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The Mediterranean diet appears to be associated with a lower incidence of cardiovascular disease (CVD) and mortality in women, new observational data suggest.

Those who had a higher adherence to a Mediterranean diet had a 24% lower risk for cardiovascular disease and 23% lower risk for death.

“A healthy diet is a huge factor in preventing heart disease. However, current guidelines on preventing heart disease lack sex-specific recommendations,” said senior author Sarah Zaman, MBBS, PhD, an associate professor of medicine and principal research fellow at the University of Sydney’s Westmead Applied Research Centre.

snyferok/Thinkstock

Analyzing cardiovascular outcomes

Dr. Zaman and colleagues conducted a systematic review and meta-analysis of 16 studies published between 2006 and 2021 that reported a Mediterranean diet score and included either all women or had stratified outcomes by sex. They excluded studies that referred to only certain components of the Mediterranean diet or combined it with other lifestyle-related factors.

The studies, which were mainly conducted in the United States and Europe, included 722,495 adult women without previous clinical or subclinical CVD, with a median follow-up of 12.5 years.

Higher Mediterranean diet adherence was defined as the highest category reporting the highest range of Mediterranean diet scores, and lower adherence was defined as the lowest category reporting lowest scores. Incident CVD included coronary heart disease, myocardial infarction, stroke, heart failure, cardiovascular death, major adverse cardiovascular events, major adverse cardiac cerebrovascular events, and patient-reported CVD.

Overall, higher adherence to a Mediterranean diet was associated with lower CVD incidence (hazard ratio, 0.76; 95% confidence interval, 0.72-0.81), total mortality (HR, 0.77; 95% CI, 0.74-0.80), and coronary heart disease (HR, 0.75; 95% CI, 0.65-0.87).

Stroke incidence was also lower among women who adhered to the Mediterranean diet, although it wasn’t considered statistically significant (HR, 0.87; 95% CI, 0.76-1.01).

Additional analyses found similar reductions in risk across women of different ethnicities. Higher Mediterranean diet adherence was associated with lower CVD incidence for both women of European descent (HR, 0.76; 95% CI, 0.59-0.98) and women of non-European descent – Asian, Native Hawaiian, and African American – (HR, 0.79; 95% CI, 0.72-0.87).

The results didn’t materially change in sensitivity analyses, the authors note. Excluding one study at a time, the pooled HRs for the highest versus the lowest Mediterranean diet adherence ranged from 0.76 (95% CI, 0.72-0.80) to 0.83 (95% CI, 0.70-0.98) for incident CVD and from 0.77 (95% CI, 0.75-0.80) to 0.77 (95% CI, 0.74-0.81) for total mortality among women.

At the same time, the authors pointed to several limitations, including the observational nature of all of the studies, the reliance on self-reported food frequency questionnaires, and heterogeneity in the adjustments for influential factors across the studies.
 

Additional considerations

Dr. Zaman and colleagues called for more sex-specific research in cardiology, including risk factors related to premature menopause, preeclampsia, gestational diabetes, and autoimmune diseases such as systemic lupus.

Future studies should also explore the underlying mechanisms that may explain the links between the Mediterranean diet, cardiovascular disease, and death, the authors write. For instance, the diet may reduce inflammation and cardiovascular risk factors through antioxidant and beneficial gut microbiome pathways. Other components of the diet – such as polyphenols, nitrates, omega-3 fatty acids, higher fiber intake, and reduced glycemic load – may also play a role.

“It was striking to see how strong the long-term cardioprotective properties of a Mediterranean-type dietary pattern were,” said Samia Mora, MD, MHS, a professor of medicine at Harvard Medical School and director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital.

Dr. Mora, who wasn’t involved with this study, has researched potential mechanisms related to the Mediterranean diet, cardiovascular events, and diabetes in women. She and colleagues have found that women with high adherence to the diet are more likely to have lower inflammation, insulin resistance, body mass index, and blood pressure, as well as improved lipid and metabolic profiles.

“This could represent an opportunity to intervene earlier and more intensively on improving inflammation, insulin resistance, and cardiometabolic health through evidence-based dietary approaches such as the Mediterranean diet,” she said. “As health care providers, we should promote the healthy dietary attributes of the Mediterranean diet, especially as many of our patients in the U.S. are less familiar with the Mediterranean diet and how to incorporate its components into daily food intake.”

The study did not receive any funding. Dr. Zaman was supported by a Heart Foundation Future Leader Fellowship. The authors declared no conflicts of interest. Dr. Mora reported no relevant financial relationships.

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

The Mediterranean diet appears to be associated with a lower incidence of cardiovascular disease (CVD) and mortality in women, new observational data suggest.

Those who had a higher adherence to a Mediterranean diet had a 24% lower risk for cardiovascular disease and 23% lower risk for death.

“A healthy diet is a huge factor in preventing heart disease. However, current guidelines on preventing heart disease lack sex-specific recommendations,” said senior author Sarah Zaman, MBBS, PhD, an associate professor of medicine and principal research fellow at the University of Sydney’s Westmead Applied Research Centre.

snyferok/Thinkstock

Analyzing cardiovascular outcomes

Dr. Zaman and colleagues conducted a systematic review and meta-analysis of 16 studies published between 2006 and 2021 that reported a Mediterranean diet score and included either all women or had stratified outcomes by sex. They excluded studies that referred to only certain components of the Mediterranean diet or combined it with other lifestyle-related factors.

The studies, which were mainly conducted in the United States and Europe, included 722,495 adult women without previous clinical or subclinical CVD, with a median follow-up of 12.5 years.

Higher Mediterranean diet adherence was defined as the highest category reporting the highest range of Mediterranean diet scores, and lower adherence was defined as the lowest category reporting lowest scores. Incident CVD included coronary heart disease, myocardial infarction, stroke, heart failure, cardiovascular death, major adverse cardiovascular events, major adverse cardiac cerebrovascular events, and patient-reported CVD.

Overall, higher adherence to a Mediterranean diet was associated with lower CVD incidence (hazard ratio, 0.76; 95% confidence interval, 0.72-0.81), total mortality (HR, 0.77; 95% CI, 0.74-0.80), and coronary heart disease (HR, 0.75; 95% CI, 0.65-0.87).

Stroke incidence was also lower among women who adhered to the Mediterranean diet, although it wasn’t considered statistically significant (HR, 0.87; 95% CI, 0.76-1.01).

Additional analyses found similar reductions in risk across women of different ethnicities. Higher Mediterranean diet adherence was associated with lower CVD incidence for both women of European descent (HR, 0.76; 95% CI, 0.59-0.98) and women of non-European descent – Asian, Native Hawaiian, and African American – (HR, 0.79; 95% CI, 0.72-0.87).

The results didn’t materially change in sensitivity analyses, the authors note. Excluding one study at a time, the pooled HRs for the highest versus the lowest Mediterranean diet adherence ranged from 0.76 (95% CI, 0.72-0.80) to 0.83 (95% CI, 0.70-0.98) for incident CVD and from 0.77 (95% CI, 0.75-0.80) to 0.77 (95% CI, 0.74-0.81) for total mortality among women.

At the same time, the authors pointed to several limitations, including the observational nature of all of the studies, the reliance on self-reported food frequency questionnaires, and heterogeneity in the adjustments for influential factors across the studies.
 

Additional considerations

Dr. Zaman and colleagues called for more sex-specific research in cardiology, including risk factors related to premature menopause, preeclampsia, gestational diabetes, and autoimmune diseases such as systemic lupus.

Future studies should also explore the underlying mechanisms that may explain the links between the Mediterranean diet, cardiovascular disease, and death, the authors write. For instance, the diet may reduce inflammation and cardiovascular risk factors through antioxidant and beneficial gut microbiome pathways. Other components of the diet – such as polyphenols, nitrates, omega-3 fatty acids, higher fiber intake, and reduced glycemic load – may also play a role.

“It was striking to see how strong the long-term cardioprotective properties of a Mediterranean-type dietary pattern were,” said Samia Mora, MD, MHS, a professor of medicine at Harvard Medical School and director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital.

Dr. Mora, who wasn’t involved with this study, has researched potential mechanisms related to the Mediterranean diet, cardiovascular events, and diabetes in women. She and colleagues have found that women with high adherence to the diet are more likely to have lower inflammation, insulin resistance, body mass index, and blood pressure, as well as improved lipid and metabolic profiles.

“This could represent an opportunity to intervene earlier and more intensively on improving inflammation, insulin resistance, and cardiometabolic health through evidence-based dietary approaches such as the Mediterranean diet,” she said. “As health care providers, we should promote the healthy dietary attributes of the Mediterranean diet, especially as many of our patients in the U.S. are less familiar with the Mediterranean diet and how to incorporate its components into daily food intake.”

The study did not receive any funding. Dr. Zaman was supported by a Heart Foundation Future Leader Fellowship. The authors declared no conflicts of interest. Dr. Mora reported no relevant financial relationships.

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

The Mediterranean diet appears to be associated with a lower incidence of cardiovascular disease (CVD) and mortality in women, new observational data suggest.

Those who had a higher adherence to a Mediterranean diet had a 24% lower risk for cardiovascular disease and 23% lower risk for death.

“A healthy diet is a huge factor in preventing heart disease. However, current guidelines on preventing heart disease lack sex-specific recommendations,” said senior author Sarah Zaman, MBBS, PhD, an associate professor of medicine and principal research fellow at the University of Sydney’s Westmead Applied Research Centre.

snyferok/Thinkstock

Analyzing cardiovascular outcomes

Dr. Zaman and colleagues conducted a systematic review and meta-analysis of 16 studies published between 2006 and 2021 that reported a Mediterranean diet score and included either all women or had stratified outcomes by sex. They excluded studies that referred to only certain components of the Mediterranean diet or combined it with other lifestyle-related factors.

The studies, which were mainly conducted in the United States and Europe, included 722,495 adult women without previous clinical or subclinical CVD, with a median follow-up of 12.5 years.

Higher Mediterranean diet adherence was defined as the highest category reporting the highest range of Mediterranean diet scores, and lower adherence was defined as the lowest category reporting lowest scores. Incident CVD included coronary heart disease, myocardial infarction, stroke, heart failure, cardiovascular death, major adverse cardiovascular events, major adverse cardiac cerebrovascular events, and patient-reported CVD.

Overall, higher adherence to a Mediterranean diet was associated with lower CVD incidence (hazard ratio, 0.76; 95% confidence interval, 0.72-0.81), total mortality (HR, 0.77; 95% CI, 0.74-0.80), and coronary heart disease (HR, 0.75; 95% CI, 0.65-0.87).

Stroke incidence was also lower among women who adhered to the Mediterranean diet, although it wasn’t considered statistically significant (HR, 0.87; 95% CI, 0.76-1.01).

Additional analyses found similar reductions in risk across women of different ethnicities. Higher Mediterranean diet adherence was associated with lower CVD incidence for both women of European descent (HR, 0.76; 95% CI, 0.59-0.98) and women of non-European descent – Asian, Native Hawaiian, and African American – (HR, 0.79; 95% CI, 0.72-0.87).

The results didn’t materially change in sensitivity analyses, the authors note. Excluding one study at a time, the pooled HRs for the highest versus the lowest Mediterranean diet adherence ranged from 0.76 (95% CI, 0.72-0.80) to 0.83 (95% CI, 0.70-0.98) for incident CVD and from 0.77 (95% CI, 0.75-0.80) to 0.77 (95% CI, 0.74-0.81) for total mortality among women.

At the same time, the authors pointed to several limitations, including the observational nature of all of the studies, the reliance on self-reported food frequency questionnaires, and heterogeneity in the adjustments for influential factors across the studies.
 

Additional considerations

Dr. Zaman and colleagues called for more sex-specific research in cardiology, including risk factors related to premature menopause, preeclampsia, gestational diabetes, and autoimmune diseases such as systemic lupus.

Future studies should also explore the underlying mechanisms that may explain the links between the Mediterranean diet, cardiovascular disease, and death, the authors write. For instance, the diet may reduce inflammation and cardiovascular risk factors through antioxidant and beneficial gut microbiome pathways. Other components of the diet – such as polyphenols, nitrates, omega-3 fatty acids, higher fiber intake, and reduced glycemic load – may also play a role.

“It was striking to see how strong the long-term cardioprotective properties of a Mediterranean-type dietary pattern were,” said Samia Mora, MD, MHS, a professor of medicine at Harvard Medical School and director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital.

Dr. Mora, who wasn’t involved with this study, has researched potential mechanisms related to the Mediterranean diet, cardiovascular events, and diabetes in women. She and colleagues have found that women with high adherence to the diet are more likely to have lower inflammation, insulin resistance, body mass index, and blood pressure, as well as improved lipid and metabolic profiles.

“This could represent an opportunity to intervene earlier and more intensively on improving inflammation, insulin resistance, and cardiometabolic health through evidence-based dietary approaches such as the Mediterranean diet,” she said. “As health care providers, we should promote the healthy dietary attributes of the Mediterranean diet, especially as many of our patients in the U.S. are less familiar with the Mediterranean diet and how to incorporate its components into daily food intake.”

The study did not receive any funding. Dr. Zaman was supported by a Heart Foundation Future Leader Fellowship. The authors declared no conflicts of interest. Dr. Mora reported no relevant financial relationships.

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

Computer-aided detection (CADe) during colonoscopy may not lead to major improvements in key measures, particularly in community-based settings, according to a new study.

In a randomized clinical trial using EndoVigilant, there wasn’t a significant difference in adenomas per colonoscopy (APC) in procedures with the CADe tool versus those without it. In addition, the adenoma detection rate (ADR) and serrated polyp detection rate were similar in the CADe and non-CADe groups.

“Although we were disappointed that AI [artificial intelligence] did not improve detection of adenomas or serrated polyps in our study, we are still optimistic that this exciting technology will eventually impact endoscopy in a very positive way,” senior author Shai Friedland, MD, a professor of medicine at Stanford (Calif.) University and gastroenterologist with the Veterans Affairs Palo Alto Health Care System, said in an interview.

“The ultimate goal should be to improve the ability of colonoscopy to prevent morbidity and mortality from colon cancer, especially for endoscopists who may not be performing as well as they could be,” he said. “AI can potentially help prevent missed lesions due to fatigue or distraction, much like a warning system that averts car accidents. It can also potentially help endoscopists recognize dangerous – but rare – subtle lesions such as small, flat, and depressed cancers.”

The study was published online in the American Journal of Gastroenterology.
 

Analyzing detection rates

Several studies have evaluated the use of different CADe devices to reduce adenoma miss rates during colonoscopy, and some have found that the technology contributed to significantly higher ADR and APC, the study authors write. However, most of these studies have been performed in academic settings.

Dr. Friedland and colleagues conducted a randomized controlled trial, called AI-SEE, to evaluate the use of CADe during colonoscopy in four community-based endoscopy centers located in California, Connecticut, Maryland, and New Jersey between September 2020 and September 2021. The trial included seven board-certified clinicians, who had ADR of 25%-37% before the study. The participants were randomly assigned to colonoscopies with or without CADe in blocks of 16 patients to ensure masking. Both groups had similar patient demographics.

The research team enrolled patients aged 45 years or older who presented for screening or low-risk surveillance colonoscopy, which was defined as a patient qualifying for a surveillance interval of 3 years or greater based on the U.S. Multi-Society Task Force 2020 Guidelines. Patients were excluded if they had a history of inflammatory bowel disease, known or suspected polyposis or hereditary colon cancer syndrome, history of colon resection, or a referral for a diagnostic colonoscopy.

Among 769 enrolled patients, 387 were randomly assigned to undergo colonoscopy with EndoVigilant, an AI-enabled CADe software for colonoscopy. It augments existing white-light colonoscopy in real time by highlighting colon polyps and displaying a graphic box around the lesion on the monitor. It can be deployed as a single- or dual-monitor device. Although the study was originally designed to use two monitors, three investigators expressed strong preference for the single-monitor mode, so the protocol allowed endoscopists to choose.

Primary outcomes included APC and adenoma per extraction (APE), which is the percentage of polyps removed that are adenomas. Secondary endpoints included procedural time, ADR, serrated polyp detection rate, serrated polyps per colonoscopy, and nonadenomatous, nonserrated polyps per colonoscopy.

Overall, the use of CADe didn’t show a significant difference in APC, at 0.73, compared with 0.67 for non-CADe.

Although the use of CADe didn’t lead to increased identification of serrated polyps per colonoscopy – both at 0.08 – CADe led to increased identification of nonadenomatous, nonserrated polyps per colonoscopy, at 0.90 versus 0.51.

There also wasn’t a significant difference in distribution regarding adenomatous polyp location, size, or morphology. However, there was a trend toward greater identification of 6-9 mm APC using CADe, at 0.13 versus 0.08.

Mean withdrawal time was longer in the CADe group, at 11.7 minutes versus 10.7 minutes. However, when no polyps were identified, the withdrawal times were similar, at 9.1 minutes versus 8.8 minutes.

In addition, there was no difference in ADR for screening colonoscopies between the non-CADe and CADe groups, at 34.6% versus 34.3%, or for surveillance procedures, at 43.9% versus 40%. CADe also didn’t improve serrated polyp detection rates for screening or surveillance.

CADe was also associated with decreased APE in all colonoscopies (44.8 vs. 56.8) as well as in screening colonoscopies (43 vs. 57.8).

A comparison of single-monitor CADe with dual-monitor CADe found no significant difference in the average number of adenomas or serrated polyps identified per colonoscopy. However, dual-monitor CADe identified significantly more non-adenomatous, nonserrated polyps per colonoscopy (1.18 vs. 0.42), more adenomas sized at least 10 mm (0.19 vs. 0.05), and more flat polyps (0.18 vs. 0).

The study was terminated early after the interim analysis point, marked by 769 valid subjects. At this point, the comparison of APC between the two groups resulted in a new sample size estimate required for final analysis of 6,557 per group. This revised large study size estimate made it impractical to continue, the study authors wrote. No adverse events were observed during the study.

“What our study shows is that current systems – and the one we used in this study performs very well when tested on a database of images or videos – don’t make a major impact on very crude outcome measures, such as the total number of adenomas detected by a group of endoscopists at typical private endoscopy centers,” Dr. Friedland said. “I’m not convinced that we have a good answer yet for where to go from here, but we need to keep working with our AI colleagues to figure out how to use this exciting technology to improve outcomes in colon cancer.”
 

Additional considerations

In a separate evaluation of EndoVigilant, the frame level sensitivity was 0.9 and the frame level specificity was 0.97. These calculations were conducted on a dataset not used in training or validation of this model, the authors noted.

In this study, it’s possible that experienced community-based endoscopists are proficient at detecting the adenomas highlighted by the CADe system, so the technology may not detect a significant number of additional adenomas, the authors wrote. It’s also possible that some endoscopists ignore lesions highlighted by CADe, including small lesions that might be difficult to identify as adenomas or are seen as clinically unimportant, which could reduce the potential benefit of CADe.

“It’s important to remember that these tools are meant to be endoscopist assistance devices, not endoscopist replacements. They provide added benefit by pointing out polyps while we do the best exam we can,” Aasma Shaukat, MD, a professor of medicine and gastroenterologist at NYU Langone Health, New York, said in an interview.

Dr. Shaukat, who wasn’t involved with this study, has researched CADe for screening and surveillance colonoscopies. She and colleagues found that CADe use improved APC without an increase in resection of nonneoplastic lesions.

“Different trials have reported different results, and at the end of the day, it’s an endoscopist assistance tool, like spellcheck in a document,” she said. “It’s nice if spellcheck points to an incorrect spelling, but you don’t have to use it. Similarly, we often don’t know in these studies what an endoscopist felt or believed about the tool when using it.”

The benefits of CADe could vary based on its software, setting, number of patients, patient characteristics, number of clinicians, provider experience and training, dual- versus single-monitor setup, and even time of day, she noted. Future studies could clarify these factors, as well as improve the technology.

“This is just the beginning of AI in this field, and while bounding boxes to indicate potential polyps is a good start, it’s not the be-all, end-all,” Dr. Shaukat said.

“We want AI software to be able to tell us more about the size of the polyp, histology, prep quality, landmarks in the colon, adequacy of resection, and more. There’s some work being geared toward developing the algorithms to do these additional aspects,” she added.

The study was sponsored by EndoVigilant. Some of the authors reported consultant roles with Neptune Medical, AgilTx, Intuitive Surgical, Capsovision, and EndoVigilant. Dr. Shaukat reported no relevant financial relationships.

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

Computer-aided detection (CADe) during colonoscopy may not lead to major improvements in key measures, particularly in community-based settings, according to a new study.

In a randomized clinical trial using EndoVigilant, there wasn’t a significant difference in adenomas per colonoscopy (APC) in procedures with the CADe tool versus those without it. In addition, the adenoma detection rate (ADR) and serrated polyp detection rate were similar in the CADe and non-CADe groups.

“Although we were disappointed that AI [artificial intelligence] did not improve detection of adenomas or serrated polyps in our study, we are still optimistic that this exciting technology will eventually impact endoscopy in a very positive way,” senior author Shai Friedland, MD, a professor of medicine at Stanford (Calif.) University and gastroenterologist with the Veterans Affairs Palo Alto Health Care System, said in an interview.

“The ultimate goal should be to improve the ability of colonoscopy to prevent morbidity and mortality from colon cancer, especially for endoscopists who may not be performing as well as they could be,” he said. “AI can potentially help prevent missed lesions due to fatigue or distraction, much like a warning system that averts car accidents. It can also potentially help endoscopists recognize dangerous – but rare – subtle lesions such as small, flat, and depressed cancers.”

The study was published online in the American Journal of Gastroenterology.
 

Analyzing detection rates

Several studies have evaluated the use of different CADe devices to reduce adenoma miss rates during colonoscopy, and some have found that the technology contributed to significantly higher ADR and APC, the study authors write. However, most of these studies have been performed in academic settings.

Dr. Friedland and colleagues conducted a randomized controlled trial, called AI-SEE, to evaluate the use of CADe during colonoscopy in four community-based endoscopy centers located in California, Connecticut, Maryland, and New Jersey between September 2020 and September 2021. The trial included seven board-certified clinicians, who had ADR of 25%-37% before the study. The participants were randomly assigned to colonoscopies with or without CADe in blocks of 16 patients to ensure masking. Both groups had similar patient demographics.

The research team enrolled patients aged 45 years or older who presented for screening or low-risk surveillance colonoscopy, which was defined as a patient qualifying for a surveillance interval of 3 years or greater based on the U.S. Multi-Society Task Force 2020 Guidelines. Patients were excluded if they had a history of inflammatory bowel disease, known or suspected polyposis or hereditary colon cancer syndrome, history of colon resection, or a referral for a diagnostic colonoscopy.

Among 769 enrolled patients, 387 were randomly assigned to undergo colonoscopy with EndoVigilant, an AI-enabled CADe software for colonoscopy. It augments existing white-light colonoscopy in real time by highlighting colon polyps and displaying a graphic box around the lesion on the monitor. It can be deployed as a single- or dual-monitor device. Although the study was originally designed to use two monitors, three investigators expressed strong preference for the single-monitor mode, so the protocol allowed endoscopists to choose.

Primary outcomes included APC and adenoma per extraction (APE), which is the percentage of polyps removed that are adenomas. Secondary endpoints included procedural time, ADR, serrated polyp detection rate, serrated polyps per colonoscopy, and nonadenomatous, nonserrated polyps per colonoscopy.

Overall, the use of CADe didn’t show a significant difference in APC, at 0.73, compared with 0.67 for non-CADe.

Although the use of CADe didn’t lead to increased identification of serrated polyps per colonoscopy – both at 0.08 – CADe led to increased identification of nonadenomatous, nonserrated polyps per colonoscopy, at 0.90 versus 0.51.

There also wasn’t a significant difference in distribution regarding adenomatous polyp location, size, or morphology. However, there was a trend toward greater identification of 6-9 mm APC using CADe, at 0.13 versus 0.08.

Mean withdrawal time was longer in the CADe group, at 11.7 minutes versus 10.7 minutes. However, when no polyps were identified, the withdrawal times were similar, at 9.1 minutes versus 8.8 minutes.

In addition, there was no difference in ADR for screening colonoscopies between the non-CADe and CADe groups, at 34.6% versus 34.3%, or for surveillance procedures, at 43.9% versus 40%. CADe also didn’t improve serrated polyp detection rates for screening or surveillance.

CADe was also associated with decreased APE in all colonoscopies (44.8 vs. 56.8) as well as in screening colonoscopies (43 vs. 57.8).

A comparison of single-monitor CADe with dual-monitor CADe found no significant difference in the average number of adenomas or serrated polyps identified per colonoscopy. However, dual-monitor CADe identified significantly more non-adenomatous, nonserrated polyps per colonoscopy (1.18 vs. 0.42), more adenomas sized at least 10 mm (0.19 vs. 0.05), and more flat polyps (0.18 vs. 0).

The study was terminated early after the interim analysis point, marked by 769 valid subjects. At this point, the comparison of APC between the two groups resulted in a new sample size estimate required for final analysis of 6,557 per group. This revised large study size estimate made it impractical to continue, the study authors wrote. No adverse events were observed during the study.

“What our study shows is that current systems – and the one we used in this study performs very well when tested on a database of images or videos – don’t make a major impact on very crude outcome measures, such as the total number of adenomas detected by a group of endoscopists at typical private endoscopy centers,” Dr. Friedland said. “I’m not convinced that we have a good answer yet for where to go from here, but we need to keep working with our AI colleagues to figure out how to use this exciting technology to improve outcomes in colon cancer.”
 

Additional considerations

In a separate evaluation of EndoVigilant, the frame level sensitivity was 0.9 and the frame level specificity was 0.97. These calculations were conducted on a dataset not used in training or validation of this model, the authors noted.

In this study, it’s possible that experienced community-based endoscopists are proficient at detecting the adenomas highlighted by the CADe system, so the technology may not detect a significant number of additional adenomas, the authors wrote. It’s also possible that some endoscopists ignore lesions highlighted by CADe, including small lesions that might be difficult to identify as adenomas or are seen as clinically unimportant, which could reduce the potential benefit of CADe.

“It’s important to remember that these tools are meant to be endoscopist assistance devices, not endoscopist replacements. They provide added benefit by pointing out polyps while we do the best exam we can,” Aasma Shaukat, MD, a professor of medicine and gastroenterologist at NYU Langone Health, New York, said in an interview.

Dr. Shaukat, who wasn’t involved with this study, has researched CADe for screening and surveillance colonoscopies. She and colleagues found that CADe use improved APC without an increase in resection of nonneoplastic lesions.

“Different trials have reported different results, and at the end of the day, it’s an endoscopist assistance tool, like spellcheck in a document,” she said. “It’s nice if spellcheck points to an incorrect spelling, but you don’t have to use it. Similarly, we often don’t know in these studies what an endoscopist felt or believed about the tool when using it.”

The benefits of CADe could vary based on its software, setting, number of patients, patient characteristics, number of clinicians, provider experience and training, dual- versus single-monitor setup, and even time of day, she noted. Future studies could clarify these factors, as well as improve the technology.

“This is just the beginning of AI in this field, and while bounding boxes to indicate potential polyps is a good start, it’s not the be-all, end-all,” Dr. Shaukat said.

“We want AI software to be able to tell us more about the size of the polyp, histology, prep quality, landmarks in the colon, adequacy of resection, and more. There’s some work being geared toward developing the algorithms to do these additional aspects,” she added.

The study was sponsored by EndoVigilant. Some of the authors reported consultant roles with Neptune Medical, AgilTx, Intuitive Surgical, Capsovision, and EndoVigilant. Dr. Shaukat reported no relevant financial relationships.

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

Computer-aided detection (CADe) during colonoscopy may not lead to major improvements in key measures, particularly in community-based settings, according to a new study.

In a randomized clinical trial using EndoVigilant, there wasn’t a significant difference in adenomas per colonoscopy (APC) in procedures with the CADe tool versus those without it. In addition, the adenoma detection rate (ADR) and serrated polyp detection rate were similar in the CADe and non-CADe groups.

“Although we were disappointed that AI [artificial intelligence] did not improve detection of adenomas or serrated polyps in our study, we are still optimistic that this exciting technology will eventually impact endoscopy in a very positive way,” senior author Shai Friedland, MD, a professor of medicine at Stanford (Calif.) University and gastroenterologist with the Veterans Affairs Palo Alto Health Care System, said in an interview.

“The ultimate goal should be to improve the ability of colonoscopy to prevent morbidity and mortality from colon cancer, especially for endoscopists who may not be performing as well as they could be,” he said. “AI can potentially help prevent missed lesions due to fatigue or distraction, much like a warning system that averts car accidents. It can also potentially help endoscopists recognize dangerous – but rare – subtle lesions such as small, flat, and depressed cancers.”

The study was published online in the American Journal of Gastroenterology.
 

Analyzing detection rates

Several studies have evaluated the use of different CADe devices to reduce adenoma miss rates during colonoscopy, and some have found that the technology contributed to significantly higher ADR and APC, the study authors write. However, most of these studies have been performed in academic settings.

Dr. Friedland and colleagues conducted a randomized controlled trial, called AI-SEE, to evaluate the use of CADe during colonoscopy in four community-based endoscopy centers located in California, Connecticut, Maryland, and New Jersey between September 2020 and September 2021. The trial included seven board-certified clinicians, who had ADR of 25%-37% before the study. The participants were randomly assigned to colonoscopies with or without CADe in blocks of 16 patients to ensure masking. Both groups had similar patient demographics.

The research team enrolled patients aged 45 years or older who presented for screening or low-risk surveillance colonoscopy, which was defined as a patient qualifying for a surveillance interval of 3 years or greater based on the U.S. Multi-Society Task Force 2020 Guidelines. Patients were excluded if they had a history of inflammatory bowel disease, known or suspected polyposis or hereditary colon cancer syndrome, history of colon resection, or a referral for a diagnostic colonoscopy.

Among 769 enrolled patients, 387 were randomly assigned to undergo colonoscopy with EndoVigilant, an AI-enabled CADe software for colonoscopy. It augments existing white-light colonoscopy in real time by highlighting colon polyps and displaying a graphic box around the lesion on the monitor. It can be deployed as a single- or dual-monitor device. Although the study was originally designed to use two monitors, three investigators expressed strong preference for the single-monitor mode, so the protocol allowed endoscopists to choose.

Primary outcomes included APC and adenoma per extraction (APE), which is the percentage of polyps removed that are adenomas. Secondary endpoints included procedural time, ADR, serrated polyp detection rate, serrated polyps per colonoscopy, and nonadenomatous, nonserrated polyps per colonoscopy.

Overall, the use of CADe didn’t show a significant difference in APC, at 0.73, compared with 0.67 for non-CADe.

Although the use of CADe didn’t lead to increased identification of serrated polyps per colonoscopy – both at 0.08 – CADe led to increased identification of nonadenomatous, nonserrated polyps per colonoscopy, at 0.90 versus 0.51.

There also wasn’t a significant difference in distribution regarding adenomatous polyp location, size, or morphology. However, there was a trend toward greater identification of 6-9 mm APC using CADe, at 0.13 versus 0.08.

Mean withdrawal time was longer in the CADe group, at 11.7 minutes versus 10.7 minutes. However, when no polyps were identified, the withdrawal times were similar, at 9.1 minutes versus 8.8 minutes.

In addition, there was no difference in ADR for screening colonoscopies between the non-CADe and CADe groups, at 34.6% versus 34.3%, or for surveillance procedures, at 43.9% versus 40%. CADe also didn’t improve serrated polyp detection rates for screening or surveillance.

CADe was also associated with decreased APE in all colonoscopies (44.8 vs. 56.8) as well as in screening colonoscopies (43 vs. 57.8).

A comparison of single-monitor CADe with dual-monitor CADe found no significant difference in the average number of adenomas or serrated polyps identified per colonoscopy. However, dual-monitor CADe identified significantly more non-adenomatous, nonserrated polyps per colonoscopy (1.18 vs. 0.42), more adenomas sized at least 10 mm (0.19 vs. 0.05), and more flat polyps (0.18 vs. 0).

The study was terminated early after the interim analysis point, marked by 769 valid subjects. At this point, the comparison of APC between the two groups resulted in a new sample size estimate required for final analysis of 6,557 per group. This revised large study size estimate made it impractical to continue, the study authors wrote. No adverse events were observed during the study.

“What our study shows is that current systems – and the one we used in this study performs very well when tested on a database of images or videos – don’t make a major impact on very crude outcome measures, such as the total number of adenomas detected by a group of endoscopists at typical private endoscopy centers,” Dr. Friedland said. “I’m not convinced that we have a good answer yet for where to go from here, but we need to keep working with our AI colleagues to figure out how to use this exciting technology to improve outcomes in colon cancer.”
 

Additional considerations

In a separate evaluation of EndoVigilant, the frame level sensitivity was 0.9 and the frame level specificity was 0.97. These calculations were conducted on a dataset not used in training or validation of this model, the authors noted.

In this study, it’s possible that experienced community-based endoscopists are proficient at detecting the adenomas highlighted by the CADe system, so the technology may not detect a significant number of additional adenomas, the authors wrote. It’s also possible that some endoscopists ignore lesions highlighted by CADe, including small lesions that might be difficult to identify as adenomas or are seen as clinically unimportant, which could reduce the potential benefit of CADe.

“It’s important to remember that these tools are meant to be endoscopist assistance devices, not endoscopist replacements. They provide added benefit by pointing out polyps while we do the best exam we can,” Aasma Shaukat, MD, a professor of medicine and gastroenterologist at NYU Langone Health, New York, said in an interview.

Dr. Shaukat, who wasn’t involved with this study, has researched CADe for screening and surveillance colonoscopies. She and colleagues found that CADe use improved APC without an increase in resection of nonneoplastic lesions.

“Different trials have reported different results, and at the end of the day, it’s an endoscopist assistance tool, like spellcheck in a document,” she said. “It’s nice if spellcheck points to an incorrect spelling, but you don’t have to use it. Similarly, we often don’t know in these studies what an endoscopist felt or believed about the tool when using it.”

The benefits of CADe could vary based on its software, setting, number of patients, patient characteristics, number of clinicians, provider experience and training, dual- versus single-monitor setup, and even time of day, she noted. Future studies could clarify these factors, as well as improve the technology.

“This is just the beginning of AI in this field, and while bounding boxes to indicate potential polyps is a good start, it’s not the be-all, end-all,” Dr. Shaukat said.

“We want AI software to be able to tell us more about the size of the polyp, histology, prep quality, landmarks in the colon, adequacy of resection, and more. There’s some work being geared toward developing the algorithms to do these additional aspects,” she added.

The study was sponsored by EndoVigilant. Some of the authors reported consultant roles with Neptune Medical, AgilTx, Intuitive Surgical, Capsovision, and EndoVigilant. Dr. Shaukat reported no relevant financial relationships.

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

Datascope/Getinge is recalling certain Cardiosave Hybrid and Cardiosave Rescue Intra-Aortic Balloon Pumps (IABPs) because the coiled cable connecting the display and base on some units may fail, causing an unexpected shutdown without warnings or alarms to alert the user.

The U.S. Food and Drug Administration has identified this as a class I recall, the most serious type of recall, because of the risk for serious injury or death.

The FDA warns that an unexpected pump shutdown and any interruption to therapy that occurs can lead to hemodynamic instability, organ damage, and/or death, especially in patients who are critically ill and most likely to receive therapy using these devices.

Wikimedia Commons/FitzColinGerald/Creative Commons License

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

Datascope/Getinge is recalling certain Cardiosave Hybrid and Cardiosave Rescue Intra-Aortic Balloon Pumps (IABPs) because the coiled cable connecting the display and base on some units may fail, causing an unexpected shutdown without warnings or alarms to alert the user.

The U.S. Food and Drug Administration has identified this as a class I recall, the most serious type of recall, because of the risk for serious injury or death.

The FDA warns that an unexpected pump shutdown and any interruption to therapy that occurs can lead to hemodynamic instability, organ damage, and/or death, especially in patients who are critically ill and most likely to receive therapy using these devices.

Wikimedia Commons/FitzColinGerald/Creative Commons License

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

Datascope/Getinge is recalling certain Cardiosave Hybrid and Cardiosave Rescue Intra-Aortic Balloon Pumps (IABPs) because the coiled cable connecting the display and base on some units may fail, causing an unexpected shutdown without warnings or alarms to alert the user.

The U.S. Food and Drug Administration has identified this as a class I recall, the most serious type of recall, because of the risk for serious injury or death.

The FDA warns that an unexpected pump shutdown and any interruption to therapy that occurs can lead to hemodynamic instability, organ damage, and/or death, especially in patients who are critically ill and most likely to receive therapy using these devices.

Wikimedia Commons/FitzColinGerald/Creative Commons License

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

Children with autism spectrum disorder (ASD) are significantly less likely to have vision screening at well visits for 3- to 5-year-olds than are typically developing children, researchers have found.

The report, by Kimberly Hoover, MD, of Thomas Jefferson University in Philadelphia, and colleagues, was published online in Pediatrics.

While 59.9% of children without ASD got vision screening in these visits, only 36.5% of children with ASD got the screening. Both screening rates miss the mark set by American Academy of Pediatrics guidelines.

The AAP recommends “annual instrument-based vision screening, if available, at well visits for children starting at age 12 months to 3 years, and direct visual acuity testing beginning at 4 years of age. However, in children with developmental delays, the AAP recommends instrument-based screening, such as photoscreening, as a useful alternative at any age.”
 

Racial, age disparities as well

Racial disparities were evident in the data as well. Of the children who had ASD, Black children had the lowest rates of screening (27.6%), while the rate for White children was 39.7%. The rate for other/multiracial children with ASD was 39.8%.

The lowest rates of screening occurred in the youngest children, at the 3-year visit.

The researchers analyzed data from 63,829 well-child visits between January 2016 and December 2019, collected from the large primary care database PEDSnet.
 

Photoscreening vs. acuity screening

The authors pointed out that children with ASD are less likely to complete a vision test, which can be problematic in a busy primary care office.

“Children with ASD were significantly less likely to have at least one completed vision screening (43.2%) compared with children without ASD (72.1%; P <. 01),” the authors wrote, “with only 6.9% of children with ASD having had two or more vision screenings compared with 22.3% of children without ASD.”

The researchers saw higher vision test completion rates with photoscreening, using a sophisticated camera, compared with acuity screening, which uses a wall chart and requires responses.

Less patient participation is required for photoscreening and it can be done in less than 2 minutes.

If ability to complete the vision tests is a concern, the authors wrote, photoscreening may be a better solution.
 

Photoscreening takes 90 seconds

“Photoscreening has high sensitivity in detecting ocular conditions in children with ASD and has an average screening time of 90 seconds, and [it has] been validated in both children with ASD and developmental delays,” the authors wrote.

Andrew Adesman, MD, chief of developmental and behavioral pediatrics at Cohen Children’s Medical Center in New Hyde Park, N.Y., said the authors of this study quantify the gap between need and reality for vision tests for those with ASD.

“Other studies have shown that children on the autism spectrum have more than three times greater risk of having eye disease or vision problems,” he said in an interview. “You’ve got a high-risk population in need of assessment and the likelihood of them getting an assessment is much reduced.”

He said in addition to attention problems in taking the test, vision screening may get lost in the plethora of concerns parents want to talk about in well-child visits.

“If you’re the parent of a child with developmental delays, language delays, poor social engagement, there are a multitude of things the visit could be focused on and it may be that vision screening possibly gets compromised or not done,” Dr. Adesman said.

That, he said, may be a focus area for improving the screening numbers.

Neither parents nor providers should forget that vision screening is important, despite the myriad other issues to address, he said. “They don’t have to take a long time.”

When it comes to vision problems and children, “the earlier they’re identified the better,” Dr. Adesman says, particularly to identify the need for eye muscle surgery or corrective lenses, the two major interventions for strabismus or refractive error.

“If those problems are significant and go untreated, there’s a risk of loss of vision in the affected eye,” he said.
 

Reimbursement concerns for photoscreening

This study strongly supports the use of routine photoscreening to help eliminate the vision screening gap in children with ASD, the authors wrote.

They noted, however, that would require insurance reimbursement for primary care practices to effectively use that screening.

The researchers advised, “Providers treating patients with race, ethnicity, region, or age categories that reduce the adjusted odds of photoscreening can take steps in their practices to address these disparities, particularly in children with ASD.”

The study authors and Dr. Adesman reported no relevant financial relationships.

Children with autism spectrum disorder (ASD) are significantly less likely to have vision screening at well visits for 3- to 5-year-olds than are typically developing children, researchers have found.

The report, by Kimberly Hoover, MD, of Thomas Jefferson University in Philadelphia, and colleagues, was published online in Pediatrics.

While 59.9% of children without ASD got vision screening in these visits, only 36.5% of children with ASD got the screening. Both screening rates miss the mark set by American Academy of Pediatrics guidelines.

The AAP recommends “annual instrument-based vision screening, if available, at well visits for children starting at age 12 months to 3 years, and direct visual acuity testing beginning at 4 years of age. However, in children with developmental delays, the AAP recommends instrument-based screening, such as photoscreening, as a useful alternative at any age.”
 

Racial, age disparities as well

Racial disparities were evident in the data as well. Of the children who had ASD, Black children had the lowest rates of screening (27.6%), while the rate for White children was 39.7%. The rate for other/multiracial children with ASD was 39.8%.

The lowest rates of screening occurred in the youngest children, at the 3-year visit.

The researchers analyzed data from 63,829 well-child visits between January 2016 and December 2019, collected from the large primary care database PEDSnet.
 

Photoscreening vs. acuity screening

The authors pointed out that children with ASD are less likely to complete a vision test, which can be problematic in a busy primary care office.

“Children with ASD were significantly less likely to have at least one completed vision screening (43.2%) compared with children without ASD (72.1%; P <. 01),” the authors wrote, “with only 6.9% of children with ASD having had two or more vision screenings compared with 22.3% of children without ASD.”

The researchers saw higher vision test completion rates with photoscreening, using a sophisticated camera, compared with acuity screening, which uses a wall chart and requires responses.

Less patient participation is required for photoscreening and it can be done in less than 2 minutes.

If ability to complete the vision tests is a concern, the authors wrote, photoscreening may be a better solution.
 

Photoscreening takes 90 seconds

“Photoscreening has high sensitivity in detecting ocular conditions in children with ASD and has an average screening time of 90 seconds, and [it has] been validated in both children with ASD and developmental delays,” the authors wrote.

Andrew Adesman, MD, chief of developmental and behavioral pediatrics at Cohen Children’s Medical Center in New Hyde Park, N.Y., said the authors of this study quantify the gap between need and reality for vision tests for those with ASD.

“Other studies have shown that children on the autism spectrum have more than three times greater risk of having eye disease or vision problems,” he said in an interview. “You’ve got a high-risk population in need of assessment and the likelihood of them getting an assessment is much reduced.”

He said in addition to attention problems in taking the test, vision screening may get lost in the plethora of concerns parents want to talk about in well-child visits.

“If you’re the parent of a child with developmental delays, language delays, poor social engagement, there are a multitude of things the visit could be focused on and it may be that vision screening possibly gets compromised or not done,” Dr. Adesman said.

That, he said, may be a focus area for improving the screening numbers.

Neither parents nor providers should forget that vision screening is important, despite the myriad other issues to address, he said. “They don’t have to take a long time.”

When it comes to vision problems and children, “the earlier they’re identified the better,” Dr. Adesman says, particularly to identify the need for eye muscle surgery or corrective lenses, the two major interventions for strabismus or refractive error.

“If those problems are significant and go untreated, there’s a risk of loss of vision in the affected eye,” he said.
 

Reimbursement concerns for photoscreening

This study strongly supports the use of routine photoscreening to help eliminate the vision screening gap in children with ASD, the authors wrote.

They noted, however, that would require insurance reimbursement for primary care practices to effectively use that screening.

The researchers advised, “Providers treating patients with race, ethnicity, region, or age categories that reduce the adjusted odds of photoscreening can take steps in their practices to address these disparities, particularly in children with ASD.”

The study authors and Dr. Adesman reported no relevant financial relationships.

Children with autism spectrum disorder (ASD) are significantly less likely to have vision screening at well visits for 3- to 5-year-olds than are typically developing children, researchers have found.

The report, by Kimberly Hoover, MD, of Thomas Jefferson University in Philadelphia, and colleagues, was published online in Pediatrics.

While 59.9% of children without ASD got vision screening in these visits, only 36.5% of children with ASD got the screening. Both screening rates miss the mark set by American Academy of Pediatrics guidelines.

The AAP recommends “annual instrument-based vision screening, if available, at well visits for children starting at age 12 months to 3 years, and direct visual acuity testing beginning at 4 years of age. However, in children with developmental delays, the AAP recommends instrument-based screening, such as photoscreening, as a useful alternative at any age.”
 

Racial, age disparities as well

Racial disparities were evident in the data as well. Of the children who had ASD, Black children had the lowest rates of screening (27.6%), while the rate for White children was 39.7%. The rate for other/multiracial children with ASD was 39.8%.

The lowest rates of screening occurred in the youngest children, at the 3-year visit.

The researchers analyzed data from 63,829 well-child visits between January 2016 and December 2019, collected from the large primary care database PEDSnet.
 

Photoscreening vs. acuity screening

The authors pointed out that children with ASD are less likely to complete a vision test, which can be problematic in a busy primary care office.

“Children with ASD were significantly less likely to have at least one completed vision screening (43.2%) compared with children without ASD (72.1%; P <. 01),” the authors wrote, “with only 6.9% of children with ASD having had two or more vision screenings compared with 22.3% of children without ASD.”

The researchers saw higher vision test completion rates with photoscreening, using a sophisticated camera, compared with acuity screening, which uses a wall chart and requires responses.

Less patient participation is required for photoscreening and it can be done in less than 2 minutes.

If ability to complete the vision tests is a concern, the authors wrote, photoscreening may be a better solution.
 

Photoscreening takes 90 seconds

“Photoscreening has high sensitivity in detecting ocular conditions in children with ASD and has an average screening time of 90 seconds, and [it has] been validated in both children with ASD and developmental delays,” the authors wrote.

Andrew Adesman, MD, chief of developmental and behavioral pediatrics at Cohen Children’s Medical Center in New Hyde Park, N.Y., said the authors of this study quantify the gap between need and reality for vision tests for those with ASD.

“Other studies have shown that children on the autism spectrum have more than three times greater risk of having eye disease or vision problems,” he said in an interview. “You’ve got a high-risk population in need of assessment and the likelihood of them getting an assessment is much reduced.”

He said in addition to attention problems in taking the test, vision screening may get lost in the plethora of concerns parents want to talk about in well-child visits.

“If you’re the parent of a child with developmental delays, language delays, poor social engagement, there are a multitude of things the visit could be focused on and it may be that vision screening possibly gets compromised or not done,” Dr. Adesman said.

That, he said, may be a focus area for improving the screening numbers.

Neither parents nor providers should forget that vision screening is important, despite the myriad other issues to address, he said. “They don’t have to take a long time.”

When it comes to vision problems and children, “the earlier they’re identified the better,” Dr. Adesman says, particularly to identify the need for eye muscle surgery or corrective lenses, the two major interventions for strabismus or refractive error.

“If those problems are significant and go untreated, there’s a risk of loss of vision in the affected eye,” he said.
 

Reimbursement concerns for photoscreening

This study strongly supports the use of routine photoscreening to help eliminate the vision screening gap in children with ASD, the authors wrote.

They noted, however, that would require insurance reimbursement for primary care practices to effectively use that screening.

The researchers advised, “Providers treating patients with race, ethnicity, region, or age categories that reduce the adjusted odds of photoscreening can take steps in their practices to address these disparities, particularly in children with ASD.”

The study authors and Dr. Adesman reported no relevant financial relationships.

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

NEW ORLEANS – In two phase 3 trials, bimekizumab, a monoclonal antibody targeting two types of interleukin-17 — IL-17A and IL-17F — reduced the abscess and inflammatory nodule count better than placebo in the chronic inflammatory skin condition hidradenitis suppurativa (HS), according to results presented together during a late-breaker session at the annual meeting of the American Academy of Dermatology.

“We are very excited to add this data to what we already have around IL-17 inhibition. This clearly validates this target for the control of HS,” reported lead investigator Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston.

Ted Bosworth

The trials, called BE HEARD I and BE HEARD II, enrolled 505 and 509 patients with HS, respectively. About 50% of patients in BE HEARD I and 60% of patients in BE HEARD II had Hurley stage 3 disease, which is the most severe of the three stratifications. The remainder were in Hurley stage 2. The mean duration of HS was 8.3 and 7.1 years, respectively.

Patients in both studies were randomized to one of four groups – either to a dosing regimen of 320 mg of bimekizumab administered by subcutaneous injection or to a placebo group. Both trials comprised double-blind 16-week initial and 32-week maintenance treatment periods.

In one experimental group, bimekizumab was given once every 2 weeks for the full course of the 48-week study (Q2W/Q2W). In another, patients started on the every-2-week schedule for 16 weeks and then were switched to every-4-week dosing (Q2W/Q4W). In the third group, patients started and remained on the every-4-week schedule (Q4W/Q4W). Patients in a fourth group started on placebo and switched at 16 weeks to the every-2-week bimekizumab schedule (placebo/Q2W).
 

Results at primary endpoint

The primary endpoint was HiSCR50, signifying a 50% reduction from baseline in abscess and inflammatory nodule count on the Hidradenitis Suppurativa Clinical Response (HiSCR) assessment tool. At 16 weeks, the initial Q2W dose in two of the groups outperformed the placebo in both BE HEARD I (47.8% vs. 28.7%) and BE HEARD II (52.0% vs. 32.2%). The response rates in the Q4W arm in BE HEARD I (45.3%) and BE HEARD II (53.8%) were also higher than the placebo, but the difference was only significant in BE HEARD II.

At 48 weeks, the proportion of patients with an HiSCR50 response climbed in all groups in both trials. The patterns were generally the same with slightly higher numerical responses among the groups that received the every-2-week dosing schedule relative to the every-4-week schedule.

In BE HEARD I at 48 weeks, the HiSCR50 response rate was about 60% for those who started and remained on every-2-week bimekizumab (Q2W/Q2W) or were switched at 16 weeks to every-4-week bimekizumab (Q2W/Q4W). For those who started and remained on every-4-week bimekizumab and the group started on placebo and switched to every-2-week bimekizumab, the response rates were 52.7% and 45.3%, respectively.  

In BE HEARD II, the HiSCR50 response rates were higher in all groups, including the placebo, and the patterns of response were similar at 48 weeks. Most patients reached the HiSCR50 response – 79.8% (Q2W/Q2W), 78.4% (Q2W/Q4W), 76.7% (Q4W/Q4W), and 65.9 % (placebo/Q2W) of patients.

It is notable that, although there was rapid increase in the proportion of placebo patients reaching HiSCR50 after the switch at 16 weeks, there appeared to be an advantage at 48 weeks for starting on full-dose bimekizumab over starting on placebo.

In this trial, patients were listed as nonresponders if they received antibiotics at any time and for any reason after randomization. This might have concealed an even greater benefit of bimekizumab, Dr. Kimball said, but the study design element was considered necessary to isolate the activity of the study drug.

“In future HS trials, it will be helpful to address the difficulty of handling the impact of antibiotics and pain medications [in assessing results],” Dr. Kimball said.

Clinically meaningful secondary endpoint

For HS patients, the secondary endpoint of HiSCR75 might be considered the most meaningful, according to Dr. Kimball. She said that this higher bar not only documents a higher level of efficacy but correlates with meaningful improvement in quality of life. In the two trials combined, more than 55% of patients on continuous bimekizumab achieved HiSCR75 at week 48 in the observed case analysis, according to a news release from biopharmaceutical company UCB, developer of bimekizumab.

In BE HEARD I, the HiSCR75 rates were 33.4% and 24.7% for the every-2-week and every-4-week bimekizumab doses, respectively. The 33.4% response was statistically superior to placebo (18.4%). In BE HEARD II, both the every-2-week dose (35.7%) and the every-4-week dose (33.7%) were superior to the 15.6% response in placebo patients.

The improvements in quality of life as measured with the Dermatology Life Quality Index (DLQI), reflected the changes in disease activity. Relative to about a 3-point reduction from baseline in the placebo groups of the two trials, the 5-point reduction for either the 2-week or 4-week bimekizumab groups in each clinical trial were highly significant, Dr. Kimball said.

Bimekizumab was relatively well tolerated, although it shares the increased risk for candidiasis observed with this agent when used in psoriasis and with other IL-17 inhibitors, such as secukinumab (Cosentyx), in general. The risk of candidiasis appeared to be dose related, but cases were generally mild and easily managed, according to Dr. Kimball. She noted that only three patients discontinued treatment for this reason. Discontinuations for a treatment-related adverse event overall was less than 4% at 16 weeks.

This is only the third phase 3 trial ever completed in patients with HS. In fact, Dr. Kimball has led all of the phase 3 trials so far, including clinical studies of adalimumab (Humira), published in 2016, and of secukinumab, published earlier this year. All were positive studies.

“This is amazing news for our patients,” Dr. Kimball said. HS remains a challenging disease, even with a growing number of options showing benefit in large studies, she said, and the high rate of response, particularly at the level of HiSCR75, “is a huge milestone for what we can achieve.”
 

Multiple treatment options important

Her assessment was echoed by other experts, including Christopher J. Sayed, MD, an associate professor of dermatology at the University of North Carolina at Chapel Hill, who publishes frequently about this disease.

“It is incredibly exciting to see the strong phase 3 data on bimekizumab, particularly the deep responses at the HiSCR75 in a majority of patients after the first year,” he said.

Importantly, he does not see the growing array of treatment options as necessarily competitive for a disease with heterogeneous manifestations and variable responses to any one agent.

“While this may be a major step forward, it will still be critical to see more drugs come along for those who do not respond fully enough or have comorbidities that prevent the use of IL-17 and TNF [tumor necrosis factor] antagonists,” he said.

Bimekizumab is not approved for any indication in the United States; it is approved for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy in the EU/EEA, where it is marketed as Bimzelx, according to UCB. Dr. Kimball reports financial relationships with AbbVie, Janssen, Kymera, Lilly, Novartis, Pfizer, and UCB. Dr. Sayed reports financial relationships with AbbVie, InflaRx, and UCB.
 

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

NEW ORLEANS – In two phase 3 trials, bimekizumab, a monoclonal antibody targeting two types of interleukin-17 — IL-17A and IL-17F — reduced the abscess and inflammatory nodule count better than placebo in the chronic inflammatory skin condition hidradenitis suppurativa (HS), according to results presented together during a late-breaker session at the annual meeting of the American Academy of Dermatology.

“We are very excited to add this data to what we already have around IL-17 inhibition. This clearly validates this target for the control of HS,” reported lead investigator Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston.

Ted Bosworth

The trials, called BE HEARD I and BE HEARD II, enrolled 505 and 509 patients with HS, respectively. About 50% of patients in BE HEARD I and 60% of patients in BE HEARD II had Hurley stage 3 disease, which is the most severe of the three stratifications. The remainder were in Hurley stage 2. The mean duration of HS was 8.3 and 7.1 years, respectively.

Patients in both studies were randomized to one of four groups – either to a dosing regimen of 320 mg of bimekizumab administered by subcutaneous injection or to a placebo group. Both trials comprised double-blind 16-week initial and 32-week maintenance treatment periods.

In one experimental group, bimekizumab was given once every 2 weeks for the full course of the 48-week study (Q2W/Q2W). In another, patients started on the every-2-week schedule for 16 weeks and then were switched to every-4-week dosing (Q2W/Q4W). In the third group, patients started and remained on the every-4-week schedule (Q4W/Q4W). Patients in a fourth group started on placebo and switched at 16 weeks to the every-2-week bimekizumab schedule (placebo/Q2W).
 

Results at primary endpoint

The primary endpoint was HiSCR50, signifying a 50% reduction from baseline in abscess and inflammatory nodule count on the Hidradenitis Suppurativa Clinical Response (HiSCR) assessment tool. At 16 weeks, the initial Q2W dose in two of the groups outperformed the placebo in both BE HEARD I (47.8% vs. 28.7%) and BE HEARD II (52.0% vs. 32.2%). The response rates in the Q4W arm in BE HEARD I (45.3%) and BE HEARD II (53.8%) were also higher than the placebo, but the difference was only significant in BE HEARD II.

At 48 weeks, the proportion of patients with an HiSCR50 response climbed in all groups in both trials. The patterns were generally the same with slightly higher numerical responses among the groups that received the every-2-week dosing schedule relative to the every-4-week schedule.

In BE HEARD I at 48 weeks, the HiSCR50 response rate was about 60% for those who started and remained on every-2-week bimekizumab (Q2W/Q2W) or were switched at 16 weeks to every-4-week bimekizumab (Q2W/Q4W). For those who started and remained on every-4-week bimekizumab and the group started on placebo and switched to every-2-week bimekizumab, the response rates were 52.7% and 45.3%, respectively.  

In BE HEARD II, the HiSCR50 response rates were higher in all groups, including the placebo, and the patterns of response were similar at 48 weeks. Most patients reached the HiSCR50 response – 79.8% (Q2W/Q2W), 78.4% (Q2W/Q4W), 76.7% (Q4W/Q4W), and 65.9 % (placebo/Q2W) of patients.

It is notable that, although there was rapid increase in the proportion of placebo patients reaching HiSCR50 after the switch at 16 weeks, there appeared to be an advantage at 48 weeks for starting on full-dose bimekizumab over starting on placebo.

In this trial, patients were listed as nonresponders if they received antibiotics at any time and for any reason after randomization. This might have concealed an even greater benefit of bimekizumab, Dr. Kimball said, but the study design element was considered necessary to isolate the activity of the study drug.

“In future HS trials, it will be helpful to address the difficulty of handling the impact of antibiotics and pain medications [in assessing results],” Dr. Kimball said.

Clinically meaningful secondary endpoint

For HS patients, the secondary endpoint of HiSCR75 might be considered the most meaningful, according to Dr. Kimball. She said that this higher bar not only documents a higher level of efficacy but correlates with meaningful improvement in quality of life. In the two trials combined, more than 55% of patients on continuous bimekizumab achieved HiSCR75 at week 48 in the observed case analysis, according to a news release from biopharmaceutical company UCB, developer of bimekizumab.

In BE HEARD I, the HiSCR75 rates were 33.4% and 24.7% for the every-2-week and every-4-week bimekizumab doses, respectively. The 33.4% response was statistically superior to placebo (18.4%). In BE HEARD II, both the every-2-week dose (35.7%) and the every-4-week dose (33.7%) were superior to the 15.6% response in placebo patients.

The improvements in quality of life as measured with the Dermatology Life Quality Index (DLQI), reflected the changes in disease activity. Relative to about a 3-point reduction from baseline in the placebo groups of the two trials, the 5-point reduction for either the 2-week or 4-week bimekizumab groups in each clinical trial were highly significant, Dr. Kimball said.

Bimekizumab was relatively well tolerated, although it shares the increased risk for candidiasis observed with this agent when used in psoriasis and with other IL-17 inhibitors, such as secukinumab (Cosentyx), in general. The risk of candidiasis appeared to be dose related, but cases were generally mild and easily managed, according to Dr. Kimball. She noted that only three patients discontinued treatment for this reason. Discontinuations for a treatment-related adverse event overall was less than 4% at 16 weeks.

This is only the third phase 3 trial ever completed in patients with HS. In fact, Dr. Kimball has led all of the phase 3 trials so far, including clinical studies of adalimumab (Humira), published in 2016, and of secukinumab, published earlier this year. All were positive studies.

“This is amazing news for our patients,” Dr. Kimball said. HS remains a challenging disease, even with a growing number of options showing benefit in large studies, she said, and the high rate of response, particularly at the level of HiSCR75, “is a huge milestone for what we can achieve.”
 

Multiple treatment options important

Her assessment was echoed by other experts, including Christopher J. Sayed, MD, an associate professor of dermatology at the University of North Carolina at Chapel Hill, who publishes frequently about this disease.

“It is incredibly exciting to see the strong phase 3 data on bimekizumab, particularly the deep responses at the HiSCR75 in a majority of patients after the first year,” he said.

Importantly, he does not see the growing array of treatment options as necessarily competitive for a disease with heterogeneous manifestations and variable responses to any one agent.

“While this may be a major step forward, it will still be critical to see more drugs come along for those who do not respond fully enough or have comorbidities that prevent the use of IL-17 and TNF [tumor necrosis factor] antagonists,” he said.

Bimekizumab is not approved for any indication in the United States; it is approved for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy in the EU/EEA, where it is marketed as Bimzelx, according to UCB. Dr. Kimball reports financial relationships with AbbVie, Janssen, Kymera, Lilly, Novartis, Pfizer, and UCB. Dr. Sayed reports financial relationships with AbbVie, InflaRx, and UCB.
 

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

NEW ORLEANS – In two phase 3 trials, bimekizumab, a monoclonal antibody targeting two types of interleukin-17 — IL-17A and IL-17F — reduced the abscess and inflammatory nodule count better than placebo in the chronic inflammatory skin condition hidradenitis suppurativa (HS), according to results presented together during a late-breaker session at the annual meeting of the American Academy of Dermatology.

“We are very excited to add this data to what we already have around IL-17 inhibition. This clearly validates this target for the control of HS,” reported lead investigator Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston.

Ted Bosworth

The trials, called BE HEARD I and BE HEARD II, enrolled 505 and 509 patients with HS, respectively. About 50% of patients in BE HEARD I and 60% of patients in BE HEARD II had Hurley stage 3 disease, which is the most severe of the three stratifications. The remainder were in Hurley stage 2. The mean duration of HS was 8.3 and 7.1 years, respectively.

Patients in both studies were randomized to one of four groups – either to a dosing regimen of 320 mg of bimekizumab administered by subcutaneous injection or to a placebo group. Both trials comprised double-blind 16-week initial and 32-week maintenance treatment periods.

In one experimental group, bimekizumab was given once every 2 weeks for the full course of the 48-week study (Q2W/Q2W). In another, patients started on the every-2-week schedule for 16 weeks and then were switched to every-4-week dosing (Q2W/Q4W). In the third group, patients started and remained on the every-4-week schedule (Q4W/Q4W). Patients in a fourth group started on placebo and switched at 16 weeks to the every-2-week bimekizumab schedule (placebo/Q2W).
 

Results at primary endpoint

The primary endpoint was HiSCR50, signifying a 50% reduction from baseline in abscess and inflammatory nodule count on the Hidradenitis Suppurativa Clinical Response (HiSCR) assessment tool. At 16 weeks, the initial Q2W dose in two of the groups outperformed the placebo in both BE HEARD I (47.8% vs. 28.7%) and BE HEARD II (52.0% vs. 32.2%). The response rates in the Q4W arm in BE HEARD I (45.3%) and BE HEARD II (53.8%) were also higher than the placebo, but the difference was only significant in BE HEARD II.

At 48 weeks, the proportion of patients with an HiSCR50 response climbed in all groups in both trials. The patterns were generally the same with slightly higher numerical responses among the groups that received the every-2-week dosing schedule relative to the every-4-week schedule.

In BE HEARD I at 48 weeks, the HiSCR50 response rate was about 60% for those who started and remained on every-2-week bimekizumab (Q2W/Q2W) or were switched at 16 weeks to every-4-week bimekizumab (Q2W/Q4W). For those who started and remained on every-4-week bimekizumab and the group started on placebo and switched to every-2-week bimekizumab, the response rates were 52.7% and 45.3%, respectively.  

In BE HEARD II, the HiSCR50 response rates were higher in all groups, including the placebo, and the patterns of response were similar at 48 weeks. Most patients reached the HiSCR50 response – 79.8% (Q2W/Q2W), 78.4% (Q2W/Q4W), 76.7% (Q4W/Q4W), and 65.9 % (placebo/Q2W) of patients.

It is notable that, although there was rapid increase in the proportion of placebo patients reaching HiSCR50 after the switch at 16 weeks, there appeared to be an advantage at 48 weeks for starting on full-dose bimekizumab over starting on placebo.

In this trial, patients were listed as nonresponders if they received antibiotics at any time and for any reason after randomization. This might have concealed an even greater benefit of bimekizumab, Dr. Kimball said, but the study design element was considered necessary to isolate the activity of the study drug.

“In future HS trials, it will be helpful to address the difficulty of handling the impact of antibiotics and pain medications [in assessing results],” Dr. Kimball said.

Clinically meaningful secondary endpoint

For HS patients, the secondary endpoint of HiSCR75 might be considered the most meaningful, according to Dr. Kimball. She said that this higher bar not only documents a higher level of efficacy but correlates with meaningful improvement in quality of life. In the two trials combined, more than 55% of patients on continuous bimekizumab achieved HiSCR75 at week 48 in the observed case analysis, according to a news release from biopharmaceutical company UCB, developer of bimekizumab.

In BE HEARD I, the HiSCR75 rates were 33.4% and 24.7% for the every-2-week and every-4-week bimekizumab doses, respectively. The 33.4% response was statistically superior to placebo (18.4%). In BE HEARD II, both the every-2-week dose (35.7%) and the every-4-week dose (33.7%) were superior to the 15.6% response in placebo patients.

The improvements in quality of life as measured with the Dermatology Life Quality Index (DLQI), reflected the changes in disease activity. Relative to about a 3-point reduction from baseline in the placebo groups of the two trials, the 5-point reduction for either the 2-week or 4-week bimekizumab groups in each clinical trial were highly significant, Dr. Kimball said.

Bimekizumab was relatively well tolerated, although it shares the increased risk for candidiasis observed with this agent when used in psoriasis and with other IL-17 inhibitors, such as secukinumab (Cosentyx), in general. The risk of candidiasis appeared to be dose related, but cases were generally mild and easily managed, according to Dr. Kimball. She noted that only three patients discontinued treatment for this reason. Discontinuations for a treatment-related adverse event overall was less than 4% at 16 weeks.

This is only the third phase 3 trial ever completed in patients with HS. In fact, Dr. Kimball has led all of the phase 3 trials so far, including clinical studies of adalimumab (Humira), published in 2016, and of secukinumab, published earlier this year. All were positive studies.

“This is amazing news for our patients,” Dr. Kimball said. HS remains a challenging disease, even with a growing number of options showing benefit in large studies, she said, and the high rate of response, particularly at the level of HiSCR75, “is a huge milestone for what we can achieve.”
 

Multiple treatment options important

Her assessment was echoed by other experts, including Christopher J. Sayed, MD, an associate professor of dermatology at the University of North Carolina at Chapel Hill, who publishes frequently about this disease.

“It is incredibly exciting to see the strong phase 3 data on bimekizumab, particularly the deep responses at the HiSCR75 in a majority of patients after the first year,” he said.

Importantly, he does not see the growing array of treatment options as necessarily competitive for a disease with heterogeneous manifestations and variable responses to any one agent.

“While this may be a major step forward, it will still be critical to see more drugs come along for those who do not respond fully enough or have comorbidities that prevent the use of IL-17 and TNF [tumor necrosis factor] antagonists,” he said.

Bimekizumab is not approved for any indication in the United States; it is approved for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy in the EU/EEA, where it is marketed as Bimzelx, according to UCB. Dr. Kimball reports financial relationships with AbbVie, Janssen, Kymera, Lilly, Novartis, Pfizer, and UCB. Dr. Sayed reports financial relationships with AbbVie, InflaRx, and UCB.
 

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

DENVER – Initiating exercise therapy early on in people who develop symptoms of knee osteoarthritis – even within their first year of pain or reduced function – is associated with modestly lower pain scores and modestly better function than in those whose symptoms have lasted longer, according to a study presented at the OARSI 2023 World Congress.

Although the benefits of exercise therapy for advanced knee osteoarthritis had already been well established, this study looked specifically at benefits from exercise therapy earlier on, in patients with a shorter duration of symptoms.

“Exercise indeed seems especially beneficial in patients with shorter symptom duration and should therefore be encouraged at first symptom presentation,” Marienke van Middelkoop, PhD, of Erasmus MC Medical University in Rotterdam, the Netherlands, told attendees at the meeting, sponsored by Osteoarthritis Research Society International. “It is, however, still a challenge how we can identify patients but also how we can motivate these patients with early symptoms of osteoarthritis.” She noted that a separate pilot study had experienced difficulty recruiting people with short-term symptom duration.

The researchers compared the effect of exercise therapy and no exercise among adults at least 45 years old with knee osteoarthritis, relying on individual participant data from the STEER OA study, a meta-analysis of 31 studies that involved 4,241 participants. After excluding studies that didn’t report symptom duration, lacked a control group or consent, or focused on hip osteoarthritis, the researchers ended up with 10 studies involving 1,895 participants. These participants were stratified based on the duration of their symptoms: up to 1 year (14.4%), 1-2 years (11%), and 2 years or longer (74%).

About two-thirds of the participants were women (65.9%), with an average age of 65 years and an average body mass index (BMI) of 30.7 kg/m². Any land-based or water-based therapeutic exercise counted for the 62% of participants in the intervention group, while the control group had no exercise. Outcomes were assessed based on self-reported pain or physical function at short-term and long-term follow-up, which were as close as possible to 3 months for short-term and the closest date to 12 months for longer term. At baseline, the participants reported an average pain score of 41.7 on a 0-to-100 scale and an average physical function score of 37.4 on a 0-to-100 scale where lower scores indicate better function.

Among those doing exercise therapy, average pain scores dropped 4.56 points in the short term and 7.43 points in the long term. Short-term and long-term pain scores were lower among those whose symptom durations were shorter. For example, those with symptoms for less than a year reported a short-term pain score of 29, compared with 30 for those with 1-2 years of pain and 32 for those with at least 2 years of pain. Results were similar for long-term pain (a score of 26, compared with 28 and 33, respectively).

Participants engaging in exercise therapy also improved average function scores, with a pattern of improvement that was similar to pain scores based on patients’ symptom duration. The average short-term function score was 26 among those with less than a year of symptoms, compared with 28 for those with symptoms for 1-2 years, and 30 for those with symptoms for at least 2 years. Longer-term function scores were 21, 24, and 29, respectively, based on increasing symptom durations.

Chris Yun Lane, PT, DPT, a physical therapist and a fourth-year PhD student at the University of North Carolina at Chapel Hill, was not surprised at the exercise benefit given the extensive evidence already showing that exercise is beneficial for patients with osteoarthritis whose symptoms have lasted longer.

“Just spending a little bit of time on education, designing kind of simple exercise programs, such as walking programs, can be very helpful,” Dr. Lane said in an interview. “Of course, some of it is dependent on the patient itself, but strengthening range of motion is often very helpful.” Dr. Lane said it’s particularly important for physicians and physical therapists to emphasize the importance of exercise to their patients because that guidance doesn’t always occur as often as it should.

Ron Ellis Jr., DO, MBA, chief strategy officer of Pacira BioSciences in Tampa, Fla., noted that a lot of patients with knee osteoarthritis have weakness in their quads, so quad strengthening is “a typical part of our improvement program for patients with osteoarthritis,” he said in an interview. Dr. Ellis also referenced a session he attended the previous day that showed exercise results in reduced inflammation.

“So you may not have weight loss, but you can lower the inflammatory state of the overall body and of the specific joints,” Dr. Ellis said, “so that would support [this study’s] conclusion.”

The STEER OA study was funded by the Chartered Society of Physiotherapy Charitable Trust and the National Institute for Health Research School of Primary Care Research. Dr. van Middelkoop and Dr. Lane both reported having no relevant financial relationships.

DENVER – Initiating exercise therapy early on in people who develop symptoms of knee osteoarthritis – even within their first year of pain or reduced function – is associated with modestly lower pain scores and modestly better function than in those whose symptoms have lasted longer, according to a study presented at the OARSI 2023 World Congress.

Although the benefits of exercise therapy for advanced knee osteoarthritis had already been well established, this study looked specifically at benefits from exercise therapy earlier on, in patients with a shorter duration of symptoms.

“Exercise indeed seems especially beneficial in patients with shorter symptom duration and should therefore be encouraged at first symptom presentation,” Marienke van Middelkoop, PhD, of Erasmus MC Medical University in Rotterdam, the Netherlands, told attendees at the meeting, sponsored by Osteoarthritis Research Society International. “It is, however, still a challenge how we can identify patients but also how we can motivate these patients with early symptoms of osteoarthritis.” She noted that a separate pilot study had experienced difficulty recruiting people with short-term symptom duration.

The researchers compared the effect of exercise therapy and no exercise among adults at least 45 years old with knee osteoarthritis, relying on individual participant data from the STEER OA study, a meta-analysis of 31 studies that involved 4,241 participants. After excluding studies that didn’t report symptom duration, lacked a control group or consent, or focused on hip osteoarthritis, the researchers ended up with 10 studies involving 1,895 participants. These participants were stratified based on the duration of their symptoms: up to 1 year (14.4%), 1-2 years (11%), and 2 years or longer (74%).

About two-thirds of the participants were women (65.9%), with an average age of 65 years and an average body mass index (BMI) of 30.7 kg/m². Any land-based or water-based therapeutic exercise counted for the 62% of participants in the intervention group, while the control group had no exercise. Outcomes were assessed based on self-reported pain or physical function at short-term and long-term follow-up, which were as close as possible to 3 months for short-term and the closest date to 12 months for longer term. At baseline, the participants reported an average pain score of 41.7 on a 0-to-100 scale and an average physical function score of 37.4 on a 0-to-100 scale where lower scores indicate better function.

Among those doing exercise therapy, average pain scores dropped 4.56 points in the short term and 7.43 points in the long term. Short-term and long-term pain scores were lower among those whose symptom durations were shorter. For example, those with symptoms for less than a year reported a short-term pain score of 29, compared with 30 for those with 1-2 years of pain and 32 for those with at least 2 years of pain. Results were similar for long-term pain (a score of 26, compared with 28 and 33, respectively).

Participants engaging in exercise therapy also improved average function scores, with a pattern of improvement that was similar to pain scores based on patients’ symptom duration. The average short-term function score was 26 among those with less than a year of symptoms, compared with 28 for those with symptoms for 1-2 years, and 30 for those with symptoms for at least 2 years. Longer-term function scores were 21, 24, and 29, respectively, based on increasing symptom durations.

Chris Yun Lane, PT, DPT, a physical therapist and a fourth-year PhD student at the University of North Carolina at Chapel Hill, was not surprised at the exercise benefit given the extensive evidence already showing that exercise is beneficial for patients with osteoarthritis whose symptoms have lasted longer.

“Just spending a little bit of time on education, designing kind of simple exercise programs, such as walking programs, can be very helpful,” Dr. Lane said in an interview. “Of course, some of it is dependent on the patient itself, but strengthening range of motion is often very helpful.” Dr. Lane said it’s particularly important for physicians and physical therapists to emphasize the importance of exercise to their patients because that guidance doesn’t always occur as often as it should.

Ron Ellis Jr., DO, MBA, chief strategy officer of Pacira BioSciences in Tampa, Fla., noted that a lot of patients with knee osteoarthritis have weakness in their quads, so quad strengthening is “a typical part of our improvement program for patients with osteoarthritis,” he said in an interview. Dr. Ellis also referenced a session he attended the previous day that showed exercise results in reduced inflammation.

“So you may not have weight loss, but you can lower the inflammatory state of the overall body and of the specific joints,” Dr. Ellis said, “so that would support [this study’s] conclusion.”

The STEER OA study was funded by the Chartered Society of Physiotherapy Charitable Trust and the National Institute for Health Research School of Primary Care Research. Dr. van Middelkoop and Dr. Lane both reported having no relevant financial relationships.

DENVER – Initiating exercise therapy early on in people who develop symptoms of knee osteoarthritis – even within their first year of pain or reduced function – is associated with modestly lower pain scores and modestly better function than in those whose symptoms have lasted longer, according to a study presented at the OARSI 2023 World Congress.

Although the benefits of exercise therapy for advanced knee osteoarthritis had already been well established, this study looked specifically at benefits from exercise therapy earlier on, in patients with a shorter duration of symptoms.

“Exercise indeed seems especially beneficial in patients with shorter symptom duration and should therefore be encouraged at first symptom presentation,” Marienke van Middelkoop, PhD, of Erasmus MC Medical University in Rotterdam, the Netherlands, told attendees at the meeting, sponsored by Osteoarthritis Research Society International. “It is, however, still a challenge how we can identify patients but also how we can motivate these patients with early symptoms of osteoarthritis.” She noted that a separate pilot study had experienced difficulty recruiting people with short-term symptom duration.

The researchers compared the effect of exercise therapy and no exercise among adults at least 45 years old with knee osteoarthritis, relying on individual participant data from the STEER OA study, a meta-analysis of 31 studies that involved 4,241 participants. After excluding studies that didn’t report symptom duration, lacked a control group or consent, or focused on hip osteoarthritis, the researchers ended up with 10 studies involving 1,895 participants. These participants were stratified based on the duration of their symptoms: up to 1 year (14.4%), 1-2 years (11%), and 2 years or longer (74%).

About two-thirds of the participants were women (65.9%), with an average age of 65 years and an average body mass index (BMI) of 30.7 kg/m². Any land-based or water-based therapeutic exercise counted for the 62% of participants in the intervention group, while the control group had no exercise. Outcomes were assessed based on self-reported pain or physical function at short-term and long-term follow-up, which were as close as possible to 3 months for short-term and the closest date to 12 months for longer term. At baseline, the participants reported an average pain score of 41.7 on a 0-to-100 scale and an average physical function score of 37.4 on a 0-to-100 scale where lower scores indicate better function.

Among those doing exercise therapy, average pain scores dropped 4.56 points in the short term and 7.43 points in the long term. Short-term and long-term pain scores were lower among those whose symptom durations were shorter. For example, those with symptoms for less than a year reported a short-term pain score of 29, compared with 30 for those with 1-2 years of pain and 32 for those with at least 2 years of pain. Results were similar for long-term pain (a score of 26, compared with 28 and 33, respectively).

Participants engaging in exercise therapy also improved average function scores, with a pattern of improvement that was similar to pain scores based on patients’ symptom duration. The average short-term function score was 26 among those with less than a year of symptoms, compared with 28 for those with symptoms for 1-2 years, and 30 for those with symptoms for at least 2 years. Longer-term function scores were 21, 24, and 29, respectively, based on increasing symptom durations.

Chris Yun Lane, PT, DPT, a physical therapist and a fourth-year PhD student at the University of North Carolina at Chapel Hill, was not surprised at the exercise benefit given the extensive evidence already showing that exercise is beneficial for patients with osteoarthritis whose symptoms have lasted longer.

“Just spending a little bit of time on education, designing kind of simple exercise programs, such as walking programs, can be very helpful,” Dr. Lane said in an interview. “Of course, some of it is dependent on the patient itself, but strengthening range of motion is often very helpful.” Dr. Lane said it’s particularly important for physicians and physical therapists to emphasize the importance of exercise to their patients because that guidance doesn’t always occur as often as it should.

Ron Ellis Jr., DO, MBA, chief strategy officer of Pacira BioSciences in Tampa, Fla., noted that a lot of patients with knee osteoarthritis have weakness in their quads, so quad strengthening is “a typical part of our improvement program for patients with osteoarthritis,” he said in an interview. Dr. Ellis also referenced a session he attended the previous day that showed exercise results in reduced inflammation.

“So you may not have weight loss, but you can lower the inflammatory state of the overall body and of the specific joints,” Dr. Ellis said, “so that would support [this study’s] conclusion.”

The STEER OA study was funded by the Chartered Society of Physiotherapy Charitable Trust and the National Institute for Health Research School of Primary Care Research. Dr. van Middelkoop and Dr. Lane both reported having no relevant financial relationships.

Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.

The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.

copyright Sergiy Serdyuk/istockphoto.com

“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.

The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.

Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.

The findings were recently published in eClinicalMedicine.

Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”

Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.

“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”

He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.

As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.

“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”

Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
 

Particulates linked to whole-body, hip, lumbar, and femoral neck BMD

The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.

With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.

In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm² per year per 10% increase in 3-year mean nitrogen dioxide concentration.

“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.

Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”

The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.

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

Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.

The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.

copyright Sergiy Serdyuk/istockphoto.com

“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.

The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.

Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.

The findings were recently published in eClinicalMedicine.

Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”

Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.

“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”

He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.

As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.

“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”

Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
 

Particulates linked to whole-body, hip, lumbar, and femoral neck BMD

The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.

With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.

In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm² per year per 10% increase in 3-year mean nitrogen dioxide concentration.

“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.

Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”

The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.

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

Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.

The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.

copyright Sergiy Serdyuk/istockphoto.com

“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.

The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.

Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.

The findings were recently published in eClinicalMedicine.

Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”

Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.

“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”

He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.

As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.

“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”

Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
 

Particulates linked to whole-body, hip, lumbar, and femoral neck BMD

The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.

With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.

In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm² per year per 10% increase in 3-year mean nitrogen dioxide concentration.

“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.

Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”

The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.

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

Long-distance runners are often warned that they are wearing out their joints, but a new study found that running mileage, frequency, and pace were not associated with an increased risk of osteoarthritis.

Runners who had undergone knee or hip surgery or had a previous hip or knee injury that prevented running were most likely to have arthritis, researchers found. Family history of arthritis, higher body mass index (BMI), and older age were also associated with increased risk of the condition.

The study was presented at the American Academy of Orthopaedic Surgeons 2023 Annual Meeting.

It has generally been thought that running may increase risk of osteoarthritis because it puts more load on joints than walking or standing, noted Grace Hsiao-Wei Lo, MD, an assistant professor of immunology, allergy, and rheumatology at the Baylor College of Medicine, Houston, who was not involved with the work. Research in this area has yielded mixed results: A 2017 analysis of multiple studies found that competitive runners did have higher rates of arthritis than recreational runners, while another study conducted by Dr. Lo found that runners did not have an increased risk of knee osteoarthritis, compared with nonrunners. A 2018 study showed that marathon runners had lower instances of arthritis, compared with the general population.

In this new study, researchers surveyed 3,804 runners who participated in the 2019 or 2021 Chicago Marathon about their running history, average mileage per week, and average running pace. The survey also asked about known risk factors for osteoarthritis, including BMI, family history of arthritis, and past knee and hip injuries that prevented running.

Runners, on average, were about 44 years old and ran 27.9 miles per week. The largest proportion of respondents had completed 2-5 marathons (37.3%), around 21% of respondents had finished 6-10 marathons, and 17% were running their first marathon. Study participants had an average of 15 years of running experience, 1,892 reported a previous hip or knee injury, and 413 had undergone knee or hip surgery. Overall, 36.4% reported experiencing hip or knee pain in the past year, and 7.3% had been diagnosed with arthritis.

Researchers found that there was no association between the risk of osteoarthritis and weekly mileage, years spent running, number of marathons completed, or running pace. Respondents who had undergone knee or hip surgery had the highest risk of osteoarthritis (odds ratio, 5.85; P < .0001), followed by those with a history of knee or hip injuries that prevented running (OR, 5.04; P < .0001). Other identified risk factors were family history of arthritis (OR, 3.47; P < .0001), BMI (OR, 1.10; P < .0001), and older age (OR, 1.08; P < .0001).

The news should be encouraging for runners, said Matthew Hartwell, MD, an orthopedic surgeon at the University of California, San Francisco, who led the research. If someone does not have injuries or surgeries that keep them from running, “you can still continue to run,” he said. “There may not necessarily be this dose-response relationship where the more you run, the more you break down your knee or your hip.”

Still, 24.2% of runners reported that their physician had advised them to reduce their mileage or stop running altogether. Most runners (94.2%) said they planned to run another marathon.

“The results of this study are consistent with the experiences of many lifelong runners and observations of sports medicine professionals that osteoarthritis is not an inevitable consequence of distance running,” said Brett Toresdahl, MD, a sports medicine physician at the Hospital for Special Surgery in New York, who was not involved with the study.

Still, he emphasized that more research is necessary to understand whether running contributes to the risk of developing osteoarthritis. The participants in the study were current marathoners, he noted, so it is likely they have healthy joints that can tolerate running longer distances. “If there is a subset of people who have joints that are negatively affected by running, they wouldn’t likely be registering for a marathon,” he said in an email interview.

Dr. Lo added that comparing these marathoners to a group who did not run would help assess whether running can be harmful to joints. “To be fair, this is a challenging subject to study,” she said. “Osteoarthritis has a long natural history, and so it is difficult to evaluate this kind of question over many years of running and many years of evaluation of arthritis.”

While the research does not answer the question of whether running can lead to osteoarthritis, it helps show the need for long-term research on how running affects joints over time as well as one’s general health, Dr. Toresdahl noted. “I would not be surprised if future longitudinal research will come to the same conclusion that running for the majority of patients is a net benefit for overall health and at least net neutral for joint health when done in moderation,” he said.

Dr. Hartwell, Dr. Lo, and Dr. Toresdahl report no relevant financial relationships.

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

Long-distance runners are often warned that they are wearing out their joints, but a new study found that running mileage, frequency, and pace were not associated with an increased risk of osteoarthritis.

Runners who had undergone knee or hip surgery or had a previous hip or knee injury that prevented running were most likely to have arthritis, researchers found. Family history of arthritis, higher body mass index (BMI), and older age were also associated with increased risk of the condition.

The study was presented at the American Academy of Orthopaedic Surgeons 2023 Annual Meeting.

It has generally been thought that running may increase risk of osteoarthritis because it puts more load on joints than walking or standing, noted Grace Hsiao-Wei Lo, MD, an assistant professor of immunology, allergy, and rheumatology at the Baylor College of Medicine, Houston, who was not involved with the work. Research in this area has yielded mixed results: A 2017 analysis of multiple studies found that competitive runners did have higher rates of arthritis than recreational runners, while another study conducted by Dr. Lo found that runners did not have an increased risk of knee osteoarthritis, compared with nonrunners. A 2018 study showed that marathon runners had lower instances of arthritis, compared with the general population.

In this new study, researchers surveyed 3,804 runners who participated in the 2019 or 2021 Chicago Marathon about their running history, average mileage per week, and average running pace. The survey also asked about known risk factors for osteoarthritis, including BMI, family history of arthritis, and past knee and hip injuries that prevented running.

Runners, on average, were about 44 years old and ran 27.9 miles per week. The largest proportion of respondents had completed 2-5 marathons (37.3%), around 21% of respondents had finished 6-10 marathons, and 17% were running their first marathon. Study participants had an average of 15 years of running experience, 1,892 reported a previous hip or knee injury, and 413 had undergone knee or hip surgery. Overall, 36.4% reported experiencing hip or knee pain in the past year, and 7.3% had been diagnosed with arthritis.

Researchers found that there was no association between the risk of osteoarthritis and weekly mileage, years spent running, number of marathons completed, or running pace. Respondents who had undergone knee or hip surgery had the highest risk of osteoarthritis (odds ratio, 5.85; P < .0001), followed by those with a history of knee or hip injuries that prevented running (OR, 5.04; P < .0001). Other identified risk factors were family history of arthritis (OR, 3.47; P < .0001), BMI (OR, 1.10; P < .0001), and older age (OR, 1.08; P < .0001).

The news should be encouraging for runners, said Matthew Hartwell, MD, an orthopedic surgeon at the University of California, San Francisco, who led the research. If someone does not have injuries or surgeries that keep them from running, “you can still continue to run,” he said. “There may not necessarily be this dose-response relationship where the more you run, the more you break down your knee or your hip.”

Still, 24.2% of runners reported that their physician had advised them to reduce their mileage or stop running altogether. Most runners (94.2%) said they planned to run another marathon.

“The results of this study are consistent with the experiences of many lifelong runners and observations of sports medicine professionals that osteoarthritis is not an inevitable consequence of distance running,” said Brett Toresdahl, MD, a sports medicine physician at the Hospital for Special Surgery in New York, who was not involved with the study.

Still, he emphasized that more research is necessary to understand whether running contributes to the risk of developing osteoarthritis. The participants in the study were current marathoners, he noted, so it is likely they have healthy joints that can tolerate running longer distances. “If there is a subset of people who have joints that are negatively affected by running, they wouldn’t likely be registering for a marathon,” he said in an email interview.

Dr. Lo added that comparing these marathoners to a group who did not run would help assess whether running can be harmful to joints. “To be fair, this is a challenging subject to study,” she said. “Osteoarthritis has a long natural history, and so it is difficult to evaluate this kind of question over many years of running and many years of evaluation of arthritis.”

While the research does not answer the question of whether running can lead to osteoarthritis, it helps show the need for long-term research on how running affects joints over time as well as one’s general health, Dr. Toresdahl noted. “I would not be surprised if future longitudinal research will come to the same conclusion that running for the majority of patients is a net benefit for overall health and at least net neutral for joint health when done in moderation,” he said.

Dr. Hartwell, Dr. Lo, and Dr. Toresdahl report no relevant financial relationships.

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

Long-distance runners are often warned that they are wearing out their joints, but a new study found that running mileage, frequency, and pace were not associated with an increased risk of osteoarthritis.

Runners who had undergone knee or hip surgery or had a previous hip or knee injury that prevented running were most likely to have arthritis, researchers found. Family history of arthritis, higher body mass index (BMI), and older age were also associated with increased risk of the condition.

The study was presented at the American Academy of Orthopaedic Surgeons 2023 Annual Meeting.

It has generally been thought that running may increase risk of osteoarthritis because it puts more load on joints than walking or standing, noted Grace Hsiao-Wei Lo, MD, an assistant professor of immunology, allergy, and rheumatology at the Baylor College of Medicine, Houston, who was not involved with the work. Research in this area has yielded mixed results: A 2017 analysis of multiple studies found that competitive runners did have higher rates of arthritis than recreational runners, while another study conducted by Dr. Lo found that runners did not have an increased risk of knee osteoarthritis, compared with nonrunners. A 2018 study showed that marathon runners had lower instances of arthritis, compared with the general population.

In this new study, researchers surveyed 3,804 runners who participated in the 2019 or 2021 Chicago Marathon about their running history, average mileage per week, and average running pace. The survey also asked about known risk factors for osteoarthritis, including BMI, family history of arthritis, and past knee and hip injuries that prevented running.

Runners, on average, were about 44 years old and ran 27.9 miles per week. The largest proportion of respondents had completed 2-5 marathons (37.3%), around 21% of respondents had finished 6-10 marathons, and 17% were running their first marathon. Study participants had an average of 15 years of running experience, 1,892 reported a previous hip or knee injury, and 413 had undergone knee or hip surgery. Overall, 36.4% reported experiencing hip or knee pain in the past year, and 7.3% had been diagnosed with arthritis.

Researchers found that there was no association between the risk of osteoarthritis and weekly mileage, years spent running, number of marathons completed, or running pace. Respondents who had undergone knee or hip surgery had the highest risk of osteoarthritis (odds ratio, 5.85; P < .0001), followed by those with a history of knee or hip injuries that prevented running (OR, 5.04; P < .0001). Other identified risk factors were family history of arthritis (OR, 3.47; P < .0001), BMI (OR, 1.10; P < .0001), and older age (OR, 1.08; P < .0001).

The news should be encouraging for runners, said Matthew Hartwell, MD, an orthopedic surgeon at the University of California, San Francisco, who led the research. If someone does not have injuries or surgeries that keep them from running, “you can still continue to run,” he said. “There may not necessarily be this dose-response relationship where the more you run, the more you break down your knee or your hip.”

Still, 24.2% of runners reported that their physician had advised them to reduce their mileage or stop running altogether. Most runners (94.2%) said they planned to run another marathon.

“The results of this study are consistent with the experiences of many lifelong runners and observations of sports medicine professionals that osteoarthritis is not an inevitable consequence of distance running,” said Brett Toresdahl, MD, a sports medicine physician at the Hospital for Special Surgery in New York, who was not involved with the study.

Still, he emphasized that more research is necessary to understand whether running contributes to the risk of developing osteoarthritis. The participants in the study were current marathoners, he noted, so it is likely they have healthy joints that can tolerate running longer distances. “If there is a subset of people who have joints that are negatively affected by running, they wouldn’t likely be registering for a marathon,” he said in an email interview.

Dr. Lo added that comparing these marathoners to a group who did not run would help assess whether running can be harmful to joints. “To be fair, this is a challenging subject to study,” she said. “Osteoarthritis has a long natural history, and so it is difficult to evaluate this kind of question over many years of running and many years of evaluation of arthritis.”

While the research does not answer the question of whether running can lead to osteoarthritis, it helps show the need for long-term research on how running affects joints over time as well as one’s general health, Dr. Toresdahl noted. “I would not be surprised if future longitudinal research will come to the same conclusion that running for the majority of patients is a net benefit for overall health and at least net neutral for joint health when done in moderation,” he said.

Dr. Hartwell, Dr. Lo, and Dr. Toresdahl report no relevant financial relationships.

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

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

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