Stress-related disorders may put individuals at increased risk of neurodegenerative conditions such as Alzheimer’s disease later in life, conceivably through a cerebrovascular pathway, according to authors of a large population- and sibling-matched cohort study. Individuals with posttraumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, or other stress reactions had an 80% increased risk of vascular neurodegenerative diseases, according to results of the study, which was based on Swedish population registry data.

Risk of primary neurodegenerative diseases was increased as well in people with those conditions, but only by 31%, according to lead author Huan Song, MD, PhD, of Sichuan University in Chengdu, China.

“The stronger association observed for neurodegenerative diseases with a vascular component, compared with primary neurodegenerative diseases, suggested a considerable role of a possible cerebrovascular pathway,” Dr. Song and coauthors said in a report on the study appearing in JAMA Neurology.

While some previous studies have linked stress-related disorders to neurodegenerative diseases – particularly PTSD and dementia – this is believed to be the first, according to the investigators, to comprehensively evaluate all stress-related disorders in relation to the most common neurodegenerative conditions.

When considering neurodegenerative conditions separately, they found a statistically significant association between stress-related disorders and Alzheimer’s disease, while linkages with Parkinson’s disease and amyotrophic lateral sclerosis (ALS) were “comparable” but associations did not reach statistical significance, according to investigators.

Based on these findings, stress reduction should be recommended in addition to daily physical activity, mental activity, and a heart-healthy diet to potentially reduce risk of onset or worsening of cognitive decline, according to Chun Lim, MD, PhD, medical director of the cognitive neurology unit at Beth Israel Deaconess Medical Center in Boston.

“We don’t really have great evidence that anything slows down the progression of Alzheimer’s disease, but there are some suggestions that for people who lead heart-healthy lifestyles or adhere to a Mediterranean diet, fewer develop cognitive issues over 5-10 years,” Dr. Lim said in an interview. “Because of this paper, stress reduction may be one additional way to hopefully help these patients these patients that have or are concerned about cognitive issues.”

The population-matched cohort of the study included 61,748 individuals with stress-related disorders and 595,335 matched individuals without those disorders, while the sibling-matched cohort included 44,839 individuals with those disorders and 78,482 without. The median age at the start of follow-up was 47 years and 39.4% of those with stress-related disorders were male.

During follow-up, the incidence of neurodegenerative diseases per 1,000 person-years was 1.50 for individuals with stress-related disorders, versus 0.82 for those without stress-related disorders, according to the report. Risk of primary neurodegenerative diseases was increased among those with stress-related disorders, compared with those without, with a hazard ratio of 1.31 (95% confidence interval, 1.15-1.48). However, the risk of vascular neurodegenerative diseases was significantly higher, with an HR of 1.80 (95% CI, 1.40-2.31; P = .03 for the difference between hazard ratios).

Results of the matched sibling cohort supported results of the population-matched cohort, though the elevated risk of vascular neurodegenerative diseases among those with stress-related disorders was “slightly lower” than in the population-based cohort, Dr. Song and coauthors wrote in their report.

Beyond causing a host of hormonal and medical issues, stress can lead to sleep issues that may have long-term consequences, Dr. Lim noted in the interview.

“There’s some thought that quality sleep is important for memory formation, and if people are under a fair amount of stress and they have really poor sleep, that can also lead to cognitive issues including memory impairment,” he said.

“There are these multiple avenues that may be contributing to the accelerated development of these kinds of issues,” he added, “so I think this paper suggests more ways to counsel the patients about using lifestyle modifications to slow down the development of these cognitive impairments.”

Funding for the study came from the Swedish Research Council, Icelandic Research Fund; ,European Research Council the Karolinska Institutet, Swedish Research Council, and West China Hospital. Authors of the study provided disclosures related to those organizations as well as Shire/Takeda and Evolan.

SOURCE: Song H et al. JAMA Neurol. 2020 Mar 9. doi: 10.1001/jamaneurol.2020.0117.

Stress-related disorders may put individuals at increased risk of neurodegenerative conditions such as Alzheimer’s disease later in life, conceivably through a cerebrovascular pathway, according to authors of a large population- and sibling-matched cohort study. Individuals with posttraumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, or other stress reactions had an 80% increased risk of vascular neurodegenerative diseases, according to results of the study, which was based on Swedish population registry data.

Risk of primary neurodegenerative diseases was increased as well in people with those conditions, but only by 31%, according to lead author Huan Song, MD, PhD, of Sichuan University in Chengdu, China.

“The stronger association observed for neurodegenerative diseases with a vascular component, compared with primary neurodegenerative diseases, suggested a considerable role of a possible cerebrovascular pathway,” Dr. Song and coauthors said in a report on the study appearing in JAMA Neurology.

While some previous studies have linked stress-related disorders to neurodegenerative diseases – particularly PTSD and dementia – this is believed to be the first, according to the investigators, to comprehensively evaluate all stress-related disorders in relation to the most common neurodegenerative conditions.

When considering neurodegenerative conditions separately, they found a statistically significant association between stress-related disorders and Alzheimer’s disease, while linkages with Parkinson’s disease and amyotrophic lateral sclerosis (ALS) were “comparable” but associations did not reach statistical significance, according to investigators.

Based on these findings, stress reduction should be recommended in addition to daily physical activity, mental activity, and a heart-healthy diet to potentially reduce risk of onset or worsening of cognitive decline, according to Chun Lim, MD, PhD, medical director of the cognitive neurology unit at Beth Israel Deaconess Medical Center in Boston.

“We don’t really have great evidence that anything slows down the progression of Alzheimer’s disease, but there are some suggestions that for people who lead heart-healthy lifestyles or adhere to a Mediterranean diet, fewer develop cognitive issues over 5-10 years,” Dr. Lim said in an interview. “Because of this paper, stress reduction may be one additional way to hopefully help these patients these patients that have or are concerned about cognitive issues.”

The population-matched cohort of the study included 61,748 individuals with stress-related disorders and 595,335 matched individuals without those disorders, while the sibling-matched cohort included 44,839 individuals with those disorders and 78,482 without. The median age at the start of follow-up was 47 years and 39.4% of those with stress-related disorders were male.

During follow-up, the incidence of neurodegenerative diseases per 1,000 person-years was 1.50 for individuals with stress-related disorders, versus 0.82 for those without stress-related disorders, according to the report. Risk of primary neurodegenerative diseases was increased among those with stress-related disorders, compared with those without, with a hazard ratio of 1.31 (95% confidence interval, 1.15-1.48). However, the risk of vascular neurodegenerative diseases was significantly higher, with an HR of 1.80 (95% CI, 1.40-2.31; P = .03 for the difference between hazard ratios).

Results of the matched sibling cohort supported results of the population-matched cohort, though the elevated risk of vascular neurodegenerative diseases among those with stress-related disorders was “slightly lower” than in the population-based cohort, Dr. Song and coauthors wrote in their report.

Beyond causing a host of hormonal and medical issues, stress can lead to sleep issues that may have long-term consequences, Dr. Lim noted in the interview.

“There’s some thought that quality sleep is important for memory formation, and if people are under a fair amount of stress and they have really poor sleep, that can also lead to cognitive issues including memory impairment,” he said.

“There are these multiple avenues that may be contributing to the accelerated development of these kinds of issues,” he added, “so I think this paper suggests more ways to counsel the patients about using lifestyle modifications to slow down the development of these cognitive impairments.”

Funding for the study came from the Swedish Research Council, Icelandic Research Fund; ,European Research Council the Karolinska Institutet, Swedish Research Council, and West China Hospital. Authors of the study provided disclosures related to those organizations as well as Shire/Takeda and Evolan.

SOURCE: Song H et al. JAMA Neurol. 2020 Mar 9. doi: 10.1001/jamaneurol.2020.0117.

Stress-related disorders may put individuals at increased risk of neurodegenerative conditions such as Alzheimer’s disease later in life, conceivably through a cerebrovascular pathway, according to authors of a large population- and sibling-matched cohort study. Individuals with posttraumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, or other stress reactions had an 80% increased risk of vascular neurodegenerative diseases, according to results of the study, which was based on Swedish population registry data.

Risk of primary neurodegenerative diseases was increased as well in people with those conditions, but only by 31%, according to lead author Huan Song, MD, PhD, of Sichuan University in Chengdu, China.

“The stronger association observed for neurodegenerative diseases with a vascular component, compared with primary neurodegenerative diseases, suggested a considerable role of a possible cerebrovascular pathway,” Dr. Song and coauthors said in a report on the study appearing in JAMA Neurology.

While some previous studies have linked stress-related disorders to neurodegenerative diseases – particularly PTSD and dementia – this is believed to be the first, according to the investigators, to comprehensively evaluate all stress-related disorders in relation to the most common neurodegenerative conditions.

When considering neurodegenerative conditions separately, they found a statistically significant association between stress-related disorders and Alzheimer’s disease, while linkages with Parkinson’s disease and amyotrophic lateral sclerosis (ALS) were “comparable” but associations did not reach statistical significance, according to investigators.

Based on these findings, stress reduction should be recommended in addition to daily physical activity, mental activity, and a heart-healthy diet to potentially reduce risk of onset or worsening of cognitive decline, according to Chun Lim, MD, PhD, medical director of the cognitive neurology unit at Beth Israel Deaconess Medical Center in Boston.

“We don’t really have great evidence that anything slows down the progression of Alzheimer’s disease, but there are some suggestions that for people who lead heart-healthy lifestyles or adhere to a Mediterranean diet, fewer develop cognitive issues over 5-10 years,” Dr. Lim said in an interview. “Because of this paper, stress reduction may be one additional way to hopefully help these patients these patients that have or are concerned about cognitive issues.”

The population-matched cohort of the study included 61,748 individuals with stress-related disorders and 595,335 matched individuals without those disorders, while the sibling-matched cohort included 44,839 individuals with those disorders and 78,482 without. The median age at the start of follow-up was 47 years and 39.4% of those with stress-related disorders were male.

During follow-up, the incidence of neurodegenerative diseases per 1,000 person-years was 1.50 for individuals with stress-related disorders, versus 0.82 for those without stress-related disorders, according to the report. Risk of primary neurodegenerative diseases was increased among those with stress-related disorders, compared with those without, with a hazard ratio of 1.31 (95% confidence interval, 1.15-1.48). However, the risk of vascular neurodegenerative diseases was significantly higher, with an HR of 1.80 (95% CI, 1.40-2.31; P = .03 for the difference between hazard ratios).

Results of the matched sibling cohort supported results of the population-matched cohort, though the elevated risk of vascular neurodegenerative diseases among those with stress-related disorders was “slightly lower” than in the population-based cohort, Dr. Song and coauthors wrote in their report.

Beyond causing a host of hormonal and medical issues, stress can lead to sleep issues that may have long-term consequences, Dr. Lim noted in the interview.

“There’s some thought that quality sleep is important for memory formation, and if people are under a fair amount of stress and they have really poor sleep, that can also lead to cognitive issues including memory impairment,” he said.

“There are these multiple avenues that may be contributing to the accelerated development of these kinds of issues,” he added, “so I think this paper suggests more ways to counsel the patients about using lifestyle modifications to slow down the development of these cognitive impairments.”

Funding for the study came from the Swedish Research Council, Icelandic Research Fund; ,European Research Council the Karolinska Institutet, Swedish Research Council, and West China Hospital. Authors of the study provided disclosures related to those organizations as well as Shire/Takeda and Evolan.

SOURCE: Song H et al. JAMA Neurol. 2020 Mar 9. doi: 10.1001/jamaneurol.2020.0117.

U.S. high school students who identify as gay, lesbian, bisexual, or questioning – “sexual minorities” – faced twice the risk of physical or sexual assault in the past year compared with their heterosexual peers, according to findings reported in a research letter.

Sexual-minority females were particularly more likely to experience physical violence while sexual-minority boys had a fourfold increased risk of sexual violence.

“The results of our study suggest the existence of a crisis of violence against sexual minority adolescents,” Theodore L. Caputi, MPH, of Harvard Medical School, Boston, and colleagues reported in JAMA Pediatrics. “Given the substantial physical and emotional consequences of violence for those subjected to it and the large existing health disparities among sexual minority adolescents, addressing both physical and sexual violence against sexual minority adolescents should become a public health priority.”

Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery in the Mount Sinai Health System, New York, said he was not surprised by the findings because adolescents who may feel more vulnerable relative to their peers are likely to be more of a target. They may not have the supports they need, he said, which will affect their resiliency and their ability to push back.

“These patients are at ages where their parents might be among their supporters,” Dr. Safer said in an interview. “People in their circle may not be aware of their circumstances.”

He emphasized the need for physicians to ensure their offices are safe places for sexual-minority youth to talk to adolescent patients about their gender and sexual identity as well as any history of victimization, and to involve parents in being an ally of their child.

The researchers analyzed data from the nationally representative 2015 and 2017 National Youth Risk Behavior Surveys administered to public and private high school students in grades 9-12 by the Centers for Disease Control and Prevention. The 28,811 total respondents represented a 60% response rate both years.

After indicating their sex as male or female and their sexual orientation, respondents reported whether, in the past year, they had experienced a physical fight at school, a physical fight anywhere, or physical violence from a romantic partner. They also reported whether they had been sexually assaulted in the past year by a romantic partner or ever been forced to have intercourse. The 2017 survey included an additional question about sexual assault by anyone in the past year.

Most youth (87%) identified themselves as heterosexual while 2% were gay/lesbian, 7% were bisexual, and 4% were unsure. Sexual minorities reported a higher prevalence of all forms of violence and assault, compared with their heterosexual counterparts. Although risk of a physical fight in the past year differed by a small amount (28% of sexual-minority youth vs. 22% of heterosexual youth), the gap was considerably greater for risk of physical violence by a romantic partner (12% of sexual-minority youth vs. 5% of heterosexual youth).

More than three times as many sexual-minority adolescents (18%) as heterosexual adolescents (5%) said they had ever been forced to have intercourse, and a similarly high proportion of sexual-minority students (21%) had been sexually assaulted in the past year, compared with heterosexual students (8%). After accounting for survey year, sex, age, race/ethnicity, English language proficiency, and grade level, youth who identified as anything other than heterosexual were about twice as likely as their heterosexual counterparts to have experienced physical or sexual violence, including physical violence by a romantic partner (adjusted risk ratio, 1.97) or sexual assault by anyone (aRR, 2.10), in the past year. The risk of physical violence by a romantic partner or sexual assault by anyone was even greater for bisexual youth (aRR, 2.22 and aRR, 2.36, respectively).

The increased likelihood of physical violence and sexual violence differed by sex. Girls who identified as lesbian, bisexual, or questioning were more likely than heterosexual girls to have been in a fight at school or anywhere else (aRR, 1.91 and aRR, 1.74, respectively). Boys who were gay, bisexual, or questioning, meanwhile, were over four times more likely than heterosexual boys to have had forced intercourse or any kind of sexual assault (aRR, 4.70 and aRR, 4.64, respectively).

These findings point to the need for physicians to be “specifically talking to youth about gender identity and sexual orientation. Validating what kids are feeling is important,” Dr. Safer said in an interview.

Key to that process is making sure the physician’s office feels like a safe place for LGBTQ youth to have these kinds of conversations. “Most primary care and pediatric and adolescent care practices are not feeling well equipped to take care of these kids and are not necessarily serving as a good resource for these kids,” Dr. Safer said.

It’s also important for physicians to ask youth about potential violence or abuse they have experienced, including depression and sequelae from lack of support, for which gender- and sexual-minority youth are at greater risk, he said. Finally, doctors need to engage parents in the conversation.

“As a medical professional, you need to be asking the questions and really be out there as an ally, especially for pediatric and adolescent patients, and you need to be helping the parents of your patients be allies too,” Dr. Safer said.

The study was limited by having a binary question only about respondent’s sex and no data collection about transgender youth. The study’s cross-sectional design also precludes the ability to claim causation about any of the associations.

The research was funded by the Marshall Aid Commemoration Commission, Stanford (Calif.) University, and the National Institutes of Health. The authors had no disclosures.

SOURCE: Caputi TL et al. JAMA Pediatr. 2019 Mar 9. doi: 10.1001/jamapediatrics.2019.6291.

U.S. high school students who identify as gay, lesbian, bisexual, or questioning – “sexual minorities” – faced twice the risk of physical or sexual assault in the past year compared with their heterosexual peers, according to findings reported in a research letter.

Sexual-minority females were particularly more likely to experience physical violence while sexual-minority boys had a fourfold increased risk of sexual violence.

“The results of our study suggest the existence of a crisis of violence against sexual minority adolescents,” Theodore L. Caputi, MPH, of Harvard Medical School, Boston, and colleagues reported in JAMA Pediatrics. “Given the substantial physical and emotional consequences of violence for those subjected to it and the large existing health disparities among sexual minority adolescents, addressing both physical and sexual violence against sexual minority adolescents should become a public health priority.”

Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery in the Mount Sinai Health System, New York, said he was not surprised by the findings because adolescents who may feel more vulnerable relative to their peers are likely to be more of a target. They may not have the supports they need, he said, which will affect their resiliency and their ability to push back.

“These patients are at ages where their parents might be among their supporters,” Dr. Safer said in an interview. “People in their circle may not be aware of their circumstances.”

He emphasized the need for physicians to ensure their offices are safe places for sexual-minority youth to talk to adolescent patients about their gender and sexual identity as well as any history of victimization, and to involve parents in being an ally of their child.

The researchers analyzed data from the nationally representative 2015 and 2017 National Youth Risk Behavior Surveys administered to public and private high school students in grades 9-12 by the Centers for Disease Control and Prevention. The 28,811 total respondents represented a 60% response rate both years.

After indicating their sex as male or female and their sexual orientation, respondents reported whether, in the past year, they had experienced a physical fight at school, a physical fight anywhere, or physical violence from a romantic partner. They also reported whether they had been sexually assaulted in the past year by a romantic partner or ever been forced to have intercourse. The 2017 survey included an additional question about sexual assault by anyone in the past year.

Most youth (87%) identified themselves as heterosexual while 2% were gay/lesbian, 7% were bisexual, and 4% were unsure. Sexual minorities reported a higher prevalence of all forms of violence and assault, compared with their heterosexual counterparts. Although risk of a physical fight in the past year differed by a small amount (28% of sexual-minority youth vs. 22% of heterosexual youth), the gap was considerably greater for risk of physical violence by a romantic partner (12% of sexual-minority youth vs. 5% of heterosexual youth).

More than three times as many sexual-minority adolescents (18%) as heterosexual adolescents (5%) said they had ever been forced to have intercourse, and a similarly high proportion of sexual-minority students (21%) had been sexually assaulted in the past year, compared with heterosexual students (8%). After accounting for survey year, sex, age, race/ethnicity, English language proficiency, and grade level, youth who identified as anything other than heterosexual were about twice as likely as their heterosexual counterparts to have experienced physical or sexual violence, including physical violence by a romantic partner (adjusted risk ratio, 1.97) or sexual assault by anyone (aRR, 2.10), in the past year. The risk of physical violence by a romantic partner or sexual assault by anyone was even greater for bisexual youth (aRR, 2.22 and aRR, 2.36, respectively).

The increased likelihood of physical violence and sexual violence differed by sex. Girls who identified as lesbian, bisexual, or questioning were more likely than heterosexual girls to have been in a fight at school or anywhere else (aRR, 1.91 and aRR, 1.74, respectively). Boys who were gay, bisexual, or questioning, meanwhile, were over four times more likely than heterosexual boys to have had forced intercourse or any kind of sexual assault (aRR, 4.70 and aRR, 4.64, respectively).

These findings point to the need for physicians to be “specifically talking to youth about gender identity and sexual orientation. Validating what kids are feeling is important,” Dr. Safer said in an interview.

Key to that process is making sure the physician’s office feels like a safe place for LGBTQ youth to have these kinds of conversations. “Most primary care and pediatric and adolescent care practices are not feeling well equipped to take care of these kids and are not necessarily serving as a good resource for these kids,” Dr. Safer said.

It’s also important for physicians to ask youth about potential violence or abuse they have experienced, including depression and sequelae from lack of support, for which gender- and sexual-minority youth are at greater risk, he said. Finally, doctors need to engage parents in the conversation.

“As a medical professional, you need to be asking the questions and really be out there as an ally, especially for pediatric and adolescent patients, and you need to be helping the parents of your patients be allies too,” Dr. Safer said.

The study was limited by having a binary question only about respondent’s sex and no data collection about transgender youth. The study’s cross-sectional design also precludes the ability to claim causation about any of the associations.

The research was funded by the Marshall Aid Commemoration Commission, Stanford (Calif.) University, and the National Institutes of Health. The authors had no disclosures.

SOURCE: Caputi TL et al. JAMA Pediatr. 2019 Mar 9. doi: 10.1001/jamapediatrics.2019.6291.

U.S. high school students who identify as gay, lesbian, bisexual, or questioning – “sexual minorities” – faced twice the risk of physical or sexual assault in the past year compared with their heterosexual peers, according to findings reported in a research letter.

Sexual-minority females were particularly more likely to experience physical violence while sexual-minority boys had a fourfold increased risk of sexual violence.

“The results of our study suggest the existence of a crisis of violence against sexual minority adolescents,” Theodore L. Caputi, MPH, of Harvard Medical School, Boston, and colleagues reported in JAMA Pediatrics. “Given the substantial physical and emotional consequences of violence for those subjected to it and the large existing health disparities among sexual minority adolescents, addressing both physical and sexual violence against sexual minority adolescents should become a public health priority.”

Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery in the Mount Sinai Health System, New York, said he was not surprised by the findings because adolescents who may feel more vulnerable relative to their peers are likely to be more of a target. They may not have the supports they need, he said, which will affect their resiliency and their ability to push back.

“These patients are at ages where their parents might be among their supporters,” Dr. Safer said in an interview. “People in their circle may not be aware of their circumstances.”

He emphasized the need for physicians to ensure their offices are safe places for sexual-minority youth to talk to adolescent patients about their gender and sexual identity as well as any history of victimization, and to involve parents in being an ally of their child.

The researchers analyzed data from the nationally representative 2015 and 2017 National Youth Risk Behavior Surveys administered to public and private high school students in grades 9-12 by the Centers for Disease Control and Prevention. The 28,811 total respondents represented a 60% response rate both years.

After indicating their sex as male or female and their sexual orientation, respondents reported whether, in the past year, they had experienced a physical fight at school, a physical fight anywhere, or physical violence from a romantic partner. They also reported whether they had been sexually assaulted in the past year by a romantic partner or ever been forced to have intercourse. The 2017 survey included an additional question about sexual assault by anyone in the past year.

Most youth (87%) identified themselves as heterosexual while 2% were gay/lesbian, 7% were bisexual, and 4% were unsure. Sexual minorities reported a higher prevalence of all forms of violence and assault, compared with their heterosexual counterparts. Although risk of a physical fight in the past year differed by a small amount (28% of sexual-minority youth vs. 22% of heterosexual youth), the gap was considerably greater for risk of physical violence by a romantic partner (12% of sexual-minority youth vs. 5% of heterosexual youth).

More than three times as many sexual-minority adolescents (18%) as heterosexual adolescents (5%) said they had ever been forced to have intercourse, and a similarly high proportion of sexual-minority students (21%) had been sexually assaulted in the past year, compared with heterosexual students (8%). After accounting for survey year, sex, age, race/ethnicity, English language proficiency, and grade level, youth who identified as anything other than heterosexual were about twice as likely as their heterosexual counterparts to have experienced physical or sexual violence, including physical violence by a romantic partner (adjusted risk ratio, 1.97) or sexual assault by anyone (aRR, 2.10), in the past year. The risk of physical violence by a romantic partner or sexual assault by anyone was even greater for bisexual youth (aRR, 2.22 and aRR, 2.36, respectively).

The increased likelihood of physical violence and sexual violence differed by sex. Girls who identified as lesbian, bisexual, or questioning were more likely than heterosexual girls to have been in a fight at school or anywhere else (aRR, 1.91 and aRR, 1.74, respectively). Boys who were gay, bisexual, or questioning, meanwhile, were over four times more likely than heterosexual boys to have had forced intercourse or any kind of sexual assault (aRR, 4.70 and aRR, 4.64, respectively).

These findings point to the need for physicians to be “specifically talking to youth about gender identity and sexual orientation. Validating what kids are feeling is important,” Dr. Safer said in an interview.

Key to that process is making sure the physician’s office feels like a safe place for LGBTQ youth to have these kinds of conversations. “Most primary care and pediatric and adolescent care practices are not feeling well equipped to take care of these kids and are not necessarily serving as a good resource for these kids,” Dr. Safer said.

It’s also important for physicians to ask youth about potential violence or abuse they have experienced, including depression and sequelae from lack of support, for which gender- and sexual-minority youth are at greater risk, he said. Finally, doctors need to engage parents in the conversation.

“As a medical professional, you need to be asking the questions and really be out there as an ally, especially for pediatric and adolescent patients, and you need to be helping the parents of your patients be allies too,” Dr. Safer said.

The study was limited by having a binary question only about respondent’s sex and no data collection about transgender youth. The study’s cross-sectional design also precludes the ability to claim causation about any of the associations.

The research was funded by the Marshall Aid Commemoration Commission, Stanford (Calif.) University, and the National Institutes of Health. The authors had no disclosures.

SOURCE: Caputi TL et al. JAMA Pediatr. 2019 Mar 9. doi: 10.1001/jamapediatrics.2019.6291.

Rotavirus vaccination was not associated with the incidence of type 1 diabetes in a study of more than 385,000 children published in JAMA Pediatrics.

Previous findings from a number of studies have indicated a possible association between rotavirus and type 1 diabetes, according to Jason M. Glanz, PhD, and colleagues. “Epidemiologic data suggest an association between gastrointestinal infection and incidence of type 1 diabetes in children followed from birth to age 10 years. Given these findings, it is biologically plausible that live, attenuated rotavirus vaccine could either increase or decrease the risk for type 1 diabetes in early childhood,” they wrote.

To examine the association between rotavirus vaccination and the incidence of type 1 diabetes in a cohort of U.S. children, Dr. Glanz, a senior investigator at the Kaiser Permanente Colorado Institute for Health Research in Aurora, and colleagues retrospectively analyzed data from seven health care organizations that participate in the Vaccine Safety Datalink.

The researchers identified children born between 2006 and 2014 who had continuous enrollment from age 6 weeks to 2 years. They excluded children with a medical contraindication to vaccination or fewer than two well-child visits by age 12 months. They followed children until a type 1 diabetes diagnosis, disenrollment, or Dec. 31, 2017. The researchers adjusted for sex, birth year, mother’s age, birth weight, gestational age, and race or ethnicity.

The cohort included 386,937 children who were followed up a median of 5.4 years for a total person-time follow-up of 2,253,879 years. In all, 386,937 children (93.1%) were fully exposed to rotavirus vaccination; 15,765 (4.1%) were partially exposed to rotavirus vaccination, meaning that they received some, but not all, vaccine doses; and 11,003 (2.8%) were unexposed to rotavirus vaccination but had received all other recommended vaccines.

There were 464 cases of type 1 diabetes in the cohort, with an incidence rate of 20 cases per 100,000 person-years in the fully exposed group, 31.2 cases per 100,000 person-years in the partially exposed group, and 22.4 cases per 100,000 person-years in the unexposed group.

The incidence of type 1 diabetes was not significantly different across the rotavirus vaccine–exposure groups. The researchers reported that, compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio for children fully exposed to rotavirus vaccination was 1.03 (95% confidence interval, 0.62-1.72), and for those partially exposed to the vaccination, it was 1.50 (95% CI, 0.81-2.77).

“Since licensure, rotavirus vaccination has been associated with a reduction in morbidity and mortality due to rotavirus infection in the United States and worldwide. ... Although rotavirus vaccination may not prevent type 1 diabetes, these results should provide additional reassurance to the public that rotavirus vaccination can be safely administered to infants,” they wrote.

The limited follow-up duration and relatively small proportion of patients unexposed to rotavirus vaccination are limitations of the study, the authors noted.

The Centers for Disease Control and Prevention funded the study. Several authors reported having received grants from the CDC. One author received grants from the National Institute of Diabetes and Digestive and Kidney Diseases, and another from pharmaceutical companies not involved in the study.

SOURCE: Glanz JM et al. JAMA Pediatr. 2020 Mar 9. doi: 10.1001/jamapediatrics.2019.6324.

Rotavirus vaccination was not associated with the incidence of type 1 diabetes in a study of more than 385,000 children published in JAMA Pediatrics.

Previous findings from a number of studies have indicated a possible association between rotavirus and type 1 diabetes, according to Jason M. Glanz, PhD, and colleagues. “Epidemiologic data suggest an association between gastrointestinal infection and incidence of type 1 diabetes in children followed from birth to age 10 years. Given these findings, it is biologically plausible that live, attenuated rotavirus vaccine could either increase or decrease the risk for type 1 diabetes in early childhood,” they wrote.

To examine the association between rotavirus vaccination and the incidence of type 1 diabetes in a cohort of U.S. children, Dr. Glanz, a senior investigator at the Kaiser Permanente Colorado Institute for Health Research in Aurora, and colleagues retrospectively analyzed data from seven health care organizations that participate in the Vaccine Safety Datalink.

The researchers identified children born between 2006 and 2014 who had continuous enrollment from age 6 weeks to 2 years. They excluded children with a medical contraindication to vaccination or fewer than two well-child visits by age 12 months. They followed children until a type 1 diabetes diagnosis, disenrollment, or Dec. 31, 2017. The researchers adjusted for sex, birth year, mother’s age, birth weight, gestational age, and race or ethnicity.

The cohort included 386,937 children who were followed up a median of 5.4 years for a total person-time follow-up of 2,253,879 years. In all, 386,937 children (93.1%) were fully exposed to rotavirus vaccination; 15,765 (4.1%) were partially exposed to rotavirus vaccination, meaning that they received some, but not all, vaccine doses; and 11,003 (2.8%) were unexposed to rotavirus vaccination but had received all other recommended vaccines.

There were 464 cases of type 1 diabetes in the cohort, with an incidence rate of 20 cases per 100,000 person-years in the fully exposed group, 31.2 cases per 100,000 person-years in the partially exposed group, and 22.4 cases per 100,000 person-years in the unexposed group.

The incidence of type 1 diabetes was not significantly different across the rotavirus vaccine–exposure groups. The researchers reported that, compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio for children fully exposed to rotavirus vaccination was 1.03 (95% confidence interval, 0.62-1.72), and for those partially exposed to the vaccination, it was 1.50 (95% CI, 0.81-2.77).

“Since licensure, rotavirus vaccination has been associated with a reduction in morbidity and mortality due to rotavirus infection in the United States and worldwide. ... Although rotavirus vaccination may not prevent type 1 diabetes, these results should provide additional reassurance to the public that rotavirus vaccination can be safely administered to infants,” they wrote.

The limited follow-up duration and relatively small proportion of patients unexposed to rotavirus vaccination are limitations of the study, the authors noted.

The Centers for Disease Control and Prevention funded the study. Several authors reported having received grants from the CDC. One author received grants from the National Institute of Diabetes and Digestive and Kidney Diseases, and another from pharmaceutical companies not involved in the study.

SOURCE: Glanz JM et al. JAMA Pediatr. 2020 Mar 9. doi: 10.1001/jamapediatrics.2019.6324.

Rotavirus vaccination was not associated with the incidence of type 1 diabetes in a study of more than 385,000 children published in JAMA Pediatrics.

Previous findings from a number of studies have indicated a possible association between rotavirus and type 1 diabetes, according to Jason M. Glanz, PhD, and colleagues. “Epidemiologic data suggest an association between gastrointestinal infection and incidence of type 1 diabetes in children followed from birth to age 10 years. Given these findings, it is biologically plausible that live, attenuated rotavirus vaccine could either increase or decrease the risk for type 1 diabetes in early childhood,” they wrote.

To examine the association between rotavirus vaccination and the incidence of type 1 diabetes in a cohort of U.S. children, Dr. Glanz, a senior investigator at the Kaiser Permanente Colorado Institute for Health Research in Aurora, and colleagues retrospectively analyzed data from seven health care organizations that participate in the Vaccine Safety Datalink.

The researchers identified children born between 2006 and 2014 who had continuous enrollment from age 6 weeks to 2 years. They excluded children with a medical contraindication to vaccination or fewer than two well-child visits by age 12 months. They followed children until a type 1 diabetes diagnosis, disenrollment, or Dec. 31, 2017. The researchers adjusted for sex, birth year, mother’s age, birth weight, gestational age, and race or ethnicity.

The cohort included 386,937 children who were followed up a median of 5.4 years for a total person-time follow-up of 2,253,879 years. In all, 386,937 children (93.1%) were fully exposed to rotavirus vaccination; 15,765 (4.1%) were partially exposed to rotavirus vaccination, meaning that they received some, but not all, vaccine doses; and 11,003 (2.8%) were unexposed to rotavirus vaccination but had received all other recommended vaccines.

There were 464 cases of type 1 diabetes in the cohort, with an incidence rate of 20 cases per 100,000 person-years in the fully exposed group, 31.2 cases per 100,000 person-years in the partially exposed group, and 22.4 cases per 100,000 person-years in the unexposed group.

The incidence of type 1 diabetes was not significantly different across the rotavirus vaccine–exposure groups. The researchers reported that, compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio for children fully exposed to rotavirus vaccination was 1.03 (95% confidence interval, 0.62-1.72), and for those partially exposed to the vaccination, it was 1.50 (95% CI, 0.81-2.77).

“Since licensure, rotavirus vaccination has been associated with a reduction in morbidity and mortality due to rotavirus infection in the United States and worldwide. ... Although rotavirus vaccination may not prevent type 1 diabetes, these results should provide additional reassurance to the public that rotavirus vaccination can be safely administered to infants,” they wrote.

The limited follow-up duration and relatively small proportion of patients unexposed to rotavirus vaccination are limitations of the study, the authors noted.

The Centers for Disease Control and Prevention funded the study. Several authors reported having received grants from the CDC. One author received grants from the National Institute of Diabetes and Digestive and Kidney Diseases, and another from pharmaceutical companies not involved in the study.

SOURCE: Glanz JM et al. JAMA Pediatr. 2020 Mar 9. doi: 10.1001/jamapediatrics.2019.6324.

Health care factors, such as type of health system and being newly diagnosed, rather than patient socioeconomic factors, were significant predictors of smoking cessation in patients with RA, according to findings published in Arthritis Care & Research.

Smoking is a known risk factor for poor outcomes in RA, but data on factors that predict smoking cessation in these patients are limited, wrote Maria Schletzbaum, a student in the MD-PhD program at the University of Wisconsin–Madison, and colleagues. “Further, most patients with RA are not aware of the associations between smoking and RA development and complications, although such knowledge could influence cessation attempts.”

To identify predictors of smoking cessation, the investigators reviewed the 2005-2016 electronic medical records for 3,577 adults aged 18 years or older and with at least two RA diagnosis codes. The records were from two health systems, one urban and one rural.

Overall, patients who were baseline smokers and who were new to rheumatology care were 60% more likely to quit smoking (adjusted odds ratio, 1.60). However, patients who were seropositive and baseline smokers were 43% less likely to quit (aOR, 0.57). Demographic factors, including age, race, and sex, were not significantly associated with smoking cessation.

“The observed increased likelihood of quitting in patients new to rheumatology care may partially be due to cessation following a new RA diagnosis, a phenomenon previously reported in RA and other chronic diseases,” the researchers noted. Notably, the significance of being new to rheumatology disappeared in an analysis controlling for health system, “potentially suggesting greater importance of system-level factors versus individual patient factors.”

In addition, patients in the rural community health system were 66% more likely to quit smoking, possibly because about half of the patients in that system were covered by the systems’ insurance, and therefore qualified for various smoking cessation interventions, they wrote.

The study population included 915 former smokers and 507 current smokers. Seropositivity was most common in current smokers (71%), followed by former smokers (64%) and never smokers (59%). The disinclination of seropositive patients to quit smoking may reflect greater smoking intensity, and these patients may need greater support, the researchers wrote.

The study findings were limited by several factors; for example, some differences in patient populations, such as education and income levels, were not measured, and there was a lack of complete information on cumulative smoking exposure. However, the results were strengthened by the large sample size and use of data from two centers and support national guidelines for health system interventions in smoking cessation for RA patients, they noted.

The study was funded in part by the Rheumatology Research Foundation, the University of Wisconsin Medical Scientist Training Program, and the University of Wisconsin Clinical and Translational Science Award. The authors did not report any financial conflicts of interest.

SOURCE: Schletzbaum M et al. Arthritis Car Res. 2020 Mar 3. doi: 10.1002/ACR.24154.

Health care factors, such as type of health system and being newly diagnosed, rather than patient socioeconomic factors, were significant predictors of smoking cessation in patients with RA, according to findings published in Arthritis Care & Research.

Smoking is a known risk factor for poor outcomes in RA, but data on factors that predict smoking cessation in these patients are limited, wrote Maria Schletzbaum, a student in the MD-PhD program at the University of Wisconsin–Madison, and colleagues. “Further, most patients with RA are not aware of the associations between smoking and RA development and complications, although such knowledge could influence cessation attempts.”

To identify predictors of smoking cessation, the investigators reviewed the 2005-2016 electronic medical records for 3,577 adults aged 18 years or older and with at least two RA diagnosis codes. The records were from two health systems, one urban and one rural.

Overall, patients who were baseline smokers and who were new to rheumatology care were 60% more likely to quit smoking (adjusted odds ratio, 1.60). However, patients who were seropositive and baseline smokers were 43% less likely to quit (aOR, 0.57). Demographic factors, including age, race, and sex, were not significantly associated with smoking cessation.

“The observed increased likelihood of quitting in patients new to rheumatology care may partially be due to cessation following a new RA diagnosis, a phenomenon previously reported in RA and other chronic diseases,” the researchers noted. Notably, the significance of being new to rheumatology disappeared in an analysis controlling for health system, “potentially suggesting greater importance of system-level factors versus individual patient factors.”

In addition, patients in the rural community health system were 66% more likely to quit smoking, possibly because about half of the patients in that system were covered by the systems’ insurance, and therefore qualified for various smoking cessation interventions, they wrote.

The study population included 915 former smokers and 507 current smokers. Seropositivity was most common in current smokers (71%), followed by former smokers (64%) and never smokers (59%). The disinclination of seropositive patients to quit smoking may reflect greater smoking intensity, and these patients may need greater support, the researchers wrote.

The study findings were limited by several factors; for example, some differences in patient populations, such as education and income levels, were not measured, and there was a lack of complete information on cumulative smoking exposure. However, the results were strengthened by the large sample size and use of data from two centers and support national guidelines for health system interventions in smoking cessation for RA patients, they noted.

The study was funded in part by the Rheumatology Research Foundation, the University of Wisconsin Medical Scientist Training Program, and the University of Wisconsin Clinical and Translational Science Award. The authors did not report any financial conflicts of interest.

SOURCE: Schletzbaum M et al. Arthritis Car Res. 2020 Mar 3. doi: 10.1002/ACR.24154.

Health care factors, such as type of health system and being newly diagnosed, rather than patient socioeconomic factors, were significant predictors of smoking cessation in patients with RA, according to findings published in Arthritis Care & Research.

Smoking is a known risk factor for poor outcomes in RA, but data on factors that predict smoking cessation in these patients are limited, wrote Maria Schletzbaum, a student in the MD-PhD program at the University of Wisconsin–Madison, and colleagues. “Further, most patients with RA are not aware of the associations between smoking and RA development and complications, although such knowledge could influence cessation attempts.”

To identify predictors of smoking cessation, the investigators reviewed the 2005-2016 electronic medical records for 3,577 adults aged 18 years or older and with at least two RA diagnosis codes. The records were from two health systems, one urban and one rural.

Overall, patients who were baseline smokers and who were new to rheumatology care were 60% more likely to quit smoking (adjusted odds ratio, 1.60). However, patients who were seropositive and baseline smokers were 43% less likely to quit (aOR, 0.57). Demographic factors, including age, race, and sex, were not significantly associated with smoking cessation.

“The observed increased likelihood of quitting in patients new to rheumatology care may partially be due to cessation following a new RA diagnosis, a phenomenon previously reported in RA and other chronic diseases,” the researchers noted. Notably, the significance of being new to rheumatology disappeared in an analysis controlling for health system, “potentially suggesting greater importance of system-level factors versus individual patient factors.”

In addition, patients in the rural community health system were 66% more likely to quit smoking, possibly because about half of the patients in that system were covered by the systems’ insurance, and therefore qualified for various smoking cessation interventions, they wrote.

The study population included 915 former smokers and 507 current smokers. Seropositivity was most common in current smokers (71%), followed by former smokers (64%) and never smokers (59%). The disinclination of seropositive patients to quit smoking may reflect greater smoking intensity, and these patients may need greater support, the researchers wrote.

The study findings were limited by several factors; for example, some differences in patient populations, such as education and income levels, were not measured, and there was a lack of complete information on cumulative smoking exposure. However, the results were strengthened by the large sample size and use of data from two centers and support national guidelines for health system interventions in smoking cessation for RA patients, they noted.

The study was funded in part by the Rheumatology Research Foundation, the University of Wisconsin Medical Scientist Training Program, and the University of Wisconsin Clinical and Translational Science Award. The authors did not report any financial conflicts of interest.

SOURCE: Schletzbaum M et al. Arthritis Car Res. 2020 Mar 3. doi: 10.1002/ACR.24154.

The predictive accuracy of assessing very preterm (VPT) children at different ages leading up to middle school improves with age and by inclusion of any (mild or severe) cognitive impairment, rather than just severe impairment, in ongoing monitoring, according to a study published in Pediatrics.

Carmina Erdei, MD, of Brigham and Women’s Hospital and the department of pediatrics at Harvard Medical school, both in Boston, and colleagues prospectively studied 103 children born VPT (32 weeks’ or less gestation) and 109 children born term. Exclusion criteria included congenital abnormalities and having non–English-speaking parents.

The investigators assessed the children’s cognitive abilities and neurodevelopment with age-appropriate measures at various ages: Bayley Scales of Infant Development (2nd ed.) at age 2 years, Wechsler Preschool and Primary Scale of Intelligence at age 4 and 6 years, and Wechsler Intelligence Scale for Children (4th ed.) at age 9 and 12 years.

When only severe cognitive impairment at ages 2, 4, and 6 years was used as the criterion for ongoing monitoring, between 18% and 44% of severely impaired children at 12 years were missed – and would not have received continued monitoring and support. However, when any cognitive impairment at the younger ages was the criterion for continued monitoring, 100% of cases of severe impairment at age 12 years were correctly predicted.

The authors suggest that adoption of this more inclusive approach may be warranted, given the long-term ramifications of even mild cognitive impairment.

Positive predictive value (66%), negative predictive value (89%), and specificity (73%) intersected in assessments performed at age 6 years, such that they had the best predictive ability for any cognitive impairment at age 12 years.

“Our findings highlight the potential benefit of monitoring children at high risk with early delay until elementary school,” the authors wrote. “We acknowledge that this would result in a higher number of referrals and potentially increased short-term costs. Developmental follow-up is costly, yet early developmental services are valuable and positively impact preterm children’s cognitive and preacademic skills.”

The investigators also assessed family-social risks, such as socioeconomic status and maternal education, and found that children born VPT were more than twice as likely to be raised in families with more risks than were those born term (33% vs. 13%, respectively).

Limitations of the study include the high false-positive rate (34%) seen with the assessments at age 6 years, but the authors suggested that could be mitigated with risk stratification.

The study was funded by the Neurological Foundation, Lottery Grants Board, Canterbury Medical Research Foundation, and Health Research Council of New Zealand. The authors reported having no relevant financial relationships or conflicts of interest.

cpalmer@mdedge.com

SOURCE: Erdei C et al. Pediatrics. 2020 Mar 6. doi: 10.1542/peds.2019-1982.

The predictive accuracy of assessing very preterm (VPT) children at different ages leading up to middle school improves with age and by inclusion of any (mild or severe) cognitive impairment, rather than just severe impairment, in ongoing monitoring, according to a study published in Pediatrics.

Carmina Erdei, MD, of Brigham and Women’s Hospital and the department of pediatrics at Harvard Medical school, both in Boston, and colleagues prospectively studied 103 children born VPT (32 weeks’ or less gestation) and 109 children born term. Exclusion criteria included congenital abnormalities and having non–English-speaking parents.

The investigators assessed the children’s cognitive abilities and neurodevelopment with age-appropriate measures at various ages: Bayley Scales of Infant Development (2nd ed.) at age 2 years, Wechsler Preschool and Primary Scale of Intelligence at age 4 and 6 years, and Wechsler Intelligence Scale for Children (4th ed.) at age 9 and 12 years.

When only severe cognitive impairment at ages 2, 4, and 6 years was used as the criterion for ongoing monitoring, between 18% and 44% of severely impaired children at 12 years were missed – and would not have received continued monitoring and support. However, when any cognitive impairment at the younger ages was the criterion for continued monitoring, 100% of cases of severe impairment at age 12 years were correctly predicted.

The authors suggest that adoption of this more inclusive approach may be warranted, given the long-term ramifications of even mild cognitive impairment.

Positive predictive value (66%), negative predictive value (89%), and specificity (73%) intersected in assessments performed at age 6 years, such that they had the best predictive ability for any cognitive impairment at age 12 years.

“Our findings highlight the potential benefit of monitoring children at high risk with early delay until elementary school,” the authors wrote. “We acknowledge that this would result in a higher number of referrals and potentially increased short-term costs. Developmental follow-up is costly, yet early developmental services are valuable and positively impact preterm children’s cognitive and preacademic skills.”

The investigators also assessed family-social risks, such as socioeconomic status and maternal education, and found that children born VPT were more than twice as likely to be raised in families with more risks than were those born term (33% vs. 13%, respectively).

Limitations of the study include the high false-positive rate (34%) seen with the assessments at age 6 years, but the authors suggested that could be mitigated with risk stratification.

The study was funded by the Neurological Foundation, Lottery Grants Board, Canterbury Medical Research Foundation, and Health Research Council of New Zealand. The authors reported having no relevant financial relationships or conflicts of interest.

cpalmer@mdedge.com

SOURCE: Erdei C et al. Pediatrics. 2020 Mar 6. doi: 10.1542/peds.2019-1982.

The predictive accuracy of assessing very preterm (VPT) children at different ages leading up to middle school improves with age and by inclusion of any (mild or severe) cognitive impairment, rather than just severe impairment, in ongoing monitoring, according to a study published in Pediatrics.

Carmina Erdei, MD, of Brigham and Women’s Hospital and the department of pediatrics at Harvard Medical school, both in Boston, and colleagues prospectively studied 103 children born VPT (32 weeks’ or less gestation) and 109 children born term. Exclusion criteria included congenital abnormalities and having non–English-speaking parents.

The investigators assessed the children’s cognitive abilities and neurodevelopment with age-appropriate measures at various ages: Bayley Scales of Infant Development (2nd ed.) at age 2 years, Wechsler Preschool and Primary Scale of Intelligence at age 4 and 6 years, and Wechsler Intelligence Scale for Children (4th ed.) at age 9 and 12 years.

When only severe cognitive impairment at ages 2, 4, and 6 years was used as the criterion for ongoing monitoring, between 18% and 44% of severely impaired children at 12 years were missed – and would not have received continued monitoring and support. However, when any cognitive impairment at the younger ages was the criterion for continued monitoring, 100% of cases of severe impairment at age 12 years were correctly predicted.

The authors suggest that adoption of this more inclusive approach may be warranted, given the long-term ramifications of even mild cognitive impairment.

Positive predictive value (66%), negative predictive value (89%), and specificity (73%) intersected in assessments performed at age 6 years, such that they had the best predictive ability for any cognitive impairment at age 12 years.

“Our findings highlight the potential benefit of monitoring children at high risk with early delay until elementary school,” the authors wrote. “We acknowledge that this would result in a higher number of referrals and potentially increased short-term costs. Developmental follow-up is costly, yet early developmental services are valuable and positively impact preterm children’s cognitive and preacademic skills.”

The investigators also assessed family-social risks, such as socioeconomic status and maternal education, and found that children born VPT were more than twice as likely to be raised in families with more risks than were those born term (33% vs. 13%, respectively).

Limitations of the study include the high false-positive rate (34%) seen with the assessments at age 6 years, but the authors suggested that could be mitigated with risk stratification.

The study was funded by the Neurological Foundation, Lottery Grants Board, Canterbury Medical Research Foundation, and Health Research Council of New Zealand. The authors reported having no relevant financial relationships or conflicts of interest.

cpalmer@mdedge.com

SOURCE: Erdei C et al. Pediatrics. 2020 Mar 6. doi: 10.1542/peds.2019-1982.

A high-risk profile from the urinary biomarker CKD273 was significantly associated with an increased risk of microalbuminuria in patients with diabetes, according to findings from a multicenter European trial.

“Although microalbuminuria is the earliest clinical index of renal damage, histological changes might already be advanced by the time it is detectable. Thus, earlier identification of at-risk individuals is essential to guide targeted preventive therapy,” wrote Nete Tofte, MD, of the Steno Diabetes Center in Copenhagen, and colleagues.

“Increases in urinary albumin to microalbuminuria levels, or higher, are not only strongly associated with progression to more serious clinical endpoints, such as clinically significant loss of renal function and eventually, end-stage kidney disease, but also with an increased risk of cardiovascular complications,” the researchers noted in the Lancet Diabetes & Endocrinology.

They identified 1,775 adults with type 2 diabetes who had normal albumin levels and preserved renal function at baseline. The average age of the patients was 62 years, and 62% were men. The participants underwent urine proteomics testing via capillary electrophoresis–mass spectrometry analysis to generate a renal risk profile based on 273 peptides (CKD273). On the basis of their CKD273 scores, 216 patients (12%) were designated to the high-risk group, and 1,556 (88%) to the low-risk group.

Over a median follow-up of 2.5 years, 61 patients (28%) in the high-risk group progressed to microalbuminuria (the primary endpoint), compared with 139 patients (9%) in the low-risk group.

Of the original 216 high-risk patients, 209 were randomized to treatment with 25 mg of the mineralocorticoid receptor antagonist spironolactone (102 patients) or placebo (107) to examine whether spironolactone would stall progression to microalbuminuria.

The researchers found, however, that spironolactone did not prevent progression to microalbuminuria. In all, 26 of the 102 patients (25%) patients in the spironolactone group developed microalbuminuria, and 35 of the 107 patients (33%) in the placebo group developed it (hazard ratio, 0.81; 95% confidence interval, 0.49-1.34; P = .41).

The total number of adverse events was not significantly different between the spironolactone and placebo groups (312 vs. 321, respectively), although more patients in the spironolactone group experienced adverse events that led to drug discontinuation (25 vs. 9, respectively).

The study findings were limited by several factors, including the use of a single urine sample for risk stratification; the lower-than-expected number of high-risk patients; not testing spironolactone in the low-risk group; and the fact that microalbuminuria, although an accepted surrogate for diabetic kidney disease, is not approved as such by regulatory agencies, the researchers noted. However, the results were strengthened by the large study population and prospective design, as well as the additional register-based follow-up that is planned when possible.

In an accompanying editorial, Susanne B. Nicholas, MD, of the University of California, Los Angeles, reiterated that microalbuminuria cannot be used to track responses to therapy even if it is an acceptable indicator of potential renal damage.

“In fact, regression from microalbuminuria to normoalbuminuria is more likely than progression toward overt proteinuria, [which exposes] a need for a more dependable biomarker for diabetic kidney disease,” she wrote.

However, Dr. Nicholas supported the potential of proteomics as a tool “that could bridge the gap between discovery of diabetic kidney disease – possibly providing a panel, rather than a single or few urinary indicators of structural changes that predate microalbuminuria – and response to therapy, given the promise of targeted therapies for this complex disease.” Additional research into patient selection, comparators to verify findings, and cost containment is needed before proteomics can become part of routine care, she added.

The study was supported by the European Union Seventh Framework Programme. Dr. Tofte had no financial conflicts to disclose. Several other authors disclosed relationships with multiple companies, including Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Sanofi. Dr. Nicholas had no financial conflicts to disclose.

SOURCES: Tofte N et al. Lancet Diabetes Endocrinol. 2020 Mar 2. doi: 10.1016/S2213-8587(20)30026-7; Nicholas SB. Lancet Diabetes Endocrinol. 2020 Mar 2. doi: 10.1016/S2213-8587(20)30067-X.

A high-risk profile from the urinary biomarker CKD273 was significantly associated with an increased risk of microalbuminuria in patients with diabetes, according to findings from a multicenter European trial.

“Although microalbuminuria is the earliest clinical index of renal damage, histological changes might already be advanced by the time it is detectable. Thus, earlier identification of at-risk individuals is essential to guide targeted preventive therapy,” wrote Nete Tofte, MD, of the Steno Diabetes Center in Copenhagen, and colleagues.

“Increases in urinary albumin to microalbuminuria levels, or higher, are not only strongly associated with progression to more serious clinical endpoints, such as clinically significant loss of renal function and eventually, end-stage kidney disease, but also with an increased risk of cardiovascular complications,” the researchers noted in the Lancet Diabetes & Endocrinology.

They identified 1,775 adults with type 2 diabetes who had normal albumin levels and preserved renal function at baseline. The average age of the patients was 62 years, and 62% were men. The participants underwent urine proteomics testing via capillary electrophoresis–mass spectrometry analysis to generate a renal risk profile based on 273 peptides (CKD273). On the basis of their CKD273 scores, 216 patients (12%) were designated to the high-risk group, and 1,556 (88%) to the low-risk group.

Over a median follow-up of 2.5 years, 61 patients (28%) in the high-risk group progressed to microalbuminuria (the primary endpoint), compared with 139 patients (9%) in the low-risk group.

Of the original 216 high-risk patients, 209 were randomized to treatment with 25 mg of the mineralocorticoid receptor antagonist spironolactone (102 patients) or placebo (107) to examine whether spironolactone would stall progression to microalbuminuria.

The researchers found, however, that spironolactone did not prevent progression to microalbuminuria. In all, 26 of the 102 patients (25%) patients in the spironolactone group developed microalbuminuria, and 35 of the 107 patients (33%) in the placebo group developed it (hazard ratio, 0.81; 95% confidence interval, 0.49-1.34; P = .41).

The total number of adverse events was not significantly different between the spironolactone and placebo groups (312 vs. 321, respectively), although more patients in the spironolactone group experienced adverse events that led to drug discontinuation (25 vs. 9, respectively).

The study findings were limited by several factors, including the use of a single urine sample for risk stratification; the lower-than-expected number of high-risk patients; not testing spironolactone in the low-risk group; and the fact that microalbuminuria, although an accepted surrogate for diabetic kidney disease, is not approved as such by regulatory agencies, the researchers noted. However, the results were strengthened by the large study population and prospective design, as well as the additional register-based follow-up that is planned when possible.

In an accompanying editorial, Susanne B. Nicholas, MD, of the University of California, Los Angeles, reiterated that microalbuminuria cannot be used to track responses to therapy even if it is an acceptable indicator of potential renal damage.

“In fact, regression from microalbuminuria to normoalbuminuria is more likely than progression toward overt proteinuria, [which exposes] a need for a more dependable biomarker for diabetic kidney disease,” she wrote.

However, Dr. Nicholas supported the potential of proteomics as a tool “that could bridge the gap between discovery of diabetic kidney disease – possibly providing a panel, rather than a single or few urinary indicators of structural changes that predate microalbuminuria – and response to therapy, given the promise of targeted therapies for this complex disease.” Additional research into patient selection, comparators to verify findings, and cost containment is needed before proteomics can become part of routine care, she added.

The study was supported by the European Union Seventh Framework Programme. Dr. Tofte had no financial conflicts to disclose. Several other authors disclosed relationships with multiple companies, including Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Sanofi. Dr. Nicholas had no financial conflicts to disclose.

SOURCES: Tofte N et al. Lancet Diabetes Endocrinol. 2020 Mar 2. doi: 10.1016/S2213-8587(20)30026-7; Nicholas SB. Lancet Diabetes Endocrinol. 2020 Mar 2. doi: 10.1016/S2213-8587(20)30067-X.

A high-risk profile from the urinary biomarker CKD273 was significantly associated with an increased risk of microalbuminuria in patients with diabetes, according to findings from a multicenter European trial.

“Although microalbuminuria is the earliest clinical index of renal damage, histological changes might already be advanced by the time it is detectable. Thus, earlier identification of at-risk individuals is essential to guide targeted preventive therapy,” wrote Nete Tofte, MD, of the Steno Diabetes Center in Copenhagen, and colleagues.

“Increases in urinary albumin to microalbuminuria levels, or higher, are not only strongly associated with progression to more serious clinical endpoints, such as clinically significant loss of renal function and eventually, end-stage kidney disease, but also with an increased risk of cardiovascular complications,” the researchers noted in the Lancet Diabetes & Endocrinology.

They identified 1,775 adults with type 2 diabetes who had normal albumin levels and preserved renal function at baseline. The average age of the patients was 62 years, and 62% were men. The participants underwent urine proteomics testing via capillary electrophoresis–mass spectrometry analysis to generate a renal risk profile based on 273 peptides (CKD273). On the basis of their CKD273 scores, 216 patients (12%) were designated to the high-risk group, and 1,556 (88%) to the low-risk group.

Over a median follow-up of 2.5 years, 61 patients (28%) in the high-risk group progressed to microalbuminuria (the primary endpoint), compared with 139 patients (9%) in the low-risk group.

Of the original 216 high-risk patients, 209 were randomized to treatment with 25 mg of the mineralocorticoid receptor antagonist spironolactone (102 patients) or placebo (107) to examine whether spironolactone would stall progression to microalbuminuria.

The researchers found, however, that spironolactone did not prevent progression to microalbuminuria. In all, 26 of the 102 patients (25%) patients in the spironolactone group developed microalbuminuria, and 35 of the 107 patients (33%) in the placebo group developed it (hazard ratio, 0.81; 95% confidence interval, 0.49-1.34; P = .41).

The total number of adverse events was not significantly different between the spironolactone and placebo groups (312 vs. 321, respectively), although more patients in the spironolactone group experienced adverse events that led to drug discontinuation (25 vs. 9, respectively).

The study findings were limited by several factors, including the use of a single urine sample for risk stratification; the lower-than-expected number of high-risk patients; not testing spironolactone in the low-risk group; and the fact that microalbuminuria, although an accepted surrogate for diabetic kidney disease, is not approved as such by regulatory agencies, the researchers noted. However, the results were strengthened by the large study population and prospective design, as well as the additional register-based follow-up that is planned when possible.

In an accompanying editorial, Susanne B. Nicholas, MD, of the University of California, Los Angeles, reiterated that microalbuminuria cannot be used to track responses to therapy even if it is an acceptable indicator of potential renal damage.

“In fact, regression from microalbuminuria to normoalbuminuria is more likely than progression toward overt proteinuria, [which exposes] a need for a more dependable biomarker for diabetic kidney disease,” she wrote.

However, Dr. Nicholas supported the potential of proteomics as a tool “that could bridge the gap between discovery of diabetic kidney disease – possibly providing a panel, rather than a single or few urinary indicators of structural changes that predate microalbuminuria – and response to therapy, given the promise of targeted therapies for this complex disease.” Additional research into patient selection, comparators to verify findings, and cost containment is needed before proteomics can become part of routine care, she added.

The study was supported by the European Union Seventh Framework Programme. Dr. Tofte had no financial conflicts to disclose. Several other authors disclosed relationships with multiple companies, including Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Sanofi. Dr. Nicholas had no financial conflicts to disclose.

SOURCES: Tofte N et al. Lancet Diabetes Endocrinol. 2020 Mar 2. doi: 10.1016/S2213-8587(20)30026-7; Nicholas SB. Lancet Diabetes Endocrinol. 2020 Mar 2. doi: 10.1016/S2213-8587(20)30067-X.

Patients with type 2 diabetes who underwent Roux-en-Y gastric bypass (RYGB) surgery experienced higher rates of diabetes remission, improved glycemic control, greater weight loss, and fewer diabetes relapse events, compared with those who had sleeve gastrectomy, according to findings from nearly 10,000 patients.

“Remission of type 2 diabetes is common after bariatric surgery and may reduce risk for subsequent microvascular and macrovascular disease,” but it is not clear which of the two most common procedures, RYGB or sleeve gastrectomy, has better long-term diabetes and weight outcomes, wrote Kathleen M. McTigue, MD, of the University of Pittsburgh, and colleagues in JAMA Surgery.

To examine the effectiveness of the two procedures, the researchers identified 9,710 adults with type 2 diabetes who were part of the National Patient-Centered Clinical Research Network Bariatric Study. They compared diabetes outcomes for up to 5 years after surgery for 6,233 patients who underwent RYGB and 3,477 who underwent sleeve gastrectomy. The average age of the patients was 50 years, and 73% were women. The average preoperative body mass index was 49 kg/m².

Overall, 6,141 patients experienced diabetes remission. The estimated adjusted cumulative remission rates for the RYGB and sleeve gastrectomy groups after 1 year were 59% and 56%, respectively, and after 5 years were 86% and 84%.

Weight loss was significantly greater in RYGB patients, compared with those who had the sleeve gastrectomy, with average differences in percentage points of 6.3 at 1 year and 8.1 at year 5. RYGB patients also showed significantly better long-term glycemic control, compared with sleeve gastrectomy patients. At 5 years, hemoglobin A_1c levels were 0.80 percentage points below baseline in the RYGB group, and 0.35 percentage points below baseline in the sleeve gastrectomy group.

In addition, after 1 year, diabetes relapse rates in the RYGB and sleeve gastrectomy groups were 8% and 11%, respectively, and 33% and 42% after 5 years.

The findings were limited by several factors, including the observational design of the study and the potential for confounding and coding inaccuracies, the researchers noted, adding that future studies should address the impact of weight loss on diabetes remission and relapse in bariatric surgery patients.

They also noted that their results were in contrast to findings in previous studies that established no significant differences in outcomes between the procedures, but emphasized that most previous studies were smaller and controlled and that outcome differences may be greater in clinical practice.

“For patients, clinicians, and policy makers to make informed decisions about which procedure is best suited to patients’ personal situations, additional data are needed to understand the adverse event profile of the procedures, as well as patient values regarding procedure choice and the role of surgery relative to other aspects of lifelong weight management,” they concluded.

In an accompanying commentary, Natalie Liu, MD, and Luke M. Funk, MD, of the department of surgery, University of Wisconsin–Madison, said the analysis made an important contribution to the existing literature, despite its limitations.

“It included long-term electronic health record data from a large cohort of U.S. patients who had bariatric surgery in a real-world setting,” they wrote, adding that, although the remission rates were high, the relapse rate in both treatment groups deserved further study.

Dr. Liu and Dr. Funk emphasized that the overall high remission rates for either surgery, compared with lifestyle interventions, suggest the need for continued advocacy for better insurance coverage of, and access to, bariatric surgery procedures for patients with type 2 diabetes, notably those with class 1 obesity.

The study was conducted using the National Patient-Centered Clinical Research Network, which was funded by the Patient-Centered Outcomes Research Institute. Dr. McTigue and Dr. Liu had reported no conflicts of interest. Dr. Funk disclosed a Veterans Affairs Health Services Research & Development Career Development Award, and grants from the VA, National Institutes of Health, and American College of Surgeons.

SOURCES: McTigue KM et al. JAMA Surg. 2020 Mar 4. doi: 10.1001/jamasurg.2020.0087; Lui N, Funk LM. JAMA Surg. 2020 Mar 4. doi: 10.1001/jamasurg.2020.0088.

Patients with type 2 diabetes who underwent Roux-en-Y gastric bypass (RYGB) surgery experienced higher rates of diabetes remission, improved glycemic control, greater weight loss, and fewer diabetes relapse events, compared with those who had sleeve gastrectomy, according to findings from nearly 10,000 patients.

“Remission of type 2 diabetes is common after bariatric surgery and may reduce risk for subsequent microvascular and macrovascular disease,” but it is not clear which of the two most common procedures, RYGB or sleeve gastrectomy, has better long-term diabetes and weight outcomes, wrote Kathleen M. McTigue, MD, of the University of Pittsburgh, and colleagues in JAMA Surgery.

To examine the effectiveness of the two procedures, the researchers identified 9,710 adults with type 2 diabetes who were part of the National Patient-Centered Clinical Research Network Bariatric Study. They compared diabetes outcomes for up to 5 years after surgery for 6,233 patients who underwent RYGB and 3,477 who underwent sleeve gastrectomy. The average age of the patients was 50 years, and 73% were women. The average preoperative body mass index was 49 kg/m².

Overall, 6,141 patients experienced diabetes remission. The estimated adjusted cumulative remission rates for the RYGB and sleeve gastrectomy groups after 1 year were 59% and 56%, respectively, and after 5 years were 86% and 84%.

Weight loss was significantly greater in RYGB patients, compared with those who had the sleeve gastrectomy, with average differences in percentage points of 6.3 at 1 year and 8.1 at year 5. RYGB patients also showed significantly better long-term glycemic control, compared with sleeve gastrectomy patients. At 5 years, hemoglobin A_1c levels were 0.80 percentage points below baseline in the RYGB group, and 0.35 percentage points below baseline in the sleeve gastrectomy group.

In addition, after 1 year, diabetes relapse rates in the RYGB and sleeve gastrectomy groups were 8% and 11%, respectively, and 33% and 42% after 5 years.

The findings were limited by several factors, including the observational design of the study and the potential for confounding and coding inaccuracies, the researchers noted, adding that future studies should address the impact of weight loss on diabetes remission and relapse in bariatric surgery patients.

They also noted that their results were in contrast to findings in previous studies that established no significant differences in outcomes between the procedures, but emphasized that most previous studies were smaller and controlled and that outcome differences may be greater in clinical practice.

“For patients, clinicians, and policy makers to make informed decisions about which procedure is best suited to patients’ personal situations, additional data are needed to understand the adverse event profile of the procedures, as well as patient values regarding procedure choice and the role of surgery relative to other aspects of lifelong weight management,” they concluded.

In an accompanying commentary, Natalie Liu, MD, and Luke M. Funk, MD, of the department of surgery, University of Wisconsin–Madison, said the analysis made an important contribution to the existing literature, despite its limitations.

“It included long-term electronic health record data from a large cohort of U.S. patients who had bariatric surgery in a real-world setting,” they wrote, adding that, although the remission rates were high, the relapse rate in both treatment groups deserved further study.

Dr. Liu and Dr. Funk emphasized that the overall high remission rates for either surgery, compared with lifestyle interventions, suggest the need for continued advocacy for better insurance coverage of, and access to, bariatric surgery procedures for patients with type 2 diabetes, notably those with class 1 obesity.

The study was conducted using the National Patient-Centered Clinical Research Network, which was funded by the Patient-Centered Outcomes Research Institute. Dr. McTigue and Dr. Liu had reported no conflicts of interest. Dr. Funk disclosed a Veterans Affairs Health Services Research & Development Career Development Award, and grants from the VA, National Institutes of Health, and American College of Surgeons.

SOURCES: McTigue KM et al. JAMA Surg. 2020 Mar 4. doi: 10.1001/jamasurg.2020.0087; Lui N, Funk LM. JAMA Surg. 2020 Mar 4. doi: 10.1001/jamasurg.2020.0088.

Patients with type 2 diabetes who underwent Roux-en-Y gastric bypass (RYGB) surgery experienced higher rates of diabetes remission, improved glycemic control, greater weight loss, and fewer diabetes relapse events, compared with those who had sleeve gastrectomy, according to findings from nearly 10,000 patients.

“Remission of type 2 diabetes is common after bariatric surgery and may reduce risk for subsequent microvascular and macrovascular disease,” but it is not clear which of the two most common procedures, RYGB or sleeve gastrectomy, has better long-term diabetes and weight outcomes, wrote Kathleen M. McTigue, MD, of the University of Pittsburgh, and colleagues in JAMA Surgery.

To examine the effectiveness of the two procedures, the researchers identified 9,710 adults with type 2 diabetes who were part of the National Patient-Centered Clinical Research Network Bariatric Study. They compared diabetes outcomes for up to 5 years after surgery for 6,233 patients who underwent RYGB and 3,477 who underwent sleeve gastrectomy. The average age of the patients was 50 years, and 73% were women. The average preoperative body mass index was 49 kg/m².

Overall, 6,141 patients experienced diabetes remission. The estimated adjusted cumulative remission rates for the RYGB and sleeve gastrectomy groups after 1 year were 59% and 56%, respectively, and after 5 years were 86% and 84%.

Weight loss was significantly greater in RYGB patients, compared with those who had the sleeve gastrectomy, with average differences in percentage points of 6.3 at 1 year and 8.1 at year 5. RYGB patients also showed significantly better long-term glycemic control, compared with sleeve gastrectomy patients. At 5 years, hemoglobin A_1c levels were 0.80 percentage points below baseline in the RYGB group, and 0.35 percentage points below baseline in the sleeve gastrectomy group.

In addition, after 1 year, diabetes relapse rates in the RYGB and sleeve gastrectomy groups were 8% and 11%, respectively, and 33% and 42% after 5 years.

The findings were limited by several factors, including the observational design of the study and the potential for confounding and coding inaccuracies, the researchers noted, adding that future studies should address the impact of weight loss on diabetes remission and relapse in bariatric surgery patients.

They also noted that their results were in contrast to findings in previous studies that established no significant differences in outcomes between the procedures, but emphasized that most previous studies were smaller and controlled and that outcome differences may be greater in clinical practice.

“For patients, clinicians, and policy makers to make informed decisions about which procedure is best suited to patients’ personal situations, additional data are needed to understand the adverse event profile of the procedures, as well as patient values regarding procedure choice and the role of surgery relative to other aspects of lifelong weight management,” they concluded.

In an accompanying commentary, Natalie Liu, MD, and Luke M. Funk, MD, of the department of surgery, University of Wisconsin–Madison, said the analysis made an important contribution to the existing literature, despite its limitations.

“It included long-term electronic health record data from a large cohort of U.S. patients who had bariatric surgery in a real-world setting,” they wrote, adding that, although the remission rates were high, the relapse rate in both treatment groups deserved further study.

Dr. Liu and Dr. Funk emphasized that the overall high remission rates for either surgery, compared with lifestyle interventions, suggest the need for continued advocacy for better insurance coverage of, and access to, bariatric surgery procedures for patients with type 2 diabetes, notably those with class 1 obesity.

The study was conducted using the National Patient-Centered Clinical Research Network, which was funded by the Patient-Centered Outcomes Research Institute. Dr. McTigue and Dr. Liu had reported no conflicts of interest. Dr. Funk disclosed a Veterans Affairs Health Services Research & Development Career Development Award, and grants from the VA, National Institutes of Health, and American College of Surgeons.

SOURCES: McTigue KM et al. JAMA Surg. 2020 Mar 4. doi: 10.1001/jamasurg.2020.0087; Lui N, Funk LM. JAMA Surg. 2020 Mar 4. doi: 10.1001/jamasurg.2020.0088.

LOS ANGELES – The edge that the direct-acting oral anticoagulant apixaban (Eliquis) has over warfarin for safely preventing ischemic events in patients with atrial fibrillation and either a recent acute coronary syndrome event or a recent percutaneous coronary intervention held up even in patients with a history of stroke, transient ischemic attack, or thromboembolic event, according to a prespecified secondary analysis of data collected in the AUGUSTUS trial.

Mitchel L. Zoler/MDedge News

The treatment advantages of apixaban, compared with warfarin, seen in the overall AUGUSTUS results, first reported in March 2019, “were consistent” with the benefits seen in the subgroup of enrolled patients with a prior stroke, transient ischemic attack (TIA), or thromboembolic (TE) event, M. Cecilia Bahit, MD, said at the International Stroke Conference sponsored by the American Heart Association.

All patients in AUGUSTUS received a P2Y12 inhibitor antiplatelet drug, which was clopidogrel for more than 90% of patients. The two-by-two factorial design of AUGUSTUS also assessed the safety and efficacy of either adding or withholding aspirin from the two-drug regimen that all patients in the study received with a P2Y12 inhibitor plus an anticoagulant (apixaban or warfarin). The most notable finding of the aspirin versus placebo analysis was that patients without a prior stroke, TIA, or TE event had a “more profound” increase in their rate of major or clinically relevant minor bleeds when also treated with aspirin, compared with patients who received aspirin and had a history of stroke, TIA, or TE event, reported Dr. Bahit, a chief of cardiology and director of clinical research at the INECO Foundation in Rosario, Argentina.

In general, the findings of the secondary analysis that took into account stroke, TIA, or TE history “confirmed” the main AUGUSTUS findings, Dr. Bahit said; an antithrombotic regimen of apixaban plus clopidogrel (or other P2Y12 inhibitor) without aspirin was superior for both efficacy and safety, compared with the alternative regimens that either substituted warfarin for apixaban or that added aspirin.

AUGUSTUS enrolled 4,614 atrial fibrillation (AFib) patients who either had a recent acute coronary syndrome (ACS) event or had recently undergone percutaneous coronary intervention (PCI) at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the incidence of major or clinically relevant minor bleeds after 6 months, which was significantly lower in the subgroups that received apixaban instead of warfarin and in patients who received placebo instead of aspirin. The secondary endpoint of death or hospitalization after 6 months was also significantly lower in the apixaban-treated patients, compared with those on warfarin, while the aspirin and placebo subgroups showed no difference in the incidence of these events (N Engl J Med. 2019 Apr 18;380[16]:1509-24).

The results reported by Dr. Bahit also highlighted both the high risk faced by patients with AFib who also have had an ACS event or PCI, as well as a prior stroke, TIA, or TE event, noted Larry B. Goldstein, MD, professor and chairman of neurology at the University of Kentucky, Lexington. “It’s difficult, because these patients had an ACS event or PCI, and you don’t want a coronary too close up, but do these patients really need a P2Y12 inhibitor plus an anticoagulant? Could these patients do as well on apixaban only? I would have liked to see that treatment arm in the study,” Dr. Goldstein commented in an interview.

“These are challenging patients because they often require anticoagulation for the AFib as well as antiplatelet agents” for the recent PCI or ACS event, commented Mitchell S.V. Elkind, MD, professor of neurology at Columbia University, New York. “The question has always been: How many blood thinners should these patients be on? Potentially they could be on three different agents [an anticoagulant and two antiplatelet drugs], and we know that all of those drugs together pretty dramatically increase the risk of bleeding. About 15% of the patients in the overall AUGUSTUS trial had either cerebrovascular disease or systemic thromboembolism, so this was a small subgroup of the overall trial, but the overall trial was large so it’s a significant number of patients who met this criteria. The results confirmed that even in a group of patients who may be considered at high risk because they have a prior history of cerebrovascular disease use of apixaban instead of warfarin seemed safer, and that those patients did not need to be on aspirin as well as their other antiplatelet agent. Patients with a history of stroke, in fact, had a lower risk of bleeding than the other patients in this trial, so one could argue that they should be on an agent like apixaban as well as an antiplatelet agent like clopidogrel without addition of aspirin,” he said in a recorded statement.

In addition to implications for using prescription drugs like apixaban and clopidogrel, the findings also send a message about the need for very aggressive implementation of lifestyle measures that can reduce cardiovascular disease risk in these patients, added Dr. Goldstein. The AUGUSTUS outcome analyses that subdivided the study population into those with a prior stroke, TIA, or TE event – 633 patients or about 14% of the 4,581 patients eligible for this analysis – and those who did not have this history showed the extremely high, incrementally elevated risk faced by patients with these prior events.

A history of stroke, TIA, or TE event linked with a jump in the 90-day rate of major or clinically relevant minor bleeds from 13% without this history to 17%, which is a 31% relative increase; it boosted the 90-day rate of death or hospitalization from 25% to 31%, a 24% relative increase; and it jacked up the rate of death or ischemic events from 6% to 9%, a 50% relative increase, Dr. Bahit reported.

These substantial increases “suggest we need to be very aggressive” in managing these high-risk patients who combine a background of AFib, a prior stroke, TIA, or TE events, and a recent ACS event or PCI, Dr. Goldstein observed. In these patients, he suggested that clinicians make sure to address smoking cessation, obesity, exercise, diet, and statin use, and get each of these to an optimal level to further cut risk. If all five of these basic interventions were successfully administered to a patient they could collectively cut the patient’s event risk by about 80%, he added.

AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer, the companies that jointly market apixaban. Dr. Bahit has received honoraria from Pfizer, and from CSL Behring and Merck. Dr. Elkind and Dr. Goldstein had no relevant disclosures.

mzoler@mdedge.com

SOURCE: Bahit MC et al. ISC 2020, Abstract LB22.

LOS ANGELES – The edge that the direct-acting oral anticoagulant apixaban (Eliquis) has over warfarin for safely preventing ischemic events in patients with atrial fibrillation and either a recent acute coronary syndrome event or a recent percutaneous coronary intervention held up even in patients with a history of stroke, transient ischemic attack, or thromboembolic event, according to a prespecified secondary analysis of data collected in the AUGUSTUS trial.

Mitchel L. Zoler/MDedge News

The treatment advantages of apixaban, compared with warfarin, seen in the overall AUGUSTUS results, first reported in March 2019, “were consistent” with the benefits seen in the subgroup of enrolled patients with a prior stroke, transient ischemic attack (TIA), or thromboembolic (TE) event, M. Cecilia Bahit, MD, said at the International Stroke Conference sponsored by the American Heart Association.

All patients in AUGUSTUS received a P2Y12 inhibitor antiplatelet drug, which was clopidogrel for more than 90% of patients. The two-by-two factorial design of AUGUSTUS also assessed the safety and efficacy of either adding or withholding aspirin from the two-drug regimen that all patients in the study received with a P2Y12 inhibitor plus an anticoagulant (apixaban or warfarin). The most notable finding of the aspirin versus placebo analysis was that patients without a prior stroke, TIA, or TE event had a “more profound” increase in their rate of major or clinically relevant minor bleeds when also treated with aspirin, compared with patients who received aspirin and had a history of stroke, TIA, or TE event, reported Dr. Bahit, a chief of cardiology and director of clinical research at the INECO Foundation in Rosario, Argentina.

In general, the findings of the secondary analysis that took into account stroke, TIA, or TE history “confirmed” the main AUGUSTUS findings, Dr. Bahit said; an antithrombotic regimen of apixaban plus clopidogrel (or other P2Y12 inhibitor) without aspirin was superior for both efficacy and safety, compared with the alternative regimens that either substituted warfarin for apixaban or that added aspirin.

AUGUSTUS enrolled 4,614 atrial fibrillation (AFib) patients who either had a recent acute coronary syndrome (ACS) event or had recently undergone percutaneous coronary intervention (PCI) at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the incidence of major or clinically relevant minor bleeds after 6 months, which was significantly lower in the subgroups that received apixaban instead of warfarin and in patients who received placebo instead of aspirin. The secondary endpoint of death or hospitalization after 6 months was also significantly lower in the apixaban-treated patients, compared with those on warfarin, while the aspirin and placebo subgroups showed no difference in the incidence of these events (N Engl J Med. 2019 Apr 18;380[16]:1509-24).

The results reported by Dr. Bahit also highlighted both the high risk faced by patients with AFib who also have had an ACS event or PCI, as well as a prior stroke, TIA, or TE event, noted Larry B. Goldstein, MD, professor and chairman of neurology at the University of Kentucky, Lexington. “It’s difficult, because these patients had an ACS event or PCI, and you don’t want a coronary too close up, but do these patients really need a P2Y12 inhibitor plus an anticoagulant? Could these patients do as well on apixaban only? I would have liked to see that treatment arm in the study,” Dr. Goldstein commented in an interview.

“These are challenging patients because they often require anticoagulation for the AFib as well as antiplatelet agents” for the recent PCI or ACS event, commented Mitchell S.V. Elkind, MD, professor of neurology at Columbia University, New York. “The question has always been: How many blood thinners should these patients be on? Potentially they could be on three different agents [an anticoagulant and two antiplatelet drugs], and we know that all of those drugs together pretty dramatically increase the risk of bleeding. About 15% of the patients in the overall AUGUSTUS trial had either cerebrovascular disease or systemic thromboembolism, so this was a small subgroup of the overall trial, but the overall trial was large so it’s a significant number of patients who met this criteria. The results confirmed that even in a group of patients who may be considered at high risk because they have a prior history of cerebrovascular disease use of apixaban instead of warfarin seemed safer, and that those patients did not need to be on aspirin as well as their other antiplatelet agent. Patients with a history of stroke, in fact, had a lower risk of bleeding than the other patients in this trial, so one could argue that they should be on an agent like apixaban as well as an antiplatelet agent like clopidogrel without addition of aspirin,” he said in a recorded statement.

In addition to implications for using prescription drugs like apixaban and clopidogrel, the findings also send a message about the need for very aggressive implementation of lifestyle measures that can reduce cardiovascular disease risk in these patients, added Dr. Goldstein. The AUGUSTUS outcome analyses that subdivided the study population into those with a prior stroke, TIA, or TE event – 633 patients or about 14% of the 4,581 patients eligible for this analysis – and those who did not have this history showed the extremely high, incrementally elevated risk faced by patients with these prior events.

A history of stroke, TIA, or TE event linked with a jump in the 90-day rate of major or clinically relevant minor bleeds from 13% without this history to 17%, which is a 31% relative increase; it boosted the 90-day rate of death or hospitalization from 25% to 31%, a 24% relative increase; and it jacked up the rate of death or ischemic events from 6% to 9%, a 50% relative increase, Dr. Bahit reported.

These substantial increases “suggest we need to be very aggressive” in managing these high-risk patients who combine a background of AFib, a prior stroke, TIA, or TE events, and a recent ACS event or PCI, Dr. Goldstein observed. In these patients, he suggested that clinicians make sure to address smoking cessation, obesity, exercise, diet, and statin use, and get each of these to an optimal level to further cut risk. If all five of these basic interventions were successfully administered to a patient they could collectively cut the patient’s event risk by about 80%, he added.

AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer, the companies that jointly market apixaban. Dr. Bahit has received honoraria from Pfizer, and from CSL Behring and Merck. Dr. Elkind and Dr. Goldstein had no relevant disclosures.

mzoler@mdedge.com

SOURCE: Bahit MC et al. ISC 2020, Abstract LB22.

LOS ANGELES – The edge that the direct-acting oral anticoagulant apixaban (Eliquis) has over warfarin for safely preventing ischemic events in patients with atrial fibrillation and either a recent acute coronary syndrome event or a recent percutaneous coronary intervention held up even in patients with a history of stroke, transient ischemic attack, or thromboembolic event, according to a prespecified secondary analysis of data collected in the AUGUSTUS trial.

Mitchel L. Zoler/MDedge News

The treatment advantages of apixaban, compared with warfarin, seen in the overall AUGUSTUS results, first reported in March 2019, “were consistent” with the benefits seen in the subgroup of enrolled patients with a prior stroke, transient ischemic attack (TIA), or thromboembolic (TE) event, M. Cecilia Bahit, MD, said at the International Stroke Conference sponsored by the American Heart Association.

All patients in AUGUSTUS received a P2Y12 inhibitor antiplatelet drug, which was clopidogrel for more than 90% of patients. The two-by-two factorial design of AUGUSTUS also assessed the safety and efficacy of either adding or withholding aspirin from the two-drug regimen that all patients in the study received with a P2Y12 inhibitor plus an anticoagulant (apixaban or warfarin). The most notable finding of the aspirin versus placebo analysis was that patients without a prior stroke, TIA, or TE event had a “more profound” increase in their rate of major or clinically relevant minor bleeds when also treated with aspirin, compared with patients who received aspirin and had a history of stroke, TIA, or TE event, reported Dr. Bahit, a chief of cardiology and director of clinical research at the INECO Foundation in Rosario, Argentina.

In general, the findings of the secondary analysis that took into account stroke, TIA, or TE history “confirmed” the main AUGUSTUS findings, Dr. Bahit said; an antithrombotic regimen of apixaban plus clopidogrel (or other P2Y12 inhibitor) without aspirin was superior for both efficacy and safety, compared with the alternative regimens that either substituted warfarin for apixaban or that added aspirin.

AUGUSTUS enrolled 4,614 atrial fibrillation (AFib) patients who either had a recent acute coronary syndrome (ACS) event or had recently undergone percutaneous coronary intervention (PCI) at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the incidence of major or clinically relevant minor bleeds after 6 months, which was significantly lower in the subgroups that received apixaban instead of warfarin and in patients who received placebo instead of aspirin. The secondary endpoint of death or hospitalization after 6 months was also significantly lower in the apixaban-treated patients, compared with those on warfarin, while the aspirin and placebo subgroups showed no difference in the incidence of these events (N Engl J Med. 2019 Apr 18;380[16]:1509-24).

The results reported by Dr. Bahit also highlighted both the high risk faced by patients with AFib who also have had an ACS event or PCI, as well as a prior stroke, TIA, or TE event, noted Larry B. Goldstein, MD, professor and chairman of neurology at the University of Kentucky, Lexington. “It’s difficult, because these patients had an ACS event or PCI, and you don’t want a coronary too close up, but do these patients really need a P2Y12 inhibitor plus an anticoagulant? Could these patients do as well on apixaban only? I would have liked to see that treatment arm in the study,” Dr. Goldstein commented in an interview.

“These are challenging patients because they often require anticoagulation for the AFib as well as antiplatelet agents” for the recent PCI or ACS event, commented Mitchell S.V. Elkind, MD, professor of neurology at Columbia University, New York. “The question has always been: How many blood thinners should these patients be on? Potentially they could be on three different agents [an anticoagulant and two antiplatelet drugs], and we know that all of those drugs together pretty dramatically increase the risk of bleeding. About 15% of the patients in the overall AUGUSTUS trial had either cerebrovascular disease or systemic thromboembolism, so this was a small subgroup of the overall trial, but the overall trial was large so it’s a significant number of patients who met this criteria. The results confirmed that even in a group of patients who may be considered at high risk because they have a prior history of cerebrovascular disease use of apixaban instead of warfarin seemed safer, and that those patients did not need to be on aspirin as well as their other antiplatelet agent. Patients with a history of stroke, in fact, had a lower risk of bleeding than the other patients in this trial, so one could argue that they should be on an agent like apixaban as well as an antiplatelet agent like clopidogrel without addition of aspirin,” he said in a recorded statement.

In addition to implications for using prescription drugs like apixaban and clopidogrel, the findings also send a message about the need for very aggressive implementation of lifestyle measures that can reduce cardiovascular disease risk in these patients, added Dr. Goldstein. The AUGUSTUS outcome analyses that subdivided the study population into those with a prior stroke, TIA, or TE event – 633 patients or about 14% of the 4,581 patients eligible for this analysis – and those who did not have this history showed the extremely high, incrementally elevated risk faced by patients with these prior events.

A history of stroke, TIA, or TE event linked with a jump in the 90-day rate of major or clinically relevant minor bleeds from 13% without this history to 17%, which is a 31% relative increase; it boosted the 90-day rate of death or hospitalization from 25% to 31%, a 24% relative increase; and it jacked up the rate of death or ischemic events from 6% to 9%, a 50% relative increase, Dr. Bahit reported.

These substantial increases “suggest we need to be very aggressive” in managing these high-risk patients who combine a background of AFib, a prior stroke, TIA, or TE events, and a recent ACS event or PCI, Dr. Goldstein observed. In these patients, he suggested that clinicians make sure to address smoking cessation, obesity, exercise, diet, and statin use, and get each of these to an optimal level to further cut risk. If all five of these basic interventions were successfully administered to a patient they could collectively cut the patient’s event risk by about 80%, he added.

AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer, the companies that jointly market apixaban. Dr. Bahit has received honoraria from Pfizer, and from CSL Behring and Merck. Dr. Elkind and Dr. Goldstein had no relevant disclosures.

mzoler@mdedge.com

SOURCE: Bahit MC et al. ISC 2020, Abstract LB22.

LONDON – Disrupting how microorganisms communicate with each other could be a way to overcome antibiotic resistance and to help heal chronic wounds in patients with epidermolysis bullosa (EB), according to presenters at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

The majority of chronic wounds in patients with EB are colonized with microorganisms, with a predominance of Staphylococcus species, said Erik Gerner, an industrial PhD student at Mölnlycke Health Care in Gothenburg, Sweden, and Gothenburg University.

Because of the growing problem of antibiotic resistance, alternative treatments are needed, and one possible alternative for treating infected wounds could be interfering with quorum sensing, the cell-to-cell communication used by bacteria, he said. He is hoping to explore this possibility as a novel treatment strategy for infected wounds.

“Quorum sensing is defined as the ability to detect and respond to population density,” Mr. Gerner said, noting that, when there is a sufficient density of bacteria, “they start to communicate with each other.” This enables them to act as a community and perform actions that they could not do as individual cells. Such actions include forming biofilms, which helps protect bacteria from their environment, such as the immune system. Other actions include collectively switching on the production of virulence factors and becoming resistant to treatments.

“Bacteria use quorum sensing to act collectively,” Mr. Gerner said. “If we could shut down this quorum sensing system, it would be very beneficial … and increase the chances to heal the wound.”

The quorum sensing system is based on the production of signaling molecules called AHL (N-acyl homoserine lactones), which are constantly produced at a low rate. This isn’t a problem until the level of bacteria increases and the level of quorum sensing breaches a threshold, he explained.

There are several benefits of inhibiting bacterial communication through disrupting quorum sensing, namely, “a low risk of resistance,” Mr. Gerner said. There is also potentially less toxin production by bacteria, and this could help the immune system in killing the invading bacteria.

One approach to disrupting quorum testing that Mr. Gerner has been investigating is the use of sodium salicylate (NaSa). So far, preclinical work shows that NaSa can reduce toxin production but not the growth rate of bacteria. The advantage of using NaSa is that it is nontoxic to human dermal fibroblasts, with similar results seen in human keratinocytes and immune cells. His work to date has shown that NaSa reduced activity of NF-kB (a proinflammatory signaling pathway) in differentiated and lipopolysaccharide-stimulated monocytes; NF-kB activated production of proinflammatory cytokines (such as interleukin-1 beta and IL-6) are elevated in EB wounds. “My studies support the bodies of evidence that bacteria use quorum sensing to coordinate … and to produce a large number of toxic factors,” Mr. Gerner concluded. Future studies will look at the potential of NaSa to disrupt this activity.
 

Skin microbiome of EB wounds

Understanding what bacteria most commonly colonize wounds in patients with EB was the subject of two unrelated presentations at the EB World Congress. Liat Samuelov, MD, of the department of molecular dermatology at Tel Aviv (Israel) Sourasky Medical Center, presented data on skin microbiome characteristics in eight patients with recessive dystrophic EB (RDEB). This showed that there was reduced bacterial diversity in wounds, and a “progressive development of dysbiosis across different stages of DEB wound formation.”

The skin microbiome has been implicated in several skin diseases, Dr. Samuelov and associates observed in a poster presentation. That includes the autoimmune blistering disease bullous pemphigoid (Exp Dermatol. 2017 Dec;26[12]:1221-7). “Colonization of DEB chronic wounds may lead to systemic infections, result in delayed healing, and possibly be involved in the development of squamous cell carcinoma,” they noted in the poster, “thus accurate delineation of the dysbiotic profile … may point to corrective measures of great therapeutic potential.”

The aim was to see what microorganisms were present in the chronic wounds of the patients. To be included in the study, patients must not have had any antibiotic treatment – oral or topical – in the past 6 months. Samples were taken from an untreated wound, around the wound, and from uninvolved skin, which were compared with samples taken from similar areas in age-matched controls.

Reduced bacterial diversity was observed in RDEB wounds, compared with uninvolved or perilesional areas and the skin of control subjects, Dr. Samuelov said in an oral presentation of the study results. There was increased abundance of Staphylococcus epidermidis and decreased Cutibacterium acnes, which she noted was in contrast to other studies where S. aureus was the most common colonizer in RDEB wounds.

Bacterial composition in each group was calculated using the beta-diversity score, while control samples showed similar microbial composition, the DEB samples had no microbial similarities among different samples. These data “suggest the need to ascertain the potential therapeutic benefit of interventions aimed at restoring normal microbiome composition in DEB,” Dr. Samuelov concluded.

Wound colonization and squamous cell carcinoma

Other research on wound microbiology was presented by Laura E. Levin, MD, a dermatologist at New York–Presbyterian, and associates. “Given the potential role of bacteria-induced inflammation in the development of wound-associated SCC [squamous cell carcinoma] in a subset of patients, we sought to improve our understanding of what microbes colonize and infect the wounds of patients with epidermolysis bullosa,” they explained in their poster.

The researchers, from New York–Presbyterian Morgan Stanley Children’s Hospital and Columbia University Irvine Medical Center, New York, presented data from a retrospective analysis of 739 wound cultures taken between 2001 and 2017 from 158 patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database. In the analysis, just under 70% of patients had DEB, of which 90% were of the RDEB subtype; 13% had EB simplex, 14% had junctional EB, and 3% had an unknown EB subtype.

At least one organism grew in 87% of cultures, with the most common microorganism isolated being Staphylococcus aureus (84% of cultures). Other commonly isolated microbes were Pseudomonas aeruginosa in 35% of cultures, Streptococcus group A in 34% of cultures (of which 22% were Streptococcus pyogenes), Corynebacterium species in 31% of cultures, and Proteus species in 18% of cultures.

“Improved understanding of what microbes are colonizing the wounds of our patients may help improve antibiotic stewardship,” the researchers stated.

Looking at the antibiotic susceptibilities, Dr. Levin and associates found that 68% of 115 cultures were sensitive to methicillin and 60% of 15 cultures were sensitive to mupirocin. “Resistance to many systemic and topical antibiotic agents in EB patients supports surveillance cultures with routine testing for mupirocin susceptibility,” they suggested.

A total of 23 patients developed SCC of whom 10 had cultures that grew S. aureus (90%) and P. aeruginosa (50%), and Proteus species (20%). Among the patients who did not develop SCC, the respective cultures positive for each of those microorganisms were 83%, 34%, and 11%. Perhaps “gram-negative and flagellated organisms may be more common in wounds of patients at risk for SCC,” they observed, adding that further studies were needed to determine if “wound microbiome interventions inhibit the risk of development of SCC and improve outcomes.”

Mr. Gerner’s research is supported by Mölnlycke Health Care. Dr. Samuelov had no disclosures. The work by Dr. Levin and associates is supported by the Pediatric Dermatology Research Alliance, EB Research Partnership, and the Epidermolysis Bullosa Medical Research Foundation.

LONDON – Disrupting how microorganisms communicate with each other could be a way to overcome antibiotic resistance and to help heal chronic wounds in patients with epidermolysis bullosa (EB), according to presenters at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

The majority of chronic wounds in patients with EB are colonized with microorganisms, with a predominance of Staphylococcus species, said Erik Gerner, an industrial PhD student at Mölnlycke Health Care in Gothenburg, Sweden, and Gothenburg University.

Because of the growing problem of antibiotic resistance, alternative treatments are needed, and one possible alternative for treating infected wounds could be interfering with quorum sensing, the cell-to-cell communication used by bacteria, he said. He is hoping to explore this possibility as a novel treatment strategy for infected wounds.

“Quorum sensing is defined as the ability to detect and respond to population density,” Mr. Gerner said, noting that, when there is a sufficient density of bacteria, “they start to communicate with each other.” This enables them to act as a community and perform actions that they could not do as individual cells. Such actions include forming biofilms, which helps protect bacteria from their environment, such as the immune system. Other actions include collectively switching on the production of virulence factors and becoming resistant to treatments.

“Bacteria use quorum sensing to act collectively,” Mr. Gerner said. “If we could shut down this quorum sensing system, it would be very beneficial … and increase the chances to heal the wound.”

The quorum sensing system is based on the production of signaling molecules called AHL (N-acyl homoserine lactones), which are constantly produced at a low rate. This isn’t a problem until the level of bacteria increases and the level of quorum sensing breaches a threshold, he explained.

There are several benefits of inhibiting bacterial communication through disrupting quorum sensing, namely, “a low risk of resistance,” Mr. Gerner said. There is also potentially less toxin production by bacteria, and this could help the immune system in killing the invading bacteria.

One approach to disrupting quorum testing that Mr. Gerner has been investigating is the use of sodium salicylate (NaSa). So far, preclinical work shows that NaSa can reduce toxin production but not the growth rate of bacteria. The advantage of using NaSa is that it is nontoxic to human dermal fibroblasts, with similar results seen in human keratinocytes and immune cells. His work to date has shown that NaSa reduced activity of NF-kB (a proinflammatory signaling pathway) in differentiated and lipopolysaccharide-stimulated monocytes; NF-kB activated production of proinflammatory cytokines (such as interleukin-1 beta and IL-6) are elevated in EB wounds. “My studies support the bodies of evidence that bacteria use quorum sensing to coordinate … and to produce a large number of toxic factors,” Mr. Gerner concluded. Future studies will look at the potential of NaSa to disrupt this activity.
 

Skin microbiome of EB wounds

Understanding what bacteria most commonly colonize wounds in patients with EB was the subject of two unrelated presentations at the EB World Congress. Liat Samuelov, MD, of the department of molecular dermatology at Tel Aviv (Israel) Sourasky Medical Center, presented data on skin microbiome characteristics in eight patients with recessive dystrophic EB (RDEB). This showed that there was reduced bacterial diversity in wounds, and a “progressive development of dysbiosis across different stages of DEB wound formation.”

The skin microbiome has been implicated in several skin diseases, Dr. Samuelov and associates observed in a poster presentation. That includes the autoimmune blistering disease bullous pemphigoid (Exp Dermatol. 2017 Dec;26[12]:1221-7). “Colonization of DEB chronic wounds may lead to systemic infections, result in delayed healing, and possibly be involved in the development of squamous cell carcinoma,” they noted in the poster, “thus accurate delineation of the dysbiotic profile … may point to corrective measures of great therapeutic potential.”

The aim was to see what microorganisms were present in the chronic wounds of the patients. To be included in the study, patients must not have had any antibiotic treatment – oral or topical – in the past 6 months. Samples were taken from an untreated wound, around the wound, and from uninvolved skin, which were compared with samples taken from similar areas in age-matched controls.

Reduced bacterial diversity was observed in RDEB wounds, compared with uninvolved or perilesional areas and the skin of control subjects, Dr. Samuelov said in an oral presentation of the study results. There was increased abundance of Staphylococcus epidermidis and decreased Cutibacterium acnes, which she noted was in contrast to other studies where S. aureus was the most common colonizer in RDEB wounds.

Bacterial composition in each group was calculated using the beta-diversity score, while control samples showed similar microbial composition, the DEB samples had no microbial similarities among different samples. These data “suggest the need to ascertain the potential therapeutic benefit of interventions aimed at restoring normal microbiome composition in DEB,” Dr. Samuelov concluded.

Wound colonization and squamous cell carcinoma

Other research on wound microbiology was presented by Laura E. Levin, MD, a dermatologist at New York–Presbyterian, and associates. “Given the potential role of bacteria-induced inflammation in the development of wound-associated SCC [squamous cell carcinoma] in a subset of patients, we sought to improve our understanding of what microbes colonize and infect the wounds of patients with epidermolysis bullosa,” they explained in their poster.

The researchers, from New York–Presbyterian Morgan Stanley Children’s Hospital and Columbia University Irvine Medical Center, New York, presented data from a retrospective analysis of 739 wound cultures taken between 2001 and 2017 from 158 patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database. In the analysis, just under 70% of patients had DEB, of which 90% were of the RDEB subtype; 13% had EB simplex, 14% had junctional EB, and 3% had an unknown EB subtype.

At least one organism grew in 87% of cultures, with the most common microorganism isolated being Staphylococcus aureus (84% of cultures). Other commonly isolated microbes were Pseudomonas aeruginosa in 35% of cultures, Streptococcus group A in 34% of cultures (of which 22% were Streptococcus pyogenes), Corynebacterium species in 31% of cultures, and Proteus species in 18% of cultures.

“Improved understanding of what microbes are colonizing the wounds of our patients may help improve antibiotic stewardship,” the researchers stated.

Looking at the antibiotic susceptibilities, Dr. Levin and associates found that 68% of 115 cultures were sensitive to methicillin and 60% of 15 cultures were sensitive to mupirocin. “Resistance to many systemic and topical antibiotic agents in EB patients supports surveillance cultures with routine testing for mupirocin susceptibility,” they suggested.

A total of 23 patients developed SCC of whom 10 had cultures that grew S. aureus (90%) and P. aeruginosa (50%), and Proteus species (20%). Among the patients who did not develop SCC, the respective cultures positive for each of those microorganisms were 83%, 34%, and 11%. Perhaps “gram-negative and flagellated organisms may be more common in wounds of patients at risk for SCC,” they observed, adding that further studies were needed to determine if “wound microbiome interventions inhibit the risk of development of SCC and improve outcomes.”

Mr. Gerner’s research is supported by Mölnlycke Health Care. Dr. Samuelov had no disclosures. The work by Dr. Levin and associates is supported by the Pediatric Dermatology Research Alliance, EB Research Partnership, and the Epidermolysis Bullosa Medical Research Foundation.

LONDON – Disrupting how microorganisms communicate with each other could be a way to overcome antibiotic resistance and to help heal chronic wounds in patients with epidermolysis bullosa (EB), according to presenters at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

The majority of chronic wounds in patients with EB are colonized with microorganisms, with a predominance of Staphylococcus species, said Erik Gerner, an industrial PhD student at Mölnlycke Health Care in Gothenburg, Sweden, and Gothenburg University.

Because of the growing problem of antibiotic resistance, alternative treatments are needed, and one possible alternative for treating infected wounds could be interfering with quorum sensing, the cell-to-cell communication used by bacteria, he said. He is hoping to explore this possibility as a novel treatment strategy for infected wounds.

“Quorum sensing is defined as the ability to detect and respond to population density,” Mr. Gerner said, noting that, when there is a sufficient density of bacteria, “they start to communicate with each other.” This enables them to act as a community and perform actions that they could not do as individual cells. Such actions include forming biofilms, which helps protect bacteria from their environment, such as the immune system. Other actions include collectively switching on the production of virulence factors and becoming resistant to treatments.

“Bacteria use quorum sensing to act collectively,” Mr. Gerner said. “If we could shut down this quorum sensing system, it would be very beneficial … and increase the chances to heal the wound.”

The quorum sensing system is based on the production of signaling molecules called AHL (N-acyl homoserine lactones), which are constantly produced at a low rate. This isn’t a problem until the level of bacteria increases and the level of quorum sensing breaches a threshold, he explained.

There are several benefits of inhibiting bacterial communication through disrupting quorum sensing, namely, “a low risk of resistance,” Mr. Gerner said. There is also potentially less toxin production by bacteria, and this could help the immune system in killing the invading bacteria.

One approach to disrupting quorum testing that Mr. Gerner has been investigating is the use of sodium salicylate (NaSa). So far, preclinical work shows that NaSa can reduce toxin production but not the growth rate of bacteria. The advantage of using NaSa is that it is nontoxic to human dermal fibroblasts, with similar results seen in human keratinocytes and immune cells. His work to date has shown that NaSa reduced activity of NF-kB (a proinflammatory signaling pathway) in differentiated and lipopolysaccharide-stimulated monocytes; NF-kB activated production of proinflammatory cytokines (such as interleukin-1 beta and IL-6) are elevated in EB wounds. “My studies support the bodies of evidence that bacteria use quorum sensing to coordinate … and to produce a large number of toxic factors,” Mr. Gerner concluded. Future studies will look at the potential of NaSa to disrupt this activity.
 

Skin microbiome of EB wounds

Understanding what bacteria most commonly colonize wounds in patients with EB was the subject of two unrelated presentations at the EB World Congress. Liat Samuelov, MD, of the department of molecular dermatology at Tel Aviv (Israel) Sourasky Medical Center, presented data on skin microbiome characteristics in eight patients with recessive dystrophic EB (RDEB). This showed that there was reduced bacterial diversity in wounds, and a “progressive development of dysbiosis across different stages of DEB wound formation.”

The skin microbiome has been implicated in several skin diseases, Dr. Samuelov and associates observed in a poster presentation. That includes the autoimmune blistering disease bullous pemphigoid (Exp Dermatol. 2017 Dec;26[12]:1221-7). “Colonization of DEB chronic wounds may lead to systemic infections, result in delayed healing, and possibly be involved in the development of squamous cell carcinoma,” they noted in the poster, “thus accurate delineation of the dysbiotic profile … may point to corrective measures of great therapeutic potential.”

The aim was to see what microorganisms were present in the chronic wounds of the patients. To be included in the study, patients must not have had any antibiotic treatment – oral or topical – in the past 6 months. Samples were taken from an untreated wound, around the wound, and from uninvolved skin, which were compared with samples taken from similar areas in age-matched controls.

Reduced bacterial diversity was observed in RDEB wounds, compared with uninvolved or perilesional areas and the skin of control subjects, Dr. Samuelov said in an oral presentation of the study results. There was increased abundance of Staphylococcus epidermidis and decreased Cutibacterium acnes, which she noted was in contrast to other studies where S. aureus was the most common colonizer in RDEB wounds.

Bacterial composition in each group was calculated using the beta-diversity score, while control samples showed similar microbial composition, the DEB samples had no microbial similarities among different samples. These data “suggest the need to ascertain the potential therapeutic benefit of interventions aimed at restoring normal microbiome composition in DEB,” Dr. Samuelov concluded.

Wound colonization and squamous cell carcinoma

Other research on wound microbiology was presented by Laura E. Levin, MD, a dermatologist at New York–Presbyterian, and associates. “Given the potential role of bacteria-induced inflammation in the development of wound-associated SCC [squamous cell carcinoma] in a subset of patients, we sought to improve our understanding of what microbes colonize and infect the wounds of patients with epidermolysis bullosa,” they explained in their poster.

The researchers, from New York–Presbyterian Morgan Stanley Children’s Hospital and Columbia University Irvine Medical Center, New York, presented data from a retrospective analysis of 739 wound cultures taken between 2001 and 2017 from 158 patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database. In the analysis, just under 70% of patients had DEB, of which 90% were of the RDEB subtype; 13% had EB simplex, 14% had junctional EB, and 3% had an unknown EB subtype.

At least one organism grew in 87% of cultures, with the most common microorganism isolated being Staphylococcus aureus (84% of cultures). Other commonly isolated microbes were Pseudomonas aeruginosa in 35% of cultures, Streptococcus group A in 34% of cultures (of which 22% were Streptococcus pyogenes), Corynebacterium species in 31% of cultures, and Proteus species in 18% of cultures.

“Improved understanding of what microbes are colonizing the wounds of our patients may help improve antibiotic stewardship,” the researchers stated.

Looking at the antibiotic susceptibilities, Dr. Levin and associates found that 68% of 115 cultures were sensitive to methicillin and 60% of 15 cultures were sensitive to mupirocin. “Resistance to many systemic and topical antibiotic agents in EB patients supports surveillance cultures with routine testing for mupirocin susceptibility,” they suggested.

A total of 23 patients developed SCC of whom 10 had cultures that grew S. aureus (90%) and P. aeruginosa (50%), and Proteus species (20%). Among the patients who did not develop SCC, the respective cultures positive for each of those microorganisms were 83%, 34%, and 11%. Perhaps “gram-negative and flagellated organisms may be more common in wounds of patients at risk for SCC,” they observed, adding that further studies were needed to determine if “wound microbiome interventions inhibit the risk of development of SCC and improve outcomes.”

Mr. Gerner’s research is supported by Mölnlycke Health Care. Dr. Samuelov had no disclosures. The work by Dr. Levin and associates is supported by the Pediatric Dermatology Research Alliance, EB Research Partnership, and the Epidermolysis Bullosa Medical Research Foundation.

ORLANDO – Biotin is the most popular consumer supplement for alopecia and highly popular online, but should patients be taking it?

Patients may want something “natural” to treat their hair loss, but “natural is not always good,” Amy McMichael, MD, professor and chair of the department of dermatology at Wake Forest Baptist Health, Winston-Salem, N.C., said at the ODAC Dermatology, Aesthetic, & Surgical Conference.

Dosages of commercially available biotin supplements can vary significantly, with some doses as high as 10,000 mcg, making supraphysiological dosing possible. Dr. McMichael said that, not only is biotin unlikely to help with a patient’s alopecia, but a high intake of biotin can interfere with certain assays that use streptavidin-biotin capture techniques (Clin Chem Lab Med. 2017 May 1;55[6]:817-25). This could present a problem for a patient who experiences an MI or has a thyroid disorder where a high level of biotin could affect lab results, she noted.

Dr. McMichael advises patients that there is a low likelihood that biotin will help their hair loss, and suggests that they stop taking the supplements, noting that all hair supplements contain biotin.

Questioning side effects of 5-alpha reductase inhibitors

Research in the early 2010s associated the 5-alpha reductase inhibitor finasteride with persistent sexual side effects and depression. But a later meta-analysis of the Prostate Cancer Prevention Trial and other trials did not find evidence of persistent sexual side effects or depression in men on finasteride, and the authors said that double-blind, placebo-controlled studies were needed (J Clin Aesthet Dermatol. 2014 Dec;7[12]:51-5).

However, two meta-analyses of 34 clinical trials published in 2015 found that none of the clinical trials evaluating finasteride treatment in patients with androgenic alopecia had accurate safety reporting (JAMA Dermatol. 2015 Jun;151[6]:600-6). Another study published by the same group in 2017 found that 0.8% of men aged 16-42 years to exposed to a 5-alpha reductase inhibitor developed persistent erectile dysfunction after a longer duration of exposure (median, 1,534 days). compared with a shorter duration of exposure (PeerJ. 2017 Mar 9;5:e3020).

The bottom line when considering use of 5-alpha reductase inhibitors in men is to discuss the outlier data on persistent sexual dysfunction in the studies, ask patients whether they have a history of sexual dysfunction and depression, and then only treat appropriate patients with no such history, Dr. McMichael said.

Use of 5-alpha reductase inhibitors also appears to be related to an increased risk of type 2 diabetes in men with benign prostatic hyperplasia, according to more recent data. In a study of patients in the U.K. Clinical Practice Research Datalink and Taiwanese National Health Insurance Research Database who received dutasteride, finasteride, or the alpha blocker tamsulosin, there was a slightly increased risk of type 2 diabetes among those who took the two 5-alpha reductase inhibitors, compared with those on tamsulosin (BMJ. 2019;365:l1204). In light of these results, Dr. McMichael advised clinicians to be aware of these risks and to consider screening patients for type 2 diabetes and ask them about their family history, but the results shouldn’t affect patients at risk for type 2 diabetes or metabolic disorder.
 

JAK inhibitors for alopecia areata

Within the past few years, promising results for Janus kinase (JAK) inhibitors like tofacitinib and ruxolitinib for alopecia areata have been reported, but they are currently not a first-line therapy, Dr. McMichael said. Consider methotrexate first in older adolescents and adults with more than 50% hair loss, followed by a JAK inhibitor if there is no improvement or methotrexate is not tolerated well.

Clinicians can consider enrolling their patients in a clinical trial to give them access to JAK inhibitors as a treatment option, she noted, and if a trial is not available, it may be worth appealing to an insurance company using an article titled “Alopecia areata is a medical disease” coauthored by Dr. McMichael and others (Am Acad Dermatol. 2018 Apr;78[4]:832-4). After two denials by insurance, the manufacturer’s patient assistance program (Xelsource) may be helpful in obtaining tofacitinib (Xeljanz) through a letter and references. There are adolescent data on JAK inhibitors for alopecia, but “absolutely no data” in very young children, so prior to adolescence, she would not recommend this treatment. In a study of 13 adolescents with alopecia areata, totalis, or universalis, those treated with tofacitinib for a mean of 6.5 months, 9 had significant hair regrowth with treatment and adverse events were mild (J Am Acad Dermatol. 2017 Jan;76[1]:29-32).

Dr. McMichael reports being an investigator for Allergan, Intendis, Proctor & Gamble, Samumed, Cassiopia, Concert, Aclaris, and Incyte; and is a consultant for Johnson & Johnson, Proctor & Gamble, Allergan, Bayer, Galderma, Incyte, Samumed, Aclaris, Anacor, Pfizer, Nutrafol, Bioniz, and Almirall.

ORLANDO – Biotin is the most popular consumer supplement for alopecia and highly popular online, but should patients be taking it?

Patients may want something “natural” to treat their hair loss, but “natural is not always good,” Amy McMichael, MD, professor and chair of the department of dermatology at Wake Forest Baptist Health, Winston-Salem, N.C., said at the ODAC Dermatology, Aesthetic, & Surgical Conference.

Dosages of commercially available biotin supplements can vary significantly, with some doses as high as 10,000 mcg, making supraphysiological dosing possible. Dr. McMichael said that, not only is biotin unlikely to help with a patient’s alopecia, but a high intake of biotin can interfere with certain assays that use streptavidin-biotin capture techniques (Clin Chem Lab Med. 2017 May 1;55[6]:817-25). This could present a problem for a patient who experiences an MI or has a thyroid disorder where a high level of biotin could affect lab results, she noted.

Dr. McMichael advises patients that there is a low likelihood that biotin will help their hair loss, and suggests that they stop taking the supplements, noting that all hair supplements contain biotin.

Questioning side effects of 5-alpha reductase inhibitors

Research in the early 2010s associated the 5-alpha reductase inhibitor finasteride with persistent sexual side effects and depression. But a later meta-analysis of the Prostate Cancer Prevention Trial and other trials did not find evidence of persistent sexual side effects or depression in men on finasteride, and the authors said that double-blind, placebo-controlled studies were needed (J Clin Aesthet Dermatol. 2014 Dec;7[12]:51-5).

However, two meta-analyses of 34 clinical trials published in 2015 found that none of the clinical trials evaluating finasteride treatment in patients with androgenic alopecia had accurate safety reporting (JAMA Dermatol. 2015 Jun;151[6]:600-6). Another study published by the same group in 2017 found that 0.8% of men aged 16-42 years to exposed to a 5-alpha reductase inhibitor developed persistent erectile dysfunction after a longer duration of exposure (median, 1,534 days). compared with a shorter duration of exposure (PeerJ. 2017 Mar 9;5:e3020).

The bottom line when considering use of 5-alpha reductase inhibitors in men is to discuss the outlier data on persistent sexual dysfunction in the studies, ask patients whether they have a history of sexual dysfunction and depression, and then only treat appropriate patients with no such history, Dr. McMichael said.

Use of 5-alpha reductase inhibitors also appears to be related to an increased risk of type 2 diabetes in men with benign prostatic hyperplasia, according to more recent data. In a study of patients in the U.K. Clinical Practice Research Datalink and Taiwanese National Health Insurance Research Database who received dutasteride, finasteride, or the alpha blocker tamsulosin, there was a slightly increased risk of type 2 diabetes among those who took the two 5-alpha reductase inhibitors, compared with those on tamsulosin (BMJ. 2019;365:l1204). In light of these results, Dr. McMichael advised clinicians to be aware of these risks and to consider screening patients for type 2 diabetes and ask them about their family history, but the results shouldn’t affect patients at risk for type 2 diabetes or metabolic disorder.
 

JAK inhibitors for alopecia areata

Within the past few years, promising results for Janus kinase (JAK) inhibitors like tofacitinib and ruxolitinib for alopecia areata have been reported, but they are currently not a first-line therapy, Dr. McMichael said. Consider methotrexate first in older adolescents and adults with more than 50% hair loss, followed by a JAK inhibitor if there is no improvement or methotrexate is not tolerated well.

Clinicians can consider enrolling their patients in a clinical trial to give them access to JAK inhibitors as a treatment option, she noted, and if a trial is not available, it may be worth appealing to an insurance company using an article titled “Alopecia areata is a medical disease” coauthored by Dr. McMichael and others (Am Acad Dermatol. 2018 Apr;78[4]:832-4). After two denials by insurance, the manufacturer’s patient assistance program (Xelsource) may be helpful in obtaining tofacitinib (Xeljanz) through a letter and references. There are adolescent data on JAK inhibitors for alopecia, but “absolutely no data” in very young children, so prior to adolescence, she would not recommend this treatment. In a study of 13 adolescents with alopecia areata, totalis, or universalis, those treated with tofacitinib for a mean of 6.5 months, 9 had significant hair regrowth with treatment and adverse events were mild (J Am Acad Dermatol. 2017 Jan;76[1]:29-32).

Dr. McMichael reports being an investigator for Allergan, Intendis, Proctor & Gamble, Samumed, Cassiopia, Concert, Aclaris, and Incyte; and is a consultant for Johnson & Johnson, Proctor & Gamble, Allergan, Bayer, Galderma, Incyte, Samumed, Aclaris, Anacor, Pfizer, Nutrafol, Bioniz, and Almirall.

ORLANDO – Biotin is the most popular consumer supplement for alopecia and highly popular online, but should patients be taking it?

Patients may want something “natural” to treat their hair loss, but “natural is not always good,” Amy McMichael, MD, professor and chair of the department of dermatology at Wake Forest Baptist Health, Winston-Salem, N.C., said at the ODAC Dermatology, Aesthetic, & Surgical Conference.

Dosages of commercially available biotin supplements can vary significantly, with some doses as high as 10,000 mcg, making supraphysiological dosing possible. Dr. McMichael said that, not only is biotin unlikely to help with a patient’s alopecia, but a high intake of biotin can interfere with certain assays that use streptavidin-biotin capture techniques (Clin Chem Lab Med. 2017 May 1;55[6]:817-25). This could present a problem for a patient who experiences an MI or has a thyroid disorder where a high level of biotin could affect lab results, she noted.

Dr. McMichael advises patients that there is a low likelihood that biotin will help their hair loss, and suggests that they stop taking the supplements, noting that all hair supplements contain biotin.

Questioning side effects of 5-alpha reductase inhibitors

Research in the early 2010s associated the 5-alpha reductase inhibitor finasteride with persistent sexual side effects and depression. But a later meta-analysis of the Prostate Cancer Prevention Trial and other trials did not find evidence of persistent sexual side effects or depression in men on finasteride, and the authors said that double-blind, placebo-controlled studies were needed (J Clin Aesthet Dermatol. 2014 Dec;7[12]:51-5).

However, two meta-analyses of 34 clinical trials published in 2015 found that none of the clinical trials evaluating finasteride treatment in patients with androgenic alopecia had accurate safety reporting (JAMA Dermatol. 2015 Jun;151[6]:600-6). Another study published by the same group in 2017 found that 0.8% of men aged 16-42 years to exposed to a 5-alpha reductase inhibitor developed persistent erectile dysfunction after a longer duration of exposure (median, 1,534 days). compared with a shorter duration of exposure (PeerJ. 2017 Mar 9;5:e3020).

The bottom line when considering use of 5-alpha reductase inhibitors in men is to discuss the outlier data on persistent sexual dysfunction in the studies, ask patients whether they have a history of sexual dysfunction and depression, and then only treat appropriate patients with no such history, Dr. McMichael said.

Use of 5-alpha reductase inhibitors also appears to be related to an increased risk of type 2 diabetes in men with benign prostatic hyperplasia, according to more recent data. In a study of patients in the U.K. Clinical Practice Research Datalink and Taiwanese National Health Insurance Research Database who received dutasteride, finasteride, or the alpha blocker tamsulosin, there was a slightly increased risk of type 2 diabetes among those who took the two 5-alpha reductase inhibitors, compared with those on tamsulosin (BMJ. 2019;365:l1204). In light of these results, Dr. McMichael advised clinicians to be aware of these risks and to consider screening patients for type 2 diabetes and ask them about their family history, but the results shouldn’t affect patients at risk for type 2 diabetes or metabolic disorder.
 

JAK inhibitors for alopecia areata

Within the past few years, promising results for Janus kinase (JAK) inhibitors like tofacitinib and ruxolitinib for alopecia areata have been reported, but they are currently not a first-line therapy, Dr. McMichael said. Consider methotrexate first in older adolescents and adults with more than 50% hair loss, followed by a JAK inhibitor if there is no improvement or methotrexate is not tolerated well.

Clinicians can consider enrolling their patients in a clinical trial to give them access to JAK inhibitors as a treatment option, she noted, and if a trial is not available, it may be worth appealing to an insurance company using an article titled “Alopecia areata is a medical disease” coauthored by Dr. McMichael and others (Am Acad Dermatol. 2018 Apr;78[4]:832-4). After two denials by insurance, the manufacturer’s patient assistance program (Xelsource) may be helpful in obtaining tofacitinib (Xeljanz) through a letter and references. There are adolescent data on JAK inhibitors for alopecia, but “absolutely no data” in very young children, so prior to adolescence, she would not recommend this treatment. In a study of 13 adolescents with alopecia areata, totalis, or universalis, those treated with tofacitinib for a mean of 6.5 months, 9 had significant hair regrowth with treatment and adverse events were mild (J Am Acad Dermatol. 2017 Jan;76[1]:29-32).

Dr. McMichael reports being an investigator for Allergan, Intendis, Proctor & Gamble, Samumed, Cassiopia, Concert, Aclaris, and Incyte; and is a consultant for Johnson & Johnson, Proctor & Gamble, Allergan, Bayer, Galderma, Incyte, Samumed, Aclaris, Anacor, Pfizer, Nutrafol, Bioniz, and Almirall.