MDedge Emergency Medicine

Exposure to per- and polyfluoroalkyl substances (PFAS) – a class of widely used synthetic chemicals dubbed “forever chemicals” – may be a modifiable risk factor for the development of hypertension.

In a large, prospective study, researchers found an association between higher blood levels of PFAS and increased risk of hypertension in middle-aged women. Women in the highest tertile of overall PFAS concentrations had a 71% increased risk of developing hypertension.

“Our findings suggest that long-term cumulative exposure, even before midlife, may increase the risk of high blood pressure, and therefore, the benefit of reducing the population exposure to PFAS and potential prevention of high blood pressure and other health conditions would be enormous,” Sung Kyun Park, ScD, MPH, University of Michigan School of Public Health, Ann Arbor, said in an interview.

The study was published online  in Hypertension.
 

Everywhere and forever

“PFAS are forever chemicals as well as everywhere chemicals,” Dr. Park noted.

Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and drinking water. They have been detected in the blood of most people and have been linked to a variety of health concerns.

“A few studies showed an association between PFAS and hypertension, but those were cross-sectional and examined prevalence of hypertension. It was unclear whether PFAS are associated with the development (incidence) of hypertension,” Dr. Park explained.

For their study, the researchers examined the association between serum concentrations of PFAS and risks of incident hypertension in 1,058 initially normotensive women participating in the Study of Women’s Health Across the Nation-Multi-Pollutant Study (SWAN-MPS). They were followed annually between 1999 and 2017.

During 11,722 person-years of follow-up, 470 of the women developed hypertension, at a rate of 40.1 cases per 1,000 person-years. Hypertension was defined as blood pressure of at least 140 mm Hg systolic or at least 90 mm Hg diastolic or receiving antihypertensive treatment.

Women in the highest tertile of baseline serum concentration of perfluorooctane sulfonate (PFOS) had a 42% higher risk of developing hypertension, compared with peers in the lowest tertile (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-1.68; P trend = .01).

Similar results were found for perfluorooctanoate (PFOA) and 2-N-ethyl-perfluorooctane sulfonamido acetate (EtFOSAA), with 47% (aHR, 1.47; 95% CI, 1.24-1.75; P trend = .01) and 42% (aHR, 1.42; 95% CI, 1.19-1.70; P trend = .01) higher risks of incident hypertension, comparing the highest to the lowest tertiles.

The risks persisted after adjusting for various factors, including race, study site, education, financial strain, smoking status, alcohol use, total calorie intake, and menopausal status.

In the PFAS “mixture” analysis, women in the highest tertile of overall PFAS concentrations were 71% more likely to develop hypertension during follow-up, compared with women in the lowest tertile (aHR, 1.71; 95% CI, 1.15-2.54; P trend = .008).

“These findings suggest that PFAS might be an underappreciated contributing factor to women’s cardiovascular disease risk,” the researchers write.

They caution that the study only included middle-aged women and that it is unclear whether the findings hold for middle-aged men.

“This is an important question, but the answer is that we do not know,” Dr. Park told this news organization.

“Women become more susceptible to metabolic changes and hypertension risk during the menopausal transition. Our findings suggest that PFAS may play a role in the development of hypertension in women during this critical life stage,” Dr. Park said.

The researchers say more research is needed to confirm and expand the findings and to find ways to reduce PFAS exposure.

“If confirmed in future studies, these findings suggest that understanding human exposure to PFAS and developing effective strategies to reduce PFAS exposure may help prevent the development of hypertension and thereby reduce the global burden of CVD,” the researchers write.
 

‘The more we learn, the worse it gets’

This is an “interesting” study and shows that “the more we learn about PFAS, the worse it seems to get,” Ankur Shah, MD, division of kidney disease and hypertension, Warren Alpert Medical School of Brown University, Providence, R.I., said in an interview.

“This multisite, multiracial and multiethnic, community-based longitudinal study establishes an association between PFAS and hypertension,” said Dr. Shah, who wasn’t involved in the study.

“This adds to a growing literature base of associations of PFAS with illnesses, including malignancy, thyroid disorders, diabetes, ulcerative colitis, hyperlipidemia, and pregnancy-induced hypertension,” he noted.

Dr. Shah also noted that the authors adjusted for race and ethnicity, study site, education, financial strain, smoking status, environmental tobacco smoke, alcohol consumption, total calorie intake, and menopausal status “and still found a strong association.”

“Still to be determined are both whether PFAS are the causative agent or if there is an unmeasured/unadjusted for entity which has resulted in both increased PFAS exposure and hypertension, as well as if PFAS are causative, if reduction in PFAS exposure would be result in blood pressure reduction,” Dr. Shah added.

The study had no sources of funding. Dr. Park and Dr. Shah have disclosed no relevant financial relationships.

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

Exposure to per- and polyfluoroalkyl substances (PFAS) – a class of widely used synthetic chemicals dubbed “forever chemicals” – may be a modifiable risk factor for the development of hypertension.

In a large, prospective study, researchers found an association between higher blood levels of PFAS and increased risk of hypertension in middle-aged women. Women in the highest tertile of overall PFAS concentrations had a 71% increased risk of developing hypertension.

“Our findings suggest that long-term cumulative exposure, even before midlife, may increase the risk of high blood pressure, and therefore, the benefit of reducing the population exposure to PFAS and potential prevention of high blood pressure and other health conditions would be enormous,” Sung Kyun Park, ScD, MPH, University of Michigan School of Public Health, Ann Arbor, said in an interview.

The study was published online  in Hypertension.
 

Everywhere and forever

“PFAS are forever chemicals as well as everywhere chemicals,” Dr. Park noted.

Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and drinking water. They have been detected in the blood of most people and have been linked to a variety of health concerns.

“A few studies showed an association between PFAS and hypertension, but those were cross-sectional and examined prevalence of hypertension. It was unclear whether PFAS are associated with the development (incidence) of hypertension,” Dr. Park explained.

For their study, the researchers examined the association between serum concentrations of PFAS and risks of incident hypertension in 1,058 initially normotensive women participating in the Study of Women’s Health Across the Nation-Multi-Pollutant Study (SWAN-MPS). They were followed annually between 1999 and 2017.

During 11,722 person-years of follow-up, 470 of the women developed hypertension, at a rate of 40.1 cases per 1,000 person-years. Hypertension was defined as blood pressure of at least 140 mm Hg systolic or at least 90 mm Hg diastolic or receiving antihypertensive treatment.

Women in the highest tertile of baseline serum concentration of perfluorooctane sulfonate (PFOS) had a 42% higher risk of developing hypertension, compared with peers in the lowest tertile (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-1.68; P trend = .01).

Similar results were found for perfluorooctanoate (PFOA) and 2-N-ethyl-perfluorooctane sulfonamido acetate (EtFOSAA), with 47% (aHR, 1.47; 95% CI, 1.24-1.75; P trend = .01) and 42% (aHR, 1.42; 95% CI, 1.19-1.70; P trend = .01) higher risks of incident hypertension, comparing the highest to the lowest tertiles.

The risks persisted after adjusting for various factors, including race, study site, education, financial strain, smoking status, alcohol use, total calorie intake, and menopausal status.

In the PFAS “mixture” analysis, women in the highest tertile of overall PFAS concentrations were 71% more likely to develop hypertension during follow-up, compared with women in the lowest tertile (aHR, 1.71; 95% CI, 1.15-2.54; P trend = .008).

“These findings suggest that PFAS might be an underappreciated contributing factor to women’s cardiovascular disease risk,” the researchers write.

They caution that the study only included middle-aged women and that it is unclear whether the findings hold for middle-aged men.

“This is an important question, but the answer is that we do not know,” Dr. Park told this news organization.

“Women become more susceptible to metabolic changes and hypertension risk during the menopausal transition. Our findings suggest that PFAS may play a role in the development of hypertension in women during this critical life stage,” Dr. Park said.

The researchers say more research is needed to confirm and expand the findings and to find ways to reduce PFAS exposure.

“If confirmed in future studies, these findings suggest that understanding human exposure to PFAS and developing effective strategies to reduce PFAS exposure may help prevent the development of hypertension and thereby reduce the global burden of CVD,” the researchers write.
 

‘The more we learn, the worse it gets’

This is an “interesting” study and shows that “the more we learn about PFAS, the worse it seems to get,” Ankur Shah, MD, division of kidney disease and hypertension, Warren Alpert Medical School of Brown University, Providence, R.I., said in an interview.

“This multisite, multiracial and multiethnic, community-based longitudinal study establishes an association between PFAS and hypertension,” said Dr. Shah, who wasn’t involved in the study.

“This adds to a growing literature base of associations of PFAS with illnesses, including malignancy, thyroid disorders, diabetes, ulcerative colitis, hyperlipidemia, and pregnancy-induced hypertension,” he noted.

Dr. Shah also noted that the authors adjusted for race and ethnicity, study site, education, financial strain, smoking status, environmental tobacco smoke, alcohol consumption, total calorie intake, and menopausal status “and still found a strong association.”

“Still to be determined are both whether PFAS are the causative agent or if there is an unmeasured/unadjusted for entity which has resulted in both increased PFAS exposure and hypertension, as well as if PFAS are causative, if reduction in PFAS exposure would be result in blood pressure reduction,” Dr. Shah added.

The study had no sources of funding. Dr. Park and Dr. Shah have disclosed no relevant financial relationships.

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

Exposure to per- and polyfluoroalkyl substances (PFAS) – a class of widely used synthetic chemicals dubbed “forever chemicals” – may be a modifiable risk factor for the development of hypertension.

In a large, prospective study, researchers found an association between higher blood levels of PFAS and increased risk of hypertension in middle-aged women. Women in the highest tertile of overall PFAS concentrations had a 71% increased risk of developing hypertension.

“Our findings suggest that long-term cumulative exposure, even before midlife, may increase the risk of high blood pressure, and therefore, the benefit of reducing the population exposure to PFAS and potential prevention of high blood pressure and other health conditions would be enormous,” Sung Kyun Park, ScD, MPH, University of Michigan School of Public Health, Ann Arbor, said in an interview.

The study was published online  in Hypertension.
 

Everywhere and forever

“PFAS are forever chemicals as well as everywhere chemicals,” Dr. Park noted.

Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and drinking water. They have been detected in the blood of most people and have been linked to a variety of health concerns.

“A few studies showed an association between PFAS and hypertension, but those were cross-sectional and examined prevalence of hypertension. It was unclear whether PFAS are associated with the development (incidence) of hypertension,” Dr. Park explained.

For their study, the researchers examined the association between serum concentrations of PFAS and risks of incident hypertension in 1,058 initially normotensive women participating in the Study of Women’s Health Across the Nation-Multi-Pollutant Study (SWAN-MPS). They were followed annually between 1999 and 2017.

During 11,722 person-years of follow-up, 470 of the women developed hypertension, at a rate of 40.1 cases per 1,000 person-years. Hypertension was defined as blood pressure of at least 140 mm Hg systolic or at least 90 mm Hg diastolic or receiving antihypertensive treatment.

Women in the highest tertile of baseline serum concentration of perfluorooctane sulfonate (PFOS) had a 42% higher risk of developing hypertension, compared with peers in the lowest tertile (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-1.68; P trend = .01).

Similar results were found for perfluorooctanoate (PFOA) and 2-N-ethyl-perfluorooctane sulfonamido acetate (EtFOSAA), with 47% (aHR, 1.47; 95% CI, 1.24-1.75; P trend = .01) and 42% (aHR, 1.42; 95% CI, 1.19-1.70; P trend = .01) higher risks of incident hypertension, comparing the highest to the lowest tertiles.

The risks persisted after adjusting for various factors, including race, study site, education, financial strain, smoking status, alcohol use, total calorie intake, and menopausal status.

In the PFAS “mixture” analysis, women in the highest tertile of overall PFAS concentrations were 71% more likely to develop hypertension during follow-up, compared with women in the lowest tertile (aHR, 1.71; 95% CI, 1.15-2.54; P trend = .008).

“These findings suggest that PFAS might be an underappreciated contributing factor to women’s cardiovascular disease risk,” the researchers write.

They caution that the study only included middle-aged women and that it is unclear whether the findings hold for middle-aged men.

“This is an important question, but the answer is that we do not know,” Dr. Park told this news organization.

“Women become more susceptible to metabolic changes and hypertension risk during the menopausal transition. Our findings suggest that PFAS may play a role in the development of hypertension in women during this critical life stage,” Dr. Park said.

The researchers say more research is needed to confirm and expand the findings and to find ways to reduce PFAS exposure.

“If confirmed in future studies, these findings suggest that understanding human exposure to PFAS and developing effective strategies to reduce PFAS exposure may help prevent the development of hypertension and thereby reduce the global burden of CVD,” the researchers write.
 

‘The more we learn, the worse it gets’

This is an “interesting” study and shows that “the more we learn about PFAS, the worse it seems to get,” Ankur Shah, MD, division of kidney disease and hypertension, Warren Alpert Medical School of Brown University, Providence, R.I., said in an interview.

“This multisite, multiracial and multiethnic, community-based longitudinal study establishes an association between PFAS and hypertension,” said Dr. Shah, who wasn’t involved in the study.

“This adds to a growing literature base of associations of PFAS with illnesses, including malignancy, thyroid disorders, diabetes, ulcerative colitis, hyperlipidemia, and pregnancy-induced hypertension,” he noted.

Dr. Shah also noted that the authors adjusted for race and ethnicity, study site, education, financial strain, smoking status, environmental tobacco smoke, alcohol consumption, total calorie intake, and menopausal status “and still found a strong association.”

“Still to be determined are both whether PFAS are the causative agent or if there is an unmeasured/unadjusted for entity which has resulted in both increased PFAS exposure and hypertension, as well as if PFAS are causative, if reduction in PFAS exposure would be result in blood pressure reduction,” Dr. Shah added.

The study had no sources of funding. Dr. Park and Dr. Shah have disclosed no relevant financial relationships.

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

The development of depression after a rheumatoid arthritis diagnosis increased the risk for death “more than sixfold” when compared with having no depression at diagnosis, according to Danish researchers.

Cumulative mortality at 10 years was approximately 37% in patients with comorbid RA and depression versus around 13.5% of RA patients with no depression, Jens Kristian Pedersen, MD, PhD, of Odense (Denmark) University Hospital–Svendborg Hospital and the department of clinical research at the University of Southern Denmark, also in Odense, reported at the annual European Congress of Rheumatology.

“According to [antidepressant] exposure status, the cumulative mortality followed two clearly different paths,” Dr. Pedersen said. “The mortality curves separated early and already within the first and second year of follow-up.”
 

RA, depression, and mortality

Rates of depression in patients with RA are high, Dr. Pedersen said, and while it’s previously been reported that their coexistence can increase mortality, this is the first time that the link has been investigated in a population newly diagnosed with RA.

In this study, Dr. Pedersen and collaborators wanted to look at the association in incident RA and defined depression as the first filling of an antidepressant prescription.

“Although antidepressants are used for different indications, we have recently described that in RA the most frequent indication for filling antidepressants is depression,” he explained. Moreover, that research found that “the frequency of filling coincides with the occurrence of depressive disorder previously reported in the scientific literature.”
 

Data sourced from multiple Danish registers

To examine the mortality risk associated with newly diagnosed RA and new-onset depression, Dr. Pedersen described how five different Danish registers were used.

First, data from the DANBIO register were used to identify patients with incident RA living in Denmark over a 10-year period ending in December 2018. Although perhaps widely known as a biologics register, DANBIO is required by the Danish National Board of Health to collect information on all patients with RA, regardless of their treatment.

Next, the Danish National Prescription Register and Danish National Patient Register were consulted to obtain data on patients who had a first prescription for antidepressant treatment and information on those who developed a diagnosis of depression. Demographic, vital status, and socioeconomic data were collated from the Danish Civil Registration System and Statistics Denmark databases.

To be sure they were looking at incident cases of RA and new cases of depression, the researchers excluded anyone with an existing prescription of antidepressants or methotrexate, or who had a confirmed diagnosis of either disorder 3 years prior to the index date of Jan. 1, 2008.

This meant that, from a total population of 18,000 patients in the DANBIO database, there were just over 11,000 who could be included in the analyses.

Overall, the median age at RA diagnosis was 61 years, two-thirds were female, and two-thirds had seropositive disease.

New-onset depression in incident RA

“During follow-up, about 10% filled a prescription of antidepressants,” said Dr. Pedersen, adding that there were 671 deaths, representing around 57,000 person-years at risk.

“The majority died from natural causes,” he said, although the cause of death was unknown in 30% of cases.

Comparing those who did and did not have a prescription for antidepressants, there were some differences in the age at which death occurred, the percentage of females to males, the presence of other comorbidities, and levels of higher education and income. These were all adjusted for in the analyses.

Adjusted hazard rate ratios were calculated to look at the mortality risk in patients who had antidepressant exposure. The highest HRR for mortality with antidepressant use was seen in patients aged 55 years or younger at 6.66, with the next highest HRRs being for male gender (3.70) and seropositive RA (3.45).

But HRRs for seronegative RA, female gender, and age 55-70 years or older than 75 years were all still around 3.0.
 

Depression definition questioned

“My only concern is about the definition of depression in your analysis,” said a member of the audience at the congress.

“You used antidepressant use as a proxy of depression diagnosis, but it might be that most or many patients have taken [medication] like duloxetine for pain control, and you are just seeing higher disease activity and more aggressive RA.”

Dr. Pedersen responded: “After the EULAR 2022 submission deadline, we reanalyzed our data using two other measures of depression.

“First, we use treatment with antidepressants with a positive indication of depression, according to the prescribing physician, and secondly, we used first diagnosis with depression according to ICD-10 Code F32 – ‘depressive episode after discharge from hospital as an outpatient,’ ” he said.

“All definitions end up with a hazard rate ratio of about three. So, in my opinion, it doesn’t matter whether you focus on one measure of depression or the other.”

David Isenberg, MD, FRCP, professor of rheumatology at University College London, wanted to know more about the antecedent history of depression and whether people who had been depressed maybe a decade or 2 decades before, were more likely to get RA.

That calculation has not been done, Dr. Pedersen said, adding that the study also can’t account for people who may have had recurrent depression. Depression treatment guidelines often recommend nonpharmacologic intervention in the first instance, “so we do not necessarily get the right picture of recurrent depression if we look further back.”

Pointing out that the sixfold increase in mortality was impressive, another delegate asked about whether it was because of a higher disease activity or joint damage and if the mortality risk might be lower in patients who are in remission.

“We don’t know that yet,” Dr. Pedersen answered. “We haven’t done the calculations, but there is the issue of residual confounding if we don’t take all relevant covariates into account. So, we need to do that calculation as well.”

The study was supported by the Danish Rheumatism Association. Dr. Pedersen had no conflicts of interest to disclose.
 

The development of depression after a rheumatoid arthritis diagnosis increased the risk for death “more than sixfold” when compared with having no depression at diagnosis, according to Danish researchers.

Cumulative mortality at 10 years was approximately 37% in patients with comorbid RA and depression versus around 13.5% of RA patients with no depression, Jens Kristian Pedersen, MD, PhD, of Odense (Denmark) University Hospital–Svendborg Hospital and the department of clinical research at the University of Southern Denmark, also in Odense, reported at the annual European Congress of Rheumatology.

“According to [antidepressant] exposure status, the cumulative mortality followed two clearly different paths,” Dr. Pedersen said. “The mortality curves separated early and already within the first and second year of follow-up.”
 

RA, depression, and mortality

Rates of depression in patients with RA are high, Dr. Pedersen said, and while it’s previously been reported that their coexistence can increase mortality, this is the first time that the link has been investigated in a population newly diagnosed with RA.

In this study, Dr. Pedersen and collaborators wanted to look at the association in incident RA and defined depression as the first filling of an antidepressant prescription.

“Although antidepressants are used for different indications, we have recently described that in RA the most frequent indication for filling antidepressants is depression,” he explained. Moreover, that research found that “the frequency of filling coincides with the occurrence of depressive disorder previously reported in the scientific literature.”
 

Data sourced from multiple Danish registers

To examine the mortality risk associated with newly diagnosed RA and new-onset depression, Dr. Pedersen described how five different Danish registers were used.

First, data from the DANBIO register were used to identify patients with incident RA living in Denmark over a 10-year period ending in December 2018. Although perhaps widely known as a biologics register, DANBIO is required by the Danish National Board of Health to collect information on all patients with RA, regardless of their treatment.

Next, the Danish National Prescription Register and Danish National Patient Register were consulted to obtain data on patients who had a first prescription for antidepressant treatment and information on those who developed a diagnosis of depression. Demographic, vital status, and socioeconomic data were collated from the Danish Civil Registration System and Statistics Denmark databases.

To be sure they were looking at incident cases of RA and new cases of depression, the researchers excluded anyone with an existing prescription of antidepressants or methotrexate, or who had a confirmed diagnosis of either disorder 3 years prior to the index date of Jan. 1, 2008.

This meant that, from a total population of 18,000 patients in the DANBIO database, there were just over 11,000 who could be included in the analyses.

Overall, the median age at RA diagnosis was 61 years, two-thirds were female, and two-thirds had seropositive disease.

New-onset depression in incident RA

“During follow-up, about 10% filled a prescription of antidepressants,” said Dr. Pedersen, adding that there were 671 deaths, representing around 57,000 person-years at risk.

“The majority died from natural causes,” he said, although the cause of death was unknown in 30% of cases.

Comparing those who did and did not have a prescription for antidepressants, there were some differences in the age at which death occurred, the percentage of females to males, the presence of other comorbidities, and levels of higher education and income. These were all adjusted for in the analyses.

Adjusted hazard rate ratios were calculated to look at the mortality risk in patients who had antidepressant exposure. The highest HRR for mortality with antidepressant use was seen in patients aged 55 years or younger at 6.66, with the next highest HRRs being for male gender (3.70) and seropositive RA (3.45).

But HRRs for seronegative RA, female gender, and age 55-70 years or older than 75 years were all still around 3.0.
 

Depression definition questioned

“My only concern is about the definition of depression in your analysis,” said a member of the audience at the congress.

“You used antidepressant use as a proxy of depression diagnosis, but it might be that most or many patients have taken [medication] like duloxetine for pain control, and you are just seeing higher disease activity and more aggressive RA.”

Dr. Pedersen responded: “After the EULAR 2022 submission deadline, we reanalyzed our data using two other measures of depression.

“First, we use treatment with antidepressants with a positive indication of depression, according to the prescribing physician, and secondly, we used first diagnosis with depression according to ICD-10 Code F32 – ‘depressive episode after discharge from hospital as an outpatient,’ ” he said.

“All definitions end up with a hazard rate ratio of about three. So, in my opinion, it doesn’t matter whether you focus on one measure of depression or the other.”

David Isenberg, MD, FRCP, professor of rheumatology at University College London, wanted to know more about the antecedent history of depression and whether people who had been depressed maybe a decade or 2 decades before, were more likely to get RA.

That calculation has not been done, Dr. Pedersen said, adding that the study also can’t account for people who may have had recurrent depression. Depression treatment guidelines often recommend nonpharmacologic intervention in the first instance, “so we do not necessarily get the right picture of recurrent depression if we look further back.”

Pointing out that the sixfold increase in mortality was impressive, another delegate asked about whether it was because of a higher disease activity or joint damage and if the mortality risk might be lower in patients who are in remission.

“We don’t know that yet,” Dr. Pedersen answered. “We haven’t done the calculations, but there is the issue of residual confounding if we don’t take all relevant covariates into account. So, we need to do that calculation as well.”

The study was supported by the Danish Rheumatism Association. Dr. Pedersen had no conflicts of interest to disclose.
 

The development of depression after a rheumatoid arthritis diagnosis increased the risk for death “more than sixfold” when compared with having no depression at diagnosis, according to Danish researchers.

Cumulative mortality at 10 years was approximately 37% in patients with comorbid RA and depression versus around 13.5% of RA patients with no depression, Jens Kristian Pedersen, MD, PhD, of Odense (Denmark) University Hospital–Svendborg Hospital and the department of clinical research at the University of Southern Denmark, also in Odense, reported at the annual European Congress of Rheumatology.

“According to [antidepressant] exposure status, the cumulative mortality followed two clearly different paths,” Dr. Pedersen said. “The mortality curves separated early and already within the first and second year of follow-up.”
 

RA, depression, and mortality

Rates of depression in patients with RA are high, Dr. Pedersen said, and while it’s previously been reported that their coexistence can increase mortality, this is the first time that the link has been investigated in a population newly diagnosed with RA.

In this study, Dr. Pedersen and collaborators wanted to look at the association in incident RA and defined depression as the first filling of an antidepressant prescription.

“Although antidepressants are used for different indications, we have recently described that in RA the most frequent indication for filling antidepressants is depression,” he explained. Moreover, that research found that “the frequency of filling coincides with the occurrence of depressive disorder previously reported in the scientific literature.”
 

Data sourced from multiple Danish registers

To examine the mortality risk associated with newly diagnosed RA and new-onset depression, Dr. Pedersen described how five different Danish registers were used.

First, data from the DANBIO register were used to identify patients with incident RA living in Denmark over a 10-year period ending in December 2018. Although perhaps widely known as a biologics register, DANBIO is required by the Danish National Board of Health to collect information on all patients with RA, regardless of their treatment.

Next, the Danish National Prescription Register and Danish National Patient Register were consulted to obtain data on patients who had a first prescription for antidepressant treatment and information on those who developed a diagnosis of depression. Demographic, vital status, and socioeconomic data were collated from the Danish Civil Registration System and Statistics Denmark databases.

To be sure they were looking at incident cases of RA and new cases of depression, the researchers excluded anyone with an existing prescription of antidepressants or methotrexate, or who had a confirmed diagnosis of either disorder 3 years prior to the index date of Jan. 1, 2008.

This meant that, from a total population of 18,000 patients in the DANBIO database, there were just over 11,000 who could be included in the analyses.

Overall, the median age at RA diagnosis was 61 years, two-thirds were female, and two-thirds had seropositive disease.

New-onset depression in incident RA

“During follow-up, about 10% filled a prescription of antidepressants,” said Dr. Pedersen, adding that there were 671 deaths, representing around 57,000 person-years at risk.

“The majority died from natural causes,” he said, although the cause of death was unknown in 30% of cases.

Comparing those who did and did not have a prescription for antidepressants, there were some differences in the age at which death occurred, the percentage of females to males, the presence of other comorbidities, and levels of higher education and income. These were all adjusted for in the analyses.

Adjusted hazard rate ratios were calculated to look at the mortality risk in patients who had antidepressant exposure. The highest HRR for mortality with antidepressant use was seen in patients aged 55 years or younger at 6.66, with the next highest HRRs being for male gender (3.70) and seropositive RA (3.45).

But HRRs for seronegative RA, female gender, and age 55-70 years or older than 75 years were all still around 3.0.
 

Depression definition questioned

“My only concern is about the definition of depression in your analysis,” said a member of the audience at the congress.

“You used antidepressant use as a proxy of depression diagnosis, but it might be that most or many patients have taken [medication] like duloxetine for pain control, and you are just seeing higher disease activity and more aggressive RA.”

Dr. Pedersen responded: “After the EULAR 2022 submission deadline, we reanalyzed our data using two other measures of depression.

“First, we use treatment with antidepressants with a positive indication of depression, according to the prescribing physician, and secondly, we used first diagnosis with depression according to ICD-10 Code F32 – ‘depressive episode after discharge from hospital as an outpatient,’ ” he said.

“All definitions end up with a hazard rate ratio of about three. So, in my opinion, it doesn’t matter whether you focus on one measure of depression or the other.”

David Isenberg, MD, FRCP, professor of rheumatology at University College London, wanted to know more about the antecedent history of depression and whether people who had been depressed maybe a decade or 2 decades before, were more likely to get RA.

That calculation has not been done, Dr. Pedersen said, adding that the study also can’t account for people who may have had recurrent depression. Depression treatment guidelines often recommend nonpharmacologic intervention in the first instance, “so we do not necessarily get the right picture of recurrent depression if we look further back.”

Pointing out that the sixfold increase in mortality was impressive, another delegate asked about whether it was because of a higher disease activity or joint damage and if the mortality risk might be lower in patients who are in remission.

“We don’t know that yet,” Dr. Pedersen answered. “We haven’t done the calculations, but there is the issue of residual confounding if we don’t take all relevant covariates into account. So, we need to do that calculation as well.”

The study was supported by the Danish Rheumatism Association. Dr. Pedersen had no conflicts of interest to disclose.
 

Synthetic opioid use in the United States increased by almost 800% over 7 years, new research shows.

The results of a national urine drug test (UDT) study come as the United States is reporting a record-high number of drug overdose deaths – more than 80% of which involved fentanyl or other synthetic opioids and prompting a push for better surveillance models.

Researchers found that UDTs can be used to accurately identify which drugs are circulating in a community, revealing in just a matter of days critically important drug use trends that current surveillance methods take a month or longer to report.

The faster turnaround could potentially allow clinicians and public health officials to be more proactive with targeted overdose prevention and harm-reduction strategies such as distribution of naloxone and fentanyl test strips.

“We’re talking about trying to come up with an early-warning system,” study author Steven Passik, PhD, vice president for scientific affairs for Millennium Health, San Diego, Calif., told this news organization. “We’re trying to find out if we can let people in the harm reduction and treatment space know about what might be coming weeks or a month or more in advance so that some interventions could be marshaled.”

The study was published online in JAMA Network Open.
 

Call for better surveillance

More than 100,000 people in the United States died of an unintended drug overdose in 2021, a record high and a 15% increase over 2020 figures, which also set a record.

Part of the federal government’s plan to address the crisis includes strengthening epidemiologic efforts by better collection and mining of public health surveillance data.

Sources currently used to detect drug use trends include mortality data, poison control centers, emergency departments, electronic health records, and crime laboratories. But analysis of these sources can take weeks or more.

“One of the real challenges in addressing and reducing overdose deaths has been the relative lack of accessible real-time data that can support agile responses to deployment of resources in a specific geographic region,” study coauthor Rebecca Jackson, MD, professor and associate dean for clinical and translational research at Ohio State University in Columbus, said in an interview.

Ohio State researchers partnered with scientists at Millennium Health, one of the largest urine test labs in the United States, on a cross-sectional study to find out if UDTs could be an accurate and speedier tool for drug surveillance.

They analyzed 500,000 unique urine samples from patients in substance use disorder (SUD) treatment facilities in all 50 states from 2013 to 2020, comparing levels of cocaine, heroin, methamphetamine, synthetic opioids, and other opioids found in the samples to levels of the same drugs from overdose mortality data at the national, state, and county level from the National Vital Statistics System.

On a national level, synthetic opioids and methamphetamine were highly correlated with overdose mortality data (Spearman’s rho = .96 for both). When synthetic opioids were coinvolved, methamphetamine (rho = .98), heroin (rho = .78), cocaine (rho = .94), and other opioids (rho = .83) were also highly correlated with overdose mortality data.

Similar correlations were found when examining state-level data from 24 states and at the county level upon analysis of 19 counties in Ohio.
 

A changing landscape

Researchers said the strong correlation between overdose deaths and UDT results for synthetic opioids and methamphetamine are likely explained by the drugs’ availability and lethality.

“The most important thing that we found was just the strength of the correlation, which goes right to the heart of why we considered correlation to be so critical,” lead author Penn Whitley, senior director of bioinformatics for Millennium Health, told this news organization. “We needed to demonstrate that there was a strong correlation of just the UDT positivity rates with mortality – in this case, fatal drug overdose rates – as a steppingstone to build out tools that could utilize UDT as a real-time data source.”

While the main goal of the study was to establish correlation between UDT results and national mortality data, the study also offers a view of a changing landscape in the opioid epidemic.

Overall, UDT positivity for total synthetic opioids increased from 2.1% in 2013 to 19.1% in 2020 (a 792.5% increase). Positivity rates for all included drug categories increased when synthetic opioids were present.

However, in the absence of synthetic opioids, UDT positivity decreased for almost all drug categories from 2013 to 2020 (from 7.7% to 4.7% for cocaine; 3.9% to 1.6% for heroin; 20.5% to 6.9% for other opioids).

Only methamphetamine positivity increased with or without involvement of synthetic opioids. With synthetic opioids, meth positivity rose from 0.1% in 2013 to 7.9% in 2020. Without them, meth positivity rates still rose, from 2.1% in 2013 to 13.1% in 2020.

The findings track with an earlier study showing methamphetamine-involved overdose deaths rose sharply between 2011 and 2018.

“The data from this manuscript support that the opioid epidemic is transitioning from an opioid epidemic to a polysubstance epidemic where illicit synthetic opioids, largely fentanyl, in combination with other substances are now responsible for upwards of 80% of OD deaths,” Dr. Jackson said.

In an accompanying editorial Jeffrey Brent, MD, PhD, clinical professor in internal medicine at the University of Colorado at Denver, Aurora, and Stephanie T. Weiss, MD, PhD, staff clinician in the Translational Addiction Medicine Branch at the National Institute on Drug Abuse, Baltimore, note that as new agents emerge, different harm-reduction strategies will be needed, adding that having a real-time tool to identify the trends will be key to preventing deaths.

“Surveillance systems are an integral component of reducing morbidity and mortality associated with illicit drug use. On local, regional, and national levels, information of this type is needed to most efficiently allocate limited resources to maximize benefit and save lives,” Dr. Brent and Dr. Weiss write.

The study was funded by Millennium Health and the National Center for Advancing Translational Sciences. Full disclosures are included in the original articles, but no sources reported conflicts related to the study.

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

Synthetic opioid use in the United States increased by almost 800% over 7 years, new research shows.

The results of a national urine drug test (UDT) study come as the United States is reporting a record-high number of drug overdose deaths – more than 80% of which involved fentanyl or other synthetic opioids and prompting a push for better surveillance models.

Researchers found that UDTs can be used to accurately identify which drugs are circulating in a community, revealing in just a matter of days critically important drug use trends that current surveillance methods take a month or longer to report.

The faster turnaround could potentially allow clinicians and public health officials to be more proactive with targeted overdose prevention and harm-reduction strategies such as distribution of naloxone and fentanyl test strips.

“We’re talking about trying to come up with an early-warning system,” study author Steven Passik, PhD, vice president for scientific affairs for Millennium Health, San Diego, Calif., told this news organization. “We’re trying to find out if we can let people in the harm reduction and treatment space know about what might be coming weeks or a month or more in advance so that some interventions could be marshaled.”

The study was published online in JAMA Network Open.
 

Call for better surveillance

More than 100,000 people in the United States died of an unintended drug overdose in 2021, a record high and a 15% increase over 2020 figures, which also set a record.

Part of the federal government’s plan to address the crisis includes strengthening epidemiologic efforts by better collection and mining of public health surveillance data.

Sources currently used to detect drug use trends include mortality data, poison control centers, emergency departments, electronic health records, and crime laboratories. But analysis of these sources can take weeks or more.

“One of the real challenges in addressing and reducing overdose deaths has been the relative lack of accessible real-time data that can support agile responses to deployment of resources in a specific geographic region,” study coauthor Rebecca Jackson, MD, professor and associate dean for clinical and translational research at Ohio State University in Columbus, said in an interview.

Ohio State researchers partnered with scientists at Millennium Health, one of the largest urine test labs in the United States, on a cross-sectional study to find out if UDTs could be an accurate and speedier tool for drug surveillance.

They analyzed 500,000 unique urine samples from patients in substance use disorder (SUD) treatment facilities in all 50 states from 2013 to 2020, comparing levels of cocaine, heroin, methamphetamine, synthetic opioids, and other opioids found in the samples to levels of the same drugs from overdose mortality data at the national, state, and county level from the National Vital Statistics System.

On a national level, synthetic opioids and methamphetamine were highly correlated with overdose mortality data (Spearman’s rho = .96 for both). When synthetic opioids were coinvolved, methamphetamine (rho = .98), heroin (rho = .78), cocaine (rho = .94), and other opioids (rho = .83) were also highly correlated with overdose mortality data.

Similar correlations were found when examining state-level data from 24 states and at the county level upon analysis of 19 counties in Ohio.
 

A changing landscape

Researchers said the strong correlation between overdose deaths and UDT results for synthetic opioids and methamphetamine are likely explained by the drugs’ availability and lethality.

“The most important thing that we found was just the strength of the correlation, which goes right to the heart of why we considered correlation to be so critical,” lead author Penn Whitley, senior director of bioinformatics for Millennium Health, told this news organization. “We needed to demonstrate that there was a strong correlation of just the UDT positivity rates with mortality – in this case, fatal drug overdose rates – as a steppingstone to build out tools that could utilize UDT as a real-time data source.”

While the main goal of the study was to establish correlation between UDT results and national mortality data, the study also offers a view of a changing landscape in the opioid epidemic.

Overall, UDT positivity for total synthetic opioids increased from 2.1% in 2013 to 19.1% in 2020 (a 792.5% increase). Positivity rates for all included drug categories increased when synthetic opioids were present.

However, in the absence of synthetic opioids, UDT positivity decreased for almost all drug categories from 2013 to 2020 (from 7.7% to 4.7% for cocaine; 3.9% to 1.6% for heroin; 20.5% to 6.9% for other opioids).

Only methamphetamine positivity increased with or without involvement of synthetic opioids. With synthetic opioids, meth positivity rose from 0.1% in 2013 to 7.9% in 2020. Without them, meth positivity rates still rose, from 2.1% in 2013 to 13.1% in 2020.

The findings track with an earlier study showing methamphetamine-involved overdose deaths rose sharply between 2011 and 2018.

“The data from this manuscript support that the opioid epidemic is transitioning from an opioid epidemic to a polysubstance epidemic where illicit synthetic opioids, largely fentanyl, in combination with other substances are now responsible for upwards of 80% of OD deaths,” Dr. Jackson said.

In an accompanying editorial Jeffrey Brent, MD, PhD, clinical professor in internal medicine at the University of Colorado at Denver, Aurora, and Stephanie T. Weiss, MD, PhD, staff clinician in the Translational Addiction Medicine Branch at the National Institute on Drug Abuse, Baltimore, note that as new agents emerge, different harm-reduction strategies will be needed, adding that having a real-time tool to identify the trends will be key to preventing deaths.

“Surveillance systems are an integral component of reducing morbidity and mortality associated with illicit drug use. On local, regional, and national levels, information of this type is needed to most efficiently allocate limited resources to maximize benefit and save lives,” Dr. Brent and Dr. Weiss write.

The study was funded by Millennium Health and the National Center for Advancing Translational Sciences. Full disclosures are included in the original articles, but no sources reported conflicts related to the study.

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

Synthetic opioid use in the United States increased by almost 800% over 7 years, new research shows.

The results of a national urine drug test (UDT) study come as the United States is reporting a record-high number of drug overdose deaths – more than 80% of which involved fentanyl or other synthetic opioids and prompting a push for better surveillance models.

Researchers found that UDTs can be used to accurately identify which drugs are circulating in a community, revealing in just a matter of days critically important drug use trends that current surveillance methods take a month or longer to report.

The faster turnaround could potentially allow clinicians and public health officials to be more proactive with targeted overdose prevention and harm-reduction strategies such as distribution of naloxone and fentanyl test strips.

“We’re talking about trying to come up with an early-warning system,” study author Steven Passik, PhD, vice president for scientific affairs for Millennium Health, San Diego, Calif., told this news organization. “We’re trying to find out if we can let people in the harm reduction and treatment space know about what might be coming weeks or a month or more in advance so that some interventions could be marshaled.”

The study was published online in JAMA Network Open.
 

Call for better surveillance

More than 100,000 people in the United States died of an unintended drug overdose in 2021, a record high and a 15% increase over 2020 figures, which also set a record.

Part of the federal government’s plan to address the crisis includes strengthening epidemiologic efforts by better collection and mining of public health surveillance data.

Sources currently used to detect drug use trends include mortality data, poison control centers, emergency departments, electronic health records, and crime laboratories. But analysis of these sources can take weeks or more.

“One of the real challenges in addressing and reducing overdose deaths has been the relative lack of accessible real-time data that can support agile responses to deployment of resources in a specific geographic region,” study coauthor Rebecca Jackson, MD, professor and associate dean for clinical and translational research at Ohio State University in Columbus, said in an interview.

Ohio State researchers partnered with scientists at Millennium Health, one of the largest urine test labs in the United States, on a cross-sectional study to find out if UDTs could be an accurate and speedier tool for drug surveillance.

They analyzed 500,000 unique urine samples from patients in substance use disorder (SUD) treatment facilities in all 50 states from 2013 to 2020, comparing levels of cocaine, heroin, methamphetamine, synthetic opioids, and other opioids found in the samples to levels of the same drugs from overdose mortality data at the national, state, and county level from the National Vital Statistics System.

On a national level, synthetic opioids and methamphetamine were highly correlated with overdose mortality data (Spearman’s rho = .96 for both). When synthetic opioids were coinvolved, methamphetamine (rho = .98), heroin (rho = .78), cocaine (rho = .94), and other opioids (rho = .83) were also highly correlated with overdose mortality data.

Similar correlations were found when examining state-level data from 24 states and at the county level upon analysis of 19 counties in Ohio.
 

A changing landscape

Researchers said the strong correlation between overdose deaths and UDT results for synthetic opioids and methamphetamine are likely explained by the drugs’ availability and lethality.

“The most important thing that we found was just the strength of the correlation, which goes right to the heart of why we considered correlation to be so critical,” lead author Penn Whitley, senior director of bioinformatics for Millennium Health, told this news organization. “We needed to demonstrate that there was a strong correlation of just the UDT positivity rates with mortality – in this case, fatal drug overdose rates – as a steppingstone to build out tools that could utilize UDT as a real-time data source.”

While the main goal of the study was to establish correlation between UDT results and national mortality data, the study also offers a view of a changing landscape in the opioid epidemic.

Overall, UDT positivity for total synthetic opioids increased from 2.1% in 2013 to 19.1% in 2020 (a 792.5% increase). Positivity rates for all included drug categories increased when synthetic opioids were present.

However, in the absence of synthetic opioids, UDT positivity decreased for almost all drug categories from 2013 to 2020 (from 7.7% to 4.7% for cocaine; 3.9% to 1.6% for heroin; 20.5% to 6.9% for other opioids).

Only methamphetamine positivity increased with or without involvement of synthetic opioids. With synthetic opioids, meth positivity rose from 0.1% in 2013 to 7.9% in 2020. Without them, meth positivity rates still rose, from 2.1% in 2013 to 13.1% in 2020.

The findings track with an earlier study showing methamphetamine-involved overdose deaths rose sharply between 2011 and 2018.

“The data from this manuscript support that the opioid epidemic is transitioning from an opioid epidemic to a polysubstance epidemic where illicit synthetic opioids, largely fentanyl, in combination with other substances are now responsible for upwards of 80% of OD deaths,” Dr. Jackson said.

In an accompanying editorial Jeffrey Brent, MD, PhD, clinical professor in internal medicine at the University of Colorado at Denver, Aurora, and Stephanie T. Weiss, MD, PhD, staff clinician in the Translational Addiction Medicine Branch at the National Institute on Drug Abuse, Baltimore, note that as new agents emerge, different harm-reduction strategies will be needed, adding that having a real-time tool to identify the trends will be key to preventing deaths.

“Surveillance systems are an integral component of reducing morbidity and mortality associated with illicit drug use. On local, regional, and national levels, information of this type is needed to most efficiently allocate limited resources to maximize benefit and save lives,” Dr. Brent and Dr. Weiss write.

The study was funded by Millennium Health and the National Center for Advancing Translational Sciences. Full disclosures are included in the original articles, but no sources reported conflicts related to the study.

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

Does the latest increase in new child COVID-19 cases indicate that the latest surge is on the decline?

The new-case count for the most recent reporting week – 87,644 for June 3-9 – did go up from the previous week, but by only 270 cases, the American Academy of Pediatrics and Children’s Hospital Association said in their weekly COVID report. That’s just 0.31% higher than a week ago and probably is affected by reduced testing and reporting because of Memorial Day, as the AAP and CHA noted earlier.

That hint of a continued decline accompanies the latest trend for new cases for all age groups: They have leveled out over the last month, with the moving 7-day daily average hovering around 100,000-110,000 since mid-May, data from the Centers for Disease Control and Prevention show.

The Food and Drug Administration, meanwhile, is in the news this week as two of its advisory panels take the next steps toward pediatric approvals of vaccines from Pfizer/BioNTtech and Moderna. The panels could advance the approvals of the Pfizer vaccine for children under the age of 5 years and the Moderna vaccine for children aged 6 months to 17 years.

Matthew Harris, MD, medical director of the COVID-19 vaccination program for Northwell Health in New Hyde Park, N.Y., emphasized the importance of vaccinations, as well as the continued challenge of convincing parents to get the shots for eligible children. “We still have a long way to go for primary vaccines and boosters for children 5 years and above,” he said in an interview.

The vaccination effort against COVID-19 has stalled somewhat as interest has waned since the Omicron surge. Weekly initial vaccinations for children aged 5-11 years, which topped 100,000 as recently as mid-March, have been about 43,000 a week for the last 3 weeks, while 12- to 17-year-olds had around 27,000 or 28,000 initial vaccinations per week over that span, the AAP said in a separate report.

The latest data available from the CDC show that overall vaccine coverage levels for the younger group are only about half those of the 12- to 17-year-olds, both in terms of initial doses and completions. The 5- to 11-year-olds are not eligible for boosters yet, but 26.5% of the older children had received one as of June 13, according to the CDC’s COVID Data Tracker.

Does the latest increase in new child COVID-19 cases indicate that the latest surge is on the decline?

The new-case count for the most recent reporting week – 87,644 for June 3-9 – did go up from the previous week, but by only 270 cases, the American Academy of Pediatrics and Children’s Hospital Association said in their weekly COVID report. That’s just 0.31% higher than a week ago and probably is affected by reduced testing and reporting because of Memorial Day, as the AAP and CHA noted earlier.

That hint of a continued decline accompanies the latest trend for new cases for all age groups: They have leveled out over the last month, with the moving 7-day daily average hovering around 100,000-110,000 since mid-May, data from the Centers for Disease Control and Prevention show.

The Food and Drug Administration, meanwhile, is in the news this week as two of its advisory panels take the next steps toward pediatric approvals of vaccines from Pfizer/BioNTtech and Moderna. The panels could advance the approvals of the Pfizer vaccine for children under the age of 5 years and the Moderna vaccine for children aged 6 months to 17 years.

Matthew Harris, MD, medical director of the COVID-19 vaccination program for Northwell Health in New Hyde Park, N.Y., emphasized the importance of vaccinations, as well as the continued challenge of convincing parents to get the shots for eligible children. “We still have a long way to go for primary vaccines and boosters for children 5 years and above,” he said in an interview.

The vaccination effort against COVID-19 has stalled somewhat as interest has waned since the Omicron surge. Weekly initial vaccinations for children aged 5-11 years, which topped 100,000 as recently as mid-March, have been about 43,000 a week for the last 3 weeks, while 12- to 17-year-olds had around 27,000 or 28,000 initial vaccinations per week over that span, the AAP said in a separate report.

The latest data available from the CDC show that overall vaccine coverage levels for the younger group are only about half those of the 12- to 17-year-olds, both in terms of initial doses and completions. The 5- to 11-year-olds are not eligible for boosters yet, but 26.5% of the older children had received one as of June 13, according to the CDC’s COVID Data Tracker.

Does the latest increase in new child COVID-19 cases indicate that the latest surge is on the decline?

The new-case count for the most recent reporting week – 87,644 for June 3-9 – did go up from the previous week, but by only 270 cases, the American Academy of Pediatrics and Children’s Hospital Association said in their weekly COVID report. That’s just 0.31% higher than a week ago and probably is affected by reduced testing and reporting because of Memorial Day, as the AAP and CHA noted earlier.

That hint of a continued decline accompanies the latest trend for new cases for all age groups: They have leveled out over the last month, with the moving 7-day daily average hovering around 100,000-110,000 since mid-May, data from the Centers for Disease Control and Prevention show.

The Food and Drug Administration, meanwhile, is in the news this week as two of its advisory panels take the next steps toward pediatric approvals of vaccines from Pfizer/BioNTtech and Moderna. The panels could advance the approvals of the Pfizer vaccine for children under the age of 5 years and the Moderna vaccine for children aged 6 months to 17 years.

Matthew Harris, MD, medical director of the COVID-19 vaccination program for Northwell Health in New Hyde Park, N.Y., emphasized the importance of vaccinations, as well as the continued challenge of convincing parents to get the shots for eligible children. “We still have a long way to go for primary vaccines and boosters for children 5 years and above,” he said in an interview.

The vaccination effort against COVID-19 has stalled somewhat as interest has waned since the Omicron surge. Weekly initial vaccinations for children aged 5-11 years, which topped 100,000 as recently as mid-March, have been about 43,000 a week for the last 3 weeks, while 12- to 17-year-olds had around 27,000 or 28,000 initial vaccinations per week over that span, the AAP said in a separate report.

The latest data available from the CDC show that overall vaccine coverage levels for the younger group are only about half those of the 12- to 17-year-olds, both in terms of initial doses and completions. The 5- to 11-year-olds are not eligible for boosters yet, but 26.5% of the older children had received one as of June 13, according to the CDC’s COVID Data Tracker.

Two new studies point to an ever-increasing number of young people in the United States who identify as transgender and nonbinary, with the figures doubling among 18- to 24-year-olds in one institute’s research – from 0.66% of the population in 2016 to 1.3% (398,900) in 2022.

In addition, 1.4% (300,100) of 13- to 17-year-olds identify as trans or nonbinary, according to the report from that group, the Williams Institute at the University of California, Los Angeles, School of Law.

Williams, which conducts independent research on sexual orientation and gender identity law and public policy, did not contain data on 13- to 17-year-olds in its 2016 study, so the growth in that group over the past 5+ years is not as well documented.

Overall, some 1.6 million Americans older than age 13 now identify as transgender, reported the Williams researchers.

And in a new Pew Research Center survey, 2% of adults aged 18-29 identify as transgender and 3% identify as nonbinary, a far greater number than in other age cohorts.

These reports are likely underestimates. The Human Rights Campaign estimates that some 2 million Americans of all ages identify as transgender.

The Pew survey is weighted to be representative but still has limitations, said the organization. The Williams analysis, based on responses to two CDC surveys – the Behavioral Risk Factor Surveillance System (BRFSS) and Youth Risk Behavior Survey (YRBS) – is incomplete, say researchers, because not every state collects data on gender identity.
 

Transgender identities more predominant among youth

The Williams researchers report that 18.3% of those who identified as trans were 13- to 17-year-olds; that age group makes up 7.6% of the United States population 13 and older.

And despite not having firm figures from earlier reports, they comment: “Youth ages 13-17 comprise a larger share of the transgender-identified population than we previously estimated, currently comprising about 18% of the transgender-identified population in the United State, up from 10% previously.”  

About one-quarter of those who identified as trans in the new 2022 report were aged 18-24; that age cohort accounts for 11% of Americans.

The number of older Americans who identify as trans are more proportionate to their representation in the population, according to Williams. Overall, about half of those who said they were trans were aged 25-64; that group accounts for 62% of the overall American population. Some 10% of trans-identified individuals were over age 65. About 20% of Americans are 65 or older, said the researchers.

The Pew research – based on the responses of 10,188 individuals surveyed in May – also found growing numbers of young people who identify as trans. “The share of U.S. adults who are transgender is particularly high among adults younger than 25,” reported Pew in a blog post.

In the 18- to 25-year-old group, 3.1% identified as a trans man or a trans woman, compared with just 0.5% of those ages 25-29.  

That compares to 0.3% of those aged 30-49 and 0.2% of those older than 50.
 

Racial and state-by-state variation

Similar percentages of youth aged 13-17 of all races and ethnicities in the Williams study report they are transgender, ranging from 1% of those who are Asian, to 1.3% of White youth, 1.4% of Black youth, 1.8% of American Indian or Alaska Native, and 1.8% of Latinx youth. The institute reported that 1.5% of biracial and multiracial youth identified as transgender.

The researchers said, however, that “transgender-identified youth and adults appear more likely to report being Latinx and less likely to report being White, as compared to the United States population.”

Transgender individuals live in every state, with the greatest percentage of both youth and adults in the Northeast and West, and lesser percentages in the Midwest and South, reported the Williams Institute.

Williams estimates as many as 3% of 13- to 17-year-olds in New York identify as trans, while just 0.6% of that age group in Wyoming is transgender. A total of 2%-2.5% of those aged 13-17 are transgender in Hawaii, New Mexico, Maryland, and Washington, D.C.

Among the states with higher percentages of trans-identifying 18- to 24-year-olds: Arizona (1.9%), Arkansas (3.6%), Colorado (2%), Delaware (2.4%), Illinois (1.9%), Maryland (1.9%), North Carolina (2.5%), Oklahoma (2.5%), Massachusetts (2.3%), Rhode Island (2.1%), and Washington (2%).

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

Two new studies point to an ever-increasing number of young people in the United States who identify as transgender and nonbinary, with the figures doubling among 18- to 24-year-olds in one institute’s research – from 0.66% of the population in 2016 to 1.3% (398,900) in 2022.

In addition, 1.4% (300,100) of 13- to 17-year-olds identify as trans or nonbinary, according to the report from that group, the Williams Institute at the University of California, Los Angeles, School of Law.

Williams, which conducts independent research on sexual orientation and gender identity law and public policy, did not contain data on 13- to 17-year-olds in its 2016 study, so the growth in that group over the past 5+ years is not as well documented.

Overall, some 1.6 million Americans older than age 13 now identify as transgender, reported the Williams researchers.

And in a new Pew Research Center survey, 2% of adults aged 18-29 identify as transgender and 3% identify as nonbinary, a far greater number than in other age cohorts.

These reports are likely underestimates. The Human Rights Campaign estimates that some 2 million Americans of all ages identify as transgender.

The Pew survey is weighted to be representative but still has limitations, said the organization. The Williams analysis, based on responses to two CDC surveys – the Behavioral Risk Factor Surveillance System (BRFSS) and Youth Risk Behavior Survey (YRBS) – is incomplete, say researchers, because not every state collects data on gender identity.
 

Transgender identities more predominant among youth

The Williams researchers report that 18.3% of those who identified as trans were 13- to 17-year-olds; that age group makes up 7.6% of the United States population 13 and older.

And despite not having firm figures from earlier reports, they comment: “Youth ages 13-17 comprise a larger share of the transgender-identified population than we previously estimated, currently comprising about 18% of the transgender-identified population in the United State, up from 10% previously.”  

About one-quarter of those who identified as trans in the new 2022 report were aged 18-24; that age cohort accounts for 11% of Americans.

The number of older Americans who identify as trans are more proportionate to their representation in the population, according to Williams. Overall, about half of those who said they were trans were aged 25-64; that group accounts for 62% of the overall American population. Some 10% of trans-identified individuals were over age 65. About 20% of Americans are 65 or older, said the researchers.

The Pew research – based on the responses of 10,188 individuals surveyed in May – also found growing numbers of young people who identify as trans. “The share of U.S. adults who are transgender is particularly high among adults younger than 25,” reported Pew in a blog post.

In the 18- to 25-year-old group, 3.1% identified as a trans man or a trans woman, compared with just 0.5% of those ages 25-29.  

That compares to 0.3% of those aged 30-49 and 0.2% of those older than 50.
 

Racial and state-by-state variation

Similar percentages of youth aged 13-17 of all races and ethnicities in the Williams study report they are transgender, ranging from 1% of those who are Asian, to 1.3% of White youth, 1.4% of Black youth, 1.8% of American Indian or Alaska Native, and 1.8% of Latinx youth. The institute reported that 1.5% of biracial and multiracial youth identified as transgender.

The researchers said, however, that “transgender-identified youth and adults appear more likely to report being Latinx and less likely to report being White, as compared to the United States population.”

Transgender individuals live in every state, with the greatest percentage of both youth and adults in the Northeast and West, and lesser percentages in the Midwest and South, reported the Williams Institute.

Williams estimates as many as 3% of 13- to 17-year-olds in New York identify as trans, while just 0.6% of that age group in Wyoming is transgender. A total of 2%-2.5% of those aged 13-17 are transgender in Hawaii, New Mexico, Maryland, and Washington, D.C.

Among the states with higher percentages of trans-identifying 18- to 24-year-olds: Arizona (1.9%), Arkansas (3.6%), Colorado (2%), Delaware (2.4%), Illinois (1.9%), Maryland (1.9%), North Carolina (2.5%), Oklahoma (2.5%), Massachusetts (2.3%), Rhode Island (2.1%), and Washington (2%).

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

Two new studies point to an ever-increasing number of young people in the United States who identify as transgender and nonbinary, with the figures doubling among 18- to 24-year-olds in one institute’s research – from 0.66% of the population in 2016 to 1.3% (398,900) in 2022.

In addition, 1.4% (300,100) of 13- to 17-year-olds identify as trans or nonbinary, according to the report from that group, the Williams Institute at the University of California, Los Angeles, School of Law.

Williams, which conducts independent research on sexual orientation and gender identity law and public policy, did not contain data on 13- to 17-year-olds in its 2016 study, so the growth in that group over the past 5+ years is not as well documented.

Overall, some 1.6 million Americans older than age 13 now identify as transgender, reported the Williams researchers.

And in a new Pew Research Center survey, 2% of adults aged 18-29 identify as transgender and 3% identify as nonbinary, a far greater number than in other age cohorts.

These reports are likely underestimates. The Human Rights Campaign estimates that some 2 million Americans of all ages identify as transgender.

The Pew survey is weighted to be representative but still has limitations, said the organization. The Williams analysis, based on responses to two CDC surveys – the Behavioral Risk Factor Surveillance System (BRFSS) and Youth Risk Behavior Survey (YRBS) – is incomplete, say researchers, because not every state collects data on gender identity.
 

Transgender identities more predominant among youth

The Williams researchers report that 18.3% of those who identified as trans were 13- to 17-year-olds; that age group makes up 7.6% of the United States population 13 and older.

And despite not having firm figures from earlier reports, they comment: “Youth ages 13-17 comprise a larger share of the transgender-identified population than we previously estimated, currently comprising about 18% of the transgender-identified population in the United State, up from 10% previously.”  

About one-quarter of those who identified as trans in the new 2022 report were aged 18-24; that age cohort accounts for 11% of Americans.

The number of older Americans who identify as trans are more proportionate to their representation in the population, according to Williams. Overall, about half of those who said they were trans were aged 25-64; that group accounts for 62% of the overall American population. Some 10% of trans-identified individuals were over age 65. About 20% of Americans are 65 or older, said the researchers.

The Pew research – based on the responses of 10,188 individuals surveyed in May – also found growing numbers of young people who identify as trans. “The share of U.S. adults who are transgender is particularly high among adults younger than 25,” reported Pew in a blog post.

In the 18- to 25-year-old group, 3.1% identified as a trans man or a trans woman, compared with just 0.5% of those ages 25-29.  

That compares to 0.3% of those aged 30-49 and 0.2% of those older than 50.
 

Racial and state-by-state variation

Similar percentages of youth aged 13-17 of all races and ethnicities in the Williams study report they are transgender, ranging from 1% of those who are Asian, to 1.3% of White youth, 1.4% of Black youth, 1.8% of American Indian or Alaska Native, and 1.8% of Latinx youth. The institute reported that 1.5% of biracial and multiracial youth identified as transgender.

The researchers said, however, that “transgender-identified youth and adults appear more likely to report being Latinx and less likely to report being White, as compared to the United States population.”

Transgender individuals live in every state, with the greatest percentage of both youth and adults in the Northeast and West, and lesser percentages in the Midwest and South, reported the Williams Institute.

Williams estimates as many as 3% of 13- to 17-year-olds in New York identify as trans, while just 0.6% of that age group in Wyoming is transgender. A total of 2%-2.5% of those aged 13-17 are transgender in Hawaii, New Mexico, Maryland, and Washington, D.C.

Among the states with higher percentages of trans-identifying 18- to 24-year-olds: Arizona (1.9%), Arkansas (3.6%), Colorado (2%), Delaware (2.4%), Illinois (1.9%), Maryland (1.9%), North Carolina (2.5%), Oklahoma (2.5%), Massachusetts (2.3%), Rhode Island (2.1%), and Washington (2%).

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

Contrary to previous analyses, women without a history of psychiatric illness who take combined hormonal contraceptives do not have an increased risk for attempted suicide but may have a reduced risk with extended use, new research suggests.

In a study of more than 800 women younger than age 50 who attempted suicide and more than 3,000 age-matched peers, results showed those who took hormonal contraceptives had a 27% reduced risk for attempted suicide.

areeya_ann/Thinkstock

Further analysis showed this was confined to women without a history of psychiatric illness and the reduction in risk rose to 43% among those who took combined hormonal contraceptives rather than progestin-only versions.

The protective effect against attempted suicide increased further to 46% if ethinyl estradiol (EE)–containing preparations were used. Moreover, the beneficial effect of contraceptive use increased over time.

The main message is the “current use of hormonal contraceptives is not associated with an increased risk of attempted suicide in our population,” study presenter Elena Toffol, MD, PhD, department of public health, University of Helsinki, told meeting attendees at the European Psychiatric Association 2022 Congress.
 

Age range differences

Dr. Toffol said there could be “several reasons” why the results are different from those in previous studies, including that the researchers included a “larger age range.” She noted it is known that “older women have a lower rate of attempted suicide and use different types of contraceptives.”

Dr. Toffol said in an interview that, although it’s “hard to estimate any causality” because this is an observational study, it is “tempting to speculate, and it is plausible, that hormones partly play a role with some, but not all, women being more sensitive to hormonal influences.”

However, the results “may also reflect life choices or a protective life status; for example, more stable relationships or more conscious and health-focused behaviors,” she said.

“It may also be that the underlying characteristics of women who are prescribed or opt for certain types of contraceptives are somehow related to their suicidal risk,” she added.

In 2019, the global age-standardized suicide rate was 9.0 per 100,000, which translates into more than 700,000 deaths every year, Dr. Toffol noted.

However, she emphasized the World Health Organization has calculated that, for every adult who dies by suicide, more than 20 people attempt suicide. In addition, data from the U.S. Centers for Disease Control and Prevention indicate that attempted suicides are three times more common among young women than in men.

“What are the reasons for this gender gap?” Dr. Toffol asked during her presentation.

“It is known that the major risk factor for suicidal behavior is a psychiatric disorder, and in particular depression and mood disorders. And depression and mood disorders are more common in women than in men,” she said.

However, there is also “growing interest into the role of biological factors” in the risk for suicide, including hormones and hormonal contraception. Some studies have also suggested that there is an increased risk for depression and “both completed and attempted suicide” after starting hormonal contraception.

Dr. Toffol added that about 70% of European women use some form of contraception and, among Finnish women, 40% choose a hormonal contraceptive.
 

Nested analysis

The researchers conducted a nested case-control analysis combining 2017 national prescription data on 587,823 women aged 15-49 years with information from general and primary healthcare registers for the years 2018 to 2019.

They were able to identify 818 cases of attempted suicide among the women. These were matched 4:1 with 3,272 age-matched healthy women who acted as the control group. Use of hormonal contraceptives in the previous 180 days was determined for the whole cohort.

Among users of hormonal contraceptives, there were 344 attempted suicides in 2017, at an incidence rate of 0.59 per 1,000 person-years. This compared with 474 attempted suicides among nonusers, at an incidence rate of 0.81 per 1000 person-years.

Kaplan-Meier analysis showed there was a significant difference in rates for attempted suicide among hormonal contraceptive users versus nonusers, at an incidence rate ratio of 0.73 (P < .0001) – and the difference increased over time.

In addition, the incidence of attempted suicide decreased with increasing age, with the highest incidence rate in women aged 15-19 years (1.62 per 1,000 person-years).

Conditional logistic regression analysis that controlled for education, marital status, chronic disease, recent psychiatric hospitalization, and current use of psychotropic medication showed hormonal contraceptive use was not linked to an increased risk of attempted suicide overall, at an odds ratio of 0.79 (95% confidence interval, 0.56-1.11).

However, when they looked specifically at women without a history of psychiatric illness, the association became significant, at an OR of 0.73 for attempted suicide among hormonal contraceptive users (95% CI, 0.58-0.91), while the relationship remained nonsignificant in women with a history of psychiatric disorders.

Further analysis suggested the significant association was confined to women taking combined hormonal contraceptives, at an OR of 0.57 for suicide attempt versus nonusers (95% CI, 0.44-0.75), and those use EE-containing preparations (OR, 0.54; 95% CI, 0.40-0.73).

There was a suggestion in the data that hormonal contraceptives containing desogestrel or drospirenone alongside EE may offer the greatest reduction in attempted suicide risk, but that did not survive multivariate analysis.

Dr. Toffol also noted that they were not able to capture data on use of intrauterine devices in their analysis.

“There is a growing number of municipalities in Finland that are providing free-of-charge contraception to young women” that is often an intrauterine device, she said. The researchers hope to include these women in a future analysis.
 

‘Age matters’

Commenting on the findings, Alexis C. Edwards, PhD, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said the current study’s findings “made a lot of sense.” Dr. Edwards wasn’t involved with this study but conducted a previous study of 216,702 Swedish women aged 15-22 years that showed use of combination or progestin-only oral contraceptives was associated with an increased risk for suicidal behavior.

She agreed with Dr. Toffol that the “much larger age range” in the new study may have played a role in showing the opposite result.

“The trajectory that we saw if we had been able to continue following the women for longer – which we couldn’t, due to limitations of the registries – [was that] using hormonal contraceptives was going to end up being protective, so I do think that it matters what age you’re looking at,” she said.

Dr. Edwards noted the takeaway from both studies “is that, even if there is a slight increase in risk from using hormonal contraceptives, it’s short lived and it’s probably specific to young women, which is important.”

She suggested the hormonal benefit from extended contraceptive use could come from the regulation of mood, as it offers a “more stable hormonal course than what their body might be putting them through in the absence of using the pill.”

Overall, it is “really lovely to see very well-executed studies on this, providing more empirical evidence on this question, because it is something that’s relevant to anyone who’s potentially going to be using hormonal contraception,” Dr. Edwards said.
 

Clinical implications?

Andrea Fiorillo, MD, PhD, department of psychiatry, University of Campania “Luigi Vanvitelli,” Naples, Italy, said in a press release that the “striking” findings of the current study need “careful evaluation.”

They also need to be replicated in “different cohorts of women and controlled for the impact of several psychosocial stressors, such as economic upheavals, social insecurity, and uncertainty due to the COVID pandemic,” said Dr. Fiorillo, who was not involved with the research.

Nevertheless, she believes the “clinical implications of the study are obvious and may help to destigmatize the use of hormonal contraceptives.”

The study was funded by the Jane and Aatos Erkko Foundation, the Avohoidon Tsukimis äätiö (Foundation for Primary Care Research), the Yrj ö Jahnsson Foundation, and the Finnish Cultural Foundation. No relevant financial relationships were reported.

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

Contrary to previous analyses, women without a history of psychiatric illness who take combined hormonal contraceptives do not have an increased risk for attempted suicide but may have a reduced risk with extended use, new research suggests.

In a study of more than 800 women younger than age 50 who attempted suicide and more than 3,000 age-matched peers, results showed those who took hormonal contraceptives had a 27% reduced risk for attempted suicide.

areeya_ann/Thinkstock

Further analysis showed this was confined to women without a history of psychiatric illness and the reduction in risk rose to 43% among those who took combined hormonal contraceptives rather than progestin-only versions.

The protective effect against attempted suicide increased further to 46% if ethinyl estradiol (EE)–containing preparations were used. Moreover, the beneficial effect of contraceptive use increased over time.

The main message is the “current use of hormonal contraceptives is not associated with an increased risk of attempted suicide in our population,” study presenter Elena Toffol, MD, PhD, department of public health, University of Helsinki, told meeting attendees at the European Psychiatric Association 2022 Congress.
 

Age range differences

Dr. Toffol said there could be “several reasons” why the results are different from those in previous studies, including that the researchers included a “larger age range.” She noted it is known that “older women have a lower rate of attempted suicide and use different types of contraceptives.”

Dr. Toffol said in an interview that, although it’s “hard to estimate any causality” because this is an observational study, it is “tempting to speculate, and it is plausible, that hormones partly play a role with some, but not all, women being more sensitive to hormonal influences.”

However, the results “may also reflect life choices or a protective life status; for example, more stable relationships or more conscious and health-focused behaviors,” she said.

“It may also be that the underlying characteristics of women who are prescribed or opt for certain types of contraceptives are somehow related to their suicidal risk,” she added.

In 2019, the global age-standardized suicide rate was 9.0 per 100,000, which translates into more than 700,000 deaths every year, Dr. Toffol noted.

However, she emphasized the World Health Organization has calculated that, for every adult who dies by suicide, more than 20 people attempt suicide. In addition, data from the U.S. Centers for Disease Control and Prevention indicate that attempted suicides are three times more common among young women than in men.

“What are the reasons for this gender gap?” Dr. Toffol asked during her presentation.

“It is known that the major risk factor for suicidal behavior is a psychiatric disorder, and in particular depression and mood disorders. And depression and mood disorders are more common in women than in men,” she said.

However, there is also “growing interest into the role of biological factors” in the risk for suicide, including hormones and hormonal contraception. Some studies have also suggested that there is an increased risk for depression and “both completed and attempted suicide” after starting hormonal contraception.

Dr. Toffol added that about 70% of European women use some form of contraception and, among Finnish women, 40% choose a hormonal contraceptive.
 

Nested analysis

The researchers conducted a nested case-control analysis combining 2017 national prescription data on 587,823 women aged 15-49 years with information from general and primary healthcare registers for the years 2018 to 2019.

They were able to identify 818 cases of attempted suicide among the women. These were matched 4:1 with 3,272 age-matched healthy women who acted as the control group. Use of hormonal contraceptives in the previous 180 days was determined for the whole cohort.

Among users of hormonal contraceptives, there were 344 attempted suicides in 2017, at an incidence rate of 0.59 per 1,000 person-years. This compared with 474 attempted suicides among nonusers, at an incidence rate of 0.81 per 1000 person-years.

Kaplan-Meier analysis showed there was a significant difference in rates for attempted suicide among hormonal contraceptive users versus nonusers, at an incidence rate ratio of 0.73 (P < .0001) – and the difference increased over time.

In addition, the incidence of attempted suicide decreased with increasing age, with the highest incidence rate in women aged 15-19 years (1.62 per 1,000 person-years).

Conditional logistic regression analysis that controlled for education, marital status, chronic disease, recent psychiatric hospitalization, and current use of psychotropic medication showed hormonal contraceptive use was not linked to an increased risk of attempted suicide overall, at an odds ratio of 0.79 (95% confidence interval, 0.56-1.11).

However, when they looked specifically at women without a history of psychiatric illness, the association became significant, at an OR of 0.73 for attempted suicide among hormonal contraceptive users (95% CI, 0.58-0.91), while the relationship remained nonsignificant in women with a history of psychiatric disorders.

Further analysis suggested the significant association was confined to women taking combined hormonal contraceptives, at an OR of 0.57 for suicide attempt versus nonusers (95% CI, 0.44-0.75), and those use EE-containing preparations (OR, 0.54; 95% CI, 0.40-0.73).

There was a suggestion in the data that hormonal contraceptives containing desogestrel or drospirenone alongside EE may offer the greatest reduction in attempted suicide risk, but that did not survive multivariate analysis.

Dr. Toffol also noted that they were not able to capture data on use of intrauterine devices in their analysis.

“There is a growing number of municipalities in Finland that are providing free-of-charge contraception to young women” that is often an intrauterine device, she said. The researchers hope to include these women in a future analysis.
 

‘Age matters’

Commenting on the findings, Alexis C. Edwards, PhD, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said the current study’s findings “made a lot of sense.” Dr. Edwards wasn’t involved with this study but conducted a previous study of 216,702 Swedish women aged 15-22 years that showed use of combination or progestin-only oral contraceptives was associated with an increased risk for suicidal behavior.

She agreed with Dr. Toffol that the “much larger age range” in the new study may have played a role in showing the opposite result.

“The trajectory that we saw if we had been able to continue following the women for longer – which we couldn’t, due to limitations of the registries – [was that] using hormonal contraceptives was going to end up being protective, so I do think that it matters what age you’re looking at,” she said.

Dr. Edwards noted the takeaway from both studies “is that, even if there is a slight increase in risk from using hormonal contraceptives, it’s short lived and it’s probably specific to young women, which is important.”

She suggested the hormonal benefit from extended contraceptive use could come from the regulation of mood, as it offers a “more stable hormonal course than what their body might be putting them through in the absence of using the pill.”

Overall, it is “really lovely to see very well-executed studies on this, providing more empirical evidence on this question, because it is something that’s relevant to anyone who’s potentially going to be using hormonal contraception,” Dr. Edwards said.
 

Clinical implications?

Andrea Fiorillo, MD, PhD, department of psychiatry, University of Campania “Luigi Vanvitelli,” Naples, Italy, said in a press release that the “striking” findings of the current study need “careful evaluation.”

They also need to be replicated in “different cohorts of women and controlled for the impact of several psychosocial stressors, such as economic upheavals, social insecurity, and uncertainty due to the COVID pandemic,” said Dr. Fiorillo, who was not involved with the research.

Nevertheless, she believes the “clinical implications of the study are obvious and may help to destigmatize the use of hormonal contraceptives.”

The study was funded by the Jane and Aatos Erkko Foundation, the Avohoidon Tsukimis äätiö (Foundation for Primary Care Research), the Yrj ö Jahnsson Foundation, and the Finnish Cultural Foundation. No relevant financial relationships were reported.

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

Contrary to previous analyses, women without a history of psychiatric illness who take combined hormonal contraceptives do not have an increased risk for attempted suicide but may have a reduced risk with extended use, new research suggests.

In a study of more than 800 women younger than age 50 who attempted suicide and more than 3,000 age-matched peers, results showed those who took hormonal contraceptives had a 27% reduced risk for attempted suicide.

areeya_ann/Thinkstock

Further analysis showed this was confined to women without a history of psychiatric illness and the reduction in risk rose to 43% among those who took combined hormonal contraceptives rather than progestin-only versions.

The protective effect against attempted suicide increased further to 46% if ethinyl estradiol (EE)–containing preparations were used. Moreover, the beneficial effect of contraceptive use increased over time.

The main message is the “current use of hormonal contraceptives is not associated with an increased risk of attempted suicide in our population,” study presenter Elena Toffol, MD, PhD, department of public health, University of Helsinki, told meeting attendees at the European Psychiatric Association 2022 Congress.
 

Age range differences

Dr. Toffol said there could be “several reasons” why the results are different from those in previous studies, including that the researchers included a “larger age range.” She noted it is known that “older women have a lower rate of attempted suicide and use different types of contraceptives.”

Dr. Toffol said in an interview that, although it’s “hard to estimate any causality” because this is an observational study, it is “tempting to speculate, and it is plausible, that hormones partly play a role with some, but not all, women being more sensitive to hormonal influences.”

However, the results “may also reflect life choices or a protective life status; for example, more stable relationships or more conscious and health-focused behaviors,” she said.

“It may also be that the underlying characteristics of women who are prescribed or opt for certain types of contraceptives are somehow related to their suicidal risk,” she added.

In 2019, the global age-standardized suicide rate was 9.0 per 100,000, which translates into more than 700,000 deaths every year, Dr. Toffol noted.

However, she emphasized the World Health Organization has calculated that, for every adult who dies by suicide, more than 20 people attempt suicide. In addition, data from the U.S. Centers for Disease Control and Prevention indicate that attempted suicides are three times more common among young women than in men.

“What are the reasons for this gender gap?” Dr. Toffol asked during her presentation.

“It is known that the major risk factor for suicidal behavior is a psychiatric disorder, and in particular depression and mood disorders. And depression and mood disorders are more common in women than in men,” she said.

However, there is also “growing interest into the role of biological factors” in the risk for suicide, including hormones and hormonal contraception. Some studies have also suggested that there is an increased risk for depression and “both completed and attempted suicide” after starting hormonal contraception.

Dr. Toffol added that about 70% of European women use some form of contraception and, among Finnish women, 40% choose a hormonal contraceptive.
 

Nested analysis

The researchers conducted a nested case-control analysis combining 2017 national prescription data on 587,823 women aged 15-49 years with information from general and primary healthcare registers for the years 2018 to 2019.

They were able to identify 818 cases of attempted suicide among the women. These were matched 4:1 with 3,272 age-matched healthy women who acted as the control group. Use of hormonal contraceptives in the previous 180 days was determined for the whole cohort.

Among users of hormonal contraceptives, there were 344 attempted suicides in 2017, at an incidence rate of 0.59 per 1,000 person-years. This compared with 474 attempted suicides among nonusers, at an incidence rate of 0.81 per 1000 person-years.

Kaplan-Meier analysis showed there was a significant difference in rates for attempted suicide among hormonal contraceptive users versus nonusers, at an incidence rate ratio of 0.73 (P < .0001) – and the difference increased over time.

In addition, the incidence of attempted suicide decreased with increasing age, with the highest incidence rate in women aged 15-19 years (1.62 per 1,000 person-years).

Conditional logistic regression analysis that controlled for education, marital status, chronic disease, recent psychiatric hospitalization, and current use of psychotropic medication showed hormonal contraceptive use was not linked to an increased risk of attempted suicide overall, at an odds ratio of 0.79 (95% confidence interval, 0.56-1.11).

However, when they looked specifically at women without a history of psychiatric illness, the association became significant, at an OR of 0.73 for attempted suicide among hormonal contraceptive users (95% CI, 0.58-0.91), while the relationship remained nonsignificant in women with a history of psychiatric disorders.

Further analysis suggested the significant association was confined to women taking combined hormonal contraceptives, at an OR of 0.57 for suicide attempt versus nonusers (95% CI, 0.44-0.75), and those use EE-containing preparations (OR, 0.54; 95% CI, 0.40-0.73).

There was a suggestion in the data that hormonal contraceptives containing desogestrel or drospirenone alongside EE may offer the greatest reduction in attempted suicide risk, but that did not survive multivariate analysis.

Dr. Toffol also noted that they were not able to capture data on use of intrauterine devices in their analysis.

“There is a growing number of municipalities in Finland that are providing free-of-charge contraception to young women” that is often an intrauterine device, she said. The researchers hope to include these women in a future analysis.
 

‘Age matters’

Commenting on the findings, Alexis C. Edwards, PhD, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said the current study’s findings “made a lot of sense.” Dr. Edwards wasn’t involved with this study but conducted a previous study of 216,702 Swedish women aged 15-22 years that showed use of combination or progestin-only oral contraceptives was associated with an increased risk for suicidal behavior.

She agreed with Dr. Toffol that the “much larger age range” in the new study may have played a role in showing the opposite result.

“The trajectory that we saw if we had been able to continue following the women for longer – which we couldn’t, due to limitations of the registries – [was that] using hormonal contraceptives was going to end up being protective, so I do think that it matters what age you’re looking at,” she said.

Dr. Edwards noted the takeaway from both studies “is that, even if there is a slight increase in risk from using hormonal contraceptives, it’s short lived and it’s probably specific to young women, which is important.”

She suggested the hormonal benefit from extended contraceptive use could come from the regulation of mood, as it offers a “more stable hormonal course than what their body might be putting them through in the absence of using the pill.”

Overall, it is “really lovely to see very well-executed studies on this, providing more empirical evidence on this question, because it is something that’s relevant to anyone who’s potentially going to be using hormonal contraception,” Dr. Edwards said.
 

Clinical implications?

Andrea Fiorillo, MD, PhD, department of psychiatry, University of Campania “Luigi Vanvitelli,” Naples, Italy, said in a press release that the “striking” findings of the current study need “careful evaluation.”

They also need to be replicated in “different cohorts of women and controlled for the impact of several psychosocial stressors, such as economic upheavals, social insecurity, and uncertainty due to the COVID pandemic,” said Dr. Fiorillo, who was not involved with the research.

Nevertheless, she believes the “clinical implications of the study are obvious and may help to destigmatize the use of hormonal contraceptives.”

The study was funded by the Jane and Aatos Erkko Foundation, the Avohoidon Tsukimis äätiö (Foundation for Primary Care Research), the Yrj ö Jahnsson Foundation, and the Finnish Cultural Foundation. No relevant financial relationships were reported.

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

The underlying cause of David Bennett’s death on March 8, two months after he received the heart of a genetically altered pig, remains unknown and is only slightly less mysterious for what can likely be ruled out, suggests a progress report on the case from the director of the cardiac xenotransplantation program where the pioneering surgery took place.

Mr. Bennett died in “diastolic heart failure,” reported Muhammad M. Mohiuddin, MBBS, University of Maryland School of Medicine, Baltimore, “but the mechanism is still under investigation.”

University of Maryland Medical Center

Rocky clinical course

Early characterizations of the patient’s death focused more on his diminished, end-stage clinical condition at the time of the surgery than on immune rejection or other direct effects of the xenograft or on the first-of-its-kind procedure itself.

The 57-year-old Mr. Bennett had presented to the University of Maryland team with nonischemic cardiomyopathy, on multiple inotropes, and requiring an intra-aortic balloon pump, Dr. Mohiuddin said in his ATC presentation. The patient had suffered multiple arrests and resuscitations, and by the time of surgery had been hospitalized for almost 2 months, including 40 days on veno-arterial extracorporeal membrane oxygenation (ECMO).

The transplant procedure itself went as planned until removal of the aortic cross clamp, which triggered a type-A aortic dissection. “We put a graft in the ascending aorta and a stent in the descending aorta. Even after 2 days, we found the dissection extending to the renal artery, so we had to go back and also put a stent in the renal artery,” Dr. Mohiuddin said.

Mr. Bennett also underwent two exploratory laparotomies in the first 10 days after transplantation, after CT imaging revealed signs of possible bowel inflammation and ischemia.

Further, he had to fight back a series of infections that led to major changes to his experimental drug regimen, which included immunosuppressants methylprednisolone and mycophenolate mofetil (MMF), the investigational anti-CD40 antibody KPL-404 (Kiniksa Pharmaceuticals), and the anti-inflammatories etanercept (Enbrel) and tocilizumab (Actemra).

One episode of sepsis, in particular, forced temporary withdrawal of MMF and a reduction in methylprednisolone dosage. It’s unknown whether the 30-day MMF suspension played a role in Mr. Bennett’s ultimate clinical deterioration and death, but it’s “highly possible,” Dr. Mohiuddin said in an interview.

Realistically, Mr. Bennett’s death was likely “multifactorial,” Dr. Mohiuddin said. He was in such poor clinical condition going into the procedure, and afterward confronted so many clinical challenges, that “it’s very difficult to say that one thing caused it.”

That hasn’t lessened speculation that the patient’s heart failed secondary to immunologic rejection or PCMV infection, either in Mr. Bennett or the donor pig.
 

A role for PCMV?

Weeks after Mr. Bennett’s death, as previously reported, his surgeon announced at a public forum that PCMV had been identified in the transplanted heart and in tissues of the donor pig. Mr. Bennett’s circulation showed traces of the viral DNA but not of the virus itself.

The presence of PCMV in transplanted porcine hearts is a well-recognized potential hazard in animal models but is considered avoidable with proper screening. In Mr. Bennett’s case, preoperative screening of the pig donor missed signs of the virus.  

Still, PCMV could potentially have contributed to Mr. Bennett’s death, acknowledged Bartley P. Griffith, MD, University of Maryland School of Medicine, who had announced the PCMV finding in an AST-sponsored April 20 webcast.

Preclinical evidence does suggest that PCMV can harm a xenograft organ, observed David H. Sachs, MD, Columbia University Medical Center, New York, from the audience during the comment period after Dr. Mohiuddin’s presentation.

“Each species has a CMV, and they’re quite species-specific,” observed the renowned surgeon and xenotransplantation immunologist. “We showed almost 10 years ago that if PCMV was in a pig kidney, it led to a much shortened survival of the pig kidney in a baboon. There was never any evidence, however, that the CMV infected the baboon or any baboon cells.”

Dr. Sachs asked Dr. Mohiuddin for confirmation that Mr. Bennett displayed no more than DNAemia, circulating cell-free PCMV DNA presumably shed from the porcine heart, but no sign of the virus itself outside of the heart’s porcine cells.

Cell-free DNA had shown up in Mr. Bennett’s circulation about 20 days after the surgery, with concentrations rising until at least day 50. Post-hoc polymerase chain reaction (PCR) testing disclosed PCMV only in the pig’s spleen and porcine cells of the transplanted heart, Dr. Mohiuddin noted.

“We have not found any evidence that the patient was infected by PCMV,” nor was there evidence of any disease related to PCMV, Dr. Mohiuddin replied.

Nor of ongoing rejection

Mr. Bennett’s new heart passed a critical test in the first post-implantation hours by avoiding acute rejection, a potentially disastrous outcome that three of the pig’s 10 gene edits had been designed to prevent.

Although chronic immune rejection was always a concern despite Mr. Bennett’s novel immunosuppressant regimen, myocardial biopsy on postoperative days 34, 50, and 56 and necropsy showed “no signs of typical xenograft rejection,” Dr. Mohiuddin said at the ATC presentation. But “there’s a chance of atypical rejection which we were not accustomed to.”

By day 50, his diastolic function showed echocardiographic signs of deterioration, and “we started seeing interstitial edema with some extravasation of red blood cells, which we thought would resolve over a period of time,” he said. Eventually, however, “we saw that turn into fibroblasts and scar tissue.”

Mr. Bennett once again went on veno-arterial ECMO but died 10 days later. Once they had seen histologic evidence of fibrosis, Dr. Mohiuddin told this news organization, the team believed the myocardial injury was irreversible. “That was the reason we gave up on recovery.”

Mr. Bennett’s xenotransplantation journey has taught the field a lot, he said. “By no means was this a failure; we consider this a huge success. You can do all the experiments in animal models, but you won’t find out the true mechanism of rejection unless you do these kinds of human experiments.”
 

Looking ahead to clinical trials

Research involving humans is always subject to vagaries of human nature, including degree of adherence to prescribed therapy and – in xenotransplantation – precautions in place to mitigate any risks to public health. Such risks theoretically include transfer of porcine viruses or other pathogens to the patient and subsequent release into the general population.

Looking ahead to the possibility of clinical trials after this successful xenotransplantation experience, transplant nephrologist and epidemiologist Peter P. Reese, MD, PhD, University of Pennsylvania, Philadelphia, raised the potentially controversial issue in discussion following Dr. Mohiuddin’s presentation.

It’s known that Mr. Bennett had been repeatedly turned down for a conventional allograft transplant primarily because of his history of treatment noncompliance. Should such a record, Dr. Reese asked, be a relative contraindication to enrollment in any future xenotransplantation trials? Or does the field need a standardized gauge of a patient’s readiness, once discharged, to adhere not only to all medications – including those that fight infection – but also with rules established for public safety, such as routine contact reporting?

“It makes me wonder about choosing a noncompliant patient for these trials,” Dr. Reese said. “If we discharge a patient from the hospital who is at risk for a zoonotic infection that could spread if they basically refuse to cooperate with us or with public health authorities, it really could have negative consequences for the reputation of the field.”

Dr. Mohiuddin agreed such concerns are valid. Mr. Bennett “and all his immediate contacts” signed consent forms acknowledging their willingness to be followed should he be discharged. Mr. Bennett himself “signed a consent to inform us if he has any other intimate contact with someone,” he said in an interview.

“But those are only on paper.” Had Mr. Bennett survived to be discharged, Dr. Mohuiddin said, “no one knows how he would have behaved.”

Dr. Mohiuddin said the research staff had prepared to monitor Mr. Bennett at his home if that’s what it took. “We were ready to follow him as long as we could. There was a surveillance plan in place.”

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

The underlying cause of David Bennett’s death on March 8, two months after he received the heart of a genetically altered pig, remains unknown and is only slightly less mysterious for what can likely be ruled out, suggests a progress report on the case from the director of the cardiac xenotransplantation program where the pioneering surgery took place.

Mr. Bennett died in “diastolic heart failure,” reported Muhammad M. Mohiuddin, MBBS, University of Maryland School of Medicine, Baltimore, “but the mechanism is still under investigation.”

University of Maryland Medical Center

Rocky clinical course

Early characterizations of the patient’s death focused more on his diminished, end-stage clinical condition at the time of the surgery than on immune rejection or other direct effects of the xenograft or on the first-of-its-kind procedure itself.

The 57-year-old Mr. Bennett had presented to the University of Maryland team with nonischemic cardiomyopathy, on multiple inotropes, and requiring an intra-aortic balloon pump, Dr. Mohiuddin said in his ATC presentation. The patient had suffered multiple arrests and resuscitations, and by the time of surgery had been hospitalized for almost 2 months, including 40 days on veno-arterial extracorporeal membrane oxygenation (ECMO).

The transplant procedure itself went as planned until removal of the aortic cross clamp, which triggered a type-A aortic dissection. “We put a graft in the ascending aorta and a stent in the descending aorta. Even after 2 days, we found the dissection extending to the renal artery, so we had to go back and also put a stent in the renal artery,” Dr. Mohiuddin said.

Mr. Bennett also underwent two exploratory laparotomies in the first 10 days after transplantation, after CT imaging revealed signs of possible bowel inflammation and ischemia.

Further, he had to fight back a series of infections that led to major changes to his experimental drug regimen, which included immunosuppressants methylprednisolone and mycophenolate mofetil (MMF), the investigational anti-CD40 antibody KPL-404 (Kiniksa Pharmaceuticals), and the anti-inflammatories etanercept (Enbrel) and tocilizumab (Actemra).

One episode of sepsis, in particular, forced temporary withdrawal of MMF and a reduction in methylprednisolone dosage. It’s unknown whether the 30-day MMF suspension played a role in Mr. Bennett’s ultimate clinical deterioration and death, but it’s “highly possible,” Dr. Mohiuddin said in an interview.

Realistically, Mr. Bennett’s death was likely “multifactorial,” Dr. Mohiuddin said. He was in such poor clinical condition going into the procedure, and afterward confronted so many clinical challenges, that “it’s very difficult to say that one thing caused it.”

That hasn’t lessened speculation that the patient’s heart failed secondary to immunologic rejection or PCMV infection, either in Mr. Bennett or the donor pig.
 

A role for PCMV?

Weeks after Mr. Bennett’s death, as previously reported, his surgeon announced at a public forum that PCMV had been identified in the transplanted heart and in tissues of the donor pig. Mr. Bennett’s circulation showed traces of the viral DNA but not of the virus itself.

The presence of PCMV in transplanted porcine hearts is a well-recognized potential hazard in animal models but is considered avoidable with proper screening. In Mr. Bennett’s case, preoperative screening of the pig donor missed signs of the virus.  

Still, PCMV could potentially have contributed to Mr. Bennett’s death, acknowledged Bartley P. Griffith, MD, University of Maryland School of Medicine, who had announced the PCMV finding in an AST-sponsored April 20 webcast.

Preclinical evidence does suggest that PCMV can harm a xenograft organ, observed David H. Sachs, MD, Columbia University Medical Center, New York, from the audience during the comment period after Dr. Mohiuddin’s presentation.

“Each species has a CMV, and they’re quite species-specific,” observed the renowned surgeon and xenotransplantation immunologist. “We showed almost 10 years ago that if PCMV was in a pig kidney, it led to a much shortened survival of the pig kidney in a baboon. There was never any evidence, however, that the CMV infected the baboon or any baboon cells.”

Dr. Sachs asked Dr. Mohiuddin for confirmation that Mr. Bennett displayed no more than DNAemia, circulating cell-free PCMV DNA presumably shed from the porcine heart, but no sign of the virus itself outside of the heart’s porcine cells.

Cell-free DNA had shown up in Mr. Bennett’s circulation about 20 days after the surgery, with concentrations rising until at least day 50. Post-hoc polymerase chain reaction (PCR) testing disclosed PCMV only in the pig’s spleen and porcine cells of the transplanted heart, Dr. Mohiuddin noted.

“We have not found any evidence that the patient was infected by PCMV,” nor was there evidence of any disease related to PCMV, Dr. Mohiuddin replied.

Nor of ongoing rejection

Mr. Bennett’s new heart passed a critical test in the first post-implantation hours by avoiding acute rejection, a potentially disastrous outcome that three of the pig’s 10 gene edits had been designed to prevent.

Although chronic immune rejection was always a concern despite Mr. Bennett’s novel immunosuppressant regimen, myocardial biopsy on postoperative days 34, 50, and 56 and necropsy showed “no signs of typical xenograft rejection,” Dr. Mohiuddin said at the ATC presentation. But “there’s a chance of atypical rejection which we were not accustomed to.”

By day 50, his diastolic function showed echocardiographic signs of deterioration, and “we started seeing interstitial edema with some extravasation of red blood cells, which we thought would resolve over a period of time,” he said. Eventually, however, “we saw that turn into fibroblasts and scar tissue.”

Mr. Bennett once again went on veno-arterial ECMO but died 10 days later. Once they had seen histologic evidence of fibrosis, Dr. Mohiuddin told this news organization, the team believed the myocardial injury was irreversible. “That was the reason we gave up on recovery.”

Mr. Bennett’s xenotransplantation journey has taught the field a lot, he said. “By no means was this a failure; we consider this a huge success. You can do all the experiments in animal models, but you won’t find out the true mechanism of rejection unless you do these kinds of human experiments.”
 

Looking ahead to clinical trials

Research involving humans is always subject to vagaries of human nature, including degree of adherence to prescribed therapy and – in xenotransplantation – precautions in place to mitigate any risks to public health. Such risks theoretically include transfer of porcine viruses or other pathogens to the patient and subsequent release into the general population.

Looking ahead to the possibility of clinical trials after this successful xenotransplantation experience, transplant nephrologist and epidemiologist Peter P. Reese, MD, PhD, University of Pennsylvania, Philadelphia, raised the potentially controversial issue in discussion following Dr. Mohiuddin’s presentation.

It’s known that Mr. Bennett had been repeatedly turned down for a conventional allograft transplant primarily because of his history of treatment noncompliance. Should such a record, Dr. Reese asked, be a relative contraindication to enrollment in any future xenotransplantation trials? Or does the field need a standardized gauge of a patient’s readiness, once discharged, to adhere not only to all medications – including those that fight infection – but also with rules established for public safety, such as routine contact reporting?

“It makes me wonder about choosing a noncompliant patient for these trials,” Dr. Reese said. “If we discharge a patient from the hospital who is at risk for a zoonotic infection that could spread if they basically refuse to cooperate with us or with public health authorities, it really could have negative consequences for the reputation of the field.”

Dr. Mohiuddin agreed such concerns are valid. Mr. Bennett “and all his immediate contacts” signed consent forms acknowledging their willingness to be followed should he be discharged. Mr. Bennett himself “signed a consent to inform us if he has any other intimate contact with someone,” he said in an interview.

“But those are only on paper.” Had Mr. Bennett survived to be discharged, Dr. Mohuiddin said, “no one knows how he would have behaved.”

Dr. Mohiuddin said the research staff had prepared to monitor Mr. Bennett at his home if that’s what it took. “We were ready to follow him as long as we could. There was a surveillance plan in place.”

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

The underlying cause of David Bennett’s death on March 8, two months after he received the heart of a genetically altered pig, remains unknown and is only slightly less mysterious for what can likely be ruled out, suggests a progress report on the case from the director of the cardiac xenotransplantation program where the pioneering surgery took place.

Mr. Bennett died in “diastolic heart failure,” reported Muhammad M. Mohiuddin, MBBS, University of Maryland School of Medicine, Baltimore, “but the mechanism is still under investigation.”

University of Maryland Medical Center

Rocky clinical course

Early characterizations of the patient’s death focused more on his diminished, end-stage clinical condition at the time of the surgery than on immune rejection or other direct effects of the xenograft or on the first-of-its-kind procedure itself.

The 57-year-old Mr. Bennett had presented to the University of Maryland team with nonischemic cardiomyopathy, on multiple inotropes, and requiring an intra-aortic balloon pump, Dr. Mohiuddin said in his ATC presentation. The patient had suffered multiple arrests and resuscitations, and by the time of surgery had been hospitalized for almost 2 months, including 40 days on veno-arterial extracorporeal membrane oxygenation (ECMO).

The transplant procedure itself went as planned until removal of the aortic cross clamp, which triggered a type-A aortic dissection. “We put a graft in the ascending aorta and a stent in the descending aorta. Even after 2 days, we found the dissection extending to the renal artery, so we had to go back and also put a stent in the renal artery,” Dr. Mohiuddin said.

Mr. Bennett also underwent two exploratory laparotomies in the first 10 days after transplantation, after CT imaging revealed signs of possible bowel inflammation and ischemia.

Further, he had to fight back a series of infections that led to major changes to his experimental drug regimen, which included immunosuppressants methylprednisolone and mycophenolate mofetil (MMF), the investigational anti-CD40 antibody KPL-404 (Kiniksa Pharmaceuticals), and the anti-inflammatories etanercept (Enbrel) and tocilizumab (Actemra).

One episode of sepsis, in particular, forced temporary withdrawal of MMF and a reduction in methylprednisolone dosage. It’s unknown whether the 30-day MMF suspension played a role in Mr. Bennett’s ultimate clinical deterioration and death, but it’s “highly possible,” Dr. Mohiuddin said in an interview.

Realistically, Mr. Bennett’s death was likely “multifactorial,” Dr. Mohiuddin said. He was in such poor clinical condition going into the procedure, and afterward confronted so many clinical challenges, that “it’s very difficult to say that one thing caused it.”

That hasn’t lessened speculation that the patient’s heart failed secondary to immunologic rejection or PCMV infection, either in Mr. Bennett or the donor pig.
 

A role for PCMV?

Weeks after Mr. Bennett’s death, as previously reported, his surgeon announced at a public forum that PCMV had been identified in the transplanted heart and in tissues of the donor pig. Mr. Bennett’s circulation showed traces of the viral DNA but not of the virus itself.

The presence of PCMV in transplanted porcine hearts is a well-recognized potential hazard in animal models but is considered avoidable with proper screening. In Mr. Bennett’s case, preoperative screening of the pig donor missed signs of the virus.  

Still, PCMV could potentially have contributed to Mr. Bennett’s death, acknowledged Bartley P. Griffith, MD, University of Maryland School of Medicine, who had announced the PCMV finding in an AST-sponsored April 20 webcast.

Preclinical evidence does suggest that PCMV can harm a xenograft organ, observed David H. Sachs, MD, Columbia University Medical Center, New York, from the audience during the comment period after Dr. Mohiuddin’s presentation.

“Each species has a CMV, and they’re quite species-specific,” observed the renowned surgeon and xenotransplantation immunologist. “We showed almost 10 years ago that if PCMV was in a pig kidney, it led to a much shortened survival of the pig kidney in a baboon. There was never any evidence, however, that the CMV infected the baboon or any baboon cells.”

Dr. Sachs asked Dr. Mohiuddin for confirmation that Mr. Bennett displayed no more than DNAemia, circulating cell-free PCMV DNA presumably shed from the porcine heart, but no sign of the virus itself outside of the heart’s porcine cells.

Cell-free DNA had shown up in Mr. Bennett’s circulation about 20 days after the surgery, with concentrations rising until at least day 50. Post-hoc polymerase chain reaction (PCR) testing disclosed PCMV only in the pig’s spleen and porcine cells of the transplanted heart, Dr. Mohiuddin noted.

“We have not found any evidence that the patient was infected by PCMV,” nor was there evidence of any disease related to PCMV, Dr. Mohiuddin replied.

Nor of ongoing rejection

Mr. Bennett’s new heart passed a critical test in the first post-implantation hours by avoiding acute rejection, a potentially disastrous outcome that three of the pig’s 10 gene edits had been designed to prevent.

Although chronic immune rejection was always a concern despite Mr. Bennett’s novel immunosuppressant regimen, myocardial biopsy on postoperative days 34, 50, and 56 and necropsy showed “no signs of typical xenograft rejection,” Dr. Mohiuddin said at the ATC presentation. But “there’s a chance of atypical rejection which we were not accustomed to.”

By day 50, his diastolic function showed echocardiographic signs of deterioration, and “we started seeing interstitial edema with some extravasation of red blood cells, which we thought would resolve over a period of time,” he said. Eventually, however, “we saw that turn into fibroblasts and scar tissue.”

Mr. Bennett once again went on veno-arterial ECMO but died 10 days later. Once they had seen histologic evidence of fibrosis, Dr. Mohiuddin told this news organization, the team believed the myocardial injury was irreversible. “That was the reason we gave up on recovery.”

Mr. Bennett’s xenotransplantation journey has taught the field a lot, he said. “By no means was this a failure; we consider this a huge success. You can do all the experiments in animal models, but you won’t find out the true mechanism of rejection unless you do these kinds of human experiments.”
 

Looking ahead to clinical trials

Research involving humans is always subject to vagaries of human nature, including degree of adherence to prescribed therapy and – in xenotransplantation – precautions in place to mitigate any risks to public health. Such risks theoretically include transfer of porcine viruses or other pathogens to the patient and subsequent release into the general population.

Looking ahead to the possibility of clinical trials after this successful xenotransplantation experience, transplant nephrologist and epidemiologist Peter P. Reese, MD, PhD, University of Pennsylvania, Philadelphia, raised the potentially controversial issue in discussion following Dr. Mohiuddin’s presentation.

It’s known that Mr. Bennett had been repeatedly turned down for a conventional allograft transplant primarily because of his history of treatment noncompliance. Should such a record, Dr. Reese asked, be a relative contraindication to enrollment in any future xenotransplantation trials? Or does the field need a standardized gauge of a patient’s readiness, once discharged, to adhere not only to all medications – including those that fight infection – but also with rules established for public safety, such as routine contact reporting?

“It makes me wonder about choosing a noncompliant patient for these trials,” Dr. Reese said. “If we discharge a patient from the hospital who is at risk for a zoonotic infection that could spread if they basically refuse to cooperate with us or with public health authorities, it really could have negative consequences for the reputation of the field.”

Dr. Mohiuddin agreed such concerns are valid. Mr. Bennett “and all his immediate contacts” signed consent forms acknowledging their willingness to be followed should he be discharged. Mr. Bennett himself “signed a consent to inform us if he has any other intimate contact with someone,” he said in an interview.

“But those are only on paper.” Had Mr. Bennett survived to be discharged, Dr. Mohuiddin said, “no one knows how he would have behaved.”

Dr. Mohiuddin said the research staff had prepared to monitor Mr. Bennett at his home if that’s what it took. “We were ready to follow him as long as we could. There was a surveillance plan in place.”

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

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.

Prediabetes is not only a predictor of diabetes and the cardiovascular complications that ensue, but it is also a risk factor by itself for myocardial infarction, according to data drawn from almost 1.8 million patients hospitalized for MI.

“Our study serves as a wakeup call for clinicians and patients to shift the focus to preventing prediabetes, and not just diabetes, said Geethika Thota, MD, at the annual meeting of the Endocrine Society.

There are plenty of data suggesting that prediabetes places patients on a trajectory toward cardiovascular disease. In a meta-analysis of 129 studies published 2 years ago, prediabetes was not only associated with a statistically significant 16% increase in coronary heart disease, but also a 13% increased risk of all-cause mortality relative to those with normoglycemia.
 

Data drawn from 1.8 million patients

In this study, 1,794,149 weighted patient hospitalizations for MI were drawn from the National Inpatient Sample database. Excluding patients who eventually developed diabetes, roughly 1% of these patients had a history of prediabetes in the past, according to a search of ICD-10 codes.

Before adjustment for other risk factors, prediabetes was linked to a greater than 40% increased odds of MI (odds ratio, 1.41; P < .01). After adjustment for a large array of known MI risk factors – including prior history of MI, dyslipidemia, hypertension, nicotine dependence, and obesity – prediabetes remained an independent risk factor, corresponding with a 25% increased risk of MI (OR, 1.25; P < .01).

A history of prediabetes was also an independent risk factor for percutaneous intervention and coronary artery bypass grafting, with increased risk of 45% and 95%, respectively.

As a retrospective study looking at prediabetes as a risk factor in those who already had a MI, it is possible that not all patients with prediabetes were properly coded, but Dr. Thota said that was unlikely to have been an issue of sufficient magnitude to have affected the major conclusions.
 

Relevance seen for community care

Although the study was drawn from hospitalized patients, its relevance is for the community setting, where screening and intervention for prediabetes has the potential to alter the risk, according to Dr. Thota.

Most clinicians are likely aware of the value of screening for prediabetes, which was defined in this study as a hemoglobin A1c of 5.7%-6.4%, but Dr. Thota suggested that many might not fully grasp the full scope of goals. Early detection and prevention will prevent diabetes and, by extension, cardiovascular disease, but her data suggest that control of prediabetes with lower cardiovascular risk by a more direct route.

“Despite mounting evidence, many clinicians are unaware that prediabetes is also a major risk factor for atherosclerotic cardiovascular disease,” said Dr. Thota, an internal medicine resident at Saint Peter’s University Hospital, New Brunswick, N.J.

Like diabetes, the prevalence of prediabetes is growing rapidly, according to data from the Centers for Disease Control that Dr. Thota cited. In 2020, the Centers for Disease Control and Prevention estimated that 38% of the adult population have prediabetes. By 2030, one model predicts a further 25% growth.

Screening for hyperglycemia is part of routine patient evaluations at Dr. Thota’s center. In an interview, she said that once a diagnosis of prediabetes is entered in the electronic medical record, the history is carried forward so that changes in status are continually monitored.
 

Worsening prediabetes should be addressed

“Prediabetes is not treated with medication, at least initially,” Dr. Thota explained. Rather, patients are educated about important lifestyle changes, such as diet and physical activity, that can reverse the diagnosis. However, patients who remain on a path of worsening hyperglycemia are candidates for more intensive lifestyle intervention and might be considered selectively for metformin.

“Early recognition of prediabetes through screening is important,” Dr. Thota emphasized. The benefit for preventing patients from progressing to diabetes is well recognized, but these data provide the basis for incentivizing lifestyle changes in patients with prediabetes by telling them that it can reduce their risk for MI.

These data have an important message, but they are not surprising, according to Deepak L. Bhatt, MD, executive director, interventional cardiovascular programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston.

“In fact, in daily practice we see a substantial percentage of patients with MI who have prediabetes that had not been previously recognized or formally diagnosed,” Dr. Bhatt said in an interview.

“Identifying these patients – preferably prior to coming in with cardiovascular complications – is important both to reduce cardiovascular risk but also to try and prevent progression at diabetes,” he added.

Dr. Bhatt went on to say that this large analysis, confirming that prediabetes is independently associated with MI, should prompt clinicians to screen patients rigorously for this condition.

“At a minimum, such patients would be candidates for intensive lifestyle modification aimed at weight loss and treatment of frequent coexistent conditions, such as hypertension and dyslipidemia,” Dr. Bhatt said.

Dr. Thota reports no potential conflicts of interest. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, many of which make products relevant to the management of diabetes and cardiovascular disease.

Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.

In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.

The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.

But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.

“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”

The EMERGE study was published online  in JAMA Cardiology.

In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.

In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.

But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).

The EMERGE trial was conducted in this latter group without ST elevation.

For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.

The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).

There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.

Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.

However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.

Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.

“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.

In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.

“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.

Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.

“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.

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

Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.

In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.

The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.

But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.

“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”

The EMERGE study was published online  in JAMA Cardiology.

In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.

In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.

But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).

The EMERGE trial was conducted in this latter group without ST elevation.

For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.

The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).

There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.

Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.

However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.

Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.

“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.

In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.

“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.

Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.

“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.

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

Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.

In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.

The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.

But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.

“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”

The EMERGE study was published online  in JAMA Cardiology.

In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.

In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.

But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).

The EMERGE trial was conducted in this latter group without ST elevation.

For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.

The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).

There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.

Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.

However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.

Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.

“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.

In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.

“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.

Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.

“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.

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

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

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

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

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

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

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