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The importance of family acceptance for LGBTQ youth
It is well established that LGBTQ individuals experience more health disparities compared with their cisgender, heterosexual counterparts. In general, LGBTQ adolescents and young adults have higher levels of depression, suicide attempts, and substance use than those of their heterosexual peers. However, a key protective factor is family acceptance and support. By encouraging families to modify and change behaviors that are experienced by their LGBTQ children as rejecting and to engage in supportive and affirming behaviors, providers can help families to decrease risk and promote healthy outcomes for LGBTQ youth and young adults. 
We all know that a supportive family can make a difference for any child, but this is especially true for LGBTQ youth and is critical during a pandemic when young people are confined with families and separated from peers and supportive adults outside the home. Several research studies show that family support can improve outcomes related to suicide, depression, homelessness, drug use, and HIV in LGBTQ young people. Family acceptance improves health outcomes, while rejection undermines family relationships and worsens both health and other serious outcomes such as homelessness and placement in custodial care. Pediatricians can help their patients by educating parents and caregivers with LGBTQ children about the critical role of family support – both those who see themselves as accepting and those who believe that being gay or transgender is wrong and are struggling with parenting a child who identifies as LGBTQ or who is gender diverse.
The Family Acceptance Project (FAP) at San Francisco State University conducted the first research on LGBTQ youth and families, developed the first evidence-informed family support model, and has published a range of studies and evidence-based resources that demonstrate the harm caused by family rejection, validate the importance of family acceptance, and provide guidance to increase family support. FAP’s research found that parents and caregivers that engage in rejecting behaviors are typically motivated by care and concern and by trying to protect their children from harm. They believe such behaviors will help their LGBTQ children fit in, have a good life, meet cultural and religious expectations, and be respected by others.1 FAP’s research identified and measured more than 50 rejecting behaviors that parents and caregivers use to respond to their LGBTQ children. Some of these commonly expressed rejecting behaviors include ridiculing and making disparaging comments about their child and other LGBTQ people; excluding them from family activities; blaming their child when others mistreat them because they are LGBTQ; blocking access to LGBTQ resources including friends, support groups, and activities; and trying to change their child’s sexual orientation and gender identity.2 LGBTQ youth experience these and other such behaviors as hurtful, harmful, and traumatic and may feel that they need to hide or repress their identity which can affect their self-esteem, increase isolation, depression, and risky behaviors.3 Providers working with families of LGBTQ youth should focus on shared goals, such as reducing risk and having a happy, healthy child. Most parents love their children and fear for their well-being. However, many are uninformed about their child’s gender identity and sexual orientation and don’t know how to nurture and support them.
In FAP’s initial study, LGB young people who reported higher levels of family rejection had substantially higher rates of attempted suicide, depression, illegal drug use, and unprotected sex.4 These rates were even more significant among Latino gay and bisexual men.4 Those who are rejected by family are less likely to want to have a family or to be parents themselves5 and have lower educational and income levels.6
To reduce risk, pediatricians should ask LGBTQ patients about family rejecting behaviors and help parents and caregivers to identify and understand the effect of such behaviors to reduce health risks and conflict that can lead to running away, expulsion, and removal from the home. Even decreasing rejecting behaviors to moderate levels can significantly improve negative outcomes.5
Caitlin Ryan, PhD, and her team also identified and measured more than 50 family accepting behaviors that help protect against risk and promote well-being. They found that young adults who experience high levels of family acceptance during adolescence report significantly higher levels of self-esteem, social support, and general health with much lower levels of depression, suicidality, and substance abuse.7 Family accepting and supportive behaviors include talking with the child about their LGBTQ identity; advocating for their LGBTQ child when others mistreat them; requiring other family members to treat their LGBTQ child with respect; and supporting their child’s gender identity.5 FAP has developed an evidence-informed family support model and multilingual educational resources for families, providers, youth and religious leaders to decrease rejection and increase family support. These are available in print copies and for download at familyproject.sfsu.edu.
In addition, Dr. Ryan and colleagues1,4,8 recommend the following guidance for providers:
- Ask LGBTQ adolescents about family reactions to their sexual orientation, gender identity, and expression, and refer to LGBTQ community support programs and for supportive counseling, as needed.
- Identify LGBTQ community support programs and online resources to educate parents about how to help their children. Parents need culturally relevant peer support to help decrease rejection and increase family support.
- Advise parents that negative reactions to their adolescent’s LGBTQ identity may negatively impact their child’s health and mental health while supportive and affirming reactions promote well-being.
- Advise parents and caregivers to modify and change family rejecting behaviors that increase their child’s risk for suicide, depression, substance abuse ,and risky sexual behaviors.
- Expand anticipatory guidance to include information on the need for support and the link between family rejection and negative health problems.
- Provide guidance on sexual orientation and gender identity as part of normative child development during well-baby and early childhood care.
- Use FAP’s multilingual family education booklets and Healthy Futures poster series in family and patient education and provide these materials in clinical and community settings. FAP’s Healthy Futures posters include a poster guidance, a version on family acceptance, a version on family rejection and a family acceptance version for conservative families and settings. They are available in camera-ready art in four sizes in English and Spanish and are forthcoming in five Asian languages: familyproject.sfsu.edu/poster.
Dr. Lawlis is assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, and an adolescent medicine specialist at OU Children’s. She has no relevant financial disclosures.
Resources
• Family Acceptance Project – consultation and training; evidence-based educational materials for families, providers, religious leaders and youth.
• PFLAG – peer support for parents and friends with LGBTQ children in all states and several other countries.
References
1. Ryan C. Generating a revolution in prevention, wellness & care for LGBT children & youth. Temple Political & Civil Rights Law Review. 2014;23(2):331-44.
2. Ryan C. Healthy Futures Poster Series – Family Accepting & Rejecting Behaviors That Impact LGBTQ Children’s Health & Well-Being. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2019.
3. Ryan C. Family Acceptance Project: Culturally grounded framework for supporting LGBTQ children and youth. J Am Acad Child Adolesc Psychiatr. 2019;58(10):S58-9.
4. Ryan C et al. Family rejection as a predictor of negative health outcomes in White and Latino lesbian, gay, and bisexual young adults. Pediatrics. 2009;123(1):346-52.
5. Ryan C. Supportive families, healthy children: Helping families with lesbian, gay, bisexual & transgender children. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2009.
6. Ryan C et al. Parent-initiated sexual orientation change efforts with LGBT adolescents: Implications for young adult mental health and adjustment. J Homosexuality. 2020;67(2):159-73.
7. Ryan C et al. Family acceptance in adolescence and the health of LGBT young adults. J Child Adolesc Psychiatr Nursing. 2010;23(4):205-13. 8. Substance Abuse and Mental Health Services Administration. A Practitioner’s Guide: Helping Families to Support Their LGBT Children. In: Administration SAaMhS, ed. Vol PEP14-LGBTKIDS. Rockville, MD: HHS Publication; 2014.
It is well established that LGBTQ individuals experience more health disparities compared with their cisgender, heterosexual counterparts. In general, LGBTQ adolescents and young adults have higher levels of depression, suicide attempts, and substance use than those of their heterosexual peers. However, a key protective factor is family acceptance and support. By encouraging families to modify and change behaviors that are experienced by their LGBTQ children as rejecting and to engage in supportive and affirming behaviors, providers can help families to decrease risk and promote healthy outcomes for LGBTQ youth and young adults.
We all know that a supportive family can make a difference for any child, but this is especially true for LGBTQ youth and is critical during a pandemic when young people are confined with families and separated from peers and supportive adults outside the home. Several research studies show that family support can improve outcomes related to suicide, depression, homelessness, drug use, and HIV in LGBTQ young people. Family acceptance improves health outcomes, while rejection undermines family relationships and worsens both health and other serious outcomes such as homelessness and placement in custodial care. Pediatricians can help their patients by educating parents and caregivers with LGBTQ children about the critical role of family support – both those who see themselves as accepting and those who believe that being gay or transgender is wrong and are struggling with parenting a child who identifies as LGBTQ or who is gender diverse.
The Family Acceptance Project (FAP) at San Francisco State University conducted the first research on LGBTQ youth and families, developed the first evidence-informed family support model, and has published a range of studies and evidence-based resources that demonstrate the harm caused by family rejection, validate the importance of family acceptance, and provide guidance to increase family support. FAP’s research found that parents and caregivers that engage in rejecting behaviors are typically motivated by care and concern and by trying to protect their children from harm. They believe such behaviors will help their LGBTQ children fit in, have a good life, meet cultural and religious expectations, and be respected by others.1 FAP’s research identified and measured more than 50 rejecting behaviors that parents and caregivers use to respond to their LGBTQ children. Some of these commonly expressed rejecting behaviors include ridiculing and making disparaging comments about their child and other LGBTQ people; excluding them from family activities; blaming their child when others mistreat them because they are LGBTQ; blocking access to LGBTQ resources including friends, support groups, and activities; and trying to change their child’s sexual orientation and gender identity.2 LGBTQ youth experience these and other such behaviors as hurtful, harmful, and traumatic and may feel that they need to hide or repress their identity which can affect their self-esteem, increase isolation, depression, and risky behaviors.3 Providers working with families of LGBTQ youth should focus on shared goals, such as reducing risk and having a happy, healthy child. Most parents love their children and fear for their well-being. However, many are uninformed about their child’s gender identity and sexual orientation and don’t know how to nurture and support them.
In FAP’s initial study, LGB young people who reported higher levels of family rejection had substantially higher rates of attempted suicide, depression, illegal drug use, and unprotected sex.4 These rates were even more significant among Latino gay and bisexual men.4 Those who are rejected by family are less likely to want to have a family or to be parents themselves5 and have lower educational and income levels.6
To reduce risk, pediatricians should ask LGBTQ patients about family rejecting behaviors and help parents and caregivers to identify and understand the effect of such behaviors to reduce health risks and conflict that can lead to running away, expulsion, and removal from the home. Even decreasing rejecting behaviors to moderate levels can significantly improve negative outcomes.5
Caitlin Ryan, PhD, and her team also identified and measured more than 50 family accepting behaviors that help protect against risk and promote well-being. They found that young adults who experience high levels of family acceptance during adolescence report significantly higher levels of self-esteem, social support, and general health with much lower levels of depression, suicidality, and substance abuse.7 Family accepting and supportive behaviors include talking with the child about their LGBTQ identity; advocating for their LGBTQ child when others mistreat them; requiring other family members to treat their LGBTQ child with respect; and supporting their child’s gender identity.5 FAP has developed an evidence-informed family support model and multilingual educational resources for families, providers, youth and religious leaders to decrease rejection and increase family support. These are available in print copies and for download at familyproject.sfsu.edu.
In addition, Dr. Ryan and colleagues1,4,8 recommend the following guidance for providers:
- Ask LGBTQ adolescents about family reactions to their sexual orientation, gender identity, and expression, and refer to LGBTQ community support programs and for supportive counseling, as needed.
- Identify LGBTQ community support programs and online resources to educate parents about how to help their children. Parents need culturally relevant peer support to help decrease rejection and increase family support.
- Advise parents that negative reactions to their adolescent’s LGBTQ identity may negatively impact their child’s health and mental health while supportive and affirming reactions promote well-being.
- Advise parents and caregivers to modify and change family rejecting behaviors that increase their child’s risk for suicide, depression, substance abuse ,and risky sexual behaviors.
- Expand anticipatory guidance to include information on the need for support and the link between family rejection and negative health problems.
- Provide guidance on sexual orientation and gender identity as part of normative child development during well-baby and early childhood care.
- Use FAP’s multilingual family education booklets and Healthy Futures poster series in family and patient education and provide these materials in clinical and community settings. FAP’s Healthy Futures posters include a poster guidance, a version on family acceptance, a version on family rejection and a family acceptance version for conservative families and settings. They are available in camera-ready art in four sizes in English and Spanish and are forthcoming in five Asian languages: familyproject.sfsu.edu/poster.
Dr. Lawlis is assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, and an adolescent medicine specialist at OU Children’s. She has no relevant financial disclosures.
Resources
• Family Acceptance Project – consultation and training; evidence-based educational materials for families, providers, religious leaders and youth.
• PFLAG – peer support for parents and friends with LGBTQ children in all states and several other countries.
References
1. Ryan C. Generating a revolution in prevention, wellness & care for LGBT children & youth. Temple Political & Civil Rights Law Review. 2014;23(2):331-44.
2. Ryan C. Healthy Futures Poster Series – Family Accepting & Rejecting Behaviors That Impact LGBTQ Children’s Health & Well-Being. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2019.
3. Ryan C. Family Acceptance Project: Culturally grounded framework for supporting LGBTQ children and youth. J Am Acad Child Adolesc Psychiatr. 2019;58(10):S58-9.
4. Ryan C et al. Family rejection as a predictor of negative health outcomes in White and Latino lesbian, gay, and bisexual young adults. Pediatrics. 2009;123(1):346-52.
5. Ryan C. Supportive families, healthy children: Helping families with lesbian, gay, bisexual & transgender children. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2009.
6. Ryan C et al. Parent-initiated sexual orientation change efforts with LGBT adolescents: Implications for young adult mental health and adjustment. J Homosexuality. 2020;67(2):159-73.
7. Ryan C et al. Family acceptance in adolescence and the health of LGBT young adults. J Child Adolesc Psychiatr Nursing. 2010;23(4):205-13. 8. Substance Abuse and Mental Health Services Administration. A Practitioner’s Guide: Helping Families to Support Their LGBT Children. In: Administration SAaMhS, ed. Vol PEP14-LGBTKIDS. Rockville, MD: HHS Publication; 2014.
It is well established that LGBTQ individuals experience more health disparities compared with their cisgender, heterosexual counterparts. In general, LGBTQ adolescents and young adults have higher levels of depression, suicide attempts, and substance use than those of their heterosexual peers. However, a key protective factor is family acceptance and support. By encouraging families to modify and change behaviors that are experienced by their LGBTQ children as rejecting and to engage in supportive and affirming behaviors, providers can help families to decrease risk and promote healthy outcomes for LGBTQ youth and young adults.
We all know that a supportive family can make a difference for any child, but this is especially true for LGBTQ youth and is critical during a pandemic when young people are confined with families and separated from peers and supportive adults outside the home. Several research studies show that family support can improve outcomes related to suicide, depression, homelessness, drug use, and HIV in LGBTQ young people. Family acceptance improves health outcomes, while rejection undermines family relationships and worsens both health and other serious outcomes such as homelessness and placement in custodial care. Pediatricians can help their patients by educating parents and caregivers with LGBTQ children about the critical role of family support – both those who see themselves as accepting and those who believe that being gay or transgender is wrong and are struggling with parenting a child who identifies as LGBTQ or who is gender diverse.
The Family Acceptance Project (FAP) at San Francisco State University conducted the first research on LGBTQ youth and families, developed the first evidence-informed family support model, and has published a range of studies and evidence-based resources that demonstrate the harm caused by family rejection, validate the importance of family acceptance, and provide guidance to increase family support. FAP’s research found that parents and caregivers that engage in rejecting behaviors are typically motivated by care and concern and by trying to protect their children from harm. They believe such behaviors will help their LGBTQ children fit in, have a good life, meet cultural and religious expectations, and be respected by others.1 FAP’s research identified and measured more than 50 rejecting behaviors that parents and caregivers use to respond to their LGBTQ children. Some of these commonly expressed rejecting behaviors include ridiculing and making disparaging comments about their child and other LGBTQ people; excluding them from family activities; blaming their child when others mistreat them because they are LGBTQ; blocking access to LGBTQ resources including friends, support groups, and activities; and trying to change their child’s sexual orientation and gender identity.2 LGBTQ youth experience these and other such behaviors as hurtful, harmful, and traumatic and may feel that they need to hide or repress their identity which can affect their self-esteem, increase isolation, depression, and risky behaviors.3 Providers working with families of LGBTQ youth should focus on shared goals, such as reducing risk and having a happy, healthy child. Most parents love their children and fear for their well-being. However, many are uninformed about their child’s gender identity and sexual orientation and don’t know how to nurture and support them.
In FAP’s initial study, LGB young people who reported higher levels of family rejection had substantially higher rates of attempted suicide, depression, illegal drug use, and unprotected sex.4 These rates were even more significant among Latino gay and bisexual men.4 Those who are rejected by family are less likely to want to have a family or to be parents themselves5 and have lower educational and income levels.6
To reduce risk, pediatricians should ask LGBTQ patients about family rejecting behaviors and help parents and caregivers to identify and understand the effect of such behaviors to reduce health risks and conflict that can lead to running away, expulsion, and removal from the home. Even decreasing rejecting behaviors to moderate levels can significantly improve negative outcomes.5
Caitlin Ryan, PhD, and her team also identified and measured more than 50 family accepting behaviors that help protect against risk and promote well-being. They found that young adults who experience high levels of family acceptance during adolescence report significantly higher levels of self-esteem, social support, and general health with much lower levels of depression, suicidality, and substance abuse.7 Family accepting and supportive behaviors include talking with the child about their LGBTQ identity; advocating for their LGBTQ child when others mistreat them; requiring other family members to treat their LGBTQ child with respect; and supporting their child’s gender identity.5 FAP has developed an evidence-informed family support model and multilingual educational resources for families, providers, youth and religious leaders to decrease rejection and increase family support. These are available in print copies and for download at familyproject.sfsu.edu.
In addition, Dr. Ryan and colleagues1,4,8 recommend the following guidance for providers:
- Ask LGBTQ adolescents about family reactions to their sexual orientation, gender identity, and expression, and refer to LGBTQ community support programs and for supportive counseling, as needed.
- Identify LGBTQ community support programs and online resources to educate parents about how to help their children. Parents need culturally relevant peer support to help decrease rejection and increase family support.
- Advise parents that negative reactions to their adolescent’s LGBTQ identity may negatively impact their child’s health and mental health while supportive and affirming reactions promote well-being.
- Advise parents and caregivers to modify and change family rejecting behaviors that increase their child’s risk for suicide, depression, substance abuse ,and risky sexual behaviors.
- Expand anticipatory guidance to include information on the need for support and the link between family rejection and negative health problems.
- Provide guidance on sexual orientation and gender identity as part of normative child development during well-baby and early childhood care.
- Use FAP’s multilingual family education booklets and Healthy Futures poster series in family and patient education and provide these materials in clinical and community settings. FAP’s Healthy Futures posters include a poster guidance, a version on family acceptance, a version on family rejection and a family acceptance version for conservative families and settings. They are available in camera-ready art in four sizes in English and Spanish and are forthcoming in five Asian languages: familyproject.sfsu.edu/poster.
Dr. Lawlis is assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, and an adolescent medicine specialist at OU Children’s. She has no relevant financial disclosures.
Resources
• Family Acceptance Project – consultation and training; evidence-based educational materials for families, providers, religious leaders and youth.
• PFLAG – peer support for parents and friends with LGBTQ children in all states and several other countries.
References
1. Ryan C. Generating a revolution in prevention, wellness & care for LGBT children & youth. Temple Political & Civil Rights Law Review. 2014;23(2):331-44.
2. Ryan C. Healthy Futures Poster Series – Family Accepting & Rejecting Behaviors That Impact LGBTQ Children’s Health & Well-Being. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2019.
3. Ryan C. Family Acceptance Project: Culturally grounded framework for supporting LGBTQ children and youth. J Am Acad Child Adolesc Psychiatr. 2019;58(10):S58-9.
4. Ryan C et al. Family rejection as a predictor of negative health outcomes in White and Latino lesbian, gay, and bisexual young adults. Pediatrics. 2009;123(1):346-52.
5. Ryan C. Supportive families, healthy children: Helping families with lesbian, gay, bisexual & transgender children. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2009.
6. Ryan C et al. Parent-initiated sexual orientation change efforts with LGBT adolescents: Implications for young adult mental health and adjustment. J Homosexuality. 2020;67(2):159-73.
7. Ryan C et al. Family acceptance in adolescence and the health of LGBT young adults. J Child Adolesc Psychiatr Nursing. 2010;23(4):205-13. 8. Substance Abuse and Mental Health Services Administration. A Practitioner’s Guide: Helping Families to Support Their LGBT Children. In: Administration SAaMhS, ed. Vol PEP14-LGBTKIDS. Rockville, MD: HHS Publication; 2014.
Child ‘Mis’behavior – What’s ‘mis’ing?
“What kind of parent are you? Why don’t you straighten him out!” rants the woman being jostled in the grocery store by your patient. “Easy for you to say,” thinks your patient’s frazzled and now insulted parent.
Blaming the parent for an out-of-control child has historically been a common refrain of neighbors, relatives, and even strangers. But considering child behavior as resulting from both parent and child factors is central to the current transactional model of child development. In this model, mismatch of the parent’s and child’s response patterns is seen as setting them up for chronically rough interactions around parent requests/demands. A parent escalating quickly from a briefly stated request to a tirade may create more tension paired with an anxious child who takes time to act, for example. Once a parent (and ultimately the child) recognize patterns in what leads to conflict, they can become more proactive in predicting and negotiating these situations. Ross Greene, PhD, explains this in his book “The Explosive Child,” calling the method Collaborative Problem Solving (now Collaborative & Proactive Solutions or CPS).
While there are general principles parents can use to modify what they consider “mis”behaviors, these methods often do not account for the “missing” skills of the individual child (and parent) predisposing to those “mis”takes. Thinking of misbehaviors as being because of a kind of “learning disability” in the child rather than willful defiance can help cool off interactions by instead focusing on solving the underlying problem.
What kinds of “gaps in skills” set a child up for defiant or explosive reactions? If you think about what features of children, and parent-child relationships are associated with harmonious interactions this becomes evident. Children over 3 who are patient, easygoing, flexible or adaptable, and good at transitions and problem-solving can delay gratification and tolerate frustration, regulate their emotions, explain their desires, and multitask. They are better at reading the parent’s needs and intent and tend to interpret requests as positive or at least neutral and are more likely to comply with parent requests without a fuss.
What? No kid you know is great at all of these? These skills, at best variable, develop with maturation. Some are part of temperament, considered normal variation in personality. For example, so-called difficult temperament includes low adaptability, high-intensity reactions, low regularity, tendency to withdraw, and negative mood. But in the extreme, weaknesses in these skills are core to or comorbid with diagnosable mental health disorders. Defiance and irritable responses are criteria for oppositional defiant disorder (ODD), and less severe categories called aggressive/oppositional problem or variation. ODD is often found in children diagnosed with ADHD (65%), Tourette’s (15%-65%), depression (70% if severe), bipolar disorder (85%), OCD, anxiety (45%), autism, and language-processing disorders (55%), or trauma. These conditions variably include lower emotion regulation, poorer executive functioning including poor task shifting and impulsivity, obsessiveness, lower expressive and receptive communication skills, and less social awareness that facilitates harmonious problem solving.
The basic components of the CPS approach to addressing parent-child conflict sound intuitive but defining them clearly is important when families are stuck. There are three levels of plans. If the problem is an emergency or nonnegotiable, e.g., child hurting the cat, it may call for Plan A – parent-imposed solutions, sometimes with consequences or rewards. As children mature, Plan A should be used less frequently. If solving the problem is not a top life priority, Plan C – postponing action, may be appropriate. Plan C highlights that behavior change is a long-term project and “picking your fights” is important.
The biggest value of CPS for resolving behavior problems comes from intermediate Plan B. In Plan B the first step of problem solving for parents facing child defiance or upset is to empathically and nonjudgmentally figure out the child’s concern. Questions such as “I’ve noticed that when I remind you that it is trash night you start shouting. What’s up with that?” then patiently asking about the who, what, where, and when of their concern and checking to ensure understanding. Specificity is important as well as noting times when the reaction occurs or not.
Once the child’s concern is clear, e.g., feeling that the demand to take out the trash now interrupts his games during the only time his friends are online, the parents should echo the child’s concern then express their own concern about how the behavior is affecting them and others, potentially including the child; e.g., mother is so upset by the shouting that she can’t sleep, and worry that the child is not learning responsibility, and then checking for child understanding.
Finally, the parent invites brainstorming for a solution that addresses both of their concerns, first asking the child for suggestions, aiming for a strategy that is realistic and specific. Children reluctant to make suggestions may need more time and the parent may be wondering “if there is a way for both of our concerns to be addressed.” Solutions chosen are then tried for several weeks, success tracked, and needed changes negotiated.
For parents, using a collaborative approach to dealing with their child’s behavior takes skills they may not have at the moment, or ever. Especially under the stresses of COVID-19 lockdown, taking a step back from an encounter to consider lack of a skill to turn off the video game promptly when a Zoom meeting starts is challenging. Parents may also genetically share the child’s predisposing ADHD, anxiety, depression, OCD, or weakness in communication or social sensitivity.
Sometimes part of the solution for a conflict is for the parent to reduce expectations. This requires understanding and accepting the child’s cognitive or emotional limitations. Reducing expectations is ideally done before a request rather than by giving in after it, which reinforces protests. For authoritarian adults rigid in their belief that parents are boss, changing expectations can be tough and can feel like losing control or failing as a leader. One benefit of working with a CPS coach (see livesinthebalance.org or ThinkKids.org) is to help parents identify their own limitations.
Predicting the types of demands that tend to create conflict, such as to act immediately or be flexible about options, allows parents to prioritize those requests for calmer moments or when there is more time for discussion. Reviewing a checklist of common gaps in skills and creating a list of expectations and triggers that are difficult for the child helps the family be more proactive in developing solutions. Authors of CPS have validated a checklist of skill deficits, “Thinking Skills Inventory,” to facilitate detection of gaps that is educational plus useful for planning specific solutions.
CPS has been shown in randomized trials with both parent groups and in home counseling to be as effective as Parent Training in reducing oppositional behavior and reducing maternal stress, with effects lasting even longer.
CPS Plan B notably has no reward or punishment components as it assumes the child wants to behave acceptably but can’t; has the “will but not the skill.” When skill deficits are worked around the child is satisfied with complying and pleasing the parents. The idea of a “function” of the misbehavior for the child of gaining attention or reward or avoiding consequences is reinterpreted as serving to communicate the problem the child is having trouble in meeting the parent’s demand. When the parent understands and helps the child solve the problem his/her misbehavior is no longer needed. A benefit of the communication and mutual problem solving used in CPS is on not only improving behavior but empowering parents and children, building parental empathy, and improving child skills.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She has no other relevant disclosures. Dr. Howard’s contribution to this publication is as a paid expert to MDedge News. Email her at pdnews@mdedge.com.
Reference
Greene RW et al. A transactional model of oppositional behavior: Underpinnings of the Collaborative Problem Solving approach. J Psychosom Res. 2003;55(1):67-75.
“What kind of parent are you? Why don’t you straighten him out!” rants the woman being jostled in the grocery store by your patient. “Easy for you to say,” thinks your patient’s frazzled and now insulted parent.
Blaming the parent for an out-of-control child has historically been a common refrain of neighbors, relatives, and even strangers. But considering child behavior as resulting from both parent and child factors is central to the current transactional model of child development. In this model, mismatch of the parent’s and child’s response patterns is seen as setting them up for chronically rough interactions around parent requests/demands. A parent escalating quickly from a briefly stated request to a tirade may create more tension paired with an anxious child who takes time to act, for example. Once a parent (and ultimately the child) recognize patterns in what leads to conflict, they can become more proactive in predicting and negotiating these situations. Ross Greene, PhD, explains this in his book “The Explosive Child,” calling the method Collaborative Problem Solving (now Collaborative & Proactive Solutions or CPS).
While there are general principles parents can use to modify what they consider “mis”behaviors, these methods often do not account for the “missing” skills of the individual child (and parent) predisposing to those “mis”takes. Thinking of misbehaviors as being because of a kind of “learning disability” in the child rather than willful defiance can help cool off interactions by instead focusing on solving the underlying problem.
What kinds of “gaps in skills” set a child up for defiant or explosive reactions? If you think about what features of children, and parent-child relationships are associated with harmonious interactions this becomes evident. Children over 3 who are patient, easygoing, flexible or adaptable, and good at transitions and problem-solving can delay gratification and tolerate frustration, regulate their emotions, explain their desires, and multitask. They are better at reading the parent’s needs and intent and tend to interpret requests as positive or at least neutral and are more likely to comply with parent requests without a fuss.
What? No kid you know is great at all of these? These skills, at best variable, develop with maturation. Some are part of temperament, considered normal variation in personality. For example, so-called difficult temperament includes low adaptability, high-intensity reactions, low regularity, tendency to withdraw, and negative mood. But in the extreme, weaknesses in these skills are core to or comorbid with diagnosable mental health disorders. Defiance and irritable responses are criteria for oppositional defiant disorder (ODD), and less severe categories called aggressive/oppositional problem or variation. ODD is often found in children diagnosed with ADHD (65%), Tourette’s (15%-65%), depression (70% if severe), bipolar disorder (85%), OCD, anxiety (45%), autism, and language-processing disorders (55%), or trauma. These conditions variably include lower emotion regulation, poorer executive functioning including poor task shifting and impulsivity, obsessiveness, lower expressive and receptive communication skills, and less social awareness that facilitates harmonious problem solving.
The basic components of the CPS approach to addressing parent-child conflict sound intuitive but defining them clearly is important when families are stuck. There are three levels of plans. If the problem is an emergency or nonnegotiable, e.g., child hurting the cat, it may call for Plan A – parent-imposed solutions, sometimes with consequences or rewards. As children mature, Plan A should be used less frequently. If solving the problem is not a top life priority, Plan C – postponing action, may be appropriate. Plan C highlights that behavior change is a long-term project and “picking your fights” is important.
The biggest value of CPS for resolving behavior problems comes from intermediate Plan B. In Plan B the first step of problem solving for parents facing child defiance or upset is to empathically and nonjudgmentally figure out the child’s concern. Questions such as “I’ve noticed that when I remind you that it is trash night you start shouting. What’s up with that?” then patiently asking about the who, what, where, and when of their concern and checking to ensure understanding. Specificity is important as well as noting times when the reaction occurs or not.
Once the child’s concern is clear, e.g., feeling that the demand to take out the trash now interrupts his games during the only time his friends are online, the parents should echo the child’s concern then express their own concern about how the behavior is affecting them and others, potentially including the child; e.g., mother is so upset by the shouting that she can’t sleep, and worry that the child is not learning responsibility, and then checking for child understanding.
Finally, the parent invites brainstorming for a solution that addresses both of their concerns, first asking the child for suggestions, aiming for a strategy that is realistic and specific. Children reluctant to make suggestions may need more time and the parent may be wondering “if there is a way for both of our concerns to be addressed.” Solutions chosen are then tried for several weeks, success tracked, and needed changes negotiated.
For parents, using a collaborative approach to dealing with their child’s behavior takes skills they may not have at the moment, or ever. Especially under the stresses of COVID-19 lockdown, taking a step back from an encounter to consider lack of a skill to turn off the video game promptly when a Zoom meeting starts is challenging. Parents may also genetically share the child’s predisposing ADHD, anxiety, depression, OCD, or weakness in communication or social sensitivity.
Sometimes part of the solution for a conflict is for the parent to reduce expectations. This requires understanding and accepting the child’s cognitive or emotional limitations. Reducing expectations is ideally done before a request rather than by giving in after it, which reinforces protests. For authoritarian adults rigid in their belief that parents are boss, changing expectations can be tough and can feel like losing control or failing as a leader. One benefit of working with a CPS coach (see livesinthebalance.org or ThinkKids.org) is to help parents identify their own limitations.
Predicting the types of demands that tend to create conflict, such as to act immediately or be flexible about options, allows parents to prioritize those requests for calmer moments or when there is more time for discussion. Reviewing a checklist of common gaps in skills and creating a list of expectations and triggers that are difficult for the child helps the family be more proactive in developing solutions. Authors of CPS have validated a checklist of skill deficits, “Thinking Skills Inventory,” to facilitate detection of gaps that is educational plus useful for planning specific solutions.
CPS has been shown in randomized trials with both parent groups and in home counseling to be as effective as Parent Training in reducing oppositional behavior and reducing maternal stress, with effects lasting even longer.
CPS Plan B notably has no reward or punishment components as it assumes the child wants to behave acceptably but can’t; has the “will but not the skill.” When skill deficits are worked around the child is satisfied with complying and pleasing the parents. The idea of a “function” of the misbehavior for the child of gaining attention or reward or avoiding consequences is reinterpreted as serving to communicate the problem the child is having trouble in meeting the parent’s demand. When the parent understands and helps the child solve the problem his/her misbehavior is no longer needed. A benefit of the communication and mutual problem solving used in CPS is on not only improving behavior but empowering parents and children, building parental empathy, and improving child skills.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She has no other relevant disclosures. Dr. Howard’s contribution to this publication is as a paid expert to MDedge News. Email her at pdnews@mdedge.com.
Reference
Greene RW et al. A transactional model of oppositional behavior: Underpinnings of the Collaborative Problem Solving approach. J Psychosom Res. 2003;55(1):67-75.
“What kind of parent are you? Why don’t you straighten him out!” rants the woman being jostled in the grocery store by your patient. “Easy for you to say,” thinks your patient’s frazzled and now insulted parent.
Blaming the parent for an out-of-control child has historically been a common refrain of neighbors, relatives, and even strangers. But considering child behavior as resulting from both parent and child factors is central to the current transactional model of child development. In this model, mismatch of the parent’s and child’s response patterns is seen as setting them up for chronically rough interactions around parent requests/demands. A parent escalating quickly from a briefly stated request to a tirade may create more tension paired with an anxious child who takes time to act, for example. Once a parent (and ultimately the child) recognize patterns in what leads to conflict, they can become more proactive in predicting and negotiating these situations. Ross Greene, PhD, explains this in his book “The Explosive Child,” calling the method Collaborative Problem Solving (now Collaborative & Proactive Solutions or CPS).
While there are general principles parents can use to modify what they consider “mis”behaviors, these methods often do not account for the “missing” skills of the individual child (and parent) predisposing to those “mis”takes. Thinking of misbehaviors as being because of a kind of “learning disability” in the child rather than willful defiance can help cool off interactions by instead focusing on solving the underlying problem.
What kinds of “gaps in skills” set a child up for defiant or explosive reactions? If you think about what features of children, and parent-child relationships are associated with harmonious interactions this becomes evident. Children over 3 who are patient, easygoing, flexible or adaptable, and good at transitions and problem-solving can delay gratification and tolerate frustration, regulate their emotions, explain their desires, and multitask. They are better at reading the parent’s needs and intent and tend to interpret requests as positive or at least neutral and are more likely to comply with parent requests without a fuss.
What? No kid you know is great at all of these? These skills, at best variable, develop with maturation. Some are part of temperament, considered normal variation in personality. For example, so-called difficult temperament includes low adaptability, high-intensity reactions, low regularity, tendency to withdraw, and negative mood. But in the extreme, weaknesses in these skills are core to or comorbid with diagnosable mental health disorders. Defiance and irritable responses are criteria for oppositional defiant disorder (ODD), and less severe categories called aggressive/oppositional problem or variation. ODD is often found in children diagnosed with ADHD (65%), Tourette’s (15%-65%), depression (70% if severe), bipolar disorder (85%), OCD, anxiety (45%), autism, and language-processing disorders (55%), or trauma. These conditions variably include lower emotion regulation, poorer executive functioning including poor task shifting and impulsivity, obsessiveness, lower expressive and receptive communication skills, and less social awareness that facilitates harmonious problem solving.
The basic components of the CPS approach to addressing parent-child conflict sound intuitive but defining them clearly is important when families are stuck. There are three levels of plans. If the problem is an emergency or nonnegotiable, e.g., child hurting the cat, it may call for Plan A – parent-imposed solutions, sometimes with consequences or rewards. As children mature, Plan A should be used less frequently. If solving the problem is not a top life priority, Plan C – postponing action, may be appropriate. Plan C highlights that behavior change is a long-term project and “picking your fights” is important.
The biggest value of CPS for resolving behavior problems comes from intermediate Plan B. In Plan B the first step of problem solving for parents facing child defiance or upset is to empathically and nonjudgmentally figure out the child’s concern. Questions such as “I’ve noticed that when I remind you that it is trash night you start shouting. What’s up with that?” then patiently asking about the who, what, where, and when of their concern and checking to ensure understanding. Specificity is important as well as noting times when the reaction occurs or not.
Once the child’s concern is clear, e.g., feeling that the demand to take out the trash now interrupts his games during the only time his friends are online, the parents should echo the child’s concern then express their own concern about how the behavior is affecting them and others, potentially including the child; e.g., mother is so upset by the shouting that she can’t sleep, and worry that the child is not learning responsibility, and then checking for child understanding.
Finally, the parent invites brainstorming for a solution that addresses both of their concerns, first asking the child for suggestions, aiming for a strategy that is realistic and specific. Children reluctant to make suggestions may need more time and the parent may be wondering “if there is a way for both of our concerns to be addressed.” Solutions chosen are then tried for several weeks, success tracked, and needed changes negotiated.
For parents, using a collaborative approach to dealing with their child’s behavior takes skills they may not have at the moment, or ever. Especially under the stresses of COVID-19 lockdown, taking a step back from an encounter to consider lack of a skill to turn off the video game promptly when a Zoom meeting starts is challenging. Parents may also genetically share the child’s predisposing ADHD, anxiety, depression, OCD, or weakness in communication or social sensitivity.
Sometimes part of the solution for a conflict is for the parent to reduce expectations. This requires understanding and accepting the child’s cognitive or emotional limitations. Reducing expectations is ideally done before a request rather than by giving in after it, which reinforces protests. For authoritarian adults rigid in their belief that parents are boss, changing expectations can be tough and can feel like losing control or failing as a leader. One benefit of working with a CPS coach (see livesinthebalance.org or ThinkKids.org) is to help parents identify their own limitations.
Predicting the types of demands that tend to create conflict, such as to act immediately or be flexible about options, allows parents to prioritize those requests for calmer moments or when there is more time for discussion. Reviewing a checklist of common gaps in skills and creating a list of expectations and triggers that are difficult for the child helps the family be more proactive in developing solutions. Authors of CPS have validated a checklist of skill deficits, “Thinking Skills Inventory,” to facilitate detection of gaps that is educational plus useful for planning specific solutions.
CPS has been shown in randomized trials with both parent groups and in home counseling to be as effective as Parent Training in reducing oppositional behavior and reducing maternal stress, with effects lasting even longer.
CPS Plan B notably has no reward or punishment components as it assumes the child wants to behave acceptably but can’t; has the “will but not the skill.” When skill deficits are worked around the child is satisfied with complying and pleasing the parents. The idea of a “function” of the misbehavior for the child of gaining attention or reward or avoiding consequences is reinterpreted as serving to communicate the problem the child is having trouble in meeting the parent’s demand. When the parent understands and helps the child solve the problem his/her misbehavior is no longer needed. A benefit of the communication and mutual problem solving used in CPS is on not only improving behavior but empowering parents and children, building parental empathy, and improving child skills.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She has no other relevant disclosures. Dr. Howard’s contribution to this publication is as a paid expert to MDedge News. Email her at pdnews@mdedge.com.
Reference
Greene RW et al. A transactional model of oppositional behavior: Underpinnings of the Collaborative Problem Solving approach. J Psychosom Res. 2003;55(1):67-75.
The lost year – even for common respiratory viruses
In this column in September 2020, you read how common respiratory viruses’ seasons are usually so predictable, each virus arising, peaking, and then dying out in a predictable virus parade (Figure 1).1 Well, the predictable virus seasonal pattern was lost in 2020. Since March of 2020, it is striking how little activity was detected for the usual seasonal viruses in Kansas City after mid-March 2020 (Figure 2).2 So, my concern in September 2020 for possible rampant coinfections of common viruses with or in tandem with SARS-CoV-2 did not pan out. That said, the seasons for non–SARS-CoV-2 viruses did change; I just didn’t expect they would nearly disappear.
The 2020 winter-spring. In the first quarter (the last part of the overall 2019-2020 respiratory viral season), viral detections were chugging along as usual up to mid-March (Figure 2); influenza, respiratory syncytial virus (RSV), and rhinovirus were the big players.
Influenza. In most years, influenza type B leads off and is quickly replaced by type A only to see B reemerge to end influenza season in March-April. In early 2020, both influenza type A and influenza type B cocirculated nearly equally, but both dropped like a rock in mid-March (Figure 2).2 Neither type has been seen since with the exception of sporadic detections – perhaps being false positives.
RSV. In the usual year in temperate mid-latitudes of the northern hemisphere, RSV season usually starts in early December, peaks in January-March, and declines gradually until the end of RSV season in April (Figure 1). In southern latitudes, RSV is less seasonal, being present most of the year, but peaking in “winter” months.3 But in 2020, RSV also disappeared in mid-March and has yet to reappear.
Other viruses. Small bumps in detection of parainfluenza of varying types usually frame influenza season, one B bump in early autumn and another in April-May. In most years, human metapneumovirus is detected on and off, with worse years at 2- to 3-year intervals. Adenovirus occurs year-round with bumps as children get back to school in autumn. Yet in 2020, almost no parainfluenza, adenovirus, common coronaviruses, or human metapneumovirus were detected in either spring or autumn. This was supposed to be a banner summer-autumn for EV-D68 – but almost none was detected. Interestingly, the cockroach of viruses, rhinovirus, has its usual year (Figure 2).
What happened? Intense social mitigation interventions, including social distancing and closing daycares and schools, were likely major factors.4 For influenza, vaccine may have helped but uptake was not remarkably better than most prior years. There may have been “viral competition,”where a new or highly transmissible virus outcompetes less-transmissible viruses with lower affinity for respiratory receptors.5,6 Note that SARS-CoV-2 has very high affinity for the ACE2 receptor and has been highly prevalent. So, SARS-CoV-2 could fit the theoretical mold for a virus that outcompetes others.
Does it matter for the future? Blunted 2019-2020 and nearly absent 2020-2021 respiratory virus season may have set the stage for intense 2021-2022 rebounds for the non–SARS-CoV-2 viruses. We now have two whole and one partial birth cohort with no experience with seasonal respiratory viruses, including EV-D68 (and nonrespiratory viruses too – like norovirus, parechovirus, and other enteroviruses). Most viruses have particularly bad seasons every 2-3 years, thought to be caused by increasing accumulation of susceptible individuals in consecutive birth cohorts until a critical mass of susceptible individuals is achieved. The excess in susceptible individuals means that each contagious case is likely to expose one or more susceptible individuals, enhancing transmission and infection numbers in an ever-extending ripple effect. We have never had this many children aged under 3 years with no immunity to influenza, RSV, etc. So unless mother nature is kind (when has that happened lately?), expect rebound years for seasonal viruses as children return to daycare/schools and as social mitigation becomes less necessary in the waning pandemic.
Options? If you ramped up telehealth visits for the pandemic, that may be a saving grace, i.e., more efficiency so more “visits” can be completed per day, and less potential contact in reception rooms between well and ill children. And if there was ever a time to really intensify efforts to immunize all our pediatric patients, the next two seasons are just that. Adding a bit of a warning to families with young children also seems warranted. If they understand that, while 2021-2022 will be better for SARS-CoV-2, it is likely going to be worse for the other viruses.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at pdnews@mdedge.com.
References
1. Harrison CJ. 2020-2021 respiratory viral season: Onset, presentations, and testing likely to differ in pandemic, Pediatric News: September 17, 2020.
2. Olsen SJ et al. MMWR Morb Mortal Wkly Rep. 2020;69:1305-9.
3. Respiratory Syncytial Virus Surveillance. http://www.floridahealth.gov/diseases-and-conditions/respiratory-syncytial-virus/_documents/2021-w4-rsv-summary.pdf
4. Baker RE et al. PNAS. Dec 2020 117;(48):30547-53.
5. Sema Nickbakhsh et al. PNAS. Dec 2019 116;(52):27142-50.
6. Kirsten M et al. PNAS. Mar 2020 117;(13):6987.
In this column in September 2020, you read how common respiratory viruses’ seasons are usually so predictable, each virus arising, peaking, and then dying out in a predictable virus parade (Figure 1).1 Well, the predictable virus seasonal pattern was lost in 2020. Since March of 2020, it is striking how little activity was detected for the usual seasonal viruses in Kansas City after mid-March 2020 (Figure 2).2 So, my concern in September 2020 for possible rampant coinfections of common viruses with or in tandem with SARS-CoV-2 did not pan out. That said, the seasons for non–SARS-CoV-2 viruses did change; I just didn’t expect they would nearly disappear.
The 2020 winter-spring. In the first quarter (the last part of the overall 2019-2020 respiratory viral season), viral detections were chugging along as usual up to mid-March (Figure 2); influenza, respiratory syncytial virus (RSV), and rhinovirus were the big players.
Influenza. In most years, influenza type B leads off and is quickly replaced by type A only to see B reemerge to end influenza season in March-April. In early 2020, both influenza type A and influenza type B cocirculated nearly equally, but both dropped like a rock in mid-March (Figure 2).2 Neither type has been seen since with the exception of sporadic detections – perhaps being false positives.
RSV. In the usual year in temperate mid-latitudes of the northern hemisphere, RSV season usually starts in early December, peaks in January-March, and declines gradually until the end of RSV season in April (Figure 1). In southern latitudes, RSV is less seasonal, being present most of the year, but peaking in “winter” months.3 But in 2020, RSV also disappeared in mid-March and has yet to reappear.
Other viruses. Small bumps in detection of parainfluenza of varying types usually frame influenza season, one B bump in early autumn and another in April-May. In most years, human metapneumovirus is detected on and off, with worse years at 2- to 3-year intervals. Adenovirus occurs year-round with bumps as children get back to school in autumn. Yet in 2020, almost no parainfluenza, adenovirus, common coronaviruses, or human metapneumovirus were detected in either spring or autumn. This was supposed to be a banner summer-autumn for EV-D68 – but almost none was detected. Interestingly, the cockroach of viruses, rhinovirus, has its usual year (Figure 2).
What happened? Intense social mitigation interventions, including social distancing and closing daycares and schools, were likely major factors.4 For influenza, vaccine may have helped but uptake was not remarkably better than most prior years. There may have been “viral competition,”where a new or highly transmissible virus outcompetes less-transmissible viruses with lower affinity for respiratory receptors.5,6 Note that SARS-CoV-2 has very high affinity for the ACE2 receptor and has been highly prevalent. So, SARS-CoV-2 could fit the theoretical mold for a virus that outcompetes others.
Does it matter for the future? Blunted 2019-2020 and nearly absent 2020-2021 respiratory virus season may have set the stage for intense 2021-2022 rebounds for the non–SARS-CoV-2 viruses. We now have two whole and one partial birth cohort with no experience with seasonal respiratory viruses, including EV-D68 (and nonrespiratory viruses too – like norovirus, parechovirus, and other enteroviruses). Most viruses have particularly bad seasons every 2-3 years, thought to be caused by increasing accumulation of susceptible individuals in consecutive birth cohorts until a critical mass of susceptible individuals is achieved. The excess in susceptible individuals means that each contagious case is likely to expose one or more susceptible individuals, enhancing transmission and infection numbers in an ever-extending ripple effect. We have never had this many children aged under 3 years with no immunity to influenza, RSV, etc. So unless mother nature is kind (when has that happened lately?), expect rebound years for seasonal viruses as children return to daycare/schools and as social mitigation becomes less necessary in the waning pandemic.
Options? If you ramped up telehealth visits for the pandemic, that may be a saving grace, i.e., more efficiency so more “visits” can be completed per day, and less potential contact in reception rooms between well and ill children. And if there was ever a time to really intensify efforts to immunize all our pediatric patients, the next two seasons are just that. Adding a bit of a warning to families with young children also seems warranted. If they understand that, while 2021-2022 will be better for SARS-CoV-2, it is likely going to be worse for the other viruses.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at pdnews@mdedge.com.
References
1. Harrison CJ. 2020-2021 respiratory viral season: Onset, presentations, and testing likely to differ in pandemic, Pediatric News: September 17, 2020.
2. Olsen SJ et al. MMWR Morb Mortal Wkly Rep. 2020;69:1305-9.
3. Respiratory Syncytial Virus Surveillance. http://www.floridahealth.gov/diseases-and-conditions/respiratory-syncytial-virus/_documents/2021-w4-rsv-summary.pdf
4. Baker RE et al. PNAS. Dec 2020 117;(48):30547-53.
5. Sema Nickbakhsh et al. PNAS. Dec 2019 116;(52):27142-50.
6. Kirsten M et al. PNAS. Mar 2020 117;(13):6987.
In this column in September 2020, you read how common respiratory viruses’ seasons are usually so predictable, each virus arising, peaking, and then dying out in a predictable virus parade (Figure 1).1 Well, the predictable virus seasonal pattern was lost in 2020. Since March of 2020, it is striking how little activity was detected for the usual seasonal viruses in Kansas City after mid-March 2020 (Figure 2).2 So, my concern in September 2020 for possible rampant coinfections of common viruses with or in tandem with SARS-CoV-2 did not pan out. That said, the seasons for non–SARS-CoV-2 viruses did change; I just didn’t expect they would nearly disappear.
The 2020 winter-spring. In the first quarter (the last part of the overall 2019-2020 respiratory viral season), viral detections were chugging along as usual up to mid-March (Figure 2); influenza, respiratory syncytial virus (RSV), and rhinovirus were the big players.
Influenza. In most years, influenza type B leads off and is quickly replaced by type A only to see B reemerge to end influenza season in March-April. In early 2020, both influenza type A and influenza type B cocirculated nearly equally, but both dropped like a rock in mid-March (Figure 2).2 Neither type has been seen since with the exception of sporadic detections – perhaps being false positives.
RSV. In the usual year in temperate mid-latitudes of the northern hemisphere, RSV season usually starts in early December, peaks in January-March, and declines gradually until the end of RSV season in April (Figure 1). In southern latitudes, RSV is less seasonal, being present most of the year, but peaking in “winter” months.3 But in 2020, RSV also disappeared in mid-March and has yet to reappear.
Other viruses. Small bumps in detection of parainfluenza of varying types usually frame influenza season, one B bump in early autumn and another in April-May. In most years, human metapneumovirus is detected on and off, with worse years at 2- to 3-year intervals. Adenovirus occurs year-round with bumps as children get back to school in autumn. Yet in 2020, almost no parainfluenza, adenovirus, common coronaviruses, or human metapneumovirus were detected in either spring or autumn. This was supposed to be a banner summer-autumn for EV-D68 – but almost none was detected. Interestingly, the cockroach of viruses, rhinovirus, has its usual year (Figure 2).
What happened? Intense social mitigation interventions, including social distancing and closing daycares and schools, were likely major factors.4 For influenza, vaccine may have helped but uptake was not remarkably better than most prior years. There may have been “viral competition,”where a new or highly transmissible virus outcompetes less-transmissible viruses with lower affinity for respiratory receptors.5,6 Note that SARS-CoV-2 has very high affinity for the ACE2 receptor and has been highly prevalent. So, SARS-CoV-2 could fit the theoretical mold for a virus that outcompetes others.
Does it matter for the future? Blunted 2019-2020 and nearly absent 2020-2021 respiratory virus season may have set the stage for intense 2021-2022 rebounds for the non–SARS-CoV-2 viruses. We now have two whole and one partial birth cohort with no experience with seasonal respiratory viruses, including EV-D68 (and nonrespiratory viruses too – like norovirus, parechovirus, and other enteroviruses). Most viruses have particularly bad seasons every 2-3 years, thought to be caused by increasing accumulation of susceptible individuals in consecutive birth cohorts until a critical mass of susceptible individuals is achieved. The excess in susceptible individuals means that each contagious case is likely to expose one or more susceptible individuals, enhancing transmission and infection numbers in an ever-extending ripple effect. We have never had this many children aged under 3 years with no immunity to influenza, RSV, etc. So unless mother nature is kind (when has that happened lately?), expect rebound years for seasonal viruses as children return to daycare/schools and as social mitigation becomes less necessary in the waning pandemic.
Options? If you ramped up telehealth visits for the pandemic, that may be a saving grace, i.e., more efficiency so more “visits” can be completed per day, and less potential contact in reception rooms between well and ill children. And if there was ever a time to really intensify efforts to immunize all our pediatric patients, the next two seasons are just that. Adding a bit of a warning to families with young children also seems warranted. If they understand that, while 2021-2022 will be better for SARS-CoV-2, it is likely going to be worse for the other viruses.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at pdnews@mdedge.com.
References
1. Harrison CJ. 2020-2021 respiratory viral season: Onset, presentations, and testing likely to differ in pandemic, Pediatric News: September 17, 2020.
2. Olsen SJ et al. MMWR Morb Mortal Wkly Rep. 2020;69:1305-9.
3. Respiratory Syncytial Virus Surveillance. http://www.floridahealth.gov/diseases-and-conditions/respiratory-syncytial-virus/_documents/2021-w4-rsv-summary.pdf
4. Baker RE et al. PNAS. Dec 2020 117;(48):30547-53.
5. Sema Nickbakhsh et al. PNAS. Dec 2019 116;(52):27142-50.
6. Kirsten M et al. PNAS. Mar 2020 117;(13):6987.
Antibiotic exposure in pregnancy linked to childhood asthma risk in study
in a Danish birth cohort study.
The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.
Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
Antibiotic use in pregnancy likely to continue
Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.
The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.
“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”
Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.
To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
Children of mothers who took and did not take antibiotics compared
In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.
During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.
In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).
Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.
The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
Mode of delivery may matter
The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.
Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.
“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.
“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.
How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.
“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”
The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.
The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.
in a Danish birth cohort study.
The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.
Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
Antibiotic use in pregnancy likely to continue
Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.
The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.
“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”
Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.
To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
Children of mothers who took and did not take antibiotics compared
In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.
During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.
In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).
Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.
The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
Mode of delivery may matter
The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.
Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.
“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.
“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.
How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.
“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”
The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.
The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.
in a Danish birth cohort study.
The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.
Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
Antibiotic use in pregnancy likely to continue
Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.
The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.
“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”
Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.
To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
Children of mothers who took and did not take antibiotics compared
In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.
During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.
In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).
Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.
The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
Mode of delivery may matter
The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.
Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.
“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.
“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.
How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.
“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”
The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.
The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.
FROM ARCHIVES OF DISEASE IN CHILDHOOD
Study finds benefits of increasing length of NICU stay unclear
Gestational age and weight at discharge for infants aged 24-29 weeks increased steadily between 2005 and 2018, reported Erika M. Edwards, PhD, MPH, of the Vermont Oxford Network, Burlington, and associates.
Although they discussed several possible influencing factors, the authors were unable to explain the associated benefits, costs, and harms associated with increased age and weight at discharge, which remain undetermined. Infants are separated a week longer than they were at the beginning of the study period, the prolonged effects of which cannot be underestimated, Dr. Edwards and colleagues observed in a large cohort study in Pediatrics.
A total of 314,811 infants 24-29 weeks’ gestational age who were admitted to 824 neonatal ICUs (NICUs) throughout the United States survived to initial discharge. The median postmenstrual age at hospital discharge was 38.3 weeks. Over the 14-year period from 2005 to 2018, unadjusted postmenstrual age at discharge increased a median 9 days, compared with a median adjusted age of 8 days.
Of the 273,109 infants initially discharged from the hospital to home, median weight at discharge was 2,600 g. Over the 14 years from 2005 to 2018, median unadjusted discharge weight increased 360 g, compared with median adjusted weight, which was estimated to have increased 316 g.
Median unadjusted z scores for weight increased 0.22 standard units over the 14-year period, compared with median adjusted z scores for weight at discharge, which increased an estimated 0.19 standard units.
The proportion of infants who were consuming human milk at discharge increased over the study period from 40% in 2005 to 48% in 2018. The use of cardiorespiratory monitors and oxygen decreased from 49% to 26%, and 27% to 22% respectively. The number of infants who were never transferred to specialized care before discharge to home also improved, from 71% to 76%.
Despite the unknowns, good news for managing pediatricians?
In a separate interview, study author Dr. Edwards noted that “infants born very preterm, who are discharged home from the NICU today, are larger and more physiologically mature than they were in 2005. Pediatricians will likely find this news to be positive as it may be easier to manage care for a more physiologically mature [infant],” and it may reduce risk of readmission.
“Infants stayed, on average, 8 days longer in 2018 than they did in 2005. That is 8 days when they were not at home with their families. Despite efforts by NICU teams to increase family-centered care, the NICU is not the same as being at home. ... That extra time in the NICU cost [some families] an estimated $28,000. ... As health care costs continue to rise, we need to understand the true cost [behind] this increase,” added Dr. Edwards, noting that more research is needed to understand what may be driving the increase in NICU length of stay and the possible implications. More research to investigate whether babies did better after discharge also is needed.
Going forward, Dr. Edwards indicated that she and her colleagues are exploring ways to measure apnea of prematurity (AOP) and use of continuous pulse oximetry (CPO) as the subject of future studies. In our study, we showed that the number of infants discharged home on a cardiorespiratory monitor decreased, but we do not know if that is explained by differences in management of AOP and CPO. “Understanding the influence of AOP and CPO management on discharge age would be an important contribution [to future research].”
AOP may drive increase in postmenstrual age
In an accompanying editorial, Cody Arnold, MD, and Alexis S. Davis, MD, said: “We have focused on apnea of prematurity and discharge countdowns in this commentary because we believe that changes in related practices are likely the most important drivers of the increases in postmenstrual age” reported by the authors in this study. “Other factors, such as increasing availability of NICU beds or decreasing availability of home support services, may have contributed to longer length of stay. But these questions should be answered by research, not by speculation,” said Dr. Arnold, neonatologist, University of Texas Health Sciences Center, Houston, and Dr. Davis, clinical associate professor, Stanford (Calif.) University.
“Prospective research comparing alternative countdown strategies on the basis of readmission rates and other outpatient outcomes is overdue.” Additional research is needed operationally to clearly outline parameters for countdown events, countdown duration, indications for CPO, outpatient caffeine use, and parental shared decision-making.”
The study was funded by the Vermont Oxford Network. Dr. Edwards received a grant from the Vermont Oxford Network; several others also had ties to the Network. Dr. Arnold and Dr. Davis had no conflicts of interest and reported no disclosures.
Gestational age and weight at discharge for infants aged 24-29 weeks increased steadily between 2005 and 2018, reported Erika M. Edwards, PhD, MPH, of the Vermont Oxford Network, Burlington, and associates.
Although they discussed several possible influencing factors, the authors were unable to explain the associated benefits, costs, and harms associated with increased age and weight at discharge, which remain undetermined. Infants are separated a week longer than they were at the beginning of the study period, the prolonged effects of which cannot be underestimated, Dr. Edwards and colleagues observed in a large cohort study in Pediatrics.
A total of 314,811 infants 24-29 weeks’ gestational age who were admitted to 824 neonatal ICUs (NICUs) throughout the United States survived to initial discharge. The median postmenstrual age at hospital discharge was 38.3 weeks. Over the 14-year period from 2005 to 2018, unadjusted postmenstrual age at discharge increased a median 9 days, compared with a median adjusted age of 8 days.
Of the 273,109 infants initially discharged from the hospital to home, median weight at discharge was 2,600 g. Over the 14 years from 2005 to 2018, median unadjusted discharge weight increased 360 g, compared with median adjusted weight, which was estimated to have increased 316 g.
Median unadjusted z scores for weight increased 0.22 standard units over the 14-year period, compared with median adjusted z scores for weight at discharge, which increased an estimated 0.19 standard units.
The proportion of infants who were consuming human milk at discharge increased over the study period from 40% in 2005 to 48% in 2018. The use of cardiorespiratory monitors and oxygen decreased from 49% to 26%, and 27% to 22% respectively. The number of infants who were never transferred to specialized care before discharge to home also improved, from 71% to 76%.
Despite the unknowns, good news for managing pediatricians?
In a separate interview, study author Dr. Edwards noted that “infants born very preterm, who are discharged home from the NICU today, are larger and more physiologically mature than they were in 2005. Pediatricians will likely find this news to be positive as it may be easier to manage care for a more physiologically mature [infant],” and it may reduce risk of readmission.
“Infants stayed, on average, 8 days longer in 2018 than they did in 2005. That is 8 days when they were not at home with their families. Despite efforts by NICU teams to increase family-centered care, the NICU is not the same as being at home. ... That extra time in the NICU cost [some families] an estimated $28,000. ... As health care costs continue to rise, we need to understand the true cost [behind] this increase,” added Dr. Edwards, noting that more research is needed to understand what may be driving the increase in NICU length of stay and the possible implications. More research to investigate whether babies did better after discharge also is needed.
Going forward, Dr. Edwards indicated that she and her colleagues are exploring ways to measure apnea of prematurity (AOP) and use of continuous pulse oximetry (CPO) as the subject of future studies. In our study, we showed that the number of infants discharged home on a cardiorespiratory monitor decreased, but we do not know if that is explained by differences in management of AOP and CPO. “Understanding the influence of AOP and CPO management on discharge age would be an important contribution [to future research].”
AOP may drive increase in postmenstrual age
In an accompanying editorial, Cody Arnold, MD, and Alexis S. Davis, MD, said: “We have focused on apnea of prematurity and discharge countdowns in this commentary because we believe that changes in related practices are likely the most important drivers of the increases in postmenstrual age” reported by the authors in this study. “Other factors, such as increasing availability of NICU beds or decreasing availability of home support services, may have contributed to longer length of stay. But these questions should be answered by research, not by speculation,” said Dr. Arnold, neonatologist, University of Texas Health Sciences Center, Houston, and Dr. Davis, clinical associate professor, Stanford (Calif.) University.
“Prospective research comparing alternative countdown strategies on the basis of readmission rates and other outpatient outcomes is overdue.” Additional research is needed operationally to clearly outline parameters for countdown events, countdown duration, indications for CPO, outpatient caffeine use, and parental shared decision-making.”
The study was funded by the Vermont Oxford Network. Dr. Edwards received a grant from the Vermont Oxford Network; several others also had ties to the Network. Dr. Arnold and Dr. Davis had no conflicts of interest and reported no disclosures.
Gestational age and weight at discharge for infants aged 24-29 weeks increased steadily between 2005 and 2018, reported Erika M. Edwards, PhD, MPH, of the Vermont Oxford Network, Burlington, and associates.
Although they discussed several possible influencing factors, the authors were unable to explain the associated benefits, costs, and harms associated with increased age and weight at discharge, which remain undetermined. Infants are separated a week longer than they were at the beginning of the study period, the prolonged effects of which cannot be underestimated, Dr. Edwards and colleagues observed in a large cohort study in Pediatrics.
A total of 314,811 infants 24-29 weeks’ gestational age who were admitted to 824 neonatal ICUs (NICUs) throughout the United States survived to initial discharge. The median postmenstrual age at hospital discharge was 38.3 weeks. Over the 14-year period from 2005 to 2018, unadjusted postmenstrual age at discharge increased a median 9 days, compared with a median adjusted age of 8 days.
Of the 273,109 infants initially discharged from the hospital to home, median weight at discharge was 2,600 g. Over the 14 years from 2005 to 2018, median unadjusted discharge weight increased 360 g, compared with median adjusted weight, which was estimated to have increased 316 g.
Median unadjusted z scores for weight increased 0.22 standard units over the 14-year period, compared with median adjusted z scores for weight at discharge, which increased an estimated 0.19 standard units.
The proportion of infants who were consuming human milk at discharge increased over the study period from 40% in 2005 to 48% in 2018. The use of cardiorespiratory monitors and oxygen decreased from 49% to 26%, and 27% to 22% respectively. The number of infants who were never transferred to specialized care before discharge to home also improved, from 71% to 76%.
Despite the unknowns, good news for managing pediatricians?
In a separate interview, study author Dr. Edwards noted that “infants born very preterm, who are discharged home from the NICU today, are larger and more physiologically mature than they were in 2005. Pediatricians will likely find this news to be positive as it may be easier to manage care for a more physiologically mature [infant],” and it may reduce risk of readmission.
“Infants stayed, on average, 8 days longer in 2018 than they did in 2005. That is 8 days when they were not at home with their families. Despite efforts by NICU teams to increase family-centered care, the NICU is not the same as being at home. ... That extra time in the NICU cost [some families] an estimated $28,000. ... As health care costs continue to rise, we need to understand the true cost [behind] this increase,” added Dr. Edwards, noting that more research is needed to understand what may be driving the increase in NICU length of stay and the possible implications. More research to investigate whether babies did better after discharge also is needed.
Going forward, Dr. Edwards indicated that she and her colleagues are exploring ways to measure apnea of prematurity (AOP) and use of continuous pulse oximetry (CPO) as the subject of future studies. In our study, we showed that the number of infants discharged home on a cardiorespiratory monitor decreased, but we do not know if that is explained by differences in management of AOP and CPO. “Understanding the influence of AOP and CPO management on discharge age would be an important contribution [to future research].”
AOP may drive increase in postmenstrual age
In an accompanying editorial, Cody Arnold, MD, and Alexis S. Davis, MD, said: “We have focused on apnea of prematurity and discharge countdowns in this commentary because we believe that changes in related practices are likely the most important drivers of the increases in postmenstrual age” reported by the authors in this study. “Other factors, such as increasing availability of NICU beds or decreasing availability of home support services, may have contributed to longer length of stay. But these questions should be answered by research, not by speculation,” said Dr. Arnold, neonatologist, University of Texas Health Sciences Center, Houston, and Dr. Davis, clinical associate professor, Stanford (Calif.) University.
“Prospective research comparing alternative countdown strategies on the basis of readmission rates and other outpatient outcomes is overdue.” Additional research is needed operationally to clearly outline parameters for countdown events, countdown duration, indications for CPO, outpatient caffeine use, and parental shared decision-making.”
The study was funded by the Vermont Oxford Network. Dr. Edwards received a grant from the Vermont Oxford Network; several others also had ties to the Network. Dr. Arnold and Dr. Davis had no conflicts of interest and reported no disclosures.
FROM PEDIATRICS
State of the evidence: Treatment-resistant depression in children and adolescents
Case
Max was a 17-year-old boy and avid video gamer who, predating COVID-19, was within a major depressive episode and continued to meet criteria through the duration of COVID-19 quarantine. He lives with his mother, who is a single mom and is working hard in a variety of jobs through the pandemic. Max had little motivation to engage in sports or other activities, and despite doing well enough in school, he spent much of his days escaping into video games and social media, where his friends communicated and bonded the most. He has had very little response to complete trials of two different selective serotonin reuptake inhibitors (SSRIs), and the off-label attempts at a serotonin-norepinephrine reuptake inhibitor and bupropion augmentation of an SSRI, as extrapolated by his pediatrician from adult data on treatment-resistant depression. He had ongoing supportive psychotherapy and his mother and pediatrician were wary of changing that relationship, as they were just happy he would engage at all. His shy nature made him very wary of attending any programs or groups. He had no other diagnosis including anxiety, substance abuse disorder, or learning disorder.
Case discussion
As a child and adolescent psychiatrist embedded in primary care practices, I (like you) am seeing more and more parents, children, and families struggling with depression through the course of this unprecedented and challenging year.
Max presented to me with his mother at the request of his primary care physician because within the course of many medication trials, it had been over 6 months of persistent symptoms without an end in sight for him, his family, or his primary care provider (PCP).
His diagnosis was treatment-resistant depression and his PCP was grasping at adult strategies to manage this all with additional psychopharmacology. As a consulting child-and-adolescent psychiatrist in primary care, how could I help the PCP? I too worry if there is anything that I can do to shift depression once standard treatments fail, and when the idea of engaging in behavioral activation or other pro-health activities is just too much for a depressed adolescent to bear. I weigh that with what is known about the evidence, and the good data driving us beyond medication solutions. I often find that it can be helpful to reiterate the following points to providers and families.
First, what to know about depression in kids
Depression looks different at different ages in children. In school-aged children, it’s widely known that irritability or psychosomatic symptoms (frequent headaches and stomach aches) can be the first preverbal signs of an emerging anxiety and depressive disorder in children. In adolescents, one would maybe expect more typical melancholic adult-like symptoms of depression; however, there is mounting evidence that adolescents actually present with more classically “atypical symptoms” of depression (low motivation, weight gain, escapism to sleep or video games, as with Max) with less persistence across setting (home, work, school) compared with adults (“Diagnosing Depression in Children and Adolescents” by Glen R. Elliott, PhD, MD, from The Carlat Child Psychiatry Report, November 2015, Antidepressant Use in Children).In addition, major life stressors (the breakup of a romantic relationship, failing a class, bullying) can be perceived as more permanent, and suicidal thinking can be acute and lethal in these contexts. With Max, it was accepted by all who were supporting him that he was struggling with depression, which is the first step in managing this well.
The idea of the designated patient
Often left out in a discussion of pediatric patients is the family. As a designated patient, much of our focus is on improving the symptoms of the patient in front of us. Parents direct their gaze at the child as the one with the condition who needs support. First following identification of depression, I find that a reframe of a diagnosis can be useful. Family systems theory approaches a child with a depression diagnosis, and says, that if one family member changes, even in a small way, a family as a system is forced to change. With a sense of an external locus of control, we often are left with a patient and parent feeling stuck. To provide a reorientation to the parents, ask how they are feeling. Can they get treatment for depression knowing the biology of the condition or consider making behavioral changes of their own and as a family? Can they consider family psychotherapy so they can cope better and break some cycles of maladaptive engagement shared across a family? These kinds of reorientations can be useful to shift the idea of treatment from the designated patient (the child) and medication options (limited data for kids who aren’t responding to them) to a family approach. Making the depression management strategy a family affair can help the entire family shift from seeing the only option as medications or interventions exclusively directed at a child. The Vermont Center for Children, Youth, and Families at the University of Vermont Medical Center has many pioneering developments in addressing family-based approaches to mental health concerns in the pediatric population, and can serve as a source of inspiration for this shift in discussing depression.
Practical strategies for the pediatrician
Medications can be useful for treating child and adolescent depression, but there is also strong evidence for psychotherapy, working with the child’s school and family, and different forms of behavioral activation (exercise, mindfulness, yoga, and other positive activities). Medications, if one is looking at standard of care treatment and Food and Drug Administration approval exclusively, is limited in scope and should not be the only intervention considered, as described in the case above.
In “The Use of Medication in Treating Childhood and Adolescent Depression: Information for Patients and Families,” which is a practical guide prepared by the American Psychiatric Association and the American Academy of Child and Adolescent Psychiatry, it is noted that Prozac and Lexapro are approved medications, as follows:
- Antidepressant medications can be effective in relieving the symptoms of depression for some children and adolescents. One antidepressant – fluoxetine, or Prozac – a medicine in the category of SSRIs, has been approved by the FDA for treating depression in children 8 years of age and older. Escitalopram, or Lexapro, has also been approved by the FDA for treating adolescents 12 years of age and older.
- About “60 percent of children and adolescents will respond to initial treatment with medication,” which leaves many children needing further interventions. “Of those who don’t [respond], a significant number may respond to another medication but also may respond to the addition of a form of psychotherapy called cognitive behavioral therapy (CBT).”
It is common, as in the case above, that a connection with a therapist or support is valued over the specific modality even if it’s not showing improvement or outcomes. It is important to consider CBT as a form of evidence-based treatment for children with depression and to cite the famous “Treatment for Adolescents with Depression Study (TADS)” funded by the National Institute of Mental Health, published in 2004, that shows the following findings: “After 12 weeks of treatment, 71 percent of the patients who received the combination of medication and CBT were much improved.” In looking at the group that does not improve with medications alone, adolescents in particular can have more gains with the addition of CBT.
Tracking progress, little by little
Often we reflexively ask parents of depressed children: Are they better? And we ask the child: How do you feel? It can be difficult for parents to reflect on that, or see progress or gains from appointment to appointment. I suggest trying to use structured measures and tools to frame a discussion with progress on medication and treatment such as what is available at the Mood Treatment Center website.I also suggest apps such as Mood Kit,which is for mood tracking with some CBT exercises in addition to behavioral activation strategies for children and parents. It can be useful to have families take some ownership of tracking their moods and what may be playing into them. In particular with the pandemic, we can reflect on how much isolation or socialization, activities, sleep, eating habits, and exercise can affect us and make corresponding behavioral changes as a family to improve our own coping. Depression itself can be like glasses clouding one’s vision in gray, and that can also cloud one’s review of progress. When we hear comments such as “nothing gets better” from a child or parent, it may be helpful to try to track any contributing factors to a persistent low mood and acknowledge any slow and steady progress.
In summary, we can strive as providers to maximize our approach to depression in children and adolescents beyond the limited FDA-approved medications, or extrapolating adult data to children. If we emphasize the evidence-based practice of CBT and other interventions in addition to encouraging a tracking and review of outcomes measures with parents and families, we can empower them to make meaningful change in both perspectives and behaviors that can perpetuate depressive states.
Dr. Pawlowski is an adult, adolescent, and child psychiatrist at the University of Vermont Medical Center and assistant professor of psychiatry at the Larner College of Medicine at UVM in Burlington.
Case
Max was a 17-year-old boy and avid video gamer who, predating COVID-19, was within a major depressive episode and continued to meet criteria through the duration of COVID-19 quarantine. He lives with his mother, who is a single mom and is working hard in a variety of jobs through the pandemic. Max had little motivation to engage in sports or other activities, and despite doing well enough in school, he spent much of his days escaping into video games and social media, where his friends communicated and bonded the most. He has had very little response to complete trials of two different selective serotonin reuptake inhibitors (SSRIs), and the off-label attempts at a serotonin-norepinephrine reuptake inhibitor and bupropion augmentation of an SSRI, as extrapolated by his pediatrician from adult data on treatment-resistant depression. He had ongoing supportive psychotherapy and his mother and pediatrician were wary of changing that relationship, as they were just happy he would engage at all. His shy nature made him very wary of attending any programs or groups. He had no other diagnosis including anxiety, substance abuse disorder, or learning disorder.
Case discussion
As a child and adolescent psychiatrist embedded in primary care practices, I (like you) am seeing more and more parents, children, and families struggling with depression through the course of this unprecedented and challenging year.
Max presented to me with his mother at the request of his primary care physician because within the course of many medication trials, it had been over 6 months of persistent symptoms without an end in sight for him, his family, or his primary care provider (PCP).
His diagnosis was treatment-resistant depression and his PCP was grasping at adult strategies to manage this all with additional psychopharmacology. As a consulting child-and-adolescent psychiatrist in primary care, how could I help the PCP? I too worry if there is anything that I can do to shift depression once standard treatments fail, and when the idea of engaging in behavioral activation or other pro-health activities is just too much for a depressed adolescent to bear. I weigh that with what is known about the evidence, and the good data driving us beyond medication solutions. I often find that it can be helpful to reiterate the following points to providers and families.
First, what to know about depression in kids
Depression looks different at different ages in children. In school-aged children, it’s widely known that irritability or psychosomatic symptoms (frequent headaches and stomach aches) can be the first preverbal signs of an emerging anxiety and depressive disorder in children. In adolescents, one would maybe expect more typical melancholic adult-like symptoms of depression; however, there is mounting evidence that adolescents actually present with more classically “atypical symptoms” of depression (low motivation, weight gain, escapism to sleep or video games, as with Max) with less persistence across setting (home, work, school) compared with adults (“Diagnosing Depression in Children and Adolescents” by Glen R. Elliott, PhD, MD, from The Carlat Child Psychiatry Report, November 2015, Antidepressant Use in Children).In addition, major life stressors (the breakup of a romantic relationship, failing a class, bullying) can be perceived as more permanent, and suicidal thinking can be acute and lethal in these contexts. With Max, it was accepted by all who were supporting him that he was struggling with depression, which is the first step in managing this well.
The idea of the designated patient
Often left out in a discussion of pediatric patients is the family. As a designated patient, much of our focus is on improving the symptoms of the patient in front of us. Parents direct their gaze at the child as the one with the condition who needs support. First following identification of depression, I find that a reframe of a diagnosis can be useful. Family systems theory approaches a child with a depression diagnosis, and says, that if one family member changes, even in a small way, a family as a system is forced to change. With a sense of an external locus of control, we often are left with a patient and parent feeling stuck. To provide a reorientation to the parents, ask how they are feeling. Can they get treatment for depression knowing the biology of the condition or consider making behavioral changes of their own and as a family? Can they consider family psychotherapy so they can cope better and break some cycles of maladaptive engagement shared across a family? These kinds of reorientations can be useful to shift the idea of treatment from the designated patient (the child) and medication options (limited data for kids who aren’t responding to them) to a family approach. Making the depression management strategy a family affair can help the entire family shift from seeing the only option as medications or interventions exclusively directed at a child. The Vermont Center for Children, Youth, and Families at the University of Vermont Medical Center has many pioneering developments in addressing family-based approaches to mental health concerns in the pediatric population, and can serve as a source of inspiration for this shift in discussing depression.
Practical strategies for the pediatrician
Medications can be useful for treating child and adolescent depression, but there is also strong evidence for psychotherapy, working with the child’s school and family, and different forms of behavioral activation (exercise, mindfulness, yoga, and other positive activities). Medications, if one is looking at standard of care treatment and Food and Drug Administration approval exclusively, is limited in scope and should not be the only intervention considered, as described in the case above.
In “The Use of Medication in Treating Childhood and Adolescent Depression: Information for Patients and Families,” which is a practical guide prepared by the American Psychiatric Association and the American Academy of Child and Adolescent Psychiatry, it is noted that Prozac and Lexapro are approved medications, as follows:
- Antidepressant medications can be effective in relieving the symptoms of depression for some children and adolescents. One antidepressant – fluoxetine, or Prozac – a medicine in the category of SSRIs, has been approved by the FDA for treating depression in children 8 years of age and older. Escitalopram, or Lexapro, has also been approved by the FDA for treating adolescents 12 years of age and older.
- About “60 percent of children and adolescents will respond to initial treatment with medication,” which leaves many children needing further interventions. “Of those who don’t [respond], a significant number may respond to another medication but also may respond to the addition of a form of psychotherapy called cognitive behavioral therapy (CBT).”
It is common, as in the case above, that a connection with a therapist or support is valued over the specific modality even if it’s not showing improvement or outcomes. It is important to consider CBT as a form of evidence-based treatment for children with depression and to cite the famous “Treatment for Adolescents with Depression Study (TADS)” funded by the National Institute of Mental Health, published in 2004, that shows the following findings: “After 12 weeks of treatment, 71 percent of the patients who received the combination of medication and CBT were much improved.” In looking at the group that does not improve with medications alone, adolescents in particular can have more gains with the addition of CBT.
Tracking progress, little by little
Often we reflexively ask parents of depressed children: Are they better? And we ask the child: How do you feel? It can be difficult for parents to reflect on that, or see progress or gains from appointment to appointment. I suggest trying to use structured measures and tools to frame a discussion with progress on medication and treatment such as what is available at the Mood Treatment Center website.I also suggest apps such as Mood Kit,which is for mood tracking with some CBT exercises in addition to behavioral activation strategies for children and parents. It can be useful to have families take some ownership of tracking their moods and what may be playing into them. In particular with the pandemic, we can reflect on how much isolation or socialization, activities, sleep, eating habits, and exercise can affect us and make corresponding behavioral changes as a family to improve our own coping. Depression itself can be like glasses clouding one’s vision in gray, and that can also cloud one’s review of progress. When we hear comments such as “nothing gets better” from a child or parent, it may be helpful to try to track any contributing factors to a persistent low mood and acknowledge any slow and steady progress.
In summary, we can strive as providers to maximize our approach to depression in children and adolescents beyond the limited FDA-approved medications, or extrapolating adult data to children. If we emphasize the evidence-based practice of CBT and other interventions in addition to encouraging a tracking and review of outcomes measures with parents and families, we can empower them to make meaningful change in both perspectives and behaviors that can perpetuate depressive states.
Dr. Pawlowski is an adult, adolescent, and child psychiatrist at the University of Vermont Medical Center and assistant professor of psychiatry at the Larner College of Medicine at UVM in Burlington.
Case
Max was a 17-year-old boy and avid video gamer who, predating COVID-19, was within a major depressive episode and continued to meet criteria through the duration of COVID-19 quarantine. He lives with his mother, who is a single mom and is working hard in a variety of jobs through the pandemic. Max had little motivation to engage in sports or other activities, and despite doing well enough in school, he spent much of his days escaping into video games and social media, where his friends communicated and bonded the most. He has had very little response to complete trials of two different selective serotonin reuptake inhibitors (SSRIs), and the off-label attempts at a serotonin-norepinephrine reuptake inhibitor and bupropion augmentation of an SSRI, as extrapolated by his pediatrician from adult data on treatment-resistant depression. He had ongoing supportive psychotherapy and his mother and pediatrician were wary of changing that relationship, as they were just happy he would engage at all. His shy nature made him very wary of attending any programs or groups. He had no other diagnosis including anxiety, substance abuse disorder, or learning disorder.
Case discussion
As a child and adolescent psychiatrist embedded in primary care practices, I (like you) am seeing more and more parents, children, and families struggling with depression through the course of this unprecedented and challenging year.
Max presented to me with his mother at the request of his primary care physician because within the course of many medication trials, it had been over 6 months of persistent symptoms without an end in sight for him, his family, or his primary care provider (PCP).
His diagnosis was treatment-resistant depression and his PCP was grasping at adult strategies to manage this all with additional psychopharmacology. As a consulting child-and-adolescent psychiatrist in primary care, how could I help the PCP? I too worry if there is anything that I can do to shift depression once standard treatments fail, and when the idea of engaging in behavioral activation or other pro-health activities is just too much for a depressed adolescent to bear. I weigh that with what is known about the evidence, and the good data driving us beyond medication solutions. I often find that it can be helpful to reiterate the following points to providers and families.
First, what to know about depression in kids
Depression looks different at different ages in children. In school-aged children, it’s widely known that irritability or psychosomatic symptoms (frequent headaches and stomach aches) can be the first preverbal signs of an emerging anxiety and depressive disorder in children. In adolescents, one would maybe expect more typical melancholic adult-like symptoms of depression; however, there is mounting evidence that adolescents actually present with more classically “atypical symptoms” of depression (low motivation, weight gain, escapism to sleep or video games, as with Max) with less persistence across setting (home, work, school) compared with adults (“Diagnosing Depression in Children and Adolescents” by Glen R. Elliott, PhD, MD, from The Carlat Child Psychiatry Report, November 2015, Antidepressant Use in Children).In addition, major life stressors (the breakup of a romantic relationship, failing a class, bullying) can be perceived as more permanent, and suicidal thinking can be acute and lethal in these contexts. With Max, it was accepted by all who were supporting him that he was struggling with depression, which is the first step in managing this well.
The idea of the designated patient
Often left out in a discussion of pediatric patients is the family. As a designated patient, much of our focus is on improving the symptoms of the patient in front of us. Parents direct their gaze at the child as the one with the condition who needs support. First following identification of depression, I find that a reframe of a diagnosis can be useful. Family systems theory approaches a child with a depression diagnosis, and says, that if one family member changes, even in a small way, a family as a system is forced to change. With a sense of an external locus of control, we often are left with a patient and parent feeling stuck. To provide a reorientation to the parents, ask how they are feeling. Can they get treatment for depression knowing the biology of the condition or consider making behavioral changes of their own and as a family? Can they consider family psychotherapy so they can cope better and break some cycles of maladaptive engagement shared across a family? These kinds of reorientations can be useful to shift the idea of treatment from the designated patient (the child) and medication options (limited data for kids who aren’t responding to them) to a family approach. Making the depression management strategy a family affair can help the entire family shift from seeing the only option as medications or interventions exclusively directed at a child. The Vermont Center for Children, Youth, and Families at the University of Vermont Medical Center has many pioneering developments in addressing family-based approaches to mental health concerns in the pediatric population, and can serve as a source of inspiration for this shift in discussing depression.
Practical strategies for the pediatrician
Medications can be useful for treating child and adolescent depression, but there is also strong evidence for psychotherapy, working with the child’s school and family, and different forms of behavioral activation (exercise, mindfulness, yoga, and other positive activities). Medications, if one is looking at standard of care treatment and Food and Drug Administration approval exclusively, is limited in scope and should not be the only intervention considered, as described in the case above.
In “The Use of Medication in Treating Childhood and Adolescent Depression: Information for Patients and Families,” which is a practical guide prepared by the American Psychiatric Association and the American Academy of Child and Adolescent Psychiatry, it is noted that Prozac and Lexapro are approved medications, as follows:
- Antidepressant medications can be effective in relieving the symptoms of depression for some children and adolescents. One antidepressant – fluoxetine, or Prozac – a medicine in the category of SSRIs, has been approved by the FDA for treating depression in children 8 years of age and older. Escitalopram, or Lexapro, has also been approved by the FDA for treating adolescents 12 years of age and older.
- About “60 percent of children and adolescents will respond to initial treatment with medication,” which leaves many children needing further interventions. “Of those who don’t [respond], a significant number may respond to another medication but also may respond to the addition of a form of psychotherapy called cognitive behavioral therapy (CBT).”
It is common, as in the case above, that a connection with a therapist or support is valued over the specific modality even if it’s not showing improvement or outcomes. It is important to consider CBT as a form of evidence-based treatment for children with depression and to cite the famous “Treatment for Adolescents with Depression Study (TADS)” funded by the National Institute of Mental Health, published in 2004, that shows the following findings: “After 12 weeks of treatment, 71 percent of the patients who received the combination of medication and CBT were much improved.” In looking at the group that does not improve with medications alone, adolescents in particular can have more gains with the addition of CBT.
Tracking progress, little by little
Often we reflexively ask parents of depressed children: Are they better? And we ask the child: How do you feel? It can be difficult for parents to reflect on that, or see progress or gains from appointment to appointment. I suggest trying to use structured measures and tools to frame a discussion with progress on medication and treatment such as what is available at the Mood Treatment Center website.I also suggest apps such as Mood Kit,which is for mood tracking with some CBT exercises in addition to behavioral activation strategies for children and parents. It can be useful to have families take some ownership of tracking their moods and what may be playing into them. In particular with the pandemic, we can reflect on how much isolation or socialization, activities, sleep, eating habits, and exercise can affect us and make corresponding behavioral changes as a family to improve our own coping. Depression itself can be like glasses clouding one’s vision in gray, and that can also cloud one’s review of progress. When we hear comments such as “nothing gets better” from a child or parent, it may be helpful to try to track any contributing factors to a persistent low mood and acknowledge any slow and steady progress.
In summary, we can strive as providers to maximize our approach to depression in children and adolescents beyond the limited FDA-approved medications, or extrapolating adult data to children. If we emphasize the evidence-based practice of CBT and other interventions in addition to encouraging a tracking and review of outcomes measures with parents and families, we can empower them to make meaningful change in both perspectives and behaviors that can perpetuate depressive states.
Dr. Pawlowski is an adult, adolescent, and child psychiatrist at the University of Vermont Medical Center and assistant professor of psychiatry at the Larner College of Medicine at UVM in Burlington.
FDA approves orphan drug evinacumab-dgnb for homozygous FH
The Food and Drug Administration has approved the fully human monoclonal antibody evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals) for use on top of other cholesterol-modifying medication in patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), the agency and Regeneron have announced.
Evinacumab had received orphan drug designation and underwent priority regulatory review based primarily on the phase 3 ELIPSE trial, presented at a meeting in March 2020 and published in August 2020 in the New England Journal of Medicine (doi: 10.1056/NEJMoa2004215).
In the trial with 65 patients with HoFH on guideline-based lipid-modifying therapy, those who also received evinacumab 15 mg/kg intravenously every 4 weeks showed a nearly 50% drop in LDL cholesterol levels after 24 weeks, compared with patients given a placebo. Only 2% of patients in both groups discontinued therapy because of adverse reactions.
The drug blocks angiopoietin-like 3, itself an inhibitor of lipoprotein lipase and endothelial lipase. It therefore lowers LDL cholesterol levels by mechanisms that don’t directly involve the LDL receptor.
Regeneron estimates that about 1300 people in the United States have the homozygous genetic disorder, which can lead to LDL cholesterol levels of a 1,000 mg/dL or higher, advanced premature atherosclerosis, and extreme risk for cardiovascular events.
The drug’s average wholesale acquisition cost per patient in the United States is expected to be about $450,000 per year, the company said, adding that it has a financial support program to help qualified patients with out-of-pocket costs.
Regeneron’s announcement included a comment from dyslipidemia-therapy expert Daniel J. Rader, MD, University of Pennsylvania, Philadelphia, who called evinacumab “a potentially transformational new treatment for people with HoFH.”
The drug is currently under regulatory review for the same indication in Europe, the company said.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the fully human monoclonal antibody evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals) for use on top of other cholesterol-modifying medication in patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), the agency and Regeneron have announced.
Evinacumab had received orphan drug designation and underwent priority regulatory review based primarily on the phase 3 ELIPSE trial, presented at a meeting in March 2020 and published in August 2020 in the New England Journal of Medicine (doi: 10.1056/NEJMoa2004215).
In the trial with 65 patients with HoFH on guideline-based lipid-modifying therapy, those who also received evinacumab 15 mg/kg intravenously every 4 weeks showed a nearly 50% drop in LDL cholesterol levels after 24 weeks, compared with patients given a placebo. Only 2% of patients in both groups discontinued therapy because of adverse reactions.
The drug blocks angiopoietin-like 3, itself an inhibitor of lipoprotein lipase and endothelial lipase. It therefore lowers LDL cholesterol levels by mechanisms that don’t directly involve the LDL receptor.
Regeneron estimates that about 1300 people in the United States have the homozygous genetic disorder, which can lead to LDL cholesterol levels of a 1,000 mg/dL or higher, advanced premature atherosclerosis, and extreme risk for cardiovascular events.
The drug’s average wholesale acquisition cost per patient in the United States is expected to be about $450,000 per year, the company said, adding that it has a financial support program to help qualified patients with out-of-pocket costs.
Regeneron’s announcement included a comment from dyslipidemia-therapy expert Daniel J. Rader, MD, University of Pennsylvania, Philadelphia, who called evinacumab “a potentially transformational new treatment for people with HoFH.”
The drug is currently under regulatory review for the same indication in Europe, the company said.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the fully human monoclonal antibody evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals) for use on top of other cholesterol-modifying medication in patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), the agency and Regeneron have announced.
Evinacumab had received orphan drug designation and underwent priority regulatory review based primarily on the phase 3 ELIPSE trial, presented at a meeting in March 2020 and published in August 2020 in the New England Journal of Medicine (doi: 10.1056/NEJMoa2004215).
In the trial with 65 patients with HoFH on guideline-based lipid-modifying therapy, those who also received evinacumab 15 mg/kg intravenously every 4 weeks showed a nearly 50% drop in LDL cholesterol levels after 24 weeks, compared with patients given a placebo. Only 2% of patients in both groups discontinued therapy because of adverse reactions.
The drug blocks angiopoietin-like 3, itself an inhibitor of lipoprotein lipase and endothelial lipase. It therefore lowers LDL cholesterol levels by mechanisms that don’t directly involve the LDL receptor.
Regeneron estimates that about 1300 people in the United States have the homozygous genetic disorder, which can lead to LDL cholesterol levels of a 1,000 mg/dL or higher, advanced premature atherosclerosis, and extreme risk for cardiovascular events.
The drug’s average wholesale acquisition cost per patient in the United States is expected to be about $450,000 per year, the company said, adding that it has a financial support program to help qualified patients with out-of-pocket costs.
Regeneron’s announcement included a comment from dyslipidemia-therapy expert Daniel J. Rader, MD, University of Pennsylvania, Philadelphia, who called evinacumab “a potentially transformational new treatment for people with HoFH.”
The drug is currently under regulatory review for the same indication in Europe, the company said.
A version of this article first appeared on Medscape.com.
Steroid and immunoglobulin standard of care for MIS-C
The combination of methylprednisolone and intravenous immunoglobulins works better than intravenous immunoglobulins alone for multisystem inflammatory syndrome in children (MIS-C), researchers say.
“I’m not sure it’s the best treatment because we have not studied every possible treatment,” François Angoulvant, MD, PhD, told this news organization, “but right now, it’s the standard of care.”
Dr. Angoulvant, a professor of pediatrics at University of Paris, and colleagues published a comparison of the two treatments in the Journal of the American Medical Association.
A small percentage of children infected with SARS-CoV-2 develop MIS-C about 2 to 4 weeks later. It is considered a separate disease entity from COVID-19 and is associated with persistent fever, digestive symptoms, rash, bilateral nonpurulent conjunctivitis, mucocutaneous inflammation signs, and frequent cardiovascular involvement. In more than 60% of cases, it leads to hemodynamic failure, with acute cardiac dysfunction.
Because MIS-C resembles Kawasaki disease, clinicians modeled their treatment on that condition and started with immunoglobulins alone, Dr. Angoulvant said.
Based on expert opinion, the National Health Service in the United Kingdom published a consensus statement in Sept. listing immunoglobulins alone as the first-line treatment.
But anecdotal reports have emerged that combining the immunoglobulins with a corticosteroid worked better. To investigate this possibility, Dr. Angoulvant and colleagues analyzed records of MIS-C cases in France, where physicians are required to report all suspected cases of MIS-C to the French National Public Health Agency.
Among the 181 cases they scrutinized, 111 fulfilled the World Health Organization criteria for MIS-C. Of these, the researchers were able to match 64 patients who had received immunoglobulins alone with 32 who had received the combined therapy and could be matched using propensity scores.
The researchers defined treatment failure as persistence of fever for 2 days after the start of therapy or recurrence of fever within a week. By this measure, the combination treatment failed in only 9% of cases while immunoglobulins alone failed in 38% of cases. The difference was statistically significant (P = .008). Most of those for whom these treatments failed received second-line treatments such as steroids or biological agents.
Patients treated with the combination therapy also had a lower risk of secondary acute left ventricular dysfunction (odds ratio, 0.20; 95% confidence interval, 0.06-0.66) and a lower risk of needing hemodynamic support (OR, 0.21; 95% CI, 0.06-0.76).
Those receiving the combination therapy spent a mean of 4 days in the pediatric intensive care unit compared with 6 days for those receiving immunoglobulins alone. (Difference in days, −2.4; 95% CI, −4.0 to −0.7; P = .005).
There are few drawbacks to the combination approach, Dr. Angoulvant said, as the side effects of corticosteroids are generally not severe and they can be anticipated because this class of medications has been used for many years.
The study raises the question of whether corticosteroids might work as well by themselves, but it could not be answered with this database as no one is using that approach in France, Dr. Angoulvant said. “I hope other teams around the world could bring us the answer.”
In the United States, most physicians appear to already be using the combination therapy, said David Teachey, MD, an associate professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia.
The reduction in time in pediatric intensive care and the reduced risk of cardiac dysfunction are important findings, he said.
This retrospective study falls short of the evidence provided by a randomized clinical trial, Dr. Teachey noted. But he acknowledged that few families would agree to participate in such a trial as they would have to take a chance that the sick children would receive a less effective therapy than what they would otherwise get. “It’s hard to [talk] about a therapy reduction,” he told this news organization.
Given that impediment, he agreed with Dr. Angoulvant that the current study and others like it may provide the best data available pointing to a treatment approach for MIS-C.
The study received an unrestricted grant from Pfizer. The French COVID-19 Paediatric Inflammation Consortium received an unrestricted grant from the Square Foundation (Grandir–Fonds de Solidarité pour L’Enfance). Dr. Angoulvant and Dr. Teachey have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The combination of methylprednisolone and intravenous immunoglobulins works better than intravenous immunoglobulins alone for multisystem inflammatory syndrome in children (MIS-C), researchers say.
“I’m not sure it’s the best treatment because we have not studied every possible treatment,” François Angoulvant, MD, PhD, told this news organization, “but right now, it’s the standard of care.”
Dr. Angoulvant, a professor of pediatrics at University of Paris, and colleagues published a comparison of the two treatments in the Journal of the American Medical Association.
A small percentage of children infected with SARS-CoV-2 develop MIS-C about 2 to 4 weeks later. It is considered a separate disease entity from COVID-19 and is associated with persistent fever, digestive symptoms, rash, bilateral nonpurulent conjunctivitis, mucocutaneous inflammation signs, and frequent cardiovascular involvement. In more than 60% of cases, it leads to hemodynamic failure, with acute cardiac dysfunction.
Because MIS-C resembles Kawasaki disease, clinicians modeled their treatment on that condition and started with immunoglobulins alone, Dr. Angoulvant said.
Based on expert opinion, the National Health Service in the United Kingdom published a consensus statement in Sept. listing immunoglobulins alone as the first-line treatment.
But anecdotal reports have emerged that combining the immunoglobulins with a corticosteroid worked better. To investigate this possibility, Dr. Angoulvant and colleagues analyzed records of MIS-C cases in France, where physicians are required to report all suspected cases of MIS-C to the French National Public Health Agency.
Among the 181 cases they scrutinized, 111 fulfilled the World Health Organization criteria for MIS-C. Of these, the researchers were able to match 64 patients who had received immunoglobulins alone with 32 who had received the combined therapy and could be matched using propensity scores.
The researchers defined treatment failure as persistence of fever for 2 days after the start of therapy or recurrence of fever within a week. By this measure, the combination treatment failed in only 9% of cases while immunoglobulins alone failed in 38% of cases. The difference was statistically significant (P = .008). Most of those for whom these treatments failed received second-line treatments such as steroids or biological agents.
Patients treated with the combination therapy also had a lower risk of secondary acute left ventricular dysfunction (odds ratio, 0.20; 95% confidence interval, 0.06-0.66) and a lower risk of needing hemodynamic support (OR, 0.21; 95% CI, 0.06-0.76).
Those receiving the combination therapy spent a mean of 4 days in the pediatric intensive care unit compared with 6 days for those receiving immunoglobulins alone. (Difference in days, −2.4; 95% CI, −4.0 to −0.7; P = .005).
There are few drawbacks to the combination approach, Dr. Angoulvant said, as the side effects of corticosteroids are generally not severe and they can be anticipated because this class of medications has been used for many years.
The study raises the question of whether corticosteroids might work as well by themselves, but it could not be answered with this database as no one is using that approach in France, Dr. Angoulvant said. “I hope other teams around the world could bring us the answer.”
In the United States, most physicians appear to already be using the combination therapy, said David Teachey, MD, an associate professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia.
The reduction in time in pediatric intensive care and the reduced risk of cardiac dysfunction are important findings, he said.
This retrospective study falls short of the evidence provided by a randomized clinical trial, Dr. Teachey noted. But he acknowledged that few families would agree to participate in such a trial as they would have to take a chance that the sick children would receive a less effective therapy than what they would otherwise get. “It’s hard to [talk] about a therapy reduction,” he told this news organization.
Given that impediment, he agreed with Dr. Angoulvant that the current study and others like it may provide the best data available pointing to a treatment approach for MIS-C.
The study received an unrestricted grant from Pfizer. The French COVID-19 Paediatric Inflammation Consortium received an unrestricted grant from the Square Foundation (Grandir–Fonds de Solidarité pour L’Enfance). Dr. Angoulvant and Dr. Teachey have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The combination of methylprednisolone and intravenous immunoglobulins works better than intravenous immunoglobulins alone for multisystem inflammatory syndrome in children (MIS-C), researchers say.
“I’m not sure it’s the best treatment because we have not studied every possible treatment,” François Angoulvant, MD, PhD, told this news organization, “but right now, it’s the standard of care.”
Dr. Angoulvant, a professor of pediatrics at University of Paris, and colleagues published a comparison of the two treatments in the Journal of the American Medical Association.
A small percentage of children infected with SARS-CoV-2 develop MIS-C about 2 to 4 weeks later. It is considered a separate disease entity from COVID-19 and is associated with persistent fever, digestive symptoms, rash, bilateral nonpurulent conjunctivitis, mucocutaneous inflammation signs, and frequent cardiovascular involvement. In more than 60% of cases, it leads to hemodynamic failure, with acute cardiac dysfunction.
Because MIS-C resembles Kawasaki disease, clinicians modeled their treatment on that condition and started with immunoglobulins alone, Dr. Angoulvant said.
Based on expert opinion, the National Health Service in the United Kingdom published a consensus statement in Sept. listing immunoglobulins alone as the first-line treatment.
But anecdotal reports have emerged that combining the immunoglobulins with a corticosteroid worked better. To investigate this possibility, Dr. Angoulvant and colleagues analyzed records of MIS-C cases in France, where physicians are required to report all suspected cases of MIS-C to the French National Public Health Agency.
Among the 181 cases they scrutinized, 111 fulfilled the World Health Organization criteria for MIS-C. Of these, the researchers were able to match 64 patients who had received immunoglobulins alone with 32 who had received the combined therapy and could be matched using propensity scores.
The researchers defined treatment failure as persistence of fever for 2 days after the start of therapy or recurrence of fever within a week. By this measure, the combination treatment failed in only 9% of cases while immunoglobulins alone failed in 38% of cases. The difference was statistically significant (P = .008). Most of those for whom these treatments failed received second-line treatments such as steroids or biological agents.
Patients treated with the combination therapy also had a lower risk of secondary acute left ventricular dysfunction (odds ratio, 0.20; 95% confidence interval, 0.06-0.66) and a lower risk of needing hemodynamic support (OR, 0.21; 95% CI, 0.06-0.76).
Those receiving the combination therapy spent a mean of 4 days in the pediatric intensive care unit compared with 6 days for those receiving immunoglobulins alone. (Difference in days, −2.4; 95% CI, −4.0 to −0.7; P = .005).
There are few drawbacks to the combination approach, Dr. Angoulvant said, as the side effects of corticosteroids are generally not severe and they can be anticipated because this class of medications has been used for many years.
The study raises the question of whether corticosteroids might work as well by themselves, but it could not be answered with this database as no one is using that approach in France, Dr. Angoulvant said. “I hope other teams around the world could bring us the answer.”
In the United States, most physicians appear to already be using the combination therapy, said David Teachey, MD, an associate professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia.
The reduction in time in pediatric intensive care and the reduced risk of cardiac dysfunction are important findings, he said.
This retrospective study falls short of the evidence provided by a randomized clinical trial, Dr. Teachey noted. But he acknowledged that few families would agree to participate in such a trial as they would have to take a chance that the sick children would receive a less effective therapy than what they would otherwise get. “It’s hard to [talk] about a therapy reduction,” he told this news organization.
Given that impediment, he agreed with Dr. Angoulvant that the current study and others like it may provide the best data available pointing to a treatment approach for MIS-C.
The study received an unrestricted grant from Pfizer. The French COVID-19 Paediatric Inflammation Consortium received an unrestricted grant from the Square Foundation (Grandir–Fonds de Solidarité pour L’Enfance). Dr. Angoulvant and Dr. Teachey have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
PPE protected critical care staff from COVID-19 transmission
, a new study has found.
“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.
She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.
The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.
“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”
The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.
The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.
“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”
All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.
Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).
Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.
“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”
Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.
The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.
“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”
There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.
These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.
In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.
“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”
Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”
, a new study has found.
“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.
She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.
The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.
“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”
The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.
The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.
“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”
All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.
Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).
Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.
“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”
Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.
The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.
“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”
There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.
These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.
In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.
“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”
Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”
, a new study has found.
“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.
She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.
The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.
“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”
The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.
The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.
“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”
All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.
Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).
Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.
“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”
Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.
The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.
“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”
There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.
These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.
In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.
“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”
Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”
FROM CCC50
ColCORONA: More questions than answers for colchicine in COVID-19
Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.
As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.
But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.
Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”
When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).
Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.
“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.
“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.
“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”
The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.
Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).
The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.
“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”
Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”
Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.
“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.
“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”
According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.
Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.
Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”
The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.
The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”
Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”
The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.
The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.
Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”
Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”
He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.
“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”
Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.
Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.
“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.
The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
A version of this article first appeared on Medscape.com.
Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.
As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.
But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.
Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”
When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).
Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.
“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.
“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.
“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”
The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.
Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).
The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.
“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”
Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”
Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.
“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.
“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”
According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.
Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.
Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”
The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.
The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”
Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”
The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.
The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.
Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”
Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”
He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.
“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”
Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.
Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.
“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.
The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
A version of this article first appeared on Medscape.com.
Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.
As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.
But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.
Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”
When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).
Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.
“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.
“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.
“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”
The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.
Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).
The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.
“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”
Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”
Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.
“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.
“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”
According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.
Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.
Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”
The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.
The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”
Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”
The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.
The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.
Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”
Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”
He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.
“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”
Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.
Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.
“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.
The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
A version of this article first appeared on Medscape.com.