An at-home investigational device is a promising noninvasive therapeutic approach for anxiety disorders, results from an open-label pilot trial suggest.

The small study showed users of the Mechanical Affective Touch Therapy (MATT) had improved anxiety and depression symptoms, which corresponded to positive changes in alpha and theta oscillatory activity.

Butler Hospital

Robust safety profile

Therapeutic noninvasive peripheral nerve stimulation is under investigation for anxiety as well as pain and depression. Nerve activation is achieved by delivering electrical or mechanical energy, although most devices to date have used electrical stimulation.

Although electrical stimulation is considered low risk, mechanical stimulation that activates somatosensory pathways has an even more robust safety profile, the investigators note.

The MATT device targets C-tactile fibers (CT) specialized unmyelinated Group C peripheral nerve fibers that fire when stroked at velocities perceived as pleasurable or comforting.

To use the device, participants wear a headset with a small vibrating piece that sits on the mastoid bone behind each ear. These pieces deliver gentle vibrations that can be adjusted by patients.  

During development of the MATT stimulation, researchers noted that an isochronic 10 Hz wave, cycling 2 seconds on and 2 seconds off, induced a state of relaxation and increased occipital alpha oscillations in pilot study participants.

The current study was designed to confirm preliminary efficacy and feasibility signals. The sample included 22 patients (mean age 37.3 years, 72.7% female, 77.3% White). All study participants were diagnosed with an anxiety disorder and had at least moderately severe anxiety symptoms. Some also had symptoms of panic or depression.

Many participants were on medications that weren’t effective, and they wanted to find a nondrug method of relieving their symptoms, said Dr. Carpenter.
 

What’s the mechanism?

Participants learned how to administer the stimulation and adjust the intensity of vibrations to a level where it was consistently detectable but not uncomfortable. Then they received a MATT device to use at home at least twice daily for 20 minutes.

Patients kept daily diaries documenting device use, adverse effects, and technological problems. In-person assessments were held at 2 and 4 weeks.

Researchers collected resting EEG immediately before, and after, the second stimulation session and again following 4 weeks of MATT use.

At baseline and after 2 and 4 weeks, patients self-reported anxiety using the 7-item Generalized Anxiety Disorder (GAD-7) scale, depression with the Beck Depression Inventory (BDI), and stress using the Perceived Stress Scale (PSS). They also reported symptoms with the Depression, Anxiety, Stress Scale (DASS).

Researchers also investigated “interoceptive awareness” or being mindful of your body and internal feelings. For this, they had participants complete the 32-item Multidimensional Assessment of Interoceptive Awareness pre- and post treatment.

Interoceptive awareness “is a whole new area of interest in neuroscience and brain health,” said Dr. Carpenter. “The hypothesis was that one way this device might work is that vibrations would travel to the insular cortex, the part of the brain that involves mindfulness and self-awareness.”
 

Symptom reduction

In the completer sample of 17 participants, mean scores on anxiety and depression symptoms fell significantly from baseline to 4 weeks (all P < .01). For example, the GAD-7 mean score fell from 14.3 to 7.1 and the BDI mean score from 30.6 to 14.8.

The study also showed that mindfulness was enhanced. The MAIA total score increased from 83.1 to 93.5 (P = .014).

Device users had increased alpha and theta brainwave activity, findings that “go along with the concept of decreased anxiety,” said Dr. Carpenter. She noted a recent study of the same patient population showed the device enhanced functional brain connectivity.

This current study was too small to pick up signals showing the device was effective in any particular subpopulation, said Dr. Carpenter.

Unlike other stimulation interventions that require clinic visits, patients use the MATT in the comfort of their own home and at their own convenience.

However, there are still questions surrounding the use of the noninvasive device. For example, said Dr. Carpenter, it’s unclear if it would be more effective if combined with psychotherapy or whether patients can use it while sleeping and driving. A next step could be a sham-controlled trial, she said.

The study was supported by Affect Neuro, developer of MATT therapy, and the National Institute of General Medical Sciences. Dr. Carpenter reports receiving a consultancy fee from Affect Neuro.

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

An at-home investigational device is a promising noninvasive therapeutic approach for anxiety disorders, results from an open-label pilot trial suggest.

The small study showed users of the Mechanical Affective Touch Therapy (MATT) had improved anxiety and depression symptoms, which corresponded to positive changes in alpha and theta oscillatory activity.

Butler Hospital

Robust safety profile

Therapeutic noninvasive peripheral nerve stimulation is under investigation for anxiety as well as pain and depression. Nerve activation is achieved by delivering electrical or mechanical energy, although most devices to date have used electrical stimulation.

Although electrical stimulation is considered low risk, mechanical stimulation that activates somatosensory pathways has an even more robust safety profile, the investigators note.

The MATT device targets C-tactile fibers (CT) specialized unmyelinated Group C peripheral nerve fibers that fire when stroked at velocities perceived as pleasurable or comforting.

To use the device, participants wear a headset with a small vibrating piece that sits on the mastoid bone behind each ear. These pieces deliver gentle vibrations that can be adjusted by patients.  

During development of the MATT stimulation, researchers noted that an isochronic 10 Hz wave, cycling 2 seconds on and 2 seconds off, induced a state of relaxation and increased occipital alpha oscillations in pilot study participants.

The current study was designed to confirm preliminary efficacy and feasibility signals. The sample included 22 patients (mean age 37.3 years, 72.7% female, 77.3% White). All study participants were diagnosed with an anxiety disorder and had at least moderately severe anxiety symptoms. Some also had symptoms of panic or depression.

Many participants were on medications that weren’t effective, and they wanted to find a nondrug method of relieving their symptoms, said Dr. Carpenter.
 

What’s the mechanism?

Participants learned how to administer the stimulation and adjust the intensity of vibrations to a level where it was consistently detectable but not uncomfortable. Then they received a MATT device to use at home at least twice daily for 20 minutes.

Patients kept daily diaries documenting device use, adverse effects, and technological problems. In-person assessments were held at 2 and 4 weeks.

Researchers collected resting EEG immediately before, and after, the second stimulation session and again following 4 weeks of MATT use.

At baseline and after 2 and 4 weeks, patients self-reported anxiety using the 7-item Generalized Anxiety Disorder (GAD-7) scale, depression with the Beck Depression Inventory (BDI), and stress using the Perceived Stress Scale (PSS). They also reported symptoms with the Depression, Anxiety, Stress Scale (DASS).

Researchers also investigated “interoceptive awareness” or being mindful of your body and internal feelings. For this, they had participants complete the 32-item Multidimensional Assessment of Interoceptive Awareness pre- and post treatment.

Interoceptive awareness “is a whole new area of interest in neuroscience and brain health,” said Dr. Carpenter. “The hypothesis was that one way this device might work is that vibrations would travel to the insular cortex, the part of the brain that involves mindfulness and self-awareness.”
 

Symptom reduction

In the completer sample of 17 participants, mean scores on anxiety and depression symptoms fell significantly from baseline to 4 weeks (all P < .01). For example, the GAD-7 mean score fell from 14.3 to 7.1 and the BDI mean score from 30.6 to 14.8.

The study also showed that mindfulness was enhanced. The MAIA total score increased from 83.1 to 93.5 (P = .014).

Device users had increased alpha and theta brainwave activity, findings that “go along with the concept of decreased anxiety,” said Dr. Carpenter. She noted a recent study of the same patient population showed the device enhanced functional brain connectivity.

This current study was too small to pick up signals showing the device was effective in any particular subpopulation, said Dr. Carpenter.

Unlike other stimulation interventions that require clinic visits, patients use the MATT in the comfort of their own home and at their own convenience.

However, there are still questions surrounding the use of the noninvasive device. For example, said Dr. Carpenter, it’s unclear if it would be more effective if combined with psychotherapy or whether patients can use it while sleeping and driving. A next step could be a sham-controlled trial, she said.

The study was supported by Affect Neuro, developer of MATT therapy, and the National Institute of General Medical Sciences. Dr. Carpenter reports receiving a consultancy fee from Affect Neuro.

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

An at-home investigational device is a promising noninvasive therapeutic approach for anxiety disorders, results from an open-label pilot trial suggest.

The small study showed users of the Mechanical Affective Touch Therapy (MATT) had improved anxiety and depression symptoms, which corresponded to positive changes in alpha and theta oscillatory activity.

Butler Hospital

Robust safety profile

Therapeutic noninvasive peripheral nerve stimulation is under investigation for anxiety as well as pain and depression. Nerve activation is achieved by delivering electrical or mechanical energy, although most devices to date have used electrical stimulation.

Although electrical stimulation is considered low risk, mechanical stimulation that activates somatosensory pathways has an even more robust safety profile, the investigators note.

The MATT device targets C-tactile fibers (CT) specialized unmyelinated Group C peripheral nerve fibers that fire when stroked at velocities perceived as pleasurable or comforting.

To use the device, participants wear a headset with a small vibrating piece that sits on the mastoid bone behind each ear. These pieces deliver gentle vibrations that can be adjusted by patients.  

During development of the MATT stimulation, researchers noted that an isochronic 10 Hz wave, cycling 2 seconds on and 2 seconds off, induced a state of relaxation and increased occipital alpha oscillations in pilot study participants.

The current study was designed to confirm preliminary efficacy and feasibility signals. The sample included 22 patients (mean age 37.3 years, 72.7% female, 77.3% White). All study participants were diagnosed with an anxiety disorder and had at least moderately severe anxiety symptoms. Some also had symptoms of panic or depression.

Many participants were on medications that weren’t effective, and they wanted to find a nondrug method of relieving their symptoms, said Dr. Carpenter.
 

What’s the mechanism?

Participants learned how to administer the stimulation and adjust the intensity of vibrations to a level where it was consistently detectable but not uncomfortable. Then they received a MATT device to use at home at least twice daily for 20 minutes.

Patients kept daily diaries documenting device use, adverse effects, and technological problems. In-person assessments were held at 2 and 4 weeks.

Researchers collected resting EEG immediately before, and after, the second stimulation session and again following 4 weeks of MATT use.

At baseline and after 2 and 4 weeks, patients self-reported anxiety using the 7-item Generalized Anxiety Disorder (GAD-7) scale, depression with the Beck Depression Inventory (BDI), and stress using the Perceived Stress Scale (PSS). They also reported symptoms with the Depression, Anxiety, Stress Scale (DASS).

Researchers also investigated “interoceptive awareness” or being mindful of your body and internal feelings. For this, they had participants complete the 32-item Multidimensional Assessment of Interoceptive Awareness pre- and post treatment.

Interoceptive awareness “is a whole new area of interest in neuroscience and brain health,” said Dr. Carpenter. “The hypothesis was that one way this device might work is that vibrations would travel to the insular cortex, the part of the brain that involves mindfulness and self-awareness.”
 

Symptom reduction

In the completer sample of 17 participants, mean scores on anxiety and depression symptoms fell significantly from baseline to 4 weeks (all P < .01). For example, the GAD-7 mean score fell from 14.3 to 7.1 and the BDI mean score from 30.6 to 14.8.

The study also showed that mindfulness was enhanced. The MAIA total score increased from 83.1 to 93.5 (P = .014).

Device users had increased alpha and theta brainwave activity, findings that “go along with the concept of decreased anxiety,” said Dr. Carpenter. She noted a recent study of the same patient population showed the device enhanced functional brain connectivity.

This current study was too small to pick up signals showing the device was effective in any particular subpopulation, said Dr. Carpenter.

Unlike other stimulation interventions that require clinic visits, patients use the MATT in the comfort of their own home and at their own convenience.

However, there are still questions surrounding the use of the noninvasive device. For example, said Dr. Carpenter, it’s unclear if it would be more effective if combined with psychotherapy or whether patients can use it while sleeping and driving. A next step could be a sham-controlled trial, she said.

The study was supported by Affect Neuro, developer of MATT therapy, and the National Institute of General Medical Sciences. Dr. Carpenter reports receiving a consultancy fee from Affect Neuro.

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

Nearly three-quarters of clinicians reported screening patients for hypertensive disorders of pregnancy, but only one-quarter comprehensively identified cardiovascular risk, based on survey data from approximately 1,500 clinicians in the United States.

Rates of hypertensive disorders of pregnancy have been on the rise in the United States for the past decade, and women with a history of these disorders require cardiovascular risk monitoring during the postpartum period and beyond, wrote Nicole D. Ford, PhD, of the Centers for Disease Control and Prevention, Atlanta, and colleagues. Specifically, the American College of Obstetricians and Gynecologists recommends cardiovascular risk evaluation and lifestyle modification for these individuals, the researchers said.

The most effective management of women with a history of hypertensive disorders of pregnancy will likely involve a team effort by primary care, ob.gyns., and cardiologists, but data on clinician screening and referrals are limited, they added.

In a study published in Obstetrics & Gynecology, the researchers reviewed data from a cross-sectional, web-based survey of clinicians practicing in the United States (Fall DocStyles 2020). The study population of 1,502 respondents with complete surveys included 1,000 primary care physicians, 251 ob.gyns., and 251 nurse practitioners or physician assistants. Approximately 60% of the respondents were male, and approximately 65% had been in practice for at least 10 years.

Overall, 73.6% of clinicians reported screening patients for a history of hypertensive disorders of pregnancy. The screening rates were highest among ob.gyns. (94.8%).

However, although 93.9% of clinicians overall correctly identified at least one potential risk associated with hypertensive disorders of pregnancy, only 24.8% correctly identified all cardiovascular risks associated with hypertensive disorders of pregnancy listed in the survey, the researchers noted.

Screening rates ranged from 49% to 91% for pregnant women, 34%-75% for postpartum women, 26%-61% for nonpregnant reproductive-age women, 20%-45% for perimenopausal or menopausal women, and 1%-4% for others outside of these categories.

The most often–cited barriers to referral were lack of patient follow-through (51.5%) and patient refusal (33.6%). To improve and facilitate referrals, respondents’ most frequent resource request was for more referral options (42.9%), followed by patient education materials (36.2%), and professional guidelines (34.1%).

In a multivariate analysis, primary care physicians were more than five times as likely to report not screening patients for hypertensive disorders of pregnancy (adjusted prevalence ratio, 5.54); nurse practitioners and physician assistants were more than seven times as likely (adjusted prevalence ratio, 7.42).

The researchers also found that clinicians who saw fewer than 80 patients per week were almost twice as likely not to screen for hypertensive disorders of pregnancy than those who saw 110 or more patients per week (adjusted prevalence ratio, 1.81).

“Beyond the immediate postpartum period, there is a lack of clear guidance on CVD [cardiovascular disease] evaluation and ongoing monitoring in women with history of hypertensive disorders of pregnancy,” the researchers wrote in their discussion. “Recognizing hypertensive disorders of pregnancy as a risk factor for CVD may allow clinicians to identify women requiring early evaluation and intervention,” they said.

The study findings were limited by several factors including potentially biased estimates of screening practices, and the potential for selection bias because of the convenience sample used to recruit survey participants, the researchers noted.

However, the results were strengthened by the inclusion of data from several clinician types and the relatively large sample size, and are consistent with those of previous studies, they said. Based on the findings, addressing barriers at both the patient and clinician level and increasing both patient and clinician education about the long-term risks of hypertensive disorders of pregnancy might increase cardiovascular screening and subsequent referrals, they concluded.
 

More education, improved screening tools needed

“Unfortunately, most CVD risk stratification scores such as the Framingham score do not include pregnancy complications, despite excellent evidence that pregnancy complications increase risk of CVD,” said Catherine M. Albright, MD, MS, of the University of Washington, Seattle, in an interview. “This is likely because these scores were developed primarily to screen for CVD risk in men. Given the rising incidence of hypertensive disorders of pregnancy and the clear evidence that this is a risk factor for future CVD, more studies like this one are needed in order to help guide patient and provider education,” said Dr. Albright, who was not involved in the study.

“It is generally well reported within the ob.gyn. literature about the increased lifetime CVD risk related to hypertensive disorders of pregnancy and we, as ob.gyns., always ask about pregnancy history because of our specialty, which gives us the opportunity to counsel about future risks,” she said.

“Women’s health [including during pregnancy] has been undervalued and underresearched for a long time,” with limited focus on pregnancy-related issues until recently, Dr. Albright noted. “This is clear in the attitudes and education of the primary care providers in this study,” she said.

A major barrier to screening in clinical practice has been that the standard screening guidelines for CVD (for example, those published by the United States Preventive Services Taskforce) have not included pregnancy history, said Dr. Albright. “Subsequently, these questions are not asked during routine annual visits,” she said. Ideally, “we should be able to leverage the electronic medical record to prompt providers to view a previously recorded pregnancy history or to ask about pregnancy history as a routine part of CVD risk assessment, and, of course, additional education outside of ob.gyn. and cardiology is needed,” she said.

The clinical takeaway from the current study is that “every annual visit with a person who has been pregnant is an opportunity to ask about and document pregnancy history,” Dr. Albright said. “After the completion of childbearing, many patients no longer see an ob.gyn., so other providers need to feel comfortable asking about and counseling about risks related to pregnancy complications,” she added.

“It is clear that adverse pregnancy outcomes pose lifetime health risks,” said Dr. Albright. “We will continue to look into the mechanisms of this through research. However, right now the additional research that is needed is to determine the optimal screening and follow-up for patients with a history of hypertensive disorders of pregnancy, as well as to examine how existing CVD-screening algorithms can be modified to include adverse pregnancy outcomes,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Nearly three-quarters of clinicians reported screening patients for hypertensive disorders of pregnancy, but only one-quarter comprehensively identified cardiovascular risk, based on survey data from approximately 1,500 clinicians in the United States.

Rates of hypertensive disorders of pregnancy have been on the rise in the United States for the past decade, and women with a history of these disorders require cardiovascular risk monitoring during the postpartum period and beyond, wrote Nicole D. Ford, PhD, of the Centers for Disease Control and Prevention, Atlanta, and colleagues. Specifically, the American College of Obstetricians and Gynecologists recommends cardiovascular risk evaluation and lifestyle modification for these individuals, the researchers said.

The most effective management of women with a history of hypertensive disorders of pregnancy will likely involve a team effort by primary care, ob.gyns., and cardiologists, but data on clinician screening and referrals are limited, they added.

In a study published in Obstetrics & Gynecology, the researchers reviewed data from a cross-sectional, web-based survey of clinicians practicing in the United States (Fall DocStyles 2020). The study population of 1,502 respondents with complete surveys included 1,000 primary care physicians, 251 ob.gyns., and 251 nurse practitioners or physician assistants. Approximately 60% of the respondents were male, and approximately 65% had been in practice for at least 10 years.

Overall, 73.6% of clinicians reported screening patients for a history of hypertensive disorders of pregnancy. The screening rates were highest among ob.gyns. (94.8%).

However, although 93.9% of clinicians overall correctly identified at least one potential risk associated with hypertensive disorders of pregnancy, only 24.8% correctly identified all cardiovascular risks associated with hypertensive disorders of pregnancy listed in the survey, the researchers noted.

Screening rates ranged from 49% to 91% for pregnant women, 34%-75% for postpartum women, 26%-61% for nonpregnant reproductive-age women, 20%-45% for perimenopausal or menopausal women, and 1%-4% for others outside of these categories.

The most often–cited barriers to referral were lack of patient follow-through (51.5%) and patient refusal (33.6%). To improve and facilitate referrals, respondents’ most frequent resource request was for more referral options (42.9%), followed by patient education materials (36.2%), and professional guidelines (34.1%).

In a multivariate analysis, primary care physicians were more than five times as likely to report not screening patients for hypertensive disorders of pregnancy (adjusted prevalence ratio, 5.54); nurse practitioners and physician assistants were more than seven times as likely (adjusted prevalence ratio, 7.42).

The researchers also found that clinicians who saw fewer than 80 patients per week were almost twice as likely not to screen for hypertensive disorders of pregnancy than those who saw 110 or more patients per week (adjusted prevalence ratio, 1.81).

“Beyond the immediate postpartum period, there is a lack of clear guidance on CVD [cardiovascular disease] evaluation and ongoing monitoring in women with history of hypertensive disorders of pregnancy,” the researchers wrote in their discussion. “Recognizing hypertensive disorders of pregnancy as a risk factor for CVD may allow clinicians to identify women requiring early evaluation and intervention,” they said.

The study findings were limited by several factors including potentially biased estimates of screening practices, and the potential for selection bias because of the convenience sample used to recruit survey participants, the researchers noted.

However, the results were strengthened by the inclusion of data from several clinician types and the relatively large sample size, and are consistent with those of previous studies, they said. Based on the findings, addressing barriers at both the patient and clinician level and increasing both patient and clinician education about the long-term risks of hypertensive disorders of pregnancy might increase cardiovascular screening and subsequent referrals, they concluded.
 

More education, improved screening tools needed

“Unfortunately, most CVD risk stratification scores such as the Framingham score do not include pregnancy complications, despite excellent evidence that pregnancy complications increase risk of CVD,” said Catherine M. Albright, MD, MS, of the University of Washington, Seattle, in an interview. “This is likely because these scores were developed primarily to screen for CVD risk in men. Given the rising incidence of hypertensive disorders of pregnancy and the clear evidence that this is a risk factor for future CVD, more studies like this one are needed in order to help guide patient and provider education,” said Dr. Albright, who was not involved in the study.

“It is generally well reported within the ob.gyn. literature about the increased lifetime CVD risk related to hypertensive disorders of pregnancy and we, as ob.gyns., always ask about pregnancy history because of our specialty, which gives us the opportunity to counsel about future risks,” she said.

“Women’s health [including during pregnancy] has been undervalued and underresearched for a long time,” with limited focus on pregnancy-related issues until recently, Dr. Albright noted. “This is clear in the attitudes and education of the primary care providers in this study,” she said.

A major barrier to screening in clinical practice has been that the standard screening guidelines for CVD (for example, those published by the United States Preventive Services Taskforce) have not included pregnancy history, said Dr. Albright. “Subsequently, these questions are not asked during routine annual visits,” she said. Ideally, “we should be able to leverage the electronic medical record to prompt providers to view a previously recorded pregnancy history or to ask about pregnancy history as a routine part of CVD risk assessment, and, of course, additional education outside of ob.gyn. and cardiology is needed,” she said.

The clinical takeaway from the current study is that “every annual visit with a person who has been pregnant is an opportunity to ask about and document pregnancy history,” Dr. Albright said. “After the completion of childbearing, many patients no longer see an ob.gyn., so other providers need to feel comfortable asking about and counseling about risks related to pregnancy complications,” she added.

“It is clear that adverse pregnancy outcomes pose lifetime health risks,” said Dr. Albright. “We will continue to look into the mechanisms of this through research. However, right now the additional research that is needed is to determine the optimal screening and follow-up for patients with a history of hypertensive disorders of pregnancy, as well as to examine how existing CVD-screening algorithms can be modified to include adverse pregnancy outcomes,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Nearly three-quarters of clinicians reported screening patients for hypertensive disorders of pregnancy, but only one-quarter comprehensively identified cardiovascular risk, based on survey data from approximately 1,500 clinicians in the United States.

Rates of hypertensive disorders of pregnancy have been on the rise in the United States for the past decade, and women with a history of these disorders require cardiovascular risk monitoring during the postpartum period and beyond, wrote Nicole D. Ford, PhD, of the Centers for Disease Control and Prevention, Atlanta, and colleagues. Specifically, the American College of Obstetricians and Gynecologists recommends cardiovascular risk evaluation and lifestyle modification for these individuals, the researchers said.

The most effective management of women with a history of hypertensive disorders of pregnancy will likely involve a team effort by primary care, ob.gyns., and cardiologists, but data on clinician screening and referrals are limited, they added.

In a study published in Obstetrics & Gynecology, the researchers reviewed data from a cross-sectional, web-based survey of clinicians practicing in the United States (Fall DocStyles 2020). The study population of 1,502 respondents with complete surveys included 1,000 primary care physicians, 251 ob.gyns., and 251 nurse practitioners or physician assistants. Approximately 60% of the respondents were male, and approximately 65% had been in practice for at least 10 years.

Overall, 73.6% of clinicians reported screening patients for a history of hypertensive disorders of pregnancy. The screening rates were highest among ob.gyns. (94.8%).

However, although 93.9% of clinicians overall correctly identified at least one potential risk associated with hypertensive disorders of pregnancy, only 24.8% correctly identified all cardiovascular risks associated with hypertensive disorders of pregnancy listed in the survey, the researchers noted.

Screening rates ranged from 49% to 91% for pregnant women, 34%-75% for postpartum women, 26%-61% for nonpregnant reproductive-age women, 20%-45% for perimenopausal or menopausal women, and 1%-4% for others outside of these categories.

The most often–cited barriers to referral were lack of patient follow-through (51.5%) and patient refusal (33.6%). To improve and facilitate referrals, respondents’ most frequent resource request was for more referral options (42.9%), followed by patient education materials (36.2%), and professional guidelines (34.1%).

In a multivariate analysis, primary care physicians were more than five times as likely to report not screening patients for hypertensive disorders of pregnancy (adjusted prevalence ratio, 5.54); nurse practitioners and physician assistants were more than seven times as likely (adjusted prevalence ratio, 7.42).

The researchers also found that clinicians who saw fewer than 80 patients per week were almost twice as likely not to screen for hypertensive disorders of pregnancy than those who saw 110 or more patients per week (adjusted prevalence ratio, 1.81).

“Beyond the immediate postpartum period, there is a lack of clear guidance on CVD [cardiovascular disease] evaluation and ongoing monitoring in women with history of hypertensive disorders of pregnancy,” the researchers wrote in their discussion. “Recognizing hypertensive disorders of pregnancy as a risk factor for CVD may allow clinicians to identify women requiring early evaluation and intervention,” they said.

The study findings were limited by several factors including potentially biased estimates of screening practices, and the potential for selection bias because of the convenience sample used to recruit survey participants, the researchers noted.

However, the results were strengthened by the inclusion of data from several clinician types and the relatively large sample size, and are consistent with those of previous studies, they said. Based on the findings, addressing barriers at both the patient and clinician level and increasing both patient and clinician education about the long-term risks of hypertensive disorders of pregnancy might increase cardiovascular screening and subsequent referrals, they concluded.
 

More education, improved screening tools needed

“Unfortunately, most CVD risk stratification scores such as the Framingham score do not include pregnancy complications, despite excellent evidence that pregnancy complications increase risk of CVD,” said Catherine M. Albright, MD, MS, of the University of Washington, Seattle, in an interview. “This is likely because these scores were developed primarily to screen for CVD risk in men. Given the rising incidence of hypertensive disorders of pregnancy and the clear evidence that this is a risk factor for future CVD, more studies like this one are needed in order to help guide patient and provider education,” said Dr. Albright, who was not involved in the study.

“It is generally well reported within the ob.gyn. literature about the increased lifetime CVD risk related to hypertensive disorders of pregnancy and we, as ob.gyns., always ask about pregnancy history because of our specialty, which gives us the opportunity to counsel about future risks,” she said.

“Women’s health [including during pregnancy] has been undervalued and underresearched for a long time,” with limited focus on pregnancy-related issues until recently, Dr. Albright noted. “This is clear in the attitudes and education of the primary care providers in this study,” she said.

A major barrier to screening in clinical practice has been that the standard screening guidelines for CVD (for example, those published by the United States Preventive Services Taskforce) have not included pregnancy history, said Dr. Albright. “Subsequently, these questions are not asked during routine annual visits,” she said. Ideally, “we should be able to leverage the electronic medical record to prompt providers to view a previously recorded pregnancy history or to ask about pregnancy history as a routine part of CVD risk assessment, and, of course, additional education outside of ob.gyn. and cardiology is needed,” she said.

The clinical takeaway from the current study is that “every annual visit with a person who has been pregnant is an opportunity to ask about and document pregnancy history,” Dr. Albright said. “After the completion of childbearing, many patients no longer see an ob.gyn., so other providers need to feel comfortable asking about and counseling about risks related to pregnancy complications,” she added.

“It is clear that adverse pregnancy outcomes pose lifetime health risks,” said Dr. Albright. “We will continue to look into the mechanisms of this through research. However, right now the additional research that is needed is to determine the optimal screening and follow-up for patients with a history of hypertensive disorders of pregnancy, as well as to examine how existing CVD-screening algorithms can be modified to include adverse pregnancy outcomes,” she emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Early-onset colorectal cancer (CRC) affecting patients younger than 50 years has risen sharply since 1988 from 7.9 to 12.9 cases in 2015 per 100,000 people. The reason for the increase isn’t well understood.

The findings were highlighted in a recent review article published online in the New England Journal of Medicine. “It’s a national phenomenon and it’s also occurring in other parts of the developed world. We’re used to seeing mostly older people who have this diagnosis. Now we’re seeing a lot of younger people with this disease. It’s rather alarming,” said author Frank Sinicrope, MD, a medical oncologist with Mayo Clinic, Rochester, Minn.

The trend contrasts with a decline in later-onset CRC likely attributable to increases in screening. As a result of the two trends, but especially the increased number of early-onset cases, the median age of diagnosis dropped from 72 in the early 2000s to 66 today.

“Although patients with early-onset colorectal cancer are more likely to have a hereditary syndrome than those who have later-onset disease, most cases are sporadic, with no identifiable cause. Furthermore, somatic mutational profiling of early-onset colorectal cancers has not revealed previously unidentified or actionable alterations to inform our understanding of the pathogenesis of these cancers or to guide treatment,” he wrote in the review.

“Early-onset colorectal cancers are most commonly detected in the rectum, followed by the distal colon; more than 70% of early-onset colorectal cancers are in the left colon at presentation,” he wrote in the review. Younger patients tend to be unfamiliar with CRC symptoms, which are often mistaken for benign conditions.

“We’ve moved the screening age down to 45, but that still is not going to capture a lot of these patients,” Dr. Sinicrope said. He estimates that 25% of rectal cancers and 10%-12% of colon cancers diagnosed in the next 10 years will be early onset.

Although the direct cause of the increased incidence isn’t clear, Dr. Sinicrope suggested it may reflect changing dietary habits and rising obesity among adolescents. “The sugar-containing beverages, the processed sugar and a lot of red meat in the diet and refined grains … reflect changes in the diet over the last 50 years. We may now be seeing the end result of many of these dietary changes that have occurred,” he said, calling for a greater emphasis on plant-based diets, which promote a healthier gut microbiome that may reduce CRC risk. Western-style diets can change the gut microbiome leading to inflammation which increases the risk of CRC.

Most patients with early CRC present with advanced disease in the left colon. And, pathogenic germline variants are present in one in six patients – half of which are associated with Lynch syndrome which increases the risk for CRC.

Dr. Sinicrope highlighted the need for more risk-based intervention, which in turn requires a better knowledge of family history.

“We need to do better job to risk stratify, and that will help us figure out who’s best to target our screening efforts toward,” Dr. Sinicrope said. He pointed out guidelines from the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society that can help physicians identify patients who might benefit from earlier screening. The American Cancer Society recommends that CRC screening be conducted at 45 years for average-risk individuals.

“The best screening test is the one that the patient will do,” Dr. Sinicrope said.

Early-onset colorectal cancer (CRC) affecting patients younger than 50 years has risen sharply since 1988 from 7.9 to 12.9 cases in 2015 per 100,000 people. The reason for the increase isn’t well understood.

The findings were highlighted in a recent review article published online in the New England Journal of Medicine. “It’s a national phenomenon and it’s also occurring in other parts of the developed world. We’re used to seeing mostly older people who have this diagnosis. Now we’re seeing a lot of younger people with this disease. It’s rather alarming,” said author Frank Sinicrope, MD, a medical oncologist with Mayo Clinic, Rochester, Minn.

The trend contrasts with a decline in later-onset CRC likely attributable to increases in screening. As a result of the two trends, but especially the increased number of early-onset cases, the median age of diagnosis dropped from 72 in the early 2000s to 66 today.

“Although patients with early-onset colorectal cancer are more likely to have a hereditary syndrome than those who have later-onset disease, most cases are sporadic, with no identifiable cause. Furthermore, somatic mutational profiling of early-onset colorectal cancers has not revealed previously unidentified or actionable alterations to inform our understanding of the pathogenesis of these cancers or to guide treatment,” he wrote in the review.

“Early-onset colorectal cancers are most commonly detected in the rectum, followed by the distal colon; more than 70% of early-onset colorectal cancers are in the left colon at presentation,” he wrote in the review. Younger patients tend to be unfamiliar with CRC symptoms, which are often mistaken for benign conditions.

“We’ve moved the screening age down to 45, but that still is not going to capture a lot of these patients,” Dr. Sinicrope said. He estimates that 25% of rectal cancers and 10%-12% of colon cancers diagnosed in the next 10 years will be early onset.

Although the direct cause of the increased incidence isn’t clear, Dr. Sinicrope suggested it may reflect changing dietary habits and rising obesity among adolescents. “The sugar-containing beverages, the processed sugar and a lot of red meat in the diet and refined grains … reflect changes in the diet over the last 50 years. We may now be seeing the end result of many of these dietary changes that have occurred,” he said, calling for a greater emphasis on plant-based diets, which promote a healthier gut microbiome that may reduce CRC risk. Western-style diets can change the gut microbiome leading to inflammation which increases the risk of CRC.

Most patients with early CRC present with advanced disease in the left colon. And, pathogenic germline variants are present in one in six patients – half of which are associated with Lynch syndrome which increases the risk for CRC.

Dr. Sinicrope highlighted the need for more risk-based intervention, which in turn requires a better knowledge of family history.

“We need to do better job to risk stratify, and that will help us figure out who’s best to target our screening efforts toward,” Dr. Sinicrope said. He pointed out guidelines from the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society that can help physicians identify patients who might benefit from earlier screening. The American Cancer Society recommends that CRC screening be conducted at 45 years for average-risk individuals.

“The best screening test is the one that the patient will do,” Dr. Sinicrope said.

Early-onset colorectal cancer (CRC) affecting patients younger than 50 years has risen sharply since 1988 from 7.9 to 12.9 cases in 2015 per 100,000 people. The reason for the increase isn’t well understood.

The findings were highlighted in a recent review article published online in the New England Journal of Medicine. “It’s a national phenomenon and it’s also occurring in other parts of the developed world. We’re used to seeing mostly older people who have this diagnosis. Now we’re seeing a lot of younger people with this disease. It’s rather alarming,” said author Frank Sinicrope, MD, a medical oncologist with Mayo Clinic, Rochester, Minn.

The trend contrasts with a decline in later-onset CRC likely attributable to increases in screening. As a result of the two trends, but especially the increased number of early-onset cases, the median age of diagnosis dropped from 72 in the early 2000s to 66 today.

“Although patients with early-onset colorectal cancer are more likely to have a hereditary syndrome than those who have later-onset disease, most cases are sporadic, with no identifiable cause. Furthermore, somatic mutational profiling of early-onset colorectal cancers has not revealed previously unidentified or actionable alterations to inform our understanding of the pathogenesis of these cancers or to guide treatment,” he wrote in the review.

“Early-onset colorectal cancers are most commonly detected in the rectum, followed by the distal colon; more than 70% of early-onset colorectal cancers are in the left colon at presentation,” he wrote in the review. Younger patients tend to be unfamiliar with CRC symptoms, which are often mistaken for benign conditions.

“We’ve moved the screening age down to 45, but that still is not going to capture a lot of these patients,” Dr. Sinicrope said. He estimates that 25% of rectal cancers and 10%-12% of colon cancers diagnosed in the next 10 years will be early onset.

Although the direct cause of the increased incidence isn’t clear, Dr. Sinicrope suggested it may reflect changing dietary habits and rising obesity among adolescents. “The sugar-containing beverages, the processed sugar and a lot of red meat in the diet and refined grains … reflect changes in the diet over the last 50 years. We may now be seeing the end result of many of these dietary changes that have occurred,” he said, calling for a greater emphasis on plant-based diets, which promote a healthier gut microbiome that may reduce CRC risk. Western-style diets can change the gut microbiome leading to inflammation which increases the risk of CRC.

Most patients with early CRC present with advanced disease in the left colon. And, pathogenic germline variants are present in one in six patients – half of which are associated with Lynch syndrome which increases the risk for CRC.

Dr. Sinicrope highlighted the need for more risk-based intervention, which in turn requires a better knowledge of family history.

“We need to do better job to risk stratify, and that will help us figure out who’s best to target our screening efforts toward,” Dr. Sinicrope said. He pointed out guidelines from the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society that can help physicians identify patients who might benefit from earlier screening. The American Cancer Society recommends that CRC screening be conducted at 45 years for average-risk individuals.

“The best screening test is the one that the patient will do,” Dr. Sinicrope said.

A qualitative analysis of 20 people with head and neck cancer (HNC) has led to recommendations for improvements in care.

HNC has a high burden of treatment-related adverse events, along with frequent trouble with speech, swallowing, facial disfigurement, and psychological distress.

Among cancer patients, “they have the highest rates of emergency department use and hospitalization during treatment. They also have the highest rates of psychological distress. We have some Ontario data that shows they’ve got the highest rates of suicide and self-harm. So I think this is a really special population that we need to support,” Christopher Noel, MD, PhD, said in an interview. Dr. Noel was the lead author of the study, which was published in JAMA Otolaryngology – Head & Neck Surgery.

These issues can strongly affect quality of life, and even patient outcomes. “Even a 1-day interruption in treatment has been shown to impact oncologic outcomes. This is a very big issue whether you’re a surgeon, a medical oncologist, or a radiation oncologist,” said Dr. Noel, who is a resident physician at the University of Toronto.

He advocates that physicians interview patients and review the results in a structured way and then act on it. “If we just rely on patient [provided] communication, we’re going to miss about 50% of patient symptoms,” he said.

The researchers aimed for the patient’s perspective on treatment. “What is the patient’s perception of going through head neck cancer and their treatment, and managing their symptoms at home? And where do they think that we could do better?” Dr. Noel asked.

The most pressing issue was that patients felt their emotional and informational needs often were not met. That challenge is even harder for patients who have trouble communicating, which in turn makes them more prone to isolation and loneliness. Many felt that they had to get the information on their own. “They wanted it to be a more effortless process,” said Dr. Noel.

He described one patient with oropharynx cancer who was able to talk to people about her grief over her diagnosis, but treatment led to her throat becoming swollen and she lost the ability to communicate. “She felt very isolated and lonely. She really highlighted the emotional and psychosocial barriers in cancer care. Her treatment inherently leaves her feeling very isolated and lonely, and she had such a hard time connecting with a psychotherapist,” Dr. Noel said.

Another common issue revolved around efforts to communicate about symptoms and adverse effects of treatment. Resources often aren’t available on evenings or weekends, and it can take time for a nurse to call them back. Patients wanted to see more modern approaches, such as use of email or apps.

The patients in the study recommended 11 health care improvements.

• 1. Nurse navigator teams should have hours extended to evenings and weekends.
• 2. Patient communication methods should be expanded, using methods like email or apps.
• 3. HNC resources should be more broadly disseminated.
• 4. Education and information approaches should be individualized to the patient.
• 5. All HNC patients should be offered psychological resources.
• 6. Mental health needs should be assessed repeatedly throughout treatment and extended care.
• 7. Physicians should recognize the added symptom burden often faced by patients who travel extensively for treatment.
• 8. Partners and caregivers should be included as part of the treatment team.
• 9. Share symptom data with patients, which can improve engagement.
• 10. Review symptom scores and act on them regularly.
• 11. A member of the care team should be identified to oversee symptom management.

Dr. Noel had no relevant financial disclosures.

A qualitative analysis of 20 people with head and neck cancer (HNC) has led to recommendations for improvements in care.

HNC has a high burden of treatment-related adverse events, along with frequent trouble with speech, swallowing, facial disfigurement, and psychological distress.

Among cancer patients, “they have the highest rates of emergency department use and hospitalization during treatment. They also have the highest rates of psychological distress. We have some Ontario data that shows they’ve got the highest rates of suicide and self-harm. So I think this is a really special population that we need to support,” Christopher Noel, MD, PhD, said in an interview. Dr. Noel was the lead author of the study, which was published in JAMA Otolaryngology – Head & Neck Surgery.

These issues can strongly affect quality of life, and even patient outcomes. “Even a 1-day interruption in treatment has been shown to impact oncologic outcomes. This is a very big issue whether you’re a surgeon, a medical oncologist, or a radiation oncologist,” said Dr. Noel, who is a resident physician at the University of Toronto.

He advocates that physicians interview patients and review the results in a structured way and then act on it. “If we just rely on patient [provided] communication, we’re going to miss about 50% of patient symptoms,” he said.

The researchers aimed for the patient’s perspective on treatment. “What is the patient’s perception of going through head neck cancer and their treatment, and managing their symptoms at home? And where do they think that we could do better?” Dr. Noel asked.

The most pressing issue was that patients felt their emotional and informational needs often were not met. That challenge is even harder for patients who have trouble communicating, which in turn makes them more prone to isolation and loneliness. Many felt that they had to get the information on their own. “They wanted it to be a more effortless process,” said Dr. Noel.

He described one patient with oropharynx cancer who was able to talk to people about her grief over her diagnosis, but treatment led to her throat becoming swollen and she lost the ability to communicate. “She felt very isolated and lonely. She really highlighted the emotional and psychosocial barriers in cancer care. Her treatment inherently leaves her feeling very isolated and lonely, and she had such a hard time connecting with a psychotherapist,” Dr. Noel said.

Another common issue revolved around efforts to communicate about symptoms and adverse effects of treatment. Resources often aren’t available on evenings or weekends, and it can take time for a nurse to call them back. Patients wanted to see more modern approaches, such as use of email or apps.

The patients in the study recommended 11 health care improvements.

• 1. Nurse navigator teams should have hours extended to evenings and weekends.
• 2. Patient communication methods should be expanded, using methods like email or apps.
• 3. HNC resources should be more broadly disseminated.
• 4. Education and information approaches should be individualized to the patient.
• 5. All HNC patients should be offered psychological resources.
• 6. Mental health needs should be assessed repeatedly throughout treatment and extended care.
• 7. Physicians should recognize the added symptom burden often faced by patients who travel extensively for treatment.
• 8. Partners and caregivers should be included as part of the treatment team.
• 9. Share symptom data with patients, which can improve engagement.
• 10. Review symptom scores and act on them regularly.
• 11. A member of the care team should be identified to oversee symptom management.

Dr. Noel had no relevant financial disclosures.

A qualitative analysis of 20 people with head and neck cancer (HNC) has led to recommendations for improvements in care.

HNC has a high burden of treatment-related adverse events, along with frequent trouble with speech, swallowing, facial disfigurement, and psychological distress.

Among cancer patients, “they have the highest rates of emergency department use and hospitalization during treatment. They also have the highest rates of psychological distress. We have some Ontario data that shows they’ve got the highest rates of suicide and self-harm. So I think this is a really special population that we need to support,” Christopher Noel, MD, PhD, said in an interview. Dr. Noel was the lead author of the study, which was published in JAMA Otolaryngology – Head & Neck Surgery.

These issues can strongly affect quality of life, and even patient outcomes. “Even a 1-day interruption in treatment has been shown to impact oncologic outcomes. This is a very big issue whether you’re a surgeon, a medical oncologist, or a radiation oncologist,” said Dr. Noel, who is a resident physician at the University of Toronto.

He advocates that physicians interview patients and review the results in a structured way and then act on it. “If we just rely on patient [provided] communication, we’re going to miss about 50% of patient symptoms,” he said.

The researchers aimed for the patient’s perspective on treatment. “What is the patient’s perception of going through head neck cancer and their treatment, and managing their symptoms at home? And where do they think that we could do better?” Dr. Noel asked.

The most pressing issue was that patients felt their emotional and informational needs often were not met. That challenge is even harder for patients who have trouble communicating, which in turn makes them more prone to isolation and loneliness. Many felt that they had to get the information on their own. “They wanted it to be a more effortless process,” said Dr. Noel.

He described one patient with oropharynx cancer who was able to talk to people about her grief over her diagnosis, but treatment led to her throat becoming swollen and she lost the ability to communicate. “She felt very isolated and lonely. She really highlighted the emotional and psychosocial barriers in cancer care. Her treatment inherently leaves her feeling very isolated and lonely, and she had such a hard time connecting with a psychotherapist,” Dr. Noel said.

Another common issue revolved around efforts to communicate about symptoms and adverse effects of treatment. Resources often aren’t available on evenings or weekends, and it can take time for a nurse to call them back. Patients wanted to see more modern approaches, such as use of email or apps.

The patients in the study recommended 11 health care improvements.

• 1. Nurse navigator teams should have hours extended to evenings and weekends.
• 2. Patient communication methods should be expanded, using methods like email or apps.
• 3. HNC resources should be more broadly disseminated.
• 4. Education and information approaches should be individualized to the patient.
• 5. All HNC patients should be offered psychological resources.
• 6. Mental health needs should be assessed repeatedly throughout treatment and extended care.
• 7. Physicians should recognize the added symptom burden often faced by patients who travel extensively for treatment.
• 8. Partners and caregivers should be included as part of the treatment team.
• 9. Share symptom data with patients, which can improve engagement.
• 10. Review symptom scores and act on them regularly.
• 11. A member of the care team should be identified to oversee symptom management.

Dr. Noel had no relevant financial disclosures.

A mutation in a gene involved in chromatin remodeling is associated with aggressive melanoma, according to a new study that combined in vitro and animal model data.

The gene, ARID2, is a part of the switch/sucrose nonfermentable (SWI/SNF) complex, which maneuvers cellular structures called nucleosomes to make cellular DNA accessible. About 20% of human cancers have a mutation within the SWI/SNF complex.

In the new study, published in Cell Reports, researchers reported that the ARID2 subunit was mutated in about 13% of melanoma patients identified through the Cancer Genome Atlas.

ARID2 mutations have been found in early melanoma lesions, which the authors suggested may play a role in early cancer cell dissemination. Other studies have shown SWI/SNF mutations, including ARID2 mutations, in melanoma metastases, especially the brain.

The researchers also found an up-regulation of synaptic pathways in melanoma cells as well as the Cancer Genome Atlas, which also suggests a potential role of ARID2 loss in metastasis or targeting the brain, since synaptic activation in cancer cells has been shown elsewhere to influence cell migration and survival in the brain.

“We look forward to future studies that investigate the role of the PBAF complex ... in order to better tailor treatments for melanoma patients,” wrote the study authors, who were led by Emily Bernstein, PhD, a professor in oncological sciences with the Icahn School of Medicine at Mount Sinai, New York.

The SWI/SNF complex includes a subcomplex that targets specific DNA sequences or chromatin reader domains. There are multiple versions of the targeting subcomplex, but two of the most frequently occurring are BAF and PBAF. The most commonly mutated subunit in melanoma is ARID2, which is part of PBAF, and contains an AT-rich region responsible for non–sequence-specific DNA interactions. There is evidence that it plays a role in tumor suppression. In mouse tumors, depletion of ARID2 is associated with increased sensitivity to immune checkpoint inhibition and destruction by T cells.

To better understand the role of ARID2 in tumor suppression, the researchers used CRISPR-Cas9 to create ARID2 deficiency in a known human metastatic melanoma cell line. They found there was reduced chromatin accessibility and accompanying gene expression among some PBAF and shared BAF-PBAF–occupied regions. There was also increased chromatin accessibility and gene expression in BAF-occupied regions, and these changes were associated with tumor aggression. In mice, they led to metastasis of distal organs.

This mechanism appears to be conserved between different melanoma cell lines, but deregulated transcriptional targets were different depending on the dominant transcription factors in the cell line. That suggests that the effect of ARID2 mutation or loss may be different depending on the stage of melanoma progression or level of invasiveness. “As melanoma comprises transcriptionally distinct, heterogeneous cell populations, we envision future studies utilizing single-cell methodologies to better understand the nuanced effects of ARID2 loss within subpopulations of cells in human melanoma tumors,” the authors wrote.

The study is limited by the fact that not all ARID2 mutations lead to complete loss of protein, and may lead instead to aberrant complexes.

The study was funded by the National Institutes of Health.

A mutation in a gene involved in chromatin remodeling is associated with aggressive melanoma, according to a new study that combined in vitro and animal model data.

The gene, ARID2, is a part of the switch/sucrose nonfermentable (SWI/SNF) complex, which maneuvers cellular structures called nucleosomes to make cellular DNA accessible. About 20% of human cancers have a mutation within the SWI/SNF complex.

In the new study, published in Cell Reports, researchers reported that the ARID2 subunit was mutated in about 13% of melanoma patients identified through the Cancer Genome Atlas.

ARID2 mutations have been found in early melanoma lesions, which the authors suggested may play a role in early cancer cell dissemination. Other studies have shown SWI/SNF mutations, including ARID2 mutations, in melanoma metastases, especially the brain.

The researchers also found an up-regulation of synaptic pathways in melanoma cells as well as the Cancer Genome Atlas, which also suggests a potential role of ARID2 loss in metastasis or targeting the brain, since synaptic activation in cancer cells has been shown elsewhere to influence cell migration and survival in the brain.

“We look forward to future studies that investigate the role of the PBAF complex ... in order to better tailor treatments for melanoma patients,” wrote the study authors, who were led by Emily Bernstein, PhD, a professor in oncological sciences with the Icahn School of Medicine at Mount Sinai, New York.

The SWI/SNF complex includes a subcomplex that targets specific DNA sequences or chromatin reader domains. There are multiple versions of the targeting subcomplex, but two of the most frequently occurring are BAF and PBAF. The most commonly mutated subunit in melanoma is ARID2, which is part of PBAF, and contains an AT-rich region responsible for non–sequence-specific DNA interactions. There is evidence that it plays a role in tumor suppression. In mouse tumors, depletion of ARID2 is associated with increased sensitivity to immune checkpoint inhibition and destruction by T cells.

To better understand the role of ARID2 in tumor suppression, the researchers used CRISPR-Cas9 to create ARID2 deficiency in a known human metastatic melanoma cell line. They found there was reduced chromatin accessibility and accompanying gene expression among some PBAF and shared BAF-PBAF–occupied regions. There was also increased chromatin accessibility and gene expression in BAF-occupied regions, and these changes were associated with tumor aggression. In mice, they led to metastasis of distal organs.

This mechanism appears to be conserved between different melanoma cell lines, but deregulated transcriptional targets were different depending on the dominant transcription factors in the cell line. That suggests that the effect of ARID2 mutation or loss may be different depending on the stage of melanoma progression or level of invasiveness. “As melanoma comprises transcriptionally distinct, heterogeneous cell populations, we envision future studies utilizing single-cell methodologies to better understand the nuanced effects of ARID2 loss within subpopulations of cells in human melanoma tumors,” the authors wrote.

The study is limited by the fact that not all ARID2 mutations lead to complete loss of protein, and may lead instead to aberrant complexes.

The study was funded by the National Institutes of Health.

A mutation in a gene involved in chromatin remodeling is associated with aggressive melanoma, according to a new study that combined in vitro and animal model data.

The gene, ARID2, is a part of the switch/sucrose nonfermentable (SWI/SNF) complex, which maneuvers cellular structures called nucleosomes to make cellular DNA accessible. About 20% of human cancers have a mutation within the SWI/SNF complex.

In the new study, published in Cell Reports, researchers reported that the ARID2 subunit was mutated in about 13% of melanoma patients identified through the Cancer Genome Atlas.

ARID2 mutations have been found in early melanoma lesions, which the authors suggested may play a role in early cancer cell dissemination. Other studies have shown SWI/SNF mutations, including ARID2 mutations, in melanoma metastases, especially the brain.

The researchers also found an up-regulation of synaptic pathways in melanoma cells as well as the Cancer Genome Atlas, which also suggests a potential role of ARID2 loss in metastasis or targeting the brain, since synaptic activation in cancer cells has been shown elsewhere to influence cell migration and survival in the brain.

“We look forward to future studies that investigate the role of the PBAF complex ... in order to better tailor treatments for melanoma patients,” wrote the study authors, who were led by Emily Bernstein, PhD, a professor in oncological sciences with the Icahn School of Medicine at Mount Sinai, New York.

The SWI/SNF complex includes a subcomplex that targets specific DNA sequences or chromatin reader domains. There are multiple versions of the targeting subcomplex, but two of the most frequently occurring are BAF and PBAF. The most commonly mutated subunit in melanoma is ARID2, which is part of PBAF, and contains an AT-rich region responsible for non–sequence-specific DNA interactions. There is evidence that it plays a role in tumor suppression. In mouse tumors, depletion of ARID2 is associated with increased sensitivity to immune checkpoint inhibition and destruction by T cells.

To better understand the role of ARID2 in tumor suppression, the researchers used CRISPR-Cas9 to create ARID2 deficiency in a known human metastatic melanoma cell line. They found there was reduced chromatin accessibility and accompanying gene expression among some PBAF and shared BAF-PBAF–occupied regions. There was also increased chromatin accessibility and gene expression in BAF-occupied regions, and these changes were associated with tumor aggression. In mice, they led to metastasis of distal organs.

This mechanism appears to be conserved between different melanoma cell lines, but deregulated transcriptional targets were different depending on the dominant transcription factors in the cell line. That suggests that the effect of ARID2 mutation or loss may be different depending on the stage of melanoma progression or level of invasiveness. “As melanoma comprises transcriptionally distinct, heterogeneous cell populations, we envision future studies utilizing single-cell methodologies to better understand the nuanced effects of ARID2 loss within subpopulations of cells in human melanoma tumors,” the authors wrote.

The study is limited by the fact that not all ARID2 mutations lead to complete loss of protein, and may lead instead to aberrant complexes.

The study was funded by the National Institutes of Health.

Concerns about the side effects of topical corticosteroids continue to be a source of anxiety for parents of children with atopic dermatitis (AD), leading some medical providers to prescribe weaker products, Nanette B. Silverberg, MD, said at the Revolutionizing Atopic Dermatitis meeting.

Up to 40% of parents of children with chronic AD cite anxiety surrounding corticosteroids, according to Dr. Silverberg, chief of pediatric dermatology at the Mount Sinai Health System, New York.

When the potential for adverse events are explained to parents who are anxious about a drug, “they take it in a different way than other individuals,” noted Dr. Silverberg, clinical professor of pediatrics and dermatology at Icahn School of Medicine at Mount Sinai.

In a systematic review of 16 studies examining topical corticosteroid phobia in AD, published between 1946 and 2016, the prevalence of corticosteroid phobia among patients with AD or their caregivers ranged from 21% to 83.7%, with definitions of phobia that ranged from “concern” to “irrational fear.” In two studies where adherence was evaluated, patients with corticosteroid phobia had a higher rate of partial adherence (49.4%) or nonadherence (14.1%) when compared with patients who didn’t have a phobia of corticosteroids (29.3 % and 9.8%, respectively)..

The source of these fears can be information from friends, relatives, media, the Internet, as well as doctors, Dr. Silverberg noted. “We have to be responsible for providing proper data to these individuals,” she said.

Primary care providers also treat young children with AD differently from older children, when compared with other specialties, according to the results of one study that involved a survey and a retrospective chart review, published in 2020. In the survey, 88% of primary care providers in Chicago said they managed AD differently in children under aged 2 years than in older children, with 65% reporting they were more likely to refer a child under 2 years to a specialist, and 64% said they were less likely to prescribe high-potency topical corticosteroids to children in this age group. The retrospective review found that at PCP visits, significantly more children with AD between aged 2 and 5 years were more likely to be prescribed medium-potency topical corticosteroids (0.66% vs. 0.37%, P < .01) and high-potency topical corticosteroids (0.15% vs. 0.05%; P < .01) than children under 2 years old, respectively.

Of the children who had seen a specialist, more dermatologists (57%) prescribed medium-potency and high-potency topical corticosteroids for children under aged 2 years than did allergists (30%) and pediatricians (15%) (P < .01), according to the study.

“These are our colleagues who are often very strong prescribers using systemic agents, and only 15% of pediatricians will do this,” Dr. Silverberg said. “We’re really looking at a big divide between us and other subspecialties and primary care, and [topical corticosteroids] are frequently underutilized because of these fears.”

In another study looking at the use of topical corticosteroids for AD in the pediatric emergency department (mean age of patients, 6.3 years), from 2012 to 2017, patients at 46 of 167 visits were prescribed over-the-counter topical hydrocortisone, while at 63 of 167 visits, patients were not prescribed or recommended any corticosteroid.

The mean class of the topical corticosteroid prescribed was 5.5, and the most commonly recommended corticosteroid was class 7 (the least potent available) in 61 of 104 patients (P < .001). A dermatologist was consulted in 14 of 167 visits (8.6%), and in those cases, topical corticosteroids were often prescribed (P = .018), as was a higher class of corticosteroids (a mean of 3.1 vs. 5.9; P < .001).

Topical corticosteroids also tend to be prescribed less by internal medicine physicians than by family medicine physicians or dermatologists. A 2020 study of ambulatory care data in the United States from 2006 to 2016 found that internists were 22 times less likely to prescribe topical corticosteroids for AD compared with dermatologists (5.1% vs. 52.2%; P = .001). But there was no significant difference in prescribing between family medicine physicians and dermatologists (39.1% vs. 52.2%, P = .27).

“We know they [corticosteroids] work, but so many people are fearful of them ... even with a low, low side effect profile,” Dr. Silverberg said.

For children with AD, corticosteroid use is “suboptimal” across the United States, with evidence that Medicaid-insured pediatric patients with AD are less likely to see a specialist and less likely to be prescribed high-potency topical corticosteroids compared with commercially-insured patients.

 

Discussing efficacy and safety
 

Dr. Silverberg said providers who care for children with AD should talk about the fear surrounding these medications and educate parents with anxiety surrounding corticosteroids. “Side effects are usually short term and limited, so we really can assure parents that there is a long safety profile,” she said.

Asked to comment on this topic, Adelaide Hebert, MD, professor of dermatology and director of pediatric dermatology at the University of Texas, Houston, said that she often sees concerns surrounding the use of topical corticosteroids, both in her practice with parents and when teaching residents in other disciplines, such as pediatrics, family medicine, and emergency medicine.

“We don’t do a good job in medical school educating the students about the safety, applicability, and proper use of topical steroids, and I think that leads to some of the confusion when it comes to properly using this class of medications in treating atopic dermatitis,” she said in an interview.

The use of a high-potency topical steroid is important, she noted, as lower doses may not adequately control AD. “If the patient has very mild disease, this may be just fine,” she noted. Those patients often do not see a pediatric dermatologist, “but the ones with moderate or severe atopic dermatitis often do, and I would say [the problem of] undertreatment is all too common.”

Like Dr. Silverberg, Dr. Hebert said that in her clinical experience, side effects from topical corticosteroids have been rare. “I could count on one hand the number of patients in a 38-year pediatric dermatology practice where they had an adverse effect from a topical steroid,” she said.

Dr. Silverberg reports receiving consulting fees from Amryt Pharma, Galderma, Incyte, and Vyne; non-CME related fees from Pfizer and Regeneron; and contracted research fees from Incyte and the Vitiligo Research Foundation. Dr. Hebert reports receiving research funds from GSK, Leo, Ortho Dermatologics, Galderma, Dermavant, Pfizer, and Arcutis Biotherapeutics paid to her institution; honoraria from Pfizer, Arcutis, Incyte; and having served on the data safety monitoring board for Regeneron-Sanofi, GSK, and Ortho Dermatologics.

Concerns about the side effects of topical corticosteroids continue to be a source of anxiety for parents of children with atopic dermatitis (AD), leading some medical providers to prescribe weaker products, Nanette B. Silverberg, MD, said at the Revolutionizing Atopic Dermatitis meeting.

Up to 40% of parents of children with chronic AD cite anxiety surrounding corticosteroids, according to Dr. Silverberg, chief of pediatric dermatology at the Mount Sinai Health System, New York.

When the potential for adverse events are explained to parents who are anxious about a drug, “they take it in a different way than other individuals,” noted Dr. Silverberg, clinical professor of pediatrics and dermatology at Icahn School of Medicine at Mount Sinai.

In a systematic review of 16 studies examining topical corticosteroid phobia in AD, published between 1946 and 2016, the prevalence of corticosteroid phobia among patients with AD or their caregivers ranged from 21% to 83.7%, with definitions of phobia that ranged from “concern” to “irrational fear.” In two studies where adherence was evaluated, patients with corticosteroid phobia had a higher rate of partial adherence (49.4%) or nonadherence (14.1%) when compared with patients who didn’t have a phobia of corticosteroids (29.3 % and 9.8%, respectively)..

The source of these fears can be information from friends, relatives, media, the Internet, as well as doctors, Dr. Silverberg noted. “We have to be responsible for providing proper data to these individuals,” she said.

Primary care providers also treat young children with AD differently from older children, when compared with other specialties, according to the results of one study that involved a survey and a retrospective chart review, published in 2020. In the survey, 88% of primary care providers in Chicago said they managed AD differently in children under aged 2 years than in older children, with 65% reporting they were more likely to refer a child under 2 years to a specialist, and 64% said they were less likely to prescribe high-potency topical corticosteroids to children in this age group. The retrospective review found that at PCP visits, significantly more children with AD between aged 2 and 5 years were more likely to be prescribed medium-potency topical corticosteroids (0.66% vs. 0.37%, P < .01) and high-potency topical corticosteroids (0.15% vs. 0.05%; P < .01) than children under 2 years old, respectively.

Of the children who had seen a specialist, more dermatologists (57%) prescribed medium-potency and high-potency topical corticosteroids for children under aged 2 years than did allergists (30%) and pediatricians (15%) (P < .01), according to the study.

“These are our colleagues who are often very strong prescribers using systemic agents, and only 15% of pediatricians will do this,” Dr. Silverberg said. “We’re really looking at a big divide between us and other subspecialties and primary care, and [topical corticosteroids] are frequently underutilized because of these fears.”

In another study looking at the use of topical corticosteroids for AD in the pediatric emergency department (mean age of patients, 6.3 years), from 2012 to 2017, patients at 46 of 167 visits were prescribed over-the-counter topical hydrocortisone, while at 63 of 167 visits, patients were not prescribed or recommended any corticosteroid.

The mean class of the topical corticosteroid prescribed was 5.5, and the most commonly recommended corticosteroid was class 7 (the least potent available) in 61 of 104 patients (P < .001). A dermatologist was consulted in 14 of 167 visits (8.6%), and in those cases, topical corticosteroids were often prescribed (P = .018), as was a higher class of corticosteroids (a mean of 3.1 vs. 5.9; P < .001).

Topical corticosteroids also tend to be prescribed less by internal medicine physicians than by family medicine physicians or dermatologists. A 2020 study of ambulatory care data in the United States from 2006 to 2016 found that internists were 22 times less likely to prescribe topical corticosteroids for AD compared with dermatologists (5.1% vs. 52.2%; P = .001). But there was no significant difference in prescribing between family medicine physicians and dermatologists (39.1% vs. 52.2%, P = .27).

“We know they [corticosteroids] work, but so many people are fearful of them ... even with a low, low side effect profile,” Dr. Silverberg said.

For children with AD, corticosteroid use is “suboptimal” across the United States, with evidence that Medicaid-insured pediatric patients with AD are less likely to see a specialist and less likely to be prescribed high-potency topical corticosteroids compared with commercially-insured patients.

 

Discussing efficacy and safety
 

Dr. Silverberg said providers who care for children with AD should talk about the fear surrounding these medications and educate parents with anxiety surrounding corticosteroids. “Side effects are usually short term and limited, so we really can assure parents that there is a long safety profile,” she said.

Asked to comment on this topic, Adelaide Hebert, MD, professor of dermatology and director of pediatric dermatology at the University of Texas, Houston, said that she often sees concerns surrounding the use of topical corticosteroids, both in her practice with parents and when teaching residents in other disciplines, such as pediatrics, family medicine, and emergency medicine.

“We don’t do a good job in medical school educating the students about the safety, applicability, and proper use of topical steroids, and I think that leads to some of the confusion when it comes to properly using this class of medications in treating atopic dermatitis,” she said in an interview.

The use of a high-potency topical steroid is important, she noted, as lower doses may not adequately control AD. “If the patient has very mild disease, this may be just fine,” she noted. Those patients often do not see a pediatric dermatologist, “but the ones with moderate or severe atopic dermatitis often do, and I would say [the problem of] undertreatment is all too common.”

Like Dr. Silverberg, Dr. Hebert said that in her clinical experience, side effects from topical corticosteroids have been rare. “I could count on one hand the number of patients in a 38-year pediatric dermatology practice where they had an adverse effect from a topical steroid,” she said.

Dr. Silverberg reports receiving consulting fees from Amryt Pharma, Galderma, Incyte, and Vyne; non-CME related fees from Pfizer and Regeneron; and contracted research fees from Incyte and the Vitiligo Research Foundation. Dr. Hebert reports receiving research funds from GSK, Leo, Ortho Dermatologics, Galderma, Dermavant, Pfizer, and Arcutis Biotherapeutics paid to her institution; honoraria from Pfizer, Arcutis, Incyte; and having served on the data safety monitoring board for Regeneron-Sanofi, GSK, and Ortho Dermatologics.

Concerns about the side effects of topical corticosteroids continue to be a source of anxiety for parents of children with atopic dermatitis (AD), leading some medical providers to prescribe weaker products, Nanette B. Silverberg, MD, said at the Revolutionizing Atopic Dermatitis meeting.

Up to 40% of parents of children with chronic AD cite anxiety surrounding corticosteroids, according to Dr. Silverberg, chief of pediatric dermatology at the Mount Sinai Health System, New York.

When the potential for adverse events are explained to parents who are anxious about a drug, “they take it in a different way than other individuals,” noted Dr. Silverberg, clinical professor of pediatrics and dermatology at Icahn School of Medicine at Mount Sinai.

In a systematic review of 16 studies examining topical corticosteroid phobia in AD, published between 1946 and 2016, the prevalence of corticosteroid phobia among patients with AD or their caregivers ranged from 21% to 83.7%, with definitions of phobia that ranged from “concern” to “irrational fear.” In two studies where adherence was evaluated, patients with corticosteroid phobia had a higher rate of partial adherence (49.4%) or nonadherence (14.1%) when compared with patients who didn’t have a phobia of corticosteroids (29.3 % and 9.8%, respectively)..

The source of these fears can be information from friends, relatives, media, the Internet, as well as doctors, Dr. Silverberg noted. “We have to be responsible for providing proper data to these individuals,” she said.

Primary care providers also treat young children with AD differently from older children, when compared with other specialties, according to the results of one study that involved a survey and a retrospective chart review, published in 2020. In the survey, 88% of primary care providers in Chicago said they managed AD differently in children under aged 2 years than in older children, with 65% reporting they were more likely to refer a child under 2 years to a specialist, and 64% said they were less likely to prescribe high-potency topical corticosteroids to children in this age group. The retrospective review found that at PCP visits, significantly more children with AD between aged 2 and 5 years were more likely to be prescribed medium-potency topical corticosteroids (0.66% vs. 0.37%, P < .01) and high-potency topical corticosteroids (0.15% vs. 0.05%; P < .01) than children under 2 years old, respectively.

Of the children who had seen a specialist, more dermatologists (57%) prescribed medium-potency and high-potency topical corticosteroids for children under aged 2 years than did allergists (30%) and pediatricians (15%) (P < .01), according to the study.

“These are our colleagues who are often very strong prescribers using systemic agents, and only 15% of pediatricians will do this,” Dr. Silverberg said. “We’re really looking at a big divide between us and other subspecialties and primary care, and [topical corticosteroids] are frequently underutilized because of these fears.”

In another study looking at the use of topical corticosteroids for AD in the pediatric emergency department (mean age of patients, 6.3 years), from 2012 to 2017, patients at 46 of 167 visits were prescribed over-the-counter topical hydrocortisone, while at 63 of 167 visits, patients were not prescribed or recommended any corticosteroid.

The mean class of the topical corticosteroid prescribed was 5.5, and the most commonly recommended corticosteroid was class 7 (the least potent available) in 61 of 104 patients (P < .001). A dermatologist was consulted in 14 of 167 visits (8.6%), and in those cases, topical corticosteroids were often prescribed (P = .018), as was a higher class of corticosteroids (a mean of 3.1 vs. 5.9; P < .001).

Topical corticosteroids also tend to be prescribed less by internal medicine physicians than by family medicine physicians or dermatologists. A 2020 study of ambulatory care data in the United States from 2006 to 2016 found that internists were 22 times less likely to prescribe topical corticosteroids for AD compared with dermatologists (5.1% vs. 52.2%; P = .001). But there was no significant difference in prescribing between family medicine physicians and dermatologists (39.1% vs. 52.2%, P = .27).

“We know they [corticosteroids] work, but so many people are fearful of them ... even with a low, low side effect profile,” Dr. Silverberg said.

For children with AD, corticosteroid use is “suboptimal” across the United States, with evidence that Medicaid-insured pediatric patients with AD are less likely to see a specialist and less likely to be prescribed high-potency topical corticosteroids compared with commercially-insured patients.

 

Discussing efficacy and safety
 

Dr. Silverberg said providers who care for children with AD should talk about the fear surrounding these medications and educate parents with anxiety surrounding corticosteroids. “Side effects are usually short term and limited, so we really can assure parents that there is a long safety profile,” she said.

Asked to comment on this topic, Adelaide Hebert, MD, professor of dermatology and director of pediatric dermatology at the University of Texas, Houston, said that she often sees concerns surrounding the use of topical corticosteroids, both in her practice with parents and when teaching residents in other disciplines, such as pediatrics, family medicine, and emergency medicine.

“We don’t do a good job in medical school educating the students about the safety, applicability, and proper use of topical steroids, and I think that leads to some of the confusion when it comes to properly using this class of medications in treating atopic dermatitis,” she said in an interview.

The use of a high-potency topical steroid is important, she noted, as lower doses may not adequately control AD. “If the patient has very mild disease, this may be just fine,” she noted. Those patients often do not see a pediatric dermatologist, “but the ones with moderate or severe atopic dermatitis often do, and I would say [the problem of] undertreatment is all too common.”

Like Dr. Silverberg, Dr. Hebert said that in her clinical experience, side effects from topical corticosteroids have been rare. “I could count on one hand the number of patients in a 38-year pediatric dermatology practice where they had an adverse effect from a topical steroid,” she said.

Dr. Silverberg reports receiving consulting fees from Amryt Pharma, Galderma, Incyte, and Vyne; non-CME related fees from Pfizer and Regeneron; and contracted research fees from Incyte and the Vitiligo Research Foundation. Dr. Hebert reports receiving research funds from GSK, Leo, Ortho Dermatologics, Galderma, Dermavant, Pfizer, and Arcutis Biotherapeutics paid to her institution; honoraria from Pfizer, Arcutis, Incyte; and having served on the data safety monitoring board for Regeneron-Sanofi, GSK, and Ortho Dermatologics.

Having had a recent acute febrile illness was associated with an increased risk for ischemic stroke, whereas having received an influenza vaccination was associated with a reduced risk for stroke in a large new case-control study.

“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.  

“Our results therefore encourage the wider use of influenza vaccination,” he concluded.

Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.

He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.

The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.

All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.

Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.

Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.

The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.

The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.

There was no association between acute febrile illness and acute cerebral hemorrhage.
 

Flu vaccine linked to halving of stroke risk

Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).

Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.

The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.

The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.  

The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
 

Mechanism: Immune stimulation?

Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”

He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.

But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.

In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.

“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.  

Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”

“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”

Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
 

‘A plausible effect’

Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.

“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.

Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.

“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.  

“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”

Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”

Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.

“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.

The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.

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

Having had a recent acute febrile illness was associated with an increased risk for ischemic stroke, whereas having received an influenza vaccination was associated with a reduced risk for stroke in a large new case-control study.

“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.  

“Our results therefore encourage the wider use of influenza vaccination,” he concluded.

Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.

He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.

The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.

All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.

Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.

Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.

The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.

The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.

There was no association between acute febrile illness and acute cerebral hemorrhage.
 

Flu vaccine linked to halving of stroke risk

Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).

Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.

The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.

The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.  

The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
 

Mechanism: Immune stimulation?

Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”

He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.

But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.

In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.

“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.  

Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”

“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”

Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
 

‘A plausible effect’

Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.

“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.

Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.

“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.  

“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”

Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”

Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.

“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.

The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.

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

Having had a recent acute febrile illness was associated with an increased risk for ischemic stroke, whereas having received an influenza vaccination was associated with a reduced risk for stroke in a large new case-control study.

“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.  

“Our results therefore encourage the wider use of influenza vaccination,” he concluded.

Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.

He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.

The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.

All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.

Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.

Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.

The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.

The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.

There was no association between acute febrile illness and acute cerebral hemorrhage.
 

Flu vaccine linked to halving of stroke risk

Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).

Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.

The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.

The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.  

The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
 

Mechanism: Immune stimulation?

Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”

He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.

But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.

In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.

“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.  

Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”

“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”

Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
 

‘A plausible effect’

Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.

“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.

Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.

“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.  

“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”

Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”

Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.

“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.

The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.

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

One in four new mothers who are physicians report experiencing postpartum depression, a rate twice that of the general population, according to new survey findings presented at the American College of Obstetricians and Gynecologists (ACOG) 2022 Annual Meeting.

The survey results weren’t all grim. More than three-fourths (78%) of new mothers reported meeting their own breastfeeding goals. Still, Alison Stuebe, MD, director of maternal-fetal medicine, University of North Carolina School of Medicine, Chapel Hill, said the high postpartum depression rates among physicians might be associated with worse patient care.

“Physicians who have had postpartum depression and provide clinical care for children and birthing people can bring their negative experiences to their clinical work, potentially impacting how they counsel and support their patients,” Dr. Stuebe, who was not involved in the study, told this news organization.

For the study, Emily Eischen, a fourth-year medical student at the University of South Florida Morsani College of Medicine, Tampa, and her colleagues sought to learn how physicians and physician trainee mothers fared in the face of the unique stressors of their jobs, including “strenuous work hours, pressures to get back to work, and limited maternity leave.”

The researchers recruited 637 physicians and medical students with a singleton pregnancy to respond to a survey adapted largely from the U.S. Centers for Disease Control and Prevention’s Infant Feeding Practices Study and the CDC’s Pregnancy Risk Assessment Monitoring System.

Most of the respondents, who were enrolled through social media physician groups and email list-serves, were married non-Hispanic White persons; 71% were practicing or training in pediatrics, family medicine, or obstetrics/gynecology, and 2% were medical students.

Data showed that 25% of participants reported postpartum depression. The highest rates were seen among Hispanic/Latino respondents (31%), Black persons (30%), and non-Hispanic White persons (25%). The lowest rates of postpartum depression were for respondents identifying as Asian (15%).
 

Guilt a driver

Most respondents (80%) with symptoms of postpartum depression attributed their condition to sleep deprivation. Other frequently cited reasons were problems related to infant feeding (44%), lack of adequate maternity leave (41%), and lack of support at work (33%).

“Feeling guilty for not fulfilling work responsibilities, especially for residents, who are in the most difficult time in their careers and have to hand the workload off to others, can be very stressful,” Ms. Eischen said.

Despite the high rates of postpartum depression in the survey, the investigators found that 99% of respondents had initiated breastfeeding, 72% were exclusively breastfeeding, and 78% said they were meeting their personal breastfeeding goals. All of those rates are higher than what is seen in the general population.

Rates of self-reported postpartum depression were higher among those who did not meet their breastfeeding goals than among those who did (36% vs. 23%; P = .003), the researchers found.

Adetola Louis-Jacques, MD, an assistant professor of medicine, USF Health Obstetrics and Gynecology, and the senior author of the study, said the high breastfeeding rates can be attributed partly to an increased appreciation among physicians that lactation and breastfeeding have proven benefits for women and infant health.

“We still have work to do, but at least the journey has started in supporting birthing and lactating physicians,” she said.

However, Dr. Stuebe wondered whether the survey captured a group of respondents more likely to meet breastfeeding goals. She said she was surprised by the high proportion of respondents who did so.

“When surveys are distributed via social media, we don’t have a clear sense of who chooses to participate and who opts out,” she said in an interview. “If the survey was shared through social media groups that focus on supporting breastfeeding among physicians, it could have affected the results.”

No relevant financial relationships have been reported.

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

One in four new mothers who are physicians report experiencing postpartum depression, a rate twice that of the general population, according to new survey findings presented at the American College of Obstetricians and Gynecologists (ACOG) 2022 Annual Meeting.

The survey results weren’t all grim. More than three-fourths (78%) of new mothers reported meeting their own breastfeeding goals. Still, Alison Stuebe, MD, director of maternal-fetal medicine, University of North Carolina School of Medicine, Chapel Hill, said the high postpartum depression rates among physicians might be associated with worse patient care.

“Physicians who have had postpartum depression and provide clinical care for children and birthing people can bring their negative experiences to their clinical work, potentially impacting how they counsel and support their patients,” Dr. Stuebe, who was not involved in the study, told this news organization.

For the study, Emily Eischen, a fourth-year medical student at the University of South Florida Morsani College of Medicine, Tampa, and her colleagues sought to learn how physicians and physician trainee mothers fared in the face of the unique stressors of their jobs, including “strenuous work hours, pressures to get back to work, and limited maternity leave.”

The researchers recruited 637 physicians and medical students with a singleton pregnancy to respond to a survey adapted largely from the U.S. Centers for Disease Control and Prevention’s Infant Feeding Practices Study and the CDC’s Pregnancy Risk Assessment Monitoring System.

Most of the respondents, who were enrolled through social media physician groups and email list-serves, were married non-Hispanic White persons; 71% were practicing or training in pediatrics, family medicine, or obstetrics/gynecology, and 2% were medical students.

Data showed that 25% of participants reported postpartum depression. The highest rates were seen among Hispanic/Latino respondents (31%), Black persons (30%), and non-Hispanic White persons (25%). The lowest rates of postpartum depression were for respondents identifying as Asian (15%).
 

Guilt a driver

Most respondents (80%) with symptoms of postpartum depression attributed their condition to sleep deprivation. Other frequently cited reasons were problems related to infant feeding (44%), lack of adequate maternity leave (41%), and lack of support at work (33%).

“Feeling guilty for not fulfilling work responsibilities, especially for residents, who are in the most difficult time in their careers and have to hand the workload off to others, can be very stressful,” Ms. Eischen said.

Despite the high rates of postpartum depression in the survey, the investigators found that 99% of respondents had initiated breastfeeding, 72% were exclusively breastfeeding, and 78% said they were meeting their personal breastfeeding goals. All of those rates are higher than what is seen in the general population.

Rates of self-reported postpartum depression were higher among those who did not meet their breastfeeding goals than among those who did (36% vs. 23%; P = .003), the researchers found.

Adetola Louis-Jacques, MD, an assistant professor of medicine, USF Health Obstetrics and Gynecology, and the senior author of the study, said the high breastfeeding rates can be attributed partly to an increased appreciation among physicians that lactation and breastfeeding have proven benefits for women and infant health.

“We still have work to do, but at least the journey has started in supporting birthing and lactating physicians,” she said.

However, Dr. Stuebe wondered whether the survey captured a group of respondents more likely to meet breastfeeding goals. She said she was surprised by the high proportion of respondents who did so.

“When surveys are distributed via social media, we don’t have a clear sense of who chooses to participate and who opts out,” she said in an interview. “If the survey was shared through social media groups that focus on supporting breastfeeding among physicians, it could have affected the results.”

No relevant financial relationships have been reported.

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

One in four new mothers who are physicians report experiencing postpartum depression, a rate twice that of the general population, according to new survey findings presented at the American College of Obstetricians and Gynecologists (ACOG) 2022 Annual Meeting.

The survey results weren’t all grim. More than three-fourths (78%) of new mothers reported meeting their own breastfeeding goals. Still, Alison Stuebe, MD, director of maternal-fetal medicine, University of North Carolina School of Medicine, Chapel Hill, said the high postpartum depression rates among physicians might be associated with worse patient care.

“Physicians who have had postpartum depression and provide clinical care for children and birthing people can bring their negative experiences to their clinical work, potentially impacting how they counsel and support their patients,” Dr. Stuebe, who was not involved in the study, told this news organization.

For the study, Emily Eischen, a fourth-year medical student at the University of South Florida Morsani College of Medicine, Tampa, and her colleagues sought to learn how physicians and physician trainee mothers fared in the face of the unique stressors of their jobs, including “strenuous work hours, pressures to get back to work, and limited maternity leave.”

The researchers recruited 637 physicians and medical students with a singleton pregnancy to respond to a survey adapted largely from the U.S. Centers for Disease Control and Prevention’s Infant Feeding Practices Study and the CDC’s Pregnancy Risk Assessment Monitoring System.

Most of the respondents, who were enrolled through social media physician groups and email list-serves, were married non-Hispanic White persons; 71% were practicing or training in pediatrics, family medicine, or obstetrics/gynecology, and 2% were medical students.

Data showed that 25% of participants reported postpartum depression. The highest rates were seen among Hispanic/Latino respondents (31%), Black persons (30%), and non-Hispanic White persons (25%). The lowest rates of postpartum depression were for respondents identifying as Asian (15%).
 

Guilt a driver

Most respondents (80%) with symptoms of postpartum depression attributed their condition to sleep deprivation. Other frequently cited reasons were problems related to infant feeding (44%), lack of adequate maternity leave (41%), and lack of support at work (33%).

“Feeling guilty for not fulfilling work responsibilities, especially for residents, who are in the most difficult time in their careers and have to hand the workload off to others, can be very stressful,” Ms. Eischen said.

Despite the high rates of postpartum depression in the survey, the investigators found that 99% of respondents had initiated breastfeeding, 72% were exclusively breastfeeding, and 78% said they were meeting their personal breastfeeding goals. All of those rates are higher than what is seen in the general population.

Rates of self-reported postpartum depression were higher among those who did not meet their breastfeeding goals than among those who did (36% vs. 23%; P = .003), the researchers found.

Adetola Louis-Jacques, MD, an assistant professor of medicine, USF Health Obstetrics and Gynecology, and the senior author of the study, said the high breastfeeding rates can be attributed partly to an increased appreciation among physicians that lactation and breastfeeding have proven benefits for women and infant health.

“We still have work to do, but at least the journey has started in supporting birthing and lactating physicians,” she said.

However, Dr. Stuebe wondered whether the survey captured a group of respondents more likely to meet breastfeeding goals. She said she was surprised by the high proportion of respondents who did so.

“When surveys are distributed via social media, we don’t have a clear sense of who chooses to participate and who opts out,” she said in an interview. “If the survey was shared through social media groups that focus on supporting breastfeeding among physicians, it could have affected the results.”

No relevant financial relationships have been reported.

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

A group of clinicians is hoping to prompt a rethink of how opioids are prescribed to new mothers after cesarean deliveries after finding that sending patients home with smaller prescriptions led to dramatic drops in use of the drugs.

In research scheduled to be presented at the annual meeting of the American College of Obstetricians and Gynecologists (ACOG) in San Diego, women undergoing cesarean delivery were randomly assigned to receive prescriptions for either 10 or 20 oxycodone tablets at discharge. Interim data revealed that not only did 10-tablet prescriptions correlate with significantly less opioid consumption, but 35% of all women left their opioid scripts unfilled.

The results suggest physicians should stop “automatically prescribing opioids for caesarean section patients at discharge and, instead, work on individualized prescribing,” said Amanda Selk, MD, associate professor of obstetrics and gynecology at the University of Toronto, who was not involved with the study.  

“We need to move away from a culture that says a patient can’t be discharged without an opioid prescription,” Dr. Selk said in an interview.

For the study, researchers at Virginia Tech Carilion School of Medicine, Roanoke, Virginia, set out to understand how discharge opioid prescription sizes impact opioid consumption in women who undergo caesarean delivery. Other specialties have found a correlation between the two.

With “no standard dose recommendation for physicians to follow when it came to prescribing opioids for post-cesarean pain management,” they also wanted to help their own clinicians optimize their prescribing, co-investigator Jaclyn Nunziato, MD, assistant professor of obstetrics and gynecology at Virginia Tech Carilion, told this news organization.

They randomly assigned 134 women undergoing a scheduled cesarean delivery to receive a prescription for 10 or 20 tablets of 5 mg oxycodone at discharge. Most women had one or more previous cesarean deliveries, and none had used opioids in the previous 30 days.

Data from 97 patients presented at the ACOG meeting showed that 35% of women had not filled their opioid prescriptions 6 weeks after surgery. For those who did fill the orders, the average consumption at week 6 of the study was 6.6 tablets in the 10-tablet group and 13.3 tablets in the 20-tablet group (P = .0005), according to the researchers. No patients in either group had requested a refill of their opioid medication.

Despite differences in opioid use, both groups reported similar pain scores throughout the study period, and almost all patients in both groups said they were satisfied with their pain management, the investigators reported.

With an average of 9.2 tablets consumed in the two groups combined, the findings indicate “a standard prescription of 10 tablets may be adequate to manage most patients’ postoperative pain,” Dr. Nunziato said.   

She said she hoped the results help change how physicians view the treatment of post-cesarean pain and also help “break down the stigma that opioids are the best treatment option for patients.”
 

Potential for ‘huge’ benefit

Given the number of cesarean deliveries performed every year in the United States – more than 1.1 million in 2020, according to the U.S. Centers for Disease Control and Prevention – providing smaller post-cesarean opioid prescriptions would be “hugely beneficial to individual patients and our larger community,” said Robyn Goodrich, a medical student at Virginia Tech and the first author of the study.

“The patient would receive an amount that is adequate for controlling their pain and keeping them comfortable but does not put them at risk of developing tolerance and addiction,” she added. “For the community, it reduces the number of prescription opioids that are left over and may be diverted or misused if not properly disposed of.”

Dr. Selk pointed to her own group’s randomized controlled trial, showing that post-cesarean patients who do not receive opioids for pain while in the hospital also do not ask for opioid prescriptions after discharge and that their pain can be well-managed with acetaminophen and nonsteroidal anti-inflammatory drugs.  

Dr. Selk, Dr. Nunziato, and Ms. Goodrich have disclosed no relevant financial relationships.

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

A group of clinicians is hoping to prompt a rethink of how opioids are prescribed to new mothers after cesarean deliveries after finding that sending patients home with smaller prescriptions led to dramatic drops in use of the drugs.

In research scheduled to be presented at the annual meeting of the American College of Obstetricians and Gynecologists (ACOG) in San Diego, women undergoing cesarean delivery were randomly assigned to receive prescriptions for either 10 or 20 oxycodone tablets at discharge. Interim data revealed that not only did 10-tablet prescriptions correlate with significantly less opioid consumption, but 35% of all women left their opioid scripts unfilled.

The results suggest physicians should stop “automatically prescribing opioids for caesarean section patients at discharge and, instead, work on individualized prescribing,” said Amanda Selk, MD, associate professor of obstetrics and gynecology at the University of Toronto, who was not involved with the study.  

“We need to move away from a culture that says a patient can’t be discharged without an opioid prescription,” Dr. Selk said in an interview.

For the study, researchers at Virginia Tech Carilion School of Medicine, Roanoke, Virginia, set out to understand how discharge opioid prescription sizes impact opioid consumption in women who undergo caesarean delivery. Other specialties have found a correlation between the two.

With “no standard dose recommendation for physicians to follow when it came to prescribing opioids for post-cesarean pain management,” they also wanted to help their own clinicians optimize their prescribing, co-investigator Jaclyn Nunziato, MD, assistant professor of obstetrics and gynecology at Virginia Tech Carilion, told this news organization.

They randomly assigned 134 women undergoing a scheduled cesarean delivery to receive a prescription for 10 or 20 tablets of 5 mg oxycodone at discharge. Most women had one or more previous cesarean deliveries, and none had used opioids in the previous 30 days.

Data from 97 patients presented at the ACOG meeting showed that 35% of women had not filled their opioid prescriptions 6 weeks after surgery. For those who did fill the orders, the average consumption at week 6 of the study was 6.6 tablets in the 10-tablet group and 13.3 tablets in the 20-tablet group (P = .0005), according to the researchers. No patients in either group had requested a refill of their opioid medication.

Despite differences in opioid use, both groups reported similar pain scores throughout the study period, and almost all patients in both groups said they were satisfied with their pain management, the investigators reported.

With an average of 9.2 tablets consumed in the two groups combined, the findings indicate “a standard prescription of 10 tablets may be adequate to manage most patients’ postoperative pain,” Dr. Nunziato said.   

She said she hoped the results help change how physicians view the treatment of post-cesarean pain and also help “break down the stigma that opioids are the best treatment option for patients.”
 

Potential for ‘huge’ benefit

Given the number of cesarean deliveries performed every year in the United States – more than 1.1 million in 2020, according to the U.S. Centers for Disease Control and Prevention – providing smaller post-cesarean opioid prescriptions would be “hugely beneficial to individual patients and our larger community,” said Robyn Goodrich, a medical student at Virginia Tech and the first author of the study.

“The patient would receive an amount that is adequate for controlling their pain and keeping them comfortable but does not put them at risk of developing tolerance and addiction,” she added. “For the community, it reduces the number of prescription opioids that are left over and may be diverted or misused if not properly disposed of.”

Dr. Selk pointed to her own group’s randomized controlled trial, showing that post-cesarean patients who do not receive opioids for pain while in the hospital also do not ask for opioid prescriptions after discharge and that their pain can be well-managed with acetaminophen and nonsteroidal anti-inflammatory drugs.  

Dr. Selk, Dr. Nunziato, and Ms. Goodrich have disclosed no relevant financial relationships.

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

A group of clinicians is hoping to prompt a rethink of how opioids are prescribed to new mothers after cesarean deliveries after finding that sending patients home with smaller prescriptions led to dramatic drops in use of the drugs.

In research scheduled to be presented at the annual meeting of the American College of Obstetricians and Gynecologists (ACOG) in San Diego, women undergoing cesarean delivery were randomly assigned to receive prescriptions for either 10 or 20 oxycodone tablets at discharge. Interim data revealed that not only did 10-tablet prescriptions correlate with significantly less opioid consumption, but 35% of all women left their opioid scripts unfilled.

The results suggest physicians should stop “automatically prescribing opioids for caesarean section patients at discharge and, instead, work on individualized prescribing,” said Amanda Selk, MD, associate professor of obstetrics and gynecology at the University of Toronto, who was not involved with the study.  

“We need to move away from a culture that says a patient can’t be discharged without an opioid prescription,” Dr. Selk said in an interview.

For the study, researchers at Virginia Tech Carilion School of Medicine, Roanoke, Virginia, set out to understand how discharge opioid prescription sizes impact opioid consumption in women who undergo caesarean delivery. Other specialties have found a correlation between the two.

With “no standard dose recommendation for physicians to follow when it came to prescribing opioids for post-cesarean pain management,” they also wanted to help their own clinicians optimize their prescribing, co-investigator Jaclyn Nunziato, MD, assistant professor of obstetrics and gynecology at Virginia Tech Carilion, told this news organization.

They randomly assigned 134 women undergoing a scheduled cesarean delivery to receive a prescription for 10 or 20 tablets of 5 mg oxycodone at discharge. Most women had one or more previous cesarean deliveries, and none had used opioids in the previous 30 days.

Data from 97 patients presented at the ACOG meeting showed that 35% of women had not filled their opioid prescriptions 6 weeks after surgery. For those who did fill the orders, the average consumption at week 6 of the study was 6.6 tablets in the 10-tablet group and 13.3 tablets in the 20-tablet group (P = .0005), according to the researchers. No patients in either group had requested a refill of their opioid medication.

Despite differences in opioid use, both groups reported similar pain scores throughout the study period, and almost all patients in both groups said they were satisfied with their pain management, the investigators reported.

With an average of 9.2 tablets consumed in the two groups combined, the findings indicate “a standard prescription of 10 tablets may be adequate to manage most patients’ postoperative pain,” Dr. Nunziato said.   

She said she hoped the results help change how physicians view the treatment of post-cesarean pain and also help “break down the stigma that opioids are the best treatment option for patients.”
 

Potential for ‘huge’ benefit

Given the number of cesarean deliveries performed every year in the United States – more than 1.1 million in 2020, according to the U.S. Centers for Disease Control and Prevention – providing smaller post-cesarean opioid prescriptions would be “hugely beneficial to individual patients and our larger community,” said Robyn Goodrich, a medical student at Virginia Tech and the first author of the study.

“The patient would receive an amount that is adequate for controlling their pain and keeping them comfortable but does not put them at risk of developing tolerance and addiction,” she added. “For the community, it reduces the number of prescription opioids that are left over and may be diverted or misused if not properly disposed of.”

Dr. Selk pointed to her own group’s randomized controlled trial, showing that post-cesarean patients who do not receive opioids for pain while in the hospital also do not ask for opioid prescriptions after discharge and that their pain can be well-managed with acetaminophen and nonsteroidal anti-inflammatory drugs.  

Dr. Selk, Dr. Nunziato, and Ms. Goodrich have disclosed no relevant financial relationships.

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

Long-term use of a proton-pump inhibitor (PPI) was associated with an increased risk of being diagnosed with type 2 diabetes in a large, population-based case-control study in Italy.

The risk of diabetes increased from 19% to 56% as treatment duration increased from 8 weeks to more than 2 years, and prolonged treatment was associated with an even higher risk of diabetes in the youngest patients (age 40-65) and those with the most comorbidities.

The results suggest that “physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use,” say Stefano Ciardullo, MD, University of Milano-Bicocca, Italy, and colleagues, in their article recently published online in the Journal of Clinical Endocrinology & Metabolism.

“Nonetheless, epidemiologic evidence on the topic remains conflicting,” they acknowledge, adding that “future studies are still needed to validate our findings.”

If the results are confirmed, these “may have important implications for both public health and clinical practice, given the high number of patients being treated with PPIs and the influence of diabetes on morbidity and mortality related to its possible micro- and macrovascular complications,” Dr. Ciardullo and colleagues conclude.
 

Not enough data to support a change in practice

The current findings align with a recent analysis of three prospective cohort studies of U.S. health care workers that showed a progressively increased risk of diabetes with longer treatment with PPIs, David A. Leiman, MD, MSHP, who was not involved with the current study, told this news organization in an email. “But the effect size remains relatively small and may be explained by residual or unmeasured confounding,” he cautioned.

“Ultimately, there do not seem to be enough data to support a change in clinical practice from this study alone, and, as a result, clinicians should continue to inform patients of the best available evidence regarding the benefits and risks of PPIs,” said Dr. Leiman, assistant professor of medicine, Division of Gastroenterology, Duke University Medical Center, Durham, N.C.

“Recent best practice advice from the American Gastroenterological Association does not recommend screening for insulin resistance among PPI users [and recommends that the decision to discontinue PPIs] should be based solely on the lack of an indication for PPI use, and not because of concern for PPI-associated adverse events,” he noted.

“Clinicians should be prepared to discuss the described risks associated with PPIs,” said Dr. Leiman, but they should “also feel comfortable affirming their safety profile and substantial efficacy in managing symptoms and preventing complications when prescribed for the appropriate indication.”

First-choice therapy for acid-related disorders

PPIs have become first-choice therapy for patients with acid-related disorders such as gastroesophageal reflux disease, Barrett esophagus, and peptic ulcer, and to prevent gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs (NSAIDs), Dr. Ciardullo and colleagues explain.

However, several studies have identified potential fractures, hypomagnesemia, gastric carcinoids, chronic kidney disease, dementia, and Clostridium difficile diarrhea with prolonged use of PPIs, and these agents can cause changes in the gut microbiome that may play a role in diabetes and other metabolic diseases.

To investigate a potential association between PPIs and type 2 diabetes, the researchers analyzed data from 777,420 patients age 40 and older who were newly treated with PPIs between 2010 and 2015 in Lombardy, Italy.

Of these, 50,540 patients were diagnosed with type 2 diabetes during follow-up until 2020 (a mean follow-up of 6.2 years and a diabetes incidence of 10.6 cases per 1,000 person-years).

The researchers matched 50,535 patients diagnosed with diabetes during follow-up with 50,535 control patients who had the same age, sex, and clinical status.

Patients were a mean age of 66 years and half were men. The most prescribed PPIs were pantoprazole and omeprazole, and the patients diagnosed with diabetes were more likely to use antihypertensives and lipid-lowering drugs.

Compared with patients who received PPIs for less than 8 weeks, those who received PPIs for 8 weeks to 6 months had a 19% increased risk of being diagnosed with diabetes during follow-up (odds ratio, 1.19; 95% confidence interval, 1.15-1.24), after adjusting for age, clinical profile, comorbidities, medical therapy, and PPI type.

Patients who received PPIs for 6 months to 2 years had a 43% increased risk of the outcome (OR, 1.43; 95% CI, 1.38-1.49), and those who received PPIs for more than 2 years had a 56% increased risk of the outcome (OR, 1.56; 95% CI, 1.49-1.64).

The researchers acknowledge limitations including that the study was not a randomized controlled trial, and it lacked information about over-the-counter medications and unmeasured confounders such as body mass index or family history of diabetes that may have affected the outcomes.

Dr. Leiman added that patients may have had prediabetes or undiagnosed diabetes and symptoms such as heartburn or dyspepsia arising from complications of insulin resistance, for which PPIs might have been prescribed.

The study was funded by a grant from the Italian Ministry of Education, University and Research. Dr. Ciardullo and Dr. Leiman have reported no relevant financial relationships.

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

Long-term use of a proton-pump inhibitor (PPI) was associated with an increased risk of being diagnosed with type 2 diabetes in a large, population-based case-control study in Italy.

The risk of diabetes increased from 19% to 56% as treatment duration increased from 8 weeks to more than 2 years, and prolonged treatment was associated with an even higher risk of diabetes in the youngest patients (age 40-65) and those with the most comorbidities.

The results suggest that “physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use,” say Stefano Ciardullo, MD, University of Milano-Bicocca, Italy, and colleagues, in their article recently published online in the Journal of Clinical Endocrinology & Metabolism.

“Nonetheless, epidemiologic evidence on the topic remains conflicting,” they acknowledge, adding that “future studies are still needed to validate our findings.”

If the results are confirmed, these “may have important implications for both public health and clinical practice, given the high number of patients being treated with PPIs and the influence of diabetes on morbidity and mortality related to its possible micro- and macrovascular complications,” Dr. Ciardullo and colleagues conclude.
 

Not enough data to support a change in practice

The current findings align with a recent analysis of three prospective cohort studies of U.S. health care workers that showed a progressively increased risk of diabetes with longer treatment with PPIs, David A. Leiman, MD, MSHP, who was not involved with the current study, told this news organization in an email. “But the effect size remains relatively small and may be explained by residual or unmeasured confounding,” he cautioned.

“Ultimately, there do not seem to be enough data to support a change in clinical practice from this study alone, and, as a result, clinicians should continue to inform patients of the best available evidence regarding the benefits and risks of PPIs,” said Dr. Leiman, assistant professor of medicine, Division of Gastroenterology, Duke University Medical Center, Durham, N.C.

“Recent best practice advice from the American Gastroenterological Association does not recommend screening for insulin resistance among PPI users [and recommends that the decision to discontinue PPIs] should be based solely on the lack of an indication for PPI use, and not because of concern for PPI-associated adverse events,” he noted.

“Clinicians should be prepared to discuss the described risks associated with PPIs,” said Dr. Leiman, but they should “also feel comfortable affirming their safety profile and substantial efficacy in managing symptoms and preventing complications when prescribed for the appropriate indication.”

First-choice therapy for acid-related disorders

PPIs have become first-choice therapy for patients with acid-related disorders such as gastroesophageal reflux disease, Barrett esophagus, and peptic ulcer, and to prevent gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs (NSAIDs), Dr. Ciardullo and colleagues explain.

However, several studies have identified potential fractures, hypomagnesemia, gastric carcinoids, chronic kidney disease, dementia, and Clostridium difficile diarrhea with prolonged use of PPIs, and these agents can cause changes in the gut microbiome that may play a role in diabetes and other metabolic diseases.

To investigate a potential association between PPIs and type 2 diabetes, the researchers analyzed data from 777,420 patients age 40 and older who were newly treated with PPIs between 2010 and 2015 in Lombardy, Italy.

Of these, 50,540 patients were diagnosed with type 2 diabetes during follow-up until 2020 (a mean follow-up of 6.2 years and a diabetes incidence of 10.6 cases per 1,000 person-years).

The researchers matched 50,535 patients diagnosed with diabetes during follow-up with 50,535 control patients who had the same age, sex, and clinical status.

Patients were a mean age of 66 years and half were men. The most prescribed PPIs were pantoprazole and omeprazole, and the patients diagnosed with diabetes were more likely to use antihypertensives and lipid-lowering drugs.

Compared with patients who received PPIs for less than 8 weeks, those who received PPIs for 8 weeks to 6 months had a 19% increased risk of being diagnosed with diabetes during follow-up (odds ratio, 1.19; 95% confidence interval, 1.15-1.24), after adjusting for age, clinical profile, comorbidities, medical therapy, and PPI type.

Patients who received PPIs for 6 months to 2 years had a 43% increased risk of the outcome (OR, 1.43; 95% CI, 1.38-1.49), and those who received PPIs for more than 2 years had a 56% increased risk of the outcome (OR, 1.56; 95% CI, 1.49-1.64).

The researchers acknowledge limitations including that the study was not a randomized controlled trial, and it lacked information about over-the-counter medications and unmeasured confounders such as body mass index or family history of diabetes that may have affected the outcomes.

Dr. Leiman added that patients may have had prediabetes or undiagnosed diabetes and symptoms such as heartburn or dyspepsia arising from complications of insulin resistance, for which PPIs might have been prescribed.

The study was funded by a grant from the Italian Ministry of Education, University and Research. Dr. Ciardullo and Dr. Leiman have reported no relevant financial relationships.

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

Long-term use of a proton-pump inhibitor (PPI) was associated with an increased risk of being diagnosed with type 2 diabetes in a large, population-based case-control study in Italy.

The risk of diabetes increased from 19% to 56% as treatment duration increased from 8 weeks to more than 2 years, and prolonged treatment was associated with an even higher risk of diabetes in the youngest patients (age 40-65) and those with the most comorbidities.

The results suggest that “physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use,” say Stefano Ciardullo, MD, University of Milano-Bicocca, Italy, and colleagues, in their article recently published online in the Journal of Clinical Endocrinology & Metabolism.

“Nonetheless, epidemiologic evidence on the topic remains conflicting,” they acknowledge, adding that “future studies are still needed to validate our findings.”

If the results are confirmed, these “may have important implications for both public health and clinical practice, given the high number of patients being treated with PPIs and the influence of diabetes on morbidity and mortality related to its possible micro- and macrovascular complications,” Dr. Ciardullo and colleagues conclude.
 

Not enough data to support a change in practice

The current findings align with a recent analysis of three prospective cohort studies of U.S. health care workers that showed a progressively increased risk of diabetes with longer treatment with PPIs, David A. Leiman, MD, MSHP, who was not involved with the current study, told this news organization in an email. “But the effect size remains relatively small and may be explained by residual or unmeasured confounding,” he cautioned.

“Ultimately, there do not seem to be enough data to support a change in clinical practice from this study alone, and, as a result, clinicians should continue to inform patients of the best available evidence regarding the benefits and risks of PPIs,” said Dr. Leiman, assistant professor of medicine, Division of Gastroenterology, Duke University Medical Center, Durham, N.C.

“Recent best practice advice from the American Gastroenterological Association does not recommend screening for insulin resistance among PPI users [and recommends that the decision to discontinue PPIs] should be based solely on the lack of an indication for PPI use, and not because of concern for PPI-associated adverse events,” he noted.

“Clinicians should be prepared to discuss the described risks associated with PPIs,” said Dr. Leiman, but they should “also feel comfortable affirming their safety profile and substantial efficacy in managing symptoms and preventing complications when prescribed for the appropriate indication.”

First-choice therapy for acid-related disorders

PPIs have become first-choice therapy for patients with acid-related disorders such as gastroesophageal reflux disease, Barrett esophagus, and peptic ulcer, and to prevent gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs (NSAIDs), Dr. Ciardullo and colleagues explain.

However, several studies have identified potential fractures, hypomagnesemia, gastric carcinoids, chronic kidney disease, dementia, and Clostridium difficile diarrhea with prolonged use of PPIs, and these agents can cause changes in the gut microbiome that may play a role in diabetes and other metabolic diseases.

To investigate a potential association between PPIs and type 2 diabetes, the researchers analyzed data from 777,420 patients age 40 and older who were newly treated with PPIs between 2010 and 2015 in Lombardy, Italy.

Of these, 50,540 patients were diagnosed with type 2 diabetes during follow-up until 2020 (a mean follow-up of 6.2 years and a diabetes incidence of 10.6 cases per 1,000 person-years).

The researchers matched 50,535 patients diagnosed with diabetes during follow-up with 50,535 control patients who had the same age, sex, and clinical status.

Patients were a mean age of 66 years and half were men. The most prescribed PPIs were pantoprazole and omeprazole, and the patients diagnosed with diabetes were more likely to use antihypertensives and lipid-lowering drugs.

Compared with patients who received PPIs for less than 8 weeks, those who received PPIs for 8 weeks to 6 months had a 19% increased risk of being diagnosed with diabetes during follow-up (odds ratio, 1.19; 95% confidence interval, 1.15-1.24), after adjusting for age, clinical profile, comorbidities, medical therapy, and PPI type.

Patients who received PPIs for 6 months to 2 years had a 43% increased risk of the outcome (OR, 1.43; 95% CI, 1.38-1.49), and those who received PPIs for more than 2 years had a 56% increased risk of the outcome (OR, 1.56; 95% CI, 1.49-1.64).

The researchers acknowledge limitations including that the study was not a randomized controlled trial, and it lacked information about over-the-counter medications and unmeasured confounders such as body mass index or family history of diabetes that may have affected the outcomes.

Dr. Leiman added that patients may have had prediabetes or undiagnosed diabetes and symptoms such as heartburn or dyspepsia arising from complications of insulin resistance, for which PPIs might have been prescribed.

The study was funded by a grant from the Italian Ministry of Education, University and Research. Dr. Ciardullo and Dr. Leiman have reported no relevant financial relationships.

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