Conference Coverage

BOSTON – There’s an intriguing plot twist in the story of SYMPLICITY HTN-3, the sham-controlled clinical trial that nearly put the kibosh on renal denervation (RDN) therapy as a promising approach to treatment-resistant hypertension (HTN).

The trial famously showed no benefit for systolic blood pressure (BP) from the invasive procedure at 6 months and 12 months, dampening enthusiasm for RDN in HTN for both physicians and industry. But it turns out that disappointment in the study may have been premature.

The procedure led to significant improvements in systolic BP, whether in-office or ambulatory, compared with a sham control procedure, in a new analysis that followed the trial’s patients out to 3 years. Those who underwent RDN also required less intense antihypertensive drug therapy.

“These findings support that durable blood pressure reductions with radiofrequency renal artery denervation, in the presence of lifestyle modification and maximal medical therapy, are safely achievable,” Deepak L. Bhatt, MD, said in a Sept. 18 presentation at the Transcatheter Cardiovascular Therapeutics annual meeting, which was sponsored by the Cardiovascular Research Foundation.

Dr. Bhatt, of Boston’s Brigham and Women’s Hospital and Harvard Medical School, is lead author on the report published in The Lancet simultaneously with his presentation.

Strides in RDN technology and trial design since the neutral primary SYMPLICITY HTN-3 results were reported in 2014 have long since restored faith in the procedure, which is currently in advanced stages of clinical trials and expected to eventually make a mark on practice.

But Roxana Mehran, MD, not connected to SYMPLICITY HTN-3, expressed caution in interpreting the current analysis based on secondary endpoints and extended follow-up time.

And elsewhere at the TCT sessions, observers of the trial as well as Dr. Bhatt urged similar cautions interpreting “positive” secondary results from trials that were “negative” in their primary analyses.

Still, “I believe there is no question that we have now enough evidence to say that renal denervation on top of medications is probably something that we’re going to be seeing in the future,” Dr. Mehran, of the Icahn School of Medicine at Mount Sinai, New York, told this news organization.

Importantly, and a bit controversially, the RDN group in the 36-month SYMPLICITY HTN-3 analysis includes patients originally assigned to the sham control group who crossed over to receive RDN after the trial was unblinded. Their “control” BP responses were thereafter imputed by accepted statistical methodology that Dr. Bhatt characterized as “last observation carried forward.”

That’s another reason to be circumspect about the current results, observed Naomi Fisher, MD, also of Brigham and Women’s and Harvard Medical School, as a panelist following Dr. Bhatt’s formal presentation.

“With all the missing data and imputational calculations,” she said, “I think we have to apply caution in the interpretation.”

She also pointed out that blinding in the trial was lifted at 6 months, allowing patients to learn their treatment assignment, and potentially influencing subsequent changes to medications.  

They were prescribed, on average, about five antihypertensive meds, Dr. Fisher noted, and “that’s already a red flag. Patients taking that many medications generally aren’t universally taking them. There’s very high likelihood that there could have been variable adherence.”

Patients who learned they were in the sham control group, for example, could have “fallen off” taking their medications, potentially worsening outcomes and amplifying the apparent benefit of RDN. Such an effect, Dr. Fisher said, “could have contributed” to the study’s long-term results.

As previously reported, the single-blind SYMPLICITY HTN-3 had randomly assigned 535 patients to either RDN or a sham control procedure, 364 and 171 patients respectively, at 88 U.S. centers. The trial used the Symplicity Flex RDN radiofrequency ablation catheter (Medtronic).

For study entry, patients were required to have office systolic BP of at least 160 mm Hg and 24-hour ambulatory systolic BP of at least 135 mm Hg despite stable, maximally tolerated dosages of a diuretic plus at least two other antihypertensive agents.

Blinding was lifted at 6 months, per protocol, after which patients in the sham control group who still met the trial’s BP entry criteria were allowed to cross over and undergo RDN. The 101 controls who crossed over were combined with the original active-therapy cohort for the current analysis.

From baseline to 36 months, mean number of medication classes per patient maintained between 4.5 and 5, with no significant difference between groups at any point.

However, medication burden expressed as number of doses daily held steady between 9.7 to 10.2 for controls while the RDN group showed a steady decline from 10.2 to 8.4. Differences between RDN patients and controls were significant at both 24 months (P = .01) and 36 months (P = .005), Dr. Bhatt reported.

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

BOSTON – There’s an intriguing plot twist in the story of SYMPLICITY HTN-3, the sham-controlled clinical trial that nearly put the kibosh on renal denervation (RDN) therapy as a promising approach to treatment-resistant hypertension (HTN).

The trial famously showed no benefit for systolic blood pressure (BP) from the invasive procedure at 6 months and 12 months, dampening enthusiasm for RDN in HTN for both physicians and industry. But it turns out that disappointment in the study may have been premature.

The procedure led to significant improvements in systolic BP, whether in-office or ambulatory, compared with a sham control procedure, in a new analysis that followed the trial’s patients out to 3 years. Those who underwent RDN also required less intense antihypertensive drug therapy.

“These findings support that durable blood pressure reductions with radiofrequency renal artery denervation, in the presence of lifestyle modification and maximal medical therapy, are safely achievable,” Deepak L. Bhatt, MD, said in a Sept. 18 presentation at the Transcatheter Cardiovascular Therapeutics annual meeting, which was sponsored by the Cardiovascular Research Foundation.

Dr. Bhatt, of Boston’s Brigham and Women’s Hospital and Harvard Medical School, is lead author on the report published in The Lancet simultaneously with his presentation.

Strides in RDN technology and trial design since the neutral primary SYMPLICITY HTN-3 results were reported in 2014 have long since restored faith in the procedure, which is currently in advanced stages of clinical trials and expected to eventually make a mark on practice.

But Roxana Mehran, MD, not connected to SYMPLICITY HTN-3, expressed caution in interpreting the current analysis based on secondary endpoints and extended follow-up time.

And elsewhere at the TCT sessions, observers of the trial as well as Dr. Bhatt urged similar cautions interpreting “positive” secondary results from trials that were “negative” in their primary analyses.

Still, “I believe there is no question that we have now enough evidence to say that renal denervation on top of medications is probably something that we’re going to be seeing in the future,” Dr. Mehran, of the Icahn School of Medicine at Mount Sinai, New York, told this news organization.

Importantly, and a bit controversially, the RDN group in the 36-month SYMPLICITY HTN-3 analysis includes patients originally assigned to the sham control group who crossed over to receive RDN after the trial was unblinded. Their “control” BP responses were thereafter imputed by accepted statistical methodology that Dr. Bhatt characterized as “last observation carried forward.”

That’s another reason to be circumspect about the current results, observed Naomi Fisher, MD, also of Brigham and Women’s and Harvard Medical School, as a panelist following Dr. Bhatt’s formal presentation.

“With all the missing data and imputational calculations,” she said, “I think we have to apply caution in the interpretation.”

She also pointed out that blinding in the trial was lifted at 6 months, allowing patients to learn their treatment assignment, and potentially influencing subsequent changes to medications.  

They were prescribed, on average, about five antihypertensive meds, Dr. Fisher noted, and “that’s already a red flag. Patients taking that many medications generally aren’t universally taking them. There’s very high likelihood that there could have been variable adherence.”

Patients who learned they were in the sham control group, for example, could have “fallen off” taking their medications, potentially worsening outcomes and amplifying the apparent benefit of RDN. Such an effect, Dr. Fisher said, “could have contributed” to the study’s long-term results.

As previously reported, the single-blind SYMPLICITY HTN-3 had randomly assigned 535 patients to either RDN or a sham control procedure, 364 and 171 patients respectively, at 88 U.S. centers. The trial used the Symplicity Flex RDN radiofrequency ablation catheter (Medtronic).

For study entry, patients were required to have office systolic BP of at least 160 mm Hg and 24-hour ambulatory systolic BP of at least 135 mm Hg despite stable, maximally tolerated dosages of a diuretic plus at least two other antihypertensive agents.

Blinding was lifted at 6 months, per protocol, after which patients in the sham control group who still met the trial’s BP entry criteria were allowed to cross over and undergo RDN. The 101 controls who crossed over were combined with the original active-therapy cohort for the current analysis.

From baseline to 36 months, mean number of medication classes per patient maintained between 4.5 and 5, with no significant difference between groups at any point.

However, medication burden expressed as number of doses daily held steady between 9.7 to 10.2 for controls while the RDN group showed a steady decline from 10.2 to 8.4. Differences between RDN patients and controls were significant at both 24 months (P = .01) and 36 months (P = .005), Dr. Bhatt reported.

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

BOSTON – There’s an intriguing plot twist in the story of SYMPLICITY HTN-3, the sham-controlled clinical trial that nearly put the kibosh on renal denervation (RDN) therapy as a promising approach to treatment-resistant hypertension (HTN).

The trial famously showed no benefit for systolic blood pressure (BP) from the invasive procedure at 6 months and 12 months, dampening enthusiasm for RDN in HTN for both physicians and industry. But it turns out that disappointment in the study may have been premature.

The procedure led to significant improvements in systolic BP, whether in-office or ambulatory, compared with a sham control procedure, in a new analysis that followed the trial’s patients out to 3 years. Those who underwent RDN also required less intense antihypertensive drug therapy.

“These findings support that durable blood pressure reductions with radiofrequency renal artery denervation, in the presence of lifestyle modification and maximal medical therapy, are safely achievable,” Deepak L. Bhatt, MD, said in a Sept. 18 presentation at the Transcatheter Cardiovascular Therapeutics annual meeting, which was sponsored by the Cardiovascular Research Foundation.

Dr. Bhatt, of Boston’s Brigham and Women’s Hospital and Harvard Medical School, is lead author on the report published in The Lancet simultaneously with his presentation.

Strides in RDN technology and trial design since the neutral primary SYMPLICITY HTN-3 results were reported in 2014 have long since restored faith in the procedure, which is currently in advanced stages of clinical trials and expected to eventually make a mark on practice.

But Roxana Mehran, MD, not connected to SYMPLICITY HTN-3, expressed caution in interpreting the current analysis based on secondary endpoints and extended follow-up time.

And elsewhere at the TCT sessions, observers of the trial as well as Dr. Bhatt urged similar cautions interpreting “positive” secondary results from trials that were “negative” in their primary analyses.

Still, “I believe there is no question that we have now enough evidence to say that renal denervation on top of medications is probably something that we’re going to be seeing in the future,” Dr. Mehran, of the Icahn School of Medicine at Mount Sinai, New York, told this news organization.

Importantly, and a bit controversially, the RDN group in the 36-month SYMPLICITY HTN-3 analysis includes patients originally assigned to the sham control group who crossed over to receive RDN after the trial was unblinded. Their “control” BP responses were thereafter imputed by accepted statistical methodology that Dr. Bhatt characterized as “last observation carried forward.”

That’s another reason to be circumspect about the current results, observed Naomi Fisher, MD, also of Brigham and Women’s and Harvard Medical School, as a panelist following Dr. Bhatt’s formal presentation.

“With all the missing data and imputational calculations,” she said, “I think we have to apply caution in the interpretation.”

She also pointed out that blinding in the trial was lifted at 6 months, allowing patients to learn their treatment assignment, and potentially influencing subsequent changes to medications.  

They were prescribed, on average, about five antihypertensive meds, Dr. Fisher noted, and “that’s already a red flag. Patients taking that many medications generally aren’t universally taking them. There’s very high likelihood that there could have been variable adherence.”

Patients who learned they were in the sham control group, for example, could have “fallen off” taking their medications, potentially worsening outcomes and amplifying the apparent benefit of RDN. Such an effect, Dr. Fisher said, “could have contributed” to the study’s long-term results.

As previously reported, the single-blind SYMPLICITY HTN-3 had randomly assigned 535 patients to either RDN or a sham control procedure, 364 and 171 patients respectively, at 88 U.S. centers. The trial used the Symplicity Flex RDN radiofrequency ablation catheter (Medtronic).

For study entry, patients were required to have office systolic BP of at least 160 mm Hg and 24-hour ambulatory systolic BP of at least 135 mm Hg despite stable, maximally tolerated dosages of a diuretic plus at least two other antihypertensive agents.

Blinding was lifted at 6 months, per protocol, after which patients in the sham control group who still met the trial’s BP entry criteria were allowed to cross over and undergo RDN. The 101 controls who crossed over were combined with the original active-therapy cohort for the current analysis.

From baseline to 36 months, mean number of medication classes per patient maintained between 4.5 and 5, with no significant difference between groups at any point.

However, medication burden expressed as number of doses daily held steady between 9.7 to 10.2 for controls while the RDN group showed a steady decline from 10.2 to 8.4. Differences between RDN patients and controls were significant at both 24 months (P = .01) and 36 months (P = .005), Dr. Bhatt reported.

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

In May 2022, the Digestive Disease Week (DDW) conference was held in person again for the first time in 3 years. Two years prior in July 2020 AGA launched the Equity Project, a six-point strategic plan to achieve equity and eradicate health disparities in digestive diseases.

President John Inadomi elected to focus his AGA Presidential Plenary session on updates in gastrointestinal and hepatic health disparities, and opened with a powerful testimony on his personal experiences encountering racism, and recognizing the need to translate spoken intentions into action.

This served as the perfect segue to the second plenary presentation in which an update was given on the progress of the Equity Project by co-chairs Byron Cryer, MD, and Sandra Quezada, MD, MS. Dr. Cryer described the vision of the Equity Project, including: a just world, free of inequities in access and health care delivery; state-of-the-art and well-funded research of multicultural populations; a diverse physician and scientist workforce and leadership; recognition of achievements of people of color; membership and staff committed to self-awareness and eliminating unconscious bias; and an engaged, large, diverse, vocal, and culturally- and socially aware early career membership.

Concrete action items were identified by a coalition of AGA members with diverse representation across specialties, practice settings, and identities. AGA staff and constituency programs have been critical in the execution of each action item. Key performance indicators were selected to gauge progress and hold the organization accountable in implementation of project tactics. These metrics demonstrate that the first 2 years of the Equity Project have been very productive. Salient accomplishments include three congressional briefings on health disparities topics, increased education and dialogue on diversity, equity, and inclusion (DEI) through podcasts, career development workshops and DDW sessions, fundraising of over $300,000 to support health disparities research, dedicated DEI sections and section editors for Gastroenterology and Clinical Gastroenterology and Hepatology, and the creation of a guide for GI fellowship program directors to promote equity and mitigate bias in the fellowship selection process.

Although the Equity Project is entering its third and final implementation year, the spirit and values of the Equity Project will live on. Excellence in equity requires ongoing, focused dedication – AGA is committed to ensuring that equity, diversity, and inclusion are inherently embedded through the fabric of the organization, and continuously integrated and assessed in all of the organization’s future strategic initiatives.

Dr. Quezada is an associate professor of medicine in the division of gastroenterology and hepatology at the University of Maryland, Baltimore. She reports being on the People of Color Advisory Board for Janssen. Dr. Cryer is chief of internal medicine and the Ralph Tompsett Endowed Chair in Medicine at Baylor University Medical Center, Dallas, and a professor of internal medicine at Texas A&M School of Medicine. He has no relevant conflicts of interest. These remarks were made during the AGA Presidential Plenary at DDW 2022.

In May 2022, the Digestive Disease Week (DDW) conference was held in person again for the first time in 3 years. Two years prior in July 2020 AGA launched the Equity Project, a six-point strategic plan to achieve equity and eradicate health disparities in digestive diseases.

President John Inadomi elected to focus his AGA Presidential Plenary session on updates in gastrointestinal and hepatic health disparities, and opened with a powerful testimony on his personal experiences encountering racism, and recognizing the need to translate spoken intentions into action.

This served as the perfect segue to the second plenary presentation in which an update was given on the progress of the Equity Project by co-chairs Byron Cryer, MD, and Sandra Quezada, MD, MS. Dr. Cryer described the vision of the Equity Project, including: a just world, free of inequities in access and health care delivery; state-of-the-art and well-funded research of multicultural populations; a diverse physician and scientist workforce and leadership; recognition of achievements of people of color; membership and staff committed to self-awareness and eliminating unconscious bias; and an engaged, large, diverse, vocal, and culturally- and socially aware early career membership.

Concrete action items were identified by a coalition of AGA members with diverse representation across specialties, practice settings, and identities. AGA staff and constituency programs have been critical in the execution of each action item. Key performance indicators were selected to gauge progress and hold the organization accountable in implementation of project tactics. These metrics demonstrate that the first 2 years of the Equity Project have been very productive. Salient accomplishments include three congressional briefings on health disparities topics, increased education and dialogue on diversity, equity, and inclusion (DEI) through podcasts, career development workshops and DDW sessions, fundraising of over $300,000 to support health disparities research, dedicated DEI sections and section editors for Gastroenterology and Clinical Gastroenterology and Hepatology, and the creation of a guide for GI fellowship program directors to promote equity and mitigate bias in the fellowship selection process.

Although the Equity Project is entering its third and final implementation year, the spirit and values of the Equity Project will live on. Excellence in equity requires ongoing, focused dedication – AGA is committed to ensuring that equity, diversity, and inclusion are inherently embedded through the fabric of the organization, and continuously integrated and assessed in all of the organization’s future strategic initiatives.

Dr. Quezada is an associate professor of medicine in the division of gastroenterology and hepatology at the University of Maryland, Baltimore. She reports being on the People of Color Advisory Board for Janssen. Dr. Cryer is chief of internal medicine and the Ralph Tompsett Endowed Chair in Medicine at Baylor University Medical Center, Dallas, and a professor of internal medicine at Texas A&M School of Medicine. He has no relevant conflicts of interest. These remarks were made during the AGA Presidential Plenary at DDW 2022.

In May 2022, the Digestive Disease Week (DDW) conference was held in person again for the first time in 3 years. Two years prior in July 2020 AGA launched the Equity Project, a six-point strategic plan to achieve equity and eradicate health disparities in digestive diseases.

President John Inadomi elected to focus his AGA Presidential Plenary session on updates in gastrointestinal and hepatic health disparities, and opened with a powerful testimony on his personal experiences encountering racism, and recognizing the need to translate spoken intentions into action.

This served as the perfect segue to the second plenary presentation in which an update was given on the progress of the Equity Project by co-chairs Byron Cryer, MD, and Sandra Quezada, MD, MS. Dr. Cryer described the vision of the Equity Project, including: a just world, free of inequities in access and health care delivery; state-of-the-art and well-funded research of multicultural populations; a diverse physician and scientist workforce and leadership; recognition of achievements of people of color; membership and staff committed to self-awareness and eliminating unconscious bias; and an engaged, large, diverse, vocal, and culturally- and socially aware early career membership.

Concrete action items were identified by a coalition of AGA members with diverse representation across specialties, practice settings, and identities. AGA staff and constituency programs have been critical in the execution of each action item. Key performance indicators were selected to gauge progress and hold the organization accountable in implementation of project tactics. These metrics demonstrate that the first 2 years of the Equity Project have been very productive. Salient accomplishments include three congressional briefings on health disparities topics, increased education and dialogue on diversity, equity, and inclusion (DEI) through podcasts, career development workshops and DDW sessions, fundraising of over $300,000 to support health disparities research, dedicated DEI sections and section editors for Gastroenterology and Clinical Gastroenterology and Hepatology, and the creation of a guide for GI fellowship program directors to promote equity and mitigate bias in the fellowship selection process.

Although the Equity Project is entering its third and final implementation year, the spirit and values of the Equity Project will live on. Excellence in equity requires ongoing, focused dedication – AGA is committed to ensuring that equity, diversity, and inclusion are inherently embedded through the fabric of the organization, and continuously integrated and assessed in all of the organization’s future strategic initiatives.

Dr. Quezada is an associate professor of medicine in the division of gastroenterology and hepatology at the University of Maryland, Baltimore. She reports being on the People of Color Advisory Board for Janssen. Dr. Cryer is chief of internal medicine and the Ralph Tompsett Endowed Chair in Medicine at Baylor University Medical Center, Dallas, and a professor of internal medicine at Texas A&M School of Medicine. He has no relevant conflicts of interest. These remarks were made during the AGA Presidential Plenary at DDW 2022.

Eosinophilic gastrointestinal diseases (EGIDs) are characterized by GI signs or symptoms occurring along with tissue eosinophilia. Eosinophilic esophagitis (EoE) is the more commonly recognized EGID as endoscopic and histopathologic diagnostic criteria have long been established. Because of a lack of consensus on biopsy protocols, poorly understood histopathologic diagnostic criteria, and vague, nonspecific gastrointestinal complaints, patients with non-EoE EGIDs go unrecognized for years. Because of this, there is increasing emphasis on better defining rare, distal eosinophilic gastrointestinal diseases (i.e., eosinophilic gastritis, enteritis, and colitis).

EGID nomenclature was standardized in 2022 in part to minimize vague terminology (i.e., eosinophilic gastroenteritis) and to provide more specific information about the location of eosinophilic disease. The 2022 nomenclature suggest that EGID be used as the umbrella term for all GI luminal eosinophilia (without a known cause) but with emphasis on the site of specific eosinophilic involvement (i.e., eosinophilic gastritis or eosinophilic gastritis and colitis). Importantly, there is much work to be done to adequately identify patients suffering from EGIDs. Symptoms are variable, ranging from abdominal pain, bloating, and nausea seen in proximal disease to loose stools and hematochezia in more distal involvement. Signs of disease, such as iron or other nutrient deficiencies and protein loss, may also occur. Endoscopic findings can vary from erythema, granularity, erosions, ulcerations, and blunting to even normal-appearing tissue. In eosinophilic gastritis, Ikuo Hirano, MD, and colleagues demonstrated that increasing endoscopic inflammatory findings in the stomach correlate with assessment of disease severity. Regardless of endoscopic findings, numerous biopsies are needed for the diagnosis of EGIDs because, as already established in EoE, eosinophil involvement is patchy. Nirmala Gonsalves, MD, and Evan Dellon, MD, found that a minimum of four biopsies each in the gastric antrum, gastric body, and small bowel are needed to detect disease. Optimal biopsy patterns have not yet been determined for eosinophilic ileitis or colitis.

Despite these advances, there is more work to be performed. Although these disease states are termed “eosinophilic,” the immunopathology driving these diseases is multifactorial, involving lymphocytes and mast cells and creating different phenotypes of disease in a similar fashion to inflammatory bowel disease. Current therapies being studied include eosinophil-depleting medications along with others targeting T2 immune pathways. Patients may need multiple therapeutic options, and personalized medicine will soon play a larger role in defining treatments. For now, researchers are fervently working on improved methods to identify, phenotype, and treat these morbid disorders.
 

Dr. Peterson is associate professor of gastroenterology at University of Utah Health, Salt Lake City. She has no relevant conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.

Eosinophilic gastrointestinal diseases (EGIDs) are characterized by GI signs or symptoms occurring along with tissue eosinophilia. Eosinophilic esophagitis (EoE) is the more commonly recognized EGID as endoscopic and histopathologic diagnostic criteria have long been established. Because of a lack of consensus on biopsy protocols, poorly understood histopathologic diagnostic criteria, and vague, nonspecific gastrointestinal complaints, patients with non-EoE EGIDs go unrecognized for years. Because of this, there is increasing emphasis on better defining rare, distal eosinophilic gastrointestinal diseases (i.e., eosinophilic gastritis, enteritis, and colitis).

EGID nomenclature was standardized in 2022 in part to minimize vague terminology (i.e., eosinophilic gastroenteritis) and to provide more specific information about the location of eosinophilic disease. The 2022 nomenclature suggest that EGID be used as the umbrella term for all GI luminal eosinophilia (without a known cause) but with emphasis on the site of specific eosinophilic involvement (i.e., eosinophilic gastritis or eosinophilic gastritis and colitis). Importantly, there is much work to be done to adequately identify patients suffering from EGIDs. Symptoms are variable, ranging from abdominal pain, bloating, and nausea seen in proximal disease to loose stools and hematochezia in more distal involvement. Signs of disease, such as iron or other nutrient deficiencies and protein loss, may also occur. Endoscopic findings can vary from erythema, granularity, erosions, ulcerations, and blunting to even normal-appearing tissue. In eosinophilic gastritis, Ikuo Hirano, MD, and colleagues demonstrated that increasing endoscopic inflammatory findings in the stomach correlate with assessment of disease severity. Regardless of endoscopic findings, numerous biopsies are needed for the diagnosis of EGIDs because, as already established in EoE, eosinophil involvement is patchy. Nirmala Gonsalves, MD, and Evan Dellon, MD, found that a minimum of four biopsies each in the gastric antrum, gastric body, and small bowel are needed to detect disease. Optimal biopsy patterns have not yet been determined for eosinophilic ileitis or colitis.

Despite these advances, there is more work to be performed. Although these disease states are termed “eosinophilic,” the immunopathology driving these diseases is multifactorial, involving lymphocytes and mast cells and creating different phenotypes of disease in a similar fashion to inflammatory bowel disease. Current therapies being studied include eosinophil-depleting medications along with others targeting T2 immune pathways. Patients may need multiple therapeutic options, and personalized medicine will soon play a larger role in defining treatments. For now, researchers are fervently working on improved methods to identify, phenotype, and treat these morbid disorders.
 

Dr. Peterson is associate professor of gastroenterology at University of Utah Health, Salt Lake City. She has no relevant conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.

Eosinophilic gastrointestinal diseases (EGIDs) are characterized by GI signs or symptoms occurring along with tissue eosinophilia. Eosinophilic esophagitis (EoE) is the more commonly recognized EGID as endoscopic and histopathologic diagnostic criteria have long been established. Because of a lack of consensus on biopsy protocols, poorly understood histopathologic diagnostic criteria, and vague, nonspecific gastrointestinal complaints, patients with non-EoE EGIDs go unrecognized for years. Because of this, there is increasing emphasis on better defining rare, distal eosinophilic gastrointestinal diseases (i.e., eosinophilic gastritis, enteritis, and colitis).

EGID nomenclature was standardized in 2022 in part to minimize vague terminology (i.e., eosinophilic gastroenteritis) and to provide more specific information about the location of eosinophilic disease. The 2022 nomenclature suggest that EGID be used as the umbrella term for all GI luminal eosinophilia (without a known cause) but with emphasis on the site of specific eosinophilic involvement (i.e., eosinophilic gastritis or eosinophilic gastritis and colitis). Importantly, there is much work to be done to adequately identify patients suffering from EGIDs. Symptoms are variable, ranging from abdominal pain, bloating, and nausea seen in proximal disease to loose stools and hematochezia in more distal involvement. Signs of disease, such as iron or other nutrient deficiencies and protein loss, may also occur. Endoscopic findings can vary from erythema, granularity, erosions, ulcerations, and blunting to even normal-appearing tissue. In eosinophilic gastritis, Ikuo Hirano, MD, and colleagues demonstrated that increasing endoscopic inflammatory findings in the stomach correlate with assessment of disease severity. Regardless of endoscopic findings, numerous biopsies are needed for the diagnosis of EGIDs because, as already established in EoE, eosinophil involvement is patchy. Nirmala Gonsalves, MD, and Evan Dellon, MD, found that a minimum of four biopsies each in the gastric antrum, gastric body, and small bowel are needed to detect disease. Optimal biopsy patterns have not yet been determined for eosinophilic ileitis or colitis.

Despite these advances, there is more work to be performed. Although these disease states are termed “eosinophilic,” the immunopathology driving these diseases is multifactorial, involving lymphocytes and mast cells and creating different phenotypes of disease in a similar fashion to inflammatory bowel disease. Current therapies being studied include eosinophil-depleting medications along with others targeting T2 immune pathways. Patients may need multiple therapeutic options, and personalized medicine will soon play a larger role in defining treatments. For now, researchers are fervently working on improved methods to identify, phenotype, and treat these morbid disorders.
 

Dr. Peterson is associate professor of gastroenterology at University of Utah Health, Salt Lake City. She has no relevant conflicts of interest. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2022.

In a new analysis of the previously published FAME 3 trial, which compared fractional flow reserve–guided percutaneous coronary interventions to coronary artery bypass surgery (CABG) in patients with three-vessel disease, post-PCI FFR was shown to predict both target vessel failure (TVF) and risk of cardiac events.

“We found that the post-PCI FFR had prognostic value both for the vessel and for the patient,” reported Zsolt Piroth, MD, PhD, deputy head, adult cardiology, György Gottsegen Institute of Cardiology, Budapest.

In this post hoc analysis, which was not a prespecified FAME 3 substudy, the goal was to look at the prognostic value of both post-PCI FFR and intravascular ultrasound, which were recommended in the study protocol. Several studies have addressed the value of these measures previously, according to Dr. Piroth, but he said the clinical value “has remained poorly defined” despite the currently available data.

The FAME 3 trial, published in the New England Journal of Medicine, was negative. It failed to confirm the study hypothesis that FFR-guided PCI is noninferior to CABG for the outcome of major adverse cardiac events (MACE) at 12 months.

However, this multinational trial has generated a large body of data with which to explore other issues relevant to revascularization. In this analysis, the goal was to evaluate whether post-PCI FFR predicted outcomes in complex multivessel revascularizations as it has been shown previously to do in single-vessel disease.

Presented at the Transcatheter Cardiovascular Therapeutics annual meeting, the focus of this analysis was on the 461 (61%) of patients in the 757-patient PCI arm of FAME 3 who underwent post-PCI FFR. The authors also looked at the predictive value of intravascular ultrasound, even though this was performed in just 11% of this group of trial participants.

As a continuous value, each 0.1-unit change in the post-PCI FFR was found to be prognostically significant for the outcome of TVF, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization (only postprocedural events were counted in this analysis). Specifically, for each 0.1-unit increase on a univariate analysis, the risk of TVF was reduced by about one-third (hazard ratio, 0.67; P = .0165).

On a patient level, a 0.1-unit increase in lowest post-PCI FFR of any assessed vessel was also associated with the same relative risk reduction (HR, 0.65; P = .0074) in the outcomes of cardiac death, target vessel MI, or target vessel revascularization, according to Dr. Piroth. On a receiver operating characteristic curve analysis, a value of 0.88 or below was predictive of TVF.

Although several other patient characteristics were also risk predictors of TVF on univariate analysis, only renal disease and the single lowest post-PCI FFR (as a continuous variable) emerged as predictors of TVF on multivariable analysis after adjustment for key clinical parameters, Dr. Piroth reported.

The reason why post-PCI FFR was not performed in almost 40% of patients randomized to PCI is unclear, but Dr. Piroth reported that the baseline characteristics of those who were or were not assessed with FFR after their procedure did not differ to any major degree.

Despite “a trend for improved outcomes in those who underwent post-PCI FFR,” Dr. Piroth, whose substudy was published in Circulation: Cardiovascular Interventions simultaneously with his TCT presentation, acknowledged that the reasons for a potential benefit cannot be derived from this post hoc analysis.

As for the prognostic value of IVUS, any conclusions are limited by the small proportion of patients who underwent this form of imaging. Overall, IVUS imaging was associated with longer procedures and more stents and “if anything, a signal for harm” in this analysis, but Dr. Piroth cautioned against any conclusions because of the small data pool.

The prognostic value of post-PCI FFR in complex multivessel disease is supported by these data, but the analysis was not designed to determine whether post-PCI FFR has relevance to intervention.

According to J. Dawn Abbott, MD, an FFR analysis conducted to identify lesions that are candidates for treatment should not be confused with FFR for physiologically guided PCI to optimize outcomes.

Noting that post-PCI FFR was encouraged in this study but not mandated and that these FFR values did not typically or necessarily lead to a change in management, take home messages about the value of post-PCI FFR in multivessel disease remain limited, said Dr. Abbott, director of interventional cardiology fellowship training, Brown University, Providence, R.I.

“There was a trend toward improved outcomes in patients who had this measurement done, but, unfortunately, we do not have data regarding whether these patients had further interventions performed,” Dr. Piroth acknowledged.

The post-PCI FFR values were made available to the treating physicians, but Dr. Piroth reiterated that it is unknown whether the physicians considered this information actionable. Moreover, “the vast majority had a nonsignificant post-PCI FFR” result, and “all of the patients had an angiographically successful PCI,” Dr. Piroth added.

Dr. Piroth has financial relationships with Abbott Vascular and Boston Scientific. Dr. Abbott reports financial relationships with Abbott Vascular, Boston Scientific, Medtronic, Microport, Philips, Penumbra, Recor, and Shockwave.


 

In a new analysis of the previously published FAME 3 trial, which compared fractional flow reserve–guided percutaneous coronary interventions to coronary artery bypass surgery (CABG) in patients with three-vessel disease, post-PCI FFR was shown to predict both target vessel failure (TVF) and risk of cardiac events.

“We found that the post-PCI FFR had prognostic value both for the vessel and for the patient,” reported Zsolt Piroth, MD, PhD, deputy head, adult cardiology, György Gottsegen Institute of Cardiology, Budapest.

In this post hoc analysis, which was not a prespecified FAME 3 substudy, the goal was to look at the prognostic value of both post-PCI FFR and intravascular ultrasound, which were recommended in the study protocol. Several studies have addressed the value of these measures previously, according to Dr. Piroth, but he said the clinical value “has remained poorly defined” despite the currently available data.

The FAME 3 trial, published in the New England Journal of Medicine, was negative. It failed to confirm the study hypothesis that FFR-guided PCI is noninferior to CABG for the outcome of major adverse cardiac events (MACE) at 12 months.

However, this multinational trial has generated a large body of data with which to explore other issues relevant to revascularization. In this analysis, the goal was to evaluate whether post-PCI FFR predicted outcomes in complex multivessel revascularizations as it has been shown previously to do in single-vessel disease.

Presented at the Transcatheter Cardiovascular Therapeutics annual meeting, the focus of this analysis was on the 461 (61%) of patients in the 757-patient PCI arm of FAME 3 who underwent post-PCI FFR. The authors also looked at the predictive value of intravascular ultrasound, even though this was performed in just 11% of this group of trial participants.

As a continuous value, each 0.1-unit change in the post-PCI FFR was found to be prognostically significant for the outcome of TVF, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization (only postprocedural events were counted in this analysis). Specifically, for each 0.1-unit increase on a univariate analysis, the risk of TVF was reduced by about one-third (hazard ratio, 0.67; P = .0165).

On a patient level, a 0.1-unit increase in lowest post-PCI FFR of any assessed vessel was also associated with the same relative risk reduction (HR, 0.65; P = .0074) in the outcomes of cardiac death, target vessel MI, or target vessel revascularization, according to Dr. Piroth. On a receiver operating characteristic curve analysis, a value of 0.88 or below was predictive of TVF.

Although several other patient characteristics were also risk predictors of TVF on univariate analysis, only renal disease and the single lowest post-PCI FFR (as a continuous variable) emerged as predictors of TVF on multivariable analysis after adjustment for key clinical parameters, Dr. Piroth reported.

The reason why post-PCI FFR was not performed in almost 40% of patients randomized to PCI is unclear, but Dr. Piroth reported that the baseline characteristics of those who were or were not assessed with FFR after their procedure did not differ to any major degree.

Despite “a trend for improved outcomes in those who underwent post-PCI FFR,” Dr. Piroth, whose substudy was published in Circulation: Cardiovascular Interventions simultaneously with his TCT presentation, acknowledged that the reasons for a potential benefit cannot be derived from this post hoc analysis.

As for the prognostic value of IVUS, any conclusions are limited by the small proportion of patients who underwent this form of imaging. Overall, IVUS imaging was associated with longer procedures and more stents and “if anything, a signal for harm” in this analysis, but Dr. Piroth cautioned against any conclusions because of the small data pool.

The prognostic value of post-PCI FFR in complex multivessel disease is supported by these data, but the analysis was not designed to determine whether post-PCI FFR has relevance to intervention.

According to J. Dawn Abbott, MD, an FFR analysis conducted to identify lesions that are candidates for treatment should not be confused with FFR for physiologically guided PCI to optimize outcomes.

Noting that post-PCI FFR was encouraged in this study but not mandated and that these FFR values did not typically or necessarily lead to a change in management, take home messages about the value of post-PCI FFR in multivessel disease remain limited, said Dr. Abbott, director of interventional cardiology fellowship training, Brown University, Providence, R.I.

“There was a trend toward improved outcomes in patients who had this measurement done, but, unfortunately, we do not have data regarding whether these patients had further interventions performed,” Dr. Piroth acknowledged.

The post-PCI FFR values were made available to the treating physicians, but Dr. Piroth reiterated that it is unknown whether the physicians considered this information actionable. Moreover, “the vast majority had a nonsignificant post-PCI FFR” result, and “all of the patients had an angiographically successful PCI,” Dr. Piroth added.

Dr. Piroth has financial relationships with Abbott Vascular and Boston Scientific. Dr. Abbott reports financial relationships with Abbott Vascular, Boston Scientific, Medtronic, Microport, Philips, Penumbra, Recor, and Shockwave.


 

In a new analysis of the previously published FAME 3 trial, which compared fractional flow reserve–guided percutaneous coronary interventions to coronary artery bypass surgery (CABG) in patients with three-vessel disease, post-PCI FFR was shown to predict both target vessel failure (TVF) and risk of cardiac events.

“We found that the post-PCI FFR had prognostic value both for the vessel and for the patient,” reported Zsolt Piroth, MD, PhD, deputy head, adult cardiology, György Gottsegen Institute of Cardiology, Budapest.

In this post hoc analysis, which was not a prespecified FAME 3 substudy, the goal was to look at the prognostic value of both post-PCI FFR and intravascular ultrasound, which were recommended in the study protocol. Several studies have addressed the value of these measures previously, according to Dr. Piroth, but he said the clinical value “has remained poorly defined” despite the currently available data.

The FAME 3 trial, published in the New England Journal of Medicine, was negative. It failed to confirm the study hypothesis that FFR-guided PCI is noninferior to CABG for the outcome of major adverse cardiac events (MACE) at 12 months.

However, this multinational trial has generated a large body of data with which to explore other issues relevant to revascularization. In this analysis, the goal was to evaluate whether post-PCI FFR predicted outcomes in complex multivessel revascularizations as it has been shown previously to do in single-vessel disease.

Presented at the Transcatheter Cardiovascular Therapeutics annual meeting, the focus of this analysis was on the 461 (61%) of patients in the 757-patient PCI arm of FAME 3 who underwent post-PCI FFR. The authors also looked at the predictive value of intravascular ultrasound, even though this was performed in just 11% of this group of trial participants.

As a continuous value, each 0.1-unit change in the post-PCI FFR was found to be prognostically significant for the outcome of TVF, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization (only postprocedural events were counted in this analysis). Specifically, for each 0.1-unit increase on a univariate analysis, the risk of TVF was reduced by about one-third (hazard ratio, 0.67; P = .0165).

On a patient level, a 0.1-unit increase in lowest post-PCI FFR of any assessed vessel was also associated with the same relative risk reduction (HR, 0.65; P = .0074) in the outcomes of cardiac death, target vessel MI, or target vessel revascularization, according to Dr. Piroth. On a receiver operating characteristic curve analysis, a value of 0.88 or below was predictive of TVF.

Although several other patient characteristics were also risk predictors of TVF on univariate analysis, only renal disease and the single lowest post-PCI FFR (as a continuous variable) emerged as predictors of TVF on multivariable analysis after adjustment for key clinical parameters, Dr. Piroth reported.

The reason why post-PCI FFR was not performed in almost 40% of patients randomized to PCI is unclear, but Dr. Piroth reported that the baseline characteristics of those who were or were not assessed with FFR after their procedure did not differ to any major degree.

Despite “a trend for improved outcomes in those who underwent post-PCI FFR,” Dr. Piroth, whose substudy was published in Circulation: Cardiovascular Interventions simultaneously with his TCT presentation, acknowledged that the reasons for a potential benefit cannot be derived from this post hoc analysis.

As for the prognostic value of IVUS, any conclusions are limited by the small proportion of patients who underwent this form of imaging. Overall, IVUS imaging was associated with longer procedures and more stents and “if anything, a signal for harm” in this analysis, but Dr. Piroth cautioned against any conclusions because of the small data pool.

The prognostic value of post-PCI FFR in complex multivessel disease is supported by these data, but the analysis was not designed to determine whether post-PCI FFR has relevance to intervention.

According to J. Dawn Abbott, MD, an FFR analysis conducted to identify lesions that are candidates for treatment should not be confused with FFR for physiologically guided PCI to optimize outcomes.

Noting that post-PCI FFR was encouraged in this study but not mandated and that these FFR values did not typically or necessarily lead to a change in management, take home messages about the value of post-PCI FFR in multivessel disease remain limited, said Dr. Abbott, director of interventional cardiology fellowship training, Brown University, Providence, R.I.

“There was a trend toward improved outcomes in patients who had this measurement done, but, unfortunately, we do not have data regarding whether these patients had further interventions performed,” Dr. Piroth acknowledged.

The post-PCI FFR values were made available to the treating physicians, but Dr. Piroth reiterated that it is unknown whether the physicians considered this information actionable. Moreover, “the vast majority had a nonsignificant post-PCI FFR” result, and “all of the patients had an angiographically successful PCI,” Dr. Piroth added.

Dr. Piroth has financial relationships with Abbott Vascular and Boston Scientific. Dr. Abbott reports financial relationships with Abbott Vascular, Boston Scientific, Medtronic, Microport, Philips, Penumbra, Recor, and Shockwave.


 

STOCKHOLM – When a clinician is unsure which of several equally viable drug options is best for a specific patient with type 2 diabetes, a rational approach is to run a serial trial with each one and then let each patient decide which agent works best for them.

That concept underwent successful testing in a recent trial with 457 patients with type 2 diabetes and already on treatment with metformin or metformin plus a sulfonylurea but needed further glycemic control. After cycling through 4-month trials (when tolerated) of canagliflozin (Invokana), pioglitazone (Actos), and sitagliptin (Januvia), 24% identified pioglitazone as the one that made them feel best, 33% favored sitagliptin, 37% said canagliflozin was tops, and 6% had no preference, Beverley Shields, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/MDedge News

After making these selections based on just their qualitative self-appraisals, researchers told patients about their hemoglobin A1c status on each of the three agents. It barely budged their choices, which became 25% calling pioglitazone best, 35% naming sitagliptin their preference, 38% opting for canagliflozin, with 2% having no preference.

Further analysis showed that the drug patients preferred was also the one that produced their lowest A1c level when compared with their 8 months on each of the two other agents tested, showing a link between lower A1c levels and improved well-being. The same relationship existed for the drug that caused the fewest adverse events for each patient.
 

Patients prefer feeling better

“Patients tended to prefer the drug that they ‘felt better’ on, with the lowest A1c level and the lowest number of side effects,” explained Dr. Shields, a medical statistician at the University of Exeter (England). Changes in weight appeared less important to patients for establishing a preference.

Mitchel L. Zoler/MDedge News

“This is for when there is equipoise” among drug options, Andrew Hattersley, BMBCh, DM, the study’s principal investigator, said in an interview. “When you are unsure what to prescribe and there is no clear indication for one drug over another, try 4 months of one and 4 months of the other, then let the patient decide.

“Patients had overwhelming positivity about being able to choose their drug,” added Dr. Hattersley, who is also professor of molecular medicine at the University of Exeter.

“This has implications across medicine,” he added. “Whenever you’re not sure how to balance adverse effects and positive effects the best person to decide is the one who experiences the effects.”

“I’m a bit worried by this approach, but it is something new” and worth considering, commented Drazenka P. Barlovic, MD, an endocrinologist at the University Medical Center in Ljubljana, Slovenia, who chaired the session where Dr. Shields gave her report. “We should also have the courage to challenge metformin, as there is no longer an obligation to make it the first drug,” she said in an interview.

The study ran as a secondary analysis of the TriMaster study, which had the primary objective of identifying patient characteristics that could predict which of the three drug options tested worked best for certain patient subgroups. That analysis, presented at the 2021 EASD annual meeting, found that factors such as body mass index and kidney function significantly linked with the clinical responses patients had to each of the three tested agents.

The new analysis focused on 457 of the TriMaster participants who had provided preference information after they had tried all three agents. By design, none of the participants enrolled in the study had a contraindication for any of the tested drugs.

Patients quickly identify adverse effects

“We picked 4 months because it not too long, but long enough to see adverse effects, and to measure on-treatment A1c. Patients quickly identify their adverse events,” Dr. Shields said in an interview.

“This could come into practice now; there is no cost involved. Do it when you’re not certain which drug to prescribe,” Dr. Hattersley suggested. “We can’t know which drug a patient might prefer.” He also stressed telling patients to return quicker than 4 months if they can’t tolerate a new drug.

The findings have already changed Dr. Hattersley’s practice, and he believes it will catch on as he introduces it to local primary care physicians.

The study received no commercial funding. Dr. Shields, Dr. Hattersley, and Dr. Barlovic had no disclosures.






 

STOCKHOLM – When a clinician is unsure which of several equally viable drug options is best for a specific patient with type 2 diabetes, a rational approach is to run a serial trial with each one and then let each patient decide which agent works best for them.

That concept underwent successful testing in a recent trial with 457 patients with type 2 diabetes and already on treatment with metformin or metformin plus a sulfonylurea but needed further glycemic control. After cycling through 4-month trials (when tolerated) of canagliflozin (Invokana), pioglitazone (Actos), and sitagliptin (Januvia), 24% identified pioglitazone as the one that made them feel best, 33% favored sitagliptin, 37% said canagliflozin was tops, and 6% had no preference, Beverley Shields, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/MDedge News

After making these selections based on just their qualitative self-appraisals, researchers told patients about their hemoglobin A1c status on each of the three agents. It barely budged their choices, which became 25% calling pioglitazone best, 35% naming sitagliptin their preference, 38% opting for canagliflozin, with 2% having no preference.

Further analysis showed that the drug patients preferred was also the one that produced their lowest A1c level when compared with their 8 months on each of the two other agents tested, showing a link between lower A1c levels and improved well-being. The same relationship existed for the drug that caused the fewest adverse events for each patient.
 

Patients prefer feeling better

“Patients tended to prefer the drug that they ‘felt better’ on, with the lowest A1c level and the lowest number of side effects,” explained Dr. Shields, a medical statistician at the University of Exeter (England). Changes in weight appeared less important to patients for establishing a preference.

Mitchel L. Zoler/MDedge News

“This is for when there is equipoise” among drug options, Andrew Hattersley, BMBCh, DM, the study’s principal investigator, said in an interview. “When you are unsure what to prescribe and there is no clear indication for one drug over another, try 4 months of one and 4 months of the other, then let the patient decide.

“Patients had overwhelming positivity about being able to choose their drug,” added Dr. Hattersley, who is also professor of molecular medicine at the University of Exeter.

“This has implications across medicine,” he added. “Whenever you’re not sure how to balance adverse effects and positive effects the best person to decide is the one who experiences the effects.”

“I’m a bit worried by this approach, but it is something new” and worth considering, commented Drazenka P. Barlovic, MD, an endocrinologist at the University Medical Center in Ljubljana, Slovenia, who chaired the session where Dr. Shields gave her report. “We should also have the courage to challenge metformin, as there is no longer an obligation to make it the first drug,” she said in an interview.

The study ran as a secondary analysis of the TriMaster study, which had the primary objective of identifying patient characteristics that could predict which of the three drug options tested worked best for certain patient subgroups. That analysis, presented at the 2021 EASD annual meeting, found that factors such as body mass index and kidney function significantly linked with the clinical responses patients had to each of the three tested agents.

The new analysis focused on 457 of the TriMaster participants who had provided preference information after they had tried all three agents. By design, none of the participants enrolled in the study had a contraindication for any of the tested drugs.

Patients quickly identify adverse effects

“We picked 4 months because it not too long, but long enough to see adverse effects, and to measure on-treatment A1c. Patients quickly identify their adverse events,” Dr. Shields said in an interview.

“This could come into practice now; there is no cost involved. Do it when you’re not certain which drug to prescribe,” Dr. Hattersley suggested. “We can’t know which drug a patient might prefer.” He also stressed telling patients to return quicker than 4 months if they can’t tolerate a new drug.

The findings have already changed Dr. Hattersley’s practice, and he believes it will catch on as he introduces it to local primary care physicians.

The study received no commercial funding. Dr. Shields, Dr. Hattersley, and Dr. Barlovic had no disclosures.






 

STOCKHOLM – When a clinician is unsure which of several equally viable drug options is best for a specific patient with type 2 diabetes, a rational approach is to run a serial trial with each one and then let each patient decide which agent works best for them.

That concept underwent successful testing in a recent trial with 457 patients with type 2 diabetes and already on treatment with metformin or metformin plus a sulfonylurea but needed further glycemic control. After cycling through 4-month trials (when tolerated) of canagliflozin (Invokana), pioglitazone (Actos), and sitagliptin (Januvia), 24% identified pioglitazone as the one that made them feel best, 33% favored sitagliptin, 37% said canagliflozin was tops, and 6% had no preference, Beverley Shields, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/MDedge News

After making these selections based on just their qualitative self-appraisals, researchers told patients about their hemoglobin A1c status on each of the three agents. It barely budged their choices, which became 25% calling pioglitazone best, 35% naming sitagliptin their preference, 38% opting for canagliflozin, with 2% having no preference.

Further analysis showed that the drug patients preferred was also the one that produced their lowest A1c level when compared with their 8 months on each of the two other agents tested, showing a link between lower A1c levels and improved well-being. The same relationship existed for the drug that caused the fewest adverse events for each patient.
 

Patients prefer feeling better

“Patients tended to prefer the drug that they ‘felt better’ on, with the lowest A1c level and the lowest number of side effects,” explained Dr. Shields, a medical statistician at the University of Exeter (England). Changes in weight appeared less important to patients for establishing a preference.

Mitchel L. Zoler/MDedge News

“This is for when there is equipoise” among drug options, Andrew Hattersley, BMBCh, DM, the study’s principal investigator, said in an interview. “When you are unsure what to prescribe and there is no clear indication for one drug over another, try 4 months of one and 4 months of the other, then let the patient decide.

“Patients had overwhelming positivity about being able to choose their drug,” added Dr. Hattersley, who is also professor of molecular medicine at the University of Exeter.

“This has implications across medicine,” he added. “Whenever you’re not sure how to balance adverse effects and positive effects the best person to decide is the one who experiences the effects.”

“I’m a bit worried by this approach, but it is something new” and worth considering, commented Drazenka P. Barlovic, MD, an endocrinologist at the University Medical Center in Ljubljana, Slovenia, who chaired the session where Dr. Shields gave her report. “We should also have the courage to challenge metformin, as there is no longer an obligation to make it the first drug,” she said in an interview.

The study ran as a secondary analysis of the TriMaster study, which had the primary objective of identifying patient characteristics that could predict which of the three drug options tested worked best for certain patient subgroups. That analysis, presented at the 2021 EASD annual meeting, found that factors such as body mass index and kidney function significantly linked with the clinical responses patients had to each of the three tested agents.

The new analysis focused on 457 of the TriMaster participants who had provided preference information after they had tried all three agents. By design, none of the participants enrolled in the study had a contraindication for any of the tested drugs.

Patients quickly identify adverse effects

“We picked 4 months because it not too long, but long enough to see adverse effects, and to measure on-treatment A1c. Patients quickly identify their adverse events,” Dr. Shields said in an interview.

“This could come into practice now; there is no cost involved. Do it when you’re not certain which drug to prescribe,” Dr. Hattersley suggested. “We can’t know which drug a patient might prefer.” He also stressed telling patients to return quicker than 4 months if they can’t tolerate a new drug.

The findings have already changed Dr. Hattersley’s practice, and he believes it will catch on as he introduces it to local primary care physicians.

The study received no commercial funding. Dr. Shields, Dr. Hattersley, and Dr. Barlovic had no disclosures.






 

Data from a large French cohort study suggest that women who have a hysterectomy before 40-45 years of age may be at particular risk of subsequently developing type 2 diabetes.

A 20% increase in the risk for incident diabetes was found comparing women of all ages who had and had not had a hysterectomy (P = .0003).

This risk jumped to a 52% increase when only women below the age of 45 were considered (P < .0001) and was still 38% higher if only women under 40 years were analyzed (P = .005).

Dr. Fabrice Bonnet

“Our findings clearly show that hysterectomy is a risk marker for diabetes,” Fabrice Bonnet, MD, PhD, of Centre Hospitalier Universitaire (CHU) de Rennes (France), said at the annual meeting of the European Association for the Study of Diabetes.

Importantly, this risk appears to occur “independently of any hormonal therapy, any reproductive factors, physical activity, and diet,” Dr. Bonnet added.
 

Findings challenged

“I would like to challenge your findings,” said Peter Nilsson, MD, PhD, a professor at Lund (Sweden) University, during the postpresentation discussion period.

“Could there be a detection bias?” queried Dr. Nilsson. “If you undergo surgery like this, there will be several postoperative visits to a physician and there’s a higher likelihood of somebody taking blood samples and detecting diabetes.

“So, if this is true, it could mean that postoperative controls of goiter or thyroid surgery would bring the same findings,” Dr. Nilsson suggested.

“It is an epidemiological cohort of woman followed for a long time,” Dr. Bonnet responded. “So of course, there probably was more blood testing than in the usual population, but we did not observe the association for another type of surgery and type 2 diabetes.”

Clarifying further, Dr. Bonnet said that they had looked at thyroid surgery but not any other types of abdominal surgery.
 

Assessing the risk of incident diabetes

Hysterectomy is a common surgery among women – more than 400,000 are estimated to be performed every year in the United States, and 80,000 in France, with a rising rate in developing countries, Dr. Bonnet said in an interview.

“We don’t know exactly why that is, but it could have long-term consequences in terms of metabolic effects and the incidence of diabetes,” he said.

Prior research has linked having a hysterectomy with an increased rate of hypertension and cardiovascular risk, and there have also been a few studies linking it to diabetes.

“Our aim was to analyze the relationship between the past history of hysterectomies and the risk of incident diabetes; and specifically, we assessed the influence of age,” Dr. Bonnet said.

To do so, data on more than 83,000 women who had participated in The French E3N Prospective Cohort Study (E3N) were obtained. This large epidemiologic study is the French component of the long-running EPIC study.

For inclusion in the analysis, women had to have no diabetes at baseline, to have had their uterus, ovaries, or both removed for benign gynecologic reasons, and to have had their surgeries performed before any diagnosis of diabetes had been made. A diagnosis of diabetes was identified through the women’s responses to self-report questionnaires and prescriptions for antidiabetic medications.

In all, 2,672 women were found to have developed diabetes during the 16-year follow-up period.

The hazard ratio for the risk of diabetes in women who had and had not had a hysterectomy was 1.30 (95% confidence interval, 1.17-1.43; P < .0001), taking age into account and stratifying for birth generation.

The association held, when there was adjustment for other factors such as smoking status, physical activity, history of diabetes, weight, and adherence to a Mediterranean diet (HR 1.27; 95% CI 1.02-1.05; P = .02).

And, after adjustment for age at menarche, menopausal status, age at which menopause was reached, oral contraceptive and hormone therapy use, and the number of pregnancies, the risk for type 2 diabetes was still apparent in those who had undergoing a hysterectomy (HR, 1.20; 95% CI, 1.09-1.33; P = .0003).
 

Risk increased with oophorectomy

“Women who had both hysterectomy with bilateral oophorectomy had the highest rates of incident diabetes, as compared to women without hysterectomy and no oophorectomy,” said Dr. Bonnet (HR, 1.26; 95% CI, 1.11-1.42; P = .0003).

“This suggests preserving ovarian function is of importance,” he added. “Try to keep the ovaries in place, so just have hysterectomy alone,” he suggested might be the advice to fellow clinicians.

“So, identifying women at higher risk could be followed by a prevention program,” he suggested. “We do this for women who have gestational diabetes,” but for women who have had a hysterectomy, “we didn’t pay attention to this until now.”
 

No increased risk for endometriosis

While hysterectomy appears to up the risk for diabetes, having endometriosis does not. In a separate analysis of data from the E3N cohort, no effect was seen despite the association between endometriosis and other cardiometabolic risk factors.

The HR for incident type 2 diabetes comparing women with and without endometriosis was 10.06 in a fully adjusted statistical model (95% CI, 0.87-1.29). While there was an increase in the risk for diabetes if a woman had endometriosis and had also had a hysterectomy, this was not significant (HR, 1.22; 95% CI, 0.96-1.54).

The E3N study was sponsored by the French Institute for Health and Research. Dr. Bonnet and Dr. Nilsson had no relevant conflicts of interest to disclose.

Data from a large French cohort study suggest that women who have a hysterectomy before 40-45 years of age may be at particular risk of subsequently developing type 2 diabetes.

A 20% increase in the risk for incident diabetes was found comparing women of all ages who had and had not had a hysterectomy (P = .0003).

This risk jumped to a 52% increase when only women below the age of 45 were considered (P < .0001) and was still 38% higher if only women under 40 years were analyzed (P = .005).

Dr. Fabrice Bonnet

“Our findings clearly show that hysterectomy is a risk marker for diabetes,” Fabrice Bonnet, MD, PhD, of Centre Hospitalier Universitaire (CHU) de Rennes (France), said at the annual meeting of the European Association for the Study of Diabetes.

Importantly, this risk appears to occur “independently of any hormonal therapy, any reproductive factors, physical activity, and diet,” Dr. Bonnet added.
 

Findings challenged

“I would like to challenge your findings,” said Peter Nilsson, MD, PhD, a professor at Lund (Sweden) University, during the postpresentation discussion period.

“Could there be a detection bias?” queried Dr. Nilsson. “If you undergo surgery like this, there will be several postoperative visits to a physician and there’s a higher likelihood of somebody taking blood samples and detecting diabetes.

“So, if this is true, it could mean that postoperative controls of goiter or thyroid surgery would bring the same findings,” Dr. Nilsson suggested.

“It is an epidemiological cohort of woman followed for a long time,” Dr. Bonnet responded. “So of course, there probably was more blood testing than in the usual population, but we did not observe the association for another type of surgery and type 2 diabetes.”

Clarifying further, Dr. Bonnet said that they had looked at thyroid surgery but not any other types of abdominal surgery.
 

Assessing the risk of incident diabetes

Hysterectomy is a common surgery among women – more than 400,000 are estimated to be performed every year in the United States, and 80,000 in France, with a rising rate in developing countries, Dr. Bonnet said in an interview.

“We don’t know exactly why that is, but it could have long-term consequences in terms of metabolic effects and the incidence of diabetes,” he said.

Prior research has linked having a hysterectomy with an increased rate of hypertension and cardiovascular risk, and there have also been a few studies linking it to diabetes.

“Our aim was to analyze the relationship between the past history of hysterectomies and the risk of incident diabetes; and specifically, we assessed the influence of age,” Dr. Bonnet said.

To do so, data on more than 83,000 women who had participated in The French E3N Prospective Cohort Study (E3N) were obtained. This large epidemiologic study is the French component of the long-running EPIC study.

For inclusion in the analysis, women had to have no diabetes at baseline, to have had their uterus, ovaries, or both removed for benign gynecologic reasons, and to have had their surgeries performed before any diagnosis of diabetes had been made. A diagnosis of diabetes was identified through the women’s responses to self-report questionnaires and prescriptions for antidiabetic medications.

In all, 2,672 women were found to have developed diabetes during the 16-year follow-up period.

The hazard ratio for the risk of diabetes in women who had and had not had a hysterectomy was 1.30 (95% confidence interval, 1.17-1.43; P < .0001), taking age into account and stratifying for birth generation.

The association held, when there was adjustment for other factors such as smoking status, physical activity, history of diabetes, weight, and adherence to a Mediterranean diet (HR 1.27; 95% CI 1.02-1.05; P = .02).

And, after adjustment for age at menarche, menopausal status, age at which menopause was reached, oral contraceptive and hormone therapy use, and the number of pregnancies, the risk for type 2 diabetes was still apparent in those who had undergoing a hysterectomy (HR, 1.20; 95% CI, 1.09-1.33; P = .0003).
 

Risk increased with oophorectomy

“Women who had both hysterectomy with bilateral oophorectomy had the highest rates of incident diabetes, as compared to women without hysterectomy and no oophorectomy,” said Dr. Bonnet (HR, 1.26; 95% CI, 1.11-1.42; P = .0003).

“This suggests preserving ovarian function is of importance,” he added. “Try to keep the ovaries in place, so just have hysterectomy alone,” he suggested might be the advice to fellow clinicians.

“So, identifying women at higher risk could be followed by a prevention program,” he suggested. “We do this for women who have gestational diabetes,” but for women who have had a hysterectomy, “we didn’t pay attention to this until now.”
 

No increased risk for endometriosis

While hysterectomy appears to up the risk for diabetes, having endometriosis does not. In a separate analysis of data from the E3N cohort, no effect was seen despite the association between endometriosis and other cardiometabolic risk factors.

The HR for incident type 2 diabetes comparing women with and without endometriosis was 10.06 in a fully adjusted statistical model (95% CI, 0.87-1.29). While there was an increase in the risk for diabetes if a woman had endometriosis and had also had a hysterectomy, this was not significant (HR, 1.22; 95% CI, 0.96-1.54).

The E3N study was sponsored by the French Institute for Health and Research. Dr. Bonnet and Dr. Nilsson had no relevant conflicts of interest to disclose.

Data from a large French cohort study suggest that women who have a hysterectomy before 40-45 years of age may be at particular risk of subsequently developing type 2 diabetes.

A 20% increase in the risk for incident diabetes was found comparing women of all ages who had and had not had a hysterectomy (P = .0003).

This risk jumped to a 52% increase when only women below the age of 45 were considered (P < .0001) and was still 38% higher if only women under 40 years were analyzed (P = .005).

Dr. Fabrice Bonnet

“Our findings clearly show that hysterectomy is a risk marker for diabetes,” Fabrice Bonnet, MD, PhD, of Centre Hospitalier Universitaire (CHU) de Rennes (France), said at the annual meeting of the European Association for the Study of Diabetes.

Importantly, this risk appears to occur “independently of any hormonal therapy, any reproductive factors, physical activity, and diet,” Dr. Bonnet added.
 

Findings challenged

“I would like to challenge your findings,” said Peter Nilsson, MD, PhD, a professor at Lund (Sweden) University, during the postpresentation discussion period.

“Could there be a detection bias?” queried Dr. Nilsson. “If you undergo surgery like this, there will be several postoperative visits to a physician and there’s a higher likelihood of somebody taking blood samples and detecting diabetes.

“So, if this is true, it could mean that postoperative controls of goiter or thyroid surgery would bring the same findings,” Dr. Nilsson suggested.

“It is an epidemiological cohort of woman followed for a long time,” Dr. Bonnet responded. “So of course, there probably was more blood testing than in the usual population, but we did not observe the association for another type of surgery and type 2 diabetes.”

Clarifying further, Dr. Bonnet said that they had looked at thyroid surgery but not any other types of abdominal surgery.
 

Assessing the risk of incident diabetes

Hysterectomy is a common surgery among women – more than 400,000 are estimated to be performed every year in the United States, and 80,000 in France, with a rising rate in developing countries, Dr. Bonnet said in an interview.

“We don’t know exactly why that is, but it could have long-term consequences in terms of metabolic effects and the incidence of diabetes,” he said.

Prior research has linked having a hysterectomy with an increased rate of hypertension and cardiovascular risk, and there have also been a few studies linking it to diabetes.

“Our aim was to analyze the relationship between the past history of hysterectomies and the risk of incident diabetes; and specifically, we assessed the influence of age,” Dr. Bonnet said.

To do so, data on more than 83,000 women who had participated in The French E3N Prospective Cohort Study (E3N) were obtained. This large epidemiologic study is the French component of the long-running EPIC study.

For inclusion in the analysis, women had to have no diabetes at baseline, to have had their uterus, ovaries, or both removed for benign gynecologic reasons, and to have had their surgeries performed before any diagnosis of diabetes had been made. A diagnosis of diabetes was identified through the women’s responses to self-report questionnaires and prescriptions for antidiabetic medications.

In all, 2,672 women were found to have developed diabetes during the 16-year follow-up period.

The hazard ratio for the risk of diabetes in women who had and had not had a hysterectomy was 1.30 (95% confidence interval, 1.17-1.43; P < .0001), taking age into account and stratifying for birth generation.

The association held, when there was adjustment for other factors such as smoking status, physical activity, history of diabetes, weight, and adherence to a Mediterranean diet (HR 1.27; 95% CI 1.02-1.05; P = .02).

And, after adjustment for age at menarche, menopausal status, age at which menopause was reached, oral contraceptive and hormone therapy use, and the number of pregnancies, the risk for type 2 diabetes was still apparent in those who had undergoing a hysterectomy (HR, 1.20; 95% CI, 1.09-1.33; P = .0003).
 

Risk increased with oophorectomy

“Women who had both hysterectomy with bilateral oophorectomy had the highest rates of incident diabetes, as compared to women without hysterectomy and no oophorectomy,” said Dr. Bonnet (HR, 1.26; 95% CI, 1.11-1.42; P = .0003).

“This suggests preserving ovarian function is of importance,” he added. “Try to keep the ovaries in place, so just have hysterectomy alone,” he suggested might be the advice to fellow clinicians.

“So, identifying women at higher risk could be followed by a prevention program,” he suggested. “We do this for women who have gestational diabetes,” but for women who have had a hysterectomy, “we didn’t pay attention to this until now.”
 

No increased risk for endometriosis

While hysterectomy appears to up the risk for diabetes, having endometriosis does not. In a separate analysis of data from the E3N cohort, no effect was seen despite the association between endometriosis and other cardiometabolic risk factors.

The HR for incident type 2 diabetes comparing women with and without endometriosis was 10.06 in a fully adjusted statistical model (95% CI, 0.87-1.29). While there was an increase in the risk for diabetes if a woman had endometriosis and had also had a hysterectomy, this was not significant (HR, 1.22; 95% CI, 0.96-1.54).

The E3N study was sponsored by the French Institute for Health and Research. Dr. Bonnet and Dr. Nilsson had no relevant conflicts of interest to disclose.

The Amplatzer Amulet (Abbott) and first-generation Watchman 2.5 (Boston Scientific) devices provide relatively comparable results out to 3 years after left atrial appendage occlusion (LAAO), longer follow-up from the Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE) trial shows.

“The dual-seal Amplatzer Amulet left atrial appendage occluder continued to demonstrate safety and effectiveness through 3 years,” principal investigator Dhanunjaya Lakkireddy, MD, said in a late-breaking session at the recent Transcatheter Cardiovascular Therapeutics annual meeting.

Preliminary results, reported last year, showed that procedural complications were higher with the Amplatzer but that it provided superior closure of the left atrial appendage (LAA) at 45 days and was noninferior with respect to safety at 12 months and efficacy at 18 months.

Amulet IDE is the largest head-to-head comparison of the two devices, enrolling 1,878 high-risk patients with nonvalvular atrial fibrillation undergoing LAA closure to reduce the risk of stroke.

Three-year follow-up was higher with the Amulet device than with the Watchman, at 721 vs. 659 patients, driven by increased deaths (85 vs. 63) and withdrawals (50 vs. 23) in the Watchman group within 18 months, noted Dr. Lakkireddy, Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kan.

Use of oral anticoagulation was higher in the Watchman group at 6 months (2.8% vs. 4.7%; P = .04), 18 months (3.1% vs. 5.6%; P = .01), and 3 years (3.7% vs. 7.3%; P < .01).

This was primarily driven by more late device-related thrombus (DRT) after 6 months with the Watchman device than with the Amulet occluder (23 vs. 10). “Perhaps the dual-closure mechanism of the Amulet explains this fundamental difference, where you have a nice smooth disc that covers the ostium,” he posited.

At 3 years, rates of cardiovascular death trended lower with Amulet than with Watchman (6.6% vs. 8.5%; P = .14), as did all-cause deaths (14.6% vs. 17.9%; P = .07).

Most cardiovascular deaths in the Amulet group were not preceded by a device factor, whereas DRT (1 vs. 4) and peridevice leak 3 mm or more (5 vs. 15) frequently preceded these deaths in the Watchman group, Dr. Lakkireddy observed. No pericardial effusion-related deaths occurred in either group.

Major bleeding, however, trended higher for the Amulet, at 16.1%, compared with 14.7% for the Watchman (P = .46). Ischemic stroke and systemic embolic rates also trended higher for Amulet, at 5%, and 4.6% for Watchman.

The protocol recommended aspirin only for both groups after 6 months. None of the 29 Amulet and 3 of the 29 Watchman patients with an ischemic stroke were on oral anticoagulation at the time of the stroke.

Device factors, however, frequently preceded ischemic strokes in the Watchman group, Dr. Lakkireddy said. DRT occurred in 1 patient with Amulet and 2 patients with Watchman and peridevice leak in 3 with Amulet and 15 with Watchman. “Again, the peridevice leak issue really stands out as an important factor,” he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Based on “data from the large trials, it’s clearly evident that the presence of peridevice leak significantly raises the risk of stroke in follow-up,” he said. “So, attention has to be paid to the choice of the device and how we can mitigate the risk of peridevice leaks in these patients.”

The composite of stroke, systemic embolism, and cardiovascular death occurred in 11.1% of patients with Amulet and 12.7% with Watchman (P = .31).

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

The Amplatzer Amulet (Abbott) and first-generation Watchman 2.5 (Boston Scientific) devices provide relatively comparable results out to 3 years after left atrial appendage occlusion (LAAO), longer follow-up from the Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE) trial shows.

“The dual-seal Amplatzer Amulet left atrial appendage occluder continued to demonstrate safety and effectiveness through 3 years,” principal investigator Dhanunjaya Lakkireddy, MD, said in a late-breaking session at the recent Transcatheter Cardiovascular Therapeutics annual meeting.

Preliminary results, reported last year, showed that procedural complications were higher with the Amplatzer but that it provided superior closure of the left atrial appendage (LAA) at 45 days and was noninferior with respect to safety at 12 months and efficacy at 18 months.

Amulet IDE is the largest head-to-head comparison of the two devices, enrolling 1,878 high-risk patients with nonvalvular atrial fibrillation undergoing LAA closure to reduce the risk of stroke.

Three-year follow-up was higher with the Amulet device than with the Watchman, at 721 vs. 659 patients, driven by increased deaths (85 vs. 63) and withdrawals (50 vs. 23) in the Watchman group within 18 months, noted Dr. Lakkireddy, Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kan.

Use of oral anticoagulation was higher in the Watchman group at 6 months (2.8% vs. 4.7%; P = .04), 18 months (3.1% vs. 5.6%; P = .01), and 3 years (3.7% vs. 7.3%; P < .01).

This was primarily driven by more late device-related thrombus (DRT) after 6 months with the Watchman device than with the Amulet occluder (23 vs. 10). “Perhaps the dual-closure mechanism of the Amulet explains this fundamental difference, where you have a nice smooth disc that covers the ostium,” he posited.

At 3 years, rates of cardiovascular death trended lower with Amulet than with Watchman (6.6% vs. 8.5%; P = .14), as did all-cause deaths (14.6% vs. 17.9%; P = .07).

Most cardiovascular deaths in the Amulet group were not preceded by a device factor, whereas DRT (1 vs. 4) and peridevice leak 3 mm or more (5 vs. 15) frequently preceded these deaths in the Watchman group, Dr. Lakkireddy observed. No pericardial effusion-related deaths occurred in either group.

Major bleeding, however, trended higher for the Amulet, at 16.1%, compared with 14.7% for the Watchman (P = .46). Ischemic stroke and systemic embolic rates also trended higher for Amulet, at 5%, and 4.6% for Watchman.

The protocol recommended aspirin only for both groups after 6 months. None of the 29 Amulet and 3 of the 29 Watchman patients with an ischemic stroke were on oral anticoagulation at the time of the stroke.

Device factors, however, frequently preceded ischemic strokes in the Watchman group, Dr. Lakkireddy said. DRT occurred in 1 patient with Amulet and 2 patients with Watchman and peridevice leak in 3 with Amulet and 15 with Watchman. “Again, the peridevice leak issue really stands out as an important factor,” he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Based on “data from the large trials, it’s clearly evident that the presence of peridevice leak significantly raises the risk of stroke in follow-up,” he said. “So, attention has to be paid to the choice of the device and how we can mitigate the risk of peridevice leaks in these patients.”

The composite of stroke, systemic embolism, and cardiovascular death occurred in 11.1% of patients with Amulet and 12.7% with Watchman (P = .31).

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

The Amplatzer Amulet (Abbott) and first-generation Watchman 2.5 (Boston Scientific) devices provide relatively comparable results out to 3 years after left atrial appendage occlusion (LAAO), longer follow-up from the Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE) trial shows.

“The dual-seal Amplatzer Amulet left atrial appendage occluder continued to demonstrate safety and effectiveness through 3 years,” principal investigator Dhanunjaya Lakkireddy, MD, said in a late-breaking session at the recent Transcatheter Cardiovascular Therapeutics annual meeting.

Preliminary results, reported last year, showed that procedural complications were higher with the Amplatzer but that it provided superior closure of the left atrial appendage (LAA) at 45 days and was noninferior with respect to safety at 12 months and efficacy at 18 months.

Amulet IDE is the largest head-to-head comparison of the two devices, enrolling 1,878 high-risk patients with nonvalvular atrial fibrillation undergoing LAA closure to reduce the risk of stroke.

Three-year follow-up was higher with the Amulet device than with the Watchman, at 721 vs. 659 patients, driven by increased deaths (85 vs. 63) and withdrawals (50 vs. 23) in the Watchman group within 18 months, noted Dr. Lakkireddy, Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kan.

Use of oral anticoagulation was higher in the Watchman group at 6 months (2.8% vs. 4.7%; P = .04), 18 months (3.1% vs. 5.6%; P = .01), and 3 years (3.7% vs. 7.3%; P < .01).

This was primarily driven by more late device-related thrombus (DRT) after 6 months with the Watchman device than with the Amulet occluder (23 vs. 10). “Perhaps the dual-closure mechanism of the Amulet explains this fundamental difference, where you have a nice smooth disc that covers the ostium,” he posited.

At 3 years, rates of cardiovascular death trended lower with Amulet than with Watchman (6.6% vs. 8.5%; P = .14), as did all-cause deaths (14.6% vs. 17.9%; P = .07).

Most cardiovascular deaths in the Amulet group were not preceded by a device factor, whereas DRT (1 vs. 4) and peridevice leak 3 mm or more (5 vs. 15) frequently preceded these deaths in the Watchman group, Dr. Lakkireddy observed. No pericardial effusion-related deaths occurred in either group.

Major bleeding, however, trended higher for the Amulet, at 16.1%, compared with 14.7% for the Watchman (P = .46). Ischemic stroke and systemic embolic rates also trended higher for Amulet, at 5%, and 4.6% for Watchman.

The protocol recommended aspirin only for both groups after 6 months. None of the 29 Amulet and 3 of the 29 Watchman patients with an ischemic stroke were on oral anticoagulation at the time of the stroke.

Device factors, however, frequently preceded ischemic strokes in the Watchman group, Dr. Lakkireddy said. DRT occurred in 1 patient with Amulet and 2 patients with Watchman and peridevice leak in 3 with Amulet and 15 with Watchman. “Again, the peridevice leak issue really stands out as an important factor,” he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Based on “data from the large trials, it’s clearly evident that the presence of peridevice leak significantly raises the risk of stroke in follow-up,” he said. “So, attention has to be paid to the choice of the device and how we can mitigate the risk of peridevice leaks in these patients.”

The composite of stroke, systemic embolism, and cardiovascular death occurred in 11.1% of patients with Amulet and 12.7% with Watchman (P = .31).

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

PORTLAND, ORE. – About 10 years ago when Arash Mostaghimi, MD, MPA, MPH, became an attending physician at Brigham and Women’s Hospital, Boston, he noticed that some of his dermatology colleagues checked the potassium levels religiously in their female patients taking spironolactone, while others never did.

“It led to this question: should we check potassium in healthy young women starting spironolactone for acne?” Dr. Mostaghimi, director of the dermatology inpatient service at Brigham and Women’s, said at the annual meeting of the Pacific Dermatologic Association.

To find out, he and his colleagues reviewed 1,802 serum potassium measurements in a study of healthy young women with no known health conditions who were taking spironolactone, published in 2015. They discovered that 13 of those tests suggested mild hyperkalemia, defined as a level greater than 5.0 mEq/L. Of these, six were rechecked and were normal; no action was taken in the other seven patients.

“This led us to conclude that we spent $78,000 at our institution on testing that did not appear to yield clinically significant information for these patients, and that routine potassium monitoring is unnecessary for most women taking spironolactone for acne,” he said. Their findings have been validated “in many cohorts of data,” he added.

The study serves as an example of efforts dermatologists can take to curb unnecessary costs within the field to be “appropriate stewards of resources,” he continued. “We have to think about the ratio of benefit over cost. It’s not just about the cost, it’s about what you’re getting for the amount of money that you’re spending. The idea of this is not restricting or not giving people medications or access to things that they need. The idea is to do it in a thoughtful way that works across the population.”
 

Value thresholds

Determining the value thresholds of a particular medicine or procedure is also essential to good dermatology practice. To illustrate, Dr. Mostaghimi cited a prospective cohort study that compared treatment patterns and clinical outcomes in 1,536 consecutive patients with nonmelanoma skin cancer (NMSC) with and without limited life expectancy. More than two-thirds of the NMSCs (69%) were treated surgically. After adjusting for tumor and patient characteristics, the researchers found that 43% of patients with low life expectancy died within 5 years, but not from NMSC.

“Does that mean we shouldn’t do surgery for NMSC patients with low life expectancy?” he asked. “Should we do it less? Should we let the patients decide? It’s complicated. As a society, we have to decide what’s worth doing and what’s not worth doing,” he said. “What about old diseases with new treatments, like alopecia areata? Is alopecia areata a cosmetic condition? Dermatologists and patients wouldn’t classify it that way, but many insurers do. How do you negotiate that?”

In 2013, the American Academy of Dermatology identified 10 evidence-based recommendations that can support conversations between patients and dermatologists about treatments, tests, and procedures that may not be necessary. One of the recommendations was not to prescribe oral antifungal therapy for suspected nail fungus without confirmation of fungal infection.

“If a clinician thinks a patient has onychomycosis, he or she is usually right,” Dr. Mostaghimi said. “But what’s the added cost/benefit of performing a KOH followed by PAS testing if negative or performing a PAS test directly versus just treating the patient?”

In 2006, he and his colleagues published the results of a decision analysis to address these questions. They determined that the costs of testing to avoid one case of clinically apparent liver injury with terbinafine treatment was $18.2-$43.7 million for the KOH screening pathway and $37.6 to $90.2 million for the PAS testing pathway.

“Is that worth it?” he asked. “Would we get more value for spending the money elsewhere? In this case, the answer is most likely yes.”

Isotretinoin lab testing

Translating research into recommendations and standards of care is one way to help curb costs in dermatology. As an example, he cited lab monitoring for patients treated with isotretinoin for acne.

“There have been a number of papers over the years that have suggested that the number of labs we do is excessive, that the value that they provide is low, and that abnormal results do not impact our decision-making,” Dr. Mostaghimi said. “Do some patients on isotretinoin get mildly elevated [liver function tests] and hypertriglyceridemia? Yes, that happens. Does it matter? Nothing has demonstrated that it matters. Does it matter that an 18-year-old has high triglycerides for 6 months? Rarely, if ever.”

To promote a new approach, he and a panel of acne experts from five continents performed a Delphi consensus study. Based on their consensus, they proposed a simple approach: For “generally healthy patients without underlying abnormalities or preexisting conditions warranting further investigation,” check ALT and triglycerides prior to initiating isotretinoin. Then start isotretinoin.

“At the peak dose, recheck ALT and triglycerides – this might be at month 2,” Dr. Mostaghimi said. “Other people wait a little bit longer. No labs are required once treatment is complete. Of course, adjust this approach based on your assessment of the patient in front of you. None of these recommendations should replace your clinical judgment and intuition.”

He proposed a new paradigm where dermatologists can ask themselves three questions for every patient they see: Why is this intervention or test being done? Why is it being done in this patient? And why do it at that time? “If we think this way, we can identify some inconsistencies in our own thinking and opportunities for improvement,” he said.

Dr. Mostaghimi reported that he is a consultant to Pfizer, Concert, Lilly, and Bioniz. He is also an advisor to Him & Hers Cosmetics and Digital Diagnostics and is an associate editor for JAMA Dermatology.

PORTLAND, ORE. – About 10 years ago when Arash Mostaghimi, MD, MPA, MPH, became an attending physician at Brigham and Women’s Hospital, Boston, he noticed that some of his dermatology colleagues checked the potassium levels religiously in their female patients taking spironolactone, while others never did.

“It led to this question: should we check potassium in healthy young women starting spironolactone for acne?” Dr. Mostaghimi, director of the dermatology inpatient service at Brigham and Women’s, said at the annual meeting of the Pacific Dermatologic Association.

To find out, he and his colleagues reviewed 1,802 serum potassium measurements in a study of healthy young women with no known health conditions who were taking spironolactone, published in 2015. They discovered that 13 of those tests suggested mild hyperkalemia, defined as a level greater than 5.0 mEq/L. Of these, six were rechecked and were normal; no action was taken in the other seven patients.

“This led us to conclude that we spent $78,000 at our institution on testing that did not appear to yield clinically significant information for these patients, and that routine potassium monitoring is unnecessary for most women taking spironolactone for acne,” he said. Their findings have been validated “in many cohorts of data,” he added.

The study serves as an example of efforts dermatologists can take to curb unnecessary costs within the field to be “appropriate stewards of resources,” he continued. “We have to think about the ratio of benefit over cost. It’s not just about the cost, it’s about what you’re getting for the amount of money that you’re spending. The idea of this is not restricting or not giving people medications or access to things that they need. The idea is to do it in a thoughtful way that works across the population.”
 

Value thresholds

Determining the value thresholds of a particular medicine or procedure is also essential to good dermatology practice. To illustrate, Dr. Mostaghimi cited a prospective cohort study that compared treatment patterns and clinical outcomes in 1,536 consecutive patients with nonmelanoma skin cancer (NMSC) with and without limited life expectancy. More than two-thirds of the NMSCs (69%) were treated surgically. After adjusting for tumor and patient characteristics, the researchers found that 43% of patients with low life expectancy died within 5 years, but not from NMSC.

“Does that mean we shouldn’t do surgery for NMSC patients with low life expectancy?” he asked. “Should we do it less? Should we let the patients decide? It’s complicated. As a society, we have to decide what’s worth doing and what’s not worth doing,” he said. “What about old diseases with new treatments, like alopecia areata? Is alopecia areata a cosmetic condition? Dermatologists and patients wouldn’t classify it that way, but many insurers do. How do you negotiate that?”

In 2013, the American Academy of Dermatology identified 10 evidence-based recommendations that can support conversations between patients and dermatologists about treatments, tests, and procedures that may not be necessary. One of the recommendations was not to prescribe oral antifungal therapy for suspected nail fungus without confirmation of fungal infection.

“If a clinician thinks a patient has onychomycosis, he or she is usually right,” Dr. Mostaghimi said. “But what’s the added cost/benefit of performing a KOH followed by PAS testing if negative or performing a PAS test directly versus just treating the patient?”

In 2006, he and his colleagues published the results of a decision analysis to address these questions. They determined that the costs of testing to avoid one case of clinically apparent liver injury with terbinafine treatment was $18.2-$43.7 million for the KOH screening pathway and $37.6 to $90.2 million for the PAS testing pathway.

“Is that worth it?” he asked. “Would we get more value for spending the money elsewhere? In this case, the answer is most likely yes.”

Isotretinoin lab testing

Translating research into recommendations and standards of care is one way to help curb costs in dermatology. As an example, he cited lab monitoring for patients treated with isotretinoin for acne.

“There have been a number of papers over the years that have suggested that the number of labs we do is excessive, that the value that they provide is low, and that abnormal results do not impact our decision-making,” Dr. Mostaghimi said. “Do some patients on isotretinoin get mildly elevated [liver function tests] and hypertriglyceridemia? Yes, that happens. Does it matter? Nothing has demonstrated that it matters. Does it matter that an 18-year-old has high triglycerides for 6 months? Rarely, if ever.”

To promote a new approach, he and a panel of acne experts from five continents performed a Delphi consensus study. Based on their consensus, they proposed a simple approach: For “generally healthy patients without underlying abnormalities or preexisting conditions warranting further investigation,” check ALT and triglycerides prior to initiating isotretinoin. Then start isotretinoin.

“At the peak dose, recheck ALT and triglycerides – this might be at month 2,” Dr. Mostaghimi said. “Other people wait a little bit longer. No labs are required once treatment is complete. Of course, adjust this approach based on your assessment of the patient in front of you. None of these recommendations should replace your clinical judgment and intuition.”

He proposed a new paradigm where dermatologists can ask themselves three questions for every patient they see: Why is this intervention or test being done? Why is it being done in this patient? And why do it at that time? “If we think this way, we can identify some inconsistencies in our own thinking and opportunities for improvement,” he said.

Dr. Mostaghimi reported that he is a consultant to Pfizer, Concert, Lilly, and Bioniz. He is also an advisor to Him & Hers Cosmetics and Digital Diagnostics and is an associate editor for JAMA Dermatology.

PORTLAND, ORE. – About 10 years ago when Arash Mostaghimi, MD, MPA, MPH, became an attending physician at Brigham and Women’s Hospital, Boston, he noticed that some of his dermatology colleagues checked the potassium levels religiously in their female patients taking spironolactone, while others never did.

“It led to this question: should we check potassium in healthy young women starting spironolactone for acne?” Dr. Mostaghimi, director of the dermatology inpatient service at Brigham and Women’s, said at the annual meeting of the Pacific Dermatologic Association.

To find out, he and his colleagues reviewed 1,802 serum potassium measurements in a study of healthy young women with no known health conditions who were taking spironolactone, published in 2015. They discovered that 13 of those tests suggested mild hyperkalemia, defined as a level greater than 5.0 mEq/L. Of these, six were rechecked and were normal; no action was taken in the other seven patients.

“This led us to conclude that we spent $78,000 at our institution on testing that did not appear to yield clinically significant information for these patients, and that routine potassium monitoring is unnecessary for most women taking spironolactone for acne,” he said. Their findings have been validated “in many cohorts of data,” he added.

The study serves as an example of efforts dermatologists can take to curb unnecessary costs within the field to be “appropriate stewards of resources,” he continued. “We have to think about the ratio of benefit over cost. It’s not just about the cost, it’s about what you’re getting for the amount of money that you’re spending. The idea of this is not restricting or not giving people medications or access to things that they need. The idea is to do it in a thoughtful way that works across the population.”
 

Value thresholds

Determining the value thresholds of a particular medicine or procedure is also essential to good dermatology practice. To illustrate, Dr. Mostaghimi cited a prospective cohort study that compared treatment patterns and clinical outcomes in 1,536 consecutive patients with nonmelanoma skin cancer (NMSC) with and without limited life expectancy. More than two-thirds of the NMSCs (69%) were treated surgically. After adjusting for tumor and patient characteristics, the researchers found that 43% of patients with low life expectancy died within 5 years, but not from NMSC.

“Does that mean we shouldn’t do surgery for NMSC patients with low life expectancy?” he asked. “Should we do it less? Should we let the patients decide? It’s complicated. As a society, we have to decide what’s worth doing and what’s not worth doing,” he said. “What about old diseases with new treatments, like alopecia areata? Is alopecia areata a cosmetic condition? Dermatologists and patients wouldn’t classify it that way, but many insurers do. How do you negotiate that?”

In 2013, the American Academy of Dermatology identified 10 evidence-based recommendations that can support conversations between patients and dermatologists about treatments, tests, and procedures that may not be necessary. One of the recommendations was not to prescribe oral antifungal therapy for suspected nail fungus without confirmation of fungal infection.

“If a clinician thinks a patient has onychomycosis, he or she is usually right,” Dr. Mostaghimi said. “But what’s the added cost/benefit of performing a KOH followed by PAS testing if negative or performing a PAS test directly versus just treating the patient?”

In 2006, he and his colleagues published the results of a decision analysis to address these questions. They determined that the costs of testing to avoid one case of clinically apparent liver injury with terbinafine treatment was $18.2-$43.7 million for the KOH screening pathway and $37.6 to $90.2 million for the PAS testing pathway.

“Is that worth it?” he asked. “Would we get more value for spending the money elsewhere? In this case, the answer is most likely yes.”

Isotretinoin lab testing

Translating research into recommendations and standards of care is one way to help curb costs in dermatology. As an example, he cited lab monitoring for patients treated with isotretinoin for acne.

“There have been a number of papers over the years that have suggested that the number of labs we do is excessive, that the value that they provide is low, and that abnormal results do not impact our decision-making,” Dr. Mostaghimi said. “Do some patients on isotretinoin get mildly elevated [liver function tests] and hypertriglyceridemia? Yes, that happens. Does it matter? Nothing has demonstrated that it matters. Does it matter that an 18-year-old has high triglycerides for 6 months? Rarely, if ever.”

To promote a new approach, he and a panel of acne experts from five continents performed a Delphi consensus study. Based on their consensus, they proposed a simple approach: For “generally healthy patients without underlying abnormalities or preexisting conditions warranting further investigation,” check ALT and triglycerides prior to initiating isotretinoin. Then start isotretinoin.

“At the peak dose, recheck ALT and triglycerides – this might be at month 2,” Dr. Mostaghimi said. “Other people wait a little bit longer. No labs are required once treatment is complete. Of course, adjust this approach based on your assessment of the patient in front of you. None of these recommendations should replace your clinical judgment and intuition.”

He proposed a new paradigm where dermatologists can ask themselves three questions for every patient they see: Why is this intervention or test being done? Why is it being done in this patient? And why do it at that time? “If we think this way, we can identify some inconsistencies in our own thinking and opportunities for improvement,” he said.

Dr. Mostaghimi reported that he is a consultant to Pfizer, Concert, Lilly, and Bioniz. He is also an advisor to Him & Hers Cosmetics and Digital Diagnostics and is an associate editor for JAMA Dermatology.

Mexican researchers found no direct association between SARS-CoV-2 vaccination and worsening symptoms among 60 patients with Parkinson’s disease. Nonmotor symptoms seemed to improve after SARS-CoV-2 vaccination, although the investigators could not verify a causal relationship.

Vaccination programs should continue for patients with Parkinson’s disease, they said, reporting their clinical results at the International Congress of Parkinson’s Disease and Movement Disorders.

The International Parkinson and Movement Disorder Society has recommended vaccining patients with Parkinson’s disease. “All approved mRNA-based and viral vector vaccines are not expected to interact with Parkinson’s disease, but patients [still] report concern with regard to the benefits, risks, and safeness in Parkinson’s disease,” Mayela Rodríguez-Violante, MD, MSc, and colleagues wrote in an abstract of their findings.

Social isolation may be contributing to these beliefs and concerns, though this is inconclusive.

Investigators from Mexico City conducted a retrospective study of patients with Parkinson’s disease to see how COVID-19 vaccination affected motor and nonmotor symptoms. They enlisted 60 patients (66.7% were male; aged 65.7 ± 11.35 years) who received either a vector-viral vaccine (Vaxzevria Coronavirus) or an mRNA vaccine (BNT162b2).

A Wilcoxon signed-rank test assessed scale differences before and after vaccination, measuring motor involvement (Unified Parkinson’s Disease Rating Scale), nonmotor involvement (Non-Motor Rating Scale [NMSS]), cognitive impairment (Montreal Cognitive Assessment), and quality of life (8-item Parkinson’s Disease Questionnaire index).

Investigators found no significant difference between scales, although they did notice a marked improvement in non-motor symptoms.

“The main takeaway is that vaccination against COVID-19 does not appear to worsen motor or nonmotor symptoms in persons with Parkinson’s disease. The benefits outweigh the risks,” said Dr. Rodríguez-Violante, the study’s lead author and a movement disorder specialist at the National Institute of Neurology and Neurosurgery, Mexico City.

Next steps are to increase the sample size to see if it’s possible to have a similar number in terms of type of vaccine, said Dr. Rodríguez-Violante. “Also, the data presented refers to primary series doses so booster effects will also be studied.”

Few studies have looked at vaccines and their possible effects on this patient population. However, a 2021 study of 181 patients with Parkinson’s disease reported that 2 (1.1%) had adverse effects after receiving the BNT162b2 mRNA vaccine. One of the patients, a 61-year-old woman with a decade-long history of Parkinson’s disease, developed severe, continuous, generalized dyskinesia 6 hours after a first dose of vaccine. The second patient was 79 years old and had Parkinson’s disease for 5 years. She developed fever, confusion, delusions, and continuous severe dyskinesia for 3 days following her vaccination.

“This highlights that there is a variability in the response triggered by the vaccine that might likely depend on individual immunological profiles … clinicians should be aware of this possibility and monitor their patients after they receive their vaccination,” Roberto Erro, MD, PhD and colleagues wrote in the Movement Disorders journal.

Mexican researchers found no direct association between SARS-CoV-2 vaccination and worsening symptoms among 60 patients with Parkinson’s disease. Nonmotor symptoms seemed to improve after SARS-CoV-2 vaccination, although the investigators could not verify a causal relationship.

Vaccination programs should continue for patients with Parkinson’s disease, they said, reporting their clinical results at the International Congress of Parkinson’s Disease and Movement Disorders.

The International Parkinson and Movement Disorder Society has recommended vaccining patients with Parkinson’s disease. “All approved mRNA-based and viral vector vaccines are not expected to interact with Parkinson’s disease, but patients [still] report concern with regard to the benefits, risks, and safeness in Parkinson’s disease,” Mayela Rodríguez-Violante, MD, MSc, and colleagues wrote in an abstract of their findings.

Social isolation may be contributing to these beliefs and concerns, though this is inconclusive.

Investigators from Mexico City conducted a retrospective study of patients with Parkinson’s disease to see how COVID-19 vaccination affected motor and nonmotor symptoms. They enlisted 60 patients (66.7% were male; aged 65.7 ± 11.35 years) who received either a vector-viral vaccine (Vaxzevria Coronavirus) or an mRNA vaccine (BNT162b2).

A Wilcoxon signed-rank test assessed scale differences before and after vaccination, measuring motor involvement (Unified Parkinson’s Disease Rating Scale), nonmotor involvement (Non-Motor Rating Scale [NMSS]), cognitive impairment (Montreal Cognitive Assessment), and quality of life (8-item Parkinson’s Disease Questionnaire index).

Investigators found no significant difference between scales, although they did notice a marked improvement in non-motor symptoms.

“The main takeaway is that vaccination against COVID-19 does not appear to worsen motor or nonmotor symptoms in persons with Parkinson’s disease. The benefits outweigh the risks,” said Dr. Rodríguez-Violante, the study’s lead author and a movement disorder specialist at the National Institute of Neurology and Neurosurgery, Mexico City.

Next steps are to increase the sample size to see if it’s possible to have a similar number in terms of type of vaccine, said Dr. Rodríguez-Violante. “Also, the data presented refers to primary series doses so booster effects will also be studied.”

Few studies have looked at vaccines and their possible effects on this patient population. However, a 2021 study of 181 patients with Parkinson’s disease reported that 2 (1.1%) had adverse effects after receiving the BNT162b2 mRNA vaccine. One of the patients, a 61-year-old woman with a decade-long history of Parkinson’s disease, developed severe, continuous, generalized dyskinesia 6 hours after a first dose of vaccine. The second patient was 79 years old and had Parkinson’s disease for 5 years. She developed fever, confusion, delusions, and continuous severe dyskinesia for 3 days following her vaccination.

“This highlights that there is a variability in the response triggered by the vaccine that might likely depend on individual immunological profiles … clinicians should be aware of this possibility and monitor their patients after they receive their vaccination,” Roberto Erro, MD, PhD and colleagues wrote in the Movement Disorders journal.

Mexican researchers found no direct association between SARS-CoV-2 vaccination and worsening symptoms among 60 patients with Parkinson’s disease. Nonmotor symptoms seemed to improve after SARS-CoV-2 vaccination, although the investigators could not verify a causal relationship.

Vaccination programs should continue for patients with Parkinson’s disease, they said, reporting their clinical results at the International Congress of Parkinson’s Disease and Movement Disorders.

The International Parkinson and Movement Disorder Society has recommended vaccining patients with Parkinson’s disease. “All approved mRNA-based and viral vector vaccines are not expected to interact with Parkinson’s disease, but patients [still] report concern with regard to the benefits, risks, and safeness in Parkinson’s disease,” Mayela Rodríguez-Violante, MD, MSc, and colleagues wrote in an abstract of their findings.

Social isolation may be contributing to these beliefs and concerns, though this is inconclusive.

Investigators from Mexico City conducted a retrospective study of patients with Parkinson’s disease to see how COVID-19 vaccination affected motor and nonmotor symptoms. They enlisted 60 patients (66.7% were male; aged 65.7 ± 11.35 years) who received either a vector-viral vaccine (Vaxzevria Coronavirus) or an mRNA vaccine (BNT162b2).

A Wilcoxon signed-rank test assessed scale differences before and after vaccination, measuring motor involvement (Unified Parkinson’s Disease Rating Scale), nonmotor involvement (Non-Motor Rating Scale [NMSS]), cognitive impairment (Montreal Cognitive Assessment), and quality of life (8-item Parkinson’s Disease Questionnaire index).

Investigators found no significant difference between scales, although they did notice a marked improvement in non-motor symptoms.

“The main takeaway is that vaccination against COVID-19 does not appear to worsen motor or nonmotor symptoms in persons with Parkinson’s disease. The benefits outweigh the risks,” said Dr. Rodríguez-Violante, the study’s lead author and a movement disorder specialist at the National Institute of Neurology and Neurosurgery, Mexico City.

Next steps are to increase the sample size to see if it’s possible to have a similar number in terms of type of vaccine, said Dr. Rodríguez-Violante. “Also, the data presented refers to primary series doses so booster effects will also be studied.”

Few studies have looked at vaccines and their possible effects on this patient population. However, a 2021 study of 181 patients with Parkinson’s disease reported that 2 (1.1%) had adverse effects after receiving the BNT162b2 mRNA vaccine. One of the patients, a 61-year-old woman with a decade-long history of Parkinson’s disease, developed severe, continuous, generalized dyskinesia 6 hours after a first dose of vaccine. The second patient was 79 years old and had Parkinson’s disease for 5 years. She developed fever, confusion, delusions, and continuous severe dyskinesia for 3 days following her vaccination.

“This highlights that there is a variability in the response triggered by the vaccine that might likely depend on individual immunological profiles … clinicians should be aware of this possibility and monitor their patients after they receive their vaccination,” Roberto Erro, MD, PhD and colleagues wrote in the Movement Disorders journal.

STOCKHOLM – Shivering upon repeated short exposures to cold improves glucose tolerance, decreases fasting blood glucose and lipid levels, and markedly reduces blood pressure, show new study results in adults with obesity and overweight.

Presenting the preliminary findings at the annual meeting of the European Association for the Study of Diabetes, Adam Sellers, a PhD student from Maastricht (the Netherlands) University, said: “The results are highly promising and may eventually suggest an alternative treatment or preventative measure for type 2 diabetes.”

Dr. Sellers found that 10 daily 1-hour sessions of shivering at 10° C led to 85% of participants showing a drop in fasting glucose, and a 32% drop in lipid levels, as well as a blood pressure drop of around 8% overall.

Although cold exposure is known to increase brown fat, Dr. Sellers doesn’t believe this explains his findings. “This research, in addition to two other prior studies, suggest that shivering and skeletal muscle may play a more important role than brown fat,” he said.

“Muscle can contract mechanically – [the concept of the] shivers – thereby generating heat, and there is considerably more muscle than brown fat in a human, so shivering can burn more calories and produce more heat,” he explained.

He added that, in the future, “in a similar way to saunas and steam rooms, there might be cold rooms where people go and sit in the cold room and shiver, or possibly patients attend hospital and shivering is induced.”

Audience member Anna Krook, PhD, professor of integrative physiology at the Karolinska Institute, Stockholm, commented on the work, saying the results are “potent” and demonstrate the metabolic effect of shivering. “One thing that struck me was, given the time the subject had to spend – 1 hour shivering over 10 days, I wonder if 1 hour of exercise would show similarly potent effects, and perhaps for those people who cannot perform exercise for whatever reason this might be a good alternative.”

She pointed out that, in terms of translation into practice, it “really depends on how tolerable this is. It also shows how important our muscle is in regulating metabolism. The study showed that you had to be shivering, and it wasn’t just enough to be cold, which has implications for the role of brown fat, especially when we consider the small amount of brown fat we have compared to muscle, which can be half of body weight.”

And Denis P. Blondin, PhD, said: “The reality is that we know it can be difficult and even painful for individuals with obesity to perform exercise, and therefore, cold exposure offers a passive way of improving our metabolic profile and cardiovascular health.”

“Some will argue that it is unrealistic to propose cold exposure as a therapy, but people overlook the fact that cold exposure [mostly through cold-water immersion] has increased in popularity over the past 5 years and has also been a cultural staple for many Nordic countries, albeit often performed with heat exposure as well [see the use of saunas and cold-water swimming in Finland and other Nordic countries],” added Dr. Blondin, of the faculty of medicine and health sciences, University of Sherbrooke (Que.)

“While it can certainly be uncomfortable at first (like starting an exercise program), we adapt very quickly,” he added.
 

1 hour in a cold-water suit to induce shivering

In the current study, Dr. Sellers exposed adults (aged 40-75 years; 11 men and 4 postmenopausal women) with overweight/obesity (body mass index, 27-35 kg/m²) to 10 consecutive cold exposures of at least 1 hour of shivering per cold exposure.

“The shivering in this new research was more intense [than in prior studies] and was induced with a different cold exposure method – a 10° C water-perfused suit [compared with a prior study of 14-15° C, 6 hours/day]. This facilitated a shorter cold exposure duration, deemed feasible for the participants,” explained Dr. Sellers.

“At baseline, participants had glucose and A1c levels at the upper end of the normal criteria [5.5 mmol/l and 5.4%, respectively],” he said, referring to measurements that were suggestive of possible progression to type 2 diabetes.

He explained how the cold exposure was applied. “We induced the cold with a water-perfused suit worn by the participant, through which water flows at 10° C, and this cools the participant. Eventually, the participant starts to shiver, and does so for at least 1 hour every morning for 10 days.”

Participants’ shivering-induced heat production was measured via surface electromyography and visual observation to confirm the presence of shivering. Both before and after the 10-day course of shivering, physiological measurements were taken in the morning while participants were at rest in an overnight fasted state, and under thermoneutral conditions. Blood pressure and fasting blood glucose were measured.

A 2-hour oral glucose tolerance test (OGTT) was conducted twice for each participant: on the morning before the 10-day course of shivering and again on the morning after the final 10th day of shivering.

The primary endpoint was change from before to after the 10-day shivering intervention, as represented by the total area under the curve of glucose levels over time during the OGTT. 

“This provides a measure of the glucose concentrations in the blood before and after the 10 shivering sessions over the 10 days.”

courtesy Sten van Beek

Fasting glucose and blood lipids fall, glucose tolerance improves

After 10 shivering sessions, mean fasting plasma glucose decreased significantly in 13 out of the 15 participants, compared with before the first session (from 5.84 mmol/L to 5.67 mmol/L; P = .013).

Glucose tolerance during the OGTT improved by 6% (P = .041). “We can see that this was not due to a change in their insulin concentrations in the blood,” remarked Dr. Sellers, referring to the finding that plasma insulin concentrations at baseline and during the OGTT did not change.

Fasting plasma triglyceride and free-fatty acid concentrations also decreased significantly by 32% (P = .001) and 11% (P = .036), respectively.

“This is important because free-fatty acids are involved in the role of insulin resistance,” said Dr. Sellers. “In addition, the large reduction in serum triglycerides could have implications for atherosclerosis, which may also be beneficial.”

Dr. Sellers also found that systolic blood pressure decreased by 10 mm Hg or 7.4% (P < .001), while diastolic blood pressure decreased by 7 mm Hg or 8.1% (P < .001) on average. This lowering was seen in all participants.

“Again, quite strikingly, all participants showed” a reduction in blood pressure, said Dr. Sellers, which he noted relates to a decrease in resting heart rate (P = .062).
 

Brown fat or skeletal muscle contraction?

Dr. Sellers pointed out that, despite nonshivering thermogenesis being involved in mild cold acclimation, the data so far suggest that some level of mild muscle activity or shivering appears crucial in provoking the beneficial metabolic effects of cold acclimation.

“Brown fat is a metabolic heating system inside our bodies, burning calories”, explained Dr. Sellers. “This generates heat and prevents calories from being deposited as normal white fat. Brown fat is activated during cold and when we eat, but its activity is less in older adults and in individuals with obesity and diabetes.”

“Going forward, we might investigate the effects of shorter duration – so more intense shivering – to try and elucidate more precisely the optimum duration and intensity of shivering needed,” said Dr. Sellers.

“Our findings are promising and may have important health implications. In future studies, we plan to assess the effect of shivering in adults with type 2 diabetes,” he concluded.

Dr. Seller and Dr. Krook have reported no relevant financial relationships.

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

STOCKHOLM – Shivering upon repeated short exposures to cold improves glucose tolerance, decreases fasting blood glucose and lipid levels, and markedly reduces blood pressure, show new study results in adults with obesity and overweight.

Presenting the preliminary findings at the annual meeting of the European Association for the Study of Diabetes, Adam Sellers, a PhD student from Maastricht (the Netherlands) University, said: “The results are highly promising and may eventually suggest an alternative treatment or preventative measure for type 2 diabetes.”

Dr. Sellers found that 10 daily 1-hour sessions of shivering at 10° C led to 85% of participants showing a drop in fasting glucose, and a 32% drop in lipid levels, as well as a blood pressure drop of around 8% overall.

Although cold exposure is known to increase brown fat, Dr. Sellers doesn’t believe this explains his findings. “This research, in addition to two other prior studies, suggest that shivering and skeletal muscle may play a more important role than brown fat,” he said.

“Muscle can contract mechanically – [the concept of the] shivers – thereby generating heat, and there is considerably more muscle than brown fat in a human, so shivering can burn more calories and produce more heat,” he explained.

He added that, in the future, “in a similar way to saunas and steam rooms, there might be cold rooms where people go and sit in the cold room and shiver, or possibly patients attend hospital and shivering is induced.”

Audience member Anna Krook, PhD, professor of integrative physiology at the Karolinska Institute, Stockholm, commented on the work, saying the results are “potent” and demonstrate the metabolic effect of shivering. “One thing that struck me was, given the time the subject had to spend – 1 hour shivering over 10 days, I wonder if 1 hour of exercise would show similarly potent effects, and perhaps for those people who cannot perform exercise for whatever reason this might be a good alternative.”

She pointed out that, in terms of translation into practice, it “really depends on how tolerable this is. It also shows how important our muscle is in regulating metabolism. The study showed that you had to be shivering, and it wasn’t just enough to be cold, which has implications for the role of brown fat, especially when we consider the small amount of brown fat we have compared to muscle, which can be half of body weight.”

And Denis P. Blondin, PhD, said: “The reality is that we know it can be difficult and even painful for individuals with obesity to perform exercise, and therefore, cold exposure offers a passive way of improving our metabolic profile and cardiovascular health.”

“Some will argue that it is unrealistic to propose cold exposure as a therapy, but people overlook the fact that cold exposure [mostly through cold-water immersion] has increased in popularity over the past 5 years and has also been a cultural staple for many Nordic countries, albeit often performed with heat exposure as well [see the use of saunas and cold-water swimming in Finland and other Nordic countries],” added Dr. Blondin, of the faculty of medicine and health sciences, University of Sherbrooke (Que.)

“While it can certainly be uncomfortable at first (like starting an exercise program), we adapt very quickly,” he added.
 

1 hour in a cold-water suit to induce shivering

In the current study, Dr. Sellers exposed adults (aged 40-75 years; 11 men and 4 postmenopausal women) with overweight/obesity (body mass index, 27-35 kg/m²) to 10 consecutive cold exposures of at least 1 hour of shivering per cold exposure.

“The shivering in this new research was more intense [than in prior studies] and was induced with a different cold exposure method – a 10° C water-perfused suit [compared with a prior study of 14-15° C, 6 hours/day]. This facilitated a shorter cold exposure duration, deemed feasible for the participants,” explained Dr. Sellers.

“At baseline, participants had glucose and A1c levels at the upper end of the normal criteria [5.5 mmol/l and 5.4%, respectively],” he said, referring to measurements that were suggestive of possible progression to type 2 diabetes.

He explained how the cold exposure was applied. “We induced the cold with a water-perfused suit worn by the participant, through which water flows at 10° C, and this cools the participant. Eventually, the participant starts to shiver, and does so for at least 1 hour every morning for 10 days.”

Participants’ shivering-induced heat production was measured via surface electromyography and visual observation to confirm the presence of shivering. Both before and after the 10-day course of shivering, physiological measurements were taken in the morning while participants were at rest in an overnight fasted state, and under thermoneutral conditions. Blood pressure and fasting blood glucose were measured.

A 2-hour oral glucose tolerance test (OGTT) was conducted twice for each participant: on the morning before the 10-day course of shivering and again on the morning after the final 10th day of shivering.

The primary endpoint was change from before to after the 10-day shivering intervention, as represented by the total area under the curve of glucose levels over time during the OGTT. 

“This provides a measure of the glucose concentrations in the blood before and after the 10 shivering sessions over the 10 days.”

courtesy Sten van Beek

Fasting glucose and blood lipids fall, glucose tolerance improves

After 10 shivering sessions, mean fasting plasma glucose decreased significantly in 13 out of the 15 participants, compared with before the first session (from 5.84 mmol/L to 5.67 mmol/L; P = .013).

Glucose tolerance during the OGTT improved by 6% (P = .041). “We can see that this was not due to a change in their insulin concentrations in the blood,” remarked Dr. Sellers, referring to the finding that plasma insulin concentrations at baseline and during the OGTT did not change.

Fasting plasma triglyceride and free-fatty acid concentrations also decreased significantly by 32% (P = .001) and 11% (P = .036), respectively.

“This is important because free-fatty acids are involved in the role of insulin resistance,” said Dr. Sellers. “In addition, the large reduction in serum triglycerides could have implications for atherosclerosis, which may also be beneficial.”

Dr. Sellers also found that systolic blood pressure decreased by 10 mm Hg or 7.4% (P < .001), while diastolic blood pressure decreased by 7 mm Hg or 8.1% (P < .001) on average. This lowering was seen in all participants.

“Again, quite strikingly, all participants showed” a reduction in blood pressure, said Dr. Sellers, which he noted relates to a decrease in resting heart rate (P = .062).
 

Brown fat or skeletal muscle contraction?

Dr. Sellers pointed out that, despite nonshivering thermogenesis being involved in mild cold acclimation, the data so far suggest that some level of mild muscle activity or shivering appears crucial in provoking the beneficial metabolic effects of cold acclimation.

“Brown fat is a metabolic heating system inside our bodies, burning calories”, explained Dr. Sellers. “This generates heat and prevents calories from being deposited as normal white fat. Brown fat is activated during cold and when we eat, but its activity is less in older adults and in individuals with obesity and diabetes.”

“Going forward, we might investigate the effects of shorter duration – so more intense shivering – to try and elucidate more precisely the optimum duration and intensity of shivering needed,” said Dr. Sellers.

“Our findings are promising and may have important health implications. In future studies, we plan to assess the effect of shivering in adults with type 2 diabetes,” he concluded.

Dr. Seller and Dr. Krook have reported no relevant financial relationships.

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

STOCKHOLM – Shivering upon repeated short exposures to cold improves glucose tolerance, decreases fasting blood glucose and lipid levels, and markedly reduces blood pressure, show new study results in adults with obesity and overweight.

Presenting the preliminary findings at the annual meeting of the European Association for the Study of Diabetes, Adam Sellers, a PhD student from Maastricht (the Netherlands) University, said: “The results are highly promising and may eventually suggest an alternative treatment or preventative measure for type 2 diabetes.”

Dr. Sellers found that 10 daily 1-hour sessions of shivering at 10° C led to 85% of participants showing a drop in fasting glucose, and a 32% drop in lipid levels, as well as a blood pressure drop of around 8% overall.

Although cold exposure is known to increase brown fat, Dr. Sellers doesn’t believe this explains his findings. “This research, in addition to two other prior studies, suggest that shivering and skeletal muscle may play a more important role than brown fat,” he said.

“Muscle can contract mechanically – [the concept of the] shivers – thereby generating heat, and there is considerably more muscle than brown fat in a human, so shivering can burn more calories and produce more heat,” he explained.

He added that, in the future, “in a similar way to saunas and steam rooms, there might be cold rooms where people go and sit in the cold room and shiver, or possibly patients attend hospital and shivering is induced.”

Audience member Anna Krook, PhD, professor of integrative physiology at the Karolinska Institute, Stockholm, commented on the work, saying the results are “potent” and demonstrate the metabolic effect of shivering. “One thing that struck me was, given the time the subject had to spend – 1 hour shivering over 10 days, I wonder if 1 hour of exercise would show similarly potent effects, and perhaps for those people who cannot perform exercise for whatever reason this might be a good alternative.”

She pointed out that, in terms of translation into practice, it “really depends on how tolerable this is. It also shows how important our muscle is in regulating metabolism. The study showed that you had to be shivering, and it wasn’t just enough to be cold, which has implications for the role of brown fat, especially when we consider the small amount of brown fat we have compared to muscle, which can be half of body weight.”

And Denis P. Blondin, PhD, said: “The reality is that we know it can be difficult and even painful for individuals with obesity to perform exercise, and therefore, cold exposure offers a passive way of improving our metabolic profile and cardiovascular health.”

“Some will argue that it is unrealistic to propose cold exposure as a therapy, but people overlook the fact that cold exposure [mostly through cold-water immersion] has increased in popularity over the past 5 years and has also been a cultural staple for many Nordic countries, albeit often performed with heat exposure as well [see the use of saunas and cold-water swimming in Finland and other Nordic countries],” added Dr. Blondin, of the faculty of medicine and health sciences, University of Sherbrooke (Que.)

“While it can certainly be uncomfortable at first (like starting an exercise program), we adapt very quickly,” he added.
 

1 hour in a cold-water suit to induce shivering

In the current study, Dr. Sellers exposed adults (aged 40-75 years; 11 men and 4 postmenopausal women) with overweight/obesity (body mass index, 27-35 kg/m²) to 10 consecutive cold exposures of at least 1 hour of shivering per cold exposure.

“The shivering in this new research was more intense [than in prior studies] and was induced with a different cold exposure method – a 10° C water-perfused suit [compared with a prior study of 14-15° C, 6 hours/day]. This facilitated a shorter cold exposure duration, deemed feasible for the participants,” explained Dr. Sellers.

“At baseline, participants had glucose and A1c levels at the upper end of the normal criteria [5.5 mmol/l and 5.4%, respectively],” he said, referring to measurements that were suggestive of possible progression to type 2 diabetes.

He explained how the cold exposure was applied. “We induced the cold with a water-perfused suit worn by the participant, through which water flows at 10° C, and this cools the participant. Eventually, the participant starts to shiver, and does so for at least 1 hour every morning for 10 days.”

Participants’ shivering-induced heat production was measured via surface electromyography and visual observation to confirm the presence of shivering. Both before and after the 10-day course of shivering, physiological measurements were taken in the morning while participants were at rest in an overnight fasted state, and under thermoneutral conditions. Blood pressure and fasting blood glucose were measured.

A 2-hour oral glucose tolerance test (OGTT) was conducted twice for each participant: on the morning before the 10-day course of shivering and again on the morning after the final 10th day of shivering.

The primary endpoint was change from before to after the 10-day shivering intervention, as represented by the total area under the curve of glucose levels over time during the OGTT. 

“This provides a measure of the glucose concentrations in the blood before and after the 10 shivering sessions over the 10 days.”

courtesy Sten van Beek

Fasting glucose and blood lipids fall, glucose tolerance improves

After 10 shivering sessions, mean fasting plasma glucose decreased significantly in 13 out of the 15 participants, compared with before the first session (from 5.84 mmol/L to 5.67 mmol/L; P = .013).

Glucose tolerance during the OGTT improved by 6% (P = .041). “We can see that this was not due to a change in their insulin concentrations in the blood,” remarked Dr. Sellers, referring to the finding that plasma insulin concentrations at baseline and during the OGTT did not change.

Fasting plasma triglyceride and free-fatty acid concentrations also decreased significantly by 32% (P = .001) and 11% (P = .036), respectively.

“This is important because free-fatty acids are involved in the role of insulin resistance,” said Dr. Sellers. “In addition, the large reduction in serum triglycerides could have implications for atherosclerosis, which may also be beneficial.”

Dr. Sellers also found that systolic blood pressure decreased by 10 mm Hg or 7.4% (P < .001), while diastolic blood pressure decreased by 7 mm Hg or 8.1% (P < .001) on average. This lowering was seen in all participants.

“Again, quite strikingly, all participants showed” a reduction in blood pressure, said Dr. Sellers, which he noted relates to a decrease in resting heart rate (P = .062).
 

Brown fat or skeletal muscle contraction?

Dr. Sellers pointed out that, despite nonshivering thermogenesis being involved in mild cold acclimation, the data so far suggest that some level of mild muscle activity or shivering appears crucial in provoking the beneficial metabolic effects of cold acclimation.

“Brown fat is a metabolic heating system inside our bodies, burning calories”, explained Dr. Sellers. “This generates heat and prevents calories from being deposited as normal white fat. Brown fat is activated during cold and when we eat, but its activity is less in older adults and in individuals with obesity and diabetes.”

“Going forward, we might investigate the effects of shorter duration – so more intense shivering – to try and elucidate more precisely the optimum duration and intensity of shivering needed,” said Dr. Sellers.

“Our findings are promising and may have important health implications. In future studies, we plan to assess the effect of shivering in adults with type 2 diabetes,” he concluded.

Dr. Seller and Dr. Krook have reported no relevant financial relationships.

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