because it is approved for use in public hospitals. Romosozumab is a very interesting drug for relatively young women, especially those with multiple vertebral fractures. This injectable treatment is more effective than teriparatide in increasing BMD values and more effective than alendronate in preventing the recurrence of fractures.

Regarding medical coverage, as it stands, in cases where patients have a T-score less than or equal to –3, the 2018 SFR–GRIO recommends starting treatment even if the patient has no fractures. In cases with severe fractures combined with very low BMD (T-score ≤ –3), injectable treatments may be used to reach a bone density target (T-score > –2.5 to –2 for the hip) at the end of the treatment plan. [These treatments include] zoledronic acid, denosumab (in case of bisphosphonate failure or intolerance), or a treatment plan with teriparatide (covered by medical insurance if the patient has at least two vertebral fractures) followed by an antiresorptive drug (bisphosphonate or denosumab).

Romosozumab is a humanized monoclonal antibody (IgG2) that binds to sclerostin and acts as an inhibitor. This increases bone formation because of the activation of [bone lining cells], the production of bone matrix by osteoblasts, and the recruitment of osteochondroprogenitor cells. Moreover, romosozumab causes changes in the expression of osteoclast mediators, which decreases bone resorption. Together, these two effects that increase bone formation and decrease bone resorption lead to the rapid increase of trabecular and cortical bone mass, as well as improvements in bone structure and strength.

Women treated with a bone anabolic agent must take an antiresorptive agent at the end of their treatment so that the benefits from the treatment remain in the long term. The French and U.S. guidelines line up on this point.

In patients with two prevalent vertebral fractures, the U.S. guidelines state that teriparatide can be prescribed as first-line treatment at diagnosis in the absence of any contraindications. We agree on this point as well.

Moreover, in women under the age of 70 years with osteoporosis requiring treatment, French experts recommend prescribing raloxifene, a selective estrogen-receptor modulator. This is if the risk of nonvertebral fracture is low, as defined by the absence of the following criteria: low hip T-score, risk of falling, and history of nonvertebral fracture. Opportunities for its use are limited, and it doesn’t even figure among the U.S. recommendations.

Q. The ACP recommends that clinicians adopt an individualized approach regarding whether to start medical treatment with a bisphosphonate in women over age 65 years with low bone mass (osteopenia) to reduce the risk of fractures. If treatment is started, they›re of the opinion that a bisphosphonate must be used. What are the recommendations in France?

A. It should be noted that this recommendation by the ACP is conditional because of the low-certainty evidence.

Here’s a brief reminder of important things to note: a T-score between –2.5 and –1 indicates osteopenia; a T-score less than or equal to –2.5 indicates osteoporosis; a T-score less than or equal to –2.5 with one or several fractures indicates severe osteoporosis. The French recommendations state that treatment is not justified if a patient’s T-score is higher than –2 and there’s no presence of fractures, even with risk factors (and/or multiple falls). For T-scores less than or equal to –2 and higher than –3, the decision to prescribe depends on the specialist.

Q. The ACP recommends that clinicians use bisphosphonates for the initial medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis.

A. The ACP recommends that clinicians use a RANK ligand inhibitor – denosumab – as second-line medical treatment to reduce the risk of fractures in men diagnosed with primary osteoporosis who present with contraindications or who are experiencing side effects of bisphosphonates. This treatment is not covered by health insurance for men in France.

Between 20% and 25% of clinical osteoporotic fractures occur in men. After age 50 years, men are roughly 20% more likely to experience an osteoporotic fracture in their lifetime. The French recommendations regarding the management and treatment of osteoporosis in men were published in 2021.

In the case of severe fractures (vertebrae, pelvis, upper end of the femur, distal femur, proximal humerus) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –1.

In the case of nonsevere fractures (particularly wrist and ankle) attributable to bone fragility, osteoporosis treatment is recommended if one of the T-scores is less than or equal to –2. If there are no fractures, osteoporosis treatment is recommended in men at risk of bone fragility or of falling and if one of the T-scores is less than or equal to –3. In patients who had a fracture of the upper end of the femur attributable to bone fragility, zoledronic acid is recommended as first-line treatment.

For men with a severe nonvertebral fracture, single vertebral fracture, or nonsevere fracture, two treatments are indicated and covered by health insurance in France: zoledronic acid and risedronate. In men with at least two vertebral fractures, the following treatments are indicated and covered by health insurance in France: teriparatide and risedronate. In this case, teriparatide is prescribed for a period of 18 months. It must be followed by a prescription of oral or intravenous bisphosphonates.

Q. What is your take on the HAS update to the proper use of osteoporosis medication that’s just been published?

A. Like in the 2018 SFR–GRIO guidelines, no update has been made to the section on postmenopausal osteoporosis, except for the HAS introduction to the proper use of romosozumab, even though it’s not covered by health insurance in France.

In accordance with the MA, it doesn’t make sense to include this drug on the list of treatment options available for women with and without fractures, as it’s not included in the HAS-selected list of drugs covered by health insurance in France.

But I’m glad that the HAS has adopted the GRIO and SFR recommendations regarding corticosteroid-induced osteoporosis. Preventive treatment for corticosteroid-induced osteoporosis must be considered as soon as the daily dose of corticosteroids reaches or exceeds the equivalent of 7.5 mg of prednisone and when the estimated duration of corticosteroid therapy exceeds 3 months.

In summary, in women and men over the age of 50 years, the intake of the equivalent of 7.5 mg/day or more of prednisone or a history of a low-trauma fracture or being age 70 years or older, even with a T-score less than or equal to –2.5 for one of the two sites, indicates prescribing a bisphosphonate. Teriparatide is indicated if the patient has two vertebral fractures.

This article was translated from Medscape’s French edition.

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

Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.

The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.

Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
 

Patients with PASC

The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.

As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.

Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.

On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).

Patients with a diagnosis of clinical aspects associated with PASC at 6 months were characterized by certain predisposing factors, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.

Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
 

Interpreting CD57

One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”

Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.

Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.

“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.

Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”

Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.

The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.

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

Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.

The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.

Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
 

Patients with PASC

The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.

As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.

Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.

On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).

Patients with a diagnosis of clinical aspects associated with PASC at 6 months were characterized by certain predisposing factors, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.

Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
 

Interpreting CD57

One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”

Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.

Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.

“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.

Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”

Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.

The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.

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

Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.

The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.

Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
 

Patients with PASC

The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.

As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.

Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.

On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).

Patients with a diagnosis of clinical aspects associated with PASC at 6 months were characterized by certain predisposing factors, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.

Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
 

Interpreting CD57

One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”

Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.

Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.

“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.

Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”

Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.

The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.

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

When it comes to a woman’s risk for a breast cancer recurrence, hormone status appears to matter.

New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.

“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.

The study was published online in Cancer.

Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.

Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.

The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease. 

Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).

Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.

The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.

Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.

“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”

What might these results mean for practice and following patients over the long term?

According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”

Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.

Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.

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

When it comes to a woman’s risk for a breast cancer recurrence, hormone status appears to matter.

New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.

“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.

The study was published online in Cancer.

Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.

Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.

The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease. 

Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).

Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.

The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.

Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.

“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”

What might these results mean for practice and following patients over the long term?

According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”

Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.

Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.

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

When it comes to a woman’s risk for a breast cancer recurrence, hormone status appears to matter.

New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.

“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.

The study was published online in Cancer.

Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.

Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.

The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease. 

Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).

Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.

The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.

Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.

“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”

What might these results mean for practice and following patients over the long term?

According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”

Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.

Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.

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

In children and adolescents with new-onset type 1 diabetes, the calcium channel blocker verapamil slowed the destruction of insulin-producing pancreatic beta cells for up to a year, new data show.

Use of daily verapamil within a month of diagnosis resulted in a 30% increase in C-peptide secretion (a measure of preserved beta-cell function), compared with placebo at 52 weeks, without serious adverse events.

To put it another way, verapamil delayed the expected decline in C-peptide production from 3 months after diagnosis of type 1 diabetes to 6 months after diagnosis.

“We think this is a really, really exciting finding that’s hopefully going to impact the care for children with type 1 diabetes in the new-onset period,” lead author Gregory P. Forlenza, MD, said during his presentation of the data on Feb. 24 at the annual Advanced Technologies & Treatments for Diabetes (ATTD) meeting in Berlin.

“In view of the favorable safety profile, particularly compared with immune-suppressive agents, once-a-day oral administration, and low cost, initiation of verapamil should be a consideration for newly diagnosed patients with type 1 diabetes,” added Dr. Forlenza, a pediatric endocrinologist at the Barbara Davis Center for Diabetes, Anschutz Medical Campus, University of Colorado, Aurora.

The data were also simultaneously published in JAMA, as part of the CLVer (Hybrid Closed Loop Therapy and Verapamil for Beta Cell Preservation in New Onset Type 1 Diabetes) trial.

The randomized, double-blind, six-center trial involved 113 participants, aged 7-17 years, with newly diagnosed type 1 diabetes. They were randomized to the most advanced commercially available automated insulin delivery systems available or standard care to test the effects of intensive glucose control on C-peptide levels for 52 weeks during the COVID-19 pandemic (July 2020 to September 2022). Eighty-eight patients who weighed 30 kg (66 lb) or more were further randomized (1:1) to daily extended-release verapamil or placebo for the same duration. 

The positive findings for verapamil, published in one paper, contrasted with the negative ones for the automated insulin delivery (AID) system. The latter did not prevent the expected decline in C-peptide, putting to rest a long-held hypothesis that reducing glucotoxicity might preserve beta-cell function in newly diagnosed individuals with type 1 diabetes, noted Dr. Forlenza.
 

Could combination therapy work?

In recent years, immune-modulating agents have increasingly been shown to preserve beta-cell function in both new-onset and preclinical type 1 diabetes. One such agent, teplizumab (Tzield, Provention Bio), was approved by the U.S. Food and Drug Administration in November 2022 to delay type 1 diabetes onset in those at high risk.

Calcium channel blockers such as verapamil – used for years to treat hypertension and cardiac arrhythmias – may accomplish the same goal as teplizumab but in a different way, by reducing the protein overexpression that induces beta-cell apoptosis and death.

Dr. Forlenza showed a slide comparing the preservation of C-peptide, which was much lower with verapamil, at 30%, than with teplizumab, at 75%.

Asked to comment, session moderator Torben Biester, MD, a pediatric diabetologist at Auf der Bult-Zentrum Diabetes-Center for Children and Adolescents, Hanover, Germany, said: “[Verapamil] is a very cheap [daily] pill. [Teplizumab] is a very high-priced ... immune therapy in the United States ... an infusion twice for 10 days, so it’s a lot more burden for the patients and a lot more risk of side effects.”

“The future might be combination therapy,” added Dr. Biester.

And in an editorial published in JAMA and accompanying the two CLVer papers, Jennifer Couper, MD, of the University of Adelaide, agrees: “A well-tolerated, inexpensive, oral treatment such as verapamil with modest benefits on C-peptide production is relevant to practice.”

The new work “supports investigation of verapamil in combination with other effective agents during the earlier stages of type 1 diabetes before insulin dependence develops,” she noted.
 

Verapamil results ‘brilliant’ but more work needed

In the verapamil part of the CLVer trial, by 52 weeks, verapamil doses in the youth who received it ranged from 120-360 mg/day based on weight and tolerance.

The primary outcome, C-peptide area under the curve, stayed stable, from 0.66 pmol/mL at baseline to 0.65 pmol/mL at 52 weeks in the verapamil group, compared with a drop from 0.60 pmol/mL down to 0.44 pmol/mL with placebo, a significant difference of 0.14 pmol/mL (P = .04), representing a 30% higher C-peptide level in the verapamil group.

“For us, this is a phenomenally exciting result,” Dr. Forlenza commented during his presentation.

At 52 weeks, A1c was 6.6% in the verapamil group versus 6.9% with placebo, which was not significantly different. Daily insulin dose was 0.65 versus 0.74 units/kg per day, respectively, also not significantly different.

One severe hypoglycemic event occurred in each group, and one diabetic ketoacidosis event occurred in the placebo group. In the verapamil group, three participants experienced “nonserious” electrocardiogram abnormalities and one had hypertension.

Dr. Biester said he isn’t “that concerned” about the small number of mild ECG abnormalities seen in the study with verapamil, as this is a known side effect. But overall, he said, “I would think that for a recommendation for routine use it’s too early after one study, even though the results are brilliant.”

He noted that he is involved in a similar ongoing study of verapamil in adults with new-onset type 1 diabetes, called Ver-A-T1D.
 

No C-peptide effect of tight glycemic control: ‘A tough pill’

In the AID part of the study, the 113 participants were randomized 2:1 to one of two commercially available AID systems (Tandem t:slim X2 with Control-IQ or Medtronic 670G or 780G) plus frequent contact (a median of 35 times) by study staff, or standard management using a continuous glucose monitor (CGM) with an insulin pump or multiple daily injections.

At 52 weeks, A1c was 6.5% for the intensive group versus 7.1% with standard care, a significant difference. Time in blood glucose range of 70-180 mg/dL was significantly longer with intensive management, at 78%, compared with standard care, at 64%.

Nonetheless, the change in C-peptide area under the curve did not differ between the two groups, decreasing from 0.57 pmol/mL at baseline to 0.45 pmol/mL at 52 weeks with the AID system, compared with a decrease from 0.60 pmol/L down to 0.50 pmol/L with standard care (P = .89).

Dr. Forlenza commented that the hypothesis that tight glycemic control would delay the decline in C-peptide secretion “is something I think a lot of endocrinologists assumed to be true and something I’ve heard lots of colleagues over the years talk about.”

Consequently, he said these findings are “a tough pill for us to swallow ... but it’s important for us in the field to understand.”

“Even with frequent contacts that are well above the level we’d be able to do in standard clinical care, and even with use of the most advanced AID systems we have ... we saw absolutely no difference in stimulated C-peptide levels at any of the timepoints throughout the first year or at 52 weeks.”

“So, in our opinion, this,” combined with a prior study from 2022, “should put this hypothesis to rest,” he said.

“Excellent glycemic control has a benefit in and of itself, but it was not a successful intervention for beta-cell preservation.”

Dr. Forlenza has reported serving as a consultant, speaker, or advisory board member for Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics, and his institution has also received funding on his behalf for research grants from these companies. Dr. Biester has reported receiving speaker’s fees from DexCom, Medtronic, Novo Nordisk, F. Hoffmann–La Roche, Sanofi, and Ypsomed Holding; serving on advisory boards for Ascensia Diabetes Care Holdings, AstraZeneca, DexCom, and Medtronic; and receiving personal fees from SYNLAB; and is a member of the European Commission Expert Panel for Medical Devices for Endocrinology and Diabetes. Dr. Couper has reported no relevant financial relationships.

The rationale for the companion CLVer analysis of the effect of reducing glucose toxicity via tight glycemic control on C-peptide progression dates back to an inpatient study published in 1989 involving 26 adolescents using an early artificial pancreas prototype called a Biostator, in which beta-cell preservation was achieved. However, two more recent studies of this approach, including one published in late 2022, did not show a difference. The CLVer analysis involved 113 participants randomized 2:1 to one of two commercially available AID systems (Tandem t:slim X2 with Control-IQ or Medtronic 670G or 780G) plus frequent contact by study staff, or standard management using a CGM with a pump or multiple daily injections.

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

In children and adolescents with new-onset type 1 diabetes, the calcium channel blocker verapamil slowed the destruction of insulin-producing pancreatic beta cells for up to a year, new data show.

Use of daily verapamil within a month of diagnosis resulted in a 30% increase in C-peptide secretion (a measure of preserved beta-cell function), compared with placebo at 52 weeks, without serious adverse events.

To put it another way, verapamil delayed the expected decline in C-peptide production from 3 months after diagnosis of type 1 diabetes to 6 months after diagnosis.

“We think this is a really, really exciting finding that’s hopefully going to impact the care for children with type 1 diabetes in the new-onset period,” lead author Gregory P. Forlenza, MD, said during his presentation of the data on Feb. 24 at the annual Advanced Technologies & Treatments for Diabetes (ATTD) meeting in Berlin.

“In view of the favorable safety profile, particularly compared with immune-suppressive agents, once-a-day oral administration, and low cost, initiation of verapamil should be a consideration for newly diagnosed patients with type 1 diabetes,” added Dr. Forlenza, a pediatric endocrinologist at the Barbara Davis Center for Diabetes, Anschutz Medical Campus, University of Colorado, Aurora.

The data were also simultaneously published in JAMA, as part of the CLVer (Hybrid Closed Loop Therapy and Verapamil for Beta Cell Preservation in New Onset Type 1 Diabetes) trial.

The randomized, double-blind, six-center trial involved 113 participants, aged 7-17 years, with newly diagnosed type 1 diabetes. They were randomized to the most advanced commercially available automated insulin delivery systems available or standard care to test the effects of intensive glucose control on C-peptide levels for 52 weeks during the COVID-19 pandemic (July 2020 to September 2022). Eighty-eight patients who weighed 30 kg (66 lb) or more were further randomized (1:1) to daily extended-release verapamil or placebo for the same duration. 

The positive findings for verapamil, published in one paper, contrasted with the negative ones for the automated insulin delivery (AID) system. The latter did not prevent the expected decline in C-peptide, putting to rest a long-held hypothesis that reducing glucotoxicity might preserve beta-cell function in newly diagnosed individuals with type 1 diabetes, noted Dr. Forlenza.
 

Could combination therapy work?

In recent years, immune-modulating agents have increasingly been shown to preserve beta-cell function in both new-onset and preclinical type 1 diabetes. One such agent, teplizumab (Tzield, Provention Bio), was approved by the U.S. Food and Drug Administration in November 2022 to delay type 1 diabetes onset in those at high risk.

Calcium channel blockers such as verapamil – used for years to treat hypertension and cardiac arrhythmias – may accomplish the same goal as teplizumab but in a different way, by reducing the protein overexpression that induces beta-cell apoptosis and death.

Dr. Forlenza showed a slide comparing the preservation of C-peptide, which was much lower with verapamil, at 30%, than with teplizumab, at 75%.

Asked to comment, session moderator Torben Biester, MD, a pediatric diabetologist at Auf der Bult-Zentrum Diabetes-Center for Children and Adolescents, Hanover, Germany, said: “[Verapamil] is a very cheap [daily] pill. [Teplizumab] is a very high-priced ... immune therapy in the United States ... an infusion twice for 10 days, so it’s a lot more burden for the patients and a lot more risk of side effects.”

“The future might be combination therapy,” added Dr. Biester.

And in an editorial published in JAMA and accompanying the two CLVer papers, Jennifer Couper, MD, of the University of Adelaide, agrees: “A well-tolerated, inexpensive, oral treatment such as verapamil with modest benefits on C-peptide production is relevant to practice.”

The new work “supports investigation of verapamil in combination with other effective agents during the earlier stages of type 1 diabetes before insulin dependence develops,” she noted.
 

Verapamil results ‘brilliant’ but more work needed

In the verapamil part of the CLVer trial, by 52 weeks, verapamil doses in the youth who received it ranged from 120-360 mg/day based on weight and tolerance.

The primary outcome, C-peptide area under the curve, stayed stable, from 0.66 pmol/mL at baseline to 0.65 pmol/mL at 52 weeks in the verapamil group, compared with a drop from 0.60 pmol/mL down to 0.44 pmol/mL with placebo, a significant difference of 0.14 pmol/mL (P = .04), representing a 30% higher C-peptide level in the verapamil group.

“For us, this is a phenomenally exciting result,” Dr. Forlenza commented during his presentation.

At 52 weeks, A1c was 6.6% in the verapamil group versus 6.9% with placebo, which was not significantly different. Daily insulin dose was 0.65 versus 0.74 units/kg per day, respectively, also not significantly different.

One severe hypoglycemic event occurred in each group, and one diabetic ketoacidosis event occurred in the placebo group. In the verapamil group, three participants experienced “nonserious” electrocardiogram abnormalities and one had hypertension.

Dr. Biester said he isn’t “that concerned” about the small number of mild ECG abnormalities seen in the study with verapamil, as this is a known side effect. But overall, he said, “I would think that for a recommendation for routine use it’s too early after one study, even though the results are brilliant.”

He noted that he is involved in a similar ongoing study of verapamil in adults with new-onset type 1 diabetes, called Ver-A-T1D.
 

No C-peptide effect of tight glycemic control: ‘A tough pill’

In the AID part of the study, the 113 participants were randomized 2:1 to one of two commercially available AID systems (Tandem t:slim X2 with Control-IQ or Medtronic 670G or 780G) plus frequent contact (a median of 35 times) by study staff, or standard management using a continuous glucose monitor (CGM) with an insulin pump or multiple daily injections.

At 52 weeks, A1c was 6.5% for the intensive group versus 7.1% with standard care, a significant difference. Time in blood glucose range of 70-180 mg/dL was significantly longer with intensive management, at 78%, compared with standard care, at 64%.

Nonetheless, the change in C-peptide area under the curve did not differ between the two groups, decreasing from 0.57 pmol/mL at baseline to 0.45 pmol/mL at 52 weeks with the AID system, compared with a decrease from 0.60 pmol/L down to 0.50 pmol/L with standard care (P = .89).

Dr. Forlenza commented that the hypothesis that tight glycemic control would delay the decline in C-peptide secretion “is something I think a lot of endocrinologists assumed to be true and something I’ve heard lots of colleagues over the years talk about.”

Consequently, he said these findings are “a tough pill for us to swallow ... but it’s important for us in the field to understand.”

“Even with frequent contacts that are well above the level we’d be able to do in standard clinical care, and even with use of the most advanced AID systems we have ... we saw absolutely no difference in stimulated C-peptide levels at any of the timepoints throughout the first year or at 52 weeks.”

“So, in our opinion, this,” combined with a prior study from 2022, “should put this hypothesis to rest,” he said.

“Excellent glycemic control has a benefit in and of itself, but it was not a successful intervention for beta-cell preservation.”

Dr. Forlenza has reported serving as a consultant, speaker, or advisory board member for Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics, and his institution has also received funding on his behalf for research grants from these companies. Dr. Biester has reported receiving speaker’s fees from DexCom, Medtronic, Novo Nordisk, F. Hoffmann–La Roche, Sanofi, and Ypsomed Holding; serving on advisory boards for Ascensia Diabetes Care Holdings, AstraZeneca, DexCom, and Medtronic; and receiving personal fees from SYNLAB; and is a member of the European Commission Expert Panel for Medical Devices for Endocrinology and Diabetes. Dr. Couper has reported no relevant financial relationships.

The rationale for the companion CLVer analysis of the effect of reducing glucose toxicity via tight glycemic control on C-peptide progression dates back to an inpatient study published in 1989 involving 26 adolescents using an early artificial pancreas prototype called a Biostator, in which beta-cell preservation was achieved. However, two more recent studies of this approach, including one published in late 2022, did not show a difference. The CLVer analysis involved 113 participants randomized 2:1 to one of two commercially available AID systems (Tandem t:slim X2 with Control-IQ or Medtronic 670G or 780G) plus frequent contact by study staff, or standard management using a CGM with a pump or multiple daily injections.

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

In children and adolescents with new-onset type 1 diabetes, the calcium channel blocker verapamil slowed the destruction of insulin-producing pancreatic beta cells for up to a year, new data show.

Use of daily verapamil within a month of diagnosis resulted in a 30% increase in C-peptide secretion (a measure of preserved beta-cell function), compared with placebo at 52 weeks, without serious adverse events.

To put it another way, verapamil delayed the expected decline in C-peptide production from 3 months after diagnosis of type 1 diabetes to 6 months after diagnosis.

“We think this is a really, really exciting finding that’s hopefully going to impact the care for children with type 1 diabetes in the new-onset period,” lead author Gregory P. Forlenza, MD, said during his presentation of the data on Feb. 24 at the annual Advanced Technologies & Treatments for Diabetes (ATTD) meeting in Berlin.

“In view of the favorable safety profile, particularly compared with immune-suppressive agents, once-a-day oral administration, and low cost, initiation of verapamil should be a consideration for newly diagnosed patients with type 1 diabetes,” added Dr. Forlenza, a pediatric endocrinologist at the Barbara Davis Center for Diabetes, Anschutz Medical Campus, University of Colorado, Aurora.

The data were also simultaneously published in JAMA, as part of the CLVer (Hybrid Closed Loop Therapy and Verapamil for Beta Cell Preservation in New Onset Type 1 Diabetes) trial.

The randomized, double-blind, six-center trial involved 113 participants, aged 7-17 years, with newly diagnosed type 1 diabetes. They were randomized to the most advanced commercially available automated insulin delivery systems available or standard care to test the effects of intensive glucose control on C-peptide levels for 52 weeks during the COVID-19 pandemic (July 2020 to September 2022). Eighty-eight patients who weighed 30 kg (66 lb) or more were further randomized (1:1) to daily extended-release verapamil or placebo for the same duration. 

The positive findings for verapamil, published in one paper, contrasted with the negative ones for the automated insulin delivery (AID) system. The latter did not prevent the expected decline in C-peptide, putting to rest a long-held hypothesis that reducing glucotoxicity might preserve beta-cell function in newly diagnosed individuals with type 1 diabetes, noted Dr. Forlenza.
 

Could combination therapy work?

In recent years, immune-modulating agents have increasingly been shown to preserve beta-cell function in both new-onset and preclinical type 1 diabetes. One such agent, teplizumab (Tzield, Provention Bio), was approved by the U.S. Food and Drug Administration in November 2022 to delay type 1 diabetes onset in those at high risk.

Calcium channel blockers such as verapamil – used for years to treat hypertension and cardiac arrhythmias – may accomplish the same goal as teplizumab but in a different way, by reducing the protein overexpression that induces beta-cell apoptosis and death.

Dr. Forlenza showed a slide comparing the preservation of C-peptide, which was much lower with verapamil, at 30%, than with teplizumab, at 75%.

Asked to comment, session moderator Torben Biester, MD, a pediatric diabetologist at Auf der Bult-Zentrum Diabetes-Center for Children and Adolescents, Hanover, Germany, said: “[Verapamil] is a very cheap [daily] pill. [Teplizumab] is a very high-priced ... immune therapy in the United States ... an infusion twice for 10 days, so it’s a lot more burden for the patients and a lot more risk of side effects.”

“The future might be combination therapy,” added Dr. Biester.

And in an editorial published in JAMA and accompanying the two CLVer papers, Jennifer Couper, MD, of the University of Adelaide, agrees: “A well-tolerated, inexpensive, oral treatment such as verapamil with modest benefits on C-peptide production is relevant to practice.”

The new work “supports investigation of verapamil in combination with other effective agents during the earlier stages of type 1 diabetes before insulin dependence develops,” she noted.
 

Verapamil results ‘brilliant’ but more work needed

In the verapamil part of the CLVer trial, by 52 weeks, verapamil doses in the youth who received it ranged from 120-360 mg/day based on weight and tolerance.

The primary outcome, C-peptide area under the curve, stayed stable, from 0.66 pmol/mL at baseline to 0.65 pmol/mL at 52 weeks in the verapamil group, compared with a drop from 0.60 pmol/mL down to 0.44 pmol/mL with placebo, a significant difference of 0.14 pmol/mL (P = .04), representing a 30% higher C-peptide level in the verapamil group.

“For us, this is a phenomenally exciting result,” Dr. Forlenza commented during his presentation.

At 52 weeks, A1c was 6.6% in the verapamil group versus 6.9% with placebo, which was not significantly different. Daily insulin dose was 0.65 versus 0.74 units/kg per day, respectively, also not significantly different.

One severe hypoglycemic event occurred in each group, and one diabetic ketoacidosis event occurred in the placebo group. In the verapamil group, three participants experienced “nonserious” electrocardiogram abnormalities and one had hypertension.

Dr. Biester said he isn’t “that concerned” about the small number of mild ECG abnormalities seen in the study with verapamil, as this is a known side effect. But overall, he said, “I would think that for a recommendation for routine use it’s too early after one study, even though the results are brilliant.”

He noted that he is involved in a similar ongoing study of verapamil in adults with new-onset type 1 diabetes, called Ver-A-T1D.
 

No C-peptide effect of tight glycemic control: ‘A tough pill’

In the AID part of the study, the 113 participants were randomized 2:1 to one of two commercially available AID systems (Tandem t:slim X2 with Control-IQ or Medtronic 670G or 780G) plus frequent contact (a median of 35 times) by study staff, or standard management using a continuous glucose monitor (CGM) with an insulin pump or multiple daily injections.

At 52 weeks, A1c was 6.5% for the intensive group versus 7.1% with standard care, a significant difference. Time in blood glucose range of 70-180 mg/dL was significantly longer with intensive management, at 78%, compared with standard care, at 64%.

Nonetheless, the change in C-peptide area under the curve did not differ between the two groups, decreasing from 0.57 pmol/mL at baseline to 0.45 pmol/mL at 52 weeks with the AID system, compared with a decrease from 0.60 pmol/L down to 0.50 pmol/L with standard care (P = .89).

Dr. Forlenza commented that the hypothesis that tight glycemic control would delay the decline in C-peptide secretion “is something I think a lot of endocrinologists assumed to be true and something I’ve heard lots of colleagues over the years talk about.”

Consequently, he said these findings are “a tough pill for us to swallow ... but it’s important for us in the field to understand.”

“Even with frequent contacts that are well above the level we’d be able to do in standard clinical care, and even with use of the most advanced AID systems we have ... we saw absolutely no difference in stimulated C-peptide levels at any of the timepoints throughout the first year or at 52 weeks.”

“So, in our opinion, this,” combined with a prior study from 2022, “should put this hypothesis to rest,” he said.

“Excellent glycemic control has a benefit in and of itself, but it was not a successful intervention for beta-cell preservation.”

Dr. Forlenza has reported serving as a consultant, speaker, or advisory board member for Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics, and his institution has also received funding on his behalf for research grants from these companies. Dr. Biester has reported receiving speaker’s fees from DexCom, Medtronic, Novo Nordisk, F. Hoffmann–La Roche, Sanofi, and Ypsomed Holding; serving on advisory boards for Ascensia Diabetes Care Holdings, AstraZeneca, DexCom, and Medtronic; and receiving personal fees from SYNLAB; and is a member of the European Commission Expert Panel for Medical Devices for Endocrinology and Diabetes. Dr. Couper has reported no relevant financial relationships.

The rationale for the companion CLVer analysis of the effect of reducing glucose toxicity via tight glycemic control on C-peptide progression dates back to an inpatient study published in 1989 involving 26 adolescents using an early artificial pancreas prototype called a Biostator, in which beta-cell preservation was achieved. However, two more recent studies of this approach, including one published in late 2022, did not show a difference. The CLVer analysis involved 113 participants randomized 2:1 to one of two commercially available AID systems (Tandem t:slim X2 with Control-IQ or Medtronic 670G or 780G) plus frequent contact by study staff, or standard management using a CGM with a pump or multiple daily injections.

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