Transgender adolescents are more likely to report all types of lifetime suicidality risk than are their cisgender peers, and transgender youth as well as nonbinary adolescents assigned female at birth are at markedly high risk for suicidal ideation and attempt, new research suggests.

The study, which included more than 2,000 adolescents and was published in the October 14 issue of Pediatrics, provides new insights into suicide risk in gender identity subgroups, according to the investigators.

“Limited measures of gender identity may have led to inaccurate estimates of suicidality among transgender females in previous studies,” wrote Brian C. Thoma, PhD, and his colleagues at the University of Pittsburgh. The researchers noted that transgender females and nonbinary adolescents assigned male at birth are frequently combined in studies.

“However, our results indicate transgender females have higher risk for suicidal ideation and attempt compared with cisgender adolescents, whereas nonbinary adolescents assigned male at birth do not,” they wrote. “It is possible that estimates of suicidality that aggregate all transgender adolescents assigned male at birth into one group underestimate rates of suicidality among transgender females.”

The study, which analyzed results from a cross-sectional online survey from July to October 2018, was comprised of 2,020 adolescents, including 1,134 transgender adolescents.

The researchers divided respondents into seven categories: Cisgender males, cisgender females, transgender males, transgender females, nonbinary adolescents assigned female at birth, nonbinary adolescents assigned male at birth, and questioning gender identity. They then assessed non-suicidal self-injury (NSSI) and lifetime suicidality.

Compared to cisgender youth, transgender adolescents overall were more likely to report all outcomes: passive death wish (odds ratio [OR]=2.60), suicidal ideation (OR=2.20), suicide plan (OR=1.82), suicide attempt (OR=1.65), attempt requiring medical care (OR=2.01), and NSSI (OR=2.88).

Using cisgender males as reference after adjustment for all demographics, “cisgender females, transgender males, and nonbinary adolescents assigned female at birth had higher odds of each suicidality outcome” (OR= 1.49-5.85; OR=2.72-12.12; OR=1.84-8.59, respectively), the authors reported. “Transgender females had higher odds of each outcome [OR=2.73-6.30] except for suicide attempt requiring medical care. Nonbinary adolescents assigned male at birth had higher odds of suicide attempt requiring medical care [OR=10.13] and NSSI [OR=3.79]. Adolescents questioning their gender identity had higher odds of all outcomes [OR=3.23-7.59] except for suicide attempt.”

When compared to cisgender females as reference, however, only transgender males and transgender females had higher odds of suicidal ideation and attempts.

The overall findings were unsurprising since the higher rates of suicidality among transgender youth have already been documented, but the classification of participants was interesting, Gerald Montano, DO, an assistant professor of pediatrics at the University of Pittsburgh School of Medicine, said in an interview. Dr Montano was not involved in the study.

“It’s always been a challenge because, in the past, they always lumped transgender youth along with lesbian, gay, and bisexual youth,” Dr Montano said. This study is one of the few to go into more detail in considering participants’ gender identity, which was wise given that suicidal risk may differ accordingly.

The biggest take-home message of this study is the importance of screening for suicidality after informing adolescent patients of the limits of confidentiality, Dr Montano said.

“I think it’s very important for the physician to be aware of the reasons for those thoughts of suicide,” he continued. “A lot of it has to do with their gender identity and from discrimination and stigma from the general population.”

The research was funded by the University of Pittsburgh Central Research Development Fund and the National Institutes of Health. The authors reported no conflicts of interest.

SOURCE: Thoma BC et al, Pediatrics, October 14, 2019. DOI: 10.1542/peds.2019-1183

Transgender adolescents are more likely to report all types of lifetime suicidality risk than are their cisgender peers, and transgender youth as well as nonbinary adolescents assigned female at birth are at markedly high risk for suicidal ideation and attempt, new research suggests.

The study, which included more than 2,000 adolescents and was published in the October 14 issue of Pediatrics, provides new insights into suicide risk in gender identity subgroups, according to the investigators.

“Limited measures of gender identity may have led to inaccurate estimates of suicidality among transgender females in previous studies,” wrote Brian C. Thoma, PhD, and his colleagues at the University of Pittsburgh. The researchers noted that transgender females and nonbinary adolescents assigned male at birth are frequently combined in studies.

“However, our results indicate transgender females have higher risk for suicidal ideation and attempt compared with cisgender adolescents, whereas nonbinary adolescents assigned male at birth do not,” they wrote. “It is possible that estimates of suicidality that aggregate all transgender adolescents assigned male at birth into one group underestimate rates of suicidality among transgender females.”

The study, which analyzed results from a cross-sectional online survey from July to October 2018, was comprised of 2,020 adolescents, including 1,134 transgender adolescents.

The researchers divided respondents into seven categories: Cisgender males, cisgender females, transgender males, transgender females, nonbinary adolescents assigned female at birth, nonbinary adolescents assigned male at birth, and questioning gender identity. They then assessed non-suicidal self-injury (NSSI) and lifetime suicidality.

Compared to cisgender youth, transgender adolescents overall were more likely to report all outcomes: passive death wish (odds ratio [OR]=2.60), suicidal ideation (OR=2.20), suicide plan (OR=1.82), suicide attempt (OR=1.65), attempt requiring medical care (OR=2.01), and NSSI (OR=2.88).

Using cisgender males as reference after adjustment for all demographics, “cisgender females, transgender males, and nonbinary adolescents assigned female at birth had higher odds of each suicidality outcome” (OR= 1.49-5.85; OR=2.72-12.12; OR=1.84-8.59, respectively), the authors reported. “Transgender females had higher odds of each outcome [OR=2.73-6.30] except for suicide attempt requiring medical care. Nonbinary adolescents assigned male at birth had higher odds of suicide attempt requiring medical care [OR=10.13] and NSSI [OR=3.79]. Adolescents questioning their gender identity had higher odds of all outcomes [OR=3.23-7.59] except for suicide attempt.”

When compared to cisgender females as reference, however, only transgender males and transgender females had higher odds of suicidal ideation and attempts.

The overall findings were unsurprising since the higher rates of suicidality among transgender youth have already been documented, but the classification of participants was interesting, Gerald Montano, DO, an assistant professor of pediatrics at the University of Pittsburgh School of Medicine, said in an interview. Dr Montano was not involved in the study.

“It’s always been a challenge because, in the past, they always lumped transgender youth along with lesbian, gay, and bisexual youth,” Dr Montano said. This study is one of the few to go into more detail in considering participants’ gender identity, which was wise given that suicidal risk may differ accordingly.

The biggest take-home message of this study is the importance of screening for suicidality after informing adolescent patients of the limits of confidentiality, Dr Montano said.

“I think it’s very important for the physician to be aware of the reasons for those thoughts of suicide,” he continued. “A lot of it has to do with their gender identity and from discrimination and stigma from the general population.”

The research was funded by the University of Pittsburgh Central Research Development Fund and the National Institutes of Health. The authors reported no conflicts of interest.

SOURCE: Thoma BC et al, Pediatrics, October 14, 2019. DOI: 10.1542/peds.2019-1183

Transgender adolescents are more likely to report all types of lifetime suicidality risk than are their cisgender peers, and transgender youth as well as nonbinary adolescents assigned female at birth are at markedly high risk for suicidal ideation and attempt, new research suggests.

The study, which included more than 2,000 adolescents and was published in the October 14 issue of Pediatrics, provides new insights into suicide risk in gender identity subgroups, according to the investigators.

“Limited measures of gender identity may have led to inaccurate estimates of suicidality among transgender females in previous studies,” wrote Brian C. Thoma, PhD, and his colleagues at the University of Pittsburgh. The researchers noted that transgender females and nonbinary adolescents assigned male at birth are frequently combined in studies.

“However, our results indicate transgender females have higher risk for suicidal ideation and attempt compared with cisgender adolescents, whereas nonbinary adolescents assigned male at birth do not,” they wrote. “It is possible that estimates of suicidality that aggregate all transgender adolescents assigned male at birth into one group underestimate rates of suicidality among transgender females.”

The study, which analyzed results from a cross-sectional online survey from July to October 2018, was comprised of 2,020 adolescents, including 1,134 transgender adolescents.

The researchers divided respondents into seven categories: Cisgender males, cisgender females, transgender males, transgender females, nonbinary adolescents assigned female at birth, nonbinary adolescents assigned male at birth, and questioning gender identity. They then assessed non-suicidal self-injury (NSSI) and lifetime suicidality.

Compared to cisgender youth, transgender adolescents overall were more likely to report all outcomes: passive death wish (odds ratio [OR]=2.60), suicidal ideation (OR=2.20), suicide plan (OR=1.82), suicide attempt (OR=1.65), attempt requiring medical care (OR=2.01), and NSSI (OR=2.88).

Using cisgender males as reference after adjustment for all demographics, “cisgender females, transgender males, and nonbinary adolescents assigned female at birth had higher odds of each suicidality outcome” (OR= 1.49-5.85; OR=2.72-12.12; OR=1.84-8.59, respectively), the authors reported. “Transgender females had higher odds of each outcome [OR=2.73-6.30] except for suicide attempt requiring medical care. Nonbinary adolescents assigned male at birth had higher odds of suicide attempt requiring medical care [OR=10.13] and NSSI [OR=3.79]. Adolescents questioning their gender identity had higher odds of all outcomes [OR=3.23-7.59] except for suicide attempt.”

When compared to cisgender females as reference, however, only transgender males and transgender females had higher odds of suicidal ideation and attempts.

The overall findings were unsurprising since the higher rates of suicidality among transgender youth have already been documented, but the classification of participants was interesting, Gerald Montano, DO, an assistant professor of pediatrics at the University of Pittsburgh School of Medicine, said in an interview. Dr Montano was not involved in the study.

“It’s always been a challenge because, in the past, they always lumped transgender youth along with lesbian, gay, and bisexual youth,” Dr Montano said. This study is one of the few to go into more detail in considering participants’ gender identity, which was wise given that suicidal risk may differ accordingly.

The biggest take-home message of this study is the importance of screening for suicidality after informing adolescent patients of the limits of confidentiality, Dr Montano said.

“I think it’s very important for the physician to be aware of the reasons for those thoughts of suicide,” he continued. “A lot of it has to do with their gender identity and from discrimination and stigma from the general population.”

The research was funded by the University of Pittsburgh Central Research Development Fund and the National Institutes of Health. The authors reported no conflicts of interest.

SOURCE: Thoma BC et al, Pediatrics, October 14, 2019. DOI: 10.1542/peds.2019-1183

New research presents a complex picture of self-reported suicidal behavior in U.S. teenagers over the last few decades. Rates of suicidal ideation and plans dipped overall from 1991 to 2017, but the rate of suicide attempts grew slightly in black adolescents.

White young people “have historically had higher rates of suicide attempts...compared with their black counterparts; however, this study provides some evidence to the contrary,” wrote the authors of the report, which appears in the November issue of Pediatrics.

The investigators, led by Michael A. Lindsey, PhD, executive director of the McSilver Institute for Poverty Policy and Research at New York University, New York, note that suicide is the second leading cause of death in the United States in those aged 12-17. (Accidents rank first.) According to recent research, black children younger than 12 are at higher risk for death by suicide, compared with whites.

For the new study, researchers analyzed data from the Youth Risk Behavior Survey, which is conducted every 2 years among high school students in all 50 states and the District of Columbia. They examined data from 198,540 teens (mean age=16, 51% male; 49% female).

During the study period, the weighted overall prevalences rates of suicidal ideation, planning, attempt, and injury due to attempt were 19%, 15%, 8%, and 3%, respectively. “Our findings reveal that over that span of time, almost 1 in 5 adolescents are thinking about suicide... and > 1 in 10 has a suicide plan,” the researchers wrote.

Rates of suicidal ideation and planning fell overall, and among females, the rate of suicide attempts fell significantly (odds ratio [OR]=0.98). But self-reported suicide attempts grew significantly among black teens (OR=1.02), and injuries due to suicide attempts grew among black males (OR=1.04).

The findings are “troubling because attempts are the most prominent risk factor associated with suicide death,” the study authors wrote. “Findings regarding the rising rates of suicide attempts in black youth may be related to the documented disparities in mental health treatment and common social etiologic factors disproportionately experienced by black youth.”

In an accompanying commentary, psychiatrist Benjamin N. Shain, MD, PhD, of the University of Chicago, noted a seemingly “counterintuitive” fact: Black teens still have lower rates of suicide than whites teens “despite the greater, long-standing difficulties encountered by black adolescents, including disparities in mental health treatment and disproportionately higher stressors, racial discrimination, and childhood abuse and neglect, as well as other adverse experiences, such as poverty.”

It’s not clear why the reported suicide rate is lower in black adolescents than their white counterparts, Dr. Shain wrote, but misclassification and “undercount as a result of violence with suicidal intent, for example, ‘suicide by cop’” may play a role. Additionally, protective factors may have kept suicide rates down. “External attributional orientation (eg, blaming others or ‘the system’ for difficulties) among blacks may have buffered this group from internalizing blame related to psychological stressors,” he wrote.

Among black adolescents, the growing rate of suicidal behavior is concerning and may be due to a weakening of the hypothesized protective mechanism. Perhaps, Dr. Shain wrote, they now are blaming themselves more for difficulties encountered, “thus leading to an increase in suicide risk factors, particularly depression.” He stressed that, regardless of the reasons for the increase in suicide and suicide attempts, prevention and intervention efforts remain critical.

No study funding is reported, and authors report no relevant disclosures. Dr. Shain reports no relevant disclosures.


SOURCE: Lindsey MA et al, Pediatrics. 2019;144(5): e20191187, DOI:10.1542/peds.2019-1187.

New research presents a complex picture of self-reported suicidal behavior in U.S. teenagers over the last few decades. Rates of suicidal ideation and plans dipped overall from 1991 to 2017, but the rate of suicide attempts grew slightly in black adolescents.

White young people “have historically had higher rates of suicide attempts...compared with their black counterparts; however, this study provides some evidence to the contrary,” wrote the authors of the report, which appears in the November issue of Pediatrics.

The investigators, led by Michael A. Lindsey, PhD, executive director of the McSilver Institute for Poverty Policy and Research at New York University, New York, note that suicide is the second leading cause of death in the United States in those aged 12-17. (Accidents rank first.) According to recent research, black children younger than 12 are at higher risk for death by suicide, compared with whites.

For the new study, researchers analyzed data from the Youth Risk Behavior Survey, which is conducted every 2 years among high school students in all 50 states and the District of Columbia. They examined data from 198,540 teens (mean age=16, 51% male; 49% female).

During the study period, the weighted overall prevalences rates of suicidal ideation, planning, attempt, and injury due to attempt were 19%, 15%, 8%, and 3%, respectively. “Our findings reveal that over that span of time, almost 1 in 5 adolescents are thinking about suicide... and > 1 in 10 has a suicide plan,” the researchers wrote.

Rates of suicidal ideation and planning fell overall, and among females, the rate of suicide attempts fell significantly (odds ratio [OR]=0.98). But self-reported suicide attempts grew significantly among black teens (OR=1.02), and injuries due to suicide attempts grew among black males (OR=1.04).

The findings are “troubling because attempts are the most prominent risk factor associated with suicide death,” the study authors wrote. “Findings regarding the rising rates of suicide attempts in black youth may be related to the documented disparities in mental health treatment and common social etiologic factors disproportionately experienced by black youth.”

In an accompanying commentary, psychiatrist Benjamin N. Shain, MD, PhD, of the University of Chicago, noted a seemingly “counterintuitive” fact: Black teens still have lower rates of suicide than whites teens “despite the greater, long-standing difficulties encountered by black adolescents, including disparities in mental health treatment and disproportionately higher stressors, racial discrimination, and childhood abuse and neglect, as well as other adverse experiences, such as poverty.”

It’s not clear why the reported suicide rate is lower in black adolescents than their white counterparts, Dr. Shain wrote, but misclassification and “undercount as a result of violence with suicidal intent, for example, ‘suicide by cop’” may play a role. Additionally, protective factors may have kept suicide rates down. “External attributional orientation (eg, blaming others or ‘the system’ for difficulties) among blacks may have buffered this group from internalizing blame related to psychological stressors,” he wrote.

Among black adolescents, the growing rate of suicidal behavior is concerning and may be due to a weakening of the hypothesized protective mechanism. Perhaps, Dr. Shain wrote, they now are blaming themselves more for difficulties encountered, “thus leading to an increase in suicide risk factors, particularly depression.” He stressed that, regardless of the reasons for the increase in suicide and suicide attempts, prevention and intervention efforts remain critical.

No study funding is reported, and authors report no relevant disclosures. Dr. Shain reports no relevant disclosures.


SOURCE: Lindsey MA et al, Pediatrics. 2019;144(5): e20191187, DOI:10.1542/peds.2019-1187.

New research presents a complex picture of self-reported suicidal behavior in U.S. teenagers over the last few decades. Rates of suicidal ideation and plans dipped overall from 1991 to 2017, but the rate of suicide attempts grew slightly in black adolescents.

White young people “have historically had higher rates of suicide attempts...compared with their black counterparts; however, this study provides some evidence to the contrary,” wrote the authors of the report, which appears in the November issue of Pediatrics.

The investigators, led by Michael A. Lindsey, PhD, executive director of the McSilver Institute for Poverty Policy and Research at New York University, New York, note that suicide is the second leading cause of death in the United States in those aged 12-17. (Accidents rank first.) According to recent research, black children younger than 12 are at higher risk for death by suicide, compared with whites.

For the new study, researchers analyzed data from the Youth Risk Behavior Survey, which is conducted every 2 years among high school students in all 50 states and the District of Columbia. They examined data from 198,540 teens (mean age=16, 51% male; 49% female).

During the study period, the weighted overall prevalences rates of suicidal ideation, planning, attempt, and injury due to attempt were 19%, 15%, 8%, and 3%, respectively. “Our findings reveal that over that span of time, almost 1 in 5 adolescents are thinking about suicide... and > 1 in 10 has a suicide plan,” the researchers wrote.

Rates of suicidal ideation and planning fell overall, and among females, the rate of suicide attempts fell significantly (odds ratio [OR]=0.98). But self-reported suicide attempts grew significantly among black teens (OR=1.02), and injuries due to suicide attempts grew among black males (OR=1.04).

The findings are “troubling because attempts are the most prominent risk factor associated with suicide death,” the study authors wrote. “Findings regarding the rising rates of suicide attempts in black youth may be related to the documented disparities in mental health treatment and common social etiologic factors disproportionately experienced by black youth.”

In an accompanying commentary, psychiatrist Benjamin N. Shain, MD, PhD, of the University of Chicago, noted a seemingly “counterintuitive” fact: Black teens still have lower rates of suicide than whites teens “despite the greater, long-standing difficulties encountered by black adolescents, including disparities in mental health treatment and disproportionately higher stressors, racial discrimination, and childhood abuse and neglect, as well as other adverse experiences, such as poverty.”

It’s not clear why the reported suicide rate is lower in black adolescents than their white counterparts, Dr. Shain wrote, but misclassification and “undercount as a result of violence with suicidal intent, for example, ‘suicide by cop’” may play a role. Additionally, protective factors may have kept suicide rates down. “External attributional orientation (eg, blaming others or ‘the system’ for difficulties) among blacks may have buffered this group from internalizing blame related to psychological stressors,” he wrote.

Among black adolescents, the growing rate of suicidal behavior is concerning and may be due to a weakening of the hypothesized protective mechanism. Perhaps, Dr. Shain wrote, they now are blaming themselves more for difficulties encountered, “thus leading to an increase in suicide risk factors, particularly depression.” He stressed that, regardless of the reasons for the increase in suicide and suicide attempts, prevention and intervention efforts remain critical.

No study funding is reported, and authors report no relevant disclosures. Dr. Shain reports no relevant disclosures.


SOURCE: Lindsey MA et al, Pediatrics. 2019;144(5): e20191187, DOI:10.1542/peds.2019-1187.

MADRID – In patients managed on mechanical ventilation in an intensive care unit following cardiac surgery, a fully automated system provides more reliable ventilatory support than highly experienced ICU nurses, suggest results of a randomized trial.

The study’s control group received usual care, which means that nurses adjusted mechanical ventilation manually in response to respiratory rate, tidal volume, positive end-respiratory pressure (PEEP), and other factors to maintain ventilation within parameters associated with safe respiration. The experimental group was managed with a fully automated closed-loop system to make these adjustments without any nurse intervention.

For those in the experimental group “the proportion of time in the optimal zone was increased and the proportion of time in the unsafe zone was decreased” relative to those randomized to conventional nursing care, Marcus J. Schultz, MD, reported at the annual congress of the European Respiratory Society.

Conducted at a hospital with an experienced ICU staff, the study had a control arm that was managed by “dedicated nurses who, I can tell you, are very eager to provide the best level of care possible,” said Dr. Schultz, professor of experimental intensive care, University of Amsterdam, the Netherlands..

The investigator-initiated POSITiVE trial randomized 220 cardiac surgery patients scheduled to receive postoperative mechanical ventilation in the ICU. Exclusions included those with class III or higher chronic obstructive pulmonary disease (COPD), a requirement for extracorporeal membrane oxygenation (ECMO), or a history of lung surgery.

The primary endpoint was the proportion of time spent in an optimal zone, an acceptable zone, or a dangerous zone of ventilation based on predefined values for tidal volume, maximum airway pressure, end-tidal CO₂, and oxygen saturation (SpO₂).

The greatest between-group difference was seen in the proportion of time spent in the optimal zone. This climbed from approximately 35% in the control arm to slightly more than 70% in the experimental arm, a significant difference. The proportion of time in the dangerous zone was reduced from approximately 6% in the control arm to 3% in the automated arm. On average nurse-managed patients spent nearly 60% of the time in the acceptable zone versus less than 30% of those in the automated experimental arm.

A heat map using green, yellow, and red to represent optimal, acceptable, and dangerous zones, respectively, for individual participants in the trial provided a more stark global impression. For the control group, the heat map was primarily yellow with scattered dashes of green and red. For the experimental group, the map was primarily green with dashes of yellow and a much smaller number of red dashes relative to the control group.

In addition, the time to spontaneous breathing was 38% shorter for those randomized to automated ventilation than to conventional care, a significant difference.

There are now many devices marketed for automated ventilation, according to Dr. Schultz. The device used in this study was the proprietary INTELLiVENT-ASV system, marketed by Hamilton Medical, which was selected based on prior satisfactory experience. Although not unique, this system has sophisticated software to adjust ventilation to reach targets set by the clinician on the basis of information it is receiving from physiologic sensors for such variables as respiratory rate, tidal volume, and inspiratory pressure.

“It is frequently adjusting the PEEP levels to reach the lowest driving pressure,” said Dr. Schultz. Among its many other features, it also “gives spontaneous breathing trials automatically.”

Uncomplicated patients were selected purposefully to test this system, but Dr. Schultz said that a second trial, called POSITiVE 2, is now being planned that will enroll more complex patients. Keeping complex patients within the optimal zone as defined by tidal volume and other critical variables has the potential to reduce the lung damage that is known to occur when these are not optimized.

“Applying safe ventilatory support in clinical practice remains a serious challenge and is extremely time consuming,” Dr. Schultz said. He reported that fully automated ventilation appears to be reliable, and “it takes out the human factor” in regard to diligence in monitoring and potential for error.

Overall, these results support the potential for a fully automated system to improve optimal ventilatory support, reduce risk of lung injury, and reduce staffing required for monitoring of mechanical ventilation, according to Dr. Schultz.

Relative costs were not evaluated in this analysis, but might be another factor relevant to the value of fully automated ventilation in ICU patients.
 

MADRID – In patients managed on mechanical ventilation in an intensive care unit following cardiac surgery, a fully automated system provides more reliable ventilatory support than highly experienced ICU nurses, suggest results of a randomized trial.

The study’s control group received usual care, which means that nurses adjusted mechanical ventilation manually in response to respiratory rate, tidal volume, positive end-respiratory pressure (PEEP), and other factors to maintain ventilation within parameters associated with safe respiration. The experimental group was managed with a fully automated closed-loop system to make these adjustments without any nurse intervention.

For those in the experimental group “the proportion of time in the optimal zone was increased and the proportion of time in the unsafe zone was decreased” relative to those randomized to conventional nursing care, Marcus J. Schultz, MD, reported at the annual congress of the European Respiratory Society.

Conducted at a hospital with an experienced ICU staff, the study had a control arm that was managed by “dedicated nurses who, I can tell you, are very eager to provide the best level of care possible,” said Dr. Schultz, professor of experimental intensive care, University of Amsterdam, the Netherlands..

The investigator-initiated POSITiVE trial randomized 220 cardiac surgery patients scheduled to receive postoperative mechanical ventilation in the ICU. Exclusions included those with class III or higher chronic obstructive pulmonary disease (COPD), a requirement for extracorporeal membrane oxygenation (ECMO), or a history of lung surgery.

The primary endpoint was the proportion of time spent in an optimal zone, an acceptable zone, or a dangerous zone of ventilation based on predefined values for tidal volume, maximum airway pressure, end-tidal CO₂, and oxygen saturation (SpO₂).

The greatest between-group difference was seen in the proportion of time spent in the optimal zone. This climbed from approximately 35% in the control arm to slightly more than 70% in the experimental arm, a significant difference. The proportion of time in the dangerous zone was reduced from approximately 6% in the control arm to 3% in the automated arm. On average nurse-managed patients spent nearly 60% of the time in the acceptable zone versus less than 30% of those in the automated experimental arm.

A heat map using green, yellow, and red to represent optimal, acceptable, and dangerous zones, respectively, for individual participants in the trial provided a more stark global impression. For the control group, the heat map was primarily yellow with scattered dashes of green and red. For the experimental group, the map was primarily green with dashes of yellow and a much smaller number of red dashes relative to the control group.

In addition, the time to spontaneous breathing was 38% shorter for those randomized to automated ventilation than to conventional care, a significant difference.

There are now many devices marketed for automated ventilation, according to Dr. Schultz. The device used in this study was the proprietary INTELLiVENT-ASV system, marketed by Hamilton Medical, which was selected based on prior satisfactory experience. Although not unique, this system has sophisticated software to adjust ventilation to reach targets set by the clinician on the basis of information it is receiving from physiologic sensors for such variables as respiratory rate, tidal volume, and inspiratory pressure.

“It is frequently adjusting the PEEP levels to reach the lowest driving pressure,” said Dr. Schultz. Among its many other features, it also “gives spontaneous breathing trials automatically.”

Uncomplicated patients were selected purposefully to test this system, but Dr. Schultz said that a second trial, called POSITiVE 2, is now being planned that will enroll more complex patients. Keeping complex patients within the optimal zone as defined by tidal volume and other critical variables has the potential to reduce the lung damage that is known to occur when these are not optimized.

“Applying safe ventilatory support in clinical practice remains a serious challenge and is extremely time consuming,” Dr. Schultz said. He reported that fully automated ventilation appears to be reliable, and “it takes out the human factor” in regard to diligence in monitoring and potential for error.

Overall, these results support the potential for a fully automated system to improve optimal ventilatory support, reduce risk of lung injury, and reduce staffing required for monitoring of mechanical ventilation, according to Dr. Schultz.

Relative costs were not evaluated in this analysis, but might be another factor relevant to the value of fully automated ventilation in ICU patients.
 

MADRID – In patients managed on mechanical ventilation in an intensive care unit following cardiac surgery, a fully automated system provides more reliable ventilatory support than highly experienced ICU nurses, suggest results of a randomized trial.

The study’s control group received usual care, which means that nurses adjusted mechanical ventilation manually in response to respiratory rate, tidal volume, positive end-respiratory pressure (PEEP), and other factors to maintain ventilation within parameters associated with safe respiration. The experimental group was managed with a fully automated closed-loop system to make these adjustments without any nurse intervention.

For those in the experimental group “the proportion of time in the optimal zone was increased and the proportion of time in the unsafe zone was decreased” relative to those randomized to conventional nursing care, Marcus J. Schultz, MD, reported at the annual congress of the European Respiratory Society.

Conducted at a hospital with an experienced ICU staff, the study had a control arm that was managed by “dedicated nurses who, I can tell you, are very eager to provide the best level of care possible,” said Dr. Schultz, professor of experimental intensive care, University of Amsterdam, the Netherlands..

The investigator-initiated POSITiVE trial randomized 220 cardiac surgery patients scheduled to receive postoperative mechanical ventilation in the ICU. Exclusions included those with class III or higher chronic obstructive pulmonary disease (COPD), a requirement for extracorporeal membrane oxygenation (ECMO), or a history of lung surgery.

The primary endpoint was the proportion of time spent in an optimal zone, an acceptable zone, or a dangerous zone of ventilation based on predefined values for tidal volume, maximum airway pressure, end-tidal CO₂, and oxygen saturation (SpO₂).

The greatest between-group difference was seen in the proportion of time spent in the optimal zone. This climbed from approximately 35% in the control arm to slightly more than 70% in the experimental arm, a significant difference. The proportion of time in the dangerous zone was reduced from approximately 6% in the control arm to 3% in the automated arm. On average nurse-managed patients spent nearly 60% of the time in the acceptable zone versus less than 30% of those in the automated experimental arm.

A heat map using green, yellow, and red to represent optimal, acceptable, and dangerous zones, respectively, for individual participants in the trial provided a more stark global impression. For the control group, the heat map was primarily yellow with scattered dashes of green and red. For the experimental group, the map was primarily green with dashes of yellow and a much smaller number of red dashes relative to the control group.

In addition, the time to spontaneous breathing was 38% shorter for those randomized to automated ventilation than to conventional care, a significant difference.

There are now many devices marketed for automated ventilation, according to Dr. Schultz. The device used in this study was the proprietary INTELLiVENT-ASV system, marketed by Hamilton Medical, which was selected based on prior satisfactory experience. Although not unique, this system has sophisticated software to adjust ventilation to reach targets set by the clinician on the basis of information it is receiving from physiologic sensors for such variables as respiratory rate, tidal volume, and inspiratory pressure.

“It is frequently adjusting the PEEP levels to reach the lowest driving pressure,” said Dr. Schultz. Among its many other features, it also “gives spontaneous breathing trials automatically.”

Uncomplicated patients were selected purposefully to test this system, but Dr. Schultz said that a second trial, called POSITiVE 2, is now being planned that will enroll more complex patients. Keeping complex patients within the optimal zone as defined by tidal volume and other critical variables has the potential to reduce the lung damage that is known to occur when these are not optimized.

“Applying safe ventilatory support in clinical practice remains a serious challenge and is extremely time consuming,” Dr. Schultz said. He reported that fully automated ventilation appears to be reliable, and “it takes out the human factor” in regard to diligence in monitoring and potential for error.

Overall, these results support the potential for a fully automated system to improve optimal ventilatory support, reduce risk of lung injury, and reduce staffing required for monitoring of mechanical ventilation, according to Dr. Schultz.

Relative costs were not evaluated in this analysis, but might be another factor relevant to the value of fully automated ventilation in ICU patients.
 

Patients given a single preoperative dose of intravenous dexamethasone had significantly less pain after total knee arthroplasty than did those given a placebo in a randomized controlled study of 100 adults.

“Corticosteroids were introduced several years ago for relieving postoperative pain in total joint replacement but, unfortunately, are not widely used due to surgeons’ concerns and the limited supporting evidence,” wrote Nattapol Tammachote, MD, of Thammasat University, Khlong Luang, Pathumthani, Thailand, and colleagues.

In a study published in the Journal of Arthroplasty, the researchers randomized 50 adults undergoing unilateral total knee surgery to a preoperative IV dexamethasone dose of 0.15 mg/kg diluted with normal saline or saline placebo. Patients, who were aged 50-85 years, were assessed every 3 hours after surgery, up to 48 hours; the primary outcomes were pain level, using the visual analog pain scale (VAS), and morphine use.

Overall, patients in the treatment group reported significant reductions on the VAS in mean pain scores of 11 points at rest and 15 points with knee movement. No significant differences in morphine use were noted between groups overall or at 12-hour intervals post-surgery.

In the first 24-48 hours after surgery dexamethasone was associated with a significantly lower rate of nausea and vomiting vs. placebo (58% vs. 84%), and a lower average C-reactive protein level (89 mg/L vs. 167 mg/L) at 48 hours after surgery. Hospital stays averaged 3 days for both groups, and no wound infections were reported.

Scores on tests of knee function using the modified Western Ontario and McMaster University Osteoarthritis Index scores and range of motion of the knee at three months were similar between the groups.

The study findings were limited by several factors, including the small sample size and use of multimodal pain control that may have impacted morphine use, a lack of data on hyperglycemia, and variation in doses of ketorolac given to patients in both groups, the researchers noted.

The results nevertheless support the potential of preoperative dexamethasone as “a promising approach in postoperative pain management and may be suitable for patients with contraindication to multimodal pain regimens,” they concluded.

The researchers reported no financial conflicts.

SOURCE: Tammachote N et al. J Arthroplasty. 2019. doi: https://doi.org/10.1016/ j.arth.2019.09.002.

Patients given a single preoperative dose of intravenous dexamethasone had significantly less pain after total knee arthroplasty than did those given a placebo in a randomized controlled study of 100 adults.

“Corticosteroids were introduced several years ago for relieving postoperative pain in total joint replacement but, unfortunately, are not widely used due to surgeons’ concerns and the limited supporting evidence,” wrote Nattapol Tammachote, MD, of Thammasat University, Khlong Luang, Pathumthani, Thailand, and colleagues.

In a study published in the Journal of Arthroplasty, the researchers randomized 50 adults undergoing unilateral total knee surgery to a preoperative IV dexamethasone dose of 0.15 mg/kg diluted with normal saline or saline placebo. Patients, who were aged 50-85 years, were assessed every 3 hours after surgery, up to 48 hours; the primary outcomes were pain level, using the visual analog pain scale (VAS), and morphine use.

Overall, patients in the treatment group reported significant reductions on the VAS in mean pain scores of 11 points at rest and 15 points with knee movement. No significant differences in morphine use were noted between groups overall or at 12-hour intervals post-surgery.

In the first 24-48 hours after surgery dexamethasone was associated with a significantly lower rate of nausea and vomiting vs. placebo (58% vs. 84%), and a lower average C-reactive protein level (89 mg/L vs. 167 mg/L) at 48 hours after surgery. Hospital stays averaged 3 days for both groups, and no wound infections were reported.

Scores on tests of knee function using the modified Western Ontario and McMaster University Osteoarthritis Index scores and range of motion of the knee at three months were similar between the groups.

The study findings were limited by several factors, including the small sample size and use of multimodal pain control that may have impacted morphine use, a lack of data on hyperglycemia, and variation in doses of ketorolac given to patients in both groups, the researchers noted.

The results nevertheless support the potential of preoperative dexamethasone as “a promising approach in postoperative pain management and may be suitable for patients with contraindication to multimodal pain regimens,” they concluded.

The researchers reported no financial conflicts.

SOURCE: Tammachote N et al. J Arthroplasty. 2019. doi: https://doi.org/10.1016/ j.arth.2019.09.002.

Patients given a single preoperative dose of intravenous dexamethasone had significantly less pain after total knee arthroplasty than did those given a placebo in a randomized controlled study of 100 adults.

“Corticosteroids were introduced several years ago for relieving postoperative pain in total joint replacement but, unfortunately, are not widely used due to surgeons’ concerns and the limited supporting evidence,” wrote Nattapol Tammachote, MD, of Thammasat University, Khlong Luang, Pathumthani, Thailand, and colleagues.

In a study published in the Journal of Arthroplasty, the researchers randomized 50 adults undergoing unilateral total knee surgery to a preoperative IV dexamethasone dose of 0.15 mg/kg diluted with normal saline or saline placebo. Patients, who were aged 50-85 years, were assessed every 3 hours after surgery, up to 48 hours; the primary outcomes were pain level, using the visual analog pain scale (VAS), and morphine use.

Overall, patients in the treatment group reported significant reductions on the VAS in mean pain scores of 11 points at rest and 15 points with knee movement. No significant differences in morphine use were noted between groups overall or at 12-hour intervals post-surgery.

In the first 24-48 hours after surgery dexamethasone was associated with a significantly lower rate of nausea and vomiting vs. placebo (58% vs. 84%), and a lower average C-reactive protein level (89 mg/L vs. 167 mg/L) at 48 hours after surgery. Hospital stays averaged 3 days for both groups, and no wound infections were reported.

Scores on tests of knee function using the modified Western Ontario and McMaster University Osteoarthritis Index scores and range of motion of the knee at three months were similar between the groups.

The study findings were limited by several factors, including the small sample size and use of multimodal pain control that may have impacted morphine use, a lack of data on hyperglycemia, and variation in doses of ketorolac given to patients in both groups, the researchers noted.

The results nevertheless support the potential of preoperative dexamethasone as “a promising approach in postoperative pain management and may be suitable for patients with contraindication to multimodal pain regimens,” they concluded.

The researchers reported no financial conflicts.

SOURCE: Tammachote N et al. J Arthroplasty. 2019. doi: https://doi.org/10.1016/ j.arth.2019.09.002.

MADRID – Low-dose azithromycin prophylaxis significantly reduced exacerbations and hospitalizations in patients with primary antibody deficiency relative to placebo, according to a randomized multicenter phase 2 trial.

The study results support routine use of low-dose azithromycin in patients with primary antibody deficiency, according to Cinzia Milito, MD, PhD, department of molecular medicine, Sapienza University, Rome. Perhaps more importantly, the long-term benefits might be even greater.

“In patients with primary antibody deficiency, the respiratory tract is the major target of acute infections, leading to inflammation, increased airway reactivity, and over time to tissue remodeling and chronic lung disease,” Dr. Milito said at the annual congress of the European Respiratory Society. “Chronic lung disease is a major cause of death in this population.”

In this study 89 patients with primary antibody deficiency were randomized at seven centers in Italy to 250 mg per day of azithromycin or placebo administered on three consecutive days of each week for three years. Patients were maintained on other treatments, such as IgG replacement.

At the end of study, 33 of the 44 patients randomized to azithromycin and 34 of the 45 patients randomized to placebo remained on therapy. When compared for the primary endpoint of exacerbations, the median incidence rates were 3.6 episodes in the azithromycin group and 5.2 episodes in the placebo group, providing a 1.6 episode or 31% relative reduction (P=0.02).

The median number of hospitalizations for any cause, which was a secondary endpoint, was also significantly lower in the azithromycin arm (0.1 vs. 0.3 episodes).

In addition, the number of additional courses of antibiotics was significantly lower (2.3 vs. 3.6), and the time to the first course of antibiotic course was significantly longer (181.5 vs. 122.4 days) in the azithromycin group, reported Dr. Milito, whose study is now published (Milito C et al. J Allergy Clin Immunol 2019;144: 584-593).

“In a six-month washout at the end of the study, the relative advantages seen for azithromycin were lost,” Dr. Milito said.

Quality of life measured with the St. George’s Respiratory Questionnaire showed an association between low-dose azithromycin prophylaxis and significant improvement in the symptom domain when evaluated during and at the end of the study. Improvement on the Short-Form 36, which was observed one year into the study, was no longer significant at the end of the study.

Azithromycin was well tolerated with no significant differences in the rate of serious adverse events observed between the experimental and control arms of the study. Over the course of the study, however, azithromycin was associated with a significant protective effect against diarrhea (13% vs. 53%) and acute rhinosinusitus (4% vs. 27%).

There was no observed increase in macrolide resistance associated with azithromycin prophylaxis.

Macrolides have been evaluated for preventing progression of several chronic lung diseases, including chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. Like other drugs in its class, “azithromycin, in addition to its antimicrobial effect, has anti-inflammatory properties,” Dr. Milito said. This increases its potential to slow the time to airway damage in patients with primary antibiotic deficiency.

“Chronic lung disease is the result of a vicious cycle that begins with the inflammatory response to infection,” Dr. Milito explained. On the basis of these data, she believes azithromycin “should be considered a valuable addition to usual treatment” for primary antibody deficiencies.
 

SOURCE: EUROPEAN RESPIRATORY SOCIETY 2019 INTERNATIONAL CONGRESS

MADRID – Low-dose azithromycin prophylaxis significantly reduced exacerbations and hospitalizations in patients with primary antibody deficiency relative to placebo, according to a randomized multicenter phase 2 trial.

The study results support routine use of low-dose azithromycin in patients with primary antibody deficiency, according to Cinzia Milito, MD, PhD, department of molecular medicine, Sapienza University, Rome. Perhaps more importantly, the long-term benefits might be even greater.

“In patients with primary antibody deficiency, the respiratory tract is the major target of acute infections, leading to inflammation, increased airway reactivity, and over time to tissue remodeling and chronic lung disease,” Dr. Milito said at the annual congress of the European Respiratory Society. “Chronic lung disease is a major cause of death in this population.”

In this study 89 patients with primary antibody deficiency were randomized at seven centers in Italy to 250 mg per day of azithromycin or placebo administered on three consecutive days of each week for three years. Patients were maintained on other treatments, such as IgG replacement.

At the end of study, 33 of the 44 patients randomized to azithromycin and 34 of the 45 patients randomized to placebo remained on therapy. When compared for the primary endpoint of exacerbations, the median incidence rates were 3.6 episodes in the azithromycin group and 5.2 episodes in the placebo group, providing a 1.6 episode or 31% relative reduction (P=0.02).

The median number of hospitalizations for any cause, which was a secondary endpoint, was also significantly lower in the azithromycin arm (0.1 vs. 0.3 episodes).

In addition, the number of additional courses of antibiotics was significantly lower (2.3 vs. 3.6), and the time to the first course of antibiotic course was significantly longer (181.5 vs. 122.4 days) in the azithromycin group, reported Dr. Milito, whose study is now published (Milito C et al. J Allergy Clin Immunol 2019;144: 584-593).

“In a six-month washout at the end of the study, the relative advantages seen for azithromycin were lost,” Dr. Milito said.

Quality of life measured with the St. George’s Respiratory Questionnaire showed an association between low-dose azithromycin prophylaxis and significant improvement in the symptom domain when evaluated during and at the end of the study. Improvement on the Short-Form 36, which was observed one year into the study, was no longer significant at the end of the study.

Azithromycin was well tolerated with no significant differences in the rate of serious adverse events observed between the experimental and control arms of the study. Over the course of the study, however, azithromycin was associated with a significant protective effect against diarrhea (13% vs. 53%) and acute rhinosinusitus (4% vs. 27%).

There was no observed increase in macrolide resistance associated with azithromycin prophylaxis.

Macrolides have been evaluated for preventing progression of several chronic lung diseases, including chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. Like other drugs in its class, “azithromycin, in addition to its antimicrobial effect, has anti-inflammatory properties,” Dr. Milito said. This increases its potential to slow the time to airway damage in patients with primary antibiotic deficiency.

“Chronic lung disease is the result of a vicious cycle that begins with the inflammatory response to infection,” Dr. Milito explained. On the basis of these data, she believes azithromycin “should be considered a valuable addition to usual treatment” for primary antibody deficiencies.
 

SOURCE: EUROPEAN RESPIRATORY SOCIETY 2019 INTERNATIONAL CONGRESS

MADRID – Low-dose azithromycin prophylaxis significantly reduced exacerbations and hospitalizations in patients with primary antibody deficiency relative to placebo, according to a randomized multicenter phase 2 trial.

The study results support routine use of low-dose azithromycin in patients with primary antibody deficiency, according to Cinzia Milito, MD, PhD, department of molecular medicine, Sapienza University, Rome. Perhaps more importantly, the long-term benefits might be even greater.

“In patients with primary antibody deficiency, the respiratory tract is the major target of acute infections, leading to inflammation, increased airway reactivity, and over time to tissue remodeling and chronic lung disease,” Dr. Milito said at the annual congress of the European Respiratory Society. “Chronic lung disease is a major cause of death in this population.”

In this study 89 patients with primary antibody deficiency were randomized at seven centers in Italy to 250 mg per day of azithromycin or placebo administered on three consecutive days of each week for three years. Patients were maintained on other treatments, such as IgG replacement.

At the end of study, 33 of the 44 patients randomized to azithromycin and 34 of the 45 patients randomized to placebo remained on therapy. When compared for the primary endpoint of exacerbations, the median incidence rates were 3.6 episodes in the azithromycin group and 5.2 episodes in the placebo group, providing a 1.6 episode or 31% relative reduction (P=0.02).

The median number of hospitalizations for any cause, which was a secondary endpoint, was also significantly lower in the azithromycin arm (0.1 vs. 0.3 episodes).

In addition, the number of additional courses of antibiotics was significantly lower (2.3 vs. 3.6), and the time to the first course of antibiotic course was significantly longer (181.5 vs. 122.4 days) in the azithromycin group, reported Dr. Milito, whose study is now published (Milito C et al. J Allergy Clin Immunol 2019;144: 584-593).

“In a six-month washout at the end of the study, the relative advantages seen for azithromycin were lost,” Dr. Milito said.

Quality of life measured with the St. George’s Respiratory Questionnaire showed an association between low-dose azithromycin prophylaxis and significant improvement in the symptom domain when evaluated during and at the end of the study. Improvement on the Short-Form 36, which was observed one year into the study, was no longer significant at the end of the study.

Azithromycin was well tolerated with no significant differences in the rate of serious adverse events observed between the experimental and control arms of the study. Over the course of the study, however, azithromycin was associated with a significant protective effect against diarrhea (13% vs. 53%) and acute rhinosinusitus (4% vs. 27%).

There was no observed increase in macrolide resistance associated with azithromycin prophylaxis.

Macrolides have been evaluated for preventing progression of several chronic lung diseases, including chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. Like other drugs in its class, “azithromycin, in addition to its antimicrobial effect, has anti-inflammatory properties,” Dr. Milito said. This increases its potential to slow the time to airway damage in patients with primary antibiotic deficiency.

“Chronic lung disease is the result of a vicious cycle that begins with the inflammatory response to infection,” Dr. Milito explained. On the basis of these data, she believes azithromycin “should be considered a valuable addition to usual treatment” for primary antibody deficiencies.
 

SOURCE: EUROPEAN RESPIRATORY SOCIETY 2019 INTERNATIONAL CONGRESS

WASHINGTON – Daily treatment with valacyclovir for at least 6 weeks safely cut the cytomegalovirus (CMV) vertical transmission rate from mothers to fetuses in women with a primary CMV infection during the three weeks before conception through their first trimester. That finding emerged from a randomized, controlled, single-center Israeli study with 92 women.

The rate of congenital fetal infection with CMV was 11% among neonates born to 45 women treated with 8 g/day of valacyclovir, compared with a 30% rate among the infants born to 47 women who received placebo, a statistically significant difference, Keren Shahar-Nissan, MD, said at an annual scientific meeting on infectious diseases. The results also showed that the valacyclovir regimen was well tolerated, with no increase compared with placebo in adverse events and with no need for dosage adjustment regardless of a 16 pill/day regimen to deliver the 8 g/day of valacyclovir or placebo that participants received.

Dr. Shahar-Nissan said that she and her associates felt comfortable administering this amount of valacyclovir to pregnant woman given previous reports of the safety of this dosage for both women and their fetuses. These reports included 20 pregnant women safely treated for 7 weeks with 8 g/day during the late second or early third trimester (BJOG. 2007 Sept;114[9]:1113-21); more than 600 women in a Danish nationwide study treated with any dosage of valacyclovir during preconception, the first trimester, or the second or third trimesters with a prevalence of births defects not significantly different from unexposed pregnancies (JAMA. 2010 Aug 25;304[8]:859-66); and a prospective, open-label study of 8 g/day valacyclovir to treat 43 women carrying CMV-infected fetuses starting at a median 26 weeks gestation and continuing through delivery (Am J Obstet Gynecol. 2016 Oct;215[4]:462.e1-462.e10).

The study she ran enrolled women seen at Helen Schneider Hospital for Women in Petah Tikva, Israel, during November 2015-October 2018 who had a serologically-proven primary CMV infection that began at any time from 3 weeks before conception through the first trimester, excluding patients with renal dysfunction, liver disease, bone-marrow suppression, or acyclovir sensitivity. Screening for active CMV infection is common among newly-pregnant Israeli women, usually at the time of their first obstetrical consultation for a suspected pregnancy, noted Dr. Shahar-Nissan, a pediatrician at Schneider Children’s Medical Center of Israel in Petah Tikva. About a quarter of the enrolled women became infected during the 3 weeks prior to conception, and nearly two-thirds became infected during the first 8 weeks of pregnancy.

The valacyclovir intervention appeared to be effective specifically for preventing vertical transmission of infection acquired early during pregnancy. In this subgroup the transmission rate was 11% with valacyclovir treatment and 48% on placebo. Valacyclovir seemed to have no effect on vertical transmission of infections that began before conception, likely because treatment began too late to prevent transmission.

“I think this study is enough” to convince the U.S. Food and Drug Administration to add this treatment indication to the labeling of valacyclovir, a drug that has been available in generic formulations for many years, Dr. Shahar-Nissan said in an interview. Before approaching the FDA, her first goal is publishing the findings, she added.

mzoler@mdedge.com

On Twitter @mitchelzoler

WASHINGTON – Daily treatment with valacyclovir for at least 6 weeks safely cut the cytomegalovirus (CMV) vertical transmission rate from mothers to fetuses in women with a primary CMV infection during the three weeks before conception through their first trimester. That finding emerged from a randomized, controlled, single-center Israeli study with 92 women.

The rate of congenital fetal infection with CMV was 11% among neonates born to 45 women treated with 8 g/day of valacyclovir, compared with a 30% rate among the infants born to 47 women who received placebo, a statistically significant difference, Keren Shahar-Nissan, MD, said at an annual scientific meeting on infectious diseases. The results also showed that the valacyclovir regimen was well tolerated, with no increase compared with placebo in adverse events and with no need for dosage adjustment regardless of a 16 pill/day regimen to deliver the 8 g/day of valacyclovir or placebo that participants received.

Dr. Shahar-Nissan said that she and her associates felt comfortable administering this amount of valacyclovir to pregnant woman given previous reports of the safety of this dosage for both women and their fetuses. These reports included 20 pregnant women safely treated for 7 weeks with 8 g/day during the late second or early third trimester (BJOG. 2007 Sept;114[9]:1113-21); more than 600 women in a Danish nationwide study treated with any dosage of valacyclovir during preconception, the first trimester, or the second or third trimesters with a prevalence of births defects not significantly different from unexposed pregnancies (JAMA. 2010 Aug 25;304[8]:859-66); and a prospective, open-label study of 8 g/day valacyclovir to treat 43 women carrying CMV-infected fetuses starting at a median 26 weeks gestation and continuing through delivery (Am J Obstet Gynecol. 2016 Oct;215[4]:462.e1-462.e10).

The study she ran enrolled women seen at Helen Schneider Hospital for Women in Petah Tikva, Israel, during November 2015-October 2018 who had a serologically-proven primary CMV infection that began at any time from 3 weeks before conception through the first trimester, excluding patients with renal dysfunction, liver disease, bone-marrow suppression, or acyclovir sensitivity. Screening for active CMV infection is common among newly-pregnant Israeli women, usually at the time of their first obstetrical consultation for a suspected pregnancy, noted Dr. Shahar-Nissan, a pediatrician at Schneider Children’s Medical Center of Israel in Petah Tikva. About a quarter of the enrolled women became infected during the 3 weeks prior to conception, and nearly two-thirds became infected during the first 8 weeks of pregnancy.

The valacyclovir intervention appeared to be effective specifically for preventing vertical transmission of infection acquired early during pregnancy. In this subgroup the transmission rate was 11% with valacyclovir treatment and 48% on placebo. Valacyclovir seemed to have no effect on vertical transmission of infections that began before conception, likely because treatment began too late to prevent transmission.

“I think this study is enough” to convince the U.S. Food and Drug Administration to add this treatment indication to the labeling of valacyclovir, a drug that has been available in generic formulations for many years, Dr. Shahar-Nissan said in an interview. Before approaching the FDA, her first goal is publishing the findings, she added.

mzoler@mdedge.com

On Twitter @mitchelzoler

WASHINGTON – Daily treatment with valacyclovir for at least 6 weeks safely cut the cytomegalovirus (CMV) vertical transmission rate from mothers to fetuses in women with a primary CMV infection during the three weeks before conception through their first trimester. That finding emerged from a randomized, controlled, single-center Israeli study with 92 women.

The rate of congenital fetal infection with CMV was 11% among neonates born to 45 women treated with 8 g/day of valacyclovir, compared with a 30% rate among the infants born to 47 women who received placebo, a statistically significant difference, Keren Shahar-Nissan, MD, said at an annual scientific meeting on infectious diseases. The results also showed that the valacyclovir regimen was well tolerated, with no increase compared with placebo in adverse events and with no need for dosage adjustment regardless of a 16 pill/day regimen to deliver the 8 g/day of valacyclovir or placebo that participants received.

Dr. Shahar-Nissan said that she and her associates felt comfortable administering this amount of valacyclovir to pregnant woman given previous reports of the safety of this dosage for both women and their fetuses. These reports included 20 pregnant women safely treated for 7 weeks with 8 g/day during the late second or early third trimester (BJOG. 2007 Sept;114[9]:1113-21); more than 600 women in a Danish nationwide study treated with any dosage of valacyclovir during preconception, the first trimester, or the second or third trimesters with a prevalence of births defects not significantly different from unexposed pregnancies (JAMA. 2010 Aug 25;304[8]:859-66); and a prospective, open-label study of 8 g/day valacyclovir to treat 43 women carrying CMV-infected fetuses starting at a median 26 weeks gestation and continuing through delivery (Am J Obstet Gynecol. 2016 Oct;215[4]:462.e1-462.e10).

The study she ran enrolled women seen at Helen Schneider Hospital for Women in Petah Tikva, Israel, during November 2015-October 2018 who had a serologically-proven primary CMV infection that began at any time from 3 weeks before conception through the first trimester, excluding patients with renal dysfunction, liver disease, bone-marrow suppression, or acyclovir sensitivity. Screening for active CMV infection is common among newly-pregnant Israeli women, usually at the time of their first obstetrical consultation for a suspected pregnancy, noted Dr. Shahar-Nissan, a pediatrician at Schneider Children’s Medical Center of Israel in Petah Tikva. About a quarter of the enrolled women became infected during the 3 weeks prior to conception, and nearly two-thirds became infected during the first 8 weeks of pregnancy.

The valacyclovir intervention appeared to be effective specifically for preventing vertical transmission of infection acquired early during pregnancy. In this subgroup the transmission rate was 11% with valacyclovir treatment and 48% on placebo. Valacyclovir seemed to have no effect on vertical transmission of infections that began before conception, likely because treatment began too late to prevent transmission.

“I think this study is enough” to convince the U.S. Food and Drug Administration to add this treatment indication to the labeling of valacyclovir, a drug that has been available in generic formulations for many years, Dr. Shahar-Nissan said in an interview. Before approaching the FDA, her first goal is publishing the findings, she added.

mzoler@mdedge.com

On Twitter @mitchelzoler

LAS VEGAS – Cannabinoids and stem cells may intrigue patients as potential treatments for osteoarthritis (OA), but evidence does not support their use. Planned clinical trials may clarify whether they benefit patients, said Joel A. Block, MD, professor of rheumatology at Rush University in Chicago.

Jake Remaly/MDedge News

Cannabinoid therapy “is on everybody’s mind, including our patients,” Dr. Block said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “Cannabinoid receptors are widely present in all joint tissues, and endocannabinoids are clearly present in OA joint tissue. There is good evidence that the receptors regulate pain responses and central sensitization in a variety of OA animal models.” Where cannabis is legal, many people use it for chronic noncancer pain. Side effects may include altered perception, dizziness, drowsiness, and gastrointestinal adverse events.

Cannabis in the literature

“Nonetheless, if you do a systematic review of all of the randomized clinical trials of cannabinoids in human rheumatic diseases, what you will find is there is a grand total of four,” he said. The trials included patients with rheumatoid arthritis, OA, and fibromyalgia. An analysis of aggregated data found that cannabinoids improved pain and sleep, but all of the trials had a high risk of bias, poor allocation concealment, and poor blinding, said Dr. Block (Arthritis Care Res [Hoboken]. 2016 May;68[5]:681-8.). “In OA, there is one randomized trial, and it was entirely null,” he said. “There was no positive effect on pain or on function in human OA” (Pain. 2012 Sep;153[9]:1837-46.).

ClinicalTrials.gov lists two planned randomized controlled trials of cannabinoids – one using vaporized cannabis in patients with knee OA, and one using cannabidiol for hand OA and psoriatic arthritis. “Clinical trials are still scarce as of right now, so it will take a while before we have evidence for or against,” said Dr. Block.

Stem cell injections

Intra-articular stem cell injections are widely offered in the United States and abroad, he said. “In every newspaper, wherever I go, I open it up and there are full-page ads on stem cell injections that will cure everything that you want,” he said.

A systematic review of the effect of stem cell injections on structural outcomes and pain-related behaviors in animals found that “for all outcomes, the evidence quality was either low or very low,” Dr. Block said (Osteoarthritis Cartilage. 2018 Apr;26[4]:445-61.). “Even in the animal models, it has been very hard to demonstrate any effect at all from just injecting stem cells into the joint.”

Systematic reviews of the evidence in humans have found that the data do not support the use of stem cell injections. The authors of one review concluded, “In the absence of high-level evidence, we do not recommend stem cell therapy” for knee OA (Br J Sports Med. 2017 Aug;51[15]:1125-33.).

For another recent review, researchers screened hundreds of articles and identified 5 trials that met their inclusion criteria. They concluded, “Current evidence does not support the use of intra-articular [mesenchymal stem cells] for improving cartilage repair in knee osteoarthritis” (Arch Orthop Trauma Surg. 2019 Jul;139[7]:971-80.).

Many clinical trials are planned, however. “Over the next several years, I would expect that we are going to get some real data on whether these are helpful or not,” Dr. Block said.

Meanwhile, some patients spend thousands of dollars to receive stem cell injections, and clinics report average patient satisfaction rates of 82%. “How can they be getting so much relief when there is no evidence that it is helpful? In fact, whatever evidence we have says that it is no better than placebo,” said Dr. Block. “Placebo itself is very potent....People always do what they feel helps them regardless of objective data, because placebo itself is very palliative.”

Dr. Block is a consultant for GlaxoSmithKline, Medivir, and Zynerba Pharmaceuticals. He has received royalties from Agios, Daiichi Sankyo, and Omeros. In addition, he has received grant or research support from AbbVie, Janssen, Novartis, Pfizer, and Kolon TissueGene.

Global Academy for Medical Education and this news organization are owned by the same parent company.
 

jremaly@mdedge.com

LAS VEGAS – Cannabinoids and stem cells may intrigue patients as potential treatments for osteoarthritis (OA), but evidence does not support their use. Planned clinical trials may clarify whether they benefit patients, said Joel A. Block, MD, professor of rheumatology at Rush University in Chicago.

Jake Remaly/MDedge News

Cannabinoid therapy “is on everybody’s mind, including our patients,” Dr. Block said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “Cannabinoid receptors are widely present in all joint tissues, and endocannabinoids are clearly present in OA joint tissue. There is good evidence that the receptors regulate pain responses and central sensitization in a variety of OA animal models.” Where cannabis is legal, many people use it for chronic noncancer pain. Side effects may include altered perception, dizziness, drowsiness, and gastrointestinal adverse events.

Cannabis in the literature

“Nonetheless, if you do a systematic review of all of the randomized clinical trials of cannabinoids in human rheumatic diseases, what you will find is there is a grand total of four,” he said. The trials included patients with rheumatoid arthritis, OA, and fibromyalgia. An analysis of aggregated data found that cannabinoids improved pain and sleep, but all of the trials had a high risk of bias, poor allocation concealment, and poor blinding, said Dr. Block (Arthritis Care Res [Hoboken]. 2016 May;68[5]:681-8.). “In OA, there is one randomized trial, and it was entirely null,” he said. “There was no positive effect on pain or on function in human OA” (Pain. 2012 Sep;153[9]:1837-46.).

ClinicalTrials.gov lists two planned randomized controlled trials of cannabinoids – one using vaporized cannabis in patients with knee OA, and one using cannabidiol for hand OA and psoriatic arthritis. “Clinical trials are still scarce as of right now, so it will take a while before we have evidence for or against,” said Dr. Block.

Stem cell injections

Intra-articular stem cell injections are widely offered in the United States and abroad, he said. “In every newspaper, wherever I go, I open it up and there are full-page ads on stem cell injections that will cure everything that you want,” he said.

A systematic review of the effect of stem cell injections on structural outcomes and pain-related behaviors in animals found that “for all outcomes, the evidence quality was either low or very low,” Dr. Block said (Osteoarthritis Cartilage. 2018 Apr;26[4]:445-61.). “Even in the animal models, it has been very hard to demonstrate any effect at all from just injecting stem cells into the joint.”

Systematic reviews of the evidence in humans have found that the data do not support the use of stem cell injections. The authors of one review concluded, “In the absence of high-level evidence, we do not recommend stem cell therapy” for knee OA (Br J Sports Med. 2017 Aug;51[15]:1125-33.).

For another recent review, researchers screened hundreds of articles and identified 5 trials that met their inclusion criteria. They concluded, “Current evidence does not support the use of intra-articular [mesenchymal stem cells] for improving cartilage repair in knee osteoarthritis” (Arch Orthop Trauma Surg. 2019 Jul;139[7]:971-80.).

Many clinical trials are planned, however. “Over the next several years, I would expect that we are going to get some real data on whether these are helpful or not,” Dr. Block said.

Meanwhile, some patients spend thousands of dollars to receive stem cell injections, and clinics report average patient satisfaction rates of 82%. “How can they be getting so much relief when there is no evidence that it is helpful? In fact, whatever evidence we have says that it is no better than placebo,” said Dr. Block. “Placebo itself is very potent....People always do what they feel helps them regardless of objective data, because placebo itself is very palliative.”

Dr. Block is a consultant for GlaxoSmithKline, Medivir, and Zynerba Pharmaceuticals. He has received royalties from Agios, Daiichi Sankyo, and Omeros. In addition, he has received grant or research support from AbbVie, Janssen, Novartis, Pfizer, and Kolon TissueGene.

Global Academy for Medical Education and this news organization are owned by the same parent company.
 

jremaly@mdedge.com

LAS VEGAS – Cannabinoids and stem cells may intrigue patients as potential treatments for osteoarthritis (OA), but evidence does not support their use. Planned clinical trials may clarify whether they benefit patients, said Joel A. Block, MD, professor of rheumatology at Rush University in Chicago.

Jake Remaly/MDedge News

Cannabinoid therapy “is on everybody’s mind, including our patients,” Dr. Block said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “Cannabinoid receptors are widely present in all joint tissues, and endocannabinoids are clearly present in OA joint tissue. There is good evidence that the receptors regulate pain responses and central sensitization in a variety of OA animal models.” Where cannabis is legal, many people use it for chronic noncancer pain. Side effects may include altered perception, dizziness, drowsiness, and gastrointestinal adverse events.

Cannabis in the literature

“Nonetheless, if you do a systematic review of all of the randomized clinical trials of cannabinoids in human rheumatic diseases, what you will find is there is a grand total of four,” he said. The trials included patients with rheumatoid arthritis, OA, and fibromyalgia. An analysis of aggregated data found that cannabinoids improved pain and sleep, but all of the trials had a high risk of bias, poor allocation concealment, and poor blinding, said Dr. Block (Arthritis Care Res [Hoboken]. 2016 May;68[5]:681-8.). “In OA, there is one randomized trial, and it was entirely null,” he said. “There was no positive effect on pain or on function in human OA” (Pain. 2012 Sep;153[9]:1837-46.).

ClinicalTrials.gov lists two planned randomized controlled trials of cannabinoids – one using vaporized cannabis in patients with knee OA, and one using cannabidiol for hand OA and psoriatic arthritis. “Clinical trials are still scarce as of right now, so it will take a while before we have evidence for or against,” said Dr. Block.

Stem cell injections

Intra-articular stem cell injections are widely offered in the United States and abroad, he said. “In every newspaper, wherever I go, I open it up and there are full-page ads on stem cell injections that will cure everything that you want,” he said.

A systematic review of the effect of stem cell injections on structural outcomes and pain-related behaviors in animals found that “for all outcomes, the evidence quality was either low or very low,” Dr. Block said (Osteoarthritis Cartilage. 2018 Apr;26[4]:445-61.). “Even in the animal models, it has been very hard to demonstrate any effect at all from just injecting stem cells into the joint.”

Systematic reviews of the evidence in humans have found that the data do not support the use of stem cell injections. The authors of one review concluded, “In the absence of high-level evidence, we do not recommend stem cell therapy” for knee OA (Br J Sports Med. 2017 Aug;51[15]:1125-33.).

For another recent review, researchers screened hundreds of articles and identified 5 trials that met their inclusion criteria. They concluded, “Current evidence does not support the use of intra-articular [mesenchymal stem cells] for improving cartilage repair in knee osteoarthritis” (Arch Orthop Trauma Surg. 2019 Jul;139[7]:971-80.).

Many clinical trials are planned, however. “Over the next several years, I would expect that we are going to get some real data on whether these are helpful or not,” Dr. Block said.

Meanwhile, some patients spend thousands of dollars to receive stem cell injections, and clinics report average patient satisfaction rates of 82%. “How can they be getting so much relief when there is no evidence that it is helpful? In fact, whatever evidence we have says that it is no better than placebo,” said Dr. Block. “Placebo itself is very potent....People always do what they feel helps them regardless of objective data, because placebo itself is very palliative.”

Dr. Block is a consultant for GlaxoSmithKline, Medivir, and Zynerba Pharmaceuticals. He has received royalties from Agios, Daiichi Sankyo, and Omeros. In addition, he has received grant or research support from AbbVie, Janssen, Novartis, Pfizer, and Kolon TissueGene.

Global Academy for Medical Education and this news organization are owned by the same parent company.
 

jremaly@mdedge.com

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

The introduction of the Medicare Inpatient Prospective Payment System (IPPS) through amendment of the Social Security Act in 1983 transformed hospital reimbursement in the United States. Under the IPPS, a new form of Medicare prospective payment that paid hospitals a fixed amount per discharge for inpatient services was created: the diagnosis-related group (DRG). This eliminated the preceding retrospective cost reimbursement system in an attempt to stop health care price inflation.

Each DRG represents a grouping of similar conditions and procedures for services provided during an inpatient hospitalization reimbursed under Medicare Part A. The Centers for Medicare & Medicaid Services uses the Medicare Severity DRG (MS-DRG) system to account for severity of illness and resource consumption. There are three levels of severity based upon secondary diagnosis: major complication/comorbidity (MCC), complication/comorbidity (CC), and noncomplication/comorbidity (non-CC).

Payment rates are defined by base rates for operating costs and capital-related costs which are adjusted for relative weight (the average cost within a DRG, compared with the average Medicare case cost) and market condition adjustments. As the largest single health care payer in the United States, CMS’ annual changes to the IPPS have a major impact on hospital reimbursement.

In May 2019, CMS released its annual proposed rule for the Hospital IPPS suggesting extensive changes to MS-DRG reimbursements. Notably, CMS proposed changing the severity level of nearly 1,500 diagnosis codes by adjusting their categorization between MCC, CC, or non-CC. The majority of these changes included downgrading MCCs to CCs or non-CCs. In fact, 87% of the changes involved a downgrade from one of the higher severity levels to a non-CC level, while only 13% involved an upgrade from a lower severity level to MCC level.

The CMS derived these changes from an algorithmic review and input from their clinical advisors to determine each diagnoses impact on resource utilization. Multiple major groups of codes were included in the downgraded groups, including secondary cancer diagnoses, organ transplant status, and hip fracture.

Evaluating codes based on coded resource use alone could have had a major negative impact on the clinical practice of hospitalists as it undervalues cognitive and clinical work associated with these secondary diagnoses. As an example, malignant neoplasm of head of pancreas (ICD-10, C25.0) was proposed to move to a non-CC. Under CMS’ proposed rule, if a patient was admitted with complications of pancreatic cancer such as cholangitis caused by biliary obstruction, the pancreatic cancer diagnosis would not serve as a CC since the primary condition for which the patient was hospitalized would be cholangitis. The anticipated increase in such a patient’s length of stay, severity of illness, and expected resource utilization would be grossly misrepresented in this case by CMS’ proposed rule changes. CMS also proposed to move major organ-transplant status (including heart, lung, kidney, and pancreas) from CC to non-CC status. Again, the cognitive work and resource utilization required to manage these patients would be underrepresented with this change, given the increased complexity of managing immunosuppressant medications or conducting an infectious diagnostic work-up in immunosuppressed patients.

The Society of Hospital Medicine Public Policy Committee provides comments annually to CMS on the IPPS, advocating for hospitalists and patients. After advocacy efforts from SHM and other groups, expressing concern about making such significant changes to the DRG system without further study, the IPPS final rule was released on August 2, 2019. SHM’s efforts paid off. The final rule excluded the proposed broad changes to the MS-DRG system that were in the proposed rule.

In deciding not to finalize the proposed severity level changes, CMS wrote that the adoption of these broad changes will be postponed in order “to fully consider the technical feedback provided” regarding the proposal. The final rule also describes making a “test GROUPER [software program] publicly available to allow for impact testing,” and allows for the possibility of phasing in changes and eliciting feedback. SHM is fully supportive of the decision to postpone major changes to the MS-DRG system in the IPPS until further review is obtained, and will continue to monitor this issue and provide appropriate input to CMS for our hospitalist members.

As hospitalists, it is important to understand the foundational role that public policy and CMS rule creation have on our work. Influencing change to the MS-DRG system is yet another example of how SHM’s work has impacted the policy domain, limiting negative effects on our members and advancing the practice of hospital medicine.

Dr. Biebelhausen is head of the section of hospital medicine at Virginia Mason Medical Center, Seattle. Dr. Cowart is a hospitalist at the Mayo Clinic in Jacksonville, Fla. Dr. Hamilton is a hospitalist and associate chief quality officer at the Cleveland Clinic.

The introduction of the Medicare Inpatient Prospective Payment System (IPPS) through amendment of the Social Security Act in 1983 transformed hospital reimbursement in the United States. Under the IPPS, a new form of Medicare prospective payment that paid hospitals a fixed amount per discharge for inpatient services was created: the diagnosis-related group (DRG). This eliminated the preceding retrospective cost reimbursement system in an attempt to stop health care price inflation.

Each DRG represents a grouping of similar conditions and procedures for services provided during an inpatient hospitalization reimbursed under Medicare Part A. The Centers for Medicare & Medicaid Services uses the Medicare Severity DRG (MS-DRG) system to account for severity of illness and resource consumption. There are three levels of severity based upon secondary diagnosis: major complication/comorbidity (MCC), complication/comorbidity (CC), and noncomplication/comorbidity (non-CC).

Payment rates are defined by base rates for operating costs and capital-related costs which are adjusted for relative weight (the average cost within a DRG, compared with the average Medicare case cost) and market condition adjustments. As the largest single health care payer in the United States, CMS’ annual changes to the IPPS have a major impact on hospital reimbursement.

In May 2019, CMS released its annual proposed rule for the Hospital IPPS suggesting extensive changes to MS-DRG reimbursements. Notably, CMS proposed changing the severity level of nearly 1,500 diagnosis codes by adjusting their categorization between MCC, CC, or non-CC. The majority of these changes included downgrading MCCs to CCs or non-CCs. In fact, 87% of the changes involved a downgrade from one of the higher severity levels to a non-CC level, while only 13% involved an upgrade from a lower severity level to MCC level.

The CMS derived these changes from an algorithmic review and input from their clinical advisors to determine each diagnoses impact on resource utilization. Multiple major groups of codes were included in the downgraded groups, including secondary cancer diagnoses, organ transplant status, and hip fracture.

Evaluating codes based on coded resource use alone could have had a major negative impact on the clinical practice of hospitalists as it undervalues cognitive and clinical work associated with these secondary diagnoses. As an example, malignant neoplasm of head of pancreas (ICD-10, C25.0) was proposed to move to a non-CC. Under CMS’ proposed rule, if a patient was admitted with complications of pancreatic cancer such as cholangitis caused by biliary obstruction, the pancreatic cancer diagnosis would not serve as a CC since the primary condition for which the patient was hospitalized would be cholangitis. The anticipated increase in such a patient’s length of stay, severity of illness, and expected resource utilization would be grossly misrepresented in this case by CMS’ proposed rule changes. CMS also proposed to move major organ-transplant status (including heart, lung, kidney, and pancreas) from CC to non-CC status. Again, the cognitive work and resource utilization required to manage these patients would be underrepresented with this change, given the increased complexity of managing immunosuppressant medications or conducting an infectious diagnostic work-up in immunosuppressed patients.

The Society of Hospital Medicine Public Policy Committee provides comments annually to CMS on the IPPS, advocating for hospitalists and patients. After advocacy efforts from SHM and other groups, expressing concern about making such significant changes to the DRG system without further study, the IPPS final rule was released on August 2, 2019. SHM’s efforts paid off. The final rule excluded the proposed broad changes to the MS-DRG system that were in the proposed rule.

In deciding not to finalize the proposed severity level changes, CMS wrote that the adoption of these broad changes will be postponed in order “to fully consider the technical feedback provided” regarding the proposal. The final rule also describes making a “test GROUPER [software program] publicly available to allow for impact testing,” and allows for the possibility of phasing in changes and eliciting feedback. SHM is fully supportive of the decision to postpone major changes to the MS-DRG system in the IPPS until further review is obtained, and will continue to monitor this issue and provide appropriate input to CMS for our hospitalist members.

As hospitalists, it is important to understand the foundational role that public policy and CMS rule creation have on our work. Influencing change to the MS-DRG system is yet another example of how SHM’s work has impacted the policy domain, limiting negative effects on our members and advancing the practice of hospital medicine.

Dr. Biebelhausen is head of the section of hospital medicine at Virginia Mason Medical Center, Seattle. Dr. Cowart is a hospitalist at the Mayo Clinic in Jacksonville, Fla. Dr. Hamilton is a hospitalist and associate chief quality officer at the Cleveland Clinic.

The introduction of the Medicare Inpatient Prospective Payment System (IPPS) through amendment of the Social Security Act in 1983 transformed hospital reimbursement in the United States. Under the IPPS, a new form of Medicare prospective payment that paid hospitals a fixed amount per discharge for inpatient services was created: the diagnosis-related group (DRG). This eliminated the preceding retrospective cost reimbursement system in an attempt to stop health care price inflation.

Each DRG represents a grouping of similar conditions and procedures for services provided during an inpatient hospitalization reimbursed under Medicare Part A. The Centers for Medicare & Medicaid Services uses the Medicare Severity DRG (MS-DRG) system to account for severity of illness and resource consumption. There are three levels of severity based upon secondary diagnosis: major complication/comorbidity (MCC), complication/comorbidity (CC), and noncomplication/comorbidity (non-CC).

Payment rates are defined by base rates for operating costs and capital-related costs which are adjusted for relative weight (the average cost within a DRG, compared with the average Medicare case cost) and market condition adjustments. As the largest single health care payer in the United States, CMS’ annual changes to the IPPS have a major impact on hospital reimbursement.

In May 2019, CMS released its annual proposed rule for the Hospital IPPS suggesting extensive changes to MS-DRG reimbursements. Notably, CMS proposed changing the severity level of nearly 1,500 diagnosis codes by adjusting their categorization between MCC, CC, or non-CC. The majority of these changes included downgrading MCCs to CCs or non-CCs. In fact, 87% of the changes involved a downgrade from one of the higher severity levels to a non-CC level, while only 13% involved an upgrade from a lower severity level to MCC level.

The CMS derived these changes from an algorithmic review and input from their clinical advisors to determine each diagnoses impact on resource utilization. Multiple major groups of codes were included in the downgraded groups, including secondary cancer diagnoses, organ transplant status, and hip fracture.

Evaluating codes based on coded resource use alone could have had a major negative impact on the clinical practice of hospitalists as it undervalues cognitive and clinical work associated with these secondary diagnoses. As an example, malignant neoplasm of head of pancreas (ICD-10, C25.0) was proposed to move to a non-CC. Under CMS’ proposed rule, if a patient was admitted with complications of pancreatic cancer such as cholangitis caused by biliary obstruction, the pancreatic cancer diagnosis would not serve as a CC since the primary condition for which the patient was hospitalized would be cholangitis. The anticipated increase in such a patient’s length of stay, severity of illness, and expected resource utilization would be grossly misrepresented in this case by CMS’ proposed rule changes. CMS also proposed to move major organ-transplant status (including heart, lung, kidney, and pancreas) from CC to non-CC status. Again, the cognitive work and resource utilization required to manage these patients would be underrepresented with this change, given the increased complexity of managing immunosuppressant medications or conducting an infectious diagnostic work-up in immunosuppressed patients.

The Society of Hospital Medicine Public Policy Committee provides comments annually to CMS on the IPPS, advocating for hospitalists and patients. After advocacy efforts from SHM and other groups, expressing concern about making such significant changes to the DRG system without further study, the IPPS final rule was released on August 2, 2019. SHM’s efforts paid off. The final rule excluded the proposed broad changes to the MS-DRG system that were in the proposed rule.

In deciding not to finalize the proposed severity level changes, CMS wrote that the adoption of these broad changes will be postponed in order “to fully consider the technical feedback provided” regarding the proposal. The final rule also describes making a “test GROUPER [software program] publicly available to allow for impact testing,” and allows for the possibility of phasing in changes and eliciting feedback. SHM is fully supportive of the decision to postpone major changes to the MS-DRG system in the IPPS until further review is obtained, and will continue to monitor this issue and provide appropriate input to CMS for our hospitalist members.

As hospitalists, it is important to understand the foundational role that public policy and CMS rule creation have on our work. Influencing change to the MS-DRG system is yet another example of how SHM’s work has impacted the policy domain, limiting negative effects on our members and advancing the practice of hospital medicine.

Dr. Biebelhausen is head of the section of hospital medicine at Virginia Mason Medical Center, Seattle. Dr. Cowart is a hospitalist at the Mayo Clinic in Jacksonville, Fla. Dr. Hamilton is a hospitalist and associate chief quality officer at the Cleveland Clinic.

Why do we forget some dreams and remember others? Researchers in a study funded by the National Institute of Neurological Disorders and Stroke say our dream memory may be controlled by a group of neurons commonly associated with appetite. Their findings could shed light on a wide range of memory-related conditions, including posttraumatic stress disorder (PTSD) and Alzheimer disease.

Studies have already shown that sleep helps the brain store new memories and eliminate excess information. Recent mouse studies have found that during sleep the brain prunes synaptic connections made between neurons involved in some types of learning.

But this study shows how that might happen.

The researchers have previously demonstrated that narcolepsy might be linked to the loss of hypocretin/orexin-making neurons in the hypothalamus. In this study, they looked at neighboring cells that produce melanin-concentrating hormone (MCH), which is involved in the control of both sleep and appetite. A majority (53%) of hypothalamic MCH cells fired in mice during REM sleep; 35% fired when they were awake, and 12% fired at both times.

Those cells also may play a role in learning and memory, the researchers suggest. To test their theory that MCH cells might help the brain store memories, they used “genetic tools” to turn MCH neurons on and off during memory tests.

Surprisingly, the researchers say, pharmacogenetic activation—turning on the MCH cells—worsened memory; genetic ablation—turning them off—improved memory. Further experiments suggested MCH neurons exclusively played this role during REM sleep.

The results suggest that MCH neurons help the brain actively forget new, possibly unimportant information. “Since dreams are thought to primarily occur during REM sleep,” says Thomas Kilduff, PhD, senior author of the study, “the sleep stage when the MCH cells turn on, activation of these cells may prevent the content of a dream from being stored in the hippocampus—consequently, the dream is quickly forgotten.”

Why do we forget some dreams and remember others? Researchers in a study funded by the National Institute of Neurological Disorders and Stroke say our dream memory may be controlled by a group of neurons commonly associated with appetite. Their findings could shed light on a wide range of memory-related conditions, including posttraumatic stress disorder (PTSD) and Alzheimer disease.

Studies have already shown that sleep helps the brain store new memories and eliminate excess information. Recent mouse studies have found that during sleep the brain prunes synaptic connections made between neurons involved in some types of learning.

But this study shows how that might happen.

The researchers have previously demonstrated that narcolepsy might be linked to the loss of hypocretin/orexin-making neurons in the hypothalamus. In this study, they looked at neighboring cells that produce melanin-concentrating hormone (MCH), which is involved in the control of both sleep and appetite. A majority (53%) of hypothalamic MCH cells fired in mice during REM sleep; 35% fired when they were awake, and 12% fired at both times.

Those cells also may play a role in learning and memory, the researchers suggest. To test their theory that MCH cells might help the brain store memories, they used “genetic tools” to turn MCH neurons on and off during memory tests.

Surprisingly, the researchers say, pharmacogenetic activation—turning on the MCH cells—worsened memory; genetic ablation—turning them off—improved memory. Further experiments suggested MCH neurons exclusively played this role during REM sleep.

The results suggest that MCH neurons help the brain actively forget new, possibly unimportant information. “Since dreams are thought to primarily occur during REM sleep,” says Thomas Kilduff, PhD, senior author of the study, “the sleep stage when the MCH cells turn on, activation of these cells may prevent the content of a dream from being stored in the hippocampus—consequently, the dream is quickly forgotten.”

Why do we forget some dreams and remember others? Researchers in a study funded by the National Institute of Neurological Disorders and Stroke say our dream memory may be controlled by a group of neurons commonly associated with appetite. Their findings could shed light on a wide range of memory-related conditions, including posttraumatic stress disorder (PTSD) and Alzheimer disease.

Studies have already shown that sleep helps the brain store new memories and eliminate excess information. Recent mouse studies have found that during sleep the brain prunes synaptic connections made between neurons involved in some types of learning.

But this study shows how that might happen.

The researchers have previously demonstrated that narcolepsy might be linked to the loss of hypocretin/orexin-making neurons in the hypothalamus. In this study, they looked at neighboring cells that produce melanin-concentrating hormone (MCH), which is involved in the control of both sleep and appetite. A majority (53%) of hypothalamic MCH cells fired in mice during REM sleep; 35% fired when they were awake, and 12% fired at both times.

Those cells also may play a role in learning and memory, the researchers suggest. To test their theory that MCH cells might help the brain store memories, they used “genetic tools” to turn MCH neurons on and off during memory tests.

Surprisingly, the researchers say, pharmacogenetic activation—turning on the MCH cells—worsened memory; genetic ablation—turning them off—improved memory. Further experiments suggested MCH neurons exclusively played this role during REM sleep.

The results suggest that MCH neurons help the brain actively forget new, possibly unimportant information. “Since dreams are thought to primarily occur during REM sleep,” says Thomas Kilduff, PhD, senior author of the study, “the sleep stage when the MCH cells turn on, activation of these cells may prevent the content of a dream from being stored in the hippocampus—consequently, the dream is quickly forgotten.”