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Boys with severe hemophilia have good physical function
Children with severe hemophilia in a U.K. study had generally good self-reported health-related quality of life and physical functioning, but impairment on both measures was greater in those who reported pain.
Of 123 boys with a mean age of 12 years who were included in the multicenter SO-FIT study, 110 had hemophilia A, 25 had a past inhibitor, and 9 had a current inhibitor. Prophylactic treatment was given in 120 of the boys, Kate Khair, PhD of Great Ormond Street Hospital for Children, London, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
In the preceding 6 months, participants experienced a median of 0 joint bleeds (range of 0-8), and a median Hemophilia Joint Health Score (HJHS) of 1 (range, 0-37). Physical function scores were good; the Haemophilia & Exercise Project questionnaire (HEP-Test-Q) mean score was 80.82, with the highest impairments seen in the domain of “endurance” (mean, 72.21), and the Paediatric Haemophilia Activities List (PedHAL) mean score was 85.13, with the highest impairments seen in the domains of “leisure activities and sports” and “lying/sitting/kneeling/standing” (mean, 82.04 and 82.97, respectively).
Health-related quality of life as assessed by the Haemo-QoL Short Form was also generally good (mean, 23.07), with the highest impairments seen in the domains of “friends” and “family” (mean, 27.08 and 26.59, respectively).
In the 27% of participants with pain, a high correlation was seen between the HEP-Test-Q and Haemo-QoL, and moderate correlation was seen between the PedHAL and Haemo-QoL, which implies that good physical functioning is related to good health-related quality of life, Dr. Khair explained.
In fact, patients who said they often or always had pain reported significantly worse subjective physical functioning in all HEP-Test-Q and PedHAL domains, as well as higher impairments in their HRQoL vs. those who said they sometimes, rarely, or never experienced pain, she said.
Interestingly, data completion by study participants was improved with use of an iPad vs. “paper and pencil” for questionnaire completion, Dr. Khair said in an interview.
“They preferred this method – it was more in keeping with how they communicate and learn at school,” she said, noting that the iPad database was set up to give real time scores, which could then be used to tailor assessments.
This is an approach that could be undertaken at home pre-clinic visits, she said.
“Gaining the views of children and young adults in patient-reported outcomes is complex, but reveals their views of their care and their lives – an area we should address more,” she added.
Dr. Khair received grant or research support from Pfizer ASPIRE.
Children with severe hemophilia in a U.K. study had generally good self-reported health-related quality of life and physical functioning, but impairment on both measures was greater in those who reported pain.
Of 123 boys with a mean age of 12 years who were included in the multicenter SO-FIT study, 110 had hemophilia A, 25 had a past inhibitor, and 9 had a current inhibitor. Prophylactic treatment was given in 120 of the boys, Kate Khair, PhD of Great Ormond Street Hospital for Children, London, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
In the preceding 6 months, participants experienced a median of 0 joint bleeds (range of 0-8), and a median Hemophilia Joint Health Score (HJHS) of 1 (range, 0-37). Physical function scores were good; the Haemophilia & Exercise Project questionnaire (HEP-Test-Q) mean score was 80.82, with the highest impairments seen in the domain of “endurance” (mean, 72.21), and the Paediatric Haemophilia Activities List (PedHAL) mean score was 85.13, with the highest impairments seen in the domains of “leisure activities and sports” and “lying/sitting/kneeling/standing” (mean, 82.04 and 82.97, respectively).
Health-related quality of life as assessed by the Haemo-QoL Short Form was also generally good (mean, 23.07), with the highest impairments seen in the domains of “friends” and “family” (mean, 27.08 and 26.59, respectively).
In the 27% of participants with pain, a high correlation was seen between the HEP-Test-Q and Haemo-QoL, and moderate correlation was seen between the PedHAL and Haemo-QoL, which implies that good physical functioning is related to good health-related quality of life, Dr. Khair explained.
In fact, patients who said they often or always had pain reported significantly worse subjective physical functioning in all HEP-Test-Q and PedHAL domains, as well as higher impairments in their HRQoL vs. those who said they sometimes, rarely, or never experienced pain, she said.
Interestingly, data completion by study participants was improved with use of an iPad vs. “paper and pencil” for questionnaire completion, Dr. Khair said in an interview.
“They preferred this method – it was more in keeping with how they communicate and learn at school,” she said, noting that the iPad database was set up to give real time scores, which could then be used to tailor assessments.
This is an approach that could be undertaken at home pre-clinic visits, she said.
“Gaining the views of children and young adults in patient-reported outcomes is complex, but reveals their views of their care and their lives – an area we should address more,” she added.
Dr. Khair received grant or research support from Pfizer ASPIRE.
Children with severe hemophilia in a U.K. study had generally good self-reported health-related quality of life and physical functioning, but impairment on both measures was greater in those who reported pain.
Of 123 boys with a mean age of 12 years who were included in the multicenter SO-FIT study, 110 had hemophilia A, 25 had a past inhibitor, and 9 had a current inhibitor. Prophylactic treatment was given in 120 of the boys, Kate Khair, PhD of Great Ormond Street Hospital for Children, London, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
In the preceding 6 months, participants experienced a median of 0 joint bleeds (range of 0-8), and a median Hemophilia Joint Health Score (HJHS) of 1 (range, 0-37). Physical function scores were good; the Haemophilia & Exercise Project questionnaire (HEP-Test-Q) mean score was 80.82, with the highest impairments seen in the domain of “endurance” (mean, 72.21), and the Paediatric Haemophilia Activities List (PedHAL) mean score was 85.13, with the highest impairments seen in the domains of “leisure activities and sports” and “lying/sitting/kneeling/standing” (mean, 82.04 and 82.97, respectively).
Health-related quality of life as assessed by the Haemo-QoL Short Form was also generally good (mean, 23.07), with the highest impairments seen in the domains of “friends” and “family” (mean, 27.08 and 26.59, respectively).
In the 27% of participants with pain, a high correlation was seen between the HEP-Test-Q and Haemo-QoL, and moderate correlation was seen between the PedHAL and Haemo-QoL, which implies that good physical functioning is related to good health-related quality of life, Dr. Khair explained.
In fact, patients who said they often or always had pain reported significantly worse subjective physical functioning in all HEP-Test-Q and PedHAL domains, as well as higher impairments in their HRQoL vs. those who said they sometimes, rarely, or never experienced pain, she said.
Interestingly, data completion by study participants was improved with use of an iPad vs. “paper and pencil” for questionnaire completion, Dr. Khair said in an interview.
“They preferred this method – it was more in keeping with how they communicate and learn at school,” she said, noting that the iPad database was set up to give real time scores, which could then be used to tailor assessments.
This is an approach that could be undertaken at home pre-clinic visits, she said.
“Gaining the views of children and young adults in patient-reported outcomes is complex, but reveals their views of their care and their lives – an area we should address more,” she added.
Dr. Khair received grant or research support from Pfizer ASPIRE.
FROM EAHAD 2017
Key clinical point:
Major finding: Physical function score (HEP-Test-Q) was a mean of 80.82, with the highest impairments seen in the domain of “endurance” (mean, 72.21).
Data source: The SO-FIT study of 123 boys with severe hemophilia.
Disclosures: Dr. Khair received grant or research support from Pfizer ASPIRE.
Study: No link between vaccines, inhibitor development
The administration of pediatric vaccinations in close proximity to factor VIII (FVIII) exposure was not associated with inhibitor development in previously untreated patients with severe hemophilia A in the PedNet Registry.
Similarly, no association was seen between recurrent vaccinations and inhibitor development, Dr. van den Berg reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Inhibitor development in this patient population is a multifactorial event, but these findings show no association between vaccinations administered early in life and increased inhibitor risk, she concluded.
Dr. van den Berg received grant/research support from Bayer, Baxalta, Pfizer, CSI, and Grifols.
The administration of pediatric vaccinations in close proximity to factor VIII (FVIII) exposure was not associated with inhibitor development in previously untreated patients with severe hemophilia A in the PedNet Registry.
Similarly, no association was seen between recurrent vaccinations and inhibitor development, Dr. van den Berg reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Inhibitor development in this patient population is a multifactorial event, but these findings show no association between vaccinations administered early in life and increased inhibitor risk, she concluded.
Dr. van den Berg received grant/research support from Bayer, Baxalta, Pfizer, CSI, and Grifols.
The administration of pediatric vaccinations in close proximity to factor VIII (FVIII) exposure was not associated with inhibitor development in previously untreated patients with severe hemophilia A in the PedNet Registry.
Similarly, no association was seen between recurrent vaccinations and inhibitor development, Dr. van den Berg reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.
Inhibitor development in this patient population is a multifactorial event, but these findings show no association between vaccinations administered early in life and increased inhibitor risk, she concluded.
Dr. van den Berg received grant/research support from Bayer, Baxalta, Pfizer, CSI, and Grifols.
FROM EAHAD 2017
Key clinical point:
Major finding: The adjusted hazard ratio for any inhibitor development related to vaccinations in close proximity to FVIII was 0.65.
Data source: A review of data from 375 children in the PedNet Registry.
Disclosures: Dr. van den Berg received grant/research support from Bayer, Baxalta, Pfizer, CSI, and Grifols.
FDA approves Emflaza for Duchenne muscular dystrophy
Emflaza, a tablet and oral suspension corticosteroid, has been approved by the Food and Drug Administration for the treatment of Duchenne muscular dystrophy in patients aged 5 years and older.
The agency’s Feb. 9 announcement notes that similar corticosteroids have been used around the world to treat Duchenne muscular dystrophy (DMD), but this is the first to gain approval in the United States. Emflaza (deflazacort) works by decreasing inflammation and immune system activity.
DMD is the most common form of muscular dystrophy but is still rare, occurring in about 1 in 3,600 male infants worldwide. One study found that patients taking deflazacort had some improvements in muscle strength at 12 weeks, compared with those taking placebo, and maintained muscle strength stability through 52 weeks. A longer-term study showed that patients who took deflazacort had better average muscle strength than did those taking placebo and suggested that deflazacort helped prolong patients’ ability to walk.
Side effects experienced by patients taking Emflaza are similar to those associated with other corticosteroids, such as facial puffiness (cushingoid appearance), weight gain, increased appetite, upper respiratory tract infection, cough, extraordinary daytime urinary frequency (pollakiuria), unwanted hair growth (hirsutism), and excessive fat around the stomach (central obesity).
In the FDA’s announcement, Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said, “We hope that this treatment option will benefit many patients with DMD.”
Emflaza, a tablet and oral suspension corticosteroid, has been approved by the Food and Drug Administration for the treatment of Duchenne muscular dystrophy in patients aged 5 years and older.
The agency’s Feb. 9 announcement notes that similar corticosteroids have been used around the world to treat Duchenne muscular dystrophy (DMD), but this is the first to gain approval in the United States. Emflaza (deflazacort) works by decreasing inflammation and immune system activity.
DMD is the most common form of muscular dystrophy but is still rare, occurring in about 1 in 3,600 male infants worldwide. One study found that patients taking deflazacort had some improvements in muscle strength at 12 weeks, compared with those taking placebo, and maintained muscle strength stability through 52 weeks. A longer-term study showed that patients who took deflazacort had better average muscle strength than did those taking placebo and suggested that deflazacort helped prolong patients’ ability to walk.
Side effects experienced by patients taking Emflaza are similar to those associated with other corticosteroids, such as facial puffiness (cushingoid appearance), weight gain, increased appetite, upper respiratory tract infection, cough, extraordinary daytime urinary frequency (pollakiuria), unwanted hair growth (hirsutism), and excessive fat around the stomach (central obesity).
In the FDA’s announcement, Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said, “We hope that this treatment option will benefit many patients with DMD.”
Emflaza, a tablet and oral suspension corticosteroid, has been approved by the Food and Drug Administration for the treatment of Duchenne muscular dystrophy in patients aged 5 years and older.
The agency’s Feb. 9 announcement notes that similar corticosteroids have been used around the world to treat Duchenne muscular dystrophy (DMD), but this is the first to gain approval in the United States. Emflaza (deflazacort) works by decreasing inflammation and immune system activity.
DMD is the most common form of muscular dystrophy but is still rare, occurring in about 1 in 3,600 male infants worldwide. One study found that patients taking deflazacort had some improvements in muscle strength at 12 weeks, compared with those taking placebo, and maintained muscle strength stability through 52 weeks. A longer-term study showed that patients who took deflazacort had better average muscle strength than did those taking placebo and suggested that deflazacort helped prolong patients’ ability to walk.
Side effects experienced by patients taking Emflaza are similar to those associated with other corticosteroids, such as facial puffiness (cushingoid appearance), weight gain, increased appetite, upper respiratory tract infection, cough, extraordinary daytime urinary frequency (pollakiuria), unwanted hair growth (hirsutism), and excessive fat around the stomach (central obesity).
In the FDA’s announcement, Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said, “We hope that this treatment option will benefit many patients with DMD.”
The last call
It’s 7:30 on a Tuesday evening, and you will be on call until 8 o’clock the next morning. You have already been in the office 9 hours. Usual start time is 8 a.m., but that extra hour at home is a perk you have earned by being on call tonight.
A quick glance at the schedule screen suggests that if nothing ugly crops up, you will finish seeing your last patient and be out the door and on your way home by 8:15 p.m. The phone has been quiet for the last half hour, but as you are making your quickstep transition between exam rooms, the nurse tells you that the receptionist has received a call from a very anxious mother who has just discovered that her 6-year-old has a fever of 103° F. The child didn’t eat any dinner and is now complaining that he has a sore throat. The mother is worried because the child had a couple of febrile seizures when he was a toddler, and she has heard of several cases of strep in his class at school.
On the other hand, you could ask the nurse to reassure the mother that a febrile seizure at age 6 is very unlikely and encourage the mother to call you if she continues to be concerned. The problem here hinges on the experience and skills of the nurse. Even if your office has a well-vetted portfolio of clinical algorithms, you may be relying on a nurse with whom you aren’t familiar. Or maybe your past experience makes you uncomfortable with this particular nurse. She or he may have missed some obvious red flags in the past or may be so unskillful at reassurance that it is very likely that you will be getting a 2 a.m. call from this worried parent.
Another option could be to suggest that after reassuring the mother, the nurse offer her a first of the morning appointment tomorrow. There are several problems with this strategy, and I have always discouraged our office staff from making these next morning appointments for sick children. The offer of the appointment seldom reassures the very anxious parents nor does it prevent the middle of the night calls. More importantly, our experience, and I suspect yours, is that half of those newly sick children with fevers will be better by the next morning or their parents ended up going to the emergency room. This will leave you with a wasted appointment slot that you would really like to have available when the phones heat up in the morning. A more efficient strategy is to promise parents that if the child is still sick in the morning, you can guarantee them a timely appointment.
Finally, there are two responses that worked best for me. The first is to have the nurse ask the parents how long it will take them to get to the office. Add 15 minutes to their estimate, and if you can accept that estimated time of arrival, have the nurse tell that family to hustle on in. Send the staff home unless they want the overtime, and see the patient yourself.
The second response is to get on the phone yourself and talk directly to the mother. You were probably going to end up speaking with her in the middle of the night anyway, so you might as well invest the time now in taking your own history. Even if your own version of reassurance fails to prevent a 2 a.m. call, at least you will have some frame of reference when you need to make one of those dangerous middle of the night clinical decisions. A quiet night may depend on how you manage that last call of the day.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at pdnews@frontlinemedcom.com.
It’s 7:30 on a Tuesday evening, and you will be on call until 8 o’clock the next morning. You have already been in the office 9 hours. Usual start time is 8 a.m., but that extra hour at home is a perk you have earned by being on call tonight.
A quick glance at the schedule screen suggests that if nothing ugly crops up, you will finish seeing your last patient and be out the door and on your way home by 8:15 p.m. The phone has been quiet for the last half hour, but as you are making your quickstep transition between exam rooms, the nurse tells you that the receptionist has received a call from a very anxious mother who has just discovered that her 6-year-old has a fever of 103° F. The child didn’t eat any dinner and is now complaining that he has a sore throat. The mother is worried because the child had a couple of febrile seizures when he was a toddler, and she has heard of several cases of strep in his class at school.
On the other hand, you could ask the nurse to reassure the mother that a febrile seizure at age 6 is very unlikely and encourage the mother to call you if she continues to be concerned. The problem here hinges on the experience and skills of the nurse. Even if your office has a well-vetted portfolio of clinical algorithms, you may be relying on a nurse with whom you aren’t familiar. Or maybe your past experience makes you uncomfortable with this particular nurse. She or he may have missed some obvious red flags in the past or may be so unskillful at reassurance that it is very likely that you will be getting a 2 a.m. call from this worried parent.
Another option could be to suggest that after reassuring the mother, the nurse offer her a first of the morning appointment tomorrow. There are several problems with this strategy, and I have always discouraged our office staff from making these next morning appointments for sick children. The offer of the appointment seldom reassures the very anxious parents nor does it prevent the middle of the night calls. More importantly, our experience, and I suspect yours, is that half of those newly sick children with fevers will be better by the next morning or their parents ended up going to the emergency room. This will leave you with a wasted appointment slot that you would really like to have available when the phones heat up in the morning. A more efficient strategy is to promise parents that if the child is still sick in the morning, you can guarantee them a timely appointment.
Finally, there are two responses that worked best for me. The first is to have the nurse ask the parents how long it will take them to get to the office. Add 15 minutes to their estimate, and if you can accept that estimated time of arrival, have the nurse tell that family to hustle on in. Send the staff home unless they want the overtime, and see the patient yourself.
The second response is to get on the phone yourself and talk directly to the mother. You were probably going to end up speaking with her in the middle of the night anyway, so you might as well invest the time now in taking your own history. Even if your own version of reassurance fails to prevent a 2 a.m. call, at least you will have some frame of reference when you need to make one of those dangerous middle of the night clinical decisions. A quiet night may depend on how you manage that last call of the day.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at pdnews@frontlinemedcom.com.
It’s 7:30 on a Tuesday evening, and you will be on call until 8 o’clock the next morning. You have already been in the office 9 hours. Usual start time is 8 a.m., but that extra hour at home is a perk you have earned by being on call tonight.
A quick glance at the schedule screen suggests that if nothing ugly crops up, you will finish seeing your last patient and be out the door and on your way home by 8:15 p.m. The phone has been quiet for the last half hour, but as you are making your quickstep transition between exam rooms, the nurse tells you that the receptionist has received a call from a very anxious mother who has just discovered that her 6-year-old has a fever of 103° F. The child didn’t eat any dinner and is now complaining that he has a sore throat. The mother is worried because the child had a couple of febrile seizures when he was a toddler, and she has heard of several cases of strep in his class at school.
On the other hand, you could ask the nurse to reassure the mother that a febrile seizure at age 6 is very unlikely and encourage the mother to call you if she continues to be concerned. The problem here hinges on the experience and skills of the nurse. Even if your office has a well-vetted portfolio of clinical algorithms, you may be relying on a nurse with whom you aren’t familiar. Or maybe your past experience makes you uncomfortable with this particular nurse. She or he may have missed some obvious red flags in the past or may be so unskillful at reassurance that it is very likely that you will be getting a 2 a.m. call from this worried parent.
Another option could be to suggest that after reassuring the mother, the nurse offer her a first of the morning appointment tomorrow. There are several problems with this strategy, and I have always discouraged our office staff from making these next morning appointments for sick children. The offer of the appointment seldom reassures the very anxious parents nor does it prevent the middle of the night calls. More importantly, our experience, and I suspect yours, is that half of those newly sick children with fevers will be better by the next morning or their parents ended up going to the emergency room. This will leave you with a wasted appointment slot that you would really like to have available when the phones heat up in the morning. A more efficient strategy is to promise parents that if the child is still sick in the morning, you can guarantee them a timely appointment.
Finally, there are two responses that worked best for me. The first is to have the nurse ask the parents how long it will take them to get to the office. Add 15 minutes to their estimate, and if you can accept that estimated time of arrival, have the nurse tell that family to hustle on in. Send the staff home unless they want the overtime, and see the patient yourself.
The second response is to get on the phone yourself and talk directly to the mother. You were probably going to end up speaking with her in the middle of the night anyway, so you might as well invest the time now in taking your own history. Even if your own version of reassurance fails to prevent a 2 a.m. call, at least you will have some frame of reference when you need to make one of those dangerous middle of the night clinical decisions. A quiet night may depend on how you manage that last call of the day.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at pdnews@frontlinemedcom.com.
Antibiotics have a role in PANS even with no infection
SAN FRANCISCO – Antibiotics might help in pediatric acute-onset neuropsychiatric syndrome (PANS) even if there’s no apparent infection, according to Kiki Chang, MD, director of PANS research at Stanford (Calif.) University.
The first step at Stanford is to look for an active infection, and knock it out with antibiotics. Dr. Chang has seen remarkable turnarounds in some of those cases, but even if there’s no infection, “we still do use antibiotics.” There are positive data, “although not a lot,” indicating that they can help. Some kids even seem to need to be on long-term antibiotics, and flair if taken off long after infections should have been cleared.
“We don’t know what’s going on. We try to stop antibiotics if we can; if patients relapse, we think the benefit [of ongoing treatment] outweighs the risks. Some kids just have to be on antibiotics for a long time, and that’s an issue.” Perhaps it has something to do with the anti-inflammatory properties of antibiotics like azithromycin and amoxicillin, or there might be a lingering infection, he said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
PANS is a recently coined term for the sudden onset of obsessive compulsive disorder (OCD) within a few days of an infection, metabolic disturbance, or other inflammatory insult. Anxiety, mood problems, and tics are common. There might be severe food restriction – only eating white foods, for instance – that are not related to body image.
PANS broadened the concept of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), which was first described in 1998, although it’s been known for generations that acute streptococcus infections can lead to abrupt psychiatric symptoms.
PANS is the topic of ongoing investigation, and Dr. Chang and many others are working to define the syndrome and its treatment, and trying especially to determine how PANS differs from typical OCD and other problems with more insidious onset. The idea is that inflammation in the patient’s brain, whatever the source, triggers an OCD mechanism in susceptible patients. As a concept, “we believe it’s true,” he said.
For now, it’s best to refer suspected cases to one of several academic PANS programs in the United States, as diagnosis and treatment isn’t ready for general practice, he said.
If more than antibiotics are needed, Stanford considers targeting inflammation. Some children respond to easy options such as ibuprofen. Dr. Chang has seen some helped with prednisone, but treatment is tricky. There might be an occult infection, and PANS can present with psychiatric issues that prednisone can make worse, including depression and mania. Intravenous immunoglobulin is another of the many options, “but we really need about four treatments” to see if it helps.
Cognitive behavioral therapy and family support also helps. As for psychotropic medication, “we often use them, but they rarely take away the acute symptoms,” and PANS children seem especially sensitive to side effects. “I’ve seen many of them become manic on SSRIs. I’ve seen some of them have very strong [extrapyramidal symptoms] with atypical antipsychotics. You have to be very careful; we don’t have any good studies” of psychiatric drugs in this population, he said.
At the moment, PANS seems to be more common in boys than girls, and most patients have a relapsing/remitting course and a family history of autoimmune disease. Suicidal and homicidal ideation can be part of the condition.
Dr. Chang believes PANS could be part of the overall increase in autoimmune disease and psychiatric disorders in children over the past few decades.
“We have more kids who have special needs than ever before,” large, objective increases in bipolar, autism, and other psychiatric problems, as well as increases in psoriasis, nut allergies, and other autoimmune issues. “What causes it is harder to say, but there has been a change for sure in kids and their immune system development that does affect the brain, and has probably led to more neuropsychiatric disturbances,” he said.
“No one talks about it. Everyone thinks that it’s some sort of pharmaceutical industry conspiracy” to sell more drugs by increasing scrutiny of children. “I think it’s caused by something in the environment interacting with genetics,” whether it’s infections, toxins, or something else. “We don’t know. Any kind of inflammation can be a trigger” and “we know inflammation” is key to “many psychiatric symptoms. I do think there’s something going on with kids over the last 30 years,” he said.
Dr. Chang is a consultant for and/or has received research support from Bristol-Myers Squibb, Lilly, Merck, GlaxoSmithKline, and other companies.
SAN FRANCISCO – Antibiotics might help in pediatric acute-onset neuropsychiatric syndrome (PANS) even if there’s no apparent infection, according to Kiki Chang, MD, director of PANS research at Stanford (Calif.) University.
The first step at Stanford is to look for an active infection, and knock it out with antibiotics. Dr. Chang has seen remarkable turnarounds in some of those cases, but even if there’s no infection, “we still do use antibiotics.” There are positive data, “although not a lot,” indicating that they can help. Some kids even seem to need to be on long-term antibiotics, and flair if taken off long after infections should have been cleared.
“We don’t know what’s going on. We try to stop antibiotics if we can; if patients relapse, we think the benefit [of ongoing treatment] outweighs the risks. Some kids just have to be on antibiotics for a long time, and that’s an issue.” Perhaps it has something to do with the anti-inflammatory properties of antibiotics like azithromycin and amoxicillin, or there might be a lingering infection, he said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
PANS is a recently coined term for the sudden onset of obsessive compulsive disorder (OCD) within a few days of an infection, metabolic disturbance, or other inflammatory insult. Anxiety, mood problems, and tics are common. There might be severe food restriction – only eating white foods, for instance – that are not related to body image.
PANS broadened the concept of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), which was first described in 1998, although it’s been known for generations that acute streptococcus infections can lead to abrupt psychiatric symptoms.
PANS is the topic of ongoing investigation, and Dr. Chang and many others are working to define the syndrome and its treatment, and trying especially to determine how PANS differs from typical OCD and other problems with more insidious onset. The idea is that inflammation in the patient’s brain, whatever the source, triggers an OCD mechanism in susceptible patients. As a concept, “we believe it’s true,” he said.
For now, it’s best to refer suspected cases to one of several academic PANS programs in the United States, as diagnosis and treatment isn’t ready for general practice, he said.
If more than antibiotics are needed, Stanford considers targeting inflammation. Some children respond to easy options such as ibuprofen. Dr. Chang has seen some helped with prednisone, but treatment is tricky. There might be an occult infection, and PANS can present with psychiatric issues that prednisone can make worse, including depression and mania. Intravenous immunoglobulin is another of the many options, “but we really need about four treatments” to see if it helps.
Cognitive behavioral therapy and family support also helps. As for psychotropic medication, “we often use them, but they rarely take away the acute symptoms,” and PANS children seem especially sensitive to side effects. “I’ve seen many of them become manic on SSRIs. I’ve seen some of them have very strong [extrapyramidal symptoms] with atypical antipsychotics. You have to be very careful; we don’t have any good studies” of psychiatric drugs in this population, he said.
At the moment, PANS seems to be more common in boys than girls, and most patients have a relapsing/remitting course and a family history of autoimmune disease. Suicidal and homicidal ideation can be part of the condition.
Dr. Chang believes PANS could be part of the overall increase in autoimmune disease and psychiatric disorders in children over the past few decades.
“We have more kids who have special needs than ever before,” large, objective increases in bipolar, autism, and other psychiatric problems, as well as increases in psoriasis, nut allergies, and other autoimmune issues. “What causes it is harder to say, but there has been a change for sure in kids and their immune system development that does affect the brain, and has probably led to more neuropsychiatric disturbances,” he said.
“No one talks about it. Everyone thinks that it’s some sort of pharmaceutical industry conspiracy” to sell more drugs by increasing scrutiny of children. “I think it’s caused by something in the environment interacting with genetics,” whether it’s infections, toxins, or something else. “We don’t know. Any kind of inflammation can be a trigger” and “we know inflammation” is key to “many psychiatric symptoms. I do think there’s something going on with kids over the last 30 years,” he said.
Dr. Chang is a consultant for and/or has received research support from Bristol-Myers Squibb, Lilly, Merck, GlaxoSmithKline, and other companies.
SAN FRANCISCO – Antibiotics might help in pediatric acute-onset neuropsychiatric syndrome (PANS) even if there’s no apparent infection, according to Kiki Chang, MD, director of PANS research at Stanford (Calif.) University.
The first step at Stanford is to look for an active infection, and knock it out with antibiotics. Dr. Chang has seen remarkable turnarounds in some of those cases, but even if there’s no infection, “we still do use antibiotics.” There are positive data, “although not a lot,” indicating that they can help. Some kids even seem to need to be on long-term antibiotics, and flair if taken off long after infections should have been cleared.
“We don’t know what’s going on. We try to stop antibiotics if we can; if patients relapse, we think the benefit [of ongoing treatment] outweighs the risks. Some kids just have to be on antibiotics for a long time, and that’s an issue.” Perhaps it has something to do with the anti-inflammatory properties of antibiotics like azithromycin and amoxicillin, or there might be a lingering infection, he said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
PANS is a recently coined term for the sudden onset of obsessive compulsive disorder (OCD) within a few days of an infection, metabolic disturbance, or other inflammatory insult. Anxiety, mood problems, and tics are common. There might be severe food restriction – only eating white foods, for instance – that are not related to body image.
PANS broadened the concept of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), which was first described in 1998, although it’s been known for generations that acute streptococcus infections can lead to abrupt psychiatric symptoms.
PANS is the topic of ongoing investigation, and Dr. Chang and many others are working to define the syndrome and its treatment, and trying especially to determine how PANS differs from typical OCD and other problems with more insidious onset. The idea is that inflammation in the patient’s brain, whatever the source, triggers an OCD mechanism in susceptible patients. As a concept, “we believe it’s true,” he said.
For now, it’s best to refer suspected cases to one of several academic PANS programs in the United States, as diagnosis and treatment isn’t ready for general practice, he said.
If more than antibiotics are needed, Stanford considers targeting inflammation. Some children respond to easy options such as ibuprofen. Dr. Chang has seen some helped with prednisone, but treatment is tricky. There might be an occult infection, and PANS can present with psychiatric issues that prednisone can make worse, including depression and mania. Intravenous immunoglobulin is another of the many options, “but we really need about four treatments” to see if it helps.
Cognitive behavioral therapy and family support also helps. As for psychotropic medication, “we often use them, but they rarely take away the acute symptoms,” and PANS children seem especially sensitive to side effects. “I’ve seen many of them become manic on SSRIs. I’ve seen some of them have very strong [extrapyramidal symptoms] with atypical antipsychotics. You have to be very careful; we don’t have any good studies” of psychiatric drugs in this population, he said.
At the moment, PANS seems to be more common in boys than girls, and most patients have a relapsing/remitting course and a family history of autoimmune disease. Suicidal and homicidal ideation can be part of the condition.
Dr. Chang believes PANS could be part of the overall increase in autoimmune disease and psychiatric disorders in children over the past few decades.
“We have more kids who have special needs than ever before,” large, objective increases in bipolar, autism, and other psychiatric problems, as well as increases in psoriasis, nut allergies, and other autoimmune issues. “What causes it is harder to say, but there has been a change for sure in kids and their immune system development that does affect the brain, and has probably led to more neuropsychiatric disturbances,” he said.
“No one talks about it. Everyone thinks that it’s some sort of pharmaceutical industry conspiracy” to sell more drugs by increasing scrutiny of children. “I think it’s caused by something in the environment interacting with genetics,” whether it’s infections, toxins, or something else. “We don’t know. Any kind of inflammation can be a trigger” and “we know inflammation” is key to “many psychiatric symptoms. I do think there’s something going on with kids over the last 30 years,” he said.
Dr. Chang is a consultant for and/or has received research support from Bristol-Myers Squibb, Lilly, Merck, GlaxoSmithKline, and other companies.
EXPERT ANALYSIS FROM THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Nicardipine okay to use after pediatric cardiac surgery
HOUSTON – The use of nicardipine following cardiac surgery in children appears to be safe and effective, results from a single-center study suggest.
“There has been a traditional hesitation to use calcium channel blockers, particularly in infants, due to underdevelopment of their calcium channels,” study investigator Matthew L. Stone, MD, PhD, said in an interview at the annual meeting of the Society of Thoracic Surgeons.
“Further, these agents have commonly lacked selectivity to the vascular smooth muscles affecting both the blood vessels and the heart. Nicardipine offers a unique advantage over other calcium channel blockers in that it has more direct effects on vascular smooth muscles than it does on the actual myocardium.”
In their study, Dr. Stone, a first-year fellow in the division of cardiothoracic surgery at the University of Virginia Health System, Charlottesville, and his associates noted that nicardipine offers a favorable pharmacokinetic profile with both rapid onset and short half-life. The purpose of the study was to evaluate the use of nicardipine as a first-line agent for treatment of postoperative hypertension and to compare outcomes between children younger than 6 months of age and those older than 6 months. The researchers retrospectively reviewed the medical records of 68 children who received nicardipine for postoperative hypertension after undergoing cardiac surgery at the University of Virginia during 2010-2015. They compared the incidence of adverse postoperative events between 33 children who were younger than 6 months (group 1) and 35 who were older than 6 months (group 2). Major events including stroke or cardiogenic shock were considered failure of therapy.
Dr. Stone and his associates found that all children received nicardipine within a median of 90 minutes following cardiac surgery; 22 (33%) were started on the drug prior to leaving the operating room and most required dosing for less than 24 hours. Clinically significant hypertension that required dose titration or cessation of therapy occurred in 13% of patients, but there were no significant differences between age groups (17% in group 1 vs. 9% in group 2; P = 0.47). “While the incidence of hypotension following nicardipine administration did not reach statistical significance, it’s important to note that going forward, a lower starting dose in infants less than 6 months of age may be most appropriate. This would certainly be an important focus for future prospective study in the development of postoperative blood pressure control protocols,” said Dr. Stone.
No significant adverse events including stroke or cardiogenic shock occurred in either group. In addition, no operative or postoperative factors reviewed were associated with the development of complications during administration of nicardipine. This included cardiopulmonary bypass time, cross-clamp time, ventilator time, nicardipine duration, ICU length of stay, and hospital length of stay.
“Our traditional hesitation to use this class of agents in infants should be reevaluated,” Dr. Stone concluded. “As we move toward standardization and optimization of perioperative care, our study supports the use and prospective clinical study of nicardipine. Additionally, further pharmacologic study of dose-specific responses within myocardial and vascular smooth muscle cells may further optimize this treatment strategy and provide a more reliable standard with which to control blood pressure.
“Our traditional agents such as beta-blockers and nitroprusside have side effects that need to be considered, the most significant of which being myocardial depression and cyanide toxicity. In a limited number of very-high-risk children, we’ve shown that nicardipine may provide an option with less deleterious side effects. It’s a foundation for future study.”
Dr. Stone reported having no financial disclosures.
HOUSTON – The use of nicardipine following cardiac surgery in children appears to be safe and effective, results from a single-center study suggest.
“There has been a traditional hesitation to use calcium channel blockers, particularly in infants, due to underdevelopment of their calcium channels,” study investigator Matthew L. Stone, MD, PhD, said in an interview at the annual meeting of the Society of Thoracic Surgeons.
“Further, these agents have commonly lacked selectivity to the vascular smooth muscles affecting both the blood vessels and the heart. Nicardipine offers a unique advantage over other calcium channel blockers in that it has more direct effects on vascular smooth muscles than it does on the actual myocardium.”
In their study, Dr. Stone, a first-year fellow in the division of cardiothoracic surgery at the University of Virginia Health System, Charlottesville, and his associates noted that nicardipine offers a favorable pharmacokinetic profile with both rapid onset and short half-life. The purpose of the study was to evaluate the use of nicardipine as a first-line agent for treatment of postoperative hypertension and to compare outcomes between children younger than 6 months of age and those older than 6 months. The researchers retrospectively reviewed the medical records of 68 children who received nicardipine for postoperative hypertension after undergoing cardiac surgery at the University of Virginia during 2010-2015. They compared the incidence of adverse postoperative events between 33 children who were younger than 6 months (group 1) and 35 who were older than 6 months (group 2). Major events including stroke or cardiogenic shock were considered failure of therapy.
Dr. Stone and his associates found that all children received nicardipine within a median of 90 minutes following cardiac surgery; 22 (33%) were started on the drug prior to leaving the operating room and most required dosing for less than 24 hours. Clinically significant hypertension that required dose titration or cessation of therapy occurred in 13% of patients, but there were no significant differences between age groups (17% in group 1 vs. 9% in group 2; P = 0.47). “While the incidence of hypotension following nicardipine administration did not reach statistical significance, it’s important to note that going forward, a lower starting dose in infants less than 6 months of age may be most appropriate. This would certainly be an important focus for future prospective study in the development of postoperative blood pressure control protocols,” said Dr. Stone.
No significant adverse events including stroke or cardiogenic shock occurred in either group. In addition, no operative or postoperative factors reviewed were associated with the development of complications during administration of nicardipine. This included cardiopulmonary bypass time, cross-clamp time, ventilator time, nicardipine duration, ICU length of stay, and hospital length of stay.
“Our traditional hesitation to use this class of agents in infants should be reevaluated,” Dr. Stone concluded. “As we move toward standardization and optimization of perioperative care, our study supports the use and prospective clinical study of nicardipine. Additionally, further pharmacologic study of dose-specific responses within myocardial and vascular smooth muscle cells may further optimize this treatment strategy and provide a more reliable standard with which to control blood pressure.
“Our traditional agents such as beta-blockers and nitroprusside have side effects that need to be considered, the most significant of which being myocardial depression and cyanide toxicity. In a limited number of very-high-risk children, we’ve shown that nicardipine may provide an option with less deleterious side effects. It’s a foundation for future study.”
Dr. Stone reported having no financial disclosures.
HOUSTON – The use of nicardipine following cardiac surgery in children appears to be safe and effective, results from a single-center study suggest.
“There has been a traditional hesitation to use calcium channel blockers, particularly in infants, due to underdevelopment of their calcium channels,” study investigator Matthew L. Stone, MD, PhD, said in an interview at the annual meeting of the Society of Thoracic Surgeons.
“Further, these agents have commonly lacked selectivity to the vascular smooth muscles affecting both the blood vessels and the heart. Nicardipine offers a unique advantage over other calcium channel blockers in that it has more direct effects on vascular smooth muscles than it does on the actual myocardium.”
In their study, Dr. Stone, a first-year fellow in the division of cardiothoracic surgery at the University of Virginia Health System, Charlottesville, and his associates noted that nicardipine offers a favorable pharmacokinetic profile with both rapid onset and short half-life. The purpose of the study was to evaluate the use of nicardipine as a first-line agent for treatment of postoperative hypertension and to compare outcomes between children younger than 6 months of age and those older than 6 months. The researchers retrospectively reviewed the medical records of 68 children who received nicardipine for postoperative hypertension after undergoing cardiac surgery at the University of Virginia during 2010-2015. They compared the incidence of adverse postoperative events between 33 children who were younger than 6 months (group 1) and 35 who were older than 6 months (group 2). Major events including stroke or cardiogenic shock were considered failure of therapy.
Dr. Stone and his associates found that all children received nicardipine within a median of 90 minutes following cardiac surgery; 22 (33%) were started on the drug prior to leaving the operating room and most required dosing for less than 24 hours. Clinically significant hypertension that required dose titration or cessation of therapy occurred in 13% of patients, but there were no significant differences between age groups (17% in group 1 vs. 9% in group 2; P = 0.47). “While the incidence of hypotension following nicardipine administration did not reach statistical significance, it’s important to note that going forward, a lower starting dose in infants less than 6 months of age may be most appropriate. This would certainly be an important focus for future prospective study in the development of postoperative blood pressure control protocols,” said Dr. Stone.
No significant adverse events including stroke or cardiogenic shock occurred in either group. In addition, no operative or postoperative factors reviewed were associated with the development of complications during administration of nicardipine. This included cardiopulmonary bypass time, cross-clamp time, ventilator time, nicardipine duration, ICU length of stay, and hospital length of stay.
“Our traditional hesitation to use this class of agents in infants should be reevaluated,” Dr. Stone concluded. “As we move toward standardization and optimization of perioperative care, our study supports the use and prospective clinical study of nicardipine. Additionally, further pharmacologic study of dose-specific responses within myocardial and vascular smooth muscle cells may further optimize this treatment strategy and provide a more reliable standard with which to control blood pressure.
“Our traditional agents such as beta-blockers and nitroprusside have side effects that need to be considered, the most significant of which being myocardial depression and cyanide toxicity. In a limited number of very-high-risk children, we’ve shown that nicardipine may provide an option with less deleterious side effects. It’s a foundation for future study.”
Dr. Stone reported having no financial disclosures.
AT THE STS ANNUAL MEETING
Key clinical point:
Major finding: The incidence of adverse postoperative events was similar between children who were younger than 6 months and those who were older than 6 months (17% vs. 9%, respectively), but no significant adverse events, including stroke and cardiogenic shock, occurred in either group.
Data source: A retrospective review of 68 children who received nicardipine for postoperative hypertension after undergoing cardiac surgery during 2010-2015.
Disclosures: Dr. Stone reported having no financial disclosures.
Review offers reassurance on prenatal Tdap vaccination safety
Combined tetanus, diphtheria, and pertussis (Tdap) vaccination during the second or third trimester of pregnancy does not appear to be associated with clinically significant harm to the fetus or neonate, according to findings from a systematic review of the literature.
However, the findings are limited by a dearth of randomized, placebo-controlled trials.
Point estimates for all anomalies after Tdap vaccination ranged from 1.20 to 1.60, Mark McMillan of the University of Adelaide, North Adelaide, Australia and his colleagues reported (Obstet Gynecol. 2017;129:560-73).
“Statistical imprecision for combined ‘all anomalies’ outcomes meant that upper 95% [confidence intervals] were 2.0 or above,” the researchers wrote. “Statistical imprecision was even greater in the individual congenital anomaly outcomes and little confidence can be placed in these estimates.”
Additionally, one of three studies assessing chorioamnionitis showed a small but significant increase in risk (relative risk, 1.19) after vaccination.
Among the studies examining medically attended adverse events, no association was seen between vaccination and such events or reactions, including neurologic events, gestational diabetes, preeclampsia or eclampsia, and cardiac events. Maternal effects included fever in 1%-3% of subjects, and headache, malaise, and myalgia, which were more common.
“Overall, despite the limitations described, the review offers reassurance for antenatal Tdap or Tdap-IPV [diphtheria, tetanus, pertussis, and polio] vaccination administered during the second or third trimester of pregnancy,” the researchers wrote. “These findings need to be interpreted in the context of the evidence of effectiveness of antenatal vaccination programs at preventing serious morbidity and mortality from pertussis in young infants.”
Mr. McMillan received travel support from GlaxoSmithKline, and institutional research grants from GSK and Sanofi Pasteur. Other researchers also reported receiving research funding and/or travel support from these companies.
Combined tetanus, diphtheria, and pertussis (Tdap) vaccination during the second or third trimester of pregnancy does not appear to be associated with clinically significant harm to the fetus or neonate, according to findings from a systematic review of the literature.
However, the findings are limited by a dearth of randomized, placebo-controlled trials.
Point estimates for all anomalies after Tdap vaccination ranged from 1.20 to 1.60, Mark McMillan of the University of Adelaide, North Adelaide, Australia and his colleagues reported (Obstet Gynecol. 2017;129:560-73).
“Statistical imprecision for combined ‘all anomalies’ outcomes meant that upper 95% [confidence intervals] were 2.0 or above,” the researchers wrote. “Statistical imprecision was even greater in the individual congenital anomaly outcomes and little confidence can be placed in these estimates.”
Additionally, one of three studies assessing chorioamnionitis showed a small but significant increase in risk (relative risk, 1.19) after vaccination.
Among the studies examining medically attended adverse events, no association was seen between vaccination and such events or reactions, including neurologic events, gestational diabetes, preeclampsia or eclampsia, and cardiac events. Maternal effects included fever in 1%-3% of subjects, and headache, malaise, and myalgia, which were more common.
“Overall, despite the limitations described, the review offers reassurance for antenatal Tdap or Tdap-IPV [diphtheria, tetanus, pertussis, and polio] vaccination administered during the second or third trimester of pregnancy,” the researchers wrote. “These findings need to be interpreted in the context of the evidence of effectiveness of antenatal vaccination programs at preventing serious morbidity and mortality from pertussis in young infants.”
Mr. McMillan received travel support from GlaxoSmithKline, and institutional research grants from GSK and Sanofi Pasteur. Other researchers also reported receiving research funding and/or travel support from these companies.
Combined tetanus, diphtheria, and pertussis (Tdap) vaccination during the second or third trimester of pregnancy does not appear to be associated with clinically significant harm to the fetus or neonate, according to findings from a systematic review of the literature.
However, the findings are limited by a dearth of randomized, placebo-controlled trials.
Point estimates for all anomalies after Tdap vaccination ranged from 1.20 to 1.60, Mark McMillan of the University of Adelaide, North Adelaide, Australia and his colleagues reported (Obstet Gynecol. 2017;129:560-73).
“Statistical imprecision for combined ‘all anomalies’ outcomes meant that upper 95% [confidence intervals] were 2.0 or above,” the researchers wrote. “Statistical imprecision was even greater in the individual congenital anomaly outcomes and little confidence can be placed in these estimates.”
Additionally, one of three studies assessing chorioamnionitis showed a small but significant increase in risk (relative risk, 1.19) after vaccination.
Among the studies examining medically attended adverse events, no association was seen between vaccination and such events or reactions, including neurologic events, gestational diabetes, preeclampsia or eclampsia, and cardiac events. Maternal effects included fever in 1%-3% of subjects, and headache, malaise, and myalgia, which were more common.
“Overall, despite the limitations described, the review offers reassurance for antenatal Tdap or Tdap-IPV [diphtheria, tetanus, pertussis, and polio] vaccination administered during the second or third trimester of pregnancy,” the researchers wrote. “These findings need to be interpreted in the context of the evidence of effectiveness of antenatal vaccination programs at preventing serious morbidity and mortality from pertussis in young infants.”
Mr. McMillan received travel support from GlaxoSmithKline, and institutional research grants from GSK and Sanofi Pasteur. Other researchers also reported receiving research funding and/or travel support from these companies.
FROM OBSTETRICS & GYNECOLOGY
Key clinical point:
Major finding: Point estimates for all anomalies after Tdap vaccination ranged from 1.20 to 1.60.
Data source: A systematic review of 21 studies.
Disclosures: Mr. McMillan received travel support from GlaxoSmithKline, and institutional research grants from GSK and Sanofi Pasteur. Other researchers also reported receiving research funding and/or travel support from these companies.
Liver transplantation largely effective in critically ill children
The use of advanced critical care in children and infants with liver failure is justified because orthotopic liver transplantation can be performed on the sickest children and achieve acceptable outcomes, results from a large analysis demonstrated.
“Hand in hand with improved care for critically ill children with liver failure, posttransplant critical care has made tremendous strides,” Abbas Rana, MD, wrote in a study published online in the Journal of the American College of Surgeons. “Our recipients have gotten sicker while our postoperative outcomes have improved. The question then becomes, have our operative skills and postoperative critical care management kept up with the abilities to keep sick children with liver failure alive? Just because transplantation is now possible in our sickest children, is it justified?”
To find out, Dr. Rana of the division of abdominal transplantation and hepatobiliary surgery at Baylor College of Medicine, Houston, and colleagues retrospectively analyzed United Network for Organ Sharing data from all orthotopic liver transplantation (OLT) recipients between Sept. 1, 1987, and June 30, 2015. The analysis paired the liver registry data with data collected by the Organ Procurement and Transplantation Network, and was limited to transplant recipients younger than age 18. The researchers followed a total of 13,723 recipients from date of transplant until either death or the date of last known follow-up (J Am Coll Surg. 2016 Dec 25. doi: 10.1016/j.jamcollsurg.2016.12.025).
In another part of the study, the researchers retrospectively reviewed the charts of 354 patients under 18 years of age who underwent OLT between March 1, 2002, and June 30, 2015, at Texas Children’s Hospital, including 65 who were admitted to the ICU at the time of transplantation.
In the analysis of national data, the researchers found that the rates of 1-year survival following OLT in children in the ICU improved from 60% in 1987 to 92% in 2013 (P less than .001). The rates of 1-year survival also improved for children on dialysis at the time of transplant (from 50% in 1995 to 95% in 2013; P less than .001) and for those dependent on a mechanical ventilator at the time of transplant (from 49% in 1994 to 94% in 2013; P less than .001). The significant risk factors were two previous transplants (hazard ratio, 4.2), one previous transplant (HR, 2.5), serum sodium greater than 150 mEq/L (HR, 2.0), dialysis or glomerular filtration rate less than 30 mL/min per 1.73 m2 (HR, 2.0), mechanical ventilator dependence (HR, 1.8), body weight under 6 kg (HR, 1.8), encephalopathy (HR, 1.8), and annual center volume of fewer than five cases (HR, 1.7).
In the experience at Texas Children’s Hospital, the researchers observed “preserved and successful patient survival outcomes” in many markers of acuity. For example, the 10-year survival rates for patients dependent on mechanical ventilation and dialysis were 85% and 96%, respectively, and reached 100% for those requiring therapeutic plasma exchange, molescular adsorbent recirculating system (MARS) liver dialysis, and vasopressors.
“Our collective ability to keep sick children alive with liver failure has improved considerably over the years,” the researchers wrote. “Keeping pace, this analysis demonstrates that the posttransplant outcomes have also improved dramatically. The survival outcomes are comparable to the general population, justifying the use of scarce donors. Although we cannot declare in absolute that no child should be left behind, we can demonstrate acceptable outcomes to date and urge the continual revisiting of our concepts of futility.
“We have learned throughout our experience that almost every child with end-stage liver disease and acute liver failure should be offered liver replacement, as long as the vasoactive medication and mechanical support are not maximized prior to the initiation of the OLT procedure. Every effort should be made to transplant our sickest children.”
This study was supported by the Cade R. Alpard Foundation. The researchers reported having no relevant financial disclosures.
The use of advanced critical care in children and infants with liver failure is justified because orthotopic liver transplantation can be performed on the sickest children and achieve acceptable outcomes, results from a large analysis demonstrated.
“Hand in hand with improved care for critically ill children with liver failure, posttransplant critical care has made tremendous strides,” Abbas Rana, MD, wrote in a study published online in the Journal of the American College of Surgeons. “Our recipients have gotten sicker while our postoperative outcomes have improved. The question then becomes, have our operative skills and postoperative critical care management kept up with the abilities to keep sick children with liver failure alive? Just because transplantation is now possible in our sickest children, is it justified?”
To find out, Dr. Rana of the division of abdominal transplantation and hepatobiliary surgery at Baylor College of Medicine, Houston, and colleagues retrospectively analyzed United Network for Organ Sharing data from all orthotopic liver transplantation (OLT) recipients between Sept. 1, 1987, and June 30, 2015. The analysis paired the liver registry data with data collected by the Organ Procurement and Transplantation Network, and was limited to transplant recipients younger than age 18. The researchers followed a total of 13,723 recipients from date of transplant until either death or the date of last known follow-up (J Am Coll Surg. 2016 Dec 25. doi: 10.1016/j.jamcollsurg.2016.12.025).
In another part of the study, the researchers retrospectively reviewed the charts of 354 patients under 18 years of age who underwent OLT between March 1, 2002, and June 30, 2015, at Texas Children’s Hospital, including 65 who were admitted to the ICU at the time of transplantation.
In the analysis of national data, the researchers found that the rates of 1-year survival following OLT in children in the ICU improved from 60% in 1987 to 92% in 2013 (P less than .001). The rates of 1-year survival also improved for children on dialysis at the time of transplant (from 50% in 1995 to 95% in 2013; P less than .001) and for those dependent on a mechanical ventilator at the time of transplant (from 49% in 1994 to 94% in 2013; P less than .001). The significant risk factors were two previous transplants (hazard ratio, 4.2), one previous transplant (HR, 2.5), serum sodium greater than 150 mEq/L (HR, 2.0), dialysis or glomerular filtration rate less than 30 mL/min per 1.73 m2 (HR, 2.0), mechanical ventilator dependence (HR, 1.8), body weight under 6 kg (HR, 1.8), encephalopathy (HR, 1.8), and annual center volume of fewer than five cases (HR, 1.7).
In the experience at Texas Children’s Hospital, the researchers observed “preserved and successful patient survival outcomes” in many markers of acuity. For example, the 10-year survival rates for patients dependent on mechanical ventilation and dialysis were 85% and 96%, respectively, and reached 100% for those requiring therapeutic plasma exchange, molescular adsorbent recirculating system (MARS) liver dialysis, and vasopressors.
“Our collective ability to keep sick children alive with liver failure has improved considerably over the years,” the researchers wrote. “Keeping pace, this analysis demonstrates that the posttransplant outcomes have also improved dramatically. The survival outcomes are comparable to the general population, justifying the use of scarce donors. Although we cannot declare in absolute that no child should be left behind, we can demonstrate acceptable outcomes to date and urge the continual revisiting of our concepts of futility.
“We have learned throughout our experience that almost every child with end-stage liver disease and acute liver failure should be offered liver replacement, as long as the vasoactive medication and mechanical support are not maximized prior to the initiation of the OLT procedure. Every effort should be made to transplant our sickest children.”
This study was supported by the Cade R. Alpard Foundation. The researchers reported having no relevant financial disclosures.
The use of advanced critical care in children and infants with liver failure is justified because orthotopic liver transplantation can be performed on the sickest children and achieve acceptable outcomes, results from a large analysis demonstrated.
“Hand in hand with improved care for critically ill children with liver failure, posttransplant critical care has made tremendous strides,” Abbas Rana, MD, wrote in a study published online in the Journal of the American College of Surgeons. “Our recipients have gotten sicker while our postoperative outcomes have improved. The question then becomes, have our operative skills and postoperative critical care management kept up with the abilities to keep sick children with liver failure alive? Just because transplantation is now possible in our sickest children, is it justified?”
To find out, Dr. Rana of the division of abdominal transplantation and hepatobiliary surgery at Baylor College of Medicine, Houston, and colleagues retrospectively analyzed United Network for Organ Sharing data from all orthotopic liver transplantation (OLT) recipients between Sept. 1, 1987, and June 30, 2015. The analysis paired the liver registry data with data collected by the Organ Procurement and Transplantation Network, and was limited to transplant recipients younger than age 18. The researchers followed a total of 13,723 recipients from date of transplant until either death or the date of last known follow-up (J Am Coll Surg. 2016 Dec 25. doi: 10.1016/j.jamcollsurg.2016.12.025).
In another part of the study, the researchers retrospectively reviewed the charts of 354 patients under 18 years of age who underwent OLT between March 1, 2002, and June 30, 2015, at Texas Children’s Hospital, including 65 who were admitted to the ICU at the time of transplantation.
In the analysis of national data, the researchers found that the rates of 1-year survival following OLT in children in the ICU improved from 60% in 1987 to 92% in 2013 (P less than .001). The rates of 1-year survival also improved for children on dialysis at the time of transplant (from 50% in 1995 to 95% in 2013; P less than .001) and for those dependent on a mechanical ventilator at the time of transplant (from 49% in 1994 to 94% in 2013; P less than .001). The significant risk factors were two previous transplants (hazard ratio, 4.2), one previous transplant (HR, 2.5), serum sodium greater than 150 mEq/L (HR, 2.0), dialysis or glomerular filtration rate less than 30 mL/min per 1.73 m2 (HR, 2.0), mechanical ventilator dependence (HR, 1.8), body weight under 6 kg (HR, 1.8), encephalopathy (HR, 1.8), and annual center volume of fewer than five cases (HR, 1.7).
In the experience at Texas Children’s Hospital, the researchers observed “preserved and successful patient survival outcomes” in many markers of acuity. For example, the 10-year survival rates for patients dependent on mechanical ventilation and dialysis were 85% and 96%, respectively, and reached 100% for those requiring therapeutic plasma exchange, molescular adsorbent recirculating system (MARS) liver dialysis, and vasopressors.
“Our collective ability to keep sick children alive with liver failure has improved considerably over the years,” the researchers wrote. “Keeping pace, this analysis demonstrates that the posttransplant outcomes have also improved dramatically. The survival outcomes are comparable to the general population, justifying the use of scarce donors. Although we cannot declare in absolute that no child should be left behind, we can demonstrate acceptable outcomes to date and urge the continual revisiting of our concepts of futility.
“We have learned throughout our experience that almost every child with end-stage liver disease and acute liver failure should be offered liver replacement, as long as the vasoactive medication and mechanical support are not maximized prior to the initiation of the OLT procedure. Every effort should be made to transplant our sickest children.”
This study was supported by the Cade R. Alpard Foundation. The researchers reported having no relevant financial disclosures.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
Key clinical point:
Major finding: The rates of 1-year survival following orthotopic liver transplantation in ICU children improved from 60% in 1987 to 92% in 2013 (P less than .001).
Data source: An analysis of 13,723 patients under the age of 18 years who underwent OLT between Sept. 1, 1987, and June 30, 2015.
Disclosures: The study was supported by the Cade R. Alpard Foundation. The researchers reported having no relevant financial disclosures.
Updated guidelines offer insight into pediatric obesity
Among other things, the guidelines offer new insight into the role of genetics in childhood obesity, provide more extensive guidance regarding bariatric surgery in adolescents, and suggest that measurements of insulin concentrations aren’t useful barometers.
The guidelines also point to research gaps in several areas and call for more studies.
Why issue new guidelines now? “Eight years have passed since the last publication. We did a very thorough job, but there’s been an incredible amount of interest in child obesity, and more information is available,” lead author Dennis M. Styne, MD, professor of pediatrics and the Yocha Dehe endowed chair in pediatric endocrinology at the University of California at Davis, said in an interview. Indeed, recent years have produced hundreds of studies into pediatric obesity, he noted.
The 49-page guidelines are cosponsored by the European Society of Endocrinology and the Pediatric Endocrine Society (J Clin Endocrinol Metab. 2017 March;102[3]:1-49).
Pediatric obesity is of special interest to endocrinologists, Dr. Styne said. “While there’s interest from many specialists now, we are at the forefront of evaluation and treatment of complications like polycystic ovary syndrome, metabolic syndrome, dyslipidemia, and type 2 diabetes.”
The guidelines provide recommendations about a wide variety of obesity-related topics including screening, diagnosis, and treatment. The Endocrine Society commissioned two systematic reviews to support the guidelines: One examined longer randomized controlled trials into medication, surgery, lifestyle, and community-based intervention treatments. The other examined how changing body mass index levels corresponded to cardiometabolic changes.
Several updated areas in the guidelines should be of special interest to endocrinologists: guidance regarding the genetic causes of pediatric obesity, the use of weight-loss medication and surgery, and the roles of insulin tests and breast-feeding, according to Dr. Styne.
In regard to genetics, the guidelines note that research suggests 7% of patients with extreme pediatric obesity “may have rare chromosomal abnormalities and/or highly penetrant genetic mutations that drive their obesity. This percentage is likely to increase with newer methods for genetic testing.”
Dr. Styne calls this finding “remarkable.” As he put it, “we didn’t appreciate that so much in the past.”
The guidelines suggest genetic testing for patients who become obese before the age of 5 years, have a family history of extreme obesity, or show clinical signs of genetic obesity syndromes, especially extreme hyperphagia.
As for the most extreme treatments for the most obese children, the guidelines recommend against weight-loss medication outside of clinical trials and note that “increasing evidence” supports bariatric surgery in teens who haven’t been able to lose enough pounds through lifestyle modification. However, “the use of surgery requires experienced teams with resources for long-term follow-up.”
The guidelines also recommend against measuring serum insulin concentrations as part of pediatric screening for obesity. “A lot of people like to get insulin levels and think it tells them about the future of the child,” Dr. Styne said. “But it doesn’t work very well.”
In another area that reflects new information, the guidelines note that breast-feeding hasn’t been definitively shown to be effective in reducing childhood obesity. “The literature is contradictory,” Dr. Styne said, although he noted that breast-feeding still has many other benefits.
The guidelines point to research gaps in several areas, including the prevention and treatment of pediatric obesity. There’s also “uncharted territory” regarding how to “effectively transition to adult care, with continued necessary monitoring, support, and intervention.”
In regard to the best treatment programs, “we didn’t come up with an answer regarding overall effectiveness,” Dr. Styne said. “School- and community-based programs have promise, but I can’t give you the percentage of success.”
As for the overall picture of pediatric obesity in the United States, “we’re in a better situation than we were 8 years ago,” he said. “Everyone is talking about the problem, and when you talk to families, they’re more aware of it.”
Still, he said, the prevalence of obesity in kids is high, estimated at 17% of those aged 2-19 years in 2014. “That’s not a good place to be,” he said. “We still have to work harder.”
The Endocrine Society funded the guidelines. Dr. Styne reports ownership interests in Teva, Bristol Myers and Organovo. Other authors report various disclosures.
Among other things, the guidelines offer new insight into the role of genetics in childhood obesity, provide more extensive guidance regarding bariatric surgery in adolescents, and suggest that measurements of insulin concentrations aren’t useful barometers.
The guidelines also point to research gaps in several areas and call for more studies.
Why issue new guidelines now? “Eight years have passed since the last publication. We did a very thorough job, but there’s been an incredible amount of interest in child obesity, and more information is available,” lead author Dennis M. Styne, MD, professor of pediatrics and the Yocha Dehe endowed chair in pediatric endocrinology at the University of California at Davis, said in an interview. Indeed, recent years have produced hundreds of studies into pediatric obesity, he noted.
The 49-page guidelines are cosponsored by the European Society of Endocrinology and the Pediatric Endocrine Society (J Clin Endocrinol Metab. 2017 March;102[3]:1-49).
Pediatric obesity is of special interest to endocrinologists, Dr. Styne said. “While there’s interest from many specialists now, we are at the forefront of evaluation and treatment of complications like polycystic ovary syndrome, metabolic syndrome, dyslipidemia, and type 2 diabetes.”
The guidelines provide recommendations about a wide variety of obesity-related topics including screening, diagnosis, and treatment. The Endocrine Society commissioned two systematic reviews to support the guidelines: One examined longer randomized controlled trials into medication, surgery, lifestyle, and community-based intervention treatments. The other examined how changing body mass index levels corresponded to cardiometabolic changes.
Several updated areas in the guidelines should be of special interest to endocrinologists: guidance regarding the genetic causes of pediatric obesity, the use of weight-loss medication and surgery, and the roles of insulin tests and breast-feeding, according to Dr. Styne.
In regard to genetics, the guidelines note that research suggests 7% of patients with extreme pediatric obesity “may have rare chromosomal abnormalities and/or highly penetrant genetic mutations that drive their obesity. This percentage is likely to increase with newer methods for genetic testing.”
Dr. Styne calls this finding “remarkable.” As he put it, “we didn’t appreciate that so much in the past.”
The guidelines suggest genetic testing for patients who become obese before the age of 5 years, have a family history of extreme obesity, or show clinical signs of genetic obesity syndromes, especially extreme hyperphagia.
As for the most extreme treatments for the most obese children, the guidelines recommend against weight-loss medication outside of clinical trials and note that “increasing evidence” supports bariatric surgery in teens who haven’t been able to lose enough pounds through lifestyle modification. However, “the use of surgery requires experienced teams with resources for long-term follow-up.”
The guidelines also recommend against measuring serum insulin concentrations as part of pediatric screening for obesity. “A lot of people like to get insulin levels and think it tells them about the future of the child,” Dr. Styne said. “But it doesn’t work very well.”
In another area that reflects new information, the guidelines note that breast-feeding hasn’t been definitively shown to be effective in reducing childhood obesity. “The literature is contradictory,” Dr. Styne said, although he noted that breast-feeding still has many other benefits.
The guidelines point to research gaps in several areas, including the prevention and treatment of pediatric obesity. There’s also “uncharted territory” regarding how to “effectively transition to adult care, with continued necessary monitoring, support, and intervention.”
In regard to the best treatment programs, “we didn’t come up with an answer regarding overall effectiveness,” Dr. Styne said. “School- and community-based programs have promise, but I can’t give you the percentage of success.”
As for the overall picture of pediatric obesity in the United States, “we’re in a better situation than we were 8 years ago,” he said. “Everyone is talking about the problem, and when you talk to families, they’re more aware of it.”
Still, he said, the prevalence of obesity in kids is high, estimated at 17% of those aged 2-19 years in 2014. “That’s not a good place to be,” he said. “We still have to work harder.”
The Endocrine Society funded the guidelines. Dr. Styne reports ownership interests in Teva, Bristol Myers and Organovo. Other authors report various disclosures.
Among other things, the guidelines offer new insight into the role of genetics in childhood obesity, provide more extensive guidance regarding bariatric surgery in adolescents, and suggest that measurements of insulin concentrations aren’t useful barometers.
The guidelines also point to research gaps in several areas and call for more studies.
Why issue new guidelines now? “Eight years have passed since the last publication. We did a very thorough job, but there’s been an incredible amount of interest in child obesity, and more information is available,” lead author Dennis M. Styne, MD, professor of pediatrics and the Yocha Dehe endowed chair in pediatric endocrinology at the University of California at Davis, said in an interview. Indeed, recent years have produced hundreds of studies into pediatric obesity, he noted.
The 49-page guidelines are cosponsored by the European Society of Endocrinology and the Pediatric Endocrine Society (J Clin Endocrinol Metab. 2017 March;102[3]:1-49).
Pediatric obesity is of special interest to endocrinologists, Dr. Styne said. “While there’s interest from many specialists now, we are at the forefront of evaluation and treatment of complications like polycystic ovary syndrome, metabolic syndrome, dyslipidemia, and type 2 diabetes.”
The guidelines provide recommendations about a wide variety of obesity-related topics including screening, diagnosis, and treatment. The Endocrine Society commissioned two systematic reviews to support the guidelines: One examined longer randomized controlled trials into medication, surgery, lifestyle, and community-based intervention treatments. The other examined how changing body mass index levels corresponded to cardiometabolic changes.
Several updated areas in the guidelines should be of special interest to endocrinologists: guidance regarding the genetic causes of pediatric obesity, the use of weight-loss medication and surgery, and the roles of insulin tests and breast-feeding, according to Dr. Styne.
In regard to genetics, the guidelines note that research suggests 7% of patients with extreme pediatric obesity “may have rare chromosomal abnormalities and/or highly penetrant genetic mutations that drive their obesity. This percentage is likely to increase with newer methods for genetic testing.”
Dr. Styne calls this finding “remarkable.” As he put it, “we didn’t appreciate that so much in the past.”
The guidelines suggest genetic testing for patients who become obese before the age of 5 years, have a family history of extreme obesity, or show clinical signs of genetic obesity syndromes, especially extreme hyperphagia.
As for the most extreme treatments for the most obese children, the guidelines recommend against weight-loss medication outside of clinical trials and note that “increasing evidence” supports bariatric surgery in teens who haven’t been able to lose enough pounds through lifestyle modification. However, “the use of surgery requires experienced teams with resources for long-term follow-up.”
The guidelines also recommend against measuring serum insulin concentrations as part of pediatric screening for obesity. “A lot of people like to get insulin levels and think it tells them about the future of the child,” Dr. Styne said. “But it doesn’t work very well.”
In another area that reflects new information, the guidelines note that breast-feeding hasn’t been definitively shown to be effective in reducing childhood obesity. “The literature is contradictory,” Dr. Styne said, although he noted that breast-feeding still has many other benefits.
The guidelines point to research gaps in several areas, including the prevention and treatment of pediatric obesity. There’s also “uncharted territory” regarding how to “effectively transition to adult care, with continued necessary monitoring, support, and intervention.”
In regard to the best treatment programs, “we didn’t come up with an answer regarding overall effectiveness,” Dr. Styne said. “School- and community-based programs have promise, but I can’t give you the percentage of success.”
As for the overall picture of pediatric obesity in the United States, “we’re in a better situation than we were 8 years ago,” he said. “Everyone is talking about the problem, and when you talk to families, they’re more aware of it.”
Still, he said, the prevalence of obesity in kids is high, estimated at 17% of those aged 2-19 years in 2014. “That’s not a good place to be,” he said. “We still have to work harder.”
The Endocrine Society funded the guidelines. Dr. Styne reports ownership interests in Teva, Bristol Myers and Organovo. Other authors report various disclosures.
Adverse event reporting in second-dose varicella vaccination shows no surprises
No new or unexpected adverse events were reported in association with second-dose varicella vaccination in children age 4-18 years during 2006-2014.
During the study period of 2006-2014, 14,641 reports regarding second-dose varicella vaccinations were made to the Vaccine Adverse Event Reporting System, according to John Su, MD, PhD, and his associates. Of these reports, only 3% were serious adverse events (AE), with the most common nonserious AE being injection-site reaction, which occurred in 48% of patients age 4-6 years reporting AEs, and in 38% of patients age 7-18 years reporting AEs.
Of the 494 serious AEs reported, pyrexia was the most common in children age 4-6 years, and headache and vomiting were the most common in children age 7-18 years. A total of seven deaths from various causes were reported, though no causal relation to vaccination was seen, and significant chronic medical problems were common in these children.
“The safety data on second-dose varicella vaccination are reassuring,” the investigators noted. “Reported AEs after second-dose varicella vaccination were mild, self limiting, and similar in reported frequency to AEs after first-dose vaccination, with no new or unexpected safety concerns.”
Find the full study in Pediatrics (2017 Feb 7. doi: 1542/peds.2016-2536).
No new or unexpected adverse events were reported in association with second-dose varicella vaccination in children age 4-18 years during 2006-2014.
During the study period of 2006-2014, 14,641 reports regarding second-dose varicella vaccinations were made to the Vaccine Adverse Event Reporting System, according to John Su, MD, PhD, and his associates. Of these reports, only 3% were serious adverse events (AE), with the most common nonserious AE being injection-site reaction, which occurred in 48% of patients age 4-6 years reporting AEs, and in 38% of patients age 7-18 years reporting AEs.
Of the 494 serious AEs reported, pyrexia was the most common in children age 4-6 years, and headache and vomiting were the most common in children age 7-18 years. A total of seven deaths from various causes were reported, though no causal relation to vaccination was seen, and significant chronic medical problems were common in these children.
“The safety data on second-dose varicella vaccination are reassuring,” the investigators noted. “Reported AEs after second-dose varicella vaccination were mild, self limiting, and similar in reported frequency to AEs after first-dose vaccination, with no new or unexpected safety concerns.”
Find the full study in Pediatrics (2017 Feb 7. doi: 1542/peds.2016-2536).
No new or unexpected adverse events were reported in association with second-dose varicella vaccination in children age 4-18 years during 2006-2014.
During the study period of 2006-2014, 14,641 reports regarding second-dose varicella vaccinations were made to the Vaccine Adverse Event Reporting System, according to John Su, MD, PhD, and his associates. Of these reports, only 3% were serious adverse events (AE), with the most common nonserious AE being injection-site reaction, which occurred in 48% of patients age 4-6 years reporting AEs, and in 38% of patients age 7-18 years reporting AEs.
Of the 494 serious AEs reported, pyrexia was the most common in children age 4-6 years, and headache and vomiting were the most common in children age 7-18 years. A total of seven deaths from various causes were reported, though no causal relation to vaccination was seen, and significant chronic medical problems were common in these children.
“The safety data on second-dose varicella vaccination are reassuring,” the investigators noted. “Reported AEs after second-dose varicella vaccination were mild, self limiting, and similar in reported frequency to AEs after first-dose vaccination, with no new or unexpected safety concerns.”
Find the full study in Pediatrics (2017 Feb 7. doi: 1542/peds.2016-2536).