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Psychopharmacology for aggression? Our field’s ‘nonconsensus’ and the risks
A 13-year-old boy with ADHD, combined type, presents to his family physician with his parents. His parents called for an appointment outside of his routine follow-up care to discuss what they should do to address their son’s new “aggressive behaviors.” He will throw objects when angry, yell, and slam doors at home when he is told to turn off video games. He used to play soccer but doesn’t anymore. He has maintained very good grades and friends. There is not a concern for substance abuse at this time.He speaks in curt sentences during the appointment, and he has his arms crossed or is looking out of the window the entire time.
His parents share in front on him that he has always been a “difficult child” (their words), but they now are struggling to adjust to his aggressive tendencies as he ages. He is growing bigger and angrier. He will not attend therapy and will not see a consultation psychiatrist in the office. A variety of stimulant trials including Ritalin and amphetamine preparations to manage impulsivity in ADHD were ineffective to curb his aggression, and he doesn’t want to take any medication.
They ask, what do we do? They are not worried for their safety but living like this is eroding their quality of life as a family, and the dynamic seems destined to get worse before it gets better.
They wonder, is there a next medication step to manage his aggression?
A family physician presented the above situation to me in my role as a child and adolescent psychiatrist in the medical home. It led us to a fruitful discussion of aggression and what can be done to help families who are all too often in situations like the above, then in your office looking for immediate solutions. The questions are, what can be done with an aggressive child, even and especially without the child’s buy-in to work on that as a problem?
Psychoeducation can go a long way in helping families rethink aggression as a symptom of something deeper, either in the environment or a diagnosis, although we all can empathize with the desire to reconcile the above behavior immediately.
Characterize the aggression
First, it can be helpful to identify a child’s aggression type. There are two types of aggression, reactive and proactive. We most often see reactive aggression in our clinics, which is aggression as a defensive and impulsive response to something in the environment (often limit-setting, as above). Proactive aggression is premeditated and may appear as aggression for aggression’s sake without the emotional drive behind it.
Secondly, it also can be helpful to know that externalizing and internalizing symptoms can represent different sides of the same coin, with the proverbial “coin” as “emotion” and the associated behaviors (throwing objects, in the above example) as the “signs” that there is a complex difficulty in managing painful emotions. Some children (and adults too!) tend to “externalize” strong emotions as aggression or irritability with others, while others “internalize” them by retreating with internal suffering such as “anxiety and depression.” These styles also can be similar among children and their parents.
With those two points in mind, it’s important to consider the diagnosis, which would guide treatment. It’s generally agreed upon that “reactive aggression” is more likely to be related to underlying untreated ADHD, or a depressive or anxiety disorder. This is much more amenable to treatment than aggression related to oppositional defiant disorder or conduct disorder, which are more defined by proactive forms of aggression.
You can pick up on family dynamics that may inadvertently reinforce the same behaviors they so wish to change. In the above example, the parents have clearly identified their son as “the problem.” You can imagine the difficulty of going to school and being a “problem,” and then coming home and feeling the same way. This negative perception can erode a child’s self-esteem over time, which may appear as disengagement or simply not caring in an appointment. It may become harder and harder to engage the child in psychotherapy or even in taking a medication as their only means of resistance to that painful notion about oneself as the “problem.”
It can be useful to begin appointments with “what is going well?” (in the example above, he “has friends and is maintaining grades”) and “what do you like most about your child?” As we all know, positive reinforcement is more powerful than its counterpart. Also problems in a family often are complex, and may involve many family members needing to change to meet their goals, not just the child.
Why you should try behavioral interventions first
Behavioral interventions are the first step always. Parents can do behavioral interventions and change their parenting and family environment through their own behavioral changes – commonly called parent management training. They can assess antecedents of aggression and their own responses, which may contribute or perpetuate a cycle of the aggression – such as giving attention or giving in to fewer limitations to avoid a fight. This small but important point can help protect against a feeling of helplessness that a child will not engage in therapy or skills-building.
In answering the clinician’s question about what to do next, I often feel like the question embedded in this is “what medication is next?” There is a felt pressure to do something “right now” conveyed to a clinician. This drives the impulse to prescribe something immediately – and likely more risky and with less of an evidence base – even before trying the known psychotherapy interventions that have the most evidence to change aggressive tendencies.
In looking deeper into this consultation case, I also found more “food for thought” for one’s thinking about aggression and psychopharmacology in cases like the above: Aggression isn’t an uncomplicated symptom that one can address immediately, and therefore we cannot rely on symptom-specific management to eradicate it. This is similar to prescribing Tylenol to manage a general ache or pain; if the pain persists, we want to know the “whys” of the pain persisting.
Thankfully, there are ways that a parent can better understand behaviors with this philosophy in mind. Applied Behavioral Analysis1 offers some helpful ideas, not only for children with autism spectrum disorder, but that can be applied to one’s understanding of other’s behavior in general. ABA pays attention to antecedents, perpetuating factors, and consequences as well as their interplay in understanding behaviors. You can encourage a family – rather than wanting to “get rid of a problem behavior” – to try to understand it and come up, with help from a psychotherapist or other professional, with a deeper evaluation of the behavior and a specific, collaborative plan.
Most experts see that ADHD, anxiety disorders, depressive disorders, and unrecognized learning disabilities, in sum, are more common underpinnings than not with aggressive children. This also can be confounded by an environment with parents who have those diagnoses untreated as well. Aggression should raise a red flag in our clinics to consider the above even if a family or child simply says aggression is the one issue, and it’s only the child with the issue.
While there have been attempts to find a “spot treatment” for aggression in a medication, medications not only fail to address the underlying issues many times, but have little evidence that support them and may do more harm long term than good.2
Kids need outlets for “normal aggressive drives.” And puberty, as in the case above, is a time of intense emotions of all varieties. In the example above, you may notice that the child is no longer playing soccer, which was likely serving some protective function in many ways for him and as a positive outlet for aggression. In the same way, you may see that kids who are more sedentary or idle (playing unrestricted video games now instead of sports, ) would benefit from revisiting outlets or finding new ones as a family.
Consider medications if the underlying diagnosis merits it
We generally seek to find and treat the underlying diagnosis, if it exists, in the following ways.
If a child has ADHD, as in the case above, you can trial a stimulant or an alpha-adrenergic agent to target impulsivity if that is suspected as the driver of aggression. This may include guanfacine (long-acting Intuniv at night, but I would choose lower dosing such as 0.5 mg to 1 mg at bedtime) to manage ADHD. However, the evidence base that management of ADHD improves aggressive behaviors at all or on their own, is scant. In addition, these medications can represent more harm than good as well, although they are perceived as more innocuous than their antipsychotic counterparts. For example, some patients can begin to have bed-wetting accidents in the evening or become sleepy in classes, which can further erode their sense of self-confidence even if this is clearly attributable to a medication side effect and resolves once the agent is reduced or removed.
In the same way to reorient to diagnosis with children with aggression, you can consider an SSRI for an anxiety disorder or irritable depression. But know that it’s a rare thing for children to say specifically that they are struggling with their emotions, whether they are angry, sad, or nervous and that a deeper dive into this may be warranted. Data by Connor DF et al.3 may indicate anxiety disorders should be highest on one’s differential diagnosis in aggression, followed by consideration for ADHD, which may be a different assumption than one would expect.
Mood stabilizers –lamotrigine (Lamictal), divalproex sodium (Depakote), and lithium – and antipsychotics – aripiprazole (Abilify) and risperidone (Risperdal) – are risky medications and the use of them contradicts the first point, agreed upon by most experts, that diagnosis should drive treatment. One is hardly ever treating a young child for psychosis or bipolar disorder in these circumstances of episodic, reactive aggression. Antipsychotics also carry the notorious risks of metabolic syndrome, among other risks to overall health, which becomes an additive risk over time and potentially into adulthood. I once heard in my child adolescent psychiatry training the haunting phase, “yes, they can ‘work’ quickly but they can work ‘almost too well,’ ” meaning they can sedate or tranquilize an aggressive child when the real goal should be to understand, diagnose, and intervene in ways that see the “big picture” of aggression.
Benzodiazepines generally are avoided in children due to disinhibition and often not even considered, in these circumstances, as they are in adults to manage agitation or aggression, due to this fact.
In many instances in working with families, our role in primary care can be one of illuminating children’s behaviors not just as symptoms to treat, but to understand deeply. This is as true for aggression as it is for anxiety.
Finally, I am reminded of the common question I receive from adult patients in primary care who ask me if anyone has yet made a medication to lose weight that’s safe and effective. Then the counseling commences on our fantasies, from our patients and ourselves, about what medications can do for us and our risks therein.
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. Email her at pdnews@mdedge.com.
References
1. ABA in the Treatment of Aggressive Behavior Disorder and Lack of Impulse Control.
2. Managing Aggression in Children: A Practical Approach, The Carlat Child Psychiatry Report, May 2010, The Explosive Child.
3. Child Psychiatry Hum Dev. 2006 May;37[1]:1-14.
A 13-year-old boy with ADHD, combined type, presents to his family physician with his parents. His parents called for an appointment outside of his routine follow-up care to discuss what they should do to address their son’s new “aggressive behaviors.” He will throw objects when angry, yell, and slam doors at home when he is told to turn off video games. He used to play soccer but doesn’t anymore. He has maintained very good grades and friends. There is not a concern for substance abuse at this time.He speaks in curt sentences during the appointment, and he has his arms crossed or is looking out of the window the entire time.
His parents share in front on him that he has always been a “difficult child” (their words), but they now are struggling to adjust to his aggressive tendencies as he ages. He is growing bigger and angrier. He will not attend therapy and will not see a consultation psychiatrist in the office. A variety of stimulant trials including Ritalin and amphetamine preparations to manage impulsivity in ADHD were ineffective to curb his aggression, and he doesn’t want to take any medication.
They ask, what do we do? They are not worried for their safety but living like this is eroding their quality of life as a family, and the dynamic seems destined to get worse before it gets better.
They wonder, is there a next medication step to manage his aggression?
A family physician presented the above situation to me in my role as a child and adolescent psychiatrist in the medical home. It led us to a fruitful discussion of aggression and what can be done to help families who are all too often in situations like the above, then in your office looking for immediate solutions. The questions are, what can be done with an aggressive child, even and especially without the child’s buy-in to work on that as a problem?
Psychoeducation can go a long way in helping families rethink aggression as a symptom of something deeper, either in the environment or a diagnosis, although we all can empathize with the desire to reconcile the above behavior immediately.
Characterize the aggression
First, it can be helpful to identify a child’s aggression type. There are two types of aggression, reactive and proactive. We most often see reactive aggression in our clinics, which is aggression as a defensive and impulsive response to something in the environment (often limit-setting, as above). Proactive aggression is premeditated and may appear as aggression for aggression’s sake without the emotional drive behind it.
Secondly, it also can be helpful to know that externalizing and internalizing symptoms can represent different sides of the same coin, with the proverbial “coin” as “emotion” and the associated behaviors (throwing objects, in the above example) as the “signs” that there is a complex difficulty in managing painful emotions. Some children (and adults too!) tend to “externalize” strong emotions as aggression or irritability with others, while others “internalize” them by retreating with internal suffering such as “anxiety and depression.” These styles also can be similar among children and their parents.
With those two points in mind, it’s important to consider the diagnosis, which would guide treatment. It’s generally agreed upon that “reactive aggression” is more likely to be related to underlying untreated ADHD, or a depressive or anxiety disorder. This is much more amenable to treatment than aggression related to oppositional defiant disorder or conduct disorder, which are more defined by proactive forms of aggression.
You can pick up on family dynamics that may inadvertently reinforce the same behaviors they so wish to change. In the above example, the parents have clearly identified their son as “the problem.” You can imagine the difficulty of going to school and being a “problem,” and then coming home and feeling the same way. This negative perception can erode a child’s self-esteem over time, which may appear as disengagement or simply not caring in an appointment. It may become harder and harder to engage the child in psychotherapy or even in taking a medication as their only means of resistance to that painful notion about oneself as the “problem.”
It can be useful to begin appointments with “what is going well?” (in the example above, he “has friends and is maintaining grades”) and “what do you like most about your child?” As we all know, positive reinforcement is more powerful than its counterpart. Also problems in a family often are complex, and may involve many family members needing to change to meet their goals, not just the child.
Why you should try behavioral interventions first
Behavioral interventions are the first step always. Parents can do behavioral interventions and change their parenting and family environment through their own behavioral changes – commonly called parent management training. They can assess antecedents of aggression and their own responses, which may contribute or perpetuate a cycle of the aggression – such as giving attention or giving in to fewer limitations to avoid a fight. This small but important point can help protect against a feeling of helplessness that a child will not engage in therapy or skills-building.
In answering the clinician’s question about what to do next, I often feel like the question embedded in this is “what medication is next?” There is a felt pressure to do something “right now” conveyed to a clinician. This drives the impulse to prescribe something immediately – and likely more risky and with less of an evidence base – even before trying the known psychotherapy interventions that have the most evidence to change aggressive tendencies.
In looking deeper into this consultation case, I also found more “food for thought” for one’s thinking about aggression and psychopharmacology in cases like the above: Aggression isn’t an uncomplicated symptom that one can address immediately, and therefore we cannot rely on symptom-specific management to eradicate it. This is similar to prescribing Tylenol to manage a general ache or pain; if the pain persists, we want to know the “whys” of the pain persisting.
Thankfully, there are ways that a parent can better understand behaviors with this philosophy in mind. Applied Behavioral Analysis1 offers some helpful ideas, not only for children with autism spectrum disorder, but that can be applied to one’s understanding of other’s behavior in general. ABA pays attention to antecedents, perpetuating factors, and consequences as well as their interplay in understanding behaviors. You can encourage a family – rather than wanting to “get rid of a problem behavior” – to try to understand it and come up, with help from a psychotherapist or other professional, with a deeper evaluation of the behavior and a specific, collaborative plan.
Most experts see that ADHD, anxiety disorders, depressive disorders, and unrecognized learning disabilities, in sum, are more common underpinnings than not with aggressive children. This also can be confounded by an environment with parents who have those diagnoses untreated as well. Aggression should raise a red flag in our clinics to consider the above even if a family or child simply says aggression is the one issue, and it’s only the child with the issue.
While there have been attempts to find a “spot treatment” for aggression in a medication, medications not only fail to address the underlying issues many times, but have little evidence that support them and may do more harm long term than good.2
Kids need outlets for “normal aggressive drives.” And puberty, as in the case above, is a time of intense emotions of all varieties. In the example above, you may notice that the child is no longer playing soccer, which was likely serving some protective function in many ways for him and as a positive outlet for aggression. In the same way, you may see that kids who are more sedentary or idle (playing unrestricted video games now instead of sports, ) would benefit from revisiting outlets or finding new ones as a family.
Consider medications if the underlying diagnosis merits it
We generally seek to find and treat the underlying diagnosis, if it exists, in the following ways.
If a child has ADHD, as in the case above, you can trial a stimulant or an alpha-adrenergic agent to target impulsivity if that is suspected as the driver of aggression. This may include guanfacine (long-acting Intuniv at night, but I would choose lower dosing such as 0.5 mg to 1 mg at bedtime) to manage ADHD. However, the evidence base that management of ADHD improves aggressive behaviors at all or on their own, is scant. In addition, these medications can represent more harm than good as well, although they are perceived as more innocuous than their antipsychotic counterparts. For example, some patients can begin to have bed-wetting accidents in the evening or become sleepy in classes, which can further erode their sense of self-confidence even if this is clearly attributable to a medication side effect and resolves once the agent is reduced or removed.
In the same way to reorient to diagnosis with children with aggression, you can consider an SSRI for an anxiety disorder or irritable depression. But know that it’s a rare thing for children to say specifically that they are struggling with their emotions, whether they are angry, sad, or nervous and that a deeper dive into this may be warranted. Data by Connor DF et al.3 may indicate anxiety disorders should be highest on one’s differential diagnosis in aggression, followed by consideration for ADHD, which may be a different assumption than one would expect.
Mood stabilizers –lamotrigine (Lamictal), divalproex sodium (Depakote), and lithium – and antipsychotics – aripiprazole (Abilify) and risperidone (Risperdal) – are risky medications and the use of them contradicts the first point, agreed upon by most experts, that diagnosis should drive treatment. One is hardly ever treating a young child for psychosis or bipolar disorder in these circumstances of episodic, reactive aggression. Antipsychotics also carry the notorious risks of metabolic syndrome, among other risks to overall health, which becomes an additive risk over time and potentially into adulthood. I once heard in my child adolescent psychiatry training the haunting phase, “yes, they can ‘work’ quickly but they can work ‘almost too well,’ ” meaning they can sedate or tranquilize an aggressive child when the real goal should be to understand, diagnose, and intervene in ways that see the “big picture” of aggression.
Benzodiazepines generally are avoided in children due to disinhibition and often not even considered, in these circumstances, as they are in adults to manage agitation or aggression, due to this fact.
In many instances in working with families, our role in primary care can be one of illuminating children’s behaviors not just as symptoms to treat, but to understand deeply. This is as true for aggression as it is for anxiety.
Finally, I am reminded of the common question I receive from adult patients in primary care who ask me if anyone has yet made a medication to lose weight that’s safe and effective. Then the counseling commences on our fantasies, from our patients and ourselves, about what medications can do for us and our risks therein.
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. Email her at pdnews@mdedge.com.
References
1. ABA in the Treatment of Aggressive Behavior Disorder and Lack of Impulse Control.
2. Managing Aggression in Children: A Practical Approach, The Carlat Child Psychiatry Report, May 2010, The Explosive Child.
3. Child Psychiatry Hum Dev. 2006 May;37[1]:1-14.
A 13-year-old boy with ADHD, combined type, presents to his family physician with his parents. His parents called for an appointment outside of his routine follow-up care to discuss what they should do to address their son’s new “aggressive behaviors.” He will throw objects when angry, yell, and slam doors at home when he is told to turn off video games. He used to play soccer but doesn’t anymore. He has maintained very good grades and friends. There is not a concern for substance abuse at this time.He speaks in curt sentences during the appointment, and he has his arms crossed or is looking out of the window the entire time.
His parents share in front on him that he has always been a “difficult child” (their words), but they now are struggling to adjust to his aggressive tendencies as he ages. He is growing bigger and angrier. He will not attend therapy and will not see a consultation psychiatrist in the office. A variety of stimulant trials including Ritalin and amphetamine preparations to manage impulsivity in ADHD were ineffective to curb his aggression, and he doesn’t want to take any medication.
They ask, what do we do? They are not worried for their safety but living like this is eroding their quality of life as a family, and the dynamic seems destined to get worse before it gets better.
They wonder, is there a next medication step to manage his aggression?
A family physician presented the above situation to me in my role as a child and adolescent psychiatrist in the medical home. It led us to a fruitful discussion of aggression and what can be done to help families who are all too often in situations like the above, then in your office looking for immediate solutions. The questions are, what can be done with an aggressive child, even and especially without the child’s buy-in to work on that as a problem?
Psychoeducation can go a long way in helping families rethink aggression as a symptom of something deeper, either in the environment or a diagnosis, although we all can empathize with the desire to reconcile the above behavior immediately.
Characterize the aggression
First, it can be helpful to identify a child’s aggression type. There are two types of aggression, reactive and proactive. We most often see reactive aggression in our clinics, which is aggression as a defensive and impulsive response to something in the environment (often limit-setting, as above). Proactive aggression is premeditated and may appear as aggression for aggression’s sake without the emotional drive behind it.
Secondly, it also can be helpful to know that externalizing and internalizing symptoms can represent different sides of the same coin, with the proverbial “coin” as “emotion” and the associated behaviors (throwing objects, in the above example) as the “signs” that there is a complex difficulty in managing painful emotions. Some children (and adults too!) tend to “externalize” strong emotions as aggression or irritability with others, while others “internalize” them by retreating with internal suffering such as “anxiety and depression.” These styles also can be similar among children and their parents.
With those two points in mind, it’s important to consider the diagnosis, which would guide treatment. It’s generally agreed upon that “reactive aggression” is more likely to be related to underlying untreated ADHD, or a depressive or anxiety disorder. This is much more amenable to treatment than aggression related to oppositional defiant disorder or conduct disorder, which are more defined by proactive forms of aggression.
You can pick up on family dynamics that may inadvertently reinforce the same behaviors they so wish to change. In the above example, the parents have clearly identified their son as “the problem.” You can imagine the difficulty of going to school and being a “problem,” and then coming home and feeling the same way. This negative perception can erode a child’s self-esteem over time, which may appear as disengagement or simply not caring in an appointment. It may become harder and harder to engage the child in psychotherapy or even in taking a medication as their only means of resistance to that painful notion about oneself as the “problem.”
It can be useful to begin appointments with “what is going well?” (in the example above, he “has friends and is maintaining grades”) and “what do you like most about your child?” As we all know, positive reinforcement is more powerful than its counterpart. Also problems in a family often are complex, and may involve many family members needing to change to meet their goals, not just the child.
Why you should try behavioral interventions first
Behavioral interventions are the first step always. Parents can do behavioral interventions and change their parenting and family environment through their own behavioral changes – commonly called parent management training. They can assess antecedents of aggression and their own responses, which may contribute or perpetuate a cycle of the aggression – such as giving attention or giving in to fewer limitations to avoid a fight. This small but important point can help protect against a feeling of helplessness that a child will not engage in therapy or skills-building.
In answering the clinician’s question about what to do next, I often feel like the question embedded in this is “what medication is next?” There is a felt pressure to do something “right now” conveyed to a clinician. This drives the impulse to prescribe something immediately – and likely more risky and with less of an evidence base – even before trying the known psychotherapy interventions that have the most evidence to change aggressive tendencies.
In looking deeper into this consultation case, I also found more “food for thought” for one’s thinking about aggression and psychopharmacology in cases like the above: Aggression isn’t an uncomplicated symptom that one can address immediately, and therefore we cannot rely on symptom-specific management to eradicate it. This is similar to prescribing Tylenol to manage a general ache or pain; if the pain persists, we want to know the “whys” of the pain persisting.
Thankfully, there are ways that a parent can better understand behaviors with this philosophy in mind. Applied Behavioral Analysis1 offers some helpful ideas, not only for children with autism spectrum disorder, but that can be applied to one’s understanding of other’s behavior in general. ABA pays attention to antecedents, perpetuating factors, and consequences as well as their interplay in understanding behaviors. You can encourage a family – rather than wanting to “get rid of a problem behavior” – to try to understand it and come up, with help from a psychotherapist or other professional, with a deeper evaluation of the behavior and a specific, collaborative plan.
Most experts see that ADHD, anxiety disorders, depressive disorders, and unrecognized learning disabilities, in sum, are more common underpinnings than not with aggressive children. This also can be confounded by an environment with parents who have those diagnoses untreated as well. Aggression should raise a red flag in our clinics to consider the above even if a family or child simply says aggression is the one issue, and it’s only the child with the issue.
While there have been attempts to find a “spot treatment” for aggression in a medication, medications not only fail to address the underlying issues many times, but have little evidence that support them and may do more harm long term than good.2
Kids need outlets for “normal aggressive drives.” And puberty, as in the case above, is a time of intense emotions of all varieties. In the example above, you may notice that the child is no longer playing soccer, which was likely serving some protective function in many ways for him and as a positive outlet for aggression. In the same way, you may see that kids who are more sedentary or idle (playing unrestricted video games now instead of sports, ) would benefit from revisiting outlets or finding new ones as a family.
Consider medications if the underlying diagnosis merits it
We generally seek to find and treat the underlying diagnosis, if it exists, in the following ways.
If a child has ADHD, as in the case above, you can trial a stimulant or an alpha-adrenergic agent to target impulsivity if that is suspected as the driver of aggression. This may include guanfacine (long-acting Intuniv at night, but I would choose lower dosing such as 0.5 mg to 1 mg at bedtime) to manage ADHD. However, the evidence base that management of ADHD improves aggressive behaviors at all or on their own, is scant. In addition, these medications can represent more harm than good as well, although they are perceived as more innocuous than their antipsychotic counterparts. For example, some patients can begin to have bed-wetting accidents in the evening or become sleepy in classes, which can further erode their sense of self-confidence even if this is clearly attributable to a medication side effect and resolves once the agent is reduced or removed.
In the same way to reorient to diagnosis with children with aggression, you can consider an SSRI for an anxiety disorder or irritable depression. But know that it’s a rare thing for children to say specifically that they are struggling with their emotions, whether they are angry, sad, or nervous and that a deeper dive into this may be warranted. Data by Connor DF et al.3 may indicate anxiety disorders should be highest on one’s differential diagnosis in aggression, followed by consideration for ADHD, which may be a different assumption than one would expect.
Mood stabilizers –lamotrigine (Lamictal), divalproex sodium (Depakote), and lithium – and antipsychotics – aripiprazole (Abilify) and risperidone (Risperdal) – are risky medications and the use of them contradicts the first point, agreed upon by most experts, that diagnosis should drive treatment. One is hardly ever treating a young child for psychosis or bipolar disorder in these circumstances of episodic, reactive aggression. Antipsychotics also carry the notorious risks of metabolic syndrome, among other risks to overall health, which becomes an additive risk over time and potentially into adulthood. I once heard in my child adolescent psychiatry training the haunting phase, “yes, they can ‘work’ quickly but they can work ‘almost too well,’ ” meaning they can sedate or tranquilize an aggressive child when the real goal should be to understand, diagnose, and intervene in ways that see the “big picture” of aggression.
Benzodiazepines generally are avoided in children due to disinhibition and often not even considered, in these circumstances, as they are in adults to manage agitation or aggression, due to this fact.
In many instances in working with families, our role in primary care can be one of illuminating children’s behaviors not just as symptoms to treat, but to understand deeply. This is as true for aggression as it is for anxiety.
Finally, I am reminded of the common question I receive from adult patients in primary care who ask me if anyone has yet made a medication to lose weight that’s safe and effective. Then the counseling commences on our fantasies, from our patients and ourselves, about what medications can do for us and our risks therein.
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. Email her at pdnews@mdedge.com.
References
1. ABA in the Treatment of Aggressive Behavior Disorder and Lack of Impulse Control.
2. Managing Aggression in Children: A Practical Approach, The Carlat Child Psychiatry Report, May 2010, The Explosive Child.
3. Child Psychiatry Hum Dev. 2006 May;37[1]:1-14.
Dupilumab for severe AD: Expert advocates continuous treatment
LAHAINA, HAWAII – rather than treatment on an as-needed basis, Andrew Blauvelt, MD, advised at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“I view atopic dermatitis as a chronic disease requiring chronic treatment. So be very careful about stopping. We know that if you start and stop biologics you’re going to be far more prone to develop antidrug antibodies resulting in drug resistance than with continual dosing,” said Dr. Blauvelt, a dermatologist and clinical trialist who is president of the Oregon Medical Research Center, Portland.
He said dupilumab (Dupixent) seldom induces disease remission as defined by clear skin while off all drugs for at least 1 year, although he has a few patients who seem to be exceptions. Yet clearly dupilumab doesn’t change an individual’s predisposing genetics or environmental allergen exposure pattern, so it’s best to think of it as a treatment for the long haul.
Dr. Blauvelt considers dupilumab far and away the best medication for treatment of adults and teenagers whose atopic dermatitis (AD) is uncontrolled with topical therapy. Payers often balk at authorizing dupilumab unless a patient has first undergone an unsuccessful trial of cyclosporine or methotrexate, which are far less expensive. But that’s not what the expert consensus guidelines recommend (Ann Allergy Asthma Immunol. 2018 Jan;120[1]:10-22.e2).
“The guidelines don’t suggest that failure on methotrexate or cyclosporine should be a prerequisite for dupilumab. So if you’re having problems with an insurance company and you really want to use dupilumab, you can point to this paper and say, ‘Look, the experts do not recommend step therapy, we can go directly to dupilumab.’ And the dupilumab label says simply that failure of topical therapy is required before being allowed to use dupilumab. So both the label and the experts say you don’t have to go through a bunch of steps in order to get to what I consider the very best drug for our patients,” he explained.
Both cyclosporine and methotrexate are far more broadly immunosuppressive and hence less safe than dupilumab. Both require laboratory monitoring. In contrast, blood work isn’t required in patients on dupilumab; in fact, Dr. Blauvelt considers it an unwise use of resources. Nor is tuberculosis testing advised prior to starting dupilumab.
When he can’t get authorization for dupilumab, Dr. Blauvelt’s go-to drug is methotrexate at 15-25 mg/week. It’s not as effective as cyclosporine for rapid clearing, but it’s safer for long-term use.
“Methotrexate is the devil we know – we know how to use it, and we know how to monitor for it,” he commented, adding that he reserves cyclosporine for a maximum of a month or 2 of acute crisis management, or as a bridge in getting patients off of systemic corticosteroids.
Set realistic efficacy expectations
Dermatologists who prescribe the newest biologics for psoriasis are accustomed to routinely seeing PASI 90 responses and even complete disease clearing. However, AD is a more challenging disease. In the landmark dupilumab phase 3 randomized trials, roughly two-thirds of patients achieved an Eczema Area and Severity Index (EASI) 75 response, with a mean 80% improvement in EASI symptom scores over baseline. Roughly 20% of dupilumab-treated adults with AD achieve disease clearance, and a similar percentage become almost clear. The improvements are durable in long-term follow-up studies.
“Dupilumab doesn’t get a lot of people to zero. They’re not going to be completely clearing their eczema. So they shouldn’t be freaking out if they still have eczema. What they can expect is diminution of the disease to much lower levels,” Dr. Blauvelt said.
The marked improvement in quality of life that occurs with dupilumab therapy isn’t adequately captured by EASI scores. “In my experience, more than 80%-90% of patients are happy on this drug,” Dr. Blauvelt said.
Conference codirector Linda Stein Gold, MD, agreed, commenting that she has found dupilumab to be “absolutely life altering” for her patients with severe AD.
“They know they still have AD, but now they can go whole days without thinking about it,” said Dr. Stein Gold, director of dermatology research and head of the division of dermatology at the Henry Ford Health System in Detroit.
Dr. Blauvelt noted that most of his patients on dupilumab remain on topical therapy, typically with triamcinolone on the body and hydrocortisone on the face. What he terms “miniflares” in patients on dupilumab are not at all unusual, but they’re readily manageable.
“Flares that used to last for weeks now last for a day or 2, maybe 3, and then it’s back to normal in patients on dupilumab,” Dr. Blauvelt said.
Safety
Dupilumab is a targeted inhibitor of interleukins-4 and -13, cytokines involved in allergy-mediated inflammation and the control of parasitic infections, but which have no bearing on control of bacterial or viral infections or malignancies. Indeed, the randomized trials have demonstrated that the incidence of skin infections is actually lower with dupilumab than with placebo.
“You’re improving the skin barrier so much that they’re not going to be getting staph or herpes simplex,” he explained.
The main side effect consists of dupilumab-associated eye issues. These occur in up to 20% of treated patients and encompass a spectrum ranging from dry eye to nonallergic conjunctivitis, inflammation of the eyelid, and keratitis. The mechanism is unknown. The condition is not infectious and doesn’t affect vision. Intriguingly, it doesn’t occur in patients with asthma, a disease for which dupilumab is also approved.
“Ask about eye issues at every office visit,” the dermatologist urged.
He sends all of his AD patients with dupilumab-associated eye issues to a single trusted local ophthalmologist and lets him manage the condition, which is generally mild to moderate. Eye issues have resulted in discontinuation of dupilumab in only 2 of the roughly 150 AD patients Dr. Blauvelt has placed on the biologic. The ophthalmologist generally relies upon lubricating eye drops and a couple of weeks of steroid eye drops or, in some cases, topical cyclosporine 0.05% ophthalmic emulsion, followed by episodic use of the steroid eye drops on an as-needed basis.
Residual facial disease in AD patients on dupilumab can be caused by a variety of causes, including breakthrough AD, rosacea, allergic contact dermatitis, steroid withdrawal, or photosensitivity, with Demodex thought to play a role in some cases.
Dr. Blauvelt reported serving as a scientific adviser to and paid clinical trial investigator for several dozen pharmaceutical companies. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – rather than treatment on an as-needed basis, Andrew Blauvelt, MD, advised at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“I view atopic dermatitis as a chronic disease requiring chronic treatment. So be very careful about stopping. We know that if you start and stop biologics you’re going to be far more prone to develop antidrug antibodies resulting in drug resistance than with continual dosing,” said Dr. Blauvelt, a dermatologist and clinical trialist who is president of the Oregon Medical Research Center, Portland.
He said dupilumab (Dupixent) seldom induces disease remission as defined by clear skin while off all drugs for at least 1 year, although he has a few patients who seem to be exceptions. Yet clearly dupilumab doesn’t change an individual’s predisposing genetics or environmental allergen exposure pattern, so it’s best to think of it as a treatment for the long haul.
Dr. Blauvelt considers dupilumab far and away the best medication for treatment of adults and teenagers whose atopic dermatitis (AD) is uncontrolled with topical therapy. Payers often balk at authorizing dupilumab unless a patient has first undergone an unsuccessful trial of cyclosporine or methotrexate, which are far less expensive. But that’s not what the expert consensus guidelines recommend (Ann Allergy Asthma Immunol. 2018 Jan;120[1]:10-22.e2).
“The guidelines don’t suggest that failure on methotrexate or cyclosporine should be a prerequisite for dupilumab. So if you’re having problems with an insurance company and you really want to use dupilumab, you can point to this paper and say, ‘Look, the experts do not recommend step therapy, we can go directly to dupilumab.’ And the dupilumab label says simply that failure of topical therapy is required before being allowed to use dupilumab. So both the label and the experts say you don’t have to go through a bunch of steps in order to get to what I consider the very best drug for our patients,” he explained.
Both cyclosporine and methotrexate are far more broadly immunosuppressive and hence less safe than dupilumab. Both require laboratory monitoring. In contrast, blood work isn’t required in patients on dupilumab; in fact, Dr. Blauvelt considers it an unwise use of resources. Nor is tuberculosis testing advised prior to starting dupilumab.
When he can’t get authorization for dupilumab, Dr. Blauvelt’s go-to drug is methotrexate at 15-25 mg/week. It’s not as effective as cyclosporine for rapid clearing, but it’s safer for long-term use.
“Methotrexate is the devil we know – we know how to use it, and we know how to monitor for it,” he commented, adding that he reserves cyclosporine for a maximum of a month or 2 of acute crisis management, or as a bridge in getting patients off of systemic corticosteroids.
Set realistic efficacy expectations
Dermatologists who prescribe the newest biologics for psoriasis are accustomed to routinely seeing PASI 90 responses and even complete disease clearing. However, AD is a more challenging disease. In the landmark dupilumab phase 3 randomized trials, roughly two-thirds of patients achieved an Eczema Area and Severity Index (EASI) 75 response, with a mean 80% improvement in EASI symptom scores over baseline. Roughly 20% of dupilumab-treated adults with AD achieve disease clearance, and a similar percentage become almost clear. The improvements are durable in long-term follow-up studies.
“Dupilumab doesn’t get a lot of people to zero. They’re not going to be completely clearing their eczema. So they shouldn’t be freaking out if they still have eczema. What they can expect is diminution of the disease to much lower levels,” Dr. Blauvelt said.
The marked improvement in quality of life that occurs with dupilumab therapy isn’t adequately captured by EASI scores. “In my experience, more than 80%-90% of patients are happy on this drug,” Dr. Blauvelt said.
Conference codirector Linda Stein Gold, MD, agreed, commenting that she has found dupilumab to be “absolutely life altering” for her patients with severe AD.
“They know they still have AD, but now they can go whole days without thinking about it,” said Dr. Stein Gold, director of dermatology research and head of the division of dermatology at the Henry Ford Health System in Detroit.
Dr. Blauvelt noted that most of his patients on dupilumab remain on topical therapy, typically with triamcinolone on the body and hydrocortisone on the face. What he terms “miniflares” in patients on dupilumab are not at all unusual, but they’re readily manageable.
“Flares that used to last for weeks now last for a day or 2, maybe 3, and then it’s back to normal in patients on dupilumab,” Dr. Blauvelt said.
Safety
Dupilumab is a targeted inhibitor of interleukins-4 and -13, cytokines involved in allergy-mediated inflammation and the control of parasitic infections, but which have no bearing on control of bacterial or viral infections or malignancies. Indeed, the randomized trials have demonstrated that the incidence of skin infections is actually lower with dupilumab than with placebo.
“You’re improving the skin barrier so much that they’re not going to be getting staph or herpes simplex,” he explained.
The main side effect consists of dupilumab-associated eye issues. These occur in up to 20% of treated patients and encompass a spectrum ranging from dry eye to nonallergic conjunctivitis, inflammation of the eyelid, and keratitis. The mechanism is unknown. The condition is not infectious and doesn’t affect vision. Intriguingly, it doesn’t occur in patients with asthma, a disease for which dupilumab is also approved.
“Ask about eye issues at every office visit,” the dermatologist urged.
He sends all of his AD patients with dupilumab-associated eye issues to a single trusted local ophthalmologist and lets him manage the condition, which is generally mild to moderate. Eye issues have resulted in discontinuation of dupilumab in only 2 of the roughly 150 AD patients Dr. Blauvelt has placed on the biologic. The ophthalmologist generally relies upon lubricating eye drops and a couple of weeks of steroid eye drops or, in some cases, topical cyclosporine 0.05% ophthalmic emulsion, followed by episodic use of the steroid eye drops on an as-needed basis.
Residual facial disease in AD patients on dupilumab can be caused by a variety of causes, including breakthrough AD, rosacea, allergic contact dermatitis, steroid withdrawal, or photosensitivity, with Demodex thought to play a role in some cases.
Dr. Blauvelt reported serving as a scientific adviser to and paid clinical trial investigator for several dozen pharmaceutical companies. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – rather than treatment on an as-needed basis, Andrew Blauvelt, MD, advised at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“I view atopic dermatitis as a chronic disease requiring chronic treatment. So be very careful about stopping. We know that if you start and stop biologics you’re going to be far more prone to develop antidrug antibodies resulting in drug resistance than with continual dosing,” said Dr. Blauvelt, a dermatologist and clinical trialist who is president of the Oregon Medical Research Center, Portland.
He said dupilumab (Dupixent) seldom induces disease remission as defined by clear skin while off all drugs for at least 1 year, although he has a few patients who seem to be exceptions. Yet clearly dupilumab doesn’t change an individual’s predisposing genetics or environmental allergen exposure pattern, so it’s best to think of it as a treatment for the long haul.
Dr. Blauvelt considers dupilumab far and away the best medication for treatment of adults and teenagers whose atopic dermatitis (AD) is uncontrolled with topical therapy. Payers often balk at authorizing dupilumab unless a patient has first undergone an unsuccessful trial of cyclosporine or methotrexate, which are far less expensive. But that’s not what the expert consensus guidelines recommend (Ann Allergy Asthma Immunol. 2018 Jan;120[1]:10-22.e2).
“The guidelines don’t suggest that failure on methotrexate or cyclosporine should be a prerequisite for dupilumab. So if you’re having problems with an insurance company and you really want to use dupilumab, you can point to this paper and say, ‘Look, the experts do not recommend step therapy, we can go directly to dupilumab.’ And the dupilumab label says simply that failure of topical therapy is required before being allowed to use dupilumab. So both the label and the experts say you don’t have to go through a bunch of steps in order to get to what I consider the very best drug for our patients,” he explained.
Both cyclosporine and methotrexate are far more broadly immunosuppressive and hence less safe than dupilumab. Both require laboratory monitoring. In contrast, blood work isn’t required in patients on dupilumab; in fact, Dr. Blauvelt considers it an unwise use of resources. Nor is tuberculosis testing advised prior to starting dupilumab.
When he can’t get authorization for dupilumab, Dr. Blauvelt’s go-to drug is methotrexate at 15-25 mg/week. It’s not as effective as cyclosporine for rapid clearing, but it’s safer for long-term use.
“Methotrexate is the devil we know – we know how to use it, and we know how to monitor for it,” he commented, adding that he reserves cyclosporine for a maximum of a month or 2 of acute crisis management, or as a bridge in getting patients off of systemic corticosteroids.
Set realistic efficacy expectations
Dermatologists who prescribe the newest biologics for psoriasis are accustomed to routinely seeing PASI 90 responses and even complete disease clearing. However, AD is a more challenging disease. In the landmark dupilumab phase 3 randomized trials, roughly two-thirds of patients achieved an Eczema Area and Severity Index (EASI) 75 response, with a mean 80% improvement in EASI symptom scores over baseline. Roughly 20% of dupilumab-treated adults with AD achieve disease clearance, and a similar percentage become almost clear. The improvements are durable in long-term follow-up studies.
“Dupilumab doesn’t get a lot of people to zero. They’re not going to be completely clearing their eczema. So they shouldn’t be freaking out if they still have eczema. What they can expect is diminution of the disease to much lower levels,” Dr. Blauvelt said.
The marked improvement in quality of life that occurs with dupilumab therapy isn’t adequately captured by EASI scores. “In my experience, more than 80%-90% of patients are happy on this drug,” Dr. Blauvelt said.
Conference codirector Linda Stein Gold, MD, agreed, commenting that she has found dupilumab to be “absolutely life altering” for her patients with severe AD.
“They know they still have AD, but now they can go whole days without thinking about it,” said Dr. Stein Gold, director of dermatology research and head of the division of dermatology at the Henry Ford Health System in Detroit.
Dr. Blauvelt noted that most of his patients on dupilumab remain on topical therapy, typically with triamcinolone on the body and hydrocortisone on the face. What he terms “miniflares” in patients on dupilumab are not at all unusual, but they’re readily manageable.
“Flares that used to last for weeks now last for a day or 2, maybe 3, and then it’s back to normal in patients on dupilumab,” Dr. Blauvelt said.
Safety
Dupilumab is a targeted inhibitor of interleukins-4 and -13, cytokines involved in allergy-mediated inflammation and the control of parasitic infections, but which have no bearing on control of bacterial or viral infections or malignancies. Indeed, the randomized trials have demonstrated that the incidence of skin infections is actually lower with dupilumab than with placebo.
“You’re improving the skin barrier so much that they’re not going to be getting staph or herpes simplex,” he explained.
The main side effect consists of dupilumab-associated eye issues. These occur in up to 20% of treated patients and encompass a spectrum ranging from dry eye to nonallergic conjunctivitis, inflammation of the eyelid, and keratitis. The mechanism is unknown. The condition is not infectious and doesn’t affect vision. Intriguingly, it doesn’t occur in patients with asthma, a disease for which dupilumab is also approved.
“Ask about eye issues at every office visit,” the dermatologist urged.
He sends all of his AD patients with dupilumab-associated eye issues to a single trusted local ophthalmologist and lets him manage the condition, which is generally mild to moderate. Eye issues have resulted in discontinuation of dupilumab in only 2 of the roughly 150 AD patients Dr. Blauvelt has placed on the biologic. The ophthalmologist generally relies upon lubricating eye drops and a couple of weeks of steroid eye drops or, in some cases, topical cyclosporine 0.05% ophthalmic emulsion, followed by episodic use of the steroid eye drops on an as-needed basis.
Residual facial disease in AD patients on dupilumab can be caused by a variety of causes, including breakthrough AD, rosacea, allergic contact dermatitis, steroid withdrawal, or photosensitivity, with Demodex thought to play a role in some cases.
Dr. Blauvelt reported serving as a scientific adviser to and paid clinical trial investigator for several dozen pharmaceutical companies. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT OPINION FROM SDEF HAWAII DERMATOLOGY SEMINAR
Sharpest spikes in pediatric diabetes seen in Asian, Pacific Islander youth
according to a review of almost 70,000 children in the SEARCH for Diabetes in Youth Study, an ongoing, population-based surveillance project of individuals younger than 20 years.
“For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites,” wrote the investigators, led by Jasmin Divers, PhD, of the division of health services research, department of foundations of medicine, at New York University. “These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.”
SEARCH identified 14,638 cases of pediatric type 1 diabetes and 3,916 cases of type 2 diabetes from 2002 to 2015. The study draws participants from all 64 counties in Colorado, plus selected Indian reservations in Arizona and New Mexico under the direction of Colorado; all 46 counties in South Carolina; 8 in Ohio; 5 in Washington; and Kaiser Permanente Southern California health plan enrollees in 7 counties.
The investigators found steeper increases in age- and sex-adjusted incidence of type 1 diabetes from 2002 to 2015 among black youth (2.7% per year), Hispanic youth (4%), and Asian and Pacific Islander youth (4.4%), than among their white counterparts (0.7%). Incidence among Asians and Pacific Islanders did not change significantly during 2002-2010, but increased steeply during 2011-2015 (8.5% per year) for unknown reasons.
“In parallel with increased obesity prevalence in U.S. youths, the incidence of type 2 diabetes among adolescents has increased at a higher rate than that of type 1 diabetes, especially among racial-/ethnic-minority youths,” the authors noted.
The number of new cases of type 2 diagnosed in children younger than 10 years were too few to report on (181 total cases during 2002-2015), so the incidence analysis was limited to children who were aged 10-19 years at diagnosis. The steepest annual percentage changes were among Asians and Pacific Islander youth (7.7% per year), followed by Hispanic (6.5%), black (6.0%), and American Indian (3.7%) youth.
“Although the SEARCH population is similar demographically to the U.S. youth population, it is not designed to be nationally representative,” which is one of the limitations of the study, the investigators wrote.
The authors reported having no conflicts of interest.
SOURCE: Divers J et al. MMWR Morb Mortal Wkly Rep. 2020;69:161-5.
according to a review of almost 70,000 children in the SEARCH for Diabetes in Youth Study, an ongoing, population-based surveillance project of individuals younger than 20 years.
“For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites,” wrote the investigators, led by Jasmin Divers, PhD, of the division of health services research, department of foundations of medicine, at New York University. “These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.”
SEARCH identified 14,638 cases of pediatric type 1 diabetes and 3,916 cases of type 2 diabetes from 2002 to 2015. The study draws participants from all 64 counties in Colorado, plus selected Indian reservations in Arizona and New Mexico under the direction of Colorado; all 46 counties in South Carolina; 8 in Ohio; 5 in Washington; and Kaiser Permanente Southern California health plan enrollees in 7 counties.
The investigators found steeper increases in age- and sex-adjusted incidence of type 1 diabetes from 2002 to 2015 among black youth (2.7% per year), Hispanic youth (4%), and Asian and Pacific Islander youth (4.4%), than among their white counterparts (0.7%). Incidence among Asians and Pacific Islanders did not change significantly during 2002-2010, but increased steeply during 2011-2015 (8.5% per year) for unknown reasons.
“In parallel with increased obesity prevalence in U.S. youths, the incidence of type 2 diabetes among adolescents has increased at a higher rate than that of type 1 diabetes, especially among racial-/ethnic-minority youths,” the authors noted.
The number of new cases of type 2 diagnosed in children younger than 10 years were too few to report on (181 total cases during 2002-2015), so the incidence analysis was limited to children who were aged 10-19 years at diagnosis. The steepest annual percentage changes were among Asians and Pacific Islander youth (7.7% per year), followed by Hispanic (6.5%), black (6.0%), and American Indian (3.7%) youth.
“Although the SEARCH population is similar demographically to the U.S. youth population, it is not designed to be nationally representative,” which is one of the limitations of the study, the investigators wrote.
The authors reported having no conflicts of interest.
SOURCE: Divers J et al. MMWR Morb Mortal Wkly Rep. 2020;69:161-5.
according to a review of almost 70,000 children in the SEARCH for Diabetes in Youth Study, an ongoing, population-based surveillance project of individuals younger than 20 years.
“For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites,” wrote the investigators, led by Jasmin Divers, PhD, of the division of health services research, department of foundations of medicine, at New York University. “These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.”
SEARCH identified 14,638 cases of pediatric type 1 diabetes and 3,916 cases of type 2 diabetes from 2002 to 2015. The study draws participants from all 64 counties in Colorado, plus selected Indian reservations in Arizona and New Mexico under the direction of Colorado; all 46 counties in South Carolina; 8 in Ohio; 5 in Washington; and Kaiser Permanente Southern California health plan enrollees in 7 counties.
The investigators found steeper increases in age- and sex-adjusted incidence of type 1 diabetes from 2002 to 2015 among black youth (2.7% per year), Hispanic youth (4%), and Asian and Pacific Islander youth (4.4%), than among their white counterparts (0.7%). Incidence among Asians and Pacific Islanders did not change significantly during 2002-2010, but increased steeply during 2011-2015 (8.5% per year) for unknown reasons.
“In parallel with increased obesity prevalence in U.S. youths, the incidence of type 2 diabetes among adolescents has increased at a higher rate than that of type 1 diabetes, especially among racial-/ethnic-minority youths,” the authors noted.
The number of new cases of type 2 diagnosed in children younger than 10 years were too few to report on (181 total cases during 2002-2015), so the incidence analysis was limited to children who were aged 10-19 years at diagnosis. The steepest annual percentage changes were among Asians and Pacific Islander youth (7.7% per year), followed by Hispanic (6.5%), black (6.0%), and American Indian (3.7%) youth.
“Although the SEARCH population is similar demographically to the U.S. youth population, it is not designed to be nationally representative,” which is one of the limitations of the study, the investigators wrote.
The authors reported having no conflicts of interest.
SOURCE: Divers J et al. MMWR Morb Mortal Wkly Rep. 2020;69:161-5.
FROM THE MORBIDITY AND MORTALITY WEEKLY REPORT
Flu increases activity but not its severity
The CDC’s latest report shows that 6.8% of outpatients visiting health care providers had influenza-like illness during the week ending Feb. 8. That’s up from the previous week’s 6.6%, but that rise of 0.2 percentage points is smaller than the 0.6-point rises that occurred each of the 2 weeks before, and that could mean that activity is slowing.
That slowing, however, is not noticeable from this week’s map, which puts 41 states (there were 35 last week) and Puerto Rico in the red at the highest level of activity on the CDC’s 1-10 scale and another three states in the “high” range with levels of 8 or 9, the CDC’s influenza division reported.
That leaves Nevada and Oregon at level 7; Alaska, Florida, and the District of Columbia at level 5; Idaho at level 3, and Delaware with insufficient data (it was at level 5 last week), the CDC said.
The 2019-2020 season’s high activity, fortunately, has not translated into high severity, as overall hospitalization and mortality rates continue to remain at fairly typical levels. Hospitalization rates are elevated among children and young adults, however, and pediatric deaths are now up to 92, the CDC said, which is high for this point in the season.
The CDC’s latest report shows that 6.8% of outpatients visiting health care providers had influenza-like illness during the week ending Feb. 8. That’s up from the previous week’s 6.6%, but that rise of 0.2 percentage points is smaller than the 0.6-point rises that occurred each of the 2 weeks before, and that could mean that activity is slowing.
That slowing, however, is not noticeable from this week’s map, which puts 41 states (there were 35 last week) and Puerto Rico in the red at the highest level of activity on the CDC’s 1-10 scale and another three states in the “high” range with levels of 8 or 9, the CDC’s influenza division reported.
That leaves Nevada and Oregon at level 7; Alaska, Florida, and the District of Columbia at level 5; Idaho at level 3, and Delaware with insufficient data (it was at level 5 last week), the CDC said.
The 2019-2020 season’s high activity, fortunately, has not translated into high severity, as overall hospitalization and mortality rates continue to remain at fairly typical levels. Hospitalization rates are elevated among children and young adults, however, and pediatric deaths are now up to 92, the CDC said, which is high for this point in the season.
The CDC’s latest report shows that 6.8% of outpatients visiting health care providers had influenza-like illness during the week ending Feb. 8. That’s up from the previous week’s 6.6%, but that rise of 0.2 percentage points is smaller than the 0.6-point rises that occurred each of the 2 weeks before, and that could mean that activity is slowing.
That slowing, however, is not noticeable from this week’s map, which puts 41 states (there were 35 last week) and Puerto Rico in the red at the highest level of activity on the CDC’s 1-10 scale and another three states in the “high” range with levels of 8 or 9, the CDC’s influenza division reported.
That leaves Nevada and Oregon at level 7; Alaska, Florida, and the District of Columbia at level 5; Idaho at level 3, and Delaware with insufficient data (it was at level 5 last week), the CDC said.
The 2019-2020 season’s high activity, fortunately, has not translated into high severity, as overall hospitalization and mortality rates continue to remain at fairly typical levels. Hospitalization rates are elevated among children and young adults, however, and pediatric deaths are now up to 92, the CDC said, which is high for this point in the season.
ACC issues guidance on cardiac implications of coronavirus
The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.
The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”
The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.
About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.
In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.
“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”
Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:
- COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
- In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
- Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
- Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
- It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
- It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
- Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
- For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
- COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.
The full clinical update is available here.
This article first appeared on Medscape.com.
The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.
The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”
The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.
About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.
In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.
“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”
Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:
- COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
- In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
- Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
- Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
- It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
- It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
- Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
- For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
- COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.
The full clinical update is available here.
This article first appeared on Medscape.com.
The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.
The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”
The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.
About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.
In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.
“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”
Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:
- COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
- In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
- Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
- Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
- It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
- It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
- Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
- For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
- COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.
The full clinical update is available here.
This article first appeared on Medscape.com.
An epidemic of fear and misinformation
As I write this, the 2019 novel coronavirus* continues to spread, exceeding 59,000 cases and 1,300 deaths worldwide. With it spreads fear. In the modern world of social media, misinformation spreads even faster than disease.
The news about a novel and deadly illness crowds out more substantial worries. Humans are not particularly good at assessing risk or responding rationally and consistently to it. Risk is hard to fully define. If you look up “risk” in Merriam Webster’s online dictionary, you get the simple definition of “possibility of loss or injury; peril.” If you look up risk in Wikipedia, you get 12 pages of explanation and 8 more pages of links and references.
People handle risk differently. Some people are more risk adverse than others. Some get a pleasurable thrill from risk, whether a slot machine or a parachute jump. Most people really don’t comprehend small probabilities, with tens of billions of dollars spent annually on U.S. lotteries.
Because 98% of people who get COVID-19 are recovering, this is not an extinction-level event or the zombie apocalypse. It is a major health hazard, and one where morbidity and mortality might be assuaged by an early and effective public health response, including the population’s adoption of good habits such as hand washing, cough etiquette, and staying home when ill.
Three key factors may help reduce the fear factor.
One key factor is accurate communication of health information to the public. This has been severely harmed in the last few years by the promotion of gossip on social media, such as Facebook, within newsfeeds without any vetting, along with a smaller component of deliberate misinformation from untraceable sources. Compare this situation with the decision in May 1988 when Surgeon General C. Everett Koop chose to snail mail a brochure on AIDS to every household in America. It was unprecedented. One element of this communication is the public’s belief that government and health care officials will responsibly and timely convey the information. There are accusations that the Chinese government initially impeded early warnings about COVID-19. Dr. Koop, to his great credit and lifesaving leadership, overcame queasiness within the Reagan administration about issues of morality and taste in discussing some of the HIV information. Alas, no similar leadership occurred in the decade of the 2010s when deaths from the opioid epidemic in the United States skyrocketed to claim more lives annually than car accidents or suicide.
A second factor is the credibility of the scientists. Antivaxxers, climate change deniers, and mercenary scientists have severely damaged that credibility of science, compared with the trust in scientists 50 years ago during the Apollo moon shot.
A third factor is perspective. Poor journalism and clickbait can focus excessively on the rare events as news. Airline crashes make the front page while fatal car accidents, claiming a hundred times more lives annually, don’t even merit a story in local media. Someone wins the lottery weekly but few pay attention to those suffering from gambling debts.
Influenza is killing many times more people than the 2019 novel coronavirus, but the news is focused on cruise ships. In the United States, influenza annually will strike tens of millions, with about 10 per 1,000 hospitalized and 0.5 per 1,000 dying. The novel coronavirus is more lethal. SARS (a coronavirus epidemic in 2003) had 8,000 cases with a mortality rate of 96 per 1,000 while the novel 2019 strain so far is killing about 20 per 1,000. That value may be an overestimate, because there may be a significant fraction of COVID-19 patients with symptoms mild enough that they do not seek medical care and do not get tested and counted.
For perspective, in 1952 the United States reported 50,000 cases of polio (meningitis or paralytic) annually with 3,000 deaths. As many as 95% of cases of poliovirus infection have no or mild symptoms and would not have been reported, so the case fatality rate estimate is skewed. In the 1950s, the United States averaged about 500,000 cases of measles per year, with about 500 deaths annually for a case fatality rate of about 1 per 1,000 in a population that was well nourished with good medical care. In malnourished children without access to modern health care, the case fatality rate can be as high as 100 per 1,000, which is why globally measles killed 142,000 people in 2018, a substantial improvement from 536,000 deaths globally in 2000, but still a leading killer of children worldwide. Vaccines had reduced the annual death toll of polio and measles in the U.S. to zero.
In comparison, in this country the annual incidences are about 70,000 overdose deaths, 50,000 suicides, and 40,000 traffic deaths.
Reassurance is the most common product sold by pediatricians. We look for low-probability, high-impact bad things. Usually we don’t find them and can reassure parents that the child will be okay. Sometimes we spot a higher-risk situation and intervene. My job is to worry professionally so that parents can worry less.
COVID-19 worries me, but irrational people worry me more. The real enemies are fear, disinformation, discrimination, and economic warfare.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.
*This article was updated 2/21/2020.
As I write this, the 2019 novel coronavirus* continues to spread, exceeding 59,000 cases and 1,300 deaths worldwide. With it spreads fear. In the modern world of social media, misinformation spreads even faster than disease.
The news about a novel and deadly illness crowds out more substantial worries. Humans are not particularly good at assessing risk or responding rationally and consistently to it. Risk is hard to fully define. If you look up “risk” in Merriam Webster’s online dictionary, you get the simple definition of “possibility of loss or injury; peril.” If you look up risk in Wikipedia, you get 12 pages of explanation and 8 more pages of links and references.
People handle risk differently. Some people are more risk adverse than others. Some get a pleasurable thrill from risk, whether a slot machine or a parachute jump. Most people really don’t comprehend small probabilities, with tens of billions of dollars spent annually on U.S. lotteries.
Because 98% of people who get COVID-19 are recovering, this is not an extinction-level event or the zombie apocalypse. It is a major health hazard, and one where morbidity and mortality might be assuaged by an early and effective public health response, including the population’s adoption of good habits such as hand washing, cough etiquette, and staying home when ill.
Three key factors may help reduce the fear factor.
One key factor is accurate communication of health information to the public. This has been severely harmed in the last few years by the promotion of gossip on social media, such as Facebook, within newsfeeds without any vetting, along with a smaller component of deliberate misinformation from untraceable sources. Compare this situation with the decision in May 1988 when Surgeon General C. Everett Koop chose to snail mail a brochure on AIDS to every household in America. It was unprecedented. One element of this communication is the public’s belief that government and health care officials will responsibly and timely convey the information. There are accusations that the Chinese government initially impeded early warnings about COVID-19. Dr. Koop, to his great credit and lifesaving leadership, overcame queasiness within the Reagan administration about issues of morality and taste in discussing some of the HIV information. Alas, no similar leadership occurred in the decade of the 2010s when deaths from the opioid epidemic in the United States skyrocketed to claim more lives annually than car accidents or suicide.
A second factor is the credibility of the scientists. Antivaxxers, climate change deniers, and mercenary scientists have severely damaged that credibility of science, compared with the trust in scientists 50 years ago during the Apollo moon shot.
A third factor is perspective. Poor journalism and clickbait can focus excessively on the rare events as news. Airline crashes make the front page while fatal car accidents, claiming a hundred times more lives annually, don’t even merit a story in local media. Someone wins the lottery weekly but few pay attention to those suffering from gambling debts.
Influenza is killing many times more people than the 2019 novel coronavirus, but the news is focused on cruise ships. In the United States, influenza annually will strike tens of millions, with about 10 per 1,000 hospitalized and 0.5 per 1,000 dying. The novel coronavirus is more lethal. SARS (a coronavirus epidemic in 2003) had 8,000 cases with a mortality rate of 96 per 1,000 while the novel 2019 strain so far is killing about 20 per 1,000. That value may be an overestimate, because there may be a significant fraction of COVID-19 patients with symptoms mild enough that they do not seek medical care and do not get tested and counted.
For perspective, in 1952 the United States reported 50,000 cases of polio (meningitis or paralytic) annually with 3,000 deaths. As many as 95% of cases of poliovirus infection have no or mild symptoms and would not have been reported, so the case fatality rate estimate is skewed. In the 1950s, the United States averaged about 500,000 cases of measles per year, with about 500 deaths annually for a case fatality rate of about 1 per 1,000 in a population that was well nourished with good medical care. In malnourished children without access to modern health care, the case fatality rate can be as high as 100 per 1,000, which is why globally measles killed 142,000 people in 2018, a substantial improvement from 536,000 deaths globally in 2000, but still a leading killer of children worldwide. Vaccines had reduced the annual death toll of polio and measles in the U.S. to zero.
In comparison, in this country the annual incidences are about 70,000 overdose deaths, 50,000 suicides, and 40,000 traffic deaths.
Reassurance is the most common product sold by pediatricians. We look for low-probability, high-impact bad things. Usually we don’t find them and can reassure parents that the child will be okay. Sometimes we spot a higher-risk situation and intervene. My job is to worry professionally so that parents can worry less.
COVID-19 worries me, but irrational people worry me more. The real enemies are fear, disinformation, discrimination, and economic warfare.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.
*This article was updated 2/21/2020.
As I write this, the 2019 novel coronavirus* continues to spread, exceeding 59,000 cases and 1,300 deaths worldwide. With it spreads fear. In the modern world of social media, misinformation spreads even faster than disease.
The news about a novel and deadly illness crowds out more substantial worries. Humans are not particularly good at assessing risk or responding rationally and consistently to it. Risk is hard to fully define. If you look up “risk” in Merriam Webster’s online dictionary, you get the simple definition of “possibility of loss or injury; peril.” If you look up risk in Wikipedia, you get 12 pages of explanation and 8 more pages of links and references.
People handle risk differently. Some people are more risk adverse than others. Some get a pleasurable thrill from risk, whether a slot machine or a parachute jump. Most people really don’t comprehend small probabilities, with tens of billions of dollars spent annually on U.S. lotteries.
Because 98% of people who get COVID-19 are recovering, this is not an extinction-level event or the zombie apocalypse. It is a major health hazard, and one where morbidity and mortality might be assuaged by an early and effective public health response, including the population’s adoption of good habits such as hand washing, cough etiquette, and staying home when ill.
Three key factors may help reduce the fear factor.
One key factor is accurate communication of health information to the public. This has been severely harmed in the last few years by the promotion of gossip on social media, such as Facebook, within newsfeeds without any vetting, along with a smaller component of deliberate misinformation from untraceable sources. Compare this situation with the decision in May 1988 when Surgeon General C. Everett Koop chose to snail mail a brochure on AIDS to every household in America. It was unprecedented. One element of this communication is the public’s belief that government and health care officials will responsibly and timely convey the information. There are accusations that the Chinese government initially impeded early warnings about COVID-19. Dr. Koop, to his great credit and lifesaving leadership, overcame queasiness within the Reagan administration about issues of morality and taste in discussing some of the HIV information. Alas, no similar leadership occurred in the decade of the 2010s when deaths from the opioid epidemic in the United States skyrocketed to claim more lives annually than car accidents or suicide.
A second factor is the credibility of the scientists. Antivaxxers, climate change deniers, and mercenary scientists have severely damaged that credibility of science, compared with the trust in scientists 50 years ago during the Apollo moon shot.
A third factor is perspective. Poor journalism and clickbait can focus excessively on the rare events as news. Airline crashes make the front page while fatal car accidents, claiming a hundred times more lives annually, don’t even merit a story in local media. Someone wins the lottery weekly but few pay attention to those suffering from gambling debts.
Influenza is killing many times more people than the 2019 novel coronavirus, but the news is focused on cruise ships. In the United States, influenza annually will strike tens of millions, with about 10 per 1,000 hospitalized and 0.5 per 1,000 dying. The novel coronavirus is more lethal. SARS (a coronavirus epidemic in 2003) had 8,000 cases with a mortality rate of 96 per 1,000 while the novel 2019 strain so far is killing about 20 per 1,000. That value may be an overestimate, because there may be a significant fraction of COVID-19 patients with symptoms mild enough that they do not seek medical care and do not get tested and counted.
For perspective, in 1952 the United States reported 50,000 cases of polio (meningitis or paralytic) annually with 3,000 deaths. As many as 95% of cases of poliovirus infection have no or mild symptoms and would not have been reported, so the case fatality rate estimate is skewed. In the 1950s, the United States averaged about 500,000 cases of measles per year, with about 500 deaths annually for a case fatality rate of about 1 per 1,000 in a population that was well nourished with good medical care. In malnourished children without access to modern health care, the case fatality rate can be as high as 100 per 1,000, which is why globally measles killed 142,000 people in 2018, a substantial improvement from 536,000 deaths globally in 2000, but still a leading killer of children worldwide. Vaccines had reduced the annual death toll of polio and measles in the U.S. to zero.
In comparison, in this country the annual incidences are about 70,000 overdose deaths, 50,000 suicides, and 40,000 traffic deaths.
Reassurance is the most common product sold by pediatricians. We look for low-probability, high-impact bad things. Usually we don’t find them and can reassure parents that the child will be okay. Sometimes we spot a higher-risk situation and intervene. My job is to worry professionally so that parents can worry less.
COVID-19 worries me, but irrational people worry me more. The real enemies are fear, disinformation, discrimination, and economic warfare.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.
*This article was updated 2/21/2020.
Two new Novel Coronavirus cases confirmed among quarantined U.S. patients
The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.
The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.
The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.
CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.
The agency is preparing for more widespread cases of 2019-nCoV.
Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.
“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.
Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.
The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.
The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.
The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.
CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.
The agency is preparing for more widespread cases of 2019-nCoV.
Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.
“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.
Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.
The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.
The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.
The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.
CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.
The agency is preparing for more widespread cases of 2019-nCoV.
Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.
“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.
Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.
Pathways to new therapeutic agents for human coronaviruses
No specific treatment is currently available for human coronaviruses to date, but numerous antiviral agents are being identified through a variety of approaches, according to Thanigaimalai Pillaiyar, PhD, and colleagues in a review published in Drug Discovery Today.
Using the six previously discovered human coronaviruses – human CoV 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1); severe acute respiratory syndrome (SARS) CoV; and Middle East respiratory syndrome (MERS) CoV – the investigators examined progress in the use and development of therapeutic drugs, focusing on the potential roles of virus inhibitors.
“Research has mainly been focused on SARS- and MERS-CoV infections, because they were responsible for severe illness when compared with other CoVs,” Dr. Pillaiyar, of the department of pharmaceutical and medicinal chemistry at the University of Bonn (Germany), and colleagues wrote.
2019-nCov has been linked genomically as most closely related to SARS, and the Coronavirus Study Group of the International Committee on Virus Taxonomy, which has the responsibility for naming viruses, has designated the new virus SARS-CoV-2.
Examining extant drugs
The first approach to identifying possible antiviral agents reevaluates known, broadly acting antiviral drugs that have been used for other viral infections or other indications. The initial research into coronavirus therapeutics, in particular, has examined current antiviral therapeutics for their effectiveness against both SARS-CoV and MERS-CoV, but with mixed results.
For example, in a search of potential antiviral agents against CoVs, researchers identified four drugs – chloroquine, chlorpromazine, loperamide, and lopinavir – by screening drug libraries approved by the Food and Drug Administration. They were all able to inhibit the replication of MERS-CoV, SARS-CoV, and HCoV-229E in the low-micromolar range, which suggested that they could be used for broad-spectrum antiviral activity, according to Dr. Pillaiyar and colleagues.
Other research groups have also reported the discovery of antiviral drugs using this drug-repurposing approach, which included a number of broad-spectrum inhibitors of HCoVs (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) that showed strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations and suppressed the replication of all CoVs in a dose-dependent manner. Findings from in vivo studies showed lycorine protected mice against lethal HCoV-OC43 infection.
Along with the aforementioned drugs, a number of others have also shown potential usefulness, but, as yet, none has been validated for use in humans.
Developing new antivirals
The second approach for anti-CoV drug discovery involves the development of new therapeutics based on the genomic and biophysical understanding of the individual CoV in order to interfere with the virus itself or to disrupt its direct metabolic requirements. This can take several approaches.
MERS-CoV and SARS-CoV PL protease inhibitors
Of particular interest are antiviral therapies that attack papain-like protease, which is an important target because it is a multifunctional protein involved in proteolytic deubiquitination and viral evasion of the innate immune response. One such potential therapeutic that takes advantage of this target is disulfiram, an FDA-approved drug for use in alcohol-aversion therapy. Disulfiram has been reported as an allosteric inhibitor of MERS-CoV papain-like protease. Numerous other drug categories are being examined, with promising results in targeting the papain-like protease enzymes of both SARS and MERS.
Replicase inhibitors
Helicase (nsP13) protein is a crucial component required for virus replication in host cells and could serve as a feasible target for anti-MERS and anti-SARS chemical therapies, the review authors wrote, citing as an example, the recent development of a small 1,2,4-triazole derivative that inhibited the viral NTPase/helicase of SARS- and MERS-CoVs and demonstrated high antiviral activity and low cytotoxicity.
Membrane-bound viral RNA synthesis inhibitors
Antiviral agents that target membrane-bound coronaviral RNA synthesis represent a novel and attractive approach, according to Dr. Pillaiyar and colleagues. And recently, an inhibitor was developed that targets membrane-bound coronaviral RNA synthesis and “showed potent antiviral activity of MERS-CoV infection with remarkable efficacy.”
Host-based, anti-CoV treatment options
An alternate therapeutic tactic is to bolster host defenses or to modify host susceptibilities to prevent virus infection or replication. The innate interferon response of the host is crucial for the control of viral replication after infection, and the addition of exogenous recombinant interferon or use of drugs to stimulate the normal host interferon response are both potential therapeutic avenues. For example, nitazoxanide is a potent type I interferon inducer that has been used in humans for parasitic infections, and a synthetic nitrothiazolyl-salicylamide derivative was found to exhibit broad-spectrum antiviral activities against RNA and DNA viruses, including some coronaviruses.
Numerous other host pathways are being investigated as potential areas to enhance defense against infection and replication, for example, using inhibitors to block nucleic acid synthesis has been shown to provide broad-spectrum activity against SARS-CoV and MERS-CoV.
One particular example is remdesivir, a novel nucleotide analog antiviral drug, that was developed as a therapy for Ebola virus disease and Marburg virus infections. It was later shown to provide “reasonable antiviral activity against more distantly related viruses, such as respiratory syncytial virus, Junin virus, Lassa fever virus, and MERS-CoV,” the authors wrote.
Also of interest regarding remdesivir’s potential broad-spectrum use is that it has shown potent in vitro “antiviral activity against Malaysian and Bangladesh genotypes of Nipah virus (an RNA virus, although not a coronavirus, that infects both humans and animals) and reduced replication of Malaysian Nipah virus in primary human lung microvascular endothelial cells by more than four orders of magnitude,” Dr. Pillaiyar and colleagues added. Of particular note, all remdesivir-treated, Nipah virus–infected animals “survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment.”
In a press briefing earlier this month, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, reported that a randomized, controlled, phase 3 trial of the antiviral drug remdesivir is currently underway in China to establish whether the drug would be an effective and safe treatment for adults patients with mild or moderate 2019 Novel Coronavirus (2019-nCoV) disease.
“Our increasing understanding of novel emerging coronaviruses will be accompanied by increasing opportunities for the reasonable design of therapeutics. Importantly, understanding this basic information about CoV protease targets will not only aid the public health against SARS-CoV and MERS-CoV but also help in advance to target new coronaviruses that might emerge in the future,” the authors concluded.
Dr. Pillaiyar and colleagues reported that they had no financial conflicts of interest.
SOURCE: Pillaiyar T et al. Drug Discov Today. 2020 Jan 30. doi: 10.1016/j.drudis.2020.01.015.
No specific treatment is currently available for human coronaviruses to date, but numerous antiviral agents are being identified through a variety of approaches, according to Thanigaimalai Pillaiyar, PhD, and colleagues in a review published in Drug Discovery Today.
Using the six previously discovered human coronaviruses – human CoV 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1); severe acute respiratory syndrome (SARS) CoV; and Middle East respiratory syndrome (MERS) CoV – the investigators examined progress in the use and development of therapeutic drugs, focusing on the potential roles of virus inhibitors.
“Research has mainly been focused on SARS- and MERS-CoV infections, because they were responsible for severe illness when compared with other CoVs,” Dr. Pillaiyar, of the department of pharmaceutical and medicinal chemistry at the University of Bonn (Germany), and colleagues wrote.
2019-nCov has been linked genomically as most closely related to SARS, and the Coronavirus Study Group of the International Committee on Virus Taxonomy, which has the responsibility for naming viruses, has designated the new virus SARS-CoV-2.
Examining extant drugs
The first approach to identifying possible antiviral agents reevaluates known, broadly acting antiviral drugs that have been used for other viral infections or other indications. The initial research into coronavirus therapeutics, in particular, has examined current antiviral therapeutics for their effectiveness against both SARS-CoV and MERS-CoV, but with mixed results.
For example, in a search of potential antiviral agents against CoVs, researchers identified four drugs – chloroquine, chlorpromazine, loperamide, and lopinavir – by screening drug libraries approved by the Food and Drug Administration. They were all able to inhibit the replication of MERS-CoV, SARS-CoV, and HCoV-229E in the low-micromolar range, which suggested that they could be used for broad-spectrum antiviral activity, according to Dr. Pillaiyar and colleagues.
Other research groups have also reported the discovery of antiviral drugs using this drug-repurposing approach, which included a number of broad-spectrum inhibitors of HCoVs (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) that showed strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations and suppressed the replication of all CoVs in a dose-dependent manner. Findings from in vivo studies showed lycorine protected mice against lethal HCoV-OC43 infection.
Along with the aforementioned drugs, a number of others have also shown potential usefulness, but, as yet, none has been validated for use in humans.
Developing new antivirals
The second approach for anti-CoV drug discovery involves the development of new therapeutics based on the genomic and biophysical understanding of the individual CoV in order to interfere with the virus itself or to disrupt its direct metabolic requirements. This can take several approaches.
MERS-CoV and SARS-CoV PL protease inhibitors
Of particular interest are antiviral therapies that attack papain-like protease, which is an important target because it is a multifunctional protein involved in proteolytic deubiquitination and viral evasion of the innate immune response. One such potential therapeutic that takes advantage of this target is disulfiram, an FDA-approved drug for use in alcohol-aversion therapy. Disulfiram has been reported as an allosteric inhibitor of MERS-CoV papain-like protease. Numerous other drug categories are being examined, with promising results in targeting the papain-like protease enzymes of both SARS and MERS.
Replicase inhibitors
Helicase (nsP13) protein is a crucial component required for virus replication in host cells and could serve as a feasible target for anti-MERS and anti-SARS chemical therapies, the review authors wrote, citing as an example, the recent development of a small 1,2,4-triazole derivative that inhibited the viral NTPase/helicase of SARS- and MERS-CoVs and demonstrated high antiviral activity and low cytotoxicity.
Membrane-bound viral RNA synthesis inhibitors
Antiviral agents that target membrane-bound coronaviral RNA synthesis represent a novel and attractive approach, according to Dr. Pillaiyar and colleagues. And recently, an inhibitor was developed that targets membrane-bound coronaviral RNA synthesis and “showed potent antiviral activity of MERS-CoV infection with remarkable efficacy.”
Host-based, anti-CoV treatment options
An alternate therapeutic tactic is to bolster host defenses or to modify host susceptibilities to prevent virus infection or replication. The innate interferon response of the host is crucial for the control of viral replication after infection, and the addition of exogenous recombinant interferon or use of drugs to stimulate the normal host interferon response are both potential therapeutic avenues. For example, nitazoxanide is a potent type I interferon inducer that has been used in humans for parasitic infections, and a synthetic nitrothiazolyl-salicylamide derivative was found to exhibit broad-spectrum antiviral activities against RNA and DNA viruses, including some coronaviruses.
Numerous other host pathways are being investigated as potential areas to enhance defense against infection and replication, for example, using inhibitors to block nucleic acid synthesis has been shown to provide broad-spectrum activity against SARS-CoV and MERS-CoV.
One particular example is remdesivir, a novel nucleotide analog antiviral drug, that was developed as a therapy for Ebola virus disease and Marburg virus infections. It was later shown to provide “reasonable antiviral activity against more distantly related viruses, such as respiratory syncytial virus, Junin virus, Lassa fever virus, and MERS-CoV,” the authors wrote.
Also of interest regarding remdesivir’s potential broad-spectrum use is that it has shown potent in vitro “antiviral activity against Malaysian and Bangladesh genotypes of Nipah virus (an RNA virus, although not a coronavirus, that infects both humans and animals) and reduced replication of Malaysian Nipah virus in primary human lung microvascular endothelial cells by more than four orders of magnitude,” Dr. Pillaiyar and colleagues added. Of particular note, all remdesivir-treated, Nipah virus–infected animals “survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment.”
In a press briefing earlier this month, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, reported that a randomized, controlled, phase 3 trial of the antiviral drug remdesivir is currently underway in China to establish whether the drug would be an effective and safe treatment for adults patients with mild or moderate 2019 Novel Coronavirus (2019-nCoV) disease.
“Our increasing understanding of novel emerging coronaviruses will be accompanied by increasing opportunities for the reasonable design of therapeutics. Importantly, understanding this basic information about CoV protease targets will not only aid the public health against SARS-CoV and MERS-CoV but also help in advance to target new coronaviruses that might emerge in the future,” the authors concluded.
Dr. Pillaiyar and colleagues reported that they had no financial conflicts of interest.
SOURCE: Pillaiyar T et al. Drug Discov Today. 2020 Jan 30. doi: 10.1016/j.drudis.2020.01.015.
No specific treatment is currently available for human coronaviruses to date, but numerous antiviral agents are being identified through a variety of approaches, according to Thanigaimalai Pillaiyar, PhD, and colleagues in a review published in Drug Discovery Today.
Using the six previously discovered human coronaviruses – human CoV 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1); severe acute respiratory syndrome (SARS) CoV; and Middle East respiratory syndrome (MERS) CoV – the investigators examined progress in the use and development of therapeutic drugs, focusing on the potential roles of virus inhibitors.
“Research has mainly been focused on SARS- and MERS-CoV infections, because they were responsible for severe illness when compared with other CoVs,” Dr. Pillaiyar, of the department of pharmaceutical and medicinal chemistry at the University of Bonn (Germany), and colleagues wrote.
2019-nCov has been linked genomically as most closely related to SARS, and the Coronavirus Study Group of the International Committee on Virus Taxonomy, which has the responsibility for naming viruses, has designated the new virus SARS-CoV-2.
Examining extant drugs
The first approach to identifying possible antiviral agents reevaluates known, broadly acting antiviral drugs that have been used for other viral infections or other indications. The initial research into coronavirus therapeutics, in particular, has examined current antiviral therapeutics for their effectiveness against both SARS-CoV and MERS-CoV, but with mixed results.
For example, in a search of potential antiviral agents against CoVs, researchers identified four drugs – chloroquine, chlorpromazine, loperamide, and lopinavir – by screening drug libraries approved by the Food and Drug Administration. They were all able to inhibit the replication of MERS-CoV, SARS-CoV, and HCoV-229E in the low-micromolar range, which suggested that they could be used for broad-spectrum antiviral activity, according to Dr. Pillaiyar and colleagues.
Other research groups have also reported the discovery of antiviral drugs using this drug-repurposing approach, which included a number of broad-spectrum inhibitors of HCoVs (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) that showed strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations and suppressed the replication of all CoVs in a dose-dependent manner. Findings from in vivo studies showed lycorine protected mice against lethal HCoV-OC43 infection.
Along with the aforementioned drugs, a number of others have also shown potential usefulness, but, as yet, none has been validated for use in humans.
Developing new antivirals
The second approach for anti-CoV drug discovery involves the development of new therapeutics based on the genomic and biophysical understanding of the individual CoV in order to interfere with the virus itself or to disrupt its direct metabolic requirements. This can take several approaches.
MERS-CoV and SARS-CoV PL protease inhibitors
Of particular interest are antiviral therapies that attack papain-like protease, which is an important target because it is a multifunctional protein involved in proteolytic deubiquitination and viral evasion of the innate immune response. One such potential therapeutic that takes advantage of this target is disulfiram, an FDA-approved drug for use in alcohol-aversion therapy. Disulfiram has been reported as an allosteric inhibitor of MERS-CoV papain-like protease. Numerous other drug categories are being examined, with promising results in targeting the papain-like protease enzymes of both SARS and MERS.
Replicase inhibitors
Helicase (nsP13) protein is a crucial component required for virus replication in host cells and could serve as a feasible target for anti-MERS and anti-SARS chemical therapies, the review authors wrote, citing as an example, the recent development of a small 1,2,4-triazole derivative that inhibited the viral NTPase/helicase of SARS- and MERS-CoVs and demonstrated high antiviral activity and low cytotoxicity.
Membrane-bound viral RNA synthesis inhibitors
Antiviral agents that target membrane-bound coronaviral RNA synthesis represent a novel and attractive approach, according to Dr. Pillaiyar and colleagues. And recently, an inhibitor was developed that targets membrane-bound coronaviral RNA synthesis and “showed potent antiviral activity of MERS-CoV infection with remarkable efficacy.”
Host-based, anti-CoV treatment options
An alternate therapeutic tactic is to bolster host defenses or to modify host susceptibilities to prevent virus infection or replication. The innate interferon response of the host is crucial for the control of viral replication after infection, and the addition of exogenous recombinant interferon or use of drugs to stimulate the normal host interferon response are both potential therapeutic avenues. For example, nitazoxanide is a potent type I interferon inducer that has been used in humans for parasitic infections, and a synthetic nitrothiazolyl-salicylamide derivative was found to exhibit broad-spectrum antiviral activities against RNA and DNA viruses, including some coronaviruses.
Numerous other host pathways are being investigated as potential areas to enhance defense against infection and replication, for example, using inhibitors to block nucleic acid synthesis has been shown to provide broad-spectrum activity against SARS-CoV and MERS-CoV.
One particular example is remdesivir, a novel nucleotide analog antiviral drug, that was developed as a therapy for Ebola virus disease and Marburg virus infections. It was later shown to provide “reasonable antiviral activity against more distantly related viruses, such as respiratory syncytial virus, Junin virus, Lassa fever virus, and MERS-CoV,” the authors wrote.
Also of interest regarding remdesivir’s potential broad-spectrum use is that it has shown potent in vitro “antiviral activity against Malaysian and Bangladesh genotypes of Nipah virus (an RNA virus, although not a coronavirus, that infects both humans and animals) and reduced replication of Malaysian Nipah virus in primary human lung microvascular endothelial cells by more than four orders of magnitude,” Dr. Pillaiyar and colleagues added. Of particular note, all remdesivir-treated, Nipah virus–infected animals “survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment.”
In a press briefing earlier this month, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, reported that a randomized, controlled, phase 3 trial of the antiviral drug remdesivir is currently underway in China to establish whether the drug would be an effective and safe treatment for adults patients with mild or moderate 2019 Novel Coronavirus (2019-nCoV) disease.
“Our increasing understanding of novel emerging coronaviruses will be accompanied by increasing opportunities for the reasonable design of therapeutics. Importantly, understanding this basic information about CoV protease targets will not only aid the public health against SARS-CoV and MERS-CoV but also help in advance to target new coronaviruses that might emerge in the future,” the authors concluded.
Dr. Pillaiyar and colleagues reported that they had no financial conflicts of interest.
SOURCE: Pillaiyar T et al. Drug Discov Today. 2020 Jan 30. doi: 10.1016/j.drudis.2020.01.015.
FROM DRUG DISCOVERY TODAY
An unusual ‘retirement’ option
Whether “retirement” is withdrawing from one’s occupation or from an active working life, it is of utmost importance to not let one’s mind degenerate. Some individuals move on to gathering new intellectual skills by attending new educational courses or meetings, some travel, some become semiprofessional golfers or fishermen, and some find other forms of personal extension. I now serve to develop cost-saving medical programs for county jails in the state of Texas while attempting to improve the overall quality of inmate care.
Initially I was a pediatrician in Houston with special training in allergy and immunology, but because of a medical problem I was forced to abandon my first love – primary pediatrics. My move to a small town at the age of 40 required me to reevaluate my professional life, and I opted to provide care only in my allergy and immunology specialty.
However, living in a small town is different from life in a metropolis, and it was not uncommon for doctors to be asked to assist the community. A number of years ago, our county judge asked if I would help evaluate why our county jail was spending so much money. After several attempts to refuse, I eventually did evaluate the program there, and was flabbergasted by how much money was being wasted. I made some rather simple suggestions as how to correct the problem, but when no primary care doctor stepped forward to implement the changes and run the jail medical program, I became its medical director. When we saved $120,000 the first year, even I was astounded.
While I continued to run my private practice, I did accept other small community’s offers to look into their county jails’ programs. I found that their problems in cost control and quality of health care mirrored those I found in the first jail, and they were easily solvable if the county judge and the local sheriff wanted solutions. I also found that politics makes strange bedfellows, as the saying goes, and often the obvious changes were met with obstruction in one form or another. Nonetheless, I found that I could serve these communities in addition to my individual patients. When it was time for retirement, I continued to have a real desire to make the towns around which I lived and my own community more livable. So
In most things, I found that the same business philosophy and personal medical approach I learned in my pediatrics training and as a private practitioner applied to the jail system. Let me mention some specifics. Using generic medicines was less expensive than using brand names. The diagnoses which patients claimed when they entered jail might or might not be correct, so reevaluating the diagnosis and treatment was appropriate as soon as possible. Hospital and ED visits should be limited to patients’ medically requiring them rather than using the ED as a screening tool.
But I did come to understand that medical care in the county jail is different from medical care outside an incarcerated facility in that sometimes the prisoners had their own reasons for seeking medical care. This was complicated by the fact that often there were critically ill patients presenting to county jails. So carefully established criteria and protocols were an absolute necessity to save lives.
Let me expand on the topic of seeking medical care by the inmate-patients. A relatively small number of these individuals required immediate emergency treatment, without which they could not do well: The diabetic who was not taking his insulin, the out-of-control paranoid schizophrenic who decided he was cured and therefore was unattended, the alcoholic or drug addict who would develop delirium tremens if medications were stopped abruptly. These people had to be identified as quickly as possible and correctly treated. Confounding the problem was the fact that many, and I repeat many, individuals try to use the medical route to manipulate their incarceration environment. I called this the B problem: beds, blankets, barter, buzz, better food, and be out of here. They might claim an illness existed, and often they might believe it did.
A related situation might exist when individuals would demand psychiatric and pain medications, often in large quantities, when they in fact had not taken them for some time in the outside world. Often these patients were addicts, and of course this could create an entire other relationship with the medical team. A third example would be the claim of hypoglycemia so that the prisoner would receive more frequent meals.
One might think that as a pediatrician I was ill prepared to treat adults, and in fact, there was much review of the general medical care needed when I began this program. However, the internists and family physicians in town were glad to assist me whenever I encountered a difficult patient. When hospitalizations were required, the inpatient always was covered by one of the internists on hospital staff. Quite frankly, the doctors seemed pleased to not be dealing with this group of individuals as much as they had in the past.
On a slightly different note, skills honed during my pediatric career were extremely valuable. Children, particularly young children, do not verbally communicate with their parents or their doctor particularly well, so pediatricians are well trained in the skill of observation. The patient who claims a guard hurt his shoulder so badly during an altercation that he cannot move it is found out when he easily whips his arms over his head when asked to remove his shirt. It is not uncommon for an individual to demand antidepressant medications from the medical staff, but when evaluated more thoroughly and for a longer period of time, the patient ends up laughing, even denying any suicidal ideation or any other sign of depression. One also deals with a lot of adolescent behavior from the inmates, such as the individuals who say that unless they don’t get their way (more food) they are not going to take their medications and thus get sicker. That’s Adolescent Medicine 101.
Some of the modalities I utilized in modifying the jail programs will be familiar to every practicing pediatrician. I educate; I teach; I train. Parents of my asthmatic patients had to know what medications to keep handy and when to use them. It is pretty easy to see how that relates to jail medicine. Many patients come into jail with inhalers and with a diagnosis of asthma. Some have the condition, and some do not. By training jail and medical staff how to observe breathing patterns and by performing pulse oximetry, we eliminated a large number of unnecessary ED visits, and we often made the diagnosis of hyperventilation syndrome rather than misdiagnosed asthma.
Jail medicine is a large part of the cost of housing inmates. I did consultation work for a large urban jail, and we saved over $7 million in 1 year. In a medium-sized jail, the cost-savings after a 4-month consultation was over $300,000. This is a lot of money to me, and I suspect is to you, too. Just as in our general communities, we have enough resources to provide medical care and to provide a high level of care for all. However, we cannot waste money by providing inappropriate care or overtesting or overtreating. The medical care must be what treats the disease the patient actually has ... nothing more and nothing less!
If it sounds as if I am cynical about inmate patients, that is not true. However, I am realistic that no one wishes to be in jail. I realize that the medical route is just one that prisoners can and do use to modify their situation. I understand that the medical staff within a jail needs constant education and supervision at first, and with time they become more astute – just like a physician in this arena – at distinguishing the very serious from the mildly serious from malingering. In spite of this, we doctors also can be fooled. However, through constant vigilance and constant education we can get better.
Jail medicine is not for everyone in retirement. Heck, it is not for everyone ever. I found it interesting because it required me to match my diagnostic skills against the diseases and the psychodynamics of individuals who often – not always – made that diagnosis more difficult. Diagnosing illness and curing it – isn’t this why we all went into medicine?
Dr. Yoffe is a retired pediatrician specializing in allergy and immunology who resides in Brenham, Tex. Email him at pdnews@mdedge.com.
This article was updated 2/13/2020.
Whether “retirement” is withdrawing from one’s occupation or from an active working life, it is of utmost importance to not let one’s mind degenerate. Some individuals move on to gathering new intellectual skills by attending new educational courses or meetings, some travel, some become semiprofessional golfers or fishermen, and some find other forms of personal extension. I now serve to develop cost-saving medical programs for county jails in the state of Texas while attempting to improve the overall quality of inmate care.
Initially I was a pediatrician in Houston with special training in allergy and immunology, but because of a medical problem I was forced to abandon my first love – primary pediatrics. My move to a small town at the age of 40 required me to reevaluate my professional life, and I opted to provide care only in my allergy and immunology specialty.
However, living in a small town is different from life in a metropolis, and it was not uncommon for doctors to be asked to assist the community. A number of years ago, our county judge asked if I would help evaluate why our county jail was spending so much money. After several attempts to refuse, I eventually did evaluate the program there, and was flabbergasted by how much money was being wasted. I made some rather simple suggestions as how to correct the problem, but when no primary care doctor stepped forward to implement the changes and run the jail medical program, I became its medical director. When we saved $120,000 the first year, even I was astounded.
While I continued to run my private practice, I did accept other small community’s offers to look into their county jails’ programs. I found that their problems in cost control and quality of health care mirrored those I found in the first jail, and they were easily solvable if the county judge and the local sheriff wanted solutions. I also found that politics makes strange bedfellows, as the saying goes, and often the obvious changes were met with obstruction in one form or another. Nonetheless, I found that I could serve these communities in addition to my individual patients. When it was time for retirement, I continued to have a real desire to make the towns around which I lived and my own community more livable. So
In most things, I found that the same business philosophy and personal medical approach I learned in my pediatrics training and as a private practitioner applied to the jail system. Let me mention some specifics. Using generic medicines was less expensive than using brand names. The diagnoses which patients claimed when they entered jail might or might not be correct, so reevaluating the diagnosis and treatment was appropriate as soon as possible. Hospital and ED visits should be limited to patients’ medically requiring them rather than using the ED as a screening tool.
But I did come to understand that medical care in the county jail is different from medical care outside an incarcerated facility in that sometimes the prisoners had their own reasons for seeking medical care. This was complicated by the fact that often there were critically ill patients presenting to county jails. So carefully established criteria and protocols were an absolute necessity to save lives.
Let me expand on the topic of seeking medical care by the inmate-patients. A relatively small number of these individuals required immediate emergency treatment, without which they could not do well: The diabetic who was not taking his insulin, the out-of-control paranoid schizophrenic who decided he was cured and therefore was unattended, the alcoholic or drug addict who would develop delirium tremens if medications were stopped abruptly. These people had to be identified as quickly as possible and correctly treated. Confounding the problem was the fact that many, and I repeat many, individuals try to use the medical route to manipulate their incarceration environment. I called this the B problem: beds, blankets, barter, buzz, better food, and be out of here. They might claim an illness existed, and often they might believe it did.
A related situation might exist when individuals would demand psychiatric and pain medications, often in large quantities, when they in fact had not taken them for some time in the outside world. Often these patients were addicts, and of course this could create an entire other relationship with the medical team. A third example would be the claim of hypoglycemia so that the prisoner would receive more frequent meals.
One might think that as a pediatrician I was ill prepared to treat adults, and in fact, there was much review of the general medical care needed when I began this program. However, the internists and family physicians in town were glad to assist me whenever I encountered a difficult patient. When hospitalizations were required, the inpatient always was covered by one of the internists on hospital staff. Quite frankly, the doctors seemed pleased to not be dealing with this group of individuals as much as they had in the past.
On a slightly different note, skills honed during my pediatric career were extremely valuable. Children, particularly young children, do not verbally communicate with their parents or their doctor particularly well, so pediatricians are well trained in the skill of observation. The patient who claims a guard hurt his shoulder so badly during an altercation that he cannot move it is found out when he easily whips his arms over his head when asked to remove his shirt. It is not uncommon for an individual to demand antidepressant medications from the medical staff, but when evaluated more thoroughly and for a longer period of time, the patient ends up laughing, even denying any suicidal ideation or any other sign of depression. One also deals with a lot of adolescent behavior from the inmates, such as the individuals who say that unless they don’t get their way (more food) they are not going to take their medications and thus get sicker. That’s Adolescent Medicine 101.
Some of the modalities I utilized in modifying the jail programs will be familiar to every practicing pediatrician. I educate; I teach; I train. Parents of my asthmatic patients had to know what medications to keep handy and when to use them. It is pretty easy to see how that relates to jail medicine. Many patients come into jail with inhalers and with a diagnosis of asthma. Some have the condition, and some do not. By training jail and medical staff how to observe breathing patterns and by performing pulse oximetry, we eliminated a large number of unnecessary ED visits, and we often made the diagnosis of hyperventilation syndrome rather than misdiagnosed asthma.
Jail medicine is a large part of the cost of housing inmates. I did consultation work for a large urban jail, and we saved over $7 million in 1 year. In a medium-sized jail, the cost-savings after a 4-month consultation was over $300,000. This is a lot of money to me, and I suspect is to you, too. Just as in our general communities, we have enough resources to provide medical care and to provide a high level of care for all. However, we cannot waste money by providing inappropriate care or overtesting or overtreating. The medical care must be what treats the disease the patient actually has ... nothing more and nothing less!
If it sounds as if I am cynical about inmate patients, that is not true. However, I am realistic that no one wishes to be in jail. I realize that the medical route is just one that prisoners can and do use to modify their situation. I understand that the medical staff within a jail needs constant education and supervision at first, and with time they become more astute – just like a physician in this arena – at distinguishing the very serious from the mildly serious from malingering. In spite of this, we doctors also can be fooled. However, through constant vigilance and constant education we can get better.
Jail medicine is not for everyone in retirement. Heck, it is not for everyone ever. I found it interesting because it required me to match my diagnostic skills against the diseases and the psychodynamics of individuals who often – not always – made that diagnosis more difficult. Diagnosing illness and curing it – isn’t this why we all went into medicine?
Dr. Yoffe is a retired pediatrician specializing in allergy and immunology who resides in Brenham, Tex. Email him at pdnews@mdedge.com.
This article was updated 2/13/2020.
Whether “retirement” is withdrawing from one’s occupation or from an active working life, it is of utmost importance to not let one’s mind degenerate. Some individuals move on to gathering new intellectual skills by attending new educational courses or meetings, some travel, some become semiprofessional golfers or fishermen, and some find other forms of personal extension. I now serve to develop cost-saving medical programs for county jails in the state of Texas while attempting to improve the overall quality of inmate care.
Initially I was a pediatrician in Houston with special training in allergy and immunology, but because of a medical problem I was forced to abandon my first love – primary pediatrics. My move to a small town at the age of 40 required me to reevaluate my professional life, and I opted to provide care only in my allergy and immunology specialty.
However, living in a small town is different from life in a metropolis, and it was not uncommon for doctors to be asked to assist the community. A number of years ago, our county judge asked if I would help evaluate why our county jail was spending so much money. After several attempts to refuse, I eventually did evaluate the program there, and was flabbergasted by how much money was being wasted. I made some rather simple suggestions as how to correct the problem, but when no primary care doctor stepped forward to implement the changes and run the jail medical program, I became its medical director. When we saved $120,000 the first year, even I was astounded.
While I continued to run my private practice, I did accept other small community’s offers to look into their county jails’ programs. I found that their problems in cost control and quality of health care mirrored those I found in the first jail, and they were easily solvable if the county judge and the local sheriff wanted solutions. I also found that politics makes strange bedfellows, as the saying goes, and often the obvious changes were met with obstruction in one form or another. Nonetheless, I found that I could serve these communities in addition to my individual patients. When it was time for retirement, I continued to have a real desire to make the towns around which I lived and my own community more livable. So
In most things, I found that the same business philosophy and personal medical approach I learned in my pediatrics training and as a private practitioner applied to the jail system. Let me mention some specifics. Using generic medicines was less expensive than using brand names. The diagnoses which patients claimed when they entered jail might or might not be correct, so reevaluating the diagnosis and treatment was appropriate as soon as possible. Hospital and ED visits should be limited to patients’ medically requiring them rather than using the ED as a screening tool.
But I did come to understand that medical care in the county jail is different from medical care outside an incarcerated facility in that sometimes the prisoners had their own reasons for seeking medical care. This was complicated by the fact that often there were critically ill patients presenting to county jails. So carefully established criteria and protocols were an absolute necessity to save lives.
Let me expand on the topic of seeking medical care by the inmate-patients. A relatively small number of these individuals required immediate emergency treatment, without which they could not do well: The diabetic who was not taking his insulin, the out-of-control paranoid schizophrenic who decided he was cured and therefore was unattended, the alcoholic or drug addict who would develop delirium tremens if medications were stopped abruptly. These people had to be identified as quickly as possible and correctly treated. Confounding the problem was the fact that many, and I repeat many, individuals try to use the medical route to manipulate their incarceration environment. I called this the B problem: beds, blankets, barter, buzz, better food, and be out of here. They might claim an illness existed, and often they might believe it did.
A related situation might exist when individuals would demand psychiatric and pain medications, often in large quantities, when they in fact had not taken them for some time in the outside world. Often these patients were addicts, and of course this could create an entire other relationship with the medical team. A third example would be the claim of hypoglycemia so that the prisoner would receive more frequent meals.
One might think that as a pediatrician I was ill prepared to treat adults, and in fact, there was much review of the general medical care needed when I began this program. However, the internists and family physicians in town were glad to assist me whenever I encountered a difficult patient. When hospitalizations were required, the inpatient always was covered by one of the internists on hospital staff. Quite frankly, the doctors seemed pleased to not be dealing with this group of individuals as much as they had in the past.
On a slightly different note, skills honed during my pediatric career were extremely valuable. Children, particularly young children, do not verbally communicate with their parents or their doctor particularly well, so pediatricians are well trained in the skill of observation. The patient who claims a guard hurt his shoulder so badly during an altercation that he cannot move it is found out when he easily whips his arms over his head when asked to remove his shirt. It is not uncommon for an individual to demand antidepressant medications from the medical staff, but when evaluated more thoroughly and for a longer period of time, the patient ends up laughing, even denying any suicidal ideation or any other sign of depression. One also deals with a lot of adolescent behavior from the inmates, such as the individuals who say that unless they don’t get their way (more food) they are not going to take their medications and thus get sicker. That’s Adolescent Medicine 101.
Some of the modalities I utilized in modifying the jail programs will be familiar to every practicing pediatrician. I educate; I teach; I train. Parents of my asthmatic patients had to know what medications to keep handy and when to use them. It is pretty easy to see how that relates to jail medicine. Many patients come into jail with inhalers and with a diagnosis of asthma. Some have the condition, and some do not. By training jail and medical staff how to observe breathing patterns and by performing pulse oximetry, we eliminated a large number of unnecessary ED visits, and we often made the diagnosis of hyperventilation syndrome rather than misdiagnosed asthma.
Jail medicine is a large part of the cost of housing inmates. I did consultation work for a large urban jail, and we saved over $7 million in 1 year. In a medium-sized jail, the cost-savings after a 4-month consultation was over $300,000. This is a lot of money to me, and I suspect is to you, too. Just as in our general communities, we have enough resources to provide medical care and to provide a high level of care for all. However, we cannot waste money by providing inappropriate care or overtesting or overtreating. The medical care must be what treats the disease the patient actually has ... nothing more and nothing less!
If it sounds as if I am cynical about inmate patients, that is not true. However, I am realistic that no one wishes to be in jail. I realize that the medical route is just one that prisoners can and do use to modify their situation. I understand that the medical staff within a jail needs constant education and supervision at first, and with time they become more astute – just like a physician in this arena – at distinguishing the very serious from the mildly serious from malingering. In spite of this, we doctors also can be fooled. However, through constant vigilance and constant education we can get better.
Jail medicine is not for everyone in retirement. Heck, it is not for everyone ever. I found it interesting because it required me to match my diagnostic skills against the diseases and the psychodynamics of individuals who often – not always – made that diagnosis more difficult. Diagnosing illness and curing it – isn’t this why we all went into medicine?
Dr. Yoffe is a retired pediatrician specializing in allergy and immunology who resides in Brenham, Tex. Email him at pdnews@mdedge.com.
This article was updated 2/13/2020.
Pediatricians twice as happy outside work than at work
Pediatricians are twice as likely to be happy outside the office than they are at work, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.
About 29% of pediatricians reported being happy at work, with dermatologists taking the top spot at 41%. Pediatricians did much better when it came to finding happiness outside the office, with 57% reporting that they were very happy when away from work, according to the Medscape report.
The biggest contributing factors to burnout in pediatricians were an overabundance of bureaucratic tasks (59%), insufficient compensation/reimbursement (37%), and spending too many hours at work (34%).
Pediatricians most commonly dealt with burnout by talking with friends/family (54%), exercising (47%), and sleeping (41%). Just over half of pediatricians reported taking 3-4 weeks of vacation, compared with 44% of all physicians; 32% took less than 3 weeks’ vacation.
About 8% of pediatricians reported that they’d contemplated suicide, but 0% reported that they’d attempted it; 85% said that they’d never thought about it. Just under one-quarter of pediatricians said that were currently seeking or planning to seek professional help for depression and/or burnout; 55% said they were not seeking help and had never made use of it in the past.
The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.
We all feel it. It is not surprising that only 29% of today's pediatricians report that they are "happy" at work and 30% report "burnout"!
This report serves to identify only some of the countless ways in which we are forced to compromise the 24-hour clock, leaving too little time for ourselves and families.
We spend too many hours at work, and other data show we are undercompensated for our efforts.
Today, electronically, most of us are reachable even when out of the office. It is difficult, if not impossible, to completely disconnect. The challenge to achieve the work/life balance we have all imagined is too great!
I try to carve out "forced escapes from reality" through novels, movies, and when possible, distant travel with my spouse. However, the bliss is too short lived. When I return to reality, some bliss fades as I jump back onto the "merry-go-round" for a few more turns.
Lillian M. Beard, MD, is a clinical professor of pediatrics at George Washington University, Washington. She is a Pediatric News Editorial Advisory Board member.
We all feel it. It is not surprising that only 29% of today's pediatricians report that they are "happy" at work and 30% report "burnout"!
This report serves to identify only some of the countless ways in which we are forced to compromise the 24-hour clock, leaving too little time for ourselves and families.
We spend too many hours at work, and other data show we are undercompensated for our efforts.
Today, electronically, most of us are reachable even when out of the office. It is difficult, if not impossible, to completely disconnect. The challenge to achieve the work/life balance we have all imagined is too great!
I try to carve out "forced escapes from reality" through novels, movies, and when possible, distant travel with my spouse. However, the bliss is too short lived. When I return to reality, some bliss fades as I jump back onto the "merry-go-round" for a few more turns.
Lillian M. Beard, MD, is a clinical professor of pediatrics at George Washington University, Washington. She is a Pediatric News Editorial Advisory Board member.
We all feel it. It is not surprising that only 29% of today's pediatricians report that they are "happy" at work and 30% report "burnout"!
This report serves to identify only some of the countless ways in which we are forced to compromise the 24-hour clock, leaving too little time for ourselves and families.
We spend too many hours at work, and other data show we are undercompensated for our efforts.
Today, electronically, most of us are reachable even when out of the office. It is difficult, if not impossible, to completely disconnect. The challenge to achieve the work/life balance we have all imagined is too great!
I try to carve out "forced escapes from reality" through novels, movies, and when possible, distant travel with my spouse. However, the bliss is too short lived. When I return to reality, some bliss fades as I jump back onto the "merry-go-round" for a few more turns.
Lillian M. Beard, MD, is a clinical professor of pediatrics at George Washington University, Washington. She is a Pediatric News Editorial Advisory Board member.
Pediatricians are twice as likely to be happy outside the office than they are at work, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.
About 29% of pediatricians reported being happy at work, with dermatologists taking the top spot at 41%. Pediatricians did much better when it came to finding happiness outside the office, with 57% reporting that they were very happy when away from work, according to the Medscape report.
The biggest contributing factors to burnout in pediatricians were an overabundance of bureaucratic tasks (59%), insufficient compensation/reimbursement (37%), and spending too many hours at work (34%).
Pediatricians most commonly dealt with burnout by talking with friends/family (54%), exercising (47%), and sleeping (41%). Just over half of pediatricians reported taking 3-4 weeks of vacation, compared with 44% of all physicians; 32% took less than 3 weeks’ vacation.
About 8% of pediatricians reported that they’d contemplated suicide, but 0% reported that they’d attempted it; 85% said that they’d never thought about it. Just under one-quarter of pediatricians said that were currently seeking or planning to seek professional help for depression and/or burnout; 55% said they were not seeking help and had never made use of it in the past.
The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.
Pediatricians are twice as likely to be happy outside the office than they are at work, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.
About 29% of pediatricians reported being happy at work, with dermatologists taking the top spot at 41%. Pediatricians did much better when it came to finding happiness outside the office, with 57% reporting that they were very happy when away from work, according to the Medscape report.
The biggest contributing factors to burnout in pediatricians were an overabundance of bureaucratic tasks (59%), insufficient compensation/reimbursement (37%), and spending too many hours at work (34%).
Pediatricians most commonly dealt with burnout by talking with friends/family (54%), exercising (47%), and sleeping (41%). Just over half of pediatricians reported taking 3-4 weeks of vacation, compared with 44% of all physicians; 32% took less than 3 weeks’ vacation.
About 8% of pediatricians reported that they’d contemplated suicide, but 0% reported that they’d attempted it; 85% said that they’d never thought about it. Just under one-quarter of pediatricians said that were currently seeking or planning to seek professional help for depression and/or burnout; 55% said they were not seeking help and had never made use of it in the past.
The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.