Walnuts have been associated with better cognitive development and psychological maturation in teens, new research shows. Adolescents who consumed walnuts for at least 100 days showed improved sustained attention and fluid intelligence as well as a reduction in symptoms of attension deficit hyperactivity disorder, compared with matched controls who did not consume the nuts. However, there were no statistically significant changes between the groups in other parameters, such as working memory and executive function.

Clinicians should advise adolescents “to eat a handful of walnuts three times a week for the rest of their lives. They may have a healthier brain with better cognitive function,” said senior investigator Jordi Julvez, PhD, group leader at the Institute of Health Research Pere Virgili, Barcelona, and associated researcher at the Barcelona Institute for Global Health.

The study was published online in eClinicalMedicine.
 

Rich source of omega-3s

Adolescence is “a period of refinement of brain connectivity and complex behaviors,” the investigators noted.  

Previous research suggests polyunsaturated fatty acids are key in central nervous system architecture and function during times of neural development, with three specific PUFAs playing an “essential developmental role.”

Two omega-3 fatty acids – docosahexaenoic acid and eicosapentaenoic acid – are PUFAs that must be obtained through diet, mainly from seafood. Walnuts are “among the richest sources” of plant-derived omega-3 fatty acids, particularly alpha-linolenic acid (ALA), a precursor for longer-chain EPA and DHA.

ALA independently “has positive effects on brain function and plasticity,” the authors wrote. In addition, walnut constituents – particularly polyphenols and other bioactive compounds – “may act synergistically with ALA to foster brain health.”

Earlier small studies have found positive associations between walnut consumption and cognitive function in children, adolescents, and young adults, but to date, no randomized controlled trial has focused on the effect of walnut consumption on adolescent neuropsychological function.

The researchers studied 771 healthy adolescents (aged 11-16 years, mean age 14) drawn from 12 Spanish high schools. Participants were instructed to follow healthy eating recommendations and were randomly assigned 1:1 to the intervention (n = 386) or the control group (n = 385).

At baseline and after 6 months, they completed neuropsychological tests and behavioral rating scales. The Attention Network Test assessed attention, and the N-back test was used to assess working memory. The Tests of Primary Mental Abilities assessed fluid intelligence. Risky decision-making was tested using the Roulettes Task.
 

Fruit and nuts

Participants also completed the Strengths and Difficulties Questionnaire, which provided a total score of problem behavior. Teachers filled out the ADHD DSM-IV form list to provide additional information about ADHD behaviors.

The intervention group received 30 grams/day of raw California walnut kernels to incorporate into their daily diet. It is estimated that this walnut contains about 9 g of ALA per 100 g.

All participants received a seasonal fruit calendar and were asked to eat at least one piece of seasonal fruit daily.

Parents reported their child’s daily walnut consumption, with adherence defined as 100 or more days of eating walnuts during the 6-month period.

All main analyses were based on an intention-to-treat method (participants were analyzed according to their original group assignment, regardless of their adherence to the intervention).

The researchers also conducted a secondary per-protocol analysis, comparing the intervention and control groups to estimate the effect if all participants had adhered to their assigned intervention. They censored data for participants who reported eating walnuts for less than 100 days during the 6-month trial period.

Secondary outcomes included changes in height, weight, waist circumference, and BMI, as well as red blood cell proportions of omega-3 fatty acids (DHA, EPA, and ALA) at baseline and after 6 months.
 

Adherence counts

Most participants had “medium” or “high” levels of adherence to the Mediterranean diet, with “no meaningful differences” at baseline between the intervention and control groups in lifestyle characteristics or mean scores in all primary endpoints.

In the ITT analysis, there were no statistically significant differences in primary outcomes between the groups following the intervention. As for secondary outcomes, the RBC ALA significantly increased in the walnuts group but not the control group (coefficient, 0.04%; 95% confidence interval, 0.03%-0.06%; P < .0001).

However, there were differences in primary outcomes between the groups in the per-protocol analysis: The adherence-adjusted effect on improvement in attention score was −11.26 ms; 95% CI, −19.92 to −2.60; P = .011) for the intervention versus the control group.

The per-protocol analysis showed other differences: an improvement in fluid intelligence score (1.78; 95% CI, 0.90 - 2.67; P < .0001) and a reduction in ADHD symptom score (−2.18; 95% CI, −3.70 to −0.67; P = .0050).

“Overall, no significant differences were found in the intervention group in relation to the control group,” Dr. Julvez said in a news release. “But if the adherence factor is considered, then positive results are observed, since participants who most closely followed the guidelines – in terms of the recommended dose of walnuts and the number of days of consumption – did show improvements in the neuropsychological functions evaluated.”

Adolescence “is a time of great biological changes. Hormonal transformation occurs, which in turn is responsible for stimulating the synaptic growth of the frontal lobe,” he continued, adding that this brain region “enables neuropsychological maturation of more complex emotional and cognitive functions.”

“Neurons that are well nourished with these types of fatty acids will be able to grow and form new, stronger synapses,” he said.
 

Food as medicine

Uma Naidoo, MD, director of nutritional and lifestyle psychiatry at Massachusetts General Hospital, Boston, “commends” the researchers for conducting an RCT with a “robust” sample size and said she is “excited to see research like this furthering functional nutrition for mental health,” as she believes that “food is medicine.”

Dr. Naidoo, a professional chef, nutritional biologist, and author of the book “This Is Your Brain on Food,” said the findings “align” with her own approach to nutritional psychiatry and are also “in line” with her clinical practice.

However, although these results are “promising,” more research is needed across more diverse populations to “make sure these results are truly generalizable,” said Dr. Naidoo, a faculty member at Harvard Medical School, Boston, who was not involved with the study.

She “envisions a future where the research is so advanced that we can ‘dose’ these healthy whole foods for specific psychiatric symptoms and conditions.”

This study was supported by Instituto de Salud Carlos III (co-funded by European Union Regional Development Fund “A way to make Europe”). The California Walnut Commission has given support by supplying the walnuts for free for the Walnuts Smart Snack Dietary Intervention Trial. Dr. Julvez holds a Miguel Servet-II contract awarded by the Instituto de Salud Carlos III (co-funded by European Union Social Fund). The other authors’ disclosures are listed in the original article. Dr. Naidoo reports no relevant financial relationships.

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

Walnuts have been associated with better cognitive development and psychological maturation in teens, new research shows. Adolescents who consumed walnuts for at least 100 days showed improved sustained attention and fluid intelligence as well as a reduction in symptoms of attension deficit hyperactivity disorder, compared with matched controls who did not consume the nuts. However, there were no statistically significant changes between the groups in other parameters, such as working memory and executive function.

Clinicians should advise adolescents “to eat a handful of walnuts three times a week for the rest of their lives. They may have a healthier brain with better cognitive function,” said senior investigator Jordi Julvez, PhD, group leader at the Institute of Health Research Pere Virgili, Barcelona, and associated researcher at the Barcelona Institute for Global Health.

The study was published online in eClinicalMedicine.
 

Rich source of omega-3s

Adolescence is “a period of refinement of brain connectivity and complex behaviors,” the investigators noted.  

Previous research suggests polyunsaturated fatty acids are key in central nervous system architecture and function during times of neural development, with three specific PUFAs playing an “essential developmental role.”

Two omega-3 fatty acids – docosahexaenoic acid and eicosapentaenoic acid – are PUFAs that must be obtained through diet, mainly from seafood. Walnuts are “among the richest sources” of plant-derived omega-3 fatty acids, particularly alpha-linolenic acid (ALA), a precursor for longer-chain EPA and DHA.

ALA independently “has positive effects on brain function and plasticity,” the authors wrote. In addition, walnut constituents – particularly polyphenols and other bioactive compounds – “may act synergistically with ALA to foster brain health.”

Earlier small studies have found positive associations between walnut consumption and cognitive function in children, adolescents, and young adults, but to date, no randomized controlled trial has focused on the effect of walnut consumption on adolescent neuropsychological function.

The researchers studied 771 healthy adolescents (aged 11-16 years, mean age 14) drawn from 12 Spanish high schools. Participants were instructed to follow healthy eating recommendations and were randomly assigned 1:1 to the intervention (n = 386) or the control group (n = 385).

At baseline and after 6 months, they completed neuropsychological tests and behavioral rating scales. The Attention Network Test assessed attention, and the N-back test was used to assess working memory. The Tests of Primary Mental Abilities assessed fluid intelligence. Risky decision-making was tested using the Roulettes Task.
 

Fruit and nuts

Participants also completed the Strengths and Difficulties Questionnaire, which provided a total score of problem behavior. Teachers filled out the ADHD DSM-IV form list to provide additional information about ADHD behaviors.

The intervention group received 30 grams/day of raw California walnut kernels to incorporate into their daily diet. It is estimated that this walnut contains about 9 g of ALA per 100 g.

All participants received a seasonal fruit calendar and were asked to eat at least one piece of seasonal fruit daily.

Parents reported their child’s daily walnut consumption, with adherence defined as 100 or more days of eating walnuts during the 6-month period.

All main analyses were based on an intention-to-treat method (participants were analyzed according to their original group assignment, regardless of their adherence to the intervention).

The researchers also conducted a secondary per-protocol analysis, comparing the intervention and control groups to estimate the effect if all participants had adhered to their assigned intervention. They censored data for participants who reported eating walnuts for less than 100 days during the 6-month trial period.

Secondary outcomes included changes in height, weight, waist circumference, and BMI, as well as red blood cell proportions of omega-3 fatty acids (DHA, EPA, and ALA) at baseline and after 6 months.
 

Adherence counts

Most participants had “medium” or “high” levels of adherence to the Mediterranean diet, with “no meaningful differences” at baseline between the intervention and control groups in lifestyle characteristics or mean scores in all primary endpoints.

In the ITT analysis, there were no statistically significant differences in primary outcomes between the groups following the intervention. As for secondary outcomes, the RBC ALA significantly increased in the walnuts group but not the control group (coefficient, 0.04%; 95% confidence interval, 0.03%-0.06%; P < .0001).

However, there were differences in primary outcomes between the groups in the per-protocol analysis: The adherence-adjusted effect on improvement in attention score was −11.26 ms; 95% CI, −19.92 to −2.60; P = .011) for the intervention versus the control group.

The per-protocol analysis showed other differences: an improvement in fluid intelligence score (1.78; 95% CI, 0.90 - 2.67; P < .0001) and a reduction in ADHD symptom score (−2.18; 95% CI, −3.70 to −0.67; P = .0050).

“Overall, no significant differences were found in the intervention group in relation to the control group,” Dr. Julvez said in a news release. “But if the adherence factor is considered, then positive results are observed, since participants who most closely followed the guidelines – in terms of the recommended dose of walnuts and the number of days of consumption – did show improvements in the neuropsychological functions evaluated.”

Adolescence “is a time of great biological changes. Hormonal transformation occurs, which in turn is responsible for stimulating the synaptic growth of the frontal lobe,” he continued, adding that this brain region “enables neuropsychological maturation of more complex emotional and cognitive functions.”

“Neurons that are well nourished with these types of fatty acids will be able to grow and form new, stronger synapses,” he said.
 

Food as medicine

Uma Naidoo, MD, director of nutritional and lifestyle psychiatry at Massachusetts General Hospital, Boston, “commends” the researchers for conducting an RCT with a “robust” sample size and said she is “excited to see research like this furthering functional nutrition for mental health,” as she believes that “food is medicine.”

Dr. Naidoo, a professional chef, nutritional biologist, and author of the book “This Is Your Brain on Food,” said the findings “align” with her own approach to nutritional psychiatry and are also “in line” with her clinical practice.

However, although these results are “promising,” more research is needed across more diverse populations to “make sure these results are truly generalizable,” said Dr. Naidoo, a faculty member at Harvard Medical School, Boston, who was not involved with the study.

She “envisions a future where the research is so advanced that we can ‘dose’ these healthy whole foods for specific psychiatric symptoms and conditions.”

This study was supported by Instituto de Salud Carlos III (co-funded by European Union Regional Development Fund “A way to make Europe”). The California Walnut Commission has given support by supplying the walnuts for free for the Walnuts Smart Snack Dietary Intervention Trial. Dr. Julvez holds a Miguel Servet-II contract awarded by the Instituto de Salud Carlos III (co-funded by European Union Social Fund). The other authors’ disclosures are listed in the original article. Dr. Naidoo reports no relevant financial relationships.

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

Walnuts have been associated with better cognitive development and psychological maturation in teens, new research shows. Adolescents who consumed walnuts for at least 100 days showed improved sustained attention and fluid intelligence as well as a reduction in symptoms of attension deficit hyperactivity disorder, compared with matched controls who did not consume the nuts. However, there were no statistically significant changes between the groups in other parameters, such as working memory and executive function.

Clinicians should advise adolescents “to eat a handful of walnuts three times a week for the rest of their lives. They may have a healthier brain with better cognitive function,” said senior investigator Jordi Julvez, PhD, group leader at the Institute of Health Research Pere Virgili, Barcelona, and associated researcher at the Barcelona Institute for Global Health.

The study was published online in eClinicalMedicine.
 

Rich source of omega-3s

Adolescence is “a period of refinement of brain connectivity and complex behaviors,” the investigators noted.  

Previous research suggests polyunsaturated fatty acids are key in central nervous system architecture and function during times of neural development, with three specific PUFAs playing an “essential developmental role.”

Two omega-3 fatty acids – docosahexaenoic acid and eicosapentaenoic acid – are PUFAs that must be obtained through diet, mainly from seafood. Walnuts are “among the richest sources” of plant-derived omega-3 fatty acids, particularly alpha-linolenic acid (ALA), a precursor for longer-chain EPA and DHA.

ALA independently “has positive effects on brain function and plasticity,” the authors wrote. In addition, walnut constituents – particularly polyphenols and other bioactive compounds – “may act synergistically with ALA to foster brain health.”

Earlier small studies have found positive associations between walnut consumption and cognitive function in children, adolescents, and young adults, but to date, no randomized controlled trial has focused on the effect of walnut consumption on adolescent neuropsychological function.

The researchers studied 771 healthy adolescents (aged 11-16 years, mean age 14) drawn from 12 Spanish high schools. Participants were instructed to follow healthy eating recommendations and were randomly assigned 1:1 to the intervention (n = 386) or the control group (n = 385).

At baseline and after 6 months, they completed neuropsychological tests and behavioral rating scales. The Attention Network Test assessed attention, and the N-back test was used to assess working memory. The Tests of Primary Mental Abilities assessed fluid intelligence. Risky decision-making was tested using the Roulettes Task.
 

Fruit and nuts

Participants also completed the Strengths and Difficulties Questionnaire, which provided a total score of problem behavior. Teachers filled out the ADHD DSM-IV form list to provide additional information about ADHD behaviors.

The intervention group received 30 grams/day of raw California walnut kernels to incorporate into their daily diet. It is estimated that this walnut contains about 9 g of ALA per 100 g.

All participants received a seasonal fruit calendar and were asked to eat at least one piece of seasonal fruit daily.

Parents reported their child’s daily walnut consumption, with adherence defined as 100 or more days of eating walnuts during the 6-month period.

All main analyses were based on an intention-to-treat method (participants were analyzed according to their original group assignment, regardless of their adherence to the intervention).

The researchers also conducted a secondary per-protocol analysis, comparing the intervention and control groups to estimate the effect if all participants had adhered to their assigned intervention. They censored data for participants who reported eating walnuts for less than 100 days during the 6-month trial period.

Secondary outcomes included changes in height, weight, waist circumference, and BMI, as well as red blood cell proportions of omega-3 fatty acids (DHA, EPA, and ALA) at baseline and after 6 months.
 

Adherence counts

Most participants had “medium” or “high” levels of adherence to the Mediterranean diet, with “no meaningful differences” at baseline between the intervention and control groups in lifestyle characteristics or mean scores in all primary endpoints.

In the ITT analysis, there were no statistically significant differences in primary outcomes between the groups following the intervention. As for secondary outcomes, the RBC ALA significantly increased in the walnuts group but not the control group (coefficient, 0.04%; 95% confidence interval, 0.03%-0.06%; P < .0001).

However, there were differences in primary outcomes between the groups in the per-protocol analysis: The adherence-adjusted effect on improvement in attention score was −11.26 ms; 95% CI, −19.92 to −2.60; P = .011) for the intervention versus the control group.

The per-protocol analysis showed other differences: an improvement in fluid intelligence score (1.78; 95% CI, 0.90 - 2.67; P < .0001) and a reduction in ADHD symptom score (−2.18; 95% CI, −3.70 to −0.67; P = .0050).

“Overall, no significant differences were found in the intervention group in relation to the control group,” Dr. Julvez said in a news release. “But if the adherence factor is considered, then positive results are observed, since participants who most closely followed the guidelines – in terms of the recommended dose of walnuts and the number of days of consumption – did show improvements in the neuropsychological functions evaluated.”

Adolescence “is a time of great biological changes. Hormonal transformation occurs, which in turn is responsible for stimulating the synaptic growth of the frontal lobe,” he continued, adding that this brain region “enables neuropsychological maturation of more complex emotional and cognitive functions.”

“Neurons that are well nourished with these types of fatty acids will be able to grow and form new, stronger synapses,” he said.
 

Food as medicine

Uma Naidoo, MD, director of nutritional and lifestyle psychiatry at Massachusetts General Hospital, Boston, “commends” the researchers for conducting an RCT with a “robust” sample size and said she is “excited to see research like this furthering functional nutrition for mental health,” as she believes that “food is medicine.”

Dr. Naidoo, a professional chef, nutritional biologist, and author of the book “This Is Your Brain on Food,” said the findings “align” with her own approach to nutritional psychiatry and are also “in line” with her clinical practice.

However, although these results are “promising,” more research is needed across more diverse populations to “make sure these results are truly generalizable,” said Dr. Naidoo, a faculty member at Harvard Medical School, Boston, who was not involved with the study.

She “envisions a future where the research is so advanced that we can ‘dose’ these healthy whole foods for specific psychiatric symptoms and conditions.”

This study was supported by Instituto de Salud Carlos III (co-funded by European Union Regional Development Fund “A way to make Europe”). The California Walnut Commission has given support by supplying the walnuts for free for the Walnuts Smart Snack Dietary Intervention Trial. Dr. Julvez holds a Miguel Servet-II contract awarded by the Instituto de Salud Carlos III (co-funded by European Union Social Fund). The other authors’ disclosures are listed in the original article. Dr. Naidoo reports no relevant financial relationships.

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

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

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

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

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

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

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

PHOENIX – Combining intense pulsed light (IPL) with topical radiofrequency (RF) for dry eye disease related to meibomian gland dysfunction resulted in about a doubling of meibomian gland expression and improved meibum quality in both upper and lower eyelids, results from an ongoing, novel study showed.

Dry eye disease affects a large proportion of people in the United States “and the factors that contribute to that are certainly not going away,” lead study author James G. Chelnis MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where he presented the results during an abstract session. “Prepandemic, we used to have meetings in person; now most are on a computer screen,” a common risk factor for worsening dry eyes, he said. Telltale dry eye symptoms include blurry vision, irritation, and corneal damage – mostly caused by meibomian gland dysfunction – which impacts the quality and quantity of meibum secreted. Common treatments include warm compresses, doxycycline, and artificial tears.

Dr. Chelnis

While some studies have shown IPL is helpful in treating dry eye disease caused by meibomian gland dysfunction, little information is available on its use alone or in combination with topical RF to preserve and improve the function of meibomian glands, said Dr. Chelnis, an ophthalmic plastic surgeon in New York City. “The theory here is that the radiofrequency would be able to vibrate the water molecules inside the meibomian glands, which would allow you to turn over the meibum faster, as well as improve the blink reflex response by building supporting collagen,” he said. “Our novel study explores the ability of this combined modality treatment to improve upon meibomian gland health.”
 

Study design, results

Dr. Chelnis and his colleagues enrolled 11 individuals with a previous diagnosis of dry eye disease and meibomian gland dysfunction with Ocular Surface Disease Index (OSDI) survey scores higher than 23, which indicate at least moderate dry eye symptoms. Inclusion criteria were being 22 years of age or older, signs of meibomian gland dysfunction as detected by biomicroscopy, a modified meibomian gland score over 12 in the lower eyelid of at least one eye, and type I-IV skin.

All patients received four treatments (each 2 weeks apart) of IPL to the lower eyelid, surrounding malar region, and nose, followed by 7 minutes of topical RF treatments at 1 MHz and 4 MHz extending to the inferior, lateral, and superior orbital rim. Evaluation of meibomian gland expression and quality of meibum upon expression was conducted following each treatment session, with a final evaluation 4 weeks after the final treatment session.

Meibum quality was evaluated on a scale of 0-3 representing clear (0), cloudy (1), inspissated (2), and blocked (3) meibum, respectively.

Following treatment, meibomian gland expression and meibum quality improved in all eyelids in all 11 patients. Specifically, in the right eye, the number of upper lid expressible glands increased from an average of 13 to 27.9 and the number of lower lid expressible glands increased from an average of 14.6 to 28.2; and in the left eye, the number of upper lid expressible glands increased from an average of 13.3 to 27.3 and the number of lower lid expressible glands increased from an average of 14.8 to 26.8 (P < .001 for all associations).

The overall percentage improvement in meibomian gland expression in the right eye was 82.7% for the upper lids and 136.6% for the lower lids, and in the left eye, 82.9% for the upper lids, and 112.2% for the lower lids.

When comparing upper against lower lids, meibomian gland expression increased 124.4% and 82.8%, respectively. Meibum quality improved in all four eyelids, although upper eyelids displayed a superior improvement compared with lower eyelids.

“We are finding that combining IPL plus RF produces a more complete and comprehensive improvement in the quality of their meibomian gland health, and as such, their dry eyes,” with “a large decrease in their symptom profile,” he concluded.

More patients to be studied

Dr. Chelnis acknowledged certain limitations of the study, including the small number of patients, but he and his colleagues have added an additional clinical site to expand the sample size. “Larger scale studies are needed to evaluate long-term effectiveness of IPL plus RF as well as a comparison with other treatment options.”

During a question-and-answer session Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, who served as one of the abstract session moderators, asked Dr. Chelnis to comment on what the mechanism of action of the IPL-RF combination in improving meibomian gland health.

“It’s not fully understood, but part of it is improved vascularity at the lid margin,” said Dr. Chelnis, who holds a faculty position in the department of ophthalmology at Icahn School of Medicine at Mount Sinai, New York. “Your ocular surface is sort of like your screen door; it catches everything that’s in the environment. An increase in vascularity and immunologic cytokines occurs in response to that. If you’re looking at the eye with a slit lamp, you can see a lot of vascularity that occurs at the lid margin and crowds the meibomian glands. When you decrease that crowding and immunogenic response, you move towards a normally functioning lid margin.”

Dr. Chelnis disclosed that he is a consultant to or an adviser for Lumenis, Horizon Therapeutics, and Soniquence.

PHOENIX – Combining intense pulsed light (IPL) with topical radiofrequency (RF) for dry eye disease related to meibomian gland dysfunction resulted in about a doubling of meibomian gland expression and improved meibum quality in both upper and lower eyelids, results from an ongoing, novel study showed.

Dry eye disease affects a large proportion of people in the United States “and the factors that contribute to that are certainly not going away,” lead study author James G. Chelnis MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where he presented the results during an abstract session. “Prepandemic, we used to have meetings in person; now most are on a computer screen,” a common risk factor for worsening dry eyes, he said. Telltale dry eye symptoms include blurry vision, irritation, and corneal damage – mostly caused by meibomian gland dysfunction – which impacts the quality and quantity of meibum secreted. Common treatments include warm compresses, doxycycline, and artificial tears.

Dr. Chelnis

While some studies have shown IPL is helpful in treating dry eye disease caused by meibomian gland dysfunction, little information is available on its use alone or in combination with topical RF to preserve and improve the function of meibomian glands, said Dr. Chelnis, an ophthalmic plastic surgeon in New York City. “The theory here is that the radiofrequency would be able to vibrate the water molecules inside the meibomian glands, which would allow you to turn over the meibum faster, as well as improve the blink reflex response by building supporting collagen,” he said. “Our novel study explores the ability of this combined modality treatment to improve upon meibomian gland health.”
 

Study design, results

Dr. Chelnis and his colleagues enrolled 11 individuals with a previous diagnosis of dry eye disease and meibomian gland dysfunction with Ocular Surface Disease Index (OSDI) survey scores higher than 23, which indicate at least moderate dry eye symptoms. Inclusion criteria were being 22 years of age or older, signs of meibomian gland dysfunction as detected by biomicroscopy, a modified meibomian gland score over 12 in the lower eyelid of at least one eye, and type I-IV skin.

All patients received four treatments (each 2 weeks apart) of IPL to the lower eyelid, surrounding malar region, and nose, followed by 7 minutes of topical RF treatments at 1 MHz and 4 MHz extending to the inferior, lateral, and superior orbital rim. Evaluation of meibomian gland expression and quality of meibum upon expression was conducted following each treatment session, with a final evaluation 4 weeks after the final treatment session.

Meibum quality was evaluated on a scale of 0-3 representing clear (0), cloudy (1), inspissated (2), and blocked (3) meibum, respectively.

Following treatment, meibomian gland expression and meibum quality improved in all eyelids in all 11 patients. Specifically, in the right eye, the number of upper lid expressible glands increased from an average of 13 to 27.9 and the number of lower lid expressible glands increased from an average of 14.6 to 28.2; and in the left eye, the number of upper lid expressible glands increased from an average of 13.3 to 27.3 and the number of lower lid expressible glands increased from an average of 14.8 to 26.8 (P < .001 for all associations).

The overall percentage improvement in meibomian gland expression in the right eye was 82.7% for the upper lids and 136.6% for the lower lids, and in the left eye, 82.9% for the upper lids, and 112.2% for the lower lids.

When comparing upper against lower lids, meibomian gland expression increased 124.4% and 82.8%, respectively. Meibum quality improved in all four eyelids, although upper eyelids displayed a superior improvement compared with lower eyelids.

“We are finding that combining IPL plus RF produces a more complete and comprehensive improvement in the quality of their meibomian gland health, and as such, their dry eyes,” with “a large decrease in their symptom profile,” he concluded.

More patients to be studied

Dr. Chelnis acknowledged certain limitations of the study, including the small number of patients, but he and his colleagues have added an additional clinical site to expand the sample size. “Larger scale studies are needed to evaluate long-term effectiveness of IPL plus RF as well as a comparison with other treatment options.”

During a question-and-answer session Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, who served as one of the abstract session moderators, asked Dr. Chelnis to comment on what the mechanism of action of the IPL-RF combination in improving meibomian gland health.

“It’s not fully understood, but part of it is improved vascularity at the lid margin,” said Dr. Chelnis, who holds a faculty position in the department of ophthalmology at Icahn School of Medicine at Mount Sinai, New York. “Your ocular surface is sort of like your screen door; it catches everything that’s in the environment. An increase in vascularity and immunologic cytokines occurs in response to that. If you’re looking at the eye with a slit lamp, you can see a lot of vascularity that occurs at the lid margin and crowds the meibomian glands. When you decrease that crowding and immunogenic response, you move towards a normally functioning lid margin.”

Dr. Chelnis disclosed that he is a consultant to or an adviser for Lumenis, Horizon Therapeutics, and Soniquence.

PHOENIX – Combining intense pulsed light (IPL) with topical radiofrequency (RF) for dry eye disease related to meibomian gland dysfunction resulted in about a doubling of meibomian gland expression and improved meibum quality in both upper and lower eyelids, results from an ongoing, novel study showed.

Dry eye disease affects a large proportion of people in the United States “and the factors that contribute to that are certainly not going away,” lead study author James G. Chelnis MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where he presented the results during an abstract session. “Prepandemic, we used to have meetings in person; now most are on a computer screen,” a common risk factor for worsening dry eyes, he said. Telltale dry eye symptoms include blurry vision, irritation, and corneal damage – mostly caused by meibomian gland dysfunction – which impacts the quality and quantity of meibum secreted. Common treatments include warm compresses, doxycycline, and artificial tears.

Dr. Chelnis

While some studies have shown IPL is helpful in treating dry eye disease caused by meibomian gland dysfunction, little information is available on its use alone or in combination with topical RF to preserve and improve the function of meibomian glands, said Dr. Chelnis, an ophthalmic plastic surgeon in New York City. “The theory here is that the radiofrequency would be able to vibrate the water molecules inside the meibomian glands, which would allow you to turn over the meibum faster, as well as improve the blink reflex response by building supporting collagen,” he said. “Our novel study explores the ability of this combined modality treatment to improve upon meibomian gland health.”
 

Study design, results

Dr. Chelnis and his colleagues enrolled 11 individuals with a previous diagnosis of dry eye disease and meibomian gland dysfunction with Ocular Surface Disease Index (OSDI) survey scores higher than 23, which indicate at least moderate dry eye symptoms. Inclusion criteria were being 22 years of age or older, signs of meibomian gland dysfunction as detected by biomicroscopy, a modified meibomian gland score over 12 in the lower eyelid of at least one eye, and type I-IV skin.

All patients received four treatments (each 2 weeks apart) of IPL to the lower eyelid, surrounding malar region, and nose, followed by 7 minutes of topical RF treatments at 1 MHz and 4 MHz extending to the inferior, lateral, and superior orbital rim. Evaluation of meibomian gland expression and quality of meibum upon expression was conducted following each treatment session, with a final evaluation 4 weeks after the final treatment session.

Meibum quality was evaluated on a scale of 0-3 representing clear (0), cloudy (1), inspissated (2), and blocked (3) meibum, respectively.

Following treatment, meibomian gland expression and meibum quality improved in all eyelids in all 11 patients. Specifically, in the right eye, the number of upper lid expressible glands increased from an average of 13 to 27.9 and the number of lower lid expressible glands increased from an average of 14.6 to 28.2; and in the left eye, the number of upper lid expressible glands increased from an average of 13.3 to 27.3 and the number of lower lid expressible glands increased from an average of 14.8 to 26.8 (P < .001 for all associations).

The overall percentage improvement in meibomian gland expression in the right eye was 82.7% for the upper lids and 136.6% for the lower lids, and in the left eye, 82.9% for the upper lids, and 112.2% for the lower lids.

When comparing upper against lower lids, meibomian gland expression increased 124.4% and 82.8%, respectively. Meibum quality improved in all four eyelids, although upper eyelids displayed a superior improvement compared with lower eyelids.

“We are finding that combining IPL plus RF produces a more complete and comprehensive improvement in the quality of their meibomian gland health, and as such, their dry eyes,” with “a large decrease in their symptom profile,” he concluded.

More patients to be studied

Dr. Chelnis acknowledged certain limitations of the study, including the small number of patients, but he and his colleagues have added an additional clinical site to expand the sample size. “Larger scale studies are needed to evaluate long-term effectiveness of IPL plus RF as well as a comparison with other treatment options.”

During a question-and-answer session Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, who served as one of the abstract session moderators, asked Dr. Chelnis to comment on what the mechanism of action of the IPL-RF combination in improving meibomian gland health.

“It’s not fully understood, but part of it is improved vascularity at the lid margin,” said Dr. Chelnis, who holds a faculty position in the department of ophthalmology at Icahn School of Medicine at Mount Sinai, New York. “Your ocular surface is sort of like your screen door; it catches everything that’s in the environment. An increase in vascularity and immunologic cytokines occurs in response to that. If you’re looking at the eye with a slit lamp, you can see a lot of vascularity that occurs at the lid margin and crowds the meibomian glands. When you decrease that crowding and immunogenic response, you move towards a normally functioning lid margin.”

Dr. Chelnis disclosed that he is a consultant to or an adviser for Lumenis, Horizon Therapeutics, and Soniquence.

The Diagnosis: Cutaneous Furuncular Myiasis

Histopathology of the punch biopsy showed an undulating chitinous exoskeleton and pigmented spines (setae) protruding from the exoskeleton with associated superficial perivascular lymphohistiocytic infiltrates on hematoxylin and eosin stain (Figure 1). Live insect larvae were observed and extracted, which immediately relieved the crawling sensation (Figure 2). Light microscopy of the larva showed a row of hooks surrounding a tapered body with a head attached anteriorly (Figure 3).

Myiasis is a parasitic infestation of the dipterous fly’s larvae in the host organ and tissue. There are 5 types of myiasis based on the location of the infestation: wound myiasis occurs with egg infestations on an open wound; furuncular myiasis results from egg placement by penetration of healthy skin by a mosquito vector; plaque myiasis comprises the placement of eggs on clothing through several maggots and flies; creeping myiasis involves the Gasterophilus fly delivering the larva intradermally; and body cavity myiasis may develop in the orbit, nasal cavity, urogenital system, and gastrointestinal tract.^1-3

Furuncular myiasis infestation occurs via a complex life cycle in which mosquitoes act as a vector and transfer the eggs to the human or animal host.^1-3 Botfly larvae then penetrate the skin and reside within the subdermis to mature. Adults then emerge after 1 month to repeat the cycle.¹Dermatobia hominis and Cordylobia anthropophaga are the most common causes of furuncular myiasis.^2,3 Furuncular myiasis commonly presents in travelers that are returning from tropical countries. Initially, an itching erythematous papule develops. After the larvae mature, they can appear as boil-like lesions with a small central punctum.^1-3 Dermoscopy can be utilized for visualization of different larvae anatomy such as a furuncularlike lesion, spines, and posterior breathing spiracle from the central punctum.⁴

Our patient’s recent travel to the Amazon in Brazil, clinical history, and histopathologic findings ruled out other differential diagnoses such as cutaneous larva migrans, gnathostomiasis, loiasis, and tungiasis.

Treatment is curative with the extraction of the intact larva from the nodule. Localized skin anesthetic injection can be used to bulge the larva outward for easier extraction. A single dose of ivermectin 15 mg can treat the parasitic infestation of myiasis.^1-3

The Diagnosis: Cutaneous Furuncular Myiasis

Histopathology of the punch biopsy showed an undulating chitinous exoskeleton and pigmented spines (setae) protruding from the exoskeleton with associated superficial perivascular lymphohistiocytic infiltrates on hematoxylin and eosin stain (Figure 1). Live insect larvae were observed and extracted, which immediately relieved the crawling sensation (Figure 2). Light microscopy of the larva showed a row of hooks surrounding a tapered body with a head attached anteriorly (Figure 3).

Myiasis is a parasitic infestation of the dipterous fly’s larvae in the host organ and tissue. There are 5 types of myiasis based on the location of the infestation: wound myiasis occurs with egg infestations on an open wound; furuncular myiasis results from egg placement by penetration of healthy skin by a mosquito vector; plaque myiasis comprises the placement of eggs on clothing through several maggots and flies; creeping myiasis involves the Gasterophilus fly delivering the larva intradermally; and body cavity myiasis may develop in the orbit, nasal cavity, urogenital system, and gastrointestinal tract.^1-3

Furuncular myiasis infestation occurs via a complex life cycle in which mosquitoes act as a vector and transfer the eggs to the human or animal host.^1-3 Botfly larvae then penetrate the skin and reside within the subdermis to mature. Adults then emerge after 1 month to repeat the cycle.¹Dermatobia hominis and Cordylobia anthropophaga are the most common causes of furuncular myiasis.^2,3 Furuncular myiasis commonly presents in travelers that are returning from tropical countries. Initially, an itching erythematous papule develops. After the larvae mature, they can appear as boil-like lesions with a small central punctum.^1-3 Dermoscopy can be utilized for visualization of different larvae anatomy such as a furuncularlike lesion, spines, and posterior breathing spiracle from the central punctum.⁴

Our patient’s recent travel to the Amazon in Brazil, clinical history, and histopathologic findings ruled out other differential diagnoses such as cutaneous larva migrans, gnathostomiasis, loiasis, and tungiasis.

Treatment is curative with the extraction of the intact larva from the nodule. Localized skin anesthetic injection can be used to bulge the larva outward for easier extraction. A single dose of ivermectin 15 mg can treat the parasitic infestation of myiasis.^1-3

The Diagnosis: Cutaneous Furuncular Myiasis

Histopathology of the punch biopsy showed an undulating chitinous exoskeleton and pigmented spines (setae) protruding from the exoskeleton with associated superficial perivascular lymphohistiocytic infiltrates on hematoxylin and eosin stain (Figure 1). Live insect larvae were observed and extracted, which immediately relieved the crawling sensation (Figure 2). Light microscopy of the larva showed a row of hooks surrounding a tapered body with a head attached anteriorly (Figure 3).

Myiasis is a parasitic infestation of the dipterous fly’s larvae in the host organ and tissue. There are 5 types of myiasis based on the location of the infestation: wound myiasis occurs with egg infestations on an open wound; furuncular myiasis results from egg placement by penetration of healthy skin by a mosquito vector; plaque myiasis comprises the placement of eggs on clothing through several maggots and flies; creeping myiasis involves the Gasterophilus fly delivering the larva intradermally; and body cavity myiasis may develop in the orbit, nasal cavity, urogenital system, and gastrointestinal tract.^1-3

Furuncular myiasis infestation occurs via a complex life cycle in which mosquitoes act as a vector and transfer the eggs to the human or animal host.^1-3 Botfly larvae then penetrate the skin and reside within the subdermis to mature. Adults then emerge after 1 month to repeat the cycle.¹Dermatobia hominis and Cordylobia anthropophaga are the most common causes of furuncular myiasis.^2,3 Furuncular myiasis commonly presents in travelers that are returning from tropical countries. Initially, an itching erythematous papule develops. After the larvae mature, they can appear as boil-like lesions with a small central punctum.^1-3 Dermoscopy can be utilized for visualization of different larvae anatomy such as a furuncularlike lesion, spines, and posterior breathing spiracle from the central punctum.⁴

Our patient’s recent travel to the Amazon in Brazil, clinical history, and histopathologic findings ruled out other differential diagnoses such as cutaneous larva migrans, gnathostomiasis, loiasis, and tungiasis.

Treatment is curative with the extraction of the intact larva from the nodule. Localized skin anesthetic injection can be used to bulge the larva outward for easier extraction. A single dose of ivermectin 15 mg can treat the parasitic infestation of myiasis.^1-3

Scent-detecting dogs have long been used to sniff out medical conditions ranging from low blood sugar and cancer to malaria, impending seizures, and migraines – not to mention explosives and narcotics.

Recently, the sensitivity of the canine nose has been tested as a strategy for screening for SARS-CoV-2 infection in schoolchildren showing no outward symptoms of the virus. A pilot study led by Carol A. Glaser, DVM, MD, of the California Department of Public Health in Richmond, found that trained dogs had an accuracy of more than 95% for detecting the odor of volatile organic compounds, or VOCs, produced by COVID-infected individuals.

California Department of Public Health

The authors believe that odor-based diagnosis with dogs could eventually provide a rapid, inexpensive, and noninvasive way to screen large groups for COVID-19 without the need for antigen testing.

“This is a new program with research ongoing, so it would be premature to consider it from a consumer’s perspective,” Dr. Glaser said in an interview. “However, the data look promising and we are hopeful we can continue to pilot various programs in various settings to see where, and if, dogs can be used for biomedical detection.”
 

In the lab and in the field

In a study published online in JAMA Pediatrics, Dr. Glaser’s group found that after 2 months’ training on COVID-19 scent samples in the laboratory, the dogs detected the presence of the virus more than 95% of the time. Antigen tests were used as a comparative reference.

In medical terms, the dogs achieved a greater than 95% accuracy on two important measures of effectiveness: sensitivity – a test’s ability to correctly detect the positive presence of disease – and specificity – the ability of a test to accurately rule out the presence of disease and identify as negative an uninfected person.

Next, the researchers piloted field tests in 50 visits at 27 schools from April 1 to May 25, 2022, to compare dogs’ detection ability with that of standard laboratory antigen testing. Participants in the completely voluntary screening numbered 1,558 and ranged in age from 9 to 17 years. Of these, 56% were girls and 89% were students. Almost 70% were screened at least twice.

Overall, the field test compared 3,897 paired antigen-vs.-dog screenings. The dogs accurately signaled the presence of 85 infections and ruled out 3,411 infections, for an overall accuracy of 90%. In 383 cases, however, they inaccurately signaled the presence of infection (false positives) and missed 18 actual infections (false negatives). That translated to a sensitivity in the field of 83%, considerably lower than that of their lab performance.

Direct screening of individuals with dogs outside of the lab involved circumstantial factors that likely contributed to decreased sensitivity and specificity, the authors acknowledged. These included such distractions as noise and the presence of excitable young children as well environmental conditions such as wind and other odors. What about dog phobia and dog hair allergy? “Dog screening takes only a few seconds per student and the dogs do not generally touch the participant as they run a line and sniff at ankles,” Dr. Glaser explained.

As for allergies, the rapid, ankle-level screening occurred in outdoor settings. “The chance of allergies is very low. This would be similar to someone who is out walking on the sidewalk and walks by a dog,” Dr. Glaser said.

Last year, a British trial of almost 4,000 adults tested six dogs trained to detect differences in VOCs between COVID-infected and uninfected individuals. Given samples from both groups, the dogs were able to distinguish between infected and uninfected samples with a sensitivity for detecting the virus ranging from 82% to 94% and a specificity for ruling it out of 76% to 92%. And they were able to smell the VOCs even when the viral load was low. The study also tested organic sensors, which proved even more accurate than the canines.

According to lead author James G. Logan, PhD, a disease control expert at the London School of Hygiene & Tropical Medicine in London, “Odour-based diagnostics using dogs and/or sensors may prove a rapid and effective tool for screening large numbers of people. Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only.”

Funding was provided by the Centers for Disease Control and Prevention Foundation (CDCF) to Early Alert Canines for the purchase and care of the dogs and the support of the handlers and trainers. The CDCF had no other role in the study. Coauthor Carol A. Edwards of Early Alert Canines reported receiving grants from the CDCF.

Scent-detecting dogs have long been used to sniff out medical conditions ranging from low blood sugar and cancer to malaria, impending seizures, and migraines – not to mention explosives and narcotics.

Recently, the sensitivity of the canine nose has been tested as a strategy for screening for SARS-CoV-2 infection in schoolchildren showing no outward symptoms of the virus. A pilot study led by Carol A. Glaser, DVM, MD, of the California Department of Public Health in Richmond, found that trained dogs had an accuracy of more than 95% for detecting the odor of volatile organic compounds, or VOCs, produced by COVID-infected individuals.

California Department of Public Health

The authors believe that odor-based diagnosis with dogs could eventually provide a rapid, inexpensive, and noninvasive way to screen large groups for COVID-19 without the need for antigen testing.

“This is a new program with research ongoing, so it would be premature to consider it from a consumer’s perspective,” Dr. Glaser said in an interview. “However, the data look promising and we are hopeful we can continue to pilot various programs in various settings to see where, and if, dogs can be used for biomedical detection.”
 

In the lab and in the field

In a study published online in JAMA Pediatrics, Dr. Glaser’s group found that after 2 months’ training on COVID-19 scent samples in the laboratory, the dogs detected the presence of the virus more than 95% of the time. Antigen tests were used as a comparative reference.

In medical terms, the dogs achieved a greater than 95% accuracy on two important measures of effectiveness: sensitivity – a test’s ability to correctly detect the positive presence of disease – and specificity – the ability of a test to accurately rule out the presence of disease and identify as negative an uninfected person.

Next, the researchers piloted field tests in 50 visits at 27 schools from April 1 to May 25, 2022, to compare dogs’ detection ability with that of standard laboratory antigen testing. Participants in the completely voluntary screening numbered 1,558 and ranged in age from 9 to 17 years. Of these, 56% were girls and 89% were students. Almost 70% were screened at least twice.

Overall, the field test compared 3,897 paired antigen-vs.-dog screenings. The dogs accurately signaled the presence of 85 infections and ruled out 3,411 infections, for an overall accuracy of 90%. In 383 cases, however, they inaccurately signaled the presence of infection (false positives) and missed 18 actual infections (false negatives). That translated to a sensitivity in the field of 83%, considerably lower than that of their lab performance.

Direct screening of individuals with dogs outside of the lab involved circumstantial factors that likely contributed to decreased sensitivity and specificity, the authors acknowledged. These included such distractions as noise and the presence of excitable young children as well environmental conditions such as wind and other odors. What about dog phobia and dog hair allergy? “Dog screening takes only a few seconds per student and the dogs do not generally touch the participant as they run a line and sniff at ankles,” Dr. Glaser explained.

As for allergies, the rapid, ankle-level screening occurred in outdoor settings. “The chance of allergies is very low. This would be similar to someone who is out walking on the sidewalk and walks by a dog,” Dr. Glaser said.

Last year, a British trial of almost 4,000 adults tested six dogs trained to detect differences in VOCs between COVID-infected and uninfected individuals. Given samples from both groups, the dogs were able to distinguish between infected and uninfected samples with a sensitivity for detecting the virus ranging from 82% to 94% and a specificity for ruling it out of 76% to 92%. And they were able to smell the VOCs even when the viral load was low. The study also tested organic sensors, which proved even more accurate than the canines.

According to lead author James G. Logan, PhD, a disease control expert at the London School of Hygiene & Tropical Medicine in London, “Odour-based diagnostics using dogs and/or sensors may prove a rapid and effective tool for screening large numbers of people. Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only.”

Funding was provided by the Centers for Disease Control and Prevention Foundation (CDCF) to Early Alert Canines for the purchase and care of the dogs and the support of the handlers and trainers. The CDCF had no other role in the study. Coauthor Carol A. Edwards of Early Alert Canines reported receiving grants from the CDCF.

Scent-detecting dogs have long been used to sniff out medical conditions ranging from low blood sugar and cancer to malaria, impending seizures, and migraines – not to mention explosives and narcotics.

Recently, the sensitivity of the canine nose has been tested as a strategy for screening for SARS-CoV-2 infection in schoolchildren showing no outward symptoms of the virus. A pilot study led by Carol A. Glaser, DVM, MD, of the California Department of Public Health in Richmond, found that trained dogs had an accuracy of more than 95% for detecting the odor of volatile organic compounds, or VOCs, produced by COVID-infected individuals.

California Department of Public Health

The authors believe that odor-based diagnosis with dogs could eventually provide a rapid, inexpensive, and noninvasive way to screen large groups for COVID-19 without the need for antigen testing.

“This is a new program with research ongoing, so it would be premature to consider it from a consumer’s perspective,” Dr. Glaser said in an interview. “However, the data look promising and we are hopeful we can continue to pilot various programs in various settings to see where, and if, dogs can be used for biomedical detection.”
 

In the lab and in the field

In a study published online in JAMA Pediatrics, Dr. Glaser’s group found that after 2 months’ training on COVID-19 scent samples in the laboratory, the dogs detected the presence of the virus more than 95% of the time. Antigen tests were used as a comparative reference.

In medical terms, the dogs achieved a greater than 95% accuracy on two important measures of effectiveness: sensitivity – a test’s ability to correctly detect the positive presence of disease – and specificity – the ability of a test to accurately rule out the presence of disease and identify as negative an uninfected person.

Next, the researchers piloted field tests in 50 visits at 27 schools from April 1 to May 25, 2022, to compare dogs’ detection ability with that of standard laboratory antigen testing. Participants in the completely voluntary screening numbered 1,558 and ranged in age from 9 to 17 years. Of these, 56% were girls and 89% were students. Almost 70% were screened at least twice.

Overall, the field test compared 3,897 paired antigen-vs.-dog screenings. The dogs accurately signaled the presence of 85 infections and ruled out 3,411 infections, for an overall accuracy of 90%. In 383 cases, however, they inaccurately signaled the presence of infection (false positives) and missed 18 actual infections (false negatives). That translated to a sensitivity in the field of 83%, considerably lower than that of their lab performance.

Direct screening of individuals with dogs outside of the lab involved circumstantial factors that likely contributed to decreased sensitivity and specificity, the authors acknowledged. These included such distractions as noise and the presence of excitable young children as well environmental conditions such as wind and other odors. What about dog phobia and dog hair allergy? “Dog screening takes only a few seconds per student and the dogs do not generally touch the participant as they run a line and sniff at ankles,” Dr. Glaser explained.

As for allergies, the rapid, ankle-level screening occurred in outdoor settings. “The chance of allergies is very low. This would be similar to someone who is out walking on the sidewalk and walks by a dog,” Dr. Glaser said.

Last year, a British trial of almost 4,000 adults tested six dogs trained to detect differences in VOCs between COVID-infected and uninfected individuals. Given samples from both groups, the dogs were able to distinguish between infected and uninfected samples with a sensitivity for detecting the virus ranging from 82% to 94% and a specificity for ruling it out of 76% to 92%. And they were able to smell the VOCs even when the viral load was low. The study also tested organic sensors, which proved even more accurate than the canines.

According to lead author James G. Logan, PhD, a disease control expert at the London School of Hygiene & Tropical Medicine in London, “Odour-based diagnostics using dogs and/or sensors may prove a rapid and effective tool for screening large numbers of people. Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only.”

Funding was provided by the Centers for Disease Control and Prevention Foundation (CDCF) to Early Alert Canines for the purchase and care of the dogs and the support of the handlers and trainers. The CDCF had no other role in the study. Coauthor Carol A. Edwards of Early Alert Canines reported receiving grants from the CDCF.

BARCELONA – Staged hybrid ablation provided superior freedom from atrial arrhythmias compared with endocardial catheter ablation alone, including the need for repeat ablations in patients with advanced atrial fibrillation (AF), new data show.

“We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase, so this is a huge difference,” concluded cardiac surgeon Nicholas Doll, MD, PhD, Schüchtermann Clinic, Bad Rothenfelde, Germany.

Dr. Doll presented the 12-month follow up results of the Combined Endoscopic Epicardial and Percutaneous Endocardial Ablation Versus Repeated Catheter Ablation in Persistent and Longstanding Persistent Atrial Fibrillation (CEASE-AF) trial at the European Heart Rhythm Association 2023 Congress, held recently in Barcelona and virtually.

He said CEASE-AF is the largest multicenter randomized clinical trial comparing these two approaches for control of atrial arrhythmias.

Safety outcomes were numerically higher in the hybrid ablation (HA) group of the trial but not statistically different from the catheter ablation (CA) group.
 

Unstable wavefront

As background, Dr. Doll explained that in advanced AF, there is a high degree of endocardial-epicardial dissociation with unstable wavefront propagation transitioning between the endocardial and epicardial surfaces. Endocardial mapping and ablation alone may be insufficient to address the mechanism of AF.

“So, the hypothesis of the CEASE-AF study was a minimally invasive hybrid ablation approach which combines endocardial and epicardial ablation to achieve superior effectiveness when compared to endocardial catheter ablation alone,” he said.

This prospective clinical trial randomized patients 2:1 at nine sites in five countries to HA (n = 102) or CA (n = 52). All had left atrial diameter of 4 cm to 6 cm and persistent AF for up to 1 year or longstanding persistent AF for greater than 1 year up to 10 years.

Any patient with a previous ablation procedure, BMI greater than 35 kg/m², or left ventricular ejection fraction less than 30% was excluded.

For HA, stage 1 consisted of epicardial lesions for pulmonary vein isolation (PVI) plus the posterior wall box plus left atrial appendage exclusion using the AtriClip (AtriCure Inc.) left atrial appendage exclusion device. Stage 2 involved endocardial mapping and catheter ablation to address gaps.

For CA, the index procedure involved catheter-mediated PVI plus repeat endocardial ablation as clinically indicated. For both HA and CA, additional ablation techniques and lesions were allowed for nonparoxysmal AF.

The HA timeline was the first stage, index procedure at time 0 (n = 102), a 90-day blanking period, and then the second stage, endocardial procedure at 90 to 180 days from the index procedure (n = 93).

For the CA arm of the trial, endocardial catheter ablation was performed on a minimal endocardial lesion set at time 0. Then after a 90-day blanking period, repeat catheter ablation was performed if clinically indicated (6/52).

Repeat ablations and electrical or pharmaceutical cardioversions were allowed during the 12-month follow-up period from time 0.

The primary efficacy endpoint was freedom from AF, atrial flutter, or atrial tachycardia of greater than 30 seconds through 12 months in the absence of class I/III antiarrhythmic drugs except ones that previously had failed, at doses not exceeding those previously failed doses. The safety endpoint was a composite rate of major complications over the course of the study.

Even with relatively modest cohort sizes, the HA and CA arms of the trial were well matched at baseline for age (approximately 60 years), gender (75.5% and 73.1% male, respectively), BMI (29.7 and 29.8 kg/m²), and persistent AF (79.4% and 82.7%).

The groups had persistent AF for 2.94 ± 3.29 years and 3.34 ± 3.52 years, respectively. The mean left atrial size was 4.7 ± 0.5 cm for the HA group and 4.7 ± 0.4 cm for the CA group.

Outcomes favored hybrid ablation over catheter ablation, the researchers reported. “We never would have expected these huge differences,” Dr. Doll told the congress. “We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase.”

‘Exceptional’ trial

After Dr. Doll’s presentation, appointed discussant Stylianos Tzeis, MD, PhD, head of the cardiology clinic and electrophysiology and pacing department at Mitera Hospital in Athens, congratulated the investigators and called CEASE-AF “an exceptional trial. It was really challenging to enroll patients in such a randomized controlled clinical trial.”

But Dr. Tzeis questioned whether pitting CA against HA was a fair comparison.

“Were the ablation targets similar between the two groups?” he asked. He noted that for the HA group, in the first stage the patients had PVI, posterior wall isolation, exclusion of the left atrial appendage, and additional lesions at the discretion of the operator. Ninety percent proceeded to the second stage, which was endocardial catheter ablation with verification of posterior wall isolation and PVI and additional lesions made if needed.

In the CA group, repeat catheter ablation could be performed after the 90-day blanking period if clinically indicated. “Please take note that only 10% were offered the second ablation. So at least in my perspective, this was a comparison of a two-stage approach versus a single-stage approach with a much more aggressive ablation protocol in the hybrid ablation group as compared to the endocardial group,” he said.

Seeing the higher success rate of the HA group in achieving the primary efficacy endpoint of freedom from all arrhythmias at 12 months, Dr. Tzeis asked, “Does this reflect the superiority of the epi-endo approach, or does it reflect the suboptimal performance of the catheter ablation approach?”

There was a 40% success rate in the CA patient population, a cohort that he deemed “not the most challenging persistent AF population in the world”: those with left atrial diameter of 47 millimeters and with 80% having an AF duration less than 12 months.

He also noted that “the average duration of the catheter ablation for the PVI in the vast majority of cases was 4 hours, which does not reflect what really happens in the everyday practice.”

All those critiques having been advanced, Dr. Tzeis said, “Definitely do not doubt my first comment that the authors should be congratulated, and I strongly believe that the main objective has been achieved to bring electrophysiologist and cardiac surgeons ... closer.”

The study sponsor was AtriCure Inc. with collaboration of Cardialysis BV. Doll has received consulting fees or royalties and/or has ownership or stockholder interest in AtriCure. Tzeis reports no relevant financial relationships.
 

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

BARCELONA – Staged hybrid ablation provided superior freedom from atrial arrhythmias compared with endocardial catheter ablation alone, including the need for repeat ablations in patients with advanced atrial fibrillation (AF), new data show.

“We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase, so this is a huge difference,” concluded cardiac surgeon Nicholas Doll, MD, PhD, Schüchtermann Clinic, Bad Rothenfelde, Germany.

Dr. Doll presented the 12-month follow up results of the Combined Endoscopic Epicardial and Percutaneous Endocardial Ablation Versus Repeated Catheter Ablation in Persistent and Longstanding Persistent Atrial Fibrillation (CEASE-AF) trial at the European Heart Rhythm Association 2023 Congress, held recently in Barcelona and virtually.

He said CEASE-AF is the largest multicenter randomized clinical trial comparing these two approaches for control of atrial arrhythmias.

Safety outcomes were numerically higher in the hybrid ablation (HA) group of the trial but not statistically different from the catheter ablation (CA) group.
 

Unstable wavefront

As background, Dr. Doll explained that in advanced AF, there is a high degree of endocardial-epicardial dissociation with unstable wavefront propagation transitioning between the endocardial and epicardial surfaces. Endocardial mapping and ablation alone may be insufficient to address the mechanism of AF.

“So, the hypothesis of the CEASE-AF study was a minimally invasive hybrid ablation approach which combines endocardial and epicardial ablation to achieve superior effectiveness when compared to endocardial catheter ablation alone,” he said.

This prospective clinical trial randomized patients 2:1 at nine sites in five countries to HA (n = 102) or CA (n = 52). All had left atrial diameter of 4 cm to 6 cm and persistent AF for up to 1 year or longstanding persistent AF for greater than 1 year up to 10 years.

Any patient with a previous ablation procedure, BMI greater than 35 kg/m², or left ventricular ejection fraction less than 30% was excluded.

For HA, stage 1 consisted of epicardial lesions for pulmonary vein isolation (PVI) plus the posterior wall box plus left atrial appendage exclusion using the AtriClip (AtriCure Inc.) left atrial appendage exclusion device. Stage 2 involved endocardial mapping and catheter ablation to address gaps.

For CA, the index procedure involved catheter-mediated PVI plus repeat endocardial ablation as clinically indicated. For both HA and CA, additional ablation techniques and lesions were allowed for nonparoxysmal AF.

The HA timeline was the first stage, index procedure at time 0 (n = 102), a 90-day blanking period, and then the second stage, endocardial procedure at 90 to 180 days from the index procedure (n = 93).

For the CA arm of the trial, endocardial catheter ablation was performed on a minimal endocardial lesion set at time 0. Then after a 90-day blanking period, repeat catheter ablation was performed if clinically indicated (6/52).

Repeat ablations and electrical or pharmaceutical cardioversions were allowed during the 12-month follow-up period from time 0.

The primary efficacy endpoint was freedom from AF, atrial flutter, or atrial tachycardia of greater than 30 seconds through 12 months in the absence of class I/III antiarrhythmic drugs except ones that previously had failed, at doses not exceeding those previously failed doses. The safety endpoint was a composite rate of major complications over the course of the study.

Even with relatively modest cohort sizes, the HA and CA arms of the trial were well matched at baseline for age (approximately 60 years), gender (75.5% and 73.1% male, respectively), BMI (29.7 and 29.8 kg/m²), and persistent AF (79.4% and 82.7%).

The groups had persistent AF for 2.94 ± 3.29 years and 3.34 ± 3.52 years, respectively. The mean left atrial size was 4.7 ± 0.5 cm for the HA group and 4.7 ± 0.4 cm for the CA group.

Outcomes favored hybrid ablation over catheter ablation, the researchers reported. “We never would have expected these huge differences,” Dr. Doll told the congress. “We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase.”

‘Exceptional’ trial

After Dr. Doll’s presentation, appointed discussant Stylianos Tzeis, MD, PhD, head of the cardiology clinic and electrophysiology and pacing department at Mitera Hospital in Athens, congratulated the investigators and called CEASE-AF “an exceptional trial. It was really challenging to enroll patients in such a randomized controlled clinical trial.”

But Dr. Tzeis questioned whether pitting CA against HA was a fair comparison.

“Were the ablation targets similar between the two groups?” he asked. He noted that for the HA group, in the first stage the patients had PVI, posterior wall isolation, exclusion of the left atrial appendage, and additional lesions at the discretion of the operator. Ninety percent proceeded to the second stage, which was endocardial catheter ablation with verification of posterior wall isolation and PVI and additional lesions made if needed.

In the CA group, repeat catheter ablation could be performed after the 90-day blanking period if clinically indicated. “Please take note that only 10% were offered the second ablation. So at least in my perspective, this was a comparison of a two-stage approach versus a single-stage approach with a much more aggressive ablation protocol in the hybrid ablation group as compared to the endocardial group,” he said.

Seeing the higher success rate of the HA group in achieving the primary efficacy endpoint of freedom from all arrhythmias at 12 months, Dr. Tzeis asked, “Does this reflect the superiority of the epi-endo approach, or does it reflect the suboptimal performance of the catheter ablation approach?”

There was a 40% success rate in the CA patient population, a cohort that he deemed “not the most challenging persistent AF population in the world”: those with left atrial diameter of 47 millimeters and with 80% having an AF duration less than 12 months.

He also noted that “the average duration of the catheter ablation for the PVI in the vast majority of cases was 4 hours, which does not reflect what really happens in the everyday practice.”

All those critiques having been advanced, Dr. Tzeis said, “Definitely do not doubt my first comment that the authors should be congratulated, and I strongly believe that the main objective has been achieved to bring electrophysiologist and cardiac surgeons ... closer.”

The study sponsor was AtriCure Inc. with collaboration of Cardialysis BV. Doll has received consulting fees or royalties and/or has ownership or stockholder interest in AtriCure. Tzeis reports no relevant financial relationships.
 

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

BARCELONA – Staged hybrid ablation provided superior freedom from atrial arrhythmias compared with endocardial catheter ablation alone, including the need for repeat ablations in patients with advanced atrial fibrillation (AF), new data show.

“We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase, so this is a huge difference,” concluded cardiac surgeon Nicholas Doll, MD, PhD, Schüchtermann Clinic, Bad Rothenfelde, Germany.

Dr. Doll presented the 12-month follow up results of the Combined Endoscopic Epicardial and Percutaneous Endocardial Ablation Versus Repeated Catheter Ablation in Persistent and Longstanding Persistent Atrial Fibrillation (CEASE-AF) trial at the European Heart Rhythm Association 2023 Congress, held recently in Barcelona and virtually.

He said CEASE-AF is the largest multicenter randomized clinical trial comparing these two approaches for control of atrial arrhythmias.

Safety outcomes were numerically higher in the hybrid ablation (HA) group of the trial but not statistically different from the catheter ablation (CA) group.
 

Unstable wavefront

As background, Dr. Doll explained that in advanced AF, there is a high degree of endocardial-epicardial dissociation with unstable wavefront propagation transitioning between the endocardial and epicardial surfaces. Endocardial mapping and ablation alone may be insufficient to address the mechanism of AF.

“So, the hypothesis of the CEASE-AF study was a minimally invasive hybrid ablation approach which combines endocardial and epicardial ablation to achieve superior effectiveness when compared to endocardial catheter ablation alone,” he said.

This prospective clinical trial randomized patients 2:1 at nine sites in five countries to HA (n = 102) or CA (n = 52). All had left atrial diameter of 4 cm to 6 cm and persistent AF for up to 1 year or longstanding persistent AF for greater than 1 year up to 10 years.

Any patient with a previous ablation procedure, BMI greater than 35 kg/m², or left ventricular ejection fraction less than 30% was excluded.

For HA, stage 1 consisted of epicardial lesions for pulmonary vein isolation (PVI) plus the posterior wall box plus left atrial appendage exclusion using the AtriClip (AtriCure Inc.) left atrial appendage exclusion device. Stage 2 involved endocardial mapping and catheter ablation to address gaps.

For CA, the index procedure involved catheter-mediated PVI plus repeat endocardial ablation as clinically indicated. For both HA and CA, additional ablation techniques and lesions were allowed for nonparoxysmal AF.

The HA timeline was the first stage, index procedure at time 0 (n = 102), a 90-day blanking period, and then the second stage, endocardial procedure at 90 to 180 days from the index procedure (n = 93).

For the CA arm of the trial, endocardial catheter ablation was performed on a minimal endocardial lesion set at time 0. Then after a 90-day blanking period, repeat catheter ablation was performed if clinically indicated (6/52).

Repeat ablations and electrical or pharmaceutical cardioversions were allowed during the 12-month follow-up period from time 0.

The primary efficacy endpoint was freedom from AF, atrial flutter, or atrial tachycardia of greater than 30 seconds through 12 months in the absence of class I/III antiarrhythmic drugs except ones that previously had failed, at doses not exceeding those previously failed doses. The safety endpoint was a composite rate of major complications over the course of the study.

Even with relatively modest cohort sizes, the HA and CA arms of the trial were well matched at baseline for age (approximately 60 years), gender (75.5% and 73.1% male, respectively), BMI (29.7 and 29.8 kg/m²), and persistent AF (79.4% and 82.7%).

The groups had persistent AF for 2.94 ± 3.29 years and 3.34 ± 3.52 years, respectively. The mean left atrial size was 4.7 ± 0.5 cm for the HA group and 4.7 ± 0.4 cm for the CA group.

Outcomes favored hybrid ablation over catheter ablation, the researchers reported. “We never would have expected these huge differences,” Dr. Doll told the congress. “We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase.”

‘Exceptional’ trial

After Dr. Doll’s presentation, appointed discussant Stylianos Tzeis, MD, PhD, head of the cardiology clinic and electrophysiology and pacing department at Mitera Hospital in Athens, congratulated the investigators and called CEASE-AF “an exceptional trial. It was really challenging to enroll patients in such a randomized controlled clinical trial.”

But Dr. Tzeis questioned whether pitting CA against HA was a fair comparison.

“Were the ablation targets similar between the two groups?” he asked. He noted that for the HA group, in the first stage the patients had PVI, posterior wall isolation, exclusion of the left atrial appendage, and additional lesions at the discretion of the operator. Ninety percent proceeded to the second stage, which was endocardial catheter ablation with verification of posterior wall isolation and PVI and additional lesions made if needed.

In the CA group, repeat catheter ablation could be performed after the 90-day blanking period if clinically indicated. “Please take note that only 10% were offered the second ablation. So at least in my perspective, this was a comparison of a two-stage approach versus a single-stage approach with a much more aggressive ablation protocol in the hybrid ablation group as compared to the endocardial group,” he said.

Seeing the higher success rate of the HA group in achieving the primary efficacy endpoint of freedom from all arrhythmias at 12 months, Dr. Tzeis asked, “Does this reflect the superiority of the epi-endo approach, or does it reflect the suboptimal performance of the catheter ablation approach?”

There was a 40% success rate in the CA patient population, a cohort that he deemed “not the most challenging persistent AF population in the world”: those with left atrial diameter of 47 millimeters and with 80% having an AF duration less than 12 months.

He also noted that “the average duration of the catheter ablation for the PVI in the vast majority of cases was 4 hours, which does not reflect what really happens in the everyday practice.”

All those critiques having been advanced, Dr. Tzeis said, “Definitely do not doubt my first comment that the authors should be congratulated, and I strongly believe that the main objective has been achieved to bring electrophysiologist and cardiac surgeons ... closer.”

The study sponsor was AtriCure Inc. with collaboration of Cardialysis BV. Doll has received consulting fees or royalties and/or has ownership or stockholder interest in AtriCure. Tzeis reports no relevant financial relationships.
 

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

The investigational drug motixafortide shows promise for improving the stem cell transplantation process in patients with multiple myeloma (MM), according to research led by investigators at Washington University in St. Louis.

Motixafortide, a   novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity , appears to increase the number of stem cells that can be harvested from transplant candidates, thereby increasing the likelihood of successful transplant, the authors reported.

An application for a new drug approval is currently under review by the Food and Drug Administration.

In the prospective, international, phase 3 GENESIS clinical trial , motixafortide plus granulocyte colony-stimulating factor (G-CSF) – the standard therapy for mobilizing stem cells – significantly increased the number stem cells harvested, when compared with standard therapy plus placebo. After one collection procedure, the combination approach allowed for harvesting of an optimal number of cells in 88% versus 9% of patients who received G-CSF plus placebo. After two collections, optimal collection occurred in 92% versus 26% of patients in the groups, respectively, first author Zachary D. Crees, MD, and colleagues found.

Motixafortide plus G-CSF was also associated with a tenfold increase in the number of primitive stem cells that could be collected. These stem cells are particularly effective for reconstituting red blood cells, white blood cells, and platelets, which all are important for patients’ recovery, they noted.

Stem cells mobilized by motixafortide were also associated with increased expression of genes and genetic pathways involved in self-renewal and regeneration, which are also of benefit for increasing the effectiveness of stem cell transplantation.

The findings were published in Nature Medicine.

“Stem cell transplantation is central to the treatment of multiple myeloma, but some patients don’t see as much benefit because standard therapies can’t harvest enough stem cells for the transplant to be effective, senior author John F. DiPersio, MD, PhD, stated in a news release . “This study suggests motixafortide works extremely well in combination with [G-CSF] in mobilizing stem cells in patients with multiple myeloma.

“The study also found that the combination worked rapidly and was generally well tolerated by patients,” added Dr. DiPersio, the Virginia E. & Sam J. Goldman Professor of Medicine at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University.

Dr. DiPersio is the lead author of another study investigating therapies beyond stem cell transplants. He and his colleagues recently reported the first comprehensive genomic and protein-based analysis of bone marrow samples from patients with multiple myeloma in an effort to identify targets for immunotherapies.

That study, published online in Cancer Research, identified 53 genes that could be targets, including 38 that are responsible for creating abnormal proteins on the surface of multiple myeloma cells; 11 of the 38 had not been previously identified as potential targets.

Dr. DiPersio and Dr. Crees, an assistant professor of medicine and the assistant clinical director of the Washington University Center for Gene and Cellular Immunotherapy, are also evaluating motixafortide’s potential for mobilizing stem cells to support “the genetic correction of the inherited disease sickle cell anemia.”

“This work is of particular importance because patients with sickle cell disease can’t be treated with G-CSF … due to dangerous side effects,” the news release stated. “The hope is that development of a novel, effective, and well-tolerated stem cell mobilizing regimen for a viral-based gene therapy approach using CRISPR-based gene editing will lead to improved outcomes for patients with sickle cell disease.”

The study published in Nature Medicine was supported by the National Institutes of Health and BioLineRx, which makes motixafortide. The study published in Cancer Research was supported by the Paula C. And Rodger O. Riney Blood Cancer Research Fund and the National Cancer Institute.

Dr. Crees reported research funding from BioLineRx. Dr. DiPersio reported relationships with Magenta Therapeutics, WUGEN, Incyte, RiverVest Venture Partners, Cellworks Group, Amphivena Therapeutics, NeoImmune Tech, Macrogenics, and BioLineRx.

Correction, 4/26/23: The headline on an earlier version of this article mischaracterized the study findings.

The investigational drug motixafortide shows promise for improving the stem cell transplantation process in patients with multiple myeloma (MM), according to research led by investigators at Washington University in St. Louis.

Motixafortide, a   novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity , appears to increase the number of stem cells that can be harvested from transplant candidates, thereby increasing the likelihood of successful transplant, the authors reported.

An application for a new drug approval is currently under review by the Food and Drug Administration.

In the prospective, international, phase 3 GENESIS clinical trial , motixafortide plus granulocyte colony-stimulating factor (G-CSF) – the standard therapy for mobilizing stem cells – significantly increased the number stem cells harvested, when compared with standard therapy plus placebo. After one collection procedure, the combination approach allowed for harvesting of an optimal number of cells in 88% versus 9% of patients who received G-CSF plus placebo. After two collections, optimal collection occurred in 92% versus 26% of patients in the groups, respectively, first author Zachary D. Crees, MD, and colleagues found.

Motixafortide plus G-CSF was also associated with a tenfold increase in the number of primitive stem cells that could be collected. These stem cells are particularly effective for reconstituting red blood cells, white blood cells, and platelets, which all are important for patients’ recovery, they noted.

Stem cells mobilized by motixafortide were also associated with increased expression of genes and genetic pathways involved in self-renewal and regeneration, which are also of benefit for increasing the effectiveness of stem cell transplantation.

The findings were published in Nature Medicine.

“Stem cell transplantation is central to the treatment of multiple myeloma, but some patients don’t see as much benefit because standard therapies can’t harvest enough stem cells for the transplant to be effective, senior author John F. DiPersio, MD, PhD, stated in a news release . “This study suggests motixafortide works extremely well in combination with [G-CSF] in mobilizing stem cells in patients with multiple myeloma.

“The study also found that the combination worked rapidly and was generally well tolerated by patients,” added Dr. DiPersio, the Virginia E. & Sam J. Goldman Professor of Medicine at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University.

Dr. DiPersio is the lead author of another study investigating therapies beyond stem cell transplants. He and his colleagues recently reported the first comprehensive genomic and protein-based analysis of bone marrow samples from patients with multiple myeloma in an effort to identify targets for immunotherapies.

That study, published online in Cancer Research, identified 53 genes that could be targets, including 38 that are responsible for creating abnormal proteins on the surface of multiple myeloma cells; 11 of the 38 had not been previously identified as potential targets.

Dr. DiPersio and Dr. Crees, an assistant professor of medicine and the assistant clinical director of the Washington University Center for Gene and Cellular Immunotherapy, are also evaluating motixafortide’s potential for mobilizing stem cells to support “the genetic correction of the inherited disease sickle cell anemia.”

“This work is of particular importance because patients with sickle cell disease can’t be treated with G-CSF … due to dangerous side effects,” the news release stated. “The hope is that development of a novel, effective, and well-tolerated stem cell mobilizing regimen for a viral-based gene therapy approach using CRISPR-based gene editing will lead to improved outcomes for patients with sickle cell disease.”

The study published in Nature Medicine was supported by the National Institutes of Health and BioLineRx, which makes motixafortide. The study published in Cancer Research was supported by the Paula C. And Rodger O. Riney Blood Cancer Research Fund and the National Cancer Institute.

Dr. Crees reported research funding from BioLineRx. Dr. DiPersio reported relationships with Magenta Therapeutics, WUGEN, Incyte, RiverVest Venture Partners, Cellworks Group, Amphivena Therapeutics, NeoImmune Tech, Macrogenics, and BioLineRx.

Correction, 4/26/23: The headline on an earlier version of this article mischaracterized the study findings.

The investigational drug motixafortide shows promise for improving the stem cell transplantation process in patients with multiple myeloma (MM), according to research led by investigators at Washington University in St. Louis.

Motixafortide, a   novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity , appears to increase the number of stem cells that can be harvested from transplant candidates, thereby increasing the likelihood of successful transplant, the authors reported.

An application for a new drug approval is currently under review by the Food and Drug Administration.

In the prospective, international, phase 3 GENESIS clinical trial , motixafortide plus granulocyte colony-stimulating factor (G-CSF) – the standard therapy for mobilizing stem cells – significantly increased the number stem cells harvested, when compared with standard therapy plus placebo. After one collection procedure, the combination approach allowed for harvesting of an optimal number of cells in 88% versus 9% of patients who received G-CSF plus placebo. After two collections, optimal collection occurred in 92% versus 26% of patients in the groups, respectively, first author Zachary D. Crees, MD, and colleagues found.

Motixafortide plus G-CSF was also associated with a tenfold increase in the number of primitive stem cells that could be collected. These stem cells are particularly effective for reconstituting red blood cells, white blood cells, and platelets, which all are important for patients’ recovery, they noted.

Stem cells mobilized by motixafortide were also associated with increased expression of genes and genetic pathways involved in self-renewal and regeneration, which are also of benefit for increasing the effectiveness of stem cell transplantation.

The findings were published in Nature Medicine.

“Stem cell transplantation is central to the treatment of multiple myeloma, but some patients don’t see as much benefit because standard therapies can’t harvest enough stem cells for the transplant to be effective, senior author John F. DiPersio, MD, PhD, stated in a news release . “This study suggests motixafortide works extremely well in combination with [G-CSF] in mobilizing stem cells in patients with multiple myeloma.

“The study also found that the combination worked rapidly and was generally well tolerated by patients,” added Dr. DiPersio, the Virginia E. & Sam J. Goldman Professor of Medicine at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University.

Dr. DiPersio is the lead author of another study investigating therapies beyond stem cell transplants. He and his colleagues recently reported the first comprehensive genomic and protein-based analysis of bone marrow samples from patients with multiple myeloma in an effort to identify targets for immunotherapies.

That study, published online in Cancer Research, identified 53 genes that could be targets, including 38 that are responsible for creating abnormal proteins on the surface of multiple myeloma cells; 11 of the 38 had not been previously identified as potential targets.

Dr. DiPersio and Dr. Crees, an assistant professor of medicine and the assistant clinical director of the Washington University Center for Gene and Cellular Immunotherapy, are also evaluating motixafortide’s potential for mobilizing stem cells to support “the genetic correction of the inherited disease sickle cell anemia.”

“This work is of particular importance because patients with sickle cell disease can’t be treated with G-CSF … due to dangerous side effects,” the news release stated. “The hope is that development of a novel, effective, and well-tolerated stem cell mobilizing regimen for a viral-based gene therapy approach using CRISPR-based gene editing will lead to improved outcomes for patients with sickle cell disease.”

The study published in Nature Medicine was supported by the National Institutes of Health and BioLineRx, which makes motixafortide. The study published in Cancer Research was supported by the Paula C. And Rodger O. Riney Blood Cancer Research Fund and the National Cancer Institute.

Dr. Crees reported research funding from BioLineRx. Dr. DiPersio reported relationships with Magenta Therapeutics, WUGEN, Incyte, RiverVest Venture Partners, Cellworks Group, Amphivena Therapeutics, NeoImmune Tech, Macrogenics, and BioLineRx.

Correction, 4/26/23: The headline on an earlier version of this article mischaracterized the study findings.

Possibly. Elevated body mass index (BMI) is associated with an increased risk for stillbirth (strength of recommendation (SOR), B; Cohort studies and meta-analysis of cohort studies). Three studies found an association between elevated BMI and stillbirth and one did not. However, no studies demonstrate that antenatal testing in pregnant people with higher BMIs decreases stillbirth rates, or that no harm is caused by unnecessary testing or resultant interventions.

Still, in 2021, the American College of Obstetricians and Gynecologists (ACOG) suggested weekly antenatal testing may be considered from 34 weeks' 0 days' gestation for pregnant people with a BMI ≥ 40.0 kg/m² and from 37 weeks' 0 days' gestation for pregnant people with a BMI between 35.0 and 39.9 kg/m² (SOR, C; consensus guideline). Thus, doing the antenatal testing recommended in the ACOG guideline in an attempt to prevent stillbirth is reasonable, given evidence that elevated BMI is associated with stillbirth.

Evidence summary

Association between higher maternal BMI and increased risk for stillbirth

The purpose of antenatal testing is to decrease the risk for stillbirth between visits. Because of the resources involved and the risk for false-positives when testing low-risk patients, antenatal testing is reserved for pregnant people with higher risk for stillbirth.

In a retrospective cohort study of more than 2.8 million singleton births including 9,030 stillbirths, pregnant people with an elevated BMI had an increased risk for stillbirth compared with those with a normal BMI. The adjusted hazard ratio was 1.71 (95% confidence interval (CI), 1.62-1.83) for those with a BMI of 30.0 to 34.9 kg/m²; 2.04 (95% CI, 1.8-2.21) for those with a BMI of 35.0 to 39.9 kg/m²; and 2.50 (95% CI, 2.28-2.74) for those with a BMI ≥ 40 kg/m².¹

A meta-analysis of 38 studies, which included data on 16,274 stillbirths, found that a 5-unit increase in BMI was associated with an increased risk for stillbirth (relative risk, 1.24; 95% CI, 1.18-1.30).²

Another meta-analysis included 6 cohort studies involving more than 1 million pregnancies and 3 case-control studies involving 2,530 stillbirths and 2,837 controls from 1980-2005. There was an association between increasing BMI and stillbirth: the odds ratio (OR) was 1.47 (95% CI, 1.08-1.94) for those with a BMI of 25.0 to 29.9 kg/m² and 2.07 (95% CI, 1.59-2.74) for those with a BMI ≥ 30.0, compared with those with a normal BMI.³

However, a retrospective cohort study of 182,362 singleton births including 442 stillbirths found no association between stillbirth and increasing BMI. The OR was 1.10 (95% CI, 0.90-1.36) for those with a BMI of 25.0 to 29.9 and 1.09 (95% CI, 0.87-1.37) for those with a BMI ≥ 30.0 kg/m2, compared with those with a normal BMI.⁴ However, this cohort study may have been underpowered to detect an association between stillbirth and BMI.

Recommendations from others

In 2021, ACOG suggested that weekly antenatal testing may be considered from 34 weeks' and 0 days' gestation for pregnant people with a BMI ≥ 40.0 kg/m² and from 37 weeks' and 0 days' gestation for pregnant people with a BMI between 35.0 and 39.9 kg/m².⁵ The 2021 ACOG Practice Bulletin on obesity in pregnancy rates this recommendation as Level C—based primarily on consensus and expert opinion.⁶

A 2018 Royal College of Obstetricians and Gynecologists Green-top Guideline recognizes “definitive recommendations for fetal surveillance are hampered by the lack of randomized controlled trials demonstrating that antepartum fetal surveillance decreases perinatal morbidity or mortality in late-term and post-term gestations…. There are no definitive studies determining the optimal type or frequency of such testing and no evidence specific for women with obesity.”⁷

A 2019 Society of Obstetricians and Gynecologists of Canada practice guideline states “stillbirth is more common with maternal obesity” and recommends “increased fetal surveillance … in the third trimester if reduced fetal movements are reported.” The guideline notes “the role for non-stress tests … in surveillance of well-being in this population is uncertain.” Also, for pregnant people with a BMI > 30 kg/m², “assessment of fetal well-being is … recommended weekly from 37 weeks until delivery.” Finally, increased fetal surveillance is recommended in the setting of increased BMI and an abnormal pulsatility index of the umbilical artery and/or maternal uterine artery.⁸

Editor’s takeaway

Evidence demonstrates that increased maternal BMI is associated with increased stillbirths. However, evidence has not shown that third-trimester antenatal testing decreases this morbidity and mortality. Expert opinion varies, with ACOG recommending weekly antenatal testing from 34 and 37 weeks’ gestation, respectively, for pregnant people with BMIs of ≥ 40 kg/m² and of 35 to 39.9 kg/m². ●

Possibly. Elevated body mass index (BMI) is associated with an increased risk for stillbirth (strength of recommendation (SOR), B; Cohort studies and meta-analysis of cohort studies). Three studies found an association between elevated BMI and stillbirth and one did not. However, no studies demonstrate that antenatal testing in pregnant people with higher BMIs decreases stillbirth rates, or that no harm is caused by unnecessary testing or resultant interventions.

Still, in 2021, the American College of Obstetricians and Gynecologists (ACOG) suggested weekly antenatal testing may be considered from 34 weeks' 0 days' gestation for pregnant people with a BMI ≥ 40.0 kg/m² and from 37 weeks' 0 days' gestation for pregnant people with a BMI between 35.0 and 39.9 kg/m² (SOR, C; consensus guideline). Thus, doing the antenatal testing recommended in the ACOG guideline in an attempt to prevent stillbirth is reasonable, given evidence that elevated BMI is associated with stillbirth.

Evidence summary

Association between higher maternal BMI and increased risk for stillbirth

The purpose of antenatal testing is to decrease the risk for stillbirth between visits. Because of the resources involved and the risk for false-positives when testing low-risk patients, antenatal testing is reserved for pregnant people with higher risk for stillbirth.

In a retrospective cohort study of more than 2.8 million singleton births including 9,030 stillbirths, pregnant people with an elevated BMI had an increased risk for stillbirth compared with those with a normal BMI. The adjusted hazard ratio was 1.71 (95% confidence interval (CI), 1.62-1.83) for those with a BMI of 30.0 to 34.9 kg/m²; 2.04 (95% CI, 1.8-2.21) for those with a BMI of 35.0 to 39.9 kg/m²; and 2.50 (95% CI, 2.28-2.74) for those with a BMI ≥ 40 kg/m².¹

A meta-analysis of 38 studies, which included data on 16,274 stillbirths, found that a 5-unit increase in BMI was associated with an increased risk for stillbirth (relative risk, 1.24; 95% CI, 1.18-1.30).²

Another meta-analysis included 6 cohort studies involving more than 1 million pregnancies and 3 case-control studies involving 2,530 stillbirths and 2,837 controls from 1980-2005. There was an association between increasing BMI and stillbirth: the odds ratio (OR) was 1.47 (95% CI, 1.08-1.94) for those with a BMI of 25.0 to 29.9 kg/m² and 2.07 (95% CI, 1.59-2.74) for those with a BMI ≥ 30.0, compared with those with a normal BMI.³

However, a retrospective cohort study of 182,362 singleton births including 442 stillbirths found no association between stillbirth and increasing BMI. The OR was 1.10 (95% CI, 0.90-1.36) for those with a BMI of 25.0 to 29.9 and 1.09 (95% CI, 0.87-1.37) for those with a BMI ≥ 30.0 kg/m2, compared with those with a normal BMI.⁴ However, this cohort study may have been underpowered to detect an association between stillbirth and BMI.

Recommendations from others

In 2021, ACOG suggested that weekly antenatal testing may be considered from 34 weeks' and 0 days' gestation for pregnant people with a BMI ≥ 40.0 kg/m² and from 37 weeks' and 0 days' gestation for pregnant people with a BMI between 35.0 and 39.9 kg/m².⁵ The 2021 ACOG Practice Bulletin on obesity in pregnancy rates this recommendation as Level C—based primarily on consensus and expert opinion.⁶

A 2018 Royal College of Obstetricians and Gynecologists Green-top Guideline recognizes “definitive recommendations for fetal surveillance are hampered by the lack of randomized controlled trials demonstrating that antepartum fetal surveillance decreases perinatal morbidity or mortality in late-term and post-term gestations…. There are no definitive studies determining the optimal type or frequency of such testing and no evidence specific for women with obesity.”⁷

A 2019 Society of Obstetricians and Gynecologists of Canada practice guideline states “stillbirth is more common with maternal obesity” and recommends “increased fetal surveillance … in the third trimester if reduced fetal movements are reported.” The guideline notes “the role for non-stress tests … in surveillance of well-being in this population is uncertain.” Also, for pregnant people with a BMI > 30 kg/m², “assessment of fetal well-being is … recommended weekly from 37 weeks until delivery.” Finally, increased fetal surveillance is recommended in the setting of increased BMI and an abnormal pulsatility index of the umbilical artery and/or maternal uterine artery.⁸

Editor’s takeaway

Evidence demonstrates that increased maternal BMI is associated with increased stillbirths. However, evidence has not shown that third-trimester antenatal testing decreases this morbidity and mortality. Expert opinion varies, with ACOG recommending weekly antenatal testing from 34 and 37 weeks’ gestation, respectively, for pregnant people with BMIs of ≥ 40 kg/m² and of 35 to 39.9 kg/m². ●

Possibly. Elevated body mass index (BMI) is associated with an increased risk for stillbirth (strength of recommendation (SOR), B; Cohort studies and meta-analysis of cohort studies). Three studies found an association between elevated BMI and stillbirth and one did not. However, no studies demonstrate that antenatal testing in pregnant people with higher BMIs decreases stillbirth rates, or that no harm is caused by unnecessary testing or resultant interventions.

Still, in 2021, the American College of Obstetricians and Gynecologists (ACOG) suggested weekly antenatal testing may be considered from 34 weeks' 0 days' gestation for pregnant people with a BMI ≥ 40.0 kg/m² and from 37 weeks' 0 days' gestation for pregnant people with a BMI between 35.0 and 39.9 kg/m² (SOR, C; consensus guideline). Thus, doing the antenatal testing recommended in the ACOG guideline in an attempt to prevent stillbirth is reasonable, given evidence that elevated BMI is associated with stillbirth.

Evidence summary

Association between higher maternal BMI and increased risk for stillbirth

The purpose of antenatal testing is to decrease the risk for stillbirth between visits. Because of the resources involved and the risk for false-positives when testing low-risk patients, antenatal testing is reserved for pregnant people with higher risk for stillbirth.

In a retrospective cohort study of more than 2.8 million singleton births including 9,030 stillbirths, pregnant people with an elevated BMI had an increased risk for stillbirth compared with those with a normal BMI. The adjusted hazard ratio was 1.71 (95% confidence interval (CI), 1.62-1.83) for those with a BMI of 30.0 to 34.9 kg/m²; 2.04 (95% CI, 1.8-2.21) for those with a BMI of 35.0 to 39.9 kg/m²; and 2.50 (95% CI, 2.28-2.74) for those with a BMI ≥ 40 kg/m².¹

A meta-analysis of 38 studies, which included data on 16,274 stillbirths, found that a 5-unit increase in BMI was associated with an increased risk for stillbirth (relative risk, 1.24; 95% CI, 1.18-1.30).²

Another meta-analysis included 6 cohort studies involving more than 1 million pregnancies and 3 case-control studies involving 2,530 stillbirths and 2,837 controls from 1980-2005. There was an association between increasing BMI and stillbirth: the odds ratio (OR) was 1.47 (95% CI, 1.08-1.94) for those with a BMI of 25.0 to 29.9 kg/m² and 2.07 (95% CI, 1.59-2.74) for those with a BMI ≥ 30.0, compared with those with a normal BMI.³

However, a retrospective cohort study of 182,362 singleton births including 442 stillbirths found no association between stillbirth and increasing BMI. The OR was 1.10 (95% CI, 0.90-1.36) for those with a BMI of 25.0 to 29.9 and 1.09 (95% CI, 0.87-1.37) for those with a BMI ≥ 30.0 kg/m2, compared with those with a normal BMI.⁴ However, this cohort study may have been underpowered to detect an association between stillbirth and BMI.

Recommendations from others

In 2021, ACOG suggested that weekly antenatal testing may be considered from 34 weeks' and 0 days' gestation for pregnant people with a BMI ≥ 40.0 kg/m² and from 37 weeks' and 0 days' gestation for pregnant people with a BMI between 35.0 and 39.9 kg/m².⁵ The 2021 ACOG Practice Bulletin on obesity in pregnancy rates this recommendation as Level C—based primarily on consensus and expert opinion.⁶

A 2018 Royal College of Obstetricians and Gynecologists Green-top Guideline recognizes “definitive recommendations for fetal surveillance are hampered by the lack of randomized controlled trials demonstrating that antepartum fetal surveillance decreases perinatal morbidity or mortality in late-term and post-term gestations…. There are no definitive studies determining the optimal type or frequency of such testing and no evidence specific for women with obesity.”⁷

A 2019 Society of Obstetricians and Gynecologists of Canada practice guideline states “stillbirth is more common with maternal obesity” and recommends “increased fetal surveillance … in the third trimester if reduced fetal movements are reported.” The guideline notes “the role for non-stress tests … in surveillance of well-being in this population is uncertain.” Also, for pregnant people with a BMI > 30 kg/m², “assessment of fetal well-being is … recommended weekly from 37 weeks until delivery.” Finally, increased fetal surveillance is recommended in the setting of increased BMI and an abnormal pulsatility index of the umbilical artery and/or maternal uterine artery.⁸

Editor’s takeaway

Evidence demonstrates that increased maternal BMI is associated with increased stillbirths. However, evidence has not shown that third-trimester antenatal testing decreases this morbidity and mortality. Expert opinion varies, with ACOG recommending weekly antenatal testing from 34 and 37 weeks’ gestation, respectively, for pregnant people with BMIs of ≥ 40 kg/m² and of 35 to 39.9 kg/m². ●

BOSTON – Treating atrial fibrillation with catheter ablation in addition to medical management may offer greater protection against cognitive impairment than medical management alone, new research suggests.

Investigators found adults who had previously undergone catheter ablation were significantly less likely to be cognitively impaired during the 2-year study period, compared with those who receive medical management alone.

“Catheter ablation is intended to stop atrial fibrillation and restore the normal rhythm of the heart. By doing so, there is an improved cerebral hemodynamic profile,” said Bahadar S. Srichawla, DO, department of neurology, University of Massachusetts, Worcester.

“Thus, long-term cognitive outcomes may be improved due to improved blood flow to the brain by restoring the normal rhythm of the heart,” he added.

This research was presented at the 2023 annual meeting of the American Academy of Neurology.
 

Heart-brain connection

The study involved 887 older adults (mean age 75; 49% women) with atrial fibrillation participating in the SAGE-AF (Systematic Assessment of Geriatric Elements) study. A total of 193 (22%) participants underwent catheter ablation prior to enrollment. These individuals more frequently had an implantable cardiac device (46% vs. 28%, P < .001) and persistent atrial fibrillation (31% vs. 23%, P < .05).

Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) tool at baseline and 1 and 2 years, with cognitive impairment defined as a MoCA score of 23 or below. Individuals who had catheter ablation had an average MoCA score of 25, compared with an average score of 23 in those who didn’t have catheter ablation.

After adjusting for potential confounding factors such as heart disease, renal disease, sleep apnea, and atrial fibrillation risk score, those who underwent catheter ablation were 36% less likely to develop cognitive impairment over 2 years than those who were treated only with medication (adjusted odds ratio, 0.64; 95% CI, 0.46-0.88).

During his presentation, Dr. Srichawla noted there is a hypothesis that individuals who are anticoagulated with warfarin may be prone to cerebral microbleeds and may be more cognitively impaired over time.

However, in a subgroup analysis, “cognitive function was similar at 2-year follow-up in those anticoagulated with warfarin, compared with all other anticoagulants. However, it should be noted that in this study, a direct head-to-head comparison was not done,” Dr. Srichawla told attendees.

“In patients with atrial fibrillation, catheter ablation should be discussed as a potential treatment strategy, particularly in patients who have or are at risk for cognitive decline and dementia,” Dr. Srichawla said.
 

Intriguing findings

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said the study is “intriguing and adds to what we know from previous research connecting cardiovascular and cognitive health.”

“However, there are limitations to this study,” Dr. Griffin said, “including its predominantly White cohort and the use of only neuropsychiatric testing to diagnose dementia. More research is needed to fully understand the impact of atrial fibrillation on cognitive outcomes in all people.”

“It’s well known that the heart and the brain are intimately connected. Individuals experiencing any cardiovascular issues should speak to their doctor,” Dr. Griffin added.

Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, agreed. “If you ever get up too quickly and feel woozy, that is your brain not getting enough blood flow and you are getting all the warning signs to correct that – or else! Similarly, with atrial fibrillation, the heart is contracting, but not effectively pumping blood to the brain,” he said.

“This line of research shows that correcting the abnormal heart rhythm by zapping the faulty circuit with a catheter is actually better for your brain health than just taking medications alone,” added Dr. Lakhan, who was not involved with the study.

The study had no commercial funding. Dr. Srichawla, Dr. Griffin, and Dr. Lakhan report no relevant financial relationships.

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

BOSTON – Treating atrial fibrillation with catheter ablation in addition to medical management may offer greater protection against cognitive impairment than medical management alone, new research suggests.

Investigators found adults who had previously undergone catheter ablation were significantly less likely to be cognitively impaired during the 2-year study period, compared with those who receive medical management alone.

“Catheter ablation is intended to stop atrial fibrillation and restore the normal rhythm of the heart. By doing so, there is an improved cerebral hemodynamic profile,” said Bahadar S. Srichawla, DO, department of neurology, University of Massachusetts, Worcester.

“Thus, long-term cognitive outcomes may be improved due to improved blood flow to the brain by restoring the normal rhythm of the heart,” he added.

This research was presented at the 2023 annual meeting of the American Academy of Neurology.
 

Heart-brain connection

The study involved 887 older adults (mean age 75; 49% women) with atrial fibrillation participating in the SAGE-AF (Systematic Assessment of Geriatric Elements) study. A total of 193 (22%) participants underwent catheter ablation prior to enrollment. These individuals more frequently had an implantable cardiac device (46% vs. 28%, P < .001) and persistent atrial fibrillation (31% vs. 23%, P < .05).

Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) tool at baseline and 1 and 2 years, with cognitive impairment defined as a MoCA score of 23 or below. Individuals who had catheter ablation had an average MoCA score of 25, compared with an average score of 23 in those who didn’t have catheter ablation.

After adjusting for potential confounding factors such as heart disease, renal disease, sleep apnea, and atrial fibrillation risk score, those who underwent catheter ablation were 36% less likely to develop cognitive impairment over 2 years than those who were treated only with medication (adjusted odds ratio, 0.64; 95% CI, 0.46-0.88).

During his presentation, Dr. Srichawla noted there is a hypothesis that individuals who are anticoagulated with warfarin may be prone to cerebral microbleeds and may be more cognitively impaired over time.

However, in a subgroup analysis, “cognitive function was similar at 2-year follow-up in those anticoagulated with warfarin, compared with all other anticoagulants. However, it should be noted that in this study, a direct head-to-head comparison was not done,” Dr. Srichawla told attendees.

“In patients with atrial fibrillation, catheter ablation should be discussed as a potential treatment strategy, particularly in patients who have or are at risk for cognitive decline and dementia,” Dr. Srichawla said.
 

Intriguing findings

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said the study is “intriguing and adds to what we know from previous research connecting cardiovascular and cognitive health.”

“However, there are limitations to this study,” Dr. Griffin said, “including its predominantly White cohort and the use of only neuropsychiatric testing to diagnose dementia. More research is needed to fully understand the impact of atrial fibrillation on cognitive outcomes in all people.”

“It’s well known that the heart and the brain are intimately connected. Individuals experiencing any cardiovascular issues should speak to their doctor,” Dr. Griffin added.

Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, agreed. “If you ever get up too quickly and feel woozy, that is your brain not getting enough blood flow and you are getting all the warning signs to correct that – or else! Similarly, with atrial fibrillation, the heart is contracting, but not effectively pumping blood to the brain,” he said.

“This line of research shows that correcting the abnormal heart rhythm by zapping the faulty circuit with a catheter is actually better for your brain health than just taking medications alone,” added Dr. Lakhan, who was not involved with the study.

The study had no commercial funding. Dr. Srichawla, Dr. Griffin, and Dr. Lakhan report no relevant financial relationships.

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

BOSTON – Treating atrial fibrillation with catheter ablation in addition to medical management may offer greater protection against cognitive impairment than medical management alone, new research suggests.

Investigators found adults who had previously undergone catheter ablation were significantly less likely to be cognitively impaired during the 2-year study period, compared with those who receive medical management alone.

“Catheter ablation is intended to stop atrial fibrillation and restore the normal rhythm of the heart. By doing so, there is an improved cerebral hemodynamic profile,” said Bahadar S. Srichawla, DO, department of neurology, University of Massachusetts, Worcester.

“Thus, long-term cognitive outcomes may be improved due to improved blood flow to the brain by restoring the normal rhythm of the heart,” he added.

This research was presented at the 2023 annual meeting of the American Academy of Neurology.
 

Heart-brain connection

The study involved 887 older adults (mean age 75; 49% women) with atrial fibrillation participating in the SAGE-AF (Systematic Assessment of Geriatric Elements) study. A total of 193 (22%) participants underwent catheter ablation prior to enrollment. These individuals more frequently had an implantable cardiac device (46% vs. 28%, P < .001) and persistent atrial fibrillation (31% vs. 23%, P < .05).

Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) tool at baseline and 1 and 2 years, with cognitive impairment defined as a MoCA score of 23 or below. Individuals who had catheter ablation had an average MoCA score of 25, compared with an average score of 23 in those who didn’t have catheter ablation.

After adjusting for potential confounding factors such as heart disease, renal disease, sleep apnea, and atrial fibrillation risk score, those who underwent catheter ablation were 36% less likely to develop cognitive impairment over 2 years than those who were treated only with medication (adjusted odds ratio, 0.64; 95% CI, 0.46-0.88).

During his presentation, Dr. Srichawla noted there is a hypothesis that individuals who are anticoagulated with warfarin may be prone to cerebral microbleeds and may be more cognitively impaired over time.

However, in a subgroup analysis, “cognitive function was similar at 2-year follow-up in those anticoagulated with warfarin, compared with all other anticoagulants. However, it should be noted that in this study, a direct head-to-head comparison was not done,” Dr. Srichawla told attendees.

“In patients with atrial fibrillation, catheter ablation should be discussed as a potential treatment strategy, particularly in patients who have or are at risk for cognitive decline and dementia,” Dr. Srichawla said.
 

Intriguing findings

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said the study is “intriguing and adds to what we know from previous research connecting cardiovascular and cognitive health.”

“However, there are limitations to this study,” Dr. Griffin said, “including its predominantly White cohort and the use of only neuropsychiatric testing to diagnose dementia. More research is needed to fully understand the impact of atrial fibrillation on cognitive outcomes in all people.”

“It’s well known that the heart and the brain are intimately connected. Individuals experiencing any cardiovascular issues should speak to their doctor,” Dr. Griffin added.

Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, agreed. “If you ever get up too quickly and feel woozy, that is your brain not getting enough blood flow and you are getting all the warning signs to correct that – or else! Similarly, with atrial fibrillation, the heart is contracting, but not effectively pumping blood to the brain,” he said.

“This line of research shows that correcting the abnormal heart rhythm by zapping the faulty circuit with a catheter is actually better for your brain health than just taking medications alone,” added Dr. Lakhan, who was not involved with the study.

The study had no commercial funding. Dr. Srichawla, Dr. Griffin, and Dr. Lakhan report no relevant financial relationships.

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

WASHINGTON – Psilocybin is safe and effective in patients with body dysmorphic disorder (BDD), preliminary findings of a small pilot study show.

“The results suggest that psilocybin appears to be relatively safe and potentially helpful for people with BDD, and that it has a broader scope than just depression,” study investigator Franklin Schneier, MD, codirector of the Anxiety Disorders Clinic, New York State Psychiatric Institute, and special lecturer in psychiatry at Columbia University Medical Center in New York City, told this news organization.

So far, psilocybin has mostly been examined in clinical trials among patients with major depression. Dr. Schneier said he is aware of only a single case in the literature of its use in BDD: a patient who self-treated with psilocybin and reported symptom improvement.

The current study was presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Few treatment options

Patients with BDD are preoccupied with a body part they perceive as ugly or defective, “and not just mildly so,” said Dr. Schneier. “It bothers them to the extreme such that they may obsess about it on and off all day long.”

Such patients may engage in compulsive behaviors like constantly checking themselves in the mirror, and going to great lengths to conceal the body part they feel is defective. “They often seek out cosmetic procedures that objectively aren’t warranted,” said Dr. Schneier.

BDD patients often have comorbid depression, and many attempt suicide. As with other anxiety and depressive disorders, BDD is twice as prevalent in women vs. men, said Dr. Schneier.

Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) are the only approved therapies for BDD.

The investigators thought there may be a good chance BDD patients could benefit from psilocybin. Psilocybin alters bodily self-awareness, which “might shake up people’s beliefs about their abnormal body perceptions,” said Dr. Schneier.

There’s also some suggestion that psilocybin relaxes inflexible thinking, he added. “People with BDD have very rigid beliefs about their body distortions that aren’t easily swayed by logic.”

The study included 12 adults (8 women, 4 men) with a mean age of 34 years and moderate to severe BDD who failed at least one SSRI course and had had BDD for an average of 21 years.

Participants had preliminary sessions with a therapist familiar with psilocybin who prepared them psychologically and discussed what to expect from the experience. On the day of the intervention, subjects took a single 25 mg oral dose of synthetic psilocybin in a comfortable setting.

Therapists were present for the next 8 hours to answer questions and support subjects through the experience.
 

High response rate

The primary efficacy outcome was change in the BDD Yale-Brown Obsessive Compulsive Disorder Scale Modified (BDD-YBOCS) total score.

The mean baseline BDD-YBOCS score was 29.17. Researchers regularly assessed this score in the following weeks.

At 12 weeks, BDD-YBOCS scores decreased significantly from baseline (P < .001) with a large effect size (partial eta squared = .54).

However, said Dr. Schneier, what really stood out was the proportion of responders. At week 12, seven (58%) of the 12 participants were responders, as defined by a 30% or greater decrease in the BDD-YBOCS score. Of these, three were “almost symptom-free,” he added.

A number of secondary outcomes, including conviction of belief, disability, and negative affect, also significantly improved.

It’s too early to determine if additional treatment is required. The investigators plan to follow-up with the cohort at 1 year.

Although exciting, these early results warrant caution, said Dr. Schneier. “On the one hand, this is a sample of people who have struggled for a long time and have failed previous therapies, so that’s good. But on the other hand, it’s an open trial with no placebo group, and everyone has high expectations, so we don’t know how much of a placebo effect there was.”

Most adverse events, including headaches and fatigue, were mild and resolved within the first week after dosing, and there were no serious adverse events.

Based on these findings, Dr. Schneier said controlled trials of psilocybin in BDD are warranted.
 

Need for scientific rigor

Commenting on the research, Charles B. Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, University of Texas at Austin, said while promising, psilocybin is “not for everyone” and patients need to be closely screened.

University of Texas at Austin

“We want to know their medical history and if they have a family history of schizophrenia or bipolar disorder. We don’t know whether these [psychedelic] medicines might trigger an episode.”

Dr. Nemeroff also noted there’s a risk of “troubling” side effects from the drug.

“My view is psilocybin clearly has therapeutic effects and we need to apply scientific rigor as we would any medicine in order to determine the risk/benefit ratio,” said Dr. Nemeroff, who was not associated with this psilocybin trial.

In addition, psilocybin is being tested in conditions other than BDD and major depression, including anorexia nervosa, postpartum depression, and alcohol use disorder, he added.

The study received funding from COMPASS Pathways PLC.

Dr. Nemeroff reports he has received research support from the NIH and Stanley Medical Research Institute; served as a consultant for Bracket (Clintara), Fortress Biotech, Intra-Cellular Therapies, Janssen Research and Development, Magstim, Navitor Pharmaceuticals, Sunovion Pharmaceuticals, Taisho Pharmaceuticals, Takeda, TC MSO, and Xhale; served on scientific advisory boards for the American Foundation for Suicide Prevention, the Anxiety and Depression Association of America, Bracket (Clintara), Brain and Behavior Research Foundation, Laureate Institute for Brain Research, Skyland Trail, and Xhale; is a stockholder in AbbVie, Antares, BI Gen Holdings, Celgene, OPKO Health, Seattle Genetics, and Xhale; serves on the board of directors for the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, and Gratitude America; has received income or equity of $10,000 or more from American Psychiatric Publishing, Bracket (Clintara), Magstim, CME Outfitters, and Intra-Cellular Therapies; and holds patents on a method and devices for transdermal delivery of lithium and a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay.

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

WASHINGTON – Psilocybin is safe and effective in patients with body dysmorphic disorder (BDD), preliminary findings of a small pilot study show.

“The results suggest that psilocybin appears to be relatively safe and potentially helpful for people with BDD, and that it has a broader scope than just depression,” study investigator Franklin Schneier, MD, codirector of the Anxiety Disorders Clinic, New York State Psychiatric Institute, and special lecturer in psychiatry at Columbia University Medical Center in New York City, told this news organization.

So far, psilocybin has mostly been examined in clinical trials among patients with major depression. Dr. Schneier said he is aware of only a single case in the literature of its use in BDD: a patient who self-treated with psilocybin and reported symptom improvement.

The current study was presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Few treatment options

Patients with BDD are preoccupied with a body part they perceive as ugly or defective, “and not just mildly so,” said Dr. Schneier. “It bothers them to the extreme such that they may obsess about it on and off all day long.”

Such patients may engage in compulsive behaviors like constantly checking themselves in the mirror, and going to great lengths to conceal the body part they feel is defective. “They often seek out cosmetic procedures that objectively aren’t warranted,” said Dr. Schneier.

BDD patients often have comorbid depression, and many attempt suicide. As with other anxiety and depressive disorders, BDD is twice as prevalent in women vs. men, said Dr. Schneier.

Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) are the only approved therapies for BDD.

The investigators thought there may be a good chance BDD patients could benefit from psilocybin. Psilocybin alters bodily self-awareness, which “might shake up people’s beliefs about their abnormal body perceptions,” said Dr. Schneier.

There’s also some suggestion that psilocybin relaxes inflexible thinking, he added. “People with BDD have very rigid beliefs about their body distortions that aren’t easily swayed by logic.”

The study included 12 adults (8 women, 4 men) with a mean age of 34 years and moderate to severe BDD who failed at least one SSRI course and had had BDD for an average of 21 years.

Participants had preliminary sessions with a therapist familiar with psilocybin who prepared them psychologically and discussed what to expect from the experience. On the day of the intervention, subjects took a single 25 mg oral dose of synthetic psilocybin in a comfortable setting.

Therapists were present for the next 8 hours to answer questions and support subjects through the experience.
 

High response rate

The primary efficacy outcome was change in the BDD Yale-Brown Obsessive Compulsive Disorder Scale Modified (BDD-YBOCS) total score.

The mean baseline BDD-YBOCS score was 29.17. Researchers regularly assessed this score in the following weeks.

At 12 weeks, BDD-YBOCS scores decreased significantly from baseline (P < .001) with a large effect size (partial eta squared = .54).

However, said Dr. Schneier, what really stood out was the proportion of responders. At week 12, seven (58%) of the 12 participants were responders, as defined by a 30% or greater decrease in the BDD-YBOCS score. Of these, three were “almost symptom-free,” he added.

A number of secondary outcomes, including conviction of belief, disability, and negative affect, also significantly improved.

It’s too early to determine if additional treatment is required. The investigators plan to follow-up with the cohort at 1 year.

Although exciting, these early results warrant caution, said Dr. Schneier. “On the one hand, this is a sample of people who have struggled for a long time and have failed previous therapies, so that’s good. But on the other hand, it’s an open trial with no placebo group, and everyone has high expectations, so we don’t know how much of a placebo effect there was.”

Most adverse events, including headaches and fatigue, were mild and resolved within the first week after dosing, and there were no serious adverse events.

Based on these findings, Dr. Schneier said controlled trials of psilocybin in BDD are warranted.
 

Need for scientific rigor

Commenting on the research, Charles B. Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, University of Texas at Austin, said while promising, psilocybin is “not for everyone” and patients need to be closely screened.

University of Texas at Austin

“We want to know their medical history and if they have a family history of schizophrenia or bipolar disorder. We don’t know whether these [psychedelic] medicines might trigger an episode.”

Dr. Nemeroff also noted there’s a risk of “troubling” side effects from the drug.

“My view is psilocybin clearly has therapeutic effects and we need to apply scientific rigor as we would any medicine in order to determine the risk/benefit ratio,” said Dr. Nemeroff, who was not associated with this psilocybin trial.

In addition, psilocybin is being tested in conditions other than BDD and major depression, including anorexia nervosa, postpartum depression, and alcohol use disorder, he added.

The study received funding from COMPASS Pathways PLC.

Dr. Nemeroff reports he has received research support from the NIH and Stanley Medical Research Institute; served as a consultant for Bracket (Clintara), Fortress Biotech, Intra-Cellular Therapies, Janssen Research and Development, Magstim, Navitor Pharmaceuticals, Sunovion Pharmaceuticals, Taisho Pharmaceuticals, Takeda, TC MSO, and Xhale; served on scientific advisory boards for the American Foundation for Suicide Prevention, the Anxiety and Depression Association of America, Bracket (Clintara), Brain and Behavior Research Foundation, Laureate Institute for Brain Research, Skyland Trail, and Xhale; is a stockholder in AbbVie, Antares, BI Gen Holdings, Celgene, OPKO Health, Seattle Genetics, and Xhale; serves on the board of directors for the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, and Gratitude America; has received income or equity of $10,000 or more from American Psychiatric Publishing, Bracket (Clintara), Magstim, CME Outfitters, and Intra-Cellular Therapies; and holds patents on a method and devices for transdermal delivery of lithium and a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay.

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

WASHINGTON – Psilocybin is safe and effective in patients with body dysmorphic disorder (BDD), preliminary findings of a small pilot study show.

“The results suggest that psilocybin appears to be relatively safe and potentially helpful for people with BDD, and that it has a broader scope than just depression,” study investigator Franklin Schneier, MD, codirector of the Anxiety Disorders Clinic, New York State Psychiatric Institute, and special lecturer in psychiatry at Columbia University Medical Center in New York City, told this news organization.

So far, psilocybin has mostly been examined in clinical trials among patients with major depression. Dr. Schneier said he is aware of only a single case in the literature of its use in BDD: a patient who self-treated with psilocybin and reported symptom improvement.

The current study was presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Few treatment options

Patients with BDD are preoccupied with a body part they perceive as ugly or defective, “and not just mildly so,” said Dr. Schneier. “It bothers them to the extreme such that they may obsess about it on and off all day long.”

Such patients may engage in compulsive behaviors like constantly checking themselves in the mirror, and going to great lengths to conceal the body part they feel is defective. “They often seek out cosmetic procedures that objectively aren’t warranted,” said Dr. Schneier.

BDD patients often have comorbid depression, and many attempt suicide. As with other anxiety and depressive disorders, BDD is twice as prevalent in women vs. men, said Dr. Schneier.

Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) are the only approved therapies for BDD.

The investigators thought there may be a good chance BDD patients could benefit from psilocybin. Psilocybin alters bodily self-awareness, which “might shake up people’s beliefs about their abnormal body perceptions,” said Dr. Schneier.

There’s also some suggestion that psilocybin relaxes inflexible thinking, he added. “People with BDD have very rigid beliefs about their body distortions that aren’t easily swayed by logic.”

The study included 12 adults (8 women, 4 men) with a mean age of 34 years and moderate to severe BDD who failed at least one SSRI course and had had BDD for an average of 21 years.

Participants had preliminary sessions with a therapist familiar with psilocybin who prepared them psychologically and discussed what to expect from the experience. On the day of the intervention, subjects took a single 25 mg oral dose of synthetic psilocybin in a comfortable setting.

Therapists were present for the next 8 hours to answer questions and support subjects through the experience.
 

High response rate

The primary efficacy outcome was change in the BDD Yale-Brown Obsessive Compulsive Disorder Scale Modified (BDD-YBOCS) total score.

The mean baseline BDD-YBOCS score was 29.17. Researchers regularly assessed this score in the following weeks.

At 12 weeks, BDD-YBOCS scores decreased significantly from baseline (P < .001) with a large effect size (partial eta squared = .54).

However, said Dr. Schneier, what really stood out was the proportion of responders. At week 12, seven (58%) of the 12 participants were responders, as defined by a 30% or greater decrease in the BDD-YBOCS score. Of these, three were “almost symptom-free,” he added.

A number of secondary outcomes, including conviction of belief, disability, and negative affect, also significantly improved.

It’s too early to determine if additional treatment is required. The investigators plan to follow-up with the cohort at 1 year.

Although exciting, these early results warrant caution, said Dr. Schneier. “On the one hand, this is a sample of people who have struggled for a long time and have failed previous therapies, so that’s good. But on the other hand, it’s an open trial with no placebo group, and everyone has high expectations, so we don’t know how much of a placebo effect there was.”

Most adverse events, including headaches and fatigue, were mild and resolved within the first week after dosing, and there were no serious adverse events.

Based on these findings, Dr. Schneier said controlled trials of psilocybin in BDD are warranted.
 

Need for scientific rigor

Commenting on the research, Charles B. Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, University of Texas at Austin, said while promising, psilocybin is “not for everyone” and patients need to be closely screened.

University of Texas at Austin

“We want to know their medical history and if they have a family history of schizophrenia or bipolar disorder. We don’t know whether these [psychedelic] medicines might trigger an episode.”

Dr. Nemeroff also noted there’s a risk of “troubling” side effects from the drug.

“My view is psilocybin clearly has therapeutic effects and we need to apply scientific rigor as we would any medicine in order to determine the risk/benefit ratio,” said Dr. Nemeroff, who was not associated with this psilocybin trial.

In addition, psilocybin is being tested in conditions other than BDD and major depression, including anorexia nervosa, postpartum depression, and alcohol use disorder, he added.

The study received funding from COMPASS Pathways PLC.

Dr. Nemeroff reports he has received research support from the NIH and Stanley Medical Research Institute; served as a consultant for Bracket (Clintara), Fortress Biotech, Intra-Cellular Therapies, Janssen Research and Development, Magstim, Navitor Pharmaceuticals, Sunovion Pharmaceuticals, Taisho Pharmaceuticals, Takeda, TC MSO, and Xhale; served on scientific advisory boards for the American Foundation for Suicide Prevention, the Anxiety and Depression Association of America, Bracket (Clintara), Brain and Behavior Research Foundation, Laureate Institute for Brain Research, Skyland Trail, and Xhale; is a stockholder in AbbVie, Antares, BI Gen Holdings, Celgene, OPKO Health, Seattle Genetics, and Xhale; serves on the board of directors for the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, and Gratitude America; has received income or equity of $10,000 or more from American Psychiatric Publishing, Bracket (Clintara), Magstim, CME Outfitters, and Intra-Cellular Therapies; and holds patents on a method and devices for transdermal delivery of lithium and a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay.

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