The American Academy of Pediatrics recently issued an updated policy statement on discipline,¹ calling for us to teach parents not to use corporal punishment or verbally abuse their children. While a 2016 survey of 787 pediatricians found only 6% endorsed spanking as a positive, and, in a 2013 Harris Poll, fewer parents (72%) endorsed spanking, compared with 87% in 1995, we still have a lot of work to do given the even clearer adverse effects of painful discipline.

Monkey Business/Fotolia

One of the difficult things about teaching parents to stop corporal punishment is that it works. A smack instantly stops many misbehaviors, but, when asked closely, parents admit that the pause is only about 10 minutes. Instant results are highly reinforcing, and smacking gives welcome emotional release for adults. Most parents who hit their children also were hit growing up. Hitting seems a natural and appropriate method of parenting because this is what their own beloved parents did. Hitting is not a logical decision but a reflex reinforced by early and current experiences.

Another barrier to stopping hitting is that, while some adverse effects appear immediately, most occur later. Immediate effects of the child screaming, telling the parent “I hate you,” throwing things, or stomping to their room may upset the parent, but also may be seen as signs that their action was effective, if retribution is their unconscious goal. Parenting comes at you like a fire hose, and our visits with families can be a special opportunity for reflection on their goals and how well their methods are working.

We can help parents see the later effects appearing hours or days after the hitting. Children feel degraded by spanking, and they may talk back; act sassy; refuse to follow directions or cooperate; and be mean to siblings, pets, or peers. Wait, you say, those were the behaviors the parent cited for hitting the child in the first place! This “hit, act up, hit” cycle perpetuating corporal punishment² may be invisible to the parent.

Corporal punishment effects

“But he knows I love him,” parents will say, “and he respects me because of the way I have raised him.” Those things may be true, but the residual of loving combined with fearing has been shown to result in adulthood with increased aggression towards loved ones, including child abuse, partner violence, and sadistic sexual behaviors.

We can explain the much-later effects of corporal punishment: A child who experiences pain from the person they love and count on the most in life may develop very mixed feelings in future relationships. Especially if the pain was not countered by affection and admiration from the parent most of the time, the child may become aggressive; numb to others and to him/herself; and develop low self-esteem, learning difficulties, and depression or other mental health disorders. In some cases, the emotionally wounded child is driven to cause similar pain in others through mean acts, stealing things, hurting animals, and violence. “People hurt me so I am going to hurt them” is their unconscious path. As an adult, coping with old hurts may include numbing it with alcohol, drugs, overeating, smoking, or excessive sexual activities.

Do these sound like the familiar aftereffects of having adverse childhood experiences (ACE)? In fact, data from the original ACEs group who were recalling their childhoods showed that corporal punishment had a similar but independent impact as abuse, increasing suicide, and alcohol and substance use disorder.³ And the brain changes on MRIs of children with repeated corporal punishment had similar reductions of the prefrontal cortex and similar abnormalities of stress-related cortisol release.⁴

Parents commonly counter our advice not to hit their child by saying they were spanked and “came out okay.” But as for other medical problems, the effects of corporal punishment vary from child to child. Feelings are more easily and permanently damaged for some than for others, and we cannot predict who will have the worst outcomes. We do know that hitting is more harmful if not counteracted with affection, that more arbitrary hitting is worse than planned hitting for breaking prespecified rules, that more frequent hitting over time and to a later age has worse outcome, and that effects are smaller in studies of African Americans. Abuse, most often an acceleration of a disciplinary encounter, of course must be stopped and reported. Considered independently of parent factors, the children most likely to get hit are those with frequent impulsive misbehavior, such as ADHD, where our counseling to distinguish intentional from ADHD-related behaviors is most crucial. Anxious children likely take hitting to heart.

Specific strategies

We can’t just count on words and a handout to counter reflexes to hit, although these have some proven benefit. We have to convince parents to take action on other invisible health conditions such as high cholesterol or blood pressure, prescribing difficult changes in family diet and exercise. While these are also challenging they are not fraught with similar emotion. Parents resorting to hitting are more likely to be depressed, stressed, or have their own histories of ACEs. While we need to advise parents in practical strategies, we need to do this while attending to their strong feelings, family loyalty, frustration with the child’s misbehavior, and personal context, not just the facts about adverse outcomes.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She reported no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

References

1. Pediatrics. 2018 Dec 1;142[6]: e20183112.

2. J Youth Adolesc. 2015 Mar;44(3):658-69.

3. Child Abuse Negl. 2017 Sep;71:24-31.

4. Neuroimage. 2009 Aug;47 Suppl 2:T66-71.

The American Academy of Pediatrics recently issued an updated policy statement on discipline,¹ calling for us to teach parents not to use corporal punishment or verbally abuse their children. While a 2016 survey of 787 pediatricians found only 6% endorsed spanking as a positive, and, in a 2013 Harris Poll, fewer parents (72%) endorsed spanking, compared with 87% in 1995, we still have a lot of work to do given the even clearer adverse effects of painful discipline.

Monkey Business/Fotolia

One of the difficult things about teaching parents to stop corporal punishment is that it works. A smack instantly stops many misbehaviors, but, when asked closely, parents admit that the pause is only about 10 minutes. Instant results are highly reinforcing, and smacking gives welcome emotional release for adults. Most parents who hit their children also were hit growing up. Hitting seems a natural and appropriate method of parenting because this is what their own beloved parents did. Hitting is not a logical decision but a reflex reinforced by early and current experiences.

Another barrier to stopping hitting is that, while some adverse effects appear immediately, most occur later. Immediate effects of the child screaming, telling the parent “I hate you,” throwing things, or stomping to their room may upset the parent, but also may be seen as signs that their action was effective, if retribution is their unconscious goal. Parenting comes at you like a fire hose, and our visits with families can be a special opportunity for reflection on their goals and how well their methods are working.

We can help parents see the later effects appearing hours or days after the hitting. Children feel degraded by spanking, and they may talk back; act sassy; refuse to follow directions or cooperate; and be mean to siblings, pets, or peers. Wait, you say, those were the behaviors the parent cited for hitting the child in the first place! This “hit, act up, hit” cycle perpetuating corporal punishment² may be invisible to the parent.

Corporal punishment effects

“But he knows I love him,” parents will say, “and he respects me because of the way I have raised him.” Those things may be true, but the residual of loving combined with fearing has been shown to result in adulthood with increased aggression towards loved ones, including child abuse, partner violence, and sadistic sexual behaviors.

We can explain the much-later effects of corporal punishment: A child who experiences pain from the person they love and count on the most in life may develop very mixed feelings in future relationships. Especially if the pain was not countered by affection and admiration from the parent most of the time, the child may become aggressive; numb to others and to him/herself; and develop low self-esteem, learning difficulties, and depression or other mental health disorders. In some cases, the emotionally wounded child is driven to cause similar pain in others through mean acts, stealing things, hurting animals, and violence. “People hurt me so I am going to hurt them” is their unconscious path. As an adult, coping with old hurts may include numbing it with alcohol, drugs, overeating, smoking, or excessive sexual activities.

Do these sound like the familiar aftereffects of having adverse childhood experiences (ACE)? In fact, data from the original ACEs group who were recalling their childhoods showed that corporal punishment had a similar but independent impact as abuse, increasing suicide, and alcohol and substance use disorder.³ And the brain changes on MRIs of children with repeated corporal punishment had similar reductions of the prefrontal cortex and similar abnormalities of stress-related cortisol release.⁴

Parents commonly counter our advice not to hit their child by saying they were spanked and “came out okay.” But as for other medical problems, the effects of corporal punishment vary from child to child. Feelings are more easily and permanently damaged for some than for others, and we cannot predict who will have the worst outcomes. We do know that hitting is more harmful if not counteracted with affection, that more arbitrary hitting is worse than planned hitting for breaking prespecified rules, that more frequent hitting over time and to a later age has worse outcome, and that effects are smaller in studies of African Americans. Abuse, most often an acceleration of a disciplinary encounter, of course must be stopped and reported. Considered independently of parent factors, the children most likely to get hit are those with frequent impulsive misbehavior, such as ADHD, where our counseling to distinguish intentional from ADHD-related behaviors is most crucial. Anxious children likely take hitting to heart.

Specific strategies

We can’t just count on words and a handout to counter reflexes to hit, although these have some proven benefit. We have to convince parents to take action on other invisible health conditions such as high cholesterol or blood pressure, prescribing difficult changes in family diet and exercise. While these are also challenging they are not fraught with similar emotion. Parents resorting to hitting are more likely to be depressed, stressed, or have their own histories of ACEs. While we need to advise parents in practical strategies, we need to do this while attending to their strong feelings, family loyalty, frustration with the child’s misbehavior, and personal context, not just the facts about adverse outcomes.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She reported no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

References

1. Pediatrics. 2018 Dec 1;142[6]: e20183112.

2. J Youth Adolesc. 2015 Mar;44(3):658-69.

3. Child Abuse Negl. 2017 Sep;71:24-31.

4. Neuroimage. 2009 Aug;47 Suppl 2:T66-71.

The American Academy of Pediatrics recently issued an updated policy statement on discipline,¹ calling for us to teach parents not to use corporal punishment or verbally abuse their children. While a 2016 survey of 787 pediatricians found only 6% endorsed spanking as a positive, and, in a 2013 Harris Poll, fewer parents (72%) endorsed spanking, compared with 87% in 1995, we still have a lot of work to do given the even clearer adverse effects of painful discipline.

Monkey Business/Fotolia

One of the difficult things about teaching parents to stop corporal punishment is that it works. A smack instantly stops many misbehaviors, but, when asked closely, parents admit that the pause is only about 10 minutes. Instant results are highly reinforcing, and smacking gives welcome emotional release for adults. Most parents who hit their children also were hit growing up. Hitting seems a natural and appropriate method of parenting because this is what their own beloved parents did. Hitting is not a logical decision but a reflex reinforced by early and current experiences.

Another barrier to stopping hitting is that, while some adverse effects appear immediately, most occur later. Immediate effects of the child screaming, telling the parent “I hate you,” throwing things, or stomping to their room may upset the parent, but also may be seen as signs that their action was effective, if retribution is their unconscious goal. Parenting comes at you like a fire hose, and our visits with families can be a special opportunity for reflection on their goals and how well their methods are working.

We can help parents see the later effects appearing hours or days after the hitting. Children feel degraded by spanking, and they may talk back; act sassy; refuse to follow directions or cooperate; and be mean to siblings, pets, or peers. Wait, you say, those were the behaviors the parent cited for hitting the child in the first place! This “hit, act up, hit” cycle perpetuating corporal punishment² may be invisible to the parent.

Corporal punishment effects

“But he knows I love him,” parents will say, “and he respects me because of the way I have raised him.” Those things may be true, but the residual of loving combined with fearing has been shown to result in adulthood with increased aggression towards loved ones, including child abuse, partner violence, and sadistic sexual behaviors.

We can explain the much-later effects of corporal punishment: A child who experiences pain from the person they love and count on the most in life may develop very mixed feelings in future relationships. Especially if the pain was not countered by affection and admiration from the parent most of the time, the child may become aggressive; numb to others and to him/herself; and develop low self-esteem, learning difficulties, and depression or other mental health disorders. In some cases, the emotionally wounded child is driven to cause similar pain in others through mean acts, stealing things, hurting animals, and violence. “People hurt me so I am going to hurt them” is their unconscious path. As an adult, coping with old hurts may include numbing it with alcohol, drugs, overeating, smoking, or excessive sexual activities.

Do these sound like the familiar aftereffects of having adverse childhood experiences (ACE)? In fact, data from the original ACEs group who were recalling their childhoods showed that corporal punishment had a similar but independent impact as abuse, increasing suicide, and alcohol and substance use disorder.³ And the brain changes on MRIs of children with repeated corporal punishment had similar reductions of the prefrontal cortex and similar abnormalities of stress-related cortisol release.⁴

Parents commonly counter our advice not to hit their child by saying they were spanked and “came out okay.” But as for other medical problems, the effects of corporal punishment vary from child to child. Feelings are more easily and permanently damaged for some than for others, and we cannot predict who will have the worst outcomes. We do know that hitting is more harmful if not counteracted with affection, that more arbitrary hitting is worse than planned hitting for breaking prespecified rules, that more frequent hitting over time and to a later age has worse outcome, and that effects are smaller in studies of African Americans. Abuse, most often an acceleration of a disciplinary encounter, of course must be stopped and reported. Considered independently of parent factors, the children most likely to get hit are those with frequent impulsive misbehavior, such as ADHD, where our counseling to distinguish intentional from ADHD-related behaviors is most crucial. Anxious children likely take hitting to heart.

Specific strategies

We can’t just count on words and a handout to counter reflexes to hit, although these have some proven benefit. We have to convince parents to take action on other invisible health conditions such as high cholesterol or blood pressure, prescribing difficult changes in family diet and exercise. While these are also challenging they are not fraught with similar emotion. Parents resorting to hitting are more likely to be depressed, stressed, or have their own histories of ACEs. While we need to advise parents in practical strategies, we need to do this while attending to their strong feelings, family loyalty, frustration with the child’s misbehavior, and personal context, not just the facts about adverse outcomes.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She reported no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

References

1. Pediatrics. 2018 Dec 1;142[6]: e20183112.

2. J Youth Adolesc. 2015 Mar;44(3):658-69.

3. Child Abuse Negl. 2017 Sep;71:24-31.

4. Neuroimage. 2009 Aug;47 Suppl 2:T66-71.

In 2016 > 6,000 young people in the US killed themselves, according to the CDC. Most visited a health care provider or medical setting in the month prior. That means health care settings are not ideal for suicide intervention efforts. Researchers from the National Institute of Mental Health (NIMH) offer advice on how hospitals can address the rising suicide rate in a way that “is flexible and mindful of limited resources”—that is, an easily administered screening survey that provides immediate actionable response.

The NIMH report presents a 3-tiered clinical pathway system, created by a subcommittee of the Pathways in Clinical Care workgroup of the Physically Ill Child committee of the American Academy of Child and Adolescent Psychiatry.

The first step is an initial screen of all patients aged 10 to 24 years (for those with mental health issues, aged > 10 years), using the Ask Suicide-Screening Questions (ASQ) tool.

The first screening tool developed specifically for pediatric patients, the ASQ is free and available in 14 languages. Four questions (for example, “In the past few weeks, have you wished you were dead?”) take about 20 seconds to administer. A “yes” to one or more identified 97% of youth at risk in an NIMH study.

The second step is the most critical, the researchers say: A brief suicide safety assessment, which takes about 10 to 15 minutes to administer. This classifies a patient’s risk of suicide based on survey responses and clinical judgment.

The third step, if deemed necessary, is a full comprehensive safety evaluation by a licensed mental health provider, with the goal of addressing safety issues and establishing an intervention plan.

One of the biggest barriers to screening, NIMH says, is how to effectively and efficiently manage the patients who screen positive. Therefore, NIMH recommends that each health care setting have a plan. The ASQ Toolkit is designed to help with such a plan and to provide tools for managing care. The toolkit is organized according to medical setting: emergency department, inpatient medical/surgical unit, and outpatient primary care and specialty clinics. The kit includes information sheets, the Brief Suicide Safety Assessment Guide, nursing scripts, and information for parents and guardians.

The ASQ Toolkit is available at https://www.nimh.nih.gov/labs-at-nimh/asq-toolkit-materials/index.shtml.

In 2016 > 6,000 young people in the US killed themselves, according to the CDC. Most visited a health care provider or medical setting in the month prior. That means health care settings are not ideal for suicide intervention efforts. Researchers from the National Institute of Mental Health (NIMH) offer advice on how hospitals can address the rising suicide rate in a way that “is flexible and mindful of limited resources”—that is, an easily administered screening survey that provides immediate actionable response.

The NIMH report presents a 3-tiered clinical pathway system, created by a subcommittee of the Pathways in Clinical Care workgroup of the Physically Ill Child committee of the American Academy of Child and Adolescent Psychiatry.

The first step is an initial screen of all patients aged 10 to 24 years (for those with mental health issues, aged > 10 years), using the Ask Suicide-Screening Questions (ASQ) tool.

The first screening tool developed specifically for pediatric patients, the ASQ is free and available in 14 languages. Four questions (for example, “In the past few weeks, have you wished you were dead?”) take about 20 seconds to administer. A “yes” to one or more identified 97% of youth at risk in an NIMH study.

The second step is the most critical, the researchers say: A brief suicide safety assessment, which takes about 10 to 15 minutes to administer. This classifies a patient’s risk of suicide based on survey responses and clinical judgment.

The third step, if deemed necessary, is a full comprehensive safety evaluation by a licensed mental health provider, with the goal of addressing safety issues and establishing an intervention plan.

One of the biggest barriers to screening, NIMH says, is how to effectively and efficiently manage the patients who screen positive. Therefore, NIMH recommends that each health care setting have a plan. The ASQ Toolkit is designed to help with such a plan and to provide tools for managing care. The toolkit is organized according to medical setting: emergency department, inpatient medical/surgical unit, and outpatient primary care and specialty clinics. The kit includes information sheets, the Brief Suicide Safety Assessment Guide, nursing scripts, and information for parents and guardians.

The ASQ Toolkit is available at https://www.nimh.nih.gov/labs-at-nimh/asq-toolkit-materials/index.shtml.

In 2016 > 6,000 young people in the US killed themselves, according to the CDC. Most visited a health care provider or medical setting in the month prior. That means health care settings are not ideal for suicide intervention efforts. Researchers from the National Institute of Mental Health (NIMH) offer advice on how hospitals can address the rising suicide rate in a way that “is flexible and mindful of limited resources”—that is, an easily administered screening survey that provides immediate actionable response.

The NIMH report presents a 3-tiered clinical pathway system, created by a subcommittee of the Pathways in Clinical Care workgroup of the Physically Ill Child committee of the American Academy of Child and Adolescent Psychiatry.

The first step is an initial screen of all patients aged 10 to 24 years (for those with mental health issues, aged > 10 years), using the Ask Suicide-Screening Questions (ASQ) tool.

The first screening tool developed specifically for pediatric patients, the ASQ is free and available in 14 languages. Four questions (for example, “In the past few weeks, have you wished you were dead?”) take about 20 seconds to administer. A “yes” to one or more identified 97% of youth at risk in an NIMH study.

The second step is the most critical, the researchers say: A brief suicide safety assessment, which takes about 10 to 15 minutes to administer. This classifies a patient’s risk of suicide based on survey responses and clinical judgment.

The third step, if deemed necessary, is a full comprehensive safety evaluation by a licensed mental health provider, with the goal of addressing safety issues and establishing an intervention plan.

One of the biggest barriers to screening, NIMH says, is how to effectively and efficiently manage the patients who screen positive. Therefore, NIMH recommends that each health care setting have a plan. The ASQ Toolkit is designed to help with such a plan and to provide tools for managing care. The toolkit is organized according to medical setting: emergency department, inpatient medical/surgical unit, and outpatient primary care and specialty clinics. The kit includes information sheets, the Brief Suicide Safety Assessment Guide, nursing scripts, and information for parents and guardians.

The ASQ Toolkit is available at https://www.nimh.nih.gov/labs-at-nimh/asq-toolkit-materials/index.shtml.

Clinical question: Can adoption of a local opioid standard of practice for hospitalized patients reduce intravenous and overall opioid exposure while providing effective pain control?

Background: Inpatient use of intravenous opioids may be excessive, considering that oral opioids may provide more consistent pain control with less risk of adverse effects. If oral treatment is not possible, subcutaneous administration of opioids is an effective and possibly less addictive alternative to the intravenous route.

Study design: Historical control pilot study.

Setting: Single adult general medicine unit in an urban academic medical center.

Synopsis: A 6-month historical period with 287 patients was compared with a 3-month intervention period with 127 patients. The intervention consisted of a clinical practice standard that was presented to medical and nursing staff via didactic sessions and email. The standard recommended the oral route for opioids in patients tolerating oral intake and endorsed subcutaneous over intravenous administration.

Intravenous doses decreased by 84% (0.06 vs. 0.39 doses/patient-day; P less than .001), the daily rate of patients receiving any parenteral opioid decreased by 57% (6% vs. 14%; P less than .001), and the mean daily overall morphine-milligram equivalents decreased by 31% (6.30 vs. 9.11). Pain scores were unchanged for hospital days 1 through 3 but were significantly improved on day 4 (P = .004) and day 5 (P = .009).

Limitations of this study include the small number of patients on one unit, in one institution, with one clinician group. Attractive features of the intervention include its scalability and potential for augmentation via additional processes such as EHR changes, prescribing restrictions, and pharmacy monitoring.

Bottom line: A standard of practice intervention with peer-to-peer education was associated with decreased intravenous opioid exposure, decreased total opioid exposure, and effective pain control.



Citation: Ackerman AL et al. Association of an opioid standard of practice intervention with intravenous opioid exposure in hospitalized patients. JAMA Int Med. 2018;178(6):759-63.

Dr. Wanner is director, hospital medicine section, and associate chief, division of general internal medicine, University of Utah, Salt Lake City.

Clinical question: Can adoption of a local opioid standard of practice for hospitalized patients reduce intravenous and overall opioid exposure while providing effective pain control?

Background: Inpatient use of intravenous opioids may be excessive, considering that oral opioids may provide more consistent pain control with less risk of adverse effects. If oral treatment is not possible, subcutaneous administration of opioids is an effective and possibly less addictive alternative to the intravenous route.

Study design: Historical control pilot study.

Setting: Single adult general medicine unit in an urban academic medical center.

Synopsis: A 6-month historical period with 287 patients was compared with a 3-month intervention period with 127 patients. The intervention consisted of a clinical practice standard that was presented to medical and nursing staff via didactic sessions and email. The standard recommended the oral route for opioids in patients tolerating oral intake and endorsed subcutaneous over intravenous administration.

Intravenous doses decreased by 84% (0.06 vs. 0.39 doses/patient-day; P less than .001), the daily rate of patients receiving any parenteral opioid decreased by 57% (6% vs. 14%; P less than .001), and the mean daily overall morphine-milligram equivalents decreased by 31% (6.30 vs. 9.11). Pain scores were unchanged for hospital days 1 through 3 but were significantly improved on day 4 (P = .004) and day 5 (P = .009).

Limitations of this study include the small number of patients on one unit, in one institution, with one clinician group. Attractive features of the intervention include its scalability and potential for augmentation via additional processes such as EHR changes, prescribing restrictions, and pharmacy monitoring.

Bottom line: A standard of practice intervention with peer-to-peer education was associated with decreased intravenous opioid exposure, decreased total opioid exposure, and effective pain control.



Citation: Ackerman AL et al. Association of an opioid standard of practice intervention with intravenous opioid exposure in hospitalized patients. JAMA Int Med. 2018;178(6):759-63.

Dr. Wanner is director, hospital medicine section, and associate chief, division of general internal medicine, University of Utah, Salt Lake City.

Clinical question: Can adoption of a local opioid standard of practice for hospitalized patients reduce intravenous and overall opioid exposure while providing effective pain control?

Background: Inpatient use of intravenous opioids may be excessive, considering that oral opioids may provide more consistent pain control with less risk of adverse effects. If oral treatment is not possible, subcutaneous administration of opioids is an effective and possibly less addictive alternative to the intravenous route.

Study design: Historical control pilot study.

Setting: Single adult general medicine unit in an urban academic medical center.

Synopsis: A 6-month historical period with 287 patients was compared with a 3-month intervention period with 127 patients. The intervention consisted of a clinical practice standard that was presented to medical and nursing staff via didactic sessions and email. The standard recommended the oral route for opioids in patients tolerating oral intake and endorsed subcutaneous over intravenous administration.

Intravenous doses decreased by 84% (0.06 vs. 0.39 doses/patient-day; P less than .001), the daily rate of patients receiving any parenteral opioid decreased by 57% (6% vs. 14%; P less than .001), and the mean daily overall morphine-milligram equivalents decreased by 31% (6.30 vs. 9.11). Pain scores were unchanged for hospital days 1 through 3 but were significantly improved on day 4 (P = .004) and day 5 (P = .009).

Limitations of this study include the small number of patients on one unit, in one institution, with one clinician group. Attractive features of the intervention include its scalability and potential for augmentation via additional processes such as EHR changes, prescribing restrictions, and pharmacy monitoring.

Bottom line: A standard of practice intervention with peer-to-peer education was associated with decreased intravenous opioid exposure, decreased total opioid exposure, and effective pain control.



Citation: Ackerman AL et al. Association of an opioid standard of practice intervention with intravenous opioid exposure in hospitalized patients. JAMA Int Med. 2018;178(6):759-63.

Dr. Wanner is director, hospital medicine section, and associate chief, division of general internal medicine, University of Utah, Salt Lake City.

Caroline Bonham, MD, and Avi Kriechman, MD, join Psychcast host Lorenzo Norris, MD, via phone to discuss enhancing resilience in rural communities. Overall U.S. life expectancy decreased from 78.7 years to 78.6 years from 2016 to 2017. Researchers from the Centers for Disease Control and Prevention noted that, along with drug overdose deaths, suicide also drove the decrease in average lifespan over that time period. Addressing suicide in rural communities presents unique challenges.

Dr. Bonham is vice chair of community behavioral health in the department of psychiatry and behavioral sciences at the University of New Mexico, Albuquerque. Dr. Kriechman is a child, adolescent and family psychiatrist at the university, where he serves as principal investigator on ASPYR – Alliance-building for Suicide Prevention & Youth Resilience.

You can hear more on resilience and suicide from the MDedge Psychcast in these past episodes:

•  
•  
•  
• Find the MDedge Psychcast where ever you listen:

Amazon

Apple Podcasts

Google Podcasts

Spotify


 

Caroline Bonham, MD, and Avi Kriechman, MD, join Psychcast host Lorenzo Norris, MD, via phone to discuss enhancing resilience in rural communities. Overall U.S. life expectancy decreased from 78.7 years to 78.6 years from 2016 to 2017. Researchers from the Centers for Disease Control and Prevention noted that, along with drug overdose deaths, suicide also drove the decrease in average lifespan over that time period. Addressing suicide in rural communities presents unique challenges.

Dr. Bonham is vice chair of community behavioral health in the department of psychiatry and behavioral sciences at the University of New Mexico, Albuquerque. Dr. Kriechman is a child, adolescent and family psychiatrist at the university, where he serves as principal investigator on ASPYR – Alliance-building for Suicide Prevention & Youth Resilience.

You can hear more on resilience and suicide from the MDedge Psychcast in these past episodes:

•  
•  
•  
• Find the MDedge Psychcast where ever you listen:

Amazon

Apple Podcasts

Google Podcasts

Spotify


 

Caroline Bonham, MD, and Avi Kriechman, MD, join Psychcast host Lorenzo Norris, MD, via phone to discuss enhancing resilience in rural communities. Overall U.S. life expectancy decreased from 78.7 years to 78.6 years from 2016 to 2017. Researchers from the Centers for Disease Control and Prevention noted that, along with drug overdose deaths, suicide also drove the decrease in average lifespan over that time period. Addressing suicide in rural communities presents unique challenges.

Dr. Bonham is vice chair of community behavioral health in the department of psychiatry and behavioral sciences at the University of New Mexico, Albuquerque. Dr. Kriechman is a child, adolescent and family psychiatrist at the university, where he serves as principal investigator on ASPYR – Alliance-building for Suicide Prevention & Youth Resilience.

You can hear more on resilience and suicide from the MDedge Psychcast in these past episodes:

•  
•  
•  
• Find the MDedge Psychcast where ever you listen:

Amazon

Apple Podcasts

Google Podcasts

Spotify


 

Federal judges have blocked the Trump administration from weakening the Affordable Care Act’s contraceptive mandate. Too much sleep and too little sleep are linked to atherosclerosis, there is no drop in gout prevalence, but there isn’t an increase either, and back pain persists in one in five patients.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Federal judges have blocked the Trump administration from weakening the Affordable Care Act’s contraceptive mandate. Too much sleep and too little sleep are linked to atherosclerosis, there is no drop in gout prevalence, but there isn’t an increase either, and back pain persists in one in five patients.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Federal judges have blocked the Trump administration from weakening the Affordable Care Act’s contraceptive mandate. Too much sleep and too little sleep are linked to atherosclerosis, there is no drop in gout prevalence, but there isn’t an increase either, and back pain persists in one in five patients.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Disease-modifying therapies give patients with relapsing-remitting multiple sclerosis a lower risk of developing secondary progressive disease that may only be topped in specific patients with highly active disease by the use of nonmyeloablative hematopoietic stem cell transplantation, according to findings from two studies published online Jan. 15 in JAMA.

copyright Zerbor/Thinkstock

The first study found that interferon-beta, glatiramer acetate (Copaxone), fingolimod (Gilenya), natalizumab (Tysabri), and alemtuzumab (Lemtrada) are associated with a lower risk of conversion to secondary progressive MS, compared with no treatment. Initial treatment with the newer therapies provided a greater risk reduction, compared with initial treatment with interferon-beta or glatiramer acetate.

The second study, described as “the first randomized trial of HSCT [nonmyeloablative hematopoietic stem cell transplantation] in patients with relapsing-remitting MS,” suggests that HSCT prolongs the time to disease progression, compared with disease-modifying therapies (DMTs). It also suggests that HSCT can lead to clinical improvement.
 

DMTs reduced risk of conversion to secondary progressive MS

Few previous studies have examined the association between DMTs and the risk of conversion from relapsing-remitting MS to secondary progressive MS. Those that have analyzed this association have not used a validated definition of secondary progressive MS. J. William L. Brown, MD, of the University of Cambridge, England, and his colleagues used a validated definition of secondary progressive MS that was published in 2016 to investigate how DMTs affect the rate of conversion, compared with no treatment. The researchers also compared the risk reduction provided by fingolimod, alemtuzumab, or natalizumab with that provided by interferon-beta or glatiramer acetate.

Dr. Brown and his colleagues analyzed prospectively collected clinical data from an international observational cohort study called MSBase. Eligible participants had relapsing-remitting MS, the complete MSBase minimum data set, at least one Expanded Disability Status Scale (EDSS) score recorded within 6 months before baseline, and at least two EDSS scores recorded after baseline. Participants initiated a DMT or began clinical monitoring during 1988-2012. The population had a minimum follow-up duration of 4 years. Patients who stopped their initial therapy within 6 months and those participating in clinical trials were excluded.

The primary outcome was conversion to secondary progressive MS. Dr. Brown and his colleagues defined this outcome as an EDSS increase of 1 point for participants with a baseline EDSS score of 5.5 or less and as an increase of 0.5 points for participants with a baseline EDSS score higher than 5.5. This increase had to occur in the absence of relapses and be confirmed at a subsequent visit 3 or fewer months later. In addition, the increased EDSS score had to be 4 or more.

After excluding ineligible participants, the investigators matched 1,555 patients from 68 centers in 21 countries. Each therapy analyzed was associated with reduced risk of converting to secondary progressive MS, compared with no treatment. The hazard ratios for conversion were 0.71 for interferon-beta or glatiramer acetate, 0.37 for fingolimod, 0.61 for natalizumab, and 0.52 for alemtuzumab, compared with no treatment.

Treatment with interferon-beta or glatiramer acetate within 5 years of disease onset was associated with a reduced risk of conversion (HR, 0.77), compared with treatment later than 5 years after disease onset. Similarly, patients who escalated treatment from interferon-beta or glatiramer acetate to any of the other three DMTs within 5 years of disease onset had a significantly lower risk of conversion (HR, 0.76) than did those who escalated later. Furthermore, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a significantly reduced risk of conversion (HR, 0.66), compared with initial treatment with interferon-beta or glatiramer acetate.

One of the study’s limitations is its observational design, which precludes the determination of causality, Dr. Brown and his colleagues said. In addition, functional score subcomponents of the EDSS were unavailable, which prevented the researchers from using the definition of secondary progressive MS with the best combination of sensitivity, specificity, and accuracy. Some analyses were limited by small numbers of patients, and the study did not evaluate the risks associated with DMTs. Nevertheless, “these findings, considered along with these therapies’ risks, may help inform decisions about DMT selection,” the authors concluded.

Financial support for this study was provided by the National Health and Medical Research Council of Australia and the University of Melbourne. Dr. Brown received a Next Generation Fellowship funded by the Grand Charity of the Freemasons and an MSBase 2017 Fellowship. Alemtuzumab studies conducted in Cambridge were supported by the National Institute for Health Research Cambridge Biomedical Research Centre and the MS Society UK.
 

HSCT delayed disease progression

In a previous case series, Richard K. Burt, MD, of Northwestern University in Chicago, and his colleagues found that patients with relapsing-remitting MS who underwent nonmyeloablative HSCT had neurologic improvement and a 70% likelihood of having a 4-year period of disease remission. Dr. Burt and his colleagues undertook the MS international stem cell transplant trial to compare the effects of nonmyeloablative HSCT with those of continued DMT treatment on disease progression in participants with highly active relapsing-remitting MS.

The researchers enrolled 110 participants at four international centers into their open-label trial. Eligible participants had two or more clinical relapses or one relapse and at least one gadolinium-enhancing lesion at a separate time within the previous 12 months, despite DMT treatment. The investigators also required participants to have an EDSS score between 2.0 and 6.0. Patients with primary or secondary progressive MS were excluded.

Dr. Burt and his colleagues randomized participants to receive HSCT or an approved DMT that was more effective or in a different class than the one they were receiving at baseline. Ocrelizumab (Ocrevus) was not administered during the study because it had not yet been approved. The investigators excluded alemtuzumab because of its association with persistent lymphopenia and autoimmune disorders. After 1 year of treatment, patients receiving a DMT who had disability progression could cross over to the HSCT arm. Patients randomized to HSCT stopped taking their usual DMT.

Time to disease progression was the study’s primary endpoint. The investigators defined disease progression as an increase in EDSS score of at least 1 point on two evaluations 6 months apart after at least 1 year of treatment. The increase was required to result from MS. The neurologist who recorded participants’ EDSS evaluations was blinded to treatment group assignment.

The researchers randomized 55 patients to each study arm. Approximately 66% of participants were women, and the sample’s mean age was 36 years. There were no significant baseline differences between groups on demographic, clinical, or imaging characteristics. Three patients in the HSCT group were withdrawn from the study, and four in the DMT group were lost to follow-up after seeking HSCT at outside facilities.

Three patients in the HSCT group and 34 patients in the DMT group had disease progression. Mean follow-up duration was 2.8 years. The investigators could not calculate the median time to progression in the HSCT group because too few events occurred. Median time to progression was 24 months in the DMT group (HR, 0.07). During the first year, mean EDSS scores decreased (indicating improvement) from 3.38 to 2.36 in the HSCT group. Mean EDSS scores increased from 3.31 to 3.98 in the DMT group. No participants died, and no patients who received HSCT-developed nonhematopoietic grade 4 toxicities.

“To our knowledge, this is the first randomized trial of HSCT in patients with relapsing-remitting MS,” Dr. Burt and his colleagues said. Although observational studies have found similar EDSS improvements following HSCT, “this degree of improvement has not been demonstrated in pharmaceutical trials even with more intensive DMT such as alemtuzumab,” they concluded.

The Danhakl Family Foundation, the Cumming Foundation, the McNamara Purcell Foundation, Morgan Stanley, and the National Institute for Health Research Sheffield Clinical Research Facility provided financial support for this study. No pharmaceutical companies supported the study.

egreb@mdedge.com

SOURCEs: Brown JWL et al. JAMA. 2019;321(2):175-87. doi: 10.1001/jama.2018.20588.; and Burt RK et al. JAMA. 2019;321(2):165-74. doi: 10.1001/jama.2018.18743.

Disease-modifying therapies give patients with relapsing-remitting multiple sclerosis a lower risk of developing secondary progressive disease that may only be topped in specific patients with highly active disease by the use of nonmyeloablative hematopoietic stem cell transplantation, according to findings from two studies published online Jan. 15 in JAMA.

copyright Zerbor/Thinkstock

The first study found that interferon-beta, glatiramer acetate (Copaxone), fingolimod (Gilenya), natalizumab (Tysabri), and alemtuzumab (Lemtrada) are associated with a lower risk of conversion to secondary progressive MS, compared with no treatment. Initial treatment with the newer therapies provided a greater risk reduction, compared with initial treatment with interferon-beta or glatiramer acetate.

The second study, described as “the first randomized trial of HSCT [nonmyeloablative hematopoietic stem cell transplantation] in patients with relapsing-remitting MS,” suggests that HSCT prolongs the time to disease progression, compared with disease-modifying therapies (DMTs). It also suggests that HSCT can lead to clinical improvement.
 

DMTs reduced risk of conversion to secondary progressive MS

Few previous studies have examined the association between DMTs and the risk of conversion from relapsing-remitting MS to secondary progressive MS. Those that have analyzed this association have not used a validated definition of secondary progressive MS. J. William L. Brown, MD, of the University of Cambridge, England, and his colleagues used a validated definition of secondary progressive MS that was published in 2016 to investigate how DMTs affect the rate of conversion, compared with no treatment. The researchers also compared the risk reduction provided by fingolimod, alemtuzumab, or natalizumab with that provided by interferon-beta or glatiramer acetate.

Dr. Brown and his colleagues analyzed prospectively collected clinical data from an international observational cohort study called MSBase. Eligible participants had relapsing-remitting MS, the complete MSBase minimum data set, at least one Expanded Disability Status Scale (EDSS) score recorded within 6 months before baseline, and at least two EDSS scores recorded after baseline. Participants initiated a DMT or began clinical monitoring during 1988-2012. The population had a minimum follow-up duration of 4 years. Patients who stopped their initial therapy within 6 months and those participating in clinical trials were excluded.

The primary outcome was conversion to secondary progressive MS. Dr. Brown and his colleagues defined this outcome as an EDSS increase of 1 point for participants with a baseline EDSS score of 5.5 or less and as an increase of 0.5 points for participants with a baseline EDSS score higher than 5.5. This increase had to occur in the absence of relapses and be confirmed at a subsequent visit 3 or fewer months later. In addition, the increased EDSS score had to be 4 or more.

After excluding ineligible participants, the investigators matched 1,555 patients from 68 centers in 21 countries. Each therapy analyzed was associated with reduced risk of converting to secondary progressive MS, compared with no treatment. The hazard ratios for conversion were 0.71 for interferon-beta or glatiramer acetate, 0.37 for fingolimod, 0.61 for natalizumab, and 0.52 for alemtuzumab, compared with no treatment.

Treatment with interferon-beta or glatiramer acetate within 5 years of disease onset was associated with a reduced risk of conversion (HR, 0.77), compared with treatment later than 5 years after disease onset. Similarly, patients who escalated treatment from interferon-beta or glatiramer acetate to any of the other three DMTs within 5 years of disease onset had a significantly lower risk of conversion (HR, 0.76) than did those who escalated later. Furthermore, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a significantly reduced risk of conversion (HR, 0.66), compared with initial treatment with interferon-beta or glatiramer acetate.

One of the study’s limitations is its observational design, which precludes the determination of causality, Dr. Brown and his colleagues said. In addition, functional score subcomponents of the EDSS were unavailable, which prevented the researchers from using the definition of secondary progressive MS with the best combination of sensitivity, specificity, and accuracy. Some analyses were limited by small numbers of patients, and the study did not evaluate the risks associated with DMTs. Nevertheless, “these findings, considered along with these therapies’ risks, may help inform decisions about DMT selection,” the authors concluded.

Financial support for this study was provided by the National Health and Medical Research Council of Australia and the University of Melbourne. Dr. Brown received a Next Generation Fellowship funded by the Grand Charity of the Freemasons and an MSBase 2017 Fellowship. Alemtuzumab studies conducted in Cambridge were supported by the National Institute for Health Research Cambridge Biomedical Research Centre and the MS Society UK.
 

HSCT delayed disease progression

In a previous case series, Richard K. Burt, MD, of Northwestern University in Chicago, and his colleagues found that patients with relapsing-remitting MS who underwent nonmyeloablative HSCT had neurologic improvement and a 70% likelihood of having a 4-year period of disease remission. Dr. Burt and his colleagues undertook the MS international stem cell transplant trial to compare the effects of nonmyeloablative HSCT with those of continued DMT treatment on disease progression in participants with highly active relapsing-remitting MS.

The researchers enrolled 110 participants at four international centers into their open-label trial. Eligible participants had two or more clinical relapses or one relapse and at least one gadolinium-enhancing lesion at a separate time within the previous 12 months, despite DMT treatment. The investigators also required participants to have an EDSS score between 2.0 and 6.0. Patients with primary or secondary progressive MS were excluded.

Dr. Burt and his colleagues randomized participants to receive HSCT or an approved DMT that was more effective or in a different class than the one they were receiving at baseline. Ocrelizumab (Ocrevus) was not administered during the study because it had not yet been approved. The investigators excluded alemtuzumab because of its association with persistent lymphopenia and autoimmune disorders. After 1 year of treatment, patients receiving a DMT who had disability progression could cross over to the HSCT arm. Patients randomized to HSCT stopped taking their usual DMT.

Time to disease progression was the study’s primary endpoint. The investigators defined disease progression as an increase in EDSS score of at least 1 point on two evaluations 6 months apart after at least 1 year of treatment. The increase was required to result from MS. The neurologist who recorded participants’ EDSS evaluations was blinded to treatment group assignment.

The researchers randomized 55 patients to each study arm. Approximately 66% of participants were women, and the sample’s mean age was 36 years. There were no significant baseline differences between groups on demographic, clinical, or imaging characteristics. Three patients in the HSCT group were withdrawn from the study, and four in the DMT group were lost to follow-up after seeking HSCT at outside facilities.

Three patients in the HSCT group and 34 patients in the DMT group had disease progression. Mean follow-up duration was 2.8 years. The investigators could not calculate the median time to progression in the HSCT group because too few events occurred. Median time to progression was 24 months in the DMT group (HR, 0.07). During the first year, mean EDSS scores decreased (indicating improvement) from 3.38 to 2.36 in the HSCT group. Mean EDSS scores increased from 3.31 to 3.98 in the DMT group. No participants died, and no patients who received HSCT-developed nonhematopoietic grade 4 toxicities.

“To our knowledge, this is the first randomized trial of HSCT in patients with relapsing-remitting MS,” Dr. Burt and his colleagues said. Although observational studies have found similar EDSS improvements following HSCT, “this degree of improvement has not been demonstrated in pharmaceutical trials even with more intensive DMT such as alemtuzumab,” they concluded.

The Danhakl Family Foundation, the Cumming Foundation, the McNamara Purcell Foundation, Morgan Stanley, and the National Institute for Health Research Sheffield Clinical Research Facility provided financial support for this study. No pharmaceutical companies supported the study.

egreb@mdedge.com

SOURCEs: Brown JWL et al. JAMA. 2019;321(2):175-87. doi: 10.1001/jama.2018.20588.; and Burt RK et al. JAMA. 2019;321(2):165-74. doi: 10.1001/jama.2018.18743.

Disease-modifying therapies give patients with relapsing-remitting multiple sclerosis a lower risk of developing secondary progressive disease that may only be topped in specific patients with highly active disease by the use of nonmyeloablative hematopoietic stem cell transplantation, according to findings from two studies published online Jan. 15 in JAMA.

copyright Zerbor/Thinkstock

The first study found that interferon-beta, glatiramer acetate (Copaxone), fingolimod (Gilenya), natalizumab (Tysabri), and alemtuzumab (Lemtrada) are associated with a lower risk of conversion to secondary progressive MS, compared with no treatment. Initial treatment with the newer therapies provided a greater risk reduction, compared with initial treatment with interferon-beta or glatiramer acetate.

The second study, described as “the first randomized trial of HSCT [nonmyeloablative hematopoietic stem cell transplantation] in patients with relapsing-remitting MS,” suggests that HSCT prolongs the time to disease progression, compared with disease-modifying therapies (DMTs). It also suggests that HSCT can lead to clinical improvement.
 

DMTs reduced risk of conversion to secondary progressive MS

Few previous studies have examined the association between DMTs and the risk of conversion from relapsing-remitting MS to secondary progressive MS. Those that have analyzed this association have not used a validated definition of secondary progressive MS. J. William L. Brown, MD, of the University of Cambridge, England, and his colleagues used a validated definition of secondary progressive MS that was published in 2016 to investigate how DMTs affect the rate of conversion, compared with no treatment. The researchers also compared the risk reduction provided by fingolimod, alemtuzumab, or natalizumab with that provided by interferon-beta or glatiramer acetate.

Dr. Brown and his colleagues analyzed prospectively collected clinical data from an international observational cohort study called MSBase. Eligible participants had relapsing-remitting MS, the complete MSBase minimum data set, at least one Expanded Disability Status Scale (EDSS) score recorded within 6 months before baseline, and at least two EDSS scores recorded after baseline. Participants initiated a DMT or began clinical monitoring during 1988-2012. The population had a minimum follow-up duration of 4 years. Patients who stopped their initial therapy within 6 months and those participating in clinical trials were excluded.

The primary outcome was conversion to secondary progressive MS. Dr. Brown and his colleagues defined this outcome as an EDSS increase of 1 point for participants with a baseline EDSS score of 5.5 or less and as an increase of 0.5 points for participants with a baseline EDSS score higher than 5.5. This increase had to occur in the absence of relapses and be confirmed at a subsequent visit 3 or fewer months later. In addition, the increased EDSS score had to be 4 or more.

After excluding ineligible participants, the investigators matched 1,555 patients from 68 centers in 21 countries. Each therapy analyzed was associated with reduced risk of converting to secondary progressive MS, compared with no treatment. The hazard ratios for conversion were 0.71 for interferon-beta or glatiramer acetate, 0.37 for fingolimod, 0.61 for natalizumab, and 0.52 for alemtuzumab, compared with no treatment.

Treatment with interferon-beta or glatiramer acetate within 5 years of disease onset was associated with a reduced risk of conversion (HR, 0.77), compared with treatment later than 5 years after disease onset. Similarly, patients who escalated treatment from interferon-beta or glatiramer acetate to any of the other three DMTs within 5 years of disease onset had a significantly lower risk of conversion (HR, 0.76) than did those who escalated later. Furthermore, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a significantly reduced risk of conversion (HR, 0.66), compared with initial treatment with interferon-beta or glatiramer acetate.

One of the study’s limitations is its observational design, which precludes the determination of causality, Dr. Brown and his colleagues said. In addition, functional score subcomponents of the EDSS were unavailable, which prevented the researchers from using the definition of secondary progressive MS with the best combination of sensitivity, specificity, and accuracy. Some analyses were limited by small numbers of patients, and the study did not evaluate the risks associated with DMTs. Nevertheless, “these findings, considered along with these therapies’ risks, may help inform decisions about DMT selection,” the authors concluded.

Financial support for this study was provided by the National Health and Medical Research Council of Australia and the University of Melbourne. Dr. Brown received a Next Generation Fellowship funded by the Grand Charity of the Freemasons and an MSBase 2017 Fellowship. Alemtuzumab studies conducted in Cambridge were supported by the National Institute for Health Research Cambridge Biomedical Research Centre and the MS Society UK.
 

HSCT delayed disease progression

In a previous case series, Richard K. Burt, MD, of Northwestern University in Chicago, and his colleagues found that patients with relapsing-remitting MS who underwent nonmyeloablative HSCT had neurologic improvement and a 70% likelihood of having a 4-year period of disease remission. Dr. Burt and his colleagues undertook the MS international stem cell transplant trial to compare the effects of nonmyeloablative HSCT with those of continued DMT treatment on disease progression in participants with highly active relapsing-remitting MS.

The researchers enrolled 110 participants at four international centers into their open-label trial. Eligible participants had two or more clinical relapses or one relapse and at least one gadolinium-enhancing lesion at a separate time within the previous 12 months, despite DMT treatment. The investigators also required participants to have an EDSS score between 2.0 and 6.0. Patients with primary or secondary progressive MS were excluded.

Dr. Burt and his colleagues randomized participants to receive HSCT or an approved DMT that was more effective or in a different class than the one they were receiving at baseline. Ocrelizumab (Ocrevus) was not administered during the study because it had not yet been approved. The investigators excluded alemtuzumab because of its association with persistent lymphopenia and autoimmune disorders. After 1 year of treatment, patients receiving a DMT who had disability progression could cross over to the HSCT arm. Patients randomized to HSCT stopped taking their usual DMT.

Time to disease progression was the study’s primary endpoint. The investigators defined disease progression as an increase in EDSS score of at least 1 point on two evaluations 6 months apart after at least 1 year of treatment. The increase was required to result from MS. The neurologist who recorded participants’ EDSS evaluations was blinded to treatment group assignment.

The researchers randomized 55 patients to each study arm. Approximately 66% of participants were women, and the sample’s mean age was 36 years. There were no significant baseline differences between groups on demographic, clinical, or imaging characteristics. Three patients in the HSCT group were withdrawn from the study, and four in the DMT group were lost to follow-up after seeking HSCT at outside facilities.

Three patients in the HSCT group and 34 patients in the DMT group had disease progression. Mean follow-up duration was 2.8 years. The investigators could not calculate the median time to progression in the HSCT group because too few events occurred. Median time to progression was 24 months in the DMT group (HR, 0.07). During the first year, mean EDSS scores decreased (indicating improvement) from 3.38 to 2.36 in the HSCT group. Mean EDSS scores increased from 3.31 to 3.98 in the DMT group. No participants died, and no patients who received HSCT-developed nonhematopoietic grade 4 toxicities.

“To our knowledge, this is the first randomized trial of HSCT in patients with relapsing-remitting MS,” Dr. Burt and his colleagues said. Although observational studies have found similar EDSS improvements following HSCT, “this degree of improvement has not been demonstrated in pharmaceutical trials even with more intensive DMT such as alemtuzumab,” they concluded.

The Danhakl Family Foundation, the Cumming Foundation, the McNamara Purcell Foundation, Morgan Stanley, and the National Institute for Health Research Sheffield Clinical Research Facility provided financial support for this study. No pharmaceutical companies supported the study.

egreb@mdedge.com

SOURCEs: Brown JWL et al. JAMA. 2019;321(2):175-87. doi: 10.1001/jama.2018.20588.; and Burt RK et al. JAMA. 2019;321(2):165-74. doi: 10.1001/jama.2018.18743.

LA JOLLA, CALIF. – New developments in epigenetics research were highlighted at the 11th annual T-cell Lymphoma Forum.

Vidyard Video

In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.

Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.

Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.

And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

LA JOLLA, CALIF. – New developments in epigenetics research were highlighted at the 11th annual T-cell Lymphoma Forum.

Vidyard Video

In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.

Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.

Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.

And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

LA JOLLA, CALIF. – New developments in epigenetics research were highlighted at the 11th annual T-cell Lymphoma Forum.

Vidyard Video

In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.

Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.

Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.

And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

CHICAGO – Bempedoic acid, a novel oral lipid-lowering agent, reduced LDL cholesterol by 21% and high-sensitivity C-reactive protein by 24% with a side-effect profile similar to placebo in statin-intolerant hypercholesterolemic patients with or at high risk for atherosclerotic cardiovascular disease in the pivotal phase 3 CLEAR Serenity trial, Ulrich Laufs, MD, PhD, reported at the American Heart Association scientific sessions.

CLEAR Serenity is one of five pivotal phase 3 trials of bempedoic acid. The others evaluated bempedoic acid as add-on therapy to obtain additional lipid lowering in patients already on a maximum-dose statin, and in combination with ezetimibe (Zetia) as a single pill, also in patients on full-dose statin therapy. All of these trials met their efficacy and safety endpoints. The drug’s developer, Esperion Therapeutics, has announced plans to file for marketing approval of bempedoic acid and for the bempedoic acid/ezetimibe combo pill with the Food and Drug Administration and the European Medicines Agency in the first months of 2019.

CLEAR Serenity was a 24-week, double-blind, placebo-controlled trial conducted at 67 North American sites. The 345 statin-intolerant participants were randomized 2:1 to bempedoic acid at 180 mg once daily or placebo.

“I think the specific contribution of this study is, importantly, that myalgia and other muscle-related symptoms were not increased with bempedoic acid versus placebo in this population that’s statin intolerant, more than 90% of whom complained of statin-related muscle symptoms,” said Dr. Laufs, professor and chair of the department of cardiology at the University of Leipzig (Germany).

Rates of major adverse cardiovascular events were too low in this relatively short-term, modest-size trial to be informative, but the results of the previously presented CLEAR Harmony trial are reassuring in this regard, according to the cardiologist. CLEAR Harmony was a 52-week study that included 2,230 patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia whose LDL was inadequately controlled despite high-intensity statin therapy. They were randomized to add-on bempedoic acid or placebo. The adjudicated major adverse cardiovascular event rate was 4.6% in the bempedoic acid group and not significantly different at 5.7% in controls.

Definitive data on the effect of bempedoic acid on cardiovascular morbidity and mortality event rates will eventually be provided by an ongoing global randomized, double-blind, placebo-controlled trial expected to enroll more than 12,000 patients.

Rates of various types of adverse events were closely similar in the bempedoic acid and placebo groups in CLEAR Serenity, with a couple of intriguing exceptions, according to Dr. Laufs. For example, the rate of new-onset or worsening diabetes was 2.1% in the bempedoic acid group, compared with 4.5% in controls.

“This is consistent with results in the other studies in the overall bempedoic acid program. It will be something of great interest to follow up in the ongoing outcomes trial,” he said. “At this point I would feel comfortable in saying that there is no deterioration of glucose tolerance, unlike with statins. Whether there is an actual improvement or not needs to be characterized a little better.”

The other difference in the safety profile between the two study arms in CLEAR Serenity was a trend for higher uric acid levels and an increased risk of developing gout in the bempedoic acid group. Gout occurred in 1.7% of the bempedoic acid group and 0.9% of placebo-treated controls. A similar signal has been seen in the other pivotal trials, but a definitive answer as to gout risk must await the large ongoing outcomes trial, Dr. Laufs continued.

Bempedoic acid is a first-in-class oral inhibitor of ATP citrate lyase, an enzyme that is inactive in skeletal muscle – thus, the lack of myalgia complaints – and lies upstream of HMG-CoA reductase in cholesterol synthesis. When combined in a single pill with ezetimibe, which lowers LDL by stimulating the LDL receptor, the lipid-lowering impact is magnified over that of either drug alone. In the phase 3 program, the combination pill resulted in a further 35% reduction in LDL when added to a maximally tolerated statin and a 43% reduction in LDL when used as monotherapy.

Session cochair Robert H. Eckel, MD, commented that bempedoic acid appears to be poised to address a significant unmet need in preventive cardiology.

“We clearly need alternative therapies in patients with statin intolerance. We see a lot of these patients in referral centers. This drug looks safe and very effective at modifying LDL, about as much so as ezetimibe and maybe a little bit more,” said Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.

Dr. Laufs reported serving as a paid consultant to Esperion Therapeutics, the study sponsor, as well as to Amgen and Sanofi.

bjancin@mdedge.com

CHICAGO – Bempedoic acid, a novel oral lipid-lowering agent, reduced LDL cholesterol by 21% and high-sensitivity C-reactive protein by 24% with a side-effect profile similar to placebo in statin-intolerant hypercholesterolemic patients with or at high risk for atherosclerotic cardiovascular disease in the pivotal phase 3 CLEAR Serenity trial, Ulrich Laufs, MD, PhD, reported at the American Heart Association scientific sessions.

CLEAR Serenity is one of five pivotal phase 3 trials of bempedoic acid. The others evaluated bempedoic acid as add-on therapy to obtain additional lipid lowering in patients already on a maximum-dose statin, and in combination with ezetimibe (Zetia) as a single pill, also in patients on full-dose statin therapy. All of these trials met their efficacy and safety endpoints. The drug’s developer, Esperion Therapeutics, has announced plans to file for marketing approval of bempedoic acid and for the bempedoic acid/ezetimibe combo pill with the Food and Drug Administration and the European Medicines Agency in the first months of 2019.

CLEAR Serenity was a 24-week, double-blind, placebo-controlled trial conducted at 67 North American sites. The 345 statin-intolerant participants were randomized 2:1 to bempedoic acid at 180 mg once daily or placebo.

“I think the specific contribution of this study is, importantly, that myalgia and other muscle-related symptoms were not increased with bempedoic acid versus placebo in this population that’s statin intolerant, more than 90% of whom complained of statin-related muscle symptoms,” said Dr. Laufs, professor and chair of the department of cardiology at the University of Leipzig (Germany).

Rates of major adverse cardiovascular events were too low in this relatively short-term, modest-size trial to be informative, but the results of the previously presented CLEAR Harmony trial are reassuring in this regard, according to the cardiologist. CLEAR Harmony was a 52-week study that included 2,230 patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia whose LDL was inadequately controlled despite high-intensity statin therapy. They were randomized to add-on bempedoic acid or placebo. The adjudicated major adverse cardiovascular event rate was 4.6% in the bempedoic acid group and not significantly different at 5.7% in controls.

Definitive data on the effect of bempedoic acid on cardiovascular morbidity and mortality event rates will eventually be provided by an ongoing global randomized, double-blind, placebo-controlled trial expected to enroll more than 12,000 patients.

Rates of various types of adverse events were closely similar in the bempedoic acid and placebo groups in CLEAR Serenity, with a couple of intriguing exceptions, according to Dr. Laufs. For example, the rate of new-onset or worsening diabetes was 2.1% in the bempedoic acid group, compared with 4.5% in controls.

“This is consistent with results in the other studies in the overall bempedoic acid program. It will be something of great interest to follow up in the ongoing outcomes trial,” he said. “At this point I would feel comfortable in saying that there is no deterioration of glucose tolerance, unlike with statins. Whether there is an actual improvement or not needs to be characterized a little better.”

The other difference in the safety profile between the two study arms in CLEAR Serenity was a trend for higher uric acid levels and an increased risk of developing gout in the bempedoic acid group. Gout occurred in 1.7% of the bempedoic acid group and 0.9% of placebo-treated controls. A similar signal has been seen in the other pivotal trials, but a definitive answer as to gout risk must await the large ongoing outcomes trial, Dr. Laufs continued.

Bempedoic acid is a first-in-class oral inhibitor of ATP citrate lyase, an enzyme that is inactive in skeletal muscle – thus, the lack of myalgia complaints – and lies upstream of HMG-CoA reductase in cholesterol synthesis. When combined in a single pill with ezetimibe, which lowers LDL by stimulating the LDL receptor, the lipid-lowering impact is magnified over that of either drug alone. In the phase 3 program, the combination pill resulted in a further 35% reduction in LDL when added to a maximally tolerated statin and a 43% reduction in LDL when used as monotherapy.

Session cochair Robert H. Eckel, MD, commented that bempedoic acid appears to be poised to address a significant unmet need in preventive cardiology.

“We clearly need alternative therapies in patients with statin intolerance. We see a lot of these patients in referral centers. This drug looks safe and very effective at modifying LDL, about as much so as ezetimibe and maybe a little bit more,” said Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.

Dr. Laufs reported serving as a paid consultant to Esperion Therapeutics, the study sponsor, as well as to Amgen and Sanofi.

bjancin@mdedge.com

CHICAGO – Bempedoic acid, a novel oral lipid-lowering agent, reduced LDL cholesterol by 21% and high-sensitivity C-reactive protein by 24% with a side-effect profile similar to placebo in statin-intolerant hypercholesterolemic patients with or at high risk for atherosclerotic cardiovascular disease in the pivotal phase 3 CLEAR Serenity trial, Ulrich Laufs, MD, PhD, reported at the American Heart Association scientific sessions.

CLEAR Serenity is one of five pivotal phase 3 trials of bempedoic acid. The others evaluated bempedoic acid as add-on therapy to obtain additional lipid lowering in patients already on a maximum-dose statin, and in combination with ezetimibe (Zetia) as a single pill, also in patients on full-dose statin therapy. All of these trials met their efficacy and safety endpoints. The drug’s developer, Esperion Therapeutics, has announced plans to file for marketing approval of bempedoic acid and for the bempedoic acid/ezetimibe combo pill with the Food and Drug Administration and the European Medicines Agency in the first months of 2019.

CLEAR Serenity was a 24-week, double-blind, placebo-controlled trial conducted at 67 North American sites. The 345 statin-intolerant participants were randomized 2:1 to bempedoic acid at 180 mg once daily or placebo.

“I think the specific contribution of this study is, importantly, that myalgia and other muscle-related symptoms were not increased with bempedoic acid versus placebo in this population that’s statin intolerant, more than 90% of whom complained of statin-related muscle symptoms,” said Dr. Laufs, professor and chair of the department of cardiology at the University of Leipzig (Germany).

Rates of major adverse cardiovascular events were too low in this relatively short-term, modest-size trial to be informative, but the results of the previously presented CLEAR Harmony trial are reassuring in this regard, according to the cardiologist. CLEAR Harmony was a 52-week study that included 2,230 patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia whose LDL was inadequately controlled despite high-intensity statin therapy. They were randomized to add-on bempedoic acid or placebo. The adjudicated major adverse cardiovascular event rate was 4.6% in the bempedoic acid group and not significantly different at 5.7% in controls.

Definitive data on the effect of bempedoic acid on cardiovascular morbidity and mortality event rates will eventually be provided by an ongoing global randomized, double-blind, placebo-controlled trial expected to enroll more than 12,000 patients.

Rates of various types of adverse events were closely similar in the bempedoic acid and placebo groups in CLEAR Serenity, with a couple of intriguing exceptions, according to Dr. Laufs. For example, the rate of new-onset or worsening diabetes was 2.1% in the bempedoic acid group, compared with 4.5% in controls.

“This is consistent with results in the other studies in the overall bempedoic acid program. It will be something of great interest to follow up in the ongoing outcomes trial,” he said. “At this point I would feel comfortable in saying that there is no deterioration of glucose tolerance, unlike with statins. Whether there is an actual improvement or not needs to be characterized a little better.”

The other difference in the safety profile between the two study arms in CLEAR Serenity was a trend for higher uric acid levels and an increased risk of developing gout in the bempedoic acid group. Gout occurred in 1.7% of the bempedoic acid group and 0.9% of placebo-treated controls. A similar signal has been seen in the other pivotal trials, but a definitive answer as to gout risk must await the large ongoing outcomes trial, Dr. Laufs continued.

Bempedoic acid is a first-in-class oral inhibitor of ATP citrate lyase, an enzyme that is inactive in skeletal muscle – thus, the lack of myalgia complaints – and lies upstream of HMG-CoA reductase in cholesterol synthesis. When combined in a single pill with ezetimibe, which lowers LDL by stimulating the LDL receptor, the lipid-lowering impact is magnified over that of either drug alone. In the phase 3 program, the combination pill resulted in a further 35% reduction in LDL when added to a maximally tolerated statin and a 43% reduction in LDL when used as monotherapy.

Session cochair Robert H. Eckel, MD, commented that bempedoic acid appears to be poised to address a significant unmet need in preventive cardiology.

“We clearly need alternative therapies in patients with statin intolerance. We see a lot of these patients in referral centers. This drug looks safe and very effective at modifying LDL, about as much so as ezetimibe and maybe a little bit more,” said Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.

Dr. Laufs reported serving as a paid consultant to Esperion Therapeutics, the study sponsor, as well as to Amgen and Sanofi.

bjancin@mdedge.com

A new smartphone app under development seeks to detect the first moments of an overdose-related respiratory crisis and summon help before it’s too late.

“We’re hoping a device that most people carry around could be transformed into technology that could save your life in an overdose,” said anesthesiologist Jacob (Jake) E. Sunshine, MD, an assistant professor with the University of Washington, Seattle, and coauthor of a study about the app’s development.

The ultimate goal is “to provide a harm reduction system that can automatically connect naloxone-equipped friends and family or emergency medical services to help prevent fatal overdose events,” Rajalakshmi Nandakumar, and her associates wrote in the study, published in Science Translational Medicine.

An estimated 70,000 people in the United States died from drug overdoses in 2017, according to a 2018 data brief from the Centers for Disease Control and Prevention. On an age-adjusted basis, the overdose death rate in 2017 was more than three times higher than in 1999.

The app, which builds on previous work aimed at detecting disordered breathing in sleep apnea, uses a “short-range active sonar system” to detect respiration in a person within the distance of about 3 feet. The approach is similar to the echolocation strategy used by a dolphin or bat, Dr. Sunshine said, and relies on sending out an audio tone that humans cannot hear.

The app’s microphone detects an “audio reflection” of the tone after it bounces off a nearby person’s body and then analyzes it to calculate the distance to the person’s chest. “We’re able to use those distances to measure when someone is taking a breath, and when they’re not taking a breath,” said Dr. Sunshine, who conceptualized the study.

If a disordered breathing pattern is detected, the app is designed to send a text message with a GPS-pinpointed location to a prespecified contact, Dr. Sunshine said. Or the app could be set to call 911.

In the study, the investigators tested the app’s algorithm at a supervised injection facility – a space designed to allow users to inject illicit drugs safely – in Vancouver. They tested the app on 94 drug users as they injected themselves; half of the users “experienced clinically important respiratory depression,” and two needed to be treated by clinic staff for overdose. Both users survived, reported Ms. Nandakumar, a PhD candidate at the University of Washington, Seattle; Shyamnath Gollakota, PhD, an associate professor at the university; and Dr. Sunshine.

The new study found that the app detected cessation of breathing for 10 seconds or longer 95.9% of the time (95% confidence interval, 86.0%-99.5%) with 97.7% specificity (95% confidence interval, 88.2%-99.9%). However, the app was less adept at identifying respiratory depression (respiratory rate equal to or less than 7 breaths per minute): The investigators reported 87.2% sensitivity (95% CI, 74.2%-95.1%) and 89.3% specificity (95% CI, 76.9%-96.4%).

Ms. Nandakumar and her associates also tested the app’s algorithm on patients undergoing anesthesia. It correctly detected disordered breathing in 19 of 20 patients.

It’s not clear how the app would work in environments full of breathing people and, potentially, breathing animals such as pets. And the app has clear limitations. Since it needs to be able to bounce audio signals off a user’s chest, it will not work if a phone is in a pocket or if a user is face down, turns around, or wanders off.

However, the app can detect sudden changes in motion, Dr. Sunshine said, and investigators are developing a way to require users to check in with the app in certain situations that might signal trouble.

“For harm reduction interventions to be efficacious, further studies with participant feedback and human factor testing are needed to ensure that the system meets the needs, values, and preferences of people who use opioids, in addition to establishing the system’s safety vis-à-vis its potential to encourage moral hazard,” the investigators wrote in the article.

The next steps are to refine the app’s user interface and figure out how to connect it to the 911 emergency-response system, Dr. Sunshine said. Meanwhile, researchers have created a company to develop the product. “We’re going to do additional development through that entity and seek [Food and Drug Administration] approval,” Dr. Sunshine said. The investigators do not plan to charge users for the product, which can be used on iPhones and Androids, he said.

The study was funded by the Foundation for Anesthesia Education and Research, the National Science Foundation, and the University of Washington’s Alcohol and Drug Abuse Institute. Dr. Sunshine, Ms. Nandakumar, and Dr. Gollakota are inventors on a provisional patient application related to the project, and all have equity stakes in a company that is developing the technology. Dr. Gollakota is a paid consultant to Jeeva Wireless and Edus Health.

SOURCE: Nandakumar R et al. Sci Transl Med. 2019 Jan 9;11(474). doi: 10.1126/scitranslmed.aau8914.

A new smartphone app under development seeks to detect the first moments of an overdose-related respiratory crisis and summon help before it’s too late.

“We’re hoping a device that most people carry around could be transformed into technology that could save your life in an overdose,” said anesthesiologist Jacob (Jake) E. Sunshine, MD, an assistant professor with the University of Washington, Seattle, and coauthor of a study about the app’s development.

The ultimate goal is “to provide a harm reduction system that can automatically connect naloxone-equipped friends and family or emergency medical services to help prevent fatal overdose events,” Rajalakshmi Nandakumar, and her associates wrote in the study, published in Science Translational Medicine.

An estimated 70,000 people in the United States died from drug overdoses in 2017, according to a 2018 data brief from the Centers for Disease Control and Prevention. On an age-adjusted basis, the overdose death rate in 2017 was more than three times higher than in 1999.

The app, which builds on previous work aimed at detecting disordered breathing in sleep apnea, uses a “short-range active sonar system” to detect respiration in a person within the distance of about 3 feet. The approach is similar to the echolocation strategy used by a dolphin or bat, Dr. Sunshine said, and relies on sending out an audio tone that humans cannot hear.

The app’s microphone detects an “audio reflection” of the tone after it bounces off a nearby person’s body and then analyzes it to calculate the distance to the person’s chest. “We’re able to use those distances to measure when someone is taking a breath, and when they’re not taking a breath,” said Dr. Sunshine, who conceptualized the study.

If a disordered breathing pattern is detected, the app is designed to send a text message with a GPS-pinpointed location to a prespecified contact, Dr. Sunshine said. Or the app could be set to call 911.

In the study, the investigators tested the app’s algorithm at a supervised injection facility – a space designed to allow users to inject illicit drugs safely – in Vancouver. They tested the app on 94 drug users as they injected themselves; half of the users “experienced clinically important respiratory depression,” and two needed to be treated by clinic staff for overdose. Both users survived, reported Ms. Nandakumar, a PhD candidate at the University of Washington, Seattle; Shyamnath Gollakota, PhD, an associate professor at the university; and Dr. Sunshine.

The new study found that the app detected cessation of breathing for 10 seconds or longer 95.9% of the time (95% confidence interval, 86.0%-99.5%) with 97.7% specificity (95% confidence interval, 88.2%-99.9%). However, the app was less adept at identifying respiratory depression (respiratory rate equal to or less than 7 breaths per minute): The investigators reported 87.2% sensitivity (95% CI, 74.2%-95.1%) and 89.3% specificity (95% CI, 76.9%-96.4%).

Ms. Nandakumar and her associates also tested the app’s algorithm on patients undergoing anesthesia. It correctly detected disordered breathing in 19 of 20 patients.

It’s not clear how the app would work in environments full of breathing people and, potentially, breathing animals such as pets. And the app has clear limitations. Since it needs to be able to bounce audio signals off a user’s chest, it will not work if a phone is in a pocket or if a user is face down, turns around, or wanders off.

However, the app can detect sudden changes in motion, Dr. Sunshine said, and investigators are developing a way to require users to check in with the app in certain situations that might signal trouble.

“For harm reduction interventions to be efficacious, further studies with participant feedback and human factor testing are needed to ensure that the system meets the needs, values, and preferences of people who use opioids, in addition to establishing the system’s safety vis-à-vis its potential to encourage moral hazard,” the investigators wrote in the article.

The next steps are to refine the app’s user interface and figure out how to connect it to the 911 emergency-response system, Dr. Sunshine said. Meanwhile, researchers have created a company to develop the product. “We’re going to do additional development through that entity and seek [Food and Drug Administration] approval,” Dr. Sunshine said. The investigators do not plan to charge users for the product, which can be used on iPhones and Androids, he said.

The study was funded by the Foundation for Anesthesia Education and Research, the National Science Foundation, and the University of Washington’s Alcohol and Drug Abuse Institute. Dr. Sunshine, Ms. Nandakumar, and Dr. Gollakota are inventors on a provisional patient application related to the project, and all have equity stakes in a company that is developing the technology. Dr. Gollakota is a paid consultant to Jeeva Wireless and Edus Health.

SOURCE: Nandakumar R et al. Sci Transl Med. 2019 Jan 9;11(474). doi: 10.1126/scitranslmed.aau8914.

A new smartphone app under development seeks to detect the first moments of an overdose-related respiratory crisis and summon help before it’s too late.

“We’re hoping a device that most people carry around could be transformed into technology that could save your life in an overdose,” said anesthesiologist Jacob (Jake) E. Sunshine, MD, an assistant professor with the University of Washington, Seattle, and coauthor of a study about the app’s development.

The ultimate goal is “to provide a harm reduction system that can automatically connect naloxone-equipped friends and family or emergency medical services to help prevent fatal overdose events,” Rajalakshmi Nandakumar, and her associates wrote in the study, published in Science Translational Medicine.

An estimated 70,000 people in the United States died from drug overdoses in 2017, according to a 2018 data brief from the Centers for Disease Control and Prevention. On an age-adjusted basis, the overdose death rate in 2017 was more than three times higher than in 1999.

The app, which builds on previous work aimed at detecting disordered breathing in sleep apnea, uses a “short-range active sonar system” to detect respiration in a person within the distance of about 3 feet. The approach is similar to the echolocation strategy used by a dolphin or bat, Dr. Sunshine said, and relies on sending out an audio tone that humans cannot hear.

The app’s microphone detects an “audio reflection” of the tone after it bounces off a nearby person’s body and then analyzes it to calculate the distance to the person’s chest. “We’re able to use those distances to measure when someone is taking a breath, and when they’re not taking a breath,” said Dr. Sunshine, who conceptualized the study.

If a disordered breathing pattern is detected, the app is designed to send a text message with a GPS-pinpointed location to a prespecified contact, Dr. Sunshine said. Or the app could be set to call 911.

In the study, the investigators tested the app’s algorithm at a supervised injection facility – a space designed to allow users to inject illicit drugs safely – in Vancouver. They tested the app on 94 drug users as they injected themselves; half of the users “experienced clinically important respiratory depression,” and two needed to be treated by clinic staff for overdose. Both users survived, reported Ms. Nandakumar, a PhD candidate at the University of Washington, Seattle; Shyamnath Gollakota, PhD, an associate professor at the university; and Dr. Sunshine.

The new study found that the app detected cessation of breathing for 10 seconds or longer 95.9% of the time (95% confidence interval, 86.0%-99.5%) with 97.7% specificity (95% confidence interval, 88.2%-99.9%). However, the app was less adept at identifying respiratory depression (respiratory rate equal to or less than 7 breaths per minute): The investigators reported 87.2% sensitivity (95% CI, 74.2%-95.1%) and 89.3% specificity (95% CI, 76.9%-96.4%).

Ms. Nandakumar and her associates also tested the app’s algorithm on patients undergoing anesthesia. It correctly detected disordered breathing in 19 of 20 patients.

It’s not clear how the app would work in environments full of breathing people and, potentially, breathing animals such as pets. And the app has clear limitations. Since it needs to be able to bounce audio signals off a user’s chest, it will not work if a phone is in a pocket or if a user is face down, turns around, or wanders off.

However, the app can detect sudden changes in motion, Dr. Sunshine said, and investigators are developing a way to require users to check in with the app in certain situations that might signal trouble.

“For harm reduction interventions to be efficacious, further studies with participant feedback and human factor testing are needed to ensure that the system meets the needs, values, and preferences of people who use opioids, in addition to establishing the system’s safety vis-à-vis its potential to encourage moral hazard,” the investigators wrote in the article.

The next steps are to refine the app’s user interface and figure out how to connect it to the 911 emergency-response system, Dr. Sunshine said. Meanwhile, researchers have created a company to develop the product. “We’re going to do additional development through that entity and seek [Food and Drug Administration] approval,” Dr. Sunshine said. The investigators do not plan to charge users for the product, which can be used on iPhones and Androids, he said.

The study was funded by the Foundation for Anesthesia Education and Research, the National Science Foundation, and the University of Washington’s Alcohol and Drug Abuse Institute. Dr. Sunshine, Ms. Nandakumar, and Dr. Gollakota are inventors on a provisional patient application related to the project, and all have equity stakes in a company that is developing the technology. Dr. Gollakota is a paid consultant to Jeeva Wireless and Edus Health.

SOURCE: Nandakumar R et al. Sci Transl Med. 2019 Jan 9;11(474). doi: 10.1126/scitranslmed.aau8914.