Federal Practitioner

DENVER – Patients with multiple sclerosis (MS) who switched from anti-CD20 monoclonal antibody therapy to fumarates showed no significant differences in relapse rates or total health care encounters, compared with those who remained on anti-CD20 mAbs, according to a retrospective study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Those who switched did, however, experience a lower rate of inpatient infection-related health care visits per year than those who continued anti-CD20 mAbs.

“As MS is a chronic disease requiring long-term treatment, switching between disease-modifying therapies [DMTs] is a common clinical strategy to optimize individual patient outcomes,” lead author Aliza Ben-Zacharia, PhD, DNP, RN, an assistant professor at the Phillips School of Nursing at Mount Sinai and Hunter College, both in New York, and colleagues reported. They noted that anti-CD20 mAbs are considered high-efficacy DMTs while fumarates are considered moderate-efficacy DMTs.

The researchers used data from the Komodo Health Sentinel Claims Database to track and compare 108 patients who were clinically stable on anti-CD20 mAbs and then switched to fumarates with 540 patients who remained on anti-CD20 mAbs for a follow-up period of approximately 1 year.

The study included adults with a diagnosis of MS between January 2015 and August 2022, and only those with a gap of no more than 9 months between anti-CD20 mAbs and fumarates were included as switchers. The researchers also required that switchers had not had any relapses in the previous year on anti-CD20 mAbs before switching, and had to have been on fumarates for at least 3 months after switching.

Women made up 70% of both groups, and both had an average age of 49 years. The racial/ethnic demographics were similar in both groups, and the average MS severity score was 5.5 in the switching group and 5.6 in the staying group. Most patients had been taking or remained on ocrelizumab (93.5%) with a smaller proportion on rituximab (5.6%). Just over a third of those who switched therapy took diroximel fumarate while 64% took dimethyl fumarate.

The researchers noted that patients who stayed on anti-CD20 mAbs had “slightly higher use of other mAbs prior to anti-CD20 mAbs.” Further, “a higher proportion of patients were DMT naive prior to anti-CD20 mAb initiation, compared with those in the switchers group.”

Patients who switched had been on anti-CD20 mAbs an average 730 days before switching to fumarates, and the average time between their last anti-CD20 mAbs dose and starting fumarates was 274 days. Average exposure to fumarates was 341 days.

The 10.2% of patients who relapsed during follow-up after switching to fumarates was not significantly statistically different than the 6.7% of patients who relapsed while remaining on anti-CD20 mAbs (P = .17). A relapse was considered “an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and a prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid 7 days or sooner after the outpatient visit,” the researchers explained. The researchers could not track mild relapses that didn’t involve a health care interaction.

There was also no significant difference in overall average health care encounters between those who switched (7.85 encounters) and those who stayed (8.08; P = .57). Further, average health care costs were statistically similar between those who switched ($22,512) and those who stayed ($20,634; P = 0.59).

The likelihood of having more than one infection-related health care encounter was greater for those who remained on anti-CD20 mAbs, but the difference was not statistically significant. The annual rate of infection-related health care encounters was also not statistically different for outpatient and ED visits, but those who switched did have a statistically lower rate of annual infection-related inpatient visits (P = .03).

Among those who switched, 2.8% were hospitalized for infections, compared with 6.5% who stayed on anti-CD20 mAbs. Urinary tract infections, sepsis, and Escherichia coli were the most common infections among those who switched to fumarates, compared with COVID-19, sepsis, and pneumonia, among those who stayed on anti-CD20 mAbs.

The research was sponsored by and funded by Biogen. Six of the authors are Biogen employees who hold stock options in the company. The other three authors reported combined consulting fees from Biogen, EMD Serono, Greenwich Biosciences, TG Therapeutics, Bristol-Myers Squibb, Horizon, and Novartis; research funding from Genentech and Novartis; and stock options in Pfizer.

DENVER – Patients with multiple sclerosis (MS) who switched from anti-CD20 monoclonal antibody therapy to fumarates showed no significant differences in relapse rates or total health care encounters, compared with those who remained on anti-CD20 mAbs, according to a retrospective study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Those who switched did, however, experience a lower rate of inpatient infection-related health care visits per year than those who continued anti-CD20 mAbs.

“As MS is a chronic disease requiring long-term treatment, switching between disease-modifying therapies [DMTs] is a common clinical strategy to optimize individual patient outcomes,” lead author Aliza Ben-Zacharia, PhD, DNP, RN, an assistant professor at the Phillips School of Nursing at Mount Sinai and Hunter College, both in New York, and colleagues reported. They noted that anti-CD20 mAbs are considered high-efficacy DMTs while fumarates are considered moderate-efficacy DMTs.

The researchers used data from the Komodo Health Sentinel Claims Database to track and compare 108 patients who were clinically stable on anti-CD20 mAbs and then switched to fumarates with 540 patients who remained on anti-CD20 mAbs for a follow-up period of approximately 1 year.

The study included adults with a diagnosis of MS between January 2015 and August 2022, and only those with a gap of no more than 9 months between anti-CD20 mAbs and fumarates were included as switchers. The researchers also required that switchers had not had any relapses in the previous year on anti-CD20 mAbs before switching, and had to have been on fumarates for at least 3 months after switching.

Women made up 70% of both groups, and both had an average age of 49 years. The racial/ethnic demographics were similar in both groups, and the average MS severity score was 5.5 in the switching group and 5.6 in the staying group. Most patients had been taking or remained on ocrelizumab (93.5%) with a smaller proportion on rituximab (5.6%). Just over a third of those who switched therapy took diroximel fumarate while 64% took dimethyl fumarate.

The researchers noted that patients who stayed on anti-CD20 mAbs had “slightly higher use of other mAbs prior to anti-CD20 mAbs.” Further, “a higher proportion of patients were DMT naive prior to anti-CD20 mAb initiation, compared with those in the switchers group.”

Patients who switched had been on anti-CD20 mAbs an average 730 days before switching to fumarates, and the average time between their last anti-CD20 mAbs dose and starting fumarates was 274 days. Average exposure to fumarates was 341 days.

The 10.2% of patients who relapsed during follow-up after switching to fumarates was not significantly statistically different than the 6.7% of patients who relapsed while remaining on anti-CD20 mAbs (P = .17). A relapse was considered “an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and a prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid 7 days or sooner after the outpatient visit,” the researchers explained. The researchers could not track mild relapses that didn’t involve a health care interaction.

There was also no significant difference in overall average health care encounters between those who switched (7.85 encounters) and those who stayed (8.08; P = .57). Further, average health care costs were statistically similar between those who switched ($22,512) and those who stayed ($20,634; P = 0.59).

The likelihood of having more than one infection-related health care encounter was greater for those who remained on anti-CD20 mAbs, but the difference was not statistically significant. The annual rate of infection-related health care encounters was also not statistically different for outpatient and ED visits, but those who switched did have a statistically lower rate of annual infection-related inpatient visits (P = .03).

Among those who switched, 2.8% were hospitalized for infections, compared with 6.5% who stayed on anti-CD20 mAbs. Urinary tract infections, sepsis, and Escherichia coli were the most common infections among those who switched to fumarates, compared with COVID-19, sepsis, and pneumonia, among those who stayed on anti-CD20 mAbs.

The research was sponsored by and funded by Biogen. Six of the authors are Biogen employees who hold stock options in the company. The other three authors reported combined consulting fees from Biogen, EMD Serono, Greenwich Biosciences, TG Therapeutics, Bristol-Myers Squibb, Horizon, and Novartis; research funding from Genentech and Novartis; and stock options in Pfizer.

DENVER – Patients with multiple sclerosis (MS) who switched from anti-CD20 monoclonal antibody therapy to fumarates showed no significant differences in relapse rates or total health care encounters, compared with those who remained on anti-CD20 mAbs, according to a retrospective study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Those who switched did, however, experience a lower rate of inpatient infection-related health care visits per year than those who continued anti-CD20 mAbs.

“As MS is a chronic disease requiring long-term treatment, switching between disease-modifying therapies [DMTs] is a common clinical strategy to optimize individual patient outcomes,” lead author Aliza Ben-Zacharia, PhD, DNP, RN, an assistant professor at the Phillips School of Nursing at Mount Sinai and Hunter College, both in New York, and colleagues reported. They noted that anti-CD20 mAbs are considered high-efficacy DMTs while fumarates are considered moderate-efficacy DMTs.

The researchers used data from the Komodo Health Sentinel Claims Database to track and compare 108 patients who were clinically stable on anti-CD20 mAbs and then switched to fumarates with 540 patients who remained on anti-CD20 mAbs for a follow-up period of approximately 1 year.

The study included adults with a diagnosis of MS between January 2015 and August 2022, and only those with a gap of no more than 9 months between anti-CD20 mAbs and fumarates were included as switchers. The researchers also required that switchers had not had any relapses in the previous year on anti-CD20 mAbs before switching, and had to have been on fumarates for at least 3 months after switching.

Women made up 70% of both groups, and both had an average age of 49 years. The racial/ethnic demographics were similar in both groups, and the average MS severity score was 5.5 in the switching group and 5.6 in the staying group. Most patients had been taking or remained on ocrelizumab (93.5%) with a smaller proportion on rituximab (5.6%). Just over a third of those who switched therapy took diroximel fumarate while 64% took dimethyl fumarate.

The researchers noted that patients who stayed on anti-CD20 mAbs had “slightly higher use of other mAbs prior to anti-CD20 mAbs.” Further, “a higher proportion of patients were DMT naive prior to anti-CD20 mAb initiation, compared with those in the switchers group.”

Patients who switched had been on anti-CD20 mAbs an average 730 days before switching to fumarates, and the average time between their last anti-CD20 mAbs dose and starting fumarates was 274 days. Average exposure to fumarates was 341 days.

The 10.2% of patients who relapsed during follow-up after switching to fumarates was not significantly statistically different than the 6.7% of patients who relapsed while remaining on anti-CD20 mAbs (P = .17). A relapse was considered “an MS-related inpatient claim with a primary diagnosis of MS or an outpatient MS-related diagnosis and a prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid 7 days or sooner after the outpatient visit,” the researchers explained. The researchers could not track mild relapses that didn’t involve a health care interaction.

There was also no significant difference in overall average health care encounters between those who switched (7.85 encounters) and those who stayed (8.08; P = .57). Further, average health care costs were statistically similar between those who switched ($22,512) and those who stayed ($20,634; P = 0.59).

The likelihood of having more than one infection-related health care encounter was greater for those who remained on anti-CD20 mAbs, but the difference was not statistically significant. The annual rate of infection-related health care encounters was also not statistically different for outpatient and ED visits, but those who switched did have a statistically lower rate of annual infection-related inpatient visits (P = .03).

Among those who switched, 2.8% were hospitalized for infections, compared with 6.5% who stayed on anti-CD20 mAbs. Urinary tract infections, sepsis, and Escherichia coli were the most common infections among those who switched to fumarates, compared with COVID-19, sepsis, and pneumonia, among those who stayed on anti-CD20 mAbs.

The research was sponsored by and funded by Biogen. Six of the authors are Biogen employees who hold stock options in the company. The other three authors reported combined consulting fees from Biogen, EMD Serono, Greenwich Biosciences, TG Therapeutics, Bristol-Myers Squibb, Horizon, and Novartis; research funding from Genentech and Novartis; and stock options in Pfizer.

MANNHEIM, GERMANY – Patients with high lipoprotein(a) (Lp[a]) levels not only have an almost twofold higher coronary plaque burden than those with low levels but also a faster rate of plaque progression, an observational imaging study shows.

This could explain the greater risk for major adverse cardiovascular events seen in patients with high Lp(a) levels, suggests the research, presented during the annual European Atherosclerosis Society Congress.

The team performed follow-up coronary CT angiography (CCTA) on almost 275 patients who had undergone imaging approximately 10 years earlier, finding that almost one-third had high Lp(a) levels.

At baseline, per cent plaque volumes were 1.8 times greater in high Lp(a) patients versus those with low levels of the protein. After 10 years, plaque volumes were 3.3 times larger in patients with high Lp(a) levels.

Over this period, the rate of increase of plaque volume was 1.9 times greater in patients with high Lp(a) levels.

Study presenter Nick S. Nurmohamed, MD, PhD candidate, department of vascular medicine, Amsterdam University Medical Centers, also showed that high Lp(a) levels were associated with a 2.1-fold increase in rates of MACE.

He said in an interview that this finding could be related to Lp(a) increasing inflammatory signaling in the plaque, “making it more prone to rupture, and we saw that on the CCTA scans,” where high Lp(a) levels were associated with the presence of more high-risk plaques.

He added that in the absence of drugs that target Lp(a) levels directly, the results underline the need to focus on other means of lipid-lowering, as well as “creating awareness that Lp(a) is associated with plaque formation.”

Dr. Nurmohamed said that “for the moment, we have to treat patients with high Lp(a) with other risk-lowering therapies, such as low-density lipoprotein [LDL] cholesterol–lowering drugs, and the management of other risk factors.”

However, he noted that “there are a couple of Lp(a)-lowering medications in trials,” with results expected in the next 2-3 years.

“Then we will have the means to treat those patients, and with CCTA we can identify the patients with the biggest risk,” Dr. Nurmohamed added.
 

Plaque burden

Philippe Moulin, MD, PhD, head of endocrinology and professor of human nutrition at Faculté Lyon Est, Claude Bernard Lyon (France) 1 University, said that the association between Lp(a) and plaque burden has been seen previously in the literature in a very similar study but with only 1-year follow-up.

Similarly, registry data have suggested that Lp(a) is associated with worsening plaque progression over time.

“Here, with 10-year follow-up, [the study] is much more interesting,” due to its greater statistical power, he said in an interview. It is also “well-documented” and uses an “appropriate” methodology.

But Dr. Moulin underlined that the number of patients with high Lp(a) levels included in the study is relatively small.

Consequently, the researchers were not able to look at the level and rate of progression of atherosclerosis between different quartiles of Lp(a), “so you have no dose-response analysis.”

It also does not “establish causality,” as it remains an observational study, despite being longitudinal, “well done, and so on.”

Dr. Moulin added that the study nevertheless adds “one more stone” to the construct of the idea of high risk around high Lp(a) levels, and “prepares the ground” for the availability of two drugs to decrease Lp(a) levels, expected in 2026 and 2027.

These are expected to substantially reduce Lp(a) levels and achieve a reduction in cardiovascular risk of around 20%-40%, “which would be interesting,” especially as “we have patients who have Lp(a) levels four times above the upper normal value.”

Crucially, they may already have normal LDL cholesterol levels, meaning that, for some patients, “there is clearly a need for such treatment, as long as it is proven that it will decrease cardiovascular risk.”

For the moment, however, the strategy for managing patients with high Lp(a) remains to increase the dose of statin and to have more stringent targets, although Dr. Moulin pointed out that, “when you give statins, you raise slightly Lp(a) levels.”

Dr. Nurmohamed said in an interview that “we know from largely genetic and observational studies that Lp(a) is causally associated with atherosclerotic cardiovascular disease.”

What is less clear is the exact underlying mechanism, he said, noting that there have been several imaging studies in high and low Lp(a) patients that have yielded conflicting results in terms of the relationship with plaque burden.

To investigate the impact of Lp(a) levels on long-term coronary plaque progression, the team invited patients who had taken part in a previous CCTA study to undergo repeat CCTA, regardless of their underlying symptoms.

In all, 299 patients underwent follow-up imaging a median of 10.2 years after their original scan. Plaque volumes were quantified and adjusted for vessel volumes, and the patients were classified as having high (≥ 70 nmol/L) or low (< 70 nmol/L) Lp(a) levels.

After excluding patients who had undergone coronary artery bypass grafting, the team analyzed 274 patients with a mean age at baseline of 57 years. Of these, 159 (58%) were men. High Lp(a) levels were identified in 87 (32%) patients.

The team found that at baseline, patients with high Lp(a) levels had significantly larger percent atheroma volumes than those with low levels, at 3.92% versus 2.17%, or an absolute difference of 1.75% (P = .013).

The difference between the two groups was even greater at the follow-up, when percent atheroma volumes reached 8.75% in patients with high Lp(a) levels versus 3.90% for those with low levels, or an absolute difference of 4.85% (P = .005).

Similar findings were seen when looking separately at percentage of noncalcified and calcified plaque volumes as well as when analyzing for the presence of low-density plaques.

Multivariate analysis taking into account clinical risk factors, statin use, and CT tube voltage found that high Lp(a) levels were associated with a greater percent atheroma volume at baseline, at an odds ratio versus low Lp(a) of 1.83 (95% confidence interval, 0.12-3.54; P = .037).

High Lp(a) levels were also linked to a larger percent atheroma volume on follow-up imaging, at an odds ratio of 3.25 (95% CI, 0.80-5.71; P = .010), and a significantly greater change in atheroma volume from baseline to follow-up imaging, at an odds ratio of 1.86 (95% CI, 0.59-3.14; P = .005)

Finally, the team showed that, after adjusting for clinical risk factors, high baseline Lp(a) levels were associated with an increased risk of MACE during the follow-up period, at a hazard ratio versus low Lp(a) levels of 2.10 (95% CI, 1.01-4.29, P = .048).

No funding was declared. Dr. Nurmohamed is cofounder of Lipid Tools. Other authors declare relationships with Amgen, Novartis, Esperion, Sanofi-Regeneron, Ackee, Cleerly, GW Heart and Vascular Institute, Siemens Healthineers, and HeartFlow.

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

MANNHEIM, GERMANY – Patients with high lipoprotein(a) (Lp[a]) levels not only have an almost twofold higher coronary plaque burden than those with low levels but also a faster rate of plaque progression, an observational imaging study shows.

This could explain the greater risk for major adverse cardiovascular events seen in patients with high Lp(a) levels, suggests the research, presented during the annual European Atherosclerosis Society Congress.

The team performed follow-up coronary CT angiography (CCTA) on almost 275 patients who had undergone imaging approximately 10 years earlier, finding that almost one-third had high Lp(a) levels.

At baseline, per cent plaque volumes were 1.8 times greater in high Lp(a) patients versus those with low levels of the protein. After 10 years, plaque volumes were 3.3 times larger in patients with high Lp(a) levels.

Over this period, the rate of increase of plaque volume was 1.9 times greater in patients with high Lp(a) levels.

Study presenter Nick S. Nurmohamed, MD, PhD candidate, department of vascular medicine, Amsterdam University Medical Centers, also showed that high Lp(a) levels were associated with a 2.1-fold increase in rates of MACE.

He said in an interview that this finding could be related to Lp(a) increasing inflammatory signaling in the plaque, “making it more prone to rupture, and we saw that on the CCTA scans,” where high Lp(a) levels were associated with the presence of more high-risk plaques.

He added that in the absence of drugs that target Lp(a) levels directly, the results underline the need to focus on other means of lipid-lowering, as well as “creating awareness that Lp(a) is associated with plaque formation.”

Dr. Nurmohamed said that “for the moment, we have to treat patients with high Lp(a) with other risk-lowering therapies, such as low-density lipoprotein [LDL] cholesterol–lowering drugs, and the management of other risk factors.”

However, he noted that “there are a couple of Lp(a)-lowering medications in trials,” with results expected in the next 2-3 years.

“Then we will have the means to treat those patients, and with CCTA we can identify the patients with the biggest risk,” Dr. Nurmohamed added.
 

Plaque burden

Philippe Moulin, MD, PhD, head of endocrinology and professor of human nutrition at Faculté Lyon Est, Claude Bernard Lyon (France) 1 University, said that the association between Lp(a) and plaque burden has been seen previously in the literature in a very similar study but with only 1-year follow-up.

Similarly, registry data have suggested that Lp(a) is associated with worsening plaque progression over time.

“Here, with 10-year follow-up, [the study] is much more interesting,” due to its greater statistical power, he said in an interview. It is also “well-documented” and uses an “appropriate” methodology.

But Dr. Moulin underlined that the number of patients with high Lp(a) levels included in the study is relatively small.

Consequently, the researchers were not able to look at the level and rate of progression of atherosclerosis between different quartiles of Lp(a), “so you have no dose-response analysis.”

It also does not “establish causality,” as it remains an observational study, despite being longitudinal, “well done, and so on.”

Dr. Moulin added that the study nevertheless adds “one more stone” to the construct of the idea of high risk around high Lp(a) levels, and “prepares the ground” for the availability of two drugs to decrease Lp(a) levels, expected in 2026 and 2027.

These are expected to substantially reduce Lp(a) levels and achieve a reduction in cardiovascular risk of around 20%-40%, “which would be interesting,” especially as “we have patients who have Lp(a) levels four times above the upper normal value.”

Crucially, they may already have normal LDL cholesterol levels, meaning that, for some patients, “there is clearly a need for such treatment, as long as it is proven that it will decrease cardiovascular risk.”

For the moment, however, the strategy for managing patients with high Lp(a) remains to increase the dose of statin and to have more stringent targets, although Dr. Moulin pointed out that, “when you give statins, you raise slightly Lp(a) levels.”

Dr. Nurmohamed said in an interview that “we know from largely genetic and observational studies that Lp(a) is causally associated with atherosclerotic cardiovascular disease.”

What is less clear is the exact underlying mechanism, he said, noting that there have been several imaging studies in high and low Lp(a) patients that have yielded conflicting results in terms of the relationship with plaque burden.

To investigate the impact of Lp(a) levels on long-term coronary plaque progression, the team invited patients who had taken part in a previous CCTA study to undergo repeat CCTA, regardless of their underlying symptoms.

In all, 299 patients underwent follow-up imaging a median of 10.2 years after their original scan. Plaque volumes were quantified and adjusted for vessel volumes, and the patients were classified as having high (≥ 70 nmol/L) or low (< 70 nmol/L) Lp(a) levels.

After excluding patients who had undergone coronary artery bypass grafting, the team analyzed 274 patients with a mean age at baseline of 57 years. Of these, 159 (58%) were men. High Lp(a) levels were identified in 87 (32%) patients.

The team found that at baseline, patients with high Lp(a) levels had significantly larger percent atheroma volumes than those with low levels, at 3.92% versus 2.17%, or an absolute difference of 1.75% (P = .013).

The difference between the two groups was even greater at the follow-up, when percent atheroma volumes reached 8.75% in patients with high Lp(a) levels versus 3.90% for those with low levels, or an absolute difference of 4.85% (P = .005).

Similar findings were seen when looking separately at percentage of noncalcified and calcified plaque volumes as well as when analyzing for the presence of low-density plaques.

Multivariate analysis taking into account clinical risk factors, statin use, and CT tube voltage found that high Lp(a) levels were associated with a greater percent atheroma volume at baseline, at an odds ratio versus low Lp(a) of 1.83 (95% confidence interval, 0.12-3.54; P = .037).

High Lp(a) levels were also linked to a larger percent atheroma volume on follow-up imaging, at an odds ratio of 3.25 (95% CI, 0.80-5.71; P = .010), and a significantly greater change in atheroma volume from baseline to follow-up imaging, at an odds ratio of 1.86 (95% CI, 0.59-3.14; P = .005)

Finally, the team showed that, after adjusting for clinical risk factors, high baseline Lp(a) levels were associated with an increased risk of MACE during the follow-up period, at a hazard ratio versus low Lp(a) levels of 2.10 (95% CI, 1.01-4.29, P = .048).

No funding was declared. Dr. Nurmohamed is cofounder of Lipid Tools. Other authors declare relationships with Amgen, Novartis, Esperion, Sanofi-Regeneron, Ackee, Cleerly, GW Heart and Vascular Institute, Siemens Healthineers, and HeartFlow.

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

MANNHEIM, GERMANY – Patients with high lipoprotein(a) (Lp[a]) levels not only have an almost twofold higher coronary plaque burden than those with low levels but also a faster rate of plaque progression, an observational imaging study shows.

This could explain the greater risk for major adverse cardiovascular events seen in patients with high Lp(a) levels, suggests the research, presented during the annual European Atherosclerosis Society Congress.

The team performed follow-up coronary CT angiography (CCTA) on almost 275 patients who had undergone imaging approximately 10 years earlier, finding that almost one-third had high Lp(a) levels.

At baseline, per cent plaque volumes were 1.8 times greater in high Lp(a) patients versus those with low levels of the protein. After 10 years, plaque volumes were 3.3 times larger in patients with high Lp(a) levels.

Over this period, the rate of increase of plaque volume was 1.9 times greater in patients with high Lp(a) levels.

Study presenter Nick S. Nurmohamed, MD, PhD candidate, department of vascular medicine, Amsterdam University Medical Centers, also showed that high Lp(a) levels were associated with a 2.1-fold increase in rates of MACE.

He said in an interview that this finding could be related to Lp(a) increasing inflammatory signaling in the plaque, “making it more prone to rupture, and we saw that on the CCTA scans,” where high Lp(a) levels were associated with the presence of more high-risk plaques.

He added that in the absence of drugs that target Lp(a) levels directly, the results underline the need to focus on other means of lipid-lowering, as well as “creating awareness that Lp(a) is associated with plaque formation.”

Dr. Nurmohamed said that “for the moment, we have to treat patients with high Lp(a) with other risk-lowering therapies, such as low-density lipoprotein [LDL] cholesterol–lowering drugs, and the management of other risk factors.”

However, he noted that “there are a couple of Lp(a)-lowering medications in trials,” with results expected in the next 2-3 years.

“Then we will have the means to treat those patients, and with CCTA we can identify the patients with the biggest risk,” Dr. Nurmohamed added.
 

Plaque burden

Philippe Moulin, MD, PhD, head of endocrinology and professor of human nutrition at Faculté Lyon Est, Claude Bernard Lyon (France) 1 University, said that the association between Lp(a) and plaque burden has been seen previously in the literature in a very similar study but with only 1-year follow-up.

Similarly, registry data have suggested that Lp(a) is associated with worsening plaque progression over time.

“Here, with 10-year follow-up, [the study] is much more interesting,” due to its greater statistical power, he said in an interview. It is also “well-documented” and uses an “appropriate” methodology.

But Dr. Moulin underlined that the number of patients with high Lp(a) levels included in the study is relatively small.

Consequently, the researchers were not able to look at the level and rate of progression of atherosclerosis between different quartiles of Lp(a), “so you have no dose-response analysis.”

It also does not “establish causality,” as it remains an observational study, despite being longitudinal, “well done, and so on.”

Dr. Moulin added that the study nevertheless adds “one more stone” to the construct of the idea of high risk around high Lp(a) levels, and “prepares the ground” for the availability of two drugs to decrease Lp(a) levels, expected in 2026 and 2027.

These are expected to substantially reduce Lp(a) levels and achieve a reduction in cardiovascular risk of around 20%-40%, “which would be interesting,” especially as “we have patients who have Lp(a) levels four times above the upper normal value.”

Crucially, they may already have normal LDL cholesterol levels, meaning that, for some patients, “there is clearly a need for such treatment, as long as it is proven that it will decrease cardiovascular risk.”

For the moment, however, the strategy for managing patients with high Lp(a) remains to increase the dose of statin and to have more stringent targets, although Dr. Moulin pointed out that, “when you give statins, you raise slightly Lp(a) levels.”

Dr. Nurmohamed said in an interview that “we know from largely genetic and observational studies that Lp(a) is causally associated with atherosclerotic cardiovascular disease.”

What is less clear is the exact underlying mechanism, he said, noting that there have been several imaging studies in high and low Lp(a) patients that have yielded conflicting results in terms of the relationship with plaque burden.

To investigate the impact of Lp(a) levels on long-term coronary plaque progression, the team invited patients who had taken part in a previous CCTA study to undergo repeat CCTA, regardless of their underlying symptoms.

In all, 299 patients underwent follow-up imaging a median of 10.2 years after their original scan. Plaque volumes were quantified and adjusted for vessel volumes, and the patients were classified as having high (≥ 70 nmol/L) or low (< 70 nmol/L) Lp(a) levels.

After excluding patients who had undergone coronary artery bypass grafting, the team analyzed 274 patients with a mean age at baseline of 57 years. Of these, 159 (58%) were men. High Lp(a) levels were identified in 87 (32%) patients.

The team found that at baseline, patients with high Lp(a) levels had significantly larger percent atheroma volumes than those with low levels, at 3.92% versus 2.17%, or an absolute difference of 1.75% (P = .013).

The difference between the two groups was even greater at the follow-up, when percent atheroma volumes reached 8.75% in patients with high Lp(a) levels versus 3.90% for those with low levels, or an absolute difference of 4.85% (P = .005).

Similar findings were seen when looking separately at percentage of noncalcified and calcified plaque volumes as well as when analyzing for the presence of low-density plaques.

Multivariate analysis taking into account clinical risk factors, statin use, and CT tube voltage found that high Lp(a) levels were associated with a greater percent atheroma volume at baseline, at an odds ratio versus low Lp(a) of 1.83 (95% confidence interval, 0.12-3.54; P = .037).

High Lp(a) levels were also linked to a larger percent atheroma volume on follow-up imaging, at an odds ratio of 3.25 (95% CI, 0.80-5.71; P = .010), and a significantly greater change in atheroma volume from baseline to follow-up imaging, at an odds ratio of 1.86 (95% CI, 0.59-3.14; P = .005)

Finally, the team showed that, after adjusting for clinical risk factors, high baseline Lp(a) levels were associated with an increased risk of MACE during the follow-up period, at a hazard ratio versus low Lp(a) levels of 2.10 (95% CI, 1.01-4.29, P = .048).

No funding was declared. Dr. Nurmohamed is cofounder of Lipid Tools. Other authors declare relationships with Amgen, Novartis, Esperion, Sanofi-Regeneron, Ackee, Cleerly, GW Heart and Vascular Institute, Siemens Healthineers, and HeartFlow.

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

Adult survivors of childhood cancer have an elevated risk of developing cognitive impairment years after their cancer diagnosis and treatment, new research shows.

Among more than 2,300 adult survivors of childhood cancer and their siblings, who served as controls, new-onset memory impairment emerged more often in survivors decades later.

The increased risk was associated with the cancer treatment that was provided as well as modifiable health behaviors and chronic health conditions.

Even 35 years after being diagnosed, cancer survivors who never received chemotherapies or radiation therapies known to damage the brain reported far greater memory impairment than did their siblings, first author Nicholas Phillips, MD, told this news organization.

What the findings suggest is that “we need to educate oncologists and primary care providers on the risks our survivors face long after completion of therapy,” said Dr. Phillips, of the epidemiology and cancer control department at St. Jude Children’s Research Hospital, Memphis, Tenn.

The study was published online in JAMA Network Open.

Cancer survivors face an elevated risk for severe neurocognitive effects that can emerge 5-10 years following their diagnosis and treatment. However, it’s unclear whether new-onset neurocognitive problems can still develop a decade or more following diagnosis.

Over a long-term follow-up, Dr. Phillips and colleagues explored this question in 2,375 adult survivors of childhood cancer from the Childhood Cancer Survivor Study and 232 of their siblings.

Among the cancer cohort, 1,316 patients were survivors of acute lymphoblastic leukemia (ALL), 488 were survivors of central nervous system (CNS) tumors, and 571 had survived Hodgkin lymphoma.

The researchers determined the prevalence of new-onset neurocognitive impairment between baseline (23 years after diagnosis) and follow-up (35 years after diagnosis). New-onset neurocognitive impairment – present at follow-up but not at baseline – was defined as having a score in the worst 10% of the sibling cohort.

A higher proportion of survivors had new-onset memory impairment at follow-up compared with siblings. Specifically, about 8% of siblings had new-onset memory trouble, compared with 14% of ALL survivors treated with chemotherapy only, 26% of ALL survivors treated with cranial radiation, 35% of CNS tumor survivors, and 17% of Hodgkin lymphoma survivors.

New-onset memory impairment was associated with cranial radiation among CNS tumor survivors (relative risk [RR], 1.97) and alkylator chemotherapy at or above 8,000 mg/m² among survivors of ALL who were treated without cranial radiation (RR, 2.80). The authors also found that smoking, low educational attainment, and low physical activity were associated with an elevated risk for new-onset memory impairment.

Dr. Phillips noted that current guidelines emphasize the importance of short-term monitoring of a survivor’s neurocognitive status on the basis of that person’s chemotherapy and radiation exposures.

However, “our study suggests that all survivors, regardless of their therapy, should be screened regularly for new-onset neurocognitive problems. And this screening should be done regularly for decades after diagnosis,” he said in an interview.

Dr. Phillips also noted the importance of communicating lifestyle modifications, such as not smoking and maintaining an active lifestyle.

“We need to start early and use the power of repetition when communicating with our survivors and their families,” Dr. Phillips said. “When our families and survivors hear the word ‘exercise,’ they think of gym memberships, lifting weights, and running on treadmills. But what we really want our survivors to do is stay active.”

What this means is engaging for about 2.5 hours a week in a range of activities, such as ballet, basketball, volleyball, bicycling, or swimming.

“And if our kids want to quit after 3 months, let them know that this is okay. They just need to replace that activity with another activity,” said Dr. Phillips. “We want them to find a fun hobby that they will enjoy that will keep them active.”

The study was supported by the National Cancer Institute. Dr. Phillips has disclosed no relevant financial relationships.

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

Adult survivors of childhood cancer have an elevated risk of developing cognitive impairment years after their cancer diagnosis and treatment, new research shows.

Among more than 2,300 adult survivors of childhood cancer and their siblings, who served as controls, new-onset memory impairment emerged more often in survivors decades later.

The increased risk was associated with the cancer treatment that was provided as well as modifiable health behaviors and chronic health conditions.

Even 35 years after being diagnosed, cancer survivors who never received chemotherapies or radiation therapies known to damage the brain reported far greater memory impairment than did their siblings, first author Nicholas Phillips, MD, told this news organization.

What the findings suggest is that “we need to educate oncologists and primary care providers on the risks our survivors face long after completion of therapy,” said Dr. Phillips, of the epidemiology and cancer control department at St. Jude Children’s Research Hospital, Memphis, Tenn.

The study was published online in JAMA Network Open.

Cancer survivors face an elevated risk for severe neurocognitive effects that can emerge 5-10 years following their diagnosis and treatment. However, it’s unclear whether new-onset neurocognitive problems can still develop a decade or more following diagnosis.

Over a long-term follow-up, Dr. Phillips and colleagues explored this question in 2,375 adult survivors of childhood cancer from the Childhood Cancer Survivor Study and 232 of their siblings.

Among the cancer cohort, 1,316 patients were survivors of acute lymphoblastic leukemia (ALL), 488 were survivors of central nervous system (CNS) tumors, and 571 had survived Hodgkin lymphoma.

The researchers determined the prevalence of new-onset neurocognitive impairment between baseline (23 years after diagnosis) and follow-up (35 years after diagnosis). New-onset neurocognitive impairment – present at follow-up but not at baseline – was defined as having a score in the worst 10% of the sibling cohort.

A higher proportion of survivors had new-onset memory impairment at follow-up compared with siblings. Specifically, about 8% of siblings had new-onset memory trouble, compared with 14% of ALL survivors treated with chemotherapy only, 26% of ALL survivors treated with cranial radiation, 35% of CNS tumor survivors, and 17% of Hodgkin lymphoma survivors.

New-onset memory impairment was associated with cranial radiation among CNS tumor survivors (relative risk [RR], 1.97) and alkylator chemotherapy at or above 8,000 mg/m² among survivors of ALL who were treated without cranial radiation (RR, 2.80). The authors also found that smoking, low educational attainment, and low physical activity were associated with an elevated risk for new-onset memory impairment.

Dr. Phillips noted that current guidelines emphasize the importance of short-term monitoring of a survivor’s neurocognitive status on the basis of that person’s chemotherapy and radiation exposures.

However, “our study suggests that all survivors, regardless of their therapy, should be screened regularly for new-onset neurocognitive problems. And this screening should be done regularly for decades after diagnosis,” he said in an interview.

Dr. Phillips also noted the importance of communicating lifestyle modifications, such as not smoking and maintaining an active lifestyle.

“We need to start early and use the power of repetition when communicating with our survivors and their families,” Dr. Phillips said. “When our families and survivors hear the word ‘exercise,’ they think of gym memberships, lifting weights, and running on treadmills. But what we really want our survivors to do is stay active.”

What this means is engaging for about 2.5 hours a week in a range of activities, such as ballet, basketball, volleyball, bicycling, or swimming.

“And if our kids want to quit after 3 months, let them know that this is okay. They just need to replace that activity with another activity,” said Dr. Phillips. “We want them to find a fun hobby that they will enjoy that will keep them active.”

The study was supported by the National Cancer Institute. Dr. Phillips has disclosed no relevant financial relationships.

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

Adult survivors of childhood cancer have an elevated risk of developing cognitive impairment years after their cancer diagnosis and treatment, new research shows.

Among more than 2,300 adult survivors of childhood cancer and their siblings, who served as controls, new-onset memory impairment emerged more often in survivors decades later.

The increased risk was associated with the cancer treatment that was provided as well as modifiable health behaviors and chronic health conditions.

Even 35 years after being diagnosed, cancer survivors who never received chemotherapies or radiation therapies known to damage the brain reported far greater memory impairment than did their siblings, first author Nicholas Phillips, MD, told this news organization.

What the findings suggest is that “we need to educate oncologists and primary care providers on the risks our survivors face long after completion of therapy,” said Dr. Phillips, of the epidemiology and cancer control department at St. Jude Children’s Research Hospital, Memphis, Tenn.

The study was published online in JAMA Network Open.

Cancer survivors face an elevated risk for severe neurocognitive effects that can emerge 5-10 years following their diagnosis and treatment. However, it’s unclear whether new-onset neurocognitive problems can still develop a decade or more following diagnosis.

Over a long-term follow-up, Dr. Phillips and colleagues explored this question in 2,375 adult survivors of childhood cancer from the Childhood Cancer Survivor Study and 232 of their siblings.

Among the cancer cohort, 1,316 patients were survivors of acute lymphoblastic leukemia (ALL), 488 were survivors of central nervous system (CNS) tumors, and 571 had survived Hodgkin lymphoma.

The researchers determined the prevalence of new-onset neurocognitive impairment between baseline (23 years after diagnosis) and follow-up (35 years after diagnosis). New-onset neurocognitive impairment – present at follow-up but not at baseline – was defined as having a score in the worst 10% of the sibling cohort.

A higher proportion of survivors had new-onset memory impairment at follow-up compared with siblings. Specifically, about 8% of siblings had new-onset memory trouble, compared with 14% of ALL survivors treated with chemotherapy only, 26% of ALL survivors treated with cranial radiation, 35% of CNS tumor survivors, and 17% of Hodgkin lymphoma survivors.

New-onset memory impairment was associated with cranial radiation among CNS tumor survivors (relative risk [RR], 1.97) and alkylator chemotherapy at or above 8,000 mg/m² among survivors of ALL who were treated without cranial radiation (RR, 2.80). The authors also found that smoking, low educational attainment, and low physical activity were associated with an elevated risk for new-onset memory impairment.

Dr. Phillips noted that current guidelines emphasize the importance of short-term monitoring of a survivor’s neurocognitive status on the basis of that person’s chemotherapy and radiation exposures.

However, “our study suggests that all survivors, regardless of their therapy, should be screened regularly for new-onset neurocognitive problems. And this screening should be done regularly for decades after diagnosis,” he said in an interview.

Dr. Phillips also noted the importance of communicating lifestyle modifications, such as not smoking and maintaining an active lifestyle.

“We need to start early and use the power of repetition when communicating with our survivors and their families,” Dr. Phillips said. “When our families and survivors hear the word ‘exercise,’ they think of gym memberships, lifting weights, and running on treadmills. But what we really want our survivors to do is stay active.”

What this means is engaging for about 2.5 hours a week in a range of activities, such as ballet, basketball, volleyball, bicycling, or swimming.

“And if our kids want to quit after 3 months, let them know that this is okay. They just need to replace that activity with another activity,” said Dr. Phillips. “We want them to find a fun hobby that they will enjoy that will keep them active.”

The study was supported by the National Cancer Institute. Dr. Phillips has disclosed no relevant financial relationships.

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

Researchers may use artificial intelligence (AI) language models such as ChatGPT to write and revise scientific manuscripts, according to a new announcement from the International Committee of Medical Journal Editors. These tools should not be listed as authors, and researchers must denote how AI-assisted technologies were used, the committee said.

These new guidelines are the latest effort for medical journals to define policies for using these large-scale language models (LLMs) in scientific publication. While these AI-assisted tools can help with tasks such as writing, analyzing data, catching mistakes, and much more, they are also prone to errors, noted Casey Greene, PhD, a professor of biomedical informatics at the University of Colorado at Denver, Aurora. It is also not totally clear how information is stored and processed in these kinds of tools, and who has access to that information, he noted.

At the same time, experts argue that these AI tools could have a positive impact on the field by limiting some of the linguistic disparities in scientific publishing as well as alleviating the burden of some monotonous or mechanical tasks that come along with manuscript writing.

What experts can agree on, though, is that the use of AI tools is here to stay. “This is going to become a common tool,” Dr. Greene said. “I don’t think there’s a way out of that at this point.”
 

A change in medical publishing

OpenAI released ChatGPT in November 2022. In its own words, ChatGPT is “a deep learning model that has been trained on a massive amount of text data to understand and generate humanlike text.” Enter a question or a prompt, and it will respond. For example, when asked how the AI tool can be used in scientific publishing, ChatGPT responded:

“ChatGPT can aid scientific publishing by generating ideas, clarifying concepts, conducting preliminary literature reviews, providing proofreading and editing suggestions, and assisting with outlining and organizing scientific papers. However, it should be used as a supportive tool alongside domain expertise and validation from trusted scientific sources.”

Just a few months after ChatGPT became available, researchers began using this tool in their own work. One individual, Som Biswas, MD, a radiologist at the University of Tennessee Health Science Center in Memphis, reportedly used ChatGPT to author 16 scientific articles in just 4 months, according to the Daily Beast. Five of these articles have been published in four different journals. Dr. Biswas declined to be interviewed for this article.

There were also reports of papers with ChatGPT as one of the listed authors, which sparked backlash. In response, JAMA, Nature, and Science all published editorials in January outlining their policies for using ChatGPT and other large language models in the scientific authoring process. Editors from the journals of the American College of Cardiology and the American College of Rheumatology also updated their policies to reflect the influence of AI authoring tools.

The consensus is that AI has no place on the author byline.

“We think that’s not appropriate, because coauthorship means that you are taking responsibility for the analysis and the generation of data that are included in a manuscript. A machine that is dictated by AI can’t take responsibility,” said Daniel Solomon, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, and the editor in chief of the ACR journal Arthritis & Rheumatology.
 

Issues with AI

One of the big concerns around using AI in writing is that it can generate text that seems plausible but is untrue or not supported by data. For example, Dr. Greene and colleague Milton Pividori, PhD, also of the University of Colorado, were writing a journal article about new software they developed that uses a large language model to revise scientific manuscripts.

“We used the same software to revise that article and at one point, it added a line that noted that the large language model had been fine-tuned on a data set of manuscripts from within the same field. This makes a lot of sense, and is absolutely something you could do, but was not something that we did,” Dr. Greene said. “Without a really careful review of the content, it becomes possible to invent things that were not actually done.”

In another case, ChatGPT falsely stated that a prominent law professor had been accused of sexual assault, citing a Washington Post article that did not exist.

“We live in a society where we are extremely concerned about fake news,” Dr. Pividori added, “and [these kinds of errors] could certainly exacerbate that in the scientific community, which is very concerning because science informs public policy.”

Another issue is the lack of transparency around how large language models like ChatGPT process and store data used to make queries.

“We have no idea how they are recording all the prompts and things that we input into ChatGPT and their systems,” Dr. Pividori said.

OpenAI recently addressed some privacy concerns by allowing users to turn off their chat history with the AI chatbot, so conversations cannot be used to train or improve the company’s models. But Dr. Greene noted that the terms of service “still remain pretty nebulous.”

Dr. Solomon is also concerned with researchers using these AI tools in authoring without knowing how they work. “The thing we are really concerned about is that fact that [LLMs] are a bit of a black box – people don’t really understand the methodologies,” he said.
 

A positive tool?

But despite these concerns, many think that these types of AI-assisted tools could have a positive impact on medical publishing, particularly for researchers for whom English is not their first language, noted Catherine Gao, MD, a pulmonary and critical care instructor at Northwestern University, Chicago. She recently led research comparing scientific abstracts written by ChatGPT and real abstracts and discovered that reviewers found it “surprisingly difficult” to differentiate the two.

“The majority of research is published in English,” she said in an email. “Responsible use of LLMs can potentially reduce the burden of writing for busy scientists and improve equity for those who are not native English speakers.”

Dr. Pividori agreed, adding that as a non-native English speaker, he spends much more time working on the structure and grammar of sentences when authoring a manuscript, compared with people who speak English as a first language. He noted that these tools can also be used to automate some of the more monotonous tasks that come along with writing manuscripts and allow researchers to focus on the more creative aspects.

In the future, “I want to focus more on the things that only a human can do and let these tools do all the rest of it,” he said.
 

New rules

But despite how individual researchers feel about LLMs, they agree that these AI tools are here to stay.

“I think that we should anticipate that they will become part of the medical research establishment over time, when we figure out how to use them appropriately,” Dr. Solomon said.

While the debate of how to best use AI in medical publications will continue, journal editors agree that all authors of a manuscript are solely responsible for content in articles that used AI-assisted technology.

“Authors should carefully review and edit the result because AI can generate authoritative-sounding output that can be incorrect, incomplete, or biased,” the ICMJE guidelines state. “Authors should be able to assert that there is no plagiarism in their paper, including in text and images produced by the AI.” This includes appropriate attribution of all cited materials.

The committee also recommends that authors write in both the cover letter and submitted work how AI was used in the manuscript writing process. Recently updated guidelines from the World Association of Medical Editors recommend that all prompts used to generate new text or analytical work should be provided in submitted work. Dr. Greene also noted that if authors used an AI tool to revise their work, they can include a version of the manuscript untouched by LLMs.

It is similar to a preprint, he said, but rather than publishing a version of a paper prior to peer review, someone is showing a version of a manuscript before it was reviewed and revised by AI. “This type of practice could be a path that lets us benefit from these models,” he said, “without having the drawbacks that many are concerned about.”

Dr. Solomon has financial relationships with AbbVie, Amgen, Janssen, CorEvitas, and Moderna. Both Dr. Greene and Dr. Pividori are inventors in the U.S. Provisional Patent Application No. 63/486,706 that the University of Colorado has filed for the “Publishing Infrastructure For AI-Assisted Academic Authoring” invention with the U.S. Patent and Trademark Office. Dr. Greene and Dr. Pividori also received a grant from the Alfred P. Sloan Foundation to improve their AI-based manuscript revision tool. Dr. Gao reported no relevant financial relationships.

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

Researchers may use artificial intelligence (AI) language models such as ChatGPT to write and revise scientific manuscripts, according to a new announcement from the International Committee of Medical Journal Editors. These tools should not be listed as authors, and researchers must denote how AI-assisted technologies were used, the committee said.

These new guidelines are the latest effort for medical journals to define policies for using these large-scale language models (LLMs) in scientific publication. While these AI-assisted tools can help with tasks such as writing, analyzing data, catching mistakes, and much more, they are also prone to errors, noted Casey Greene, PhD, a professor of biomedical informatics at the University of Colorado at Denver, Aurora. It is also not totally clear how information is stored and processed in these kinds of tools, and who has access to that information, he noted.

At the same time, experts argue that these AI tools could have a positive impact on the field by limiting some of the linguistic disparities in scientific publishing as well as alleviating the burden of some monotonous or mechanical tasks that come along with manuscript writing.

What experts can agree on, though, is that the use of AI tools is here to stay. “This is going to become a common tool,” Dr. Greene said. “I don’t think there’s a way out of that at this point.”
 

A change in medical publishing

OpenAI released ChatGPT in November 2022. In its own words, ChatGPT is “a deep learning model that has been trained on a massive amount of text data to understand and generate humanlike text.” Enter a question or a prompt, and it will respond. For example, when asked how the AI tool can be used in scientific publishing, ChatGPT responded:

“ChatGPT can aid scientific publishing by generating ideas, clarifying concepts, conducting preliminary literature reviews, providing proofreading and editing suggestions, and assisting with outlining and organizing scientific papers. However, it should be used as a supportive tool alongside domain expertise and validation from trusted scientific sources.”

Just a few months after ChatGPT became available, researchers began using this tool in their own work. One individual, Som Biswas, MD, a radiologist at the University of Tennessee Health Science Center in Memphis, reportedly used ChatGPT to author 16 scientific articles in just 4 months, according to the Daily Beast. Five of these articles have been published in four different journals. Dr. Biswas declined to be interviewed for this article.

There were also reports of papers with ChatGPT as one of the listed authors, which sparked backlash. In response, JAMA, Nature, and Science all published editorials in January outlining their policies for using ChatGPT and other large language models in the scientific authoring process. Editors from the journals of the American College of Cardiology and the American College of Rheumatology also updated their policies to reflect the influence of AI authoring tools.

The consensus is that AI has no place on the author byline.

“We think that’s not appropriate, because coauthorship means that you are taking responsibility for the analysis and the generation of data that are included in a manuscript. A machine that is dictated by AI can’t take responsibility,” said Daniel Solomon, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, and the editor in chief of the ACR journal Arthritis & Rheumatology.
 

Issues with AI

One of the big concerns around using AI in writing is that it can generate text that seems plausible but is untrue or not supported by data. For example, Dr. Greene and colleague Milton Pividori, PhD, also of the University of Colorado, were writing a journal article about new software they developed that uses a large language model to revise scientific manuscripts.

“We used the same software to revise that article and at one point, it added a line that noted that the large language model had been fine-tuned on a data set of manuscripts from within the same field. This makes a lot of sense, and is absolutely something you could do, but was not something that we did,” Dr. Greene said. “Without a really careful review of the content, it becomes possible to invent things that were not actually done.”

In another case, ChatGPT falsely stated that a prominent law professor had been accused of sexual assault, citing a Washington Post article that did not exist.

“We live in a society where we are extremely concerned about fake news,” Dr. Pividori added, “and [these kinds of errors] could certainly exacerbate that in the scientific community, which is very concerning because science informs public policy.”

Another issue is the lack of transparency around how large language models like ChatGPT process and store data used to make queries.

“We have no idea how they are recording all the prompts and things that we input into ChatGPT and their systems,” Dr. Pividori said.

OpenAI recently addressed some privacy concerns by allowing users to turn off their chat history with the AI chatbot, so conversations cannot be used to train or improve the company’s models. But Dr. Greene noted that the terms of service “still remain pretty nebulous.”

Dr. Solomon is also concerned with researchers using these AI tools in authoring without knowing how they work. “The thing we are really concerned about is that fact that [LLMs] are a bit of a black box – people don’t really understand the methodologies,” he said.
 

A positive tool?

But despite these concerns, many think that these types of AI-assisted tools could have a positive impact on medical publishing, particularly for researchers for whom English is not their first language, noted Catherine Gao, MD, a pulmonary and critical care instructor at Northwestern University, Chicago. She recently led research comparing scientific abstracts written by ChatGPT and real abstracts and discovered that reviewers found it “surprisingly difficult” to differentiate the two.

“The majority of research is published in English,” she said in an email. “Responsible use of LLMs can potentially reduce the burden of writing for busy scientists and improve equity for those who are not native English speakers.”

Dr. Pividori agreed, adding that as a non-native English speaker, he spends much more time working on the structure and grammar of sentences when authoring a manuscript, compared with people who speak English as a first language. He noted that these tools can also be used to automate some of the more monotonous tasks that come along with writing manuscripts and allow researchers to focus on the more creative aspects.

In the future, “I want to focus more on the things that only a human can do and let these tools do all the rest of it,” he said.
 

New rules

But despite how individual researchers feel about LLMs, they agree that these AI tools are here to stay.

“I think that we should anticipate that they will become part of the medical research establishment over time, when we figure out how to use them appropriately,” Dr. Solomon said.

While the debate of how to best use AI in medical publications will continue, journal editors agree that all authors of a manuscript are solely responsible for content in articles that used AI-assisted technology.

“Authors should carefully review and edit the result because AI can generate authoritative-sounding output that can be incorrect, incomplete, or biased,” the ICMJE guidelines state. “Authors should be able to assert that there is no plagiarism in their paper, including in text and images produced by the AI.” This includes appropriate attribution of all cited materials.

The committee also recommends that authors write in both the cover letter and submitted work how AI was used in the manuscript writing process. Recently updated guidelines from the World Association of Medical Editors recommend that all prompts used to generate new text or analytical work should be provided in submitted work. Dr. Greene also noted that if authors used an AI tool to revise their work, they can include a version of the manuscript untouched by LLMs.

It is similar to a preprint, he said, but rather than publishing a version of a paper prior to peer review, someone is showing a version of a manuscript before it was reviewed and revised by AI. “This type of practice could be a path that lets us benefit from these models,” he said, “without having the drawbacks that many are concerned about.”

Dr. Solomon has financial relationships with AbbVie, Amgen, Janssen, CorEvitas, and Moderna. Both Dr. Greene and Dr. Pividori are inventors in the U.S. Provisional Patent Application No. 63/486,706 that the University of Colorado has filed for the “Publishing Infrastructure For AI-Assisted Academic Authoring” invention with the U.S. Patent and Trademark Office. Dr. Greene and Dr. Pividori also received a grant from the Alfred P. Sloan Foundation to improve their AI-based manuscript revision tool. Dr. Gao reported no relevant financial relationships.

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

Researchers may use artificial intelligence (AI) language models such as ChatGPT to write and revise scientific manuscripts, according to a new announcement from the International Committee of Medical Journal Editors. These tools should not be listed as authors, and researchers must denote how AI-assisted technologies were used, the committee said.

These new guidelines are the latest effort for medical journals to define policies for using these large-scale language models (LLMs) in scientific publication. While these AI-assisted tools can help with tasks such as writing, analyzing data, catching mistakes, and much more, they are also prone to errors, noted Casey Greene, PhD, a professor of biomedical informatics at the University of Colorado at Denver, Aurora. It is also not totally clear how information is stored and processed in these kinds of tools, and who has access to that information, he noted.

At the same time, experts argue that these AI tools could have a positive impact on the field by limiting some of the linguistic disparities in scientific publishing as well as alleviating the burden of some monotonous or mechanical tasks that come along with manuscript writing.

What experts can agree on, though, is that the use of AI tools is here to stay. “This is going to become a common tool,” Dr. Greene said. “I don’t think there’s a way out of that at this point.”
 

A change in medical publishing

OpenAI released ChatGPT in November 2022. In its own words, ChatGPT is “a deep learning model that has been trained on a massive amount of text data to understand and generate humanlike text.” Enter a question or a prompt, and it will respond. For example, when asked how the AI tool can be used in scientific publishing, ChatGPT responded:

“ChatGPT can aid scientific publishing by generating ideas, clarifying concepts, conducting preliminary literature reviews, providing proofreading and editing suggestions, and assisting with outlining and organizing scientific papers. However, it should be used as a supportive tool alongside domain expertise and validation from trusted scientific sources.”

Just a few months after ChatGPT became available, researchers began using this tool in their own work. One individual, Som Biswas, MD, a radiologist at the University of Tennessee Health Science Center in Memphis, reportedly used ChatGPT to author 16 scientific articles in just 4 months, according to the Daily Beast. Five of these articles have been published in four different journals. Dr. Biswas declined to be interviewed for this article.

There were also reports of papers with ChatGPT as one of the listed authors, which sparked backlash. In response, JAMA, Nature, and Science all published editorials in January outlining their policies for using ChatGPT and other large language models in the scientific authoring process. Editors from the journals of the American College of Cardiology and the American College of Rheumatology also updated their policies to reflect the influence of AI authoring tools.

The consensus is that AI has no place on the author byline.

“We think that’s not appropriate, because coauthorship means that you are taking responsibility for the analysis and the generation of data that are included in a manuscript. A machine that is dictated by AI can’t take responsibility,” said Daniel Solomon, MD, MPH, a rheumatologist at Brigham and Women’s Hospital, Boston, and the editor in chief of the ACR journal Arthritis & Rheumatology.
 

Issues with AI

One of the big concerns around using AI in writing is that it can generate text that seems plausible but is untrue or not supported by data. For example, Dr. Greene and colleague Milton Pividori, PhD, also of the University of Colorado, were writing a journal article about new software they developed that uses a large language model to revise scientific manuscripts.

“We used the same software to revise that article and at one point, it added a line that noted that the large language model had been fine-tuned on a data set of manuscripts from within the same field. This makes a lot of sense, and is absolutely something you could do, but was not something that we did,” Dr. Greene said. “Without a really careful review of the content, it becomes possible to invent things that were not actually done.”

In another case, ChatGPT falsely stated that a prominent law professor had been accused of sexual assault, citing a Washington Post article that did not exist.

“We live in a society where we are extremely concerned about fake news,” Dr. Pividori added, “and [these kinds of errors] could certainly exacerbate that in the scientific community, which is very concerning because science informs public policy.”

Another issue is the lack of transparency around how large language models like ChatGPT process and store data used to make queries.

“We have no idea how they are recording all the prompts and things that we input into ChatGPT and their systems,” Dr. Pividori said.

OpenAI recently addressed some privacy concerns by allowing users to turn off their chat history with the AI chatbot, so conversations cannot be used to train or improve the company’s models. But Dr. Greene noted that the terms of service “still remain pretty nebulous.”

Dr. Solomon is also concerned with researchers using these AI tools in authoring without knowing how they work. “The thing we are really concerned about is that fact that [LLMs] are a bit of a black box – people don’t really understand the methodologies,” he said.
 

A positive tool?

But despite these concerns, many think that these types of AI-assisted tools could have a positive impact on medical publishing, particularly for researchers for whom English is not their first language, noted Catherine Gao, MD, a pulmonary and critical care instructor at Northwestern University, Chicago. She recently led research comparing scientific abstracts written by ChatGPT and real abstracts and discovered that reviewers found it “surprisingly difficult” to differentiate the two.

“The majority of research is published in English,” she said in an email. “Responsible use of LLMs can potentially reduce the burden of writing for busy scientists and improve equity for those who are not native English speakers.”

Dr. Pividori agreed, adding that as a non-native English speaker, he spends much more time working on the structure and grammar of sentences when authoring a manuscript, compared with people who speak English as a first language. He noted that these tools can also be used to automate some of the more monotonous tasks that come along with writing manuscripts and allow researchers to focus on the more creative aspects.

In the future, “I want to focus more on the things that only a human can do and let these tools do all the rest of it,” he said.
 

New rules

But despite how individual researchers feel about LLMs, they agree that these AI tools are here to stay.

“I think that we should anticipate that they will become part of the medical research establishment over time, when we figure out how to use them appropriately,” Dr. Solomon said.

While the debate of how to best use AI in medical publications will continue, journal editors agree that all authors of a manuscript are solely responsible for content in articles that used AI-assisted technology.

“Authors should carefully review and edit the result because AI can generate authoritative-sounding output that can be incorrect, incomplete, or biased,” the ICMJE guidelines state. “Authors should be able to assert that there is no plagiarism in their paper, including in text and images produced by the AI.” This includes appropriate attribution of all cited materials.

The committee also recommends that authors write in both the cover letter and submitted work how AI was used in the manuscript writing process. Recently updated guidelines from the World Association of Medical Editors recommend that all prompts used to generate new text or analytical work should be provided in submitted work. Dr. Greene also noted that if authors used an AI tool to revise their work, they can include a version of the manuscript untouched by LLMs.

It is similar to a preprint, he said, but rather than publishing a version of a paper prior to peer review, someone is showing a version of a manuscript before it was reviewed and revised by AI. “This type of practice could be a path that lets us benefit from these models,” he said, “without having the drawbacks that many are concerned about.”

Dr. Solomon has financial relationships with AbbVie, Amgen, Janssen, CorEvitas, and Moderna. Both Dr. Greene and Dr. Pividori are inventors in the U.S. Provisional Patent Application No. 63/486,706 that the University of Colorado has filed for the “Publishing Infrastructure For AI-Assisted Academic Authoring” invention with the U.S. Patent and Trademark Office. Dr. Greene and Dr. Pividori also received a grant from the Alfred P. Sloan Foundation to improve their AI-based manuscript revision tool. Dr. Gao reported no relevant financial relationships.

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

Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.

However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.

These drugs come with a substantial risk of cognitive problems and fatigue and increase the risk of falls by 87%, the authors reported.

These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.

The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.

The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.

Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.

The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.

The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.

The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
 

Study details

The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.

The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).

Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).

The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).

The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.

Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.

The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.

The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.

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

Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.

However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.

These drugs come with a substantial risk of cognitive problems and fatigue and increase the risk of falls by 87%, the authors reported.

These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.

The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.

The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.

Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.

The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.

The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.

The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
 

Study details

The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.

The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).

Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).

The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).

The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.

Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.

The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.

The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.

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

Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.

However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.

These drugs come with a substantial risk of cognitive problems and fatigue and increase the risk of falls by 87%, the authors reported.

These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.

The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.

The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.

Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.

The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.

The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.

The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
 

Study details

The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.

The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).

Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).

The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).

The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.

Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.

The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.

The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.

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

INDIANAPOLIS – Maintaining a regular healthy sleep schedule may help guard against premature death, new research suggests.

In a diverse group of older adults, those with regular and optimal sleep had about a 40% lower risk of dying of any cause during follow-up compared with peers who had irregular and insufficient sleep.

“If sleep were an 8-hour pill, it would be beneficial to take the full dose at regular times consistently,” lead researcher Joon Chung, PhD, of Harvard Medical School and Brigham and Women’s Hospital, Boston, said in a news release.

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.
 

Broad adverse health effects

“Evidence is mounting that irregular sleep is associated with pretty broad adverse health outcomes, most prominently cardiometabolic disease, obesity, and cardiovascular disease,” Dr. Chungsaid in an interview.

JGI/Tom Grill/Getty Images

In the current study, the researchers estimated the association of regular sleep of optimal sleep duration with all-cause mortality using data from 1,759 adults the Multi-Ethnic Study of Atherosclerosis Sleep Study.

Sleep regularity and duration were classified using 7 days of data gathered by wrist actigraphy. Adults were categorized as “regular-optimal” sleepers (n = 1,015) or “irregular-insufficient” sleepers (n = 744).

During 7 years of follow-up, 176 people died. In the fully adjusted model, the regular-optimal group had a 39% lower mortality risk compared with the irregular-insufficient sleep group (hazard ratio, 0.61;95% confidence interval [CI], 0.45-0.83). The findings were robust in sensitivity analyses.

The regular and optimal duration sleep pattern maps behaviorally to regular bed and wake times, suggesting potential health benefits of adherence to recommended sleep practices, the researchers noted.

“Results suggest benefits of expanding the public conversation on getting ‘a good night’s sleep’ and broadening this goal to getting many good nights of sleep, in a row, on weekdays and weekends,” Dr. Chung said in the release.

He further said that “getting adequate, regular sleep seems to be something that is good for all. I don’t know of anyone who wouldn’t benefit.”

Fariha Abassi-Feinberg, MD, spokesperson for the American Academy of Sleep Medicine and sleep specialist with the Millennium Physician Group, Fort Myers, Fla., agreed.

“We know our bodies have an internal clock, known as the circadian rhythm, which regulates various biological processes, including sleep-wake cycles. Sticking to a consistent sleep schedule allows your body to align its natural rhythm with the external day-night cycle. This synchronization promotes better sleep quality and therefore better health,” said Dr. Abassi-Feinberg, who wasn’t involved in the study.

“The AASM recommends adults try to aim for at least 7 hours of sleep and I often tell my patients that keeping a regular routine is best for your sleep and health,” she said in an interview.

Funding for the study was provided by the American Academy of Sleep Medicine Foundation and the National Institutes of Health. Dr. Chung and Dr. Abassi-Feinberg report no relevant financial relationships.

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

INDIANAPOLIS – Maintaining a regular healthy sleep schedule may help guard against premature death, new research suggests.

In a diverse group of older adults, those with regular and optimal sleep had about a 40% lower risk of dying of any cause during follow-up compared with peers who had irregular and insufficient sleep.

“If sleep were an 8-hour pill, it would be beneficial to take the full dose at regular times consistently,” lead researcher Joon Chung, PhD, of Harvard Medical School and Brigham and Women’s Hospital, Boston, said in a news release.

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.
 

Broad adverse health effects

“Evidence is mounting that irregular sleep is associated with pretty broad adverse health outcomes, most prominently cardiometabolic disease, obesity, and cardiovascular disease,” Dr. Chungsaid in an interview.

JGI/Tom Grill/Getty Images

In the current study, the researchers estimated the association of regular sleep of optimal sleep duration with all-cause mortality using data from 1,759 adults the Multi-Ethnic Study of Atherosclerosis Sleep Study.

Sleep regularity and duration were classified using 7 days of data gathered by wrist actigraphy. Adults were categorized as “regular-optimal” sleepers (n = 1,015) or “irregular-insufficient” sleepers (n = 744).

During 7 years of follow-up, 176 people died. In the fully adjusted model, the regular-optimal group had a 39% lower mortality risk compared with the irregular-insufficient sleep group (hazard ratio, 0.61;95% confidence interval [CI], 0.45-0.83). The findings were robust in sensitivity analyses.

The regular and optimal duration sleep pattern maps behaviorally to regular bed and wake times, suggesting potential health benefits of adherence to recommended sleep practices, the researchers noted.

“Results suggest benefits of expanding the public conversation on getting ‘a good night’s sleep’ and broadening this goal to getting many good nights of sleep, in a row, on weekdays and weekends,” Dr. Chung said in the release.

He further said that “getting adequate, regular sleep seems to be something that is good for all. I don’t know of anyone who wouldn’t benefit.”

Fariha Abassi-Feinberg, MD, spokesperson for the American Academy of Sleep Medicine and sleep specialist with the Millennium Physician Group, Fort Myers, Fla., agreed.

“We know our bodies have an internal clock, known as the circadian rhythm, which regulates various biological processes, including sleep-wake cycles. Sticking to a consistent sleep schedule allows your body to align its natural rhythm with the external day-night cycle. This synchronization promotes better sleep quality and therefore better health,” said Dr. Abassi-Feinberg, who wasn’t involved in the study.

“The AASM recommends adults try to aim for at least 7 hours of sleep and I often tell my patients that keeping a regular routine is best for your sleep and health,” she said in an interview.

Funding for the study was provided by the American Academy of Sleep Medicine Foundation and the National Institutes of Health. Dr. Chung and Dr. Abassi-Feinberg report no relevant financial relationships.

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

INDIANAPOLIS – Maintaining a regular healthy sleep schedule may help guard against premature death, new research suggests.

In a diverse group of older adults, those with regular and optimal sleep had about a 40% lower risk of dying of any cause during follow-up compared with peers who had irregular and insufficient sleep.

“If sleep were an 8-hour pill, it would be beneficial to take the full dose at regular times consistently,” lead researcher Joon Chung, PhD, of Harvard Medical School and Brigham and Women’s Hospital, Boston, said in a news release.

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.
 

Broad adverse health effects

“Evidence is mounting that irregular sleep is associated with pretty broad adverse health outcomes, most prominently cardiometabolic disease, obesity, and cardiovascular disease,” Dr. Chungsaid in an interview.

JGI/Tom Grill/Getty Images

In the current study, the researchers estimated the association of regular sleep of optimal sleep duration with all-cause mortality using data from 1,759 adults the Multi-Ethnic Study of Atherosclerosis Sleep Study.

Sleep regularity and duration were classified using 7 days of data gathered by wrist actigraphy. Adults were categorized as “regular-optimal” sleepers (n = 1,015) or “irregular-insufficient” sleepers (n = 744).

During 7 years of follow-up, 176 people died. In the fully adjusted model, the regular-optimal group had a 39% lower mortality risk compared with the irregular-insufficient sleep group (hazard ratio, 0.61;95% confidence interval [CI], 0.45-0.83). The findings were robust in sensitivity analyses.

The regular and optimal duration sleep pattern maps behaviorally to regular bed and wake times, suggesting potential health benefits of adherence to recommended sleep practices, the researchers noted.

“Results suggest benefits of expanding the public conversation on getting ‘a good night’s sleep’ and broadening this goal to getting many good nights of sleep, in a row, on weekdays and weekends,” Dr. Chung said in the release.

He further said that “getting adequate, regular sleep seems to be something that is good for all. I don’t know of anyone who wouldn’t benefit.”

Fariha Abassi-Feinberg, MD, spokesperson for the American Academy of Sleep Medicine and sleep specialist with the Millennium Physician Group, Fort Myers, Fla., agreed.

“We know our bodies have an internal clock, known as the circadian rhythm, which regulates various biological processes, including sleep-wake cycles. Sticking to a consistent sleep schedule allows your body to align its natural rhythm with the external day-night cycle. This synchronization promotes better sleep quality and therefore better health,” said Dr. Abassi-Feinberg, who wasn’t involved in the study.

“The AASM recommends adults try to aim for at least 7 hours of sleep and I often tell my patients that keeping a regular routine is best for your sleep and health,” she said in an interview.

Funding for the study was provided by the American Academy of Sleep Medicine Foundation and the National Institutes of Health. Dr. Chung and Dr. Abassi-Feinberg report no relevant financial relationships.

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

Muscle adiposity may be a novel risk factor for cognitive decline in older adults, new research suggests.

Investigators assessed muscle fat in more than 1,600 adults in their 70s and evaluated their cognitive function over a 10-year period. They found that increases in muscle adiposity from year 1 to year 6 were associated with greater cognitive decline over time, independent of total weight, other fat deposits, muscle characteristics, and traditional dementia risk factors.

The findings were similar between Black and White people and between men and women.

“Increasing adiposity – or fat deposition – in skeletal muscles predicted faster cognitive decline, irrespective of demographics or other disease, and this effect was distinct from that of other types of fat or other muscle characteristics, such as strength or mass,” study investigator Caterina Rosano MD, MPH, professor of epidemiology at the University of Pittsburgh, said in an interview.

The study was published in the Journal of the American Geriatrics Society.
 

Biologically plausible

“There has been a growing recognition that overall adiposity and muscle measures, such as strength and mass, are individual indicators of future dementia risk and both strengthen the algorithms to predict cognitive decline,” said Dr. Rosano, associate director for clinical translation at the University of Pittsburgh’s Aging Institute. “However, adiposity in the muscle has not been examined.”

Some evidence supports a “biologically plausible link” between muscle adiposity and dementia risk. For example, muscle adiposity increases the risk for type 2 diabetes and hypertension, both of which are dementia risk factors.

Skeletal muscle adiposity increases with older age, even in older adults who lose weight, and is “highly prevalent” among older adults of African ancestry.

The researchers examined a large, biracial sample of older adults participating in the Health, Aging and Body Composition study, which enrolled men and women aged between 70 and 79 years. Participants were followed for an average of 9.0 ± 1.8 years.

During years 1 and 6, participants’ body composition was analyzed, including intermuscular adipose tissue (IMAT), visceral and subcutaneous adiposity, total fat mass, and muscle area.

In years 1, 3, 5, 8, and 10, participants’ cognition was measured using the modified Mini-Mental State (3MS) exam.

The main independent variable was 5-year change in thigh IMAT (year 6 minus year 1), and the main dependent variable was 3MS decline (from year 5 to year 10).

The researchers adjusted all the models for traditional dementia risk factors at baseline including 3MS, education, apo E4 allele, diabetes, hypertension, and physical activity and also calculated interactions between IMAT change by race or sex.

These models also accounted for change in muscle strength, muscle area, body weight, abdominal subcutaneous and visceral adiposity, and total body fat mass as well as cytokines related to adiposity.
 

‘Rich and engaging crosstalk’

The final sample included 1634 participants (mean age, 73.38 years at baseline; 48% female; 35% Black; mean baseline 3MS score, 91.6).

Thigh IMAT increased by 39.0% in all participants from year 1 to year 6, which corresponded to an increase of 4.85 cm² or 0.97 cm²/year. During the same time period, muscle strength decreased by 14.0% (P < .05), although thigh muscle area remained stable, decreasing less than 0.5%.

There were decreases in both abdominal subcutaneous and visceral adiposity of 3.92% and 6.43%, respectively (P < .05). There was a decrease of 3.3% in 3MS from year 5 to year 10.

Several variables were associated with 3MS decline, independent of any change in thigh IMAT: older age, less education, and having at least one copy of the APOe4 allele. These variables were included in the model of IMAT change predicting 3MS change.

A statistically significant association of IMAT increase with 3MS decline was found. The IMAT increase of 4.85 cm² corresponded to a 3MS decline of an additional 3.6 points (P < .0001) from year 5 to year 10, “indicating a clinically important change.”

The association between increasing thigh IMAT with declining 3MS “remained statistically significant” after adjusting for race, age, education, and apo E4 (P < .0001) and was independent of changes in thigh muscle area, muscle strength, and other adiposity measures.

In participants with increased IMAT in years 1-6, the mean 3MS score fell to approximately 87 points at year 10, compared with those without increased IMAT, with a 3MS score that dropped to approximately 89 points.

Interactions by race and sex were not statistically significant (P > .08).

“Our results suggest that adiposity in muscles can predict cognitive decline, in addition to (not instead of) other traditional dementia risk factors,” said Dr. Rosano.

There is “a rich and engaging crosstalk between muscle, adipose tissue, and the brain all throughout our lives, happening through factors released in the bloodstream that can reach the brain, however, the specific identity of the factors responsible for the crosstalk of muscle adiposity and brain in older adults has not yet been discovered,” she noted.

Although muscle adiposity is “not yet routinely measured in clinical settings, it is being measured opportunistically on clinical CT scans obtained as part of routine patient care,” she added. “These CT measurements have already been validated in many studies of older adults; thus, clinicians could have access to this novel information without additional cost, time, or radiation exposure.”
 

Causality not proven

In a comment, Bruce Albala, PhD, professor, department of environmental and occupational health, University of California, Irvine, noted that the 3MS assessment is scored on a 100-point scale, with a score less than 78 “generally regarded as indicating cognitive impairment or approaching a dementia condition.” In the current study, the mean 3MS score of participants with increased IMAT was still “well above the dementia cut-off.”

Moreover, “even if there is a relationship or correlation between IMAT and cognition, this does not prove or even suggest causality, especially from a biological mechanistic approach,” said Dr. Albaba, an adjunct professor of neurology, who was not involved in the study. “Clearly, more research is needed even to understand the relationship between these two factors.”

The study was supported by the National Institute on Aging. Dr. Rosano and coauthors and Dr. Albala declared no relevant financial relationships.

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

Muscle adiposity may be a novel risk factor for cognitive decline in older adults, new research suggests.

Investigators assessed muscle fat in more than 1,600 adults in their 70s and evaluated their cognitive function over a 10-year period. They found that increases in muscle adiposity from year 1 to year 6 were associated with greater cognitive decline over time, independent of total weight, other fat deposits, muscle characteristics, and traditional dementia risk factors.

The findings were similar between Black and White people and between men and women.

“Increasing adiposity – or fat deposition – in skeletal muscles predicted faster cognitive decline, irrespective of demographics or other disease, and this effect was distinct from that of other types of fat or other muscle characteristics, such as strength or mass,” study investigator Caterina Rosano MD, MPH, professor of epidemiology at the University of Pittsburgh, said in an interview.

The study was published in the Journal of the American Geriatrics Society.
 

Biologically plausible

“There has been a growing recognition that overall adiposity and muscle measures, such as strength and mass, are individual indicators of future dementia risk and both strengthen the algorithms to predict cognitive decline,” said Dr. Rosano, associate director for clinical translation at the University of Pittsburgh’s Aging Institute. “However, adiposity in the muscle has not been examined.”

Some evidence supports a “biologically plausible link” between muscle adiposity and dementia risk. For example, muscle adiposity increases the risk for type 2 diabetes and hypertension, both of which are dementia risk factors.

Skeletal muscle adiposity increases with older age, even in older adults who lose weight, and is “highly prevalent” among older adults of African ancestry.

The researchers examined a large, biracial sample of older adults participating in the Health, Aging and Body Composition study, which enrolled men and women aged between 70 and 79 years. Participants were followed for an average of 9.0 ± 1.8 years.

During years 1 and 6, participants’ body composition was analyzed, including intermuscular adipose tissue (IMAT), visceral and subcutaneous adiposity, total fat mass, and muscle area.

In years 1, 3, 5, 8, and 10, participants’ cognition was measured using the modified Mini-Mental State (3MS) exam.

The main independent variable was 5-year change in thigh IMAT (year 6 minus year 1), and the main dependent variable was 3MS decline (from year 5 to year 10).

The researchers adjusted all the models for traditional dementia risk factors at baseline including 3MS, education, apo E4 allele, diabetes, hypertension, and physical activity and also calculated interactions between IMAT change by race or sex.

These models also accounted for change in muscle strength, muscle area, body weight, abdominal subcutaneous and visceral adiposity, and total body fat mass as well as cytokines related to adiposity.
 

‘Rich and engaging crosstalk’

The final sample included 1634 participants (mean age, 73.38 years at baseline; 48% female; 35% Black; mean baseline 3MS score, 91.6).

Thigh IMAT increased by 39.0% in all participants from year 1 to year 6, which corresponded to an increase of 4.85 cm² or 0.97 cm²/year. During the same time period, muscle strength decreased by 14.0% (P < .05), although thigh muscle area remained stable, decreasing less than 0.5%.

There were decreases in both abdominal subcutaneous and visceral adiposity of 3.92% and 6.43%, respectively (P < .05). There was a decrease of 3.3% in 3MS from year 5 to year 10.

Several variables were associated with 3MS decline, independent of any change in thigh IMAT: older age, less education, and having at least one copy of the APOe4 allele. These variables were included in the model of IMAT change predicting 3MS change.

A statistically significant association of IMAT increase with 3MS decline was found. The IMAT increase of 4.85 cm² corresponded to a 3MS decline of an additional 3.6 points (P < .0001) from year 5 to year 10, “indicating a clinically important change.”

The association between increasing thigh IMAT with declining 3MS “remained statistically significant” after adjusting for race, age, education, and apo E4 (P < .0001) and was independent of changes in thigh muscle area, muscle strength, and other adiposity measures.

In participants with increased IMAT in years 1-6, the mean 3MS score fell to approximately 87 points at year 10, compared with those without increased IMAT, with a 3MS score that dropped to approximately 89 points.

Interactions by race and sex were not statistically significant (P > .08).

“Our results suggest that adiposity in muscles can predict cognitive decline, in addition to (not instead of) other traditional dementia risk factors,” said Dr. Rosano.

There is “a rich and engaging crosstalk between muscle, adipose tissue, and the brain all throughout our lives, happening through factors released in the bloodstream that can reach the brain, however, the specific identity of the factors responsible for the crosstalk of muscle adiposity and brain in older adults has not yet been discovered,” she noted.

Although muscle adiposity is “not yet routinely measured in clinical settings, it is being measured opportunistically on clinical CT scans obtained as part of routine patient care,” she added. “These CT measurements have already been validated in many studies of older adults; thus, clinicians could have access to this novel information without additional cost, time, or radiation exposure.”
 

Causality not proven

In a comment, Bruce Albala, PhD, professor, department of environmental and occupational health, University of California, Irvine, noted that the 3MS assessment is scored on a 100-point scale, with a score less than 78 “generally regarded as indicating cognitive impairment or approaching a dementia condition.” In the current study, the mean 3MS score of participants with increased IMAT was still “well above the dementia cut-off.”

Moreover, “even if there is a relationship or correlation between IMAT and cognition, this does not prove or even suggest causality, especially from a biological mechanistic approach,” said Dr. Albaba, an adjunct professor of neurology, who was not involved in the study. “Clearly, more research is needed even to understand the relationship between these two factors.”

The study was supported by the National Institute on Aging. Dr. Rosano and coauthors and Dr. Albala declared no relevant financial relationships.

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

Muscle adiposity may be a novel risk factor for cognitive decline in older adults, new research suggests.

Investigators assessed muscle fat in more than 1,600 adults in their 70s and evaluated their cognitive function over a 10-year period. They found that increases in muscle adiposity from year 1 to year 6 were associated with greater cognitive decline over time, independent of total weight, other fat deposits, muscle characteristics, and traditional dementia risk factors.

The findings were similar between Black and White people and between men and women.

“Increasing adiposity – or fat deposition – in skeletal muscles predicted faster cognitive decline, irrespective of demographics or other disease, and this effect was distinct from that of other types of fat or other muscle characteristics, such as strength or mass,” study investigator Caterina Rosano MD, MPH, professor of epidemiology at the University of Pittsburgh, said in an interview.

The study was published in the Journal of the American Geriatrics Society.
 

Biologically plausible

“There has been a growing recognition that overall adiposity and muscle measures, such as strength and mass, are individual indicators of future dementia risk and both strengthen the algorithms to predict cognitive decline,” said Dr. Rosano, associate director for clinical translation at the University of Pittsburgh’s Aging Institute. “However, adiposity in the muscle has not been examined.”

Some evidence supports a “biologically plausible link” between muscle adiposity and dementia risk. For example, muscle adiposity increases the risk for type 2 diabetes and hypertension, both of which are dementia risk factors.

Skeletal muscle adiposity increases with older age, even in older adults who lose weight, and is “highly prevalent” among older adults of African ancestry.

The researchers examined a large, biracial sample of older adults participating in the Health, Aging and Body Composition study, which enrolled men and women aged between 70 and 79 years. Participants were followed for an average of 9.0 ± 1.8 years.

During years 1 and 6, participants’ body composition was analyzed, including intermuscular adipose tissue (IMAT), visceral and subcutaneous adiposity, total fat mass, and muscle area.

In years 1, 3, 5, 8, and 10, participants’ cognition was measured using the modified Mini-Mental State (3MS) exam.

The main independent variable was 5-year change in thigh IMAT (year 6 minus year 1), and the main dependent variable was 3MS decline (from year 5 to year 10).

The researchers adjusted all the models for traditional dementia risk factors at baseline including 3MS, education, apo E4 allele, diabetes, hypertension, and physical activity and also calculated interactions between IMAT change by race or sex.

These models also accounted for change in muscle strength, muscle area, body weight, abdominal subcutaneous and visceral adiposity, and total body fat mass as well as cytokines related to adiposity.
 

‘Rich and engaging crosstalk’

The final sample included 1634 participants (mean age, 73.38 years at baseline; 48% female; 35% Black; mean baseline 3MS score, 91.6).

Thigh IMAT increased by 39.0% in all participants from year 1 to year 6, which corresponded to an increase of 4.85 cm² or 0.97 cm²/year. During the same time period, muscle strength decreased by 14.0% (P < .05), although thigh muscle area remained stable, decreasing less than 0.5%.

There were decreases in both abdominal subcutaneous and visceral adiposity of 3.92% and 6.43%, respectively (P < .05). There was a decrease of 3.3% in 3MS from year 5 to year 10.

Several variables were associated with 3MS decline, independent of any change in thigh IMAT: older age, less education, and having at least one copy of the APOe4 allele. These variables were included in the model of IMAT change predicting 3MS change.

A statistically significant association of IMAT increase with 3MS decline was found. The IMAT increase of 4.85 cm² corresponded to a 3MS decline of an additional 3.6 points (P < .0001) from year 5 to year 10, “indicating a clinically important change.”

The association between increasing thigh IMAT with declining 3MS “remained statistically significant” after adjusting for race, age, education, and apo E4 (P < .0001) and was independent of changes in thigh muscle area, muscle strength, and other adiposity measures.

In participants with increased IMAT in years 1-6, the mean 3MS score fell to approximately 87 points at year 10, compared with those without increased IMAT, with a 3MS score that dropped to approximately 89 points.

Interactions by race and sex were not statistically significant (P > .08).

“Our results suggest that adiposity in muscles can predict cognitive decline, in addition to (not instead of) other traditional dementia risk factors,” said Dr. Rosano.

There is “a rich and engaging crosstalk between muscle, adipose tissue, and the brain all throughout our lives, happening through factors released in the bloodstream that can reach the brain, however, the specific identity of the factors responsible for the crosstalk of muscle adiposity and brain in older adults has not yet been discovered,” she noted.

Although muscle adiposity is “not yet routinely measured in clinical settings, it is being measured opportunistically on clinical CT scans obtained as part of routine patient care,” she added. “These CT measurements have already been validated in many studies of older adults; thus, clinicians could have access to this novel information without additional cost, time, or radiation exposure.”
 

Causality not proven

In a comment, Bruce Albala, PhD, professor, department of environmental and occupational health, University of California, Irvine, noted that the 3MS assessment is scored on a 100-point scale, with a score less than 78 “generally regarded as indicating cognitive impairment or approaching a dementia condition.” In the current study, the mean 3MS score of participants with increased IMAT was still “well above the dementia cut-off.”

Moreover, “even if there is a relationship or correlation between IMAT and cognition, this does not prove or even suggest causality, especially from a biological mechanistic approach,” said Dr. Albaba, an adjunct professor of neurology, who was not involved in the study. “Clearly, more research is needed even to understand the relationship between these two factors.”

The study was supported by the National Institute on Aging. Dr. Rosano and coauthors and Dr. Albala declared no relevant financial relationships.

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

CHICAGO – Research regarding some of the most challenging cases of macular dermal hyperpigmentation is sparse, but at the Pigmentary Disorders Exchange Symposium, an expert shared treatment tips based on cases she has treated in her practice.

Heather Woolery-Lloyd, MD, director of the skin of color division in the dermatology department at University of Miami, provided three general pointers.

• When in doubt, biopsy.
• For inflammatory disorders, always treat the inflammation in addition to the hyperpigmentation.
• Avoid long-term hydroquinone use in these patients.

Dr. Woolery-Lloyd also reviewed examples of what she has found successful in treating her patients with these conditions.
 

Lichen planus pigmentosus (LPP)

“It’s one of the hardest things that we treat,” said Dr. Woolery-Lloyd, who often sees cases of LPP in patients in their 30s, 40s, and 50s.

MedscapeLive!

Lesions first appear as small, ill-defined oval-to-round macules, which later become confluent and form large areas of pigmentation. In different patients, the pigment on the face and neck, and sometimes on the forearms can be slate gray or brownish black.

In 2013, dermatologist N.C. Dlova, MD, at the University of KwaZulu‐Natal, Durban, South Africa, reported a link between frontal fibrosing alopecia and LPP in the British Journal of Dermatology. “I definitely see this connection in my practice,” said Dr. Woolery-Lloyd, noting that “both conditions often result in the loss of both eyebrows.”

She recommends always using a topical anti-inflammatory that is safe for the face. One combination she uses is azelaic acid 20% plus hydrocortisone 2.5%.

“We do use a lot of azelaic acid in my practice because it’s affordable,” she said, at the meeting, provided by MedscapeLive! She added that the hardest area to treat in women is around the chin.

Two other conditions, ashy dermatosis and erythema dyschromicum perstans (EDP), are similar. Ashy dermatosis mimics LPP but occurs more prominently on the trunk and extremities. EDP often has a preceding ring of erythema.

Dr. Woolery-Lloyd said the term EDP is often used to cover both EDP and ashy dermatosis in North America because “ashy” can have a negative connotation.

She noted there is no consensus on effective therapy for LPP, ashy dermatosis, or EDP.

A review of the literature on EDP, which included 16 studies on treatment outcomes, found the following:

• Narrow-band ultraviolet B and tacrolimus were effective treatments with minimal side effects.
• Clofazimine was effective, but had side effects, which, ironically, included pigmentary changes.
• Griseofulvin, isotretinoin, and dapsone were comparatively ineffective as lesions recurred after discontinuation.
• Lasers were largely ineffective and can also result in postinflammatory hyperpigmentation and fibrosis.

Ochronosis

Dr. Woolery-Lloyd said she may see one to two patients a year with ochronosis, which is characterized by paradoxical darkening of the skin with long-term hydroquinone use. It usually starts with redness followed by blue-black patches on the face where hydroquinone is applied. In severe cases, blue-black papules and nodules can occur.

“When I give a patient hydroquinone, I always say: ‘I don’t want to see any redness,’” Dr. Woolery-Lloyd said. “If you have any redness, please stop because ochronosis is typically preceded by this redness.”

But, she noted, “people will come in actively using hydroquinone, will have the dark brown or deep black papules or macules on their face, and then this background of redness because they are so inflamed.”

She said that ochronosis can occur in any skin type, not just in patients with darker skin tones. Dr. Woolery-Lloyd advised: “Do not hesitate to biopsy the face if ochronosis is suspected. I always biopsy ochronosis.”

There are two reasons for doing so, she explained. It can help with the diagnosis but it will also provide the patient with an incentive to stop using hydroquinone. “People who are using hydroquinone are addicted to it. They love it. They don’t want to stop. They keep using it despite the fact that their face is getting darker.” When they see a biopsy report, they may be convinced to stop.

Dr. Woolery-Lloyd said she does a 2-mm punch biopsy in the crow’s feet area because there’s almost always ochronosis in that area and it does not leave an obvious scar.

Eventually, she said, if the person stops using hydroquinone, it will clear up, “but it will take years.” Again, here she has had success with her “special formula” of azelaic acid 20% plus hydrocortisone 2.5%

“Don’t tell patients there’s no treatment. That’s the take-home,” she said.
 

Drug-induced facial hyperpigmentation

“I see this all the time in my African American patients,” Dr. Woolery-Lloyd said. The condition usually is characterized by dark brown hyperpigmentation on the face.

In this situation, the first question to ask is whether the patient is taking medication for hypertension, and the second question is whether it is “HCTZ.” It’s important to use the abbreviation for hydrochlorothiazide – the most common cause of drug-induced facial hyperpigmentation – because that’s what a patient sees on the bottle.

If they are taking HCTZ or another blood pressure medication associated with photosensitivity, they need to switch to a nonphotosensitizing antihypertensive agent (there are several options) and they should start treatment with a topical anti-inflammatory, Dr. Woolery-Lloyd said. Then, she suggests introducing hydrocortisone 2.5% cream and a hydroquinone-free skin brightener (azelaic acid, for example).

Importantly, with any of these conditions, Dr Woolery-Lloyd said, dermatologists should talk with patients about realistic expectations. “It takes a long time for dermal pigment to clear,” she emphasized.

Dr. Woolery-Lloyd has been a speaker for Ortho Dermatologics, L’Oreal, and EPI; has done research for Pfizer, Galderma, Allergan, Arcutis, Vyne, Merz, and Eirion; and has been on advisory boards for L’Oreal, Allergan, Ortho Dermatologics, Pfizer, and Merz.

CHICAGO – Research regarding some of the most challenging cases of macular dermal hyperpigmentation is sparse, but at the Pigmentary Disorders Exchange Symposium, an expert shared treatment tips based on cases she has treated in her practice.

Heather Woolery-Lloyd, MD, director of the skin of color division in the dermatology department at University of Miami, provided three general pointers.

• When in doubt, biopsy.
• For inflammatory disorders, always treat the inflammation in addition to the hyperpigmentation.
• Avoid long-term hydroquinone use in these patients.

Dr. Woolery-Lloyd also reviewed examples of what she has found successful in treating her patients with these conditions.
 

Lichen planus pigmentosus (LPP)

“It’s one of the hardest things that we treat,” said Dr. Woolery-Lloyd, who often sees cases of LPP in patients in their 30s, 40s, and 50s.

MedscapeLive!

Lesions first appear as small, ill-defined oval-to-round macules, which later become confluent and form large areas of pigmentation. In different patients, the pigment on the face and neck, and sometimes on the forearms can be slate gray or brownish black.

In 2013, dermatologist N.C. Dlova, MD, at the University of KwaZulu‐Natal, Durban, South Africa, reported a link between frontal fibrosing alopecia and LPP in the British Journal of Dermatology. “I definitely see this connection in my practice,” said Dr. Woolery-Lloyd, noting that “both conditions often result in the loss of both eyebrows.”

She recommends always using a topical anti-inflammatory that is safe for the face. One combination she uses is azelaic acid 20% plus hydrocortisone 2.5%.

“We do use a lot of azelaic acid in my practice because it’s affordable,” she said, at the meeting, provided by MedscapeLive! She added that the hardest area to treat in women is around the chin.

Two other conditions, ashy dermatosis and erythema dyschromicum perstans (EDP), are similar. Ashy dermatosis mimics LPP but occurs more prominently on the trunk and extremities. EDP often has a preceding ring of erythema.

Dr. Woolery-Lloyd said the term EDP is often used to cover both EDP and ashy dermatosis in North America because “ashy” can have a negative connotation.

She noted there is no consensus on effective therapy for LPP, ashy dermatosis, or EDP.

A review of the literature on EDP, which included 16 studies on treatment outcomes, found the following:

• Narrow-band ultraviolet B and tacrolimus were effective treatments with minimal side effects.
• Clofazimine was effective, but had side effects, which, ironically, included pigmentary changes.
• Griseofulvin, isotretinoin, and dapsone were comparatively ineffective as lesions recurred after discontinuation.
• Lasers were largely ineffective and can also result in postinflammatory hyperpigmentation and fibrosis.

Ochronosis

Dr. Woolery-Lloyd said she may see one to two patients a year with ochronosis, which is characterized by paradoxical darkening of the skin with long-term hydroquinone use. It usually starts with redness followed by blue-black patches on the face where hydroquinone is applied. In severe cases, blue-black papules and nodules can occur.

“When I give a patient hydroquinone, I always say: ‘I don’t want to see any redness,’” Dr. Woolery-Lloyd said. “If you have any redness, please stop because ochronosis is typically preceded by this redness.”

But, she noted, “people will come in actively using hydroquinone, will have the dark brown or deep black papules or macules on their face, and then this background of redness because they are so inflamed.”

She said that ochronosis can occur in any skin type, not just in patients with darker skin tones. Dr. Woolery-Lloyd advised: “Do not hesitate to biopsy the face if ochronosis is suspected. I always biopsy ochronosis.”

There are two reasons for doing so, she explained. It can help with the diagnosis but it will also provide the patient with an incentive to stop using hydroquinone. “People who are using hydroquinone are addicted to it. They love it. They don’t want to stop. They keep using it despite the fact that their face is getting darker.” When they see a biopsy report, they may be convinced to stop.

Dr. Woolery-Lloyd said she does a 2-mm punch biopsy in the crow’s feet area because there’s almost always ochronosis in that area and it does not leave an obvious scar.

Eventually, she said, if the person stops using hydroquinone, it will clear up, “but it will take years.” Again, here she has had success with her “special formula” of azelaic acid 20% plus hydrocortisone 2.5%

“Don’t tell patients there’s no treatment. That’s the take-home,” she said.
 

Drug-induced facial hyperpigmentation

“I see this all the time in my African American patients,” Dr. Woolery-Lloyd said. The condition usually is characterized by dark brown hyperpigmentation on the face.

In this situation, the first question to ask is whether the patient is taking medication for hypertension, and the second question is whether it is “HCTZ.” It’s important to use the abbreviation for hydrochlorothiazide – the most common cause of drug-induced facial hyperpigmentation – because that’s what a patient sees on the bottle.

If they are taking HCTZ or another blood pressure medication associated with photosensitivity, they need to switch to a nonphotosensitizing antihypertensive agent (there are several options) and they should start treatment with a topical anti-inflammatory, Dr. Woolery-Lloyd said. Then, she suggests introducing hydrocortisone 2.5% cream and a hydroquinone-free skin brightener (azelaic acid, for example).

Importantly, with any of these conditions, Dr Woolery-Lloyd said, dermatologists should talk with patients about realistic expectations. “It takes a long time for dermal pigment to clear,” she emphasized.

Dr. Woolery-Lloyd has been a speaker for Ortho Dermatologics, L’Oreal, and EPI; has done research for Pfizer, Galderma, Allergan, Arcutis, Vyne, Merz, and Eirion; and has been on advisory boards for L’Oreal, Allergan, Ortho Dermatologics, Pfizer, and Merz.

CHICAGO – Research regarding some of the most challenging cases of macular dermal hyperpigmentation is sparse, but at the Pigmentary Disorders Exchange Symposium, an expert shared treatment tips based on cases she has treated in her practice.

Heather Woolery-Lloyd, MD, director of the skin of color division in the dermatology department at University of Miami, provided three general pointers.

• When in doubt, biopsy.
• For inflammatory disorders, always treat the inflammation in addition to the hyperpigmentation.
• Avoid long-term hydroquinone use in these patients.

Dr. Woolery-Lloyd also reviewed examples of what she has found successful in treating her patients with these conditions.
 

Lichen planus pigmentosus (LPP)

“It’s one of the hardest things that we treat,” said Dr. Woolery-Lloyd, who often sees cases of LPP in patients in their 30s, 40s, and 50s.

MedscapeLive!

Lesions first appear as small, ill-defined oval-to-round macules, which later become confluent and form large areas of pigmentation. In different patients, the pigment on the face and neck, and sometimes on the forearms can be slate gray or brownish black.

In 2013, dermatologist N.C. Dlova, MD, at the University of KwaZulu‐Natal, Durban, South Africa, reported a link between frontal fibrosing alopecia and LPP in the British Journal of Dermatology. “I definitely see this connection in my practice,” said Dr. Woolery-Lloyd, noting that “both conditions often result in the loss of both eyebrows.”

She recommends always using a topical anti-inflammatory that is safe for the face. One combination she uses is azelaic acid 20% plus hydrocortisone 2.5%.

“We do use a lot of azelaic acid in my practice because it’s affordable,” she said, at the meeting, provided by MedscapeLive! She added that the hardest area to treat in women is around the chin.

Two other conditions, ashy dermatosis and erythema dyschromicum perstans (EDP), are similar. Ashy dermatosis mimics LPP but occurs more prominently on the trunk and extremities. EDP often has a preceding ring of erythema.

Dr. Woolery-Lloyd said the term EDP is often used to cover both EDP and ashy dermatosis in North America because “ashy” can have a negative connotation.

She noted there is no consensus on effective therapy for LPP, ashy dermatosis, or EDP.

A review of the literature on EDP, which included 16 studies on treatment outcomes, found the following:

• Narrow-band ultraviolet B and tacrolimus were effective treatments with minimal side effects.
• Clofazimine was effective, but had side effects, which, ironically, included pigmentary changes.
• Griseofulvin, isotretinoin, and dapsone were comparatively ineffective as lesions recurred after discontinuation.
• Lasers were largely ineffective and can also result in postinflammatory hyperpigmentation and fibrosis.

Ochronosis

Dr. Woolery-Lloyd said she may see one to two patients a year with ochronosis, which is characterized by paradoxical darkening of the skin with long-term hydroquinone use. It usually starts with redness followed by blue-black patches on the face where hydroquinone is applied. In severe cases, blue-black papules and nodules can occur.

“When I give a patient hydroquinone, I always say: ‘I don’t want to see any redness,’” Dr. Woolery-Lloyd said. “If you have any redness, please stop because ochronosis is typically preceded by this redness.”

But, she noted, “people will come in actively using hydroquinone, will have the dark brown or deep black papules or macules on their face, and then this background of redness because they are so inflamed.”

She said that ochronosis can occur in any skin type, not just in patients with darker skin tones. Dr. Woolery-Lloyd advised: “Do not hesitate to biopsy the face if ochronosis is suspected. I always biopsy ochronosis.”

There are two reasons for doing so, she explained. It can help with the diagnosis but it will also provide the patient with an incentive to stop using hydroquinone. “People who are using hydroquinone are addicted to it. They love it. They don’t want to stop. They keep using it despite the fact that their face is getting darker.” When they see a biopsy report, they may be convinced to stop.

Dr. Woolery-Lloyd said she does a 2-mm punch biopsy in the crow’s feet area because there’s almost always ochronosis in that area and it does not leave an obvious scar.

Eventually, she said, if the person stops using hydroquinone, it will clear up, “but it will take years.” Again, here she has had success with her “special formula” of azelaic acid 20% plus hydrocortisone 2.5%

“Don’t tell patients there’s no treatment. That’s the take-home,” she said.
 

Drug-induced facial hyperpigmentation

“I see this all the time in my African American patients,” Dr. Woolery-Lloyd said. The condition usually is characterized by dark brown hyperpigmentation on the face.

In this situation, the first question to ask is whether the patient is taking medication for hypertension, and the second question is whether it is “HCTZ.” It’s important to use the abbreviation for hydrochlorothiazide – the most common cause of drug-induced facial hyperpigmentation – because that’s what a patient sees on the bottle.

If they are taking HCTZ or another blood pressure medication associated with photosensitivity, they need to switch to a nonphotosensitizing antihypertensive agent (there are several options) and they should start treatment with a topical anti-inflammatory, Dr. Woolery-Lloyd said. Then, she suggests introducing hydrocortisone 2.5% cream and a hydroquinone-free skin brightener (azelaic acid, for example).

Importantly, with any of these conditions, Dr Woolery-Lloyd said, dermatologists should talk with patients about realistic expectations. “It takes a long time for dermal pigment to clear,” she emphasized.

Dr. Woolery-Lloyd has been a speaker for Ortho Dermatologics, L’Oreal, and EPI; has done research for Pfizer, Galderma, Allergan, Arcutis, Vyne, Merz, and Eirion; and has been on advisory boards for L’Oreal, Allergan, Ortho Dermatologics, Pfizer, and Merz.

DENVER – Patients with multiple sclerosis (MS) are significantly more likely to develop herpes zoster infections than immunocompetent individuals, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. “Herpes zoster and its complications are associated with increased health care cost and decreased quality of life,” lead author Nikita Stempniewicz, MSc, director of U.S. Health Outcomes & Epidemiology at GSK Vaccines, Alexandria, Va., reported.

“The take-home finding is that herpes zoster incidence is high among people with MS overall,” Mr. Stempniewicz said in an interview. “We also found that herpes zoster incidence is numerically higher among MS patients with higher levels of baseline immunosuppression, so another conclusion is that herpes zoster prevention may be warranted among this population given the high level of immunosuppression and the high risk of developing herpes zoster infection.” GSK manufactures Shingrix, the only currently approved and recommended herpes zoster vaccine available in the United States

Lawrence Steinman, MD, a professor of neurology and neurological sciences, pediatrics, and genetics at Stanford (Calif.) Medicine, was not involved in the research but said in an interview that the findings “raise the issue of whether not enough individuals with MS are getting Shingrix, and also whether there is a need for rapid intervention with an antiviral, for those individuals who develop shingles.”
 

Real-world data

For the study, researchers analyzed U.S. administrative claims data from the Optum Research Database between October 2015 and March 2022 to compare shingles infections between adults with MS (and no other immunocompromising conditions) and a random sample of one million people without any immunocompromising conditions. The study excluded anyone who had been vaccinated against herpes zoster or diagnosed with it in the year before October 2015.

Among the 42,185 adults with MS included in the cohort, just over half (53%) were commercially insured, and 47% had Medicare Advantage. Their average age was 53, and 75% were female. Just over half the cohort (55%) had no immunosuppression because of medications while 35% had low immunosuppression from MS therapy and 10% had high immunosuppression from therapy. High suppression meant patients were taking fingolimod, siponimod, ozanimod, ponesimod, cladribine, or a monoclonal antibody except natalizumab. Those with low suppression were taking natalizumab, fumarates, IVIG, glatiramer acetate, interferon beta or a related drug, teriflunomide, azathioprine, methotrexate, or mycophenolate mofetil.

The rate of shingles infections in the MS patient population was 13.8 per 1,000 people per year, compared with 5.6 infections per 1,000 immunocompetent people per year (adjusted incident rate ratio, 1.69; 95% confidenceinterval, 1.58-1.81. When broken down by age, younger adults aged 18-49 with MS were more than three times more likely to develop shingles (incidence rate, 11.6 per 1,000 people per year) than immunocompetent younger adults (IR, 3.5). The gap was narrower for those age 50 and older, where adults with MS had a rate of 15.2 infections per 1,000 people per year versus 8.6 per 1,000 immunocompetent people per year.

Although MS patients with a higher baseline level of immunosuppression from therapy had higher herpes zoster infection rates (18 cases per 1,000 people per year) than those with low immunosuppression (14 cases per 1,000 people per year) or no immunosuppression from medication (13 cases per 1,000 people per year), rates for all three remained higher than for the immunocompetent population.
 

Herpes and MS: Some questions still unanswered

“We’ve known that herpes zoster is more common in people with MS, and we’ve known that it is seen in people on MS therapies,” Robert Fox, MD, a staff neurologist at the Mellen Center for MS and vice-chair for research at the Neurological Institute at the Cleveland Clinic, said in an interview. “What we haven’t known is just how much more common it is in people with MS than the rest of the adult population and whether it truly is more common in people taking MS therapies than people not taking MS therapies. This study puts real, population-based numbers on the incidence rates.”

Dr. Fox, who was not involved in the research, noted that a limitation of the study was the inability to know the risk of shingles according to specific MS therapies since all the therapies were grouped together.

”So I can’t say to a patient that their particular therapy increases their risk,” Dr. Fox said. “Similarly with the MS therapies listed in the ‘high’ immunosuppression category: We don’t know that each of the therapies listed do in fact increase the rate of herpes zoster. We just know that the group of MS therapies bunched into the ‘high’ category, on the whole, increase the rate of herpes zoster.”

The study does not provide any information about the impact of Shingrix vaccination, he added, since vaccinated individuals were excluded from the analysis.
 

Timing the vaccination with MS therapy

Dr. Steinman said in an interview that he recommends herpes zoster vaccination to his patients with MS.

“The mistake that people make with MS is that they don’t want to take the [herpes zoster] vaccine, and they should be taking it,”

Dr. Steinman said. “In a perfect world, they would get it before they went on their [immunosuppressive] drug. But now we’ll have a lot of people who didn’t take the vaccine; they can get it while they’re on their drug.” Although it depends on the particular therapy they’re taking, Dr. Steinman said that most people can get the shingles vaccine while continuing their medication.

The Centers for Disease Control and Prevention recommends that adults who are or will be immunodeficient or immunosuppressed because of a disease or therapy get two doses of the Shingrix vaccine against herpes zoster, regardless of whether they have previously been vaccinated with Zostavax or have ever had shingles. The agency has also issued detailed clinical guidance regarding how to administer the vaccine to individuals taking immunosuppressive therapy, including the option to administer the second dose 1-2 months after the first instead of 2-6 months to “facilitate avoiding vaccination during periods of more intense immunosuppression,” the agency wrote.

The research was sponsored, funded, and analyzed by GSK, which manufactures the shingles vaccine Shingrix, and Mr. Stempniewicz is a GSK employee. Two other authors are GSK employees, and three authors are employees of Optum who received fees from GSK for this study. Dr. Steinman and Dr. Fox reported no relevant disclosures.

DENVER – Patients with multiple sclerosis (MS) are significantly more likely to develop herpes zoster infections than immunocompetent individuals, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. “Herpes zoster and its complications are associated with increased health care cost and decreased quality of life,” lead author Nikita Stempniewicz, MSc, director of U.S. Health Outcomes & Epidemiology at GSK Vaccines, Alexandria, Va., reported.

“The take-home finding is that herpes zoster incidence is high among people with MS overall,” Mr. Stempniewicz said in an interview. “We also found that herpes zoster incidence is numerically higher among MS patients with higher levels of baseline immunosuppression, so another conclusion is that herpes zoster prevention may be warranted among this population given the high level of immunosuppression and the high risk of developing herpes zoster infection.” GSK manufactures Shingrix, the only currently approved and recommended herpes zoster vaccine available in the United States

Lawrence Steinman, MD, a professor of neurology and neurological sciences, pediatrics, and genetics at Stanford (Calif.) Medicine, was not involved in the research but said in an interview that the findings “raise the issue of whether not enough individuals with MS are getting Shingrix, and also whether there is a need for rapid intervention with an antiviral, for those individuals who develop shingles.”
 

Real-world data

For the study, researchers analyzed U.S. administrative claims data from the Optum Research Database between October 2015 and March 2022 to compare shingles infections between adults with MS (and no other immunocompromising conditions) and a random sample of one million people without any immunocompromising conditions. The study excluded anyone who had been vaccinated against herpes zoster or diagnosed with it in the year before October 2015.

Among the 42,185 adults with MS included in the cohort, just over half (53%) were commercially insured, and 47% had Medicare Advantage. Their average age was 53, and 75% were female. Just over half the cohort (55%) had no immunosuppression because of medications while 35% had low immunosuppression from MS therapy and 10% had high immunosuppression from therapy. High suppression meant patients were taking fingolimod, siponimod, ozanimod, ponesimod, cladribine, or a monoclonal antibody except natalizumab. Those with low suppression were taking natalizumab, fumarates, IVIG, glatiramer acetate, interferon beta or a related drug, teriflunomide, azathioprine, methotrexate, or mycophenolate mofetil.

The rate of shingles infections in the MS patient population was 13.8 per 1,000 people per year, compared with 5.6 infections per 1,000 immunocompetent people per year (adjusted incident rate ratio, 1.69; 95% confidenceinterval, 1.58-1.81. When broken down by age, younger adults aged 18-49 with MS were more than three times more likely to develop shingles (incidence rate, 11.6 per 1,000 people per year) than immunocompetent younger adults (IR, 3.5). The gap was narrower for those age 50 and older, where adults with MS had a rate of 15.2 infections per 1,000 people per year versus 8.6 per 1,000 immunocompetent people per year.

Although MS patients with a higher baseline level of immunosuppression from therapy had higher herpes zoster infection rates (18 cases per 1,000 people per year) than those with low immunosuppression (14 cases per 1,000 people per year) or no immunosuppression from medication (13 cases per 1,000 people per year), rates for all three remained higher than for the immunocompetent population.