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Infant hepatitis B vaccine protection lingers into adolescence
Adolescents who received hepatitis B virus (HBV) vaccinations as infants still showed protection despite little evidence of residual antibodies, a study showed.
This finding was based on data from a prospective study of 137 children, aged 10-11 years, and 213 children, aged 15-16 years, with no history of HBV infection who were vaccinated at 2, 4, and 6 months of age. Michelle Pinto, MD, of the Vaccine Evaluation Center in Vancouver and her colleagues measured residual immunity to determine whether HBV boosters might be needed in adolescents vaccinated as infants to prolong immunity and reduce disease transmission in adulthood.
Overall, 97% of the younger age group and 91% of the older age group showed reactions to an HBV vaccine challenge. An additional 3 (2%) younger children and 12 (6%) older children responded to a second vaccine challenge after failing to respond to the first.
Limitations of the study included a “limited ability of the challenge vaccine procedure to accurately identify immune memory and anamnestic responses” and the differences between the findings and those from long-term outcome data in similar studies in other countries, Dr. Pinto and her associates wrote.
However, “the fact that substantial differences exist in measures of residual protection among teenagers after infant or adolescent HBV vaccinations warrants close ongoing scrutiny of whether important differences will emerge in long-term protection, with or without booster vaccination,” they said (Pediatr Infect Dis J. 2017. doi: 10.1097/INF.0000000000001543).
Adolescents who received hepatitis B virus (HBV) vaccinations as infants still showed protection despite little evidence of residual antibodies, a study showed.
This finding was based on data from a prospective study of 137 children, aged 10-11 years, and 213 children, aged 15-16 years, with no history of HBV infection who were vaccinated at 2, 4, and 6 months of age. Michelle Pinto, MD, of the Vaccine Evaluation Center in Vancouver and her colleagues measured residual immunity to determine whether HBV boosters might be needed in adolescents vaccinated as infants to prolong immunity and reduce disease transmission in adulthood.
Overall, 97% of the younger age group and 91% of the older age group showed reactions to an HBV vaccine challenge. An additional 3 (2%) younger children and 12 (6%) older children responded to a second vaccine challenge after failing to respond to the first.
Limitations of the study included a “limited ability of the challenge vaccine procedure to accurately identify immune memory and anamnestic responses” and the differences between the findings and those from long-term outcome data in similar studies in other countries, Dr. Pinto and her associates wrote.
However, “the fact that substantial differences exist in measures of residual protection among teenagers after infant or adolescent HBV vaccinations warrants close ongoing scrutiny of whether important differences will emerge in long-term protection, with or without booster vaccination,” they said (Pediatr Infect Dis J. 2017. doi: 10.1097/INF.0000000000001543).
Adolescents who received hepatitis B virus (HBV) vaccinations as infants still showed protection despite little evidence of residual antibodies, a study showed.
This finding was based on data from a prospective study of 137 children, aged 10-11 years, and 213 children, aged 15-16 years, with no history of HBV infection who were vaccinated at 2, 4, and 6 months of age. Michelle Pinto, MD, of the Vaccine Evaluation Center in Vancouver and her colleagues measured residual immunity to determine whether HBV boosters might be needed in adolescents vaccinated as infants to prolong immunity and reduce disease transmission in adulthood.
Overall, 97% of the younger age group and 91% of the older age group showed reactions to an HBV vaccine challenge. An additional 3 (2%) younger children and 12 (6%) older children responded to a second vaccine challenge after failing to respond to the first.
Limitations of the study included a “limited ability of the challenge vaccine procedure to accurately identify immune memory and anamnestic responses” and the differences between the findings and those from long-term outcome data in similar studies in other countries, Dr. Pinto and her associates wrote.
However, “the fact that substantial differences exist in measures of residual protection among teenagers after infant or adolescent HBV vaccinations warrants close ongoing scrutiny of whether important differences will emerge in long-term protection, with or without booster vaccination,” they said (Pediatr Infect Dis J. 2017. doi: 10.1097/INF.0000000000001543).
FROM THE PEDIATRIC INFECTIOUS DISEASE JOURNAL
Children with poor lung function develop ACOS
Children with poor lung function will be more likely to develop asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), suggesting that prevention of this disease should be attempted in early life, a study shows.
While other research has found that patients with poor lung function in early life have poor lung function as adults, this was the first study to investigate the relationship between childhood lung function and ACOS in adult life, according to Dinh S. Bui of the University of Melbourne, and his colleagues.
The study, published in the American Journal of Respiratory and Critical Care Medicine, used multinomial regression models to investigate associations between childhood lung parameters at age 7 years and asthma, COPD, and ACOS at age 45 years (Am J Respir Crit Care Med. 2017 Feb 1. doi: 10.1164/rccm.201606-1272OC).
“We found that ACOS participants showed evidence of persistently lower FEV1 [forced expiratory volume in 1 second] and FEV1/FVC [forced vital capacity] from childhood. This suggests that poorer childhood lung function tracked to early adult life, leading to impaired maximally attained lung function,” the researchers said.
“The study highlights that low childhood lung function is a risk factor for COPD (and ACOS) independent of smoking,” they noted.
The 1,355 study participants who had postbronchodilator (post-BD) lung function available were categorized into the following four mutually exclusive groups at age 45 years based on their asthma and COPD status: having neither asthma nor COPD (unaffected) (n = 959); having asthma alone (n = 269); having COPD alone (n = 59); having ACOS (n = 68).
Once adjusted for the sampling weights, the prevalence of current asthma alone was 13.5%, COPD alone was 4.1%, and ACOS was 2.9%. The researchers defined COPD at age 45 years as post-BD FEV1/FVC less than the Global Lung Initiative lower limit of normal. Because the associations between childhood lung function and both ACOS and COPD alone were nonlinear, the patients were grouped into quartiles based on their characteristics, such as their percent predicted FEV1 and percent predicted FEV1/FVC at 7 years, the investigators said.
Patients in the lowest quartile for FEV1 percent predicted at 7 years were 2.93 times more likely to have ACOS, compared with patients in the other quartiles for FEV1 percent predicted. Patients in the lowest quartile for FEV1/FVC percent predicted at 7 years were 16.3 times more likely to have ACOS and 5.76 times more likely to have COPD alone, compared with patients in the higher quartiles.
The researchers found large variation in childhood lung function among patients in the lowest quartiles for FEV1 and FEV1/FVC. To account for this, they conducted a sensitivity analysis, which excluded those with less than 80% predicted FEV1 and FEV1/FVC (n = 76 and 13, respectively).The associations between lung function measures and diseases in adulthood for patients in the lowest quartiles differed slightly following this adjustment. The sensitivity analysis showed that patients in the lowest quartile for FEV1 had an odds ratio of 2.4 for ACOS and that those patients in the lowest quartile for FEV1/FVC had an odds ratio of 5.2 for COPD alone and 15.1 for ACOS.
A sensitivity analysis that excluded patients with remitted asthma from the unaffected group showed childhood FEV1 was more strongly associated with ACOS for patients in the lowest quartile, compared with patients in the highest quartile (OR: 7.0, 95% CI: 2.7-18.3). This same analysis found that patients from the lowest quartile and second quartile for childhood FEV1/FVC were 6.8 and 3.9 times more likely to have COPD, respectively, compared with patients in the other quartiles. This sensitivity analysis also found that patients in the first quartile for FEV1/FVC were 19.1 times more likely to have ACOS, and patients in the second quartile for FEV1/FVC were 5.3 times more likely to have ACOS.
The researchers analyzed data from the Tasmanian Longitudinal Health Study, which began in 1968 when Tasmanian children born in 1961 and attending school in Tasmania were studied with respiratory health surveys and prebronchodilator (pre-BD) spirometry measurements. The most recent survey started in 2002. Survey respondents who had participated in past follow-up studies and/or reported symptoms of asthma or cough were invited to participate in a more detailed laboratory study from 2006 to 2008. That study included completing a questionnaire, pre-BD and post-BD spirometry, and skin prick testing. The predicted and percent predicted values for spirometry were derived from the Global Lung Initiative reference equations.
The final multinomial model was adjusted for various factors including childhood asthma, maternal smoking, and paternal smoking during childhood.
History of active smoking was significantly more frequent in patients with ACOS (73.5%) and COPD alone (73%) than in the unaffected (57%) groups. Childhood asthma, maternal asthma and atopy were more prevalent in the ACOS and asthma alone groups. ACOS and COPD participants had a higher prevalence of maternal smoking during childhood.
Individuals with ACOS had the lowest pre-BD FEV1 (percent predicted values) over time. Those with COPD alone or ACOS had significantly lower pre-BD FEV1/FVC (percent predicted values) at all time points, when patients were assessed, compared with unaffected participants. “Participants with COPD alone had significantly higher FVC at 7 and 13 years, while ACOS participants had significantly lower FVC at 45 years,” the researchers said.
“There was no evidence of effect modification by childhood lung infections, childhood asthma, maternal asthma, maternal smoking, or paternal smoking during childhood on the associations between childhood lung and the disease groups,” they noted.
The study was limited by its “relatively small sample sizes for the ACOS and COPD alone groups” and the absence of post-BD spirometry at 7 years, they added.
The researchers concluded that “screening of lung function in school-aged children may provide an opportunity to detect children likely to have ongoing poorer lung health, such as those with lung function below the lower limit of normal,” and that “[multifaceted] intervention strategies could then be implemented to reduce the burden of COPD and ACOS in adulthood.”
“I suspect that genetics may play a big role in the results, and there is increasing interest in learning how genetics are involved in COPD. A better understanding of the risk factors for lower lung function in children may also provide targets of intervention. The groups with ACOS and COPD have higher rates of maternal smoking, and while this study determined that the association between childhood low lung function and development of COPD and ACOS is independent of maternal smoking, maternal smoking still seems like a good area to target,” she said in an interview.
It would also be interesting to further study the first quartile of patients, she added. “The clinical disease for this quartile of patients covers a wide range of severities. I would be interested in dividing this group up further and learning the outcomes of their lung function and development of COPD and ACOS.”
Using inhaled corticosteroids and other medications for maintenance control, reducing and monitoring impairment, educating patients and patients’ guardians on triggers, avoiding triggers, and having an action plan for changing therapy based on symptoms or measured flows are ways to aggressively treat such conditions, said Dr. Gartman, assistant professor of medicine at Brown University, Providence, R.I*. He cited avoiding exposure to smoke, environmental pollutants, and living near highways, for those with low childhood function, as interventions that might prevent people with low lung function from later developing COPD.
Dr. Gartman added that differences between the availability of medication for children with asthma today and at the time of the study may mean there are differences between the children with low lung function in the study and those children who have low function today. A population of children with low lung function now may be experiencing relatively less asthma and more chronic lung disorders brought on by prematurity or cystic fibrosis, he noted. “As such, identification of poor function in today’s young children may carry with it a significantly different set of interventions and challenges,” Dr. Gartman said.
While asthma in children is better controlled now than it was at the time of the study, because the researchers did not provide any information about the asthma control of the study participants, “it [is] hard for me to say if better asthma drugs in those children would have made a difference in long-term outcomes of COPD and ACOS as an adult,” Dr. Swaminathan noted.
“The best thing we currently can do for children with low lung function is try and determine the underlying cause and treat any active diseases [such as asthma] that we can. This study reminds us of the need to keep searching for causes of low lung function that may be reversible,” she said.
The investigators recommended future research to understand the risk factors for lower lung function in children. They called for studies that address “the risk factors over adulthood that interact with lower lung function to increase the risk of rapid lung function decline.”
The study was supported by a National Health and Medical Research Council of Australia research grant, the University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, the Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, GlaxoSmithKline, and John L Hopper. Five authors were supported by the research grant; the others reported no conflicts. Dr. Swaminathan and Dr. Gartman had no disclosures.
*This story was updated March 16, 2017, with Dr. Gartman's full affiliation.
Children with poor lung function will be more likely to develop asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), suggesting that prevention of this disease should be attempted in early life, a study shows.
While other research has found that patients with poor lung function in early life have poor lung function as adults, this was the first study to investigate the relationship between childhood lung function and ACOS in adult life, according to Dinh S. Bui of the University of Melbourne, and his colleagues.
The study, published in the American Journal of Respiratory and Critical Care Medicine, used multinomial regression models to investigate associations between childhood lung parameters at age 7 years and asthma, COPD, and ACOS at age 45 years (Am J Respir Crit Care Med. 2017 Feb 1. doi: 10.1164/rccm.201606-1272OC).
“We found that ACOS participants showed evidence of persistently lower FEV1 [forced expiratory volume in 1 second] and FEV1/FVC [forced vital capacity] from childhood. This suggests that poorer childhood lung function tracked to early adult life, leading to impaired maximally attained lung function,” the researchers said.
“The study highlights that low childhood lung function is a risk factor for COPD (and ACOS) independent of smoking,” they noted.
The 1,355 study participants who had postbronchodilator (post-BD) lung function available were categorized into the following four mutually exclusive groups at age 45 years based on their asthma and COPD status: having neither asthma nor COPD (unaffected) (n = 959); having asthma alone (n = 269); having COPD alone (n = 59); having ACOS (n = 68).
Once adjusted for the sampling weights, the prevalence of current asthma alone was 13.5%, COPD alone was 4.1%, and ACOS was 2.9%. The researchers defined COPD at age 45 years as post-BD FEV1/FVC less than the Global Lung Initiative lower limit of normal. Because the associations between childhood lung function and both ACOS and COPD alone were nonlinear, the patients were grouped into quartiles based on their characteristics, such as their percent predicted FEV1 and percent predicted FEV1/FVC at 7 years, the investigators said.
Patients in the lowest quartile for FEV1 percent predicted at 7 years were 2.93 times more likely to have ACOS, compared with patients in the other quartiles for FEV1 percent predicted. Patients in the lowest quartile for FEV1/FVC percent predicted at 7 years were 16.3 times more likely to have ACOS and 5.76 times more likely to have COPD alone, compared with patients in the higher quartiles.
The researchers found large variation in childhood lung function among patients in the lowest quartiles for FEV1 and FEV1/FVC. To account for this, they conducted a sensitivity analysis, which excluded those with less than 80% predicted FEV1 and FEV1/FVC (n = 76 and 13, respectively).The associations between lung function measures and diseases in adulthood for patients in the lowest quartiles differed slightly following this adjustment. The sensitivity analysis showed that patients in the lowest quartile for FEV1 had an odds ratio of 2.4 for ACOS and that those patients in the lowest quartile for FEV1/FVC had an odds ratio of 5.2 for COPD alone and 15.1 for ACOS.
A sensitivity analysis that excluded patients with remitted asthma from the unaffected group showed childhood FEV1 was more strongly associated with ACOS for patients in the lowest quartile, compared with patients in the highest quartile (OR: 7.0, 95% CI: 2.7-18.3). This same analysis found that patients from the lowest quartile and second quartile for childhood FEV1/FVC were 6.8 and 3.9 times more likely to have COPD, respectively, compared with patients in the other quartiles. This sensitivity analysis also found that patients in the first quartile for FEV1/FVC were 19.1 times more likely to have ACOS, and patients in the second quartile for FEV1/FVC were 5.3 times more likely to have ACOS.
The researchers analyzed data from the Tasmanian Longitudinal Health Study, which began in 1968 when Tasmanian children born in 1961 and attending school in Tasmania were studied with respiratory health surveys and prebronchodilator (pre-BD) spirometry measurements. The most recent survey started in 2002. Survey respondents who had participated in past follow-up studies and/or reported symptoms of asthma or cough were invited to participate in a more detailed laboratory study from 2006 to 2008. That study included completing a questionnaire, pre-BD and post-BD spirometry, and skin prick testing. The predicted and percent predicted values for spirometry were derived from the Global Lung Initiative reference equations.
The final multinomial model was adjusted for various factors including childhood asthma, maternal smoking, and paternal smoking during childhood.
History of active smoking was significantly more frequent in patients with ACOS (73.5%) and COPD alone (73%) than in the unaffected (57%) groups. Childhood asthma, maternal asthma and atopy were more prevalent in the ACOS and asthma alone groups. ACOS and COPD participants had a higher prevalence of maternal smoking during childhood.
Individuals with ACOS had the lowest pre-BD FEV1 (percent predicted values) over time. Those with COPD alone or ACOS had significantly lower pre-BD FEV1/FVC (percent predicted values) at all time points, when patients were assessed, compared with unaffected participants. “Participants with COPD alone had significantly higher FVC at 7 and 13 years, while ACOS participants had significantly lower FVC at 45 years,” the researchers said.
“There was no evidence of effect modification by childhood lung infections, childhood asthma, maternal asthma, maternal smoking, or paternal smoking during childhood on the associations between childhood lung and the disease groups,” they noted.
The study was limited by its “relatively small sample sizes for the ACOS and COPD alone groups” and the absence of post-BD spirometry at 7 years, they added.
The researchers concluded that “screening of lung function in school-aged children may provide an opportunity to detect children likely to have ongoing poorer lung health, such as those with lung function below the lower limit of normal,” and that “[multifaceted] intervention strategies could then be implemented to reduce the burden of COPD and ACOS in adulthood.”
“I suspect that genetics may play a big role in the results, and there is increasing interest in learning how genetics are involved in COPD. A better understanding of the risk factors for lower lung function in children may also provide targets of intervention. The groups with ACOS and COPD have higher rates of maternal smoking, and while this study determined that the association between childhood low lung function and development of COPD and ACOS is independent of maternal smoking, maternal smoking still seems like a good area to target,” she said in an interview.
It would also be interesting to further study the first quartile of patients, she added. “The clinical disease for this quartile of patients covers a wide range of severities. I would be interested in dividing this group up further and learning the outcomes of their lung function and development of COPD and ACOS.”
Using inhaled corticosteroids and other medications for maintenance control, reducing and monitoring impairment, educating patients and patients’ guardians on triggers, avoiding triggers, and having an action plan for changing therapy based on symptoms or measured flows are ways to aggressively treat such conditions, said Dr. Gartman, assistant professor of medicine at Brown University, Providence, R.I*. He cited avoiding exposure to smoke, environmental pollutants, and living near highways, for those with low childhood function, as interventions that might prevent people with low lung function from later developing COPD.
Dr. Gartman added that differences between the availability of medication for children with asthma today and at the time of the study may mean there are differences between the children with low lung function in the study and those children who have low function today. A population of children with low lung function now may be experiencing relatively less asthma and more chronic lung disorders brought on by prematurity or cystic fibrosis, he noted. “As such, identification of poor function in today’s young children may carry with it a significantly different set of interventions and challenges,” Dr. Gartman said.
While asthma in children is better controlled now than it was at the time of the study, because the researchers did not provide any information about the asthma control of the study participants, “it [is] hard for me to say if better asthma drugs in those children would have made a difference in long-term outcomes of COPD and ACOS as an adult,” Dr. Swaminathan noted.
“The best thing we currently can do for children with low lung function is try and determine the underlying cause and treat any active diseases [such as asthma] that we can. This study reminds us of the need to keep searching for causes of low lung function that may be reversible,” she said.
The investigators recommended future research to understand the risk factors for lower lung function in children. They called for studies that address “the risk factors over adulthood that interact with lower lung function to increase the risk of rapid lung function decline.”
The study was supported by a National Health and Medical Research Council of Australia research grant, the University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, the Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, GlaxoSmithKline, and John L Hopper. Five authors were supported by the research grant; the others reported no conflicts. Dr. Swaminathan and Dr. Gartman had no disclosures.
*This story was updated March 16, 2017, with Dr. Gartman's full affiliation.
Children with poor lung function will be more likely to develop asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), suggesting that prevention of this disease should be attempted in early life, a study shows.
While other research has found that patients with poor lung function in early life have poor lung function as adults, this was the first study to investigate the relationship between childhood lung function and ACOS in adult life, according to Dinh S. Bui of the University of Melbourne, and his colleagues.
The study, published in the American Journal of Respiratory and Critical Care Medicine, used multinomial regression models to investigate associations between childhood lung parameters at age 7 years and asthma, COPD, and ACOS at age 45 years (Am J Respir Crit Care Med. 2017 Feb 1. doi: 10.1164/rccm.201606-1272OC).
“We found that ACOS participants showed evidence of persistently lower FEV1 [forced expiratory volume in 1 second] and FEV1/FVC [forced vital capacity] from childhood. This suggests that poorer childhood lung function tracked to early adult life, leading to impaired maximally attained lung function,” the researchers said.
“The study highlights that low childhood lung function is a risk factor for COPD (and ACOS) independent of smoking,” they noted.
The 1,355 study participants who had postbronchodilator (post-BD) lung function available were categorized into the following four mutually exclusive groups at age 45 years based on their asthma and COPD status: having neither asthma nor COPD (unaffected) (n = 959); having asthma alone (n = 269); having COPD alone (n = 59); having ACOS (n = 68).
Once adjusted for the sampling weights, the prevalence of current asthma alone was 13.5%, COPD alone was 4.1%, and ACOS was 2.9%. The researchers defined COPD at age 45 years as post-BD FEV1/FVC less than the Global Lung Initiative lower limit of normal. Because the associations between childhood lung function and both ACOS and COPD alone were nonlinear, the patients were grouped into quartiles based on their characteristics, such as their percent predicted FEV1 and percent predicted FEV1/FVC at 7 years, the investigators said.
Patients in the lowest quartile for FEV1 percent predicted at 7 years were 2.93 times more likely to have ACOS, compared with patients in the other quartiles for FEV1 percent predicted. Patients in the lowest quartile for FEV1/FVC percent predicted at 7 years were 16.3 times more likely to have ACOS and 5.76 times more likely to have COPD alone, compared with patients in the higher quartiles.
The researchers found large variation in childhood lung function among patients in the lowest quartiles for FEV1 and FEV1/FVC. To account for this, they conducted a sensitivity analysis, which excluded those with less than 80% predicted FEV1 and FEV1/FVC (n = 76 and 13, respectively).The associations between lung function measures and diseases in adulthood for patients in the lowest quartiles differed slightly following this adjustment. The sensitivity analysis showed that patients in the lowest quartile for FEV1 had an odds ratio of 2.4 for ACOS and that those patients in the lowest quartile for FEV1/FVC had an odds ratio of 5.2 for COPD alone and 15.1 for ACOS.
A sensitivity analysis that excluded patients with remitted asthma from the unaffected group showed childhood FEV1 was more strongly associated with ACOS for patients in the lowest quartile, compared with patients in the highest quartile (OR: 7.0, 95% CI: 2.7-18.3). This same analysis found that patients from the lowest quartile and second quartile for childhood FEV1/FVC were 6.8 and 3.9 times more likely to have COPD, respectively, compared with patients in the other quartiles. This sensitivity analysis also found that patients in the first quartile for FEV1/FVC were 19.1 times more likely to have ACOS, and patients in the second quartile for FEV1/FVC were 5.3 times more likely to have ACOS.
The researchers analyzed data from the Tasmanian Longitudinal Health Study, which began in 1968 when Tasmanian children born in 1961 and attending school in Tasmania were studied with respiratory health surveys and prebronchodilator (pre-BD) spirometry measurements. The most recent survey started in 2002. Survey respondents who had participated in past follow-up studies and/or reported symptoms of asthma or cough were invited to participate in a more detailed laboratory study from 2006 to 2008. That study included completing a questionnaire, pre-BD and post-BD spirometry, and skin prick testing. The predicted and percent predicted values for spirometry were derived from the Global Lung Initiative reference equations.
The final multinomial model was adjusted for various factors including childhood asthma, maternal smoking, and paternal smoking during childhood.
History of active smoking was significantly more frequent in patients with ACOS (73.5%) and COPD alone (73%) than in the unaffected (57%) groups. Childhood asthma, maternal asthma and atopy were more prevalent in the ACOS and asthma alone groups. ACOS and COPD participants had a higher prevalence of maternal smoking during childhood.
Individuals with ACOS had the lowest pre-BD FEV1 (percent predicted values) over time. Those with COPD alone or ACOS had significantly lower pre-BD FEV1/FVC (percent predicted values) at all time points, when patients were assessed, compared with unaffected participants. “Participants with COPD alone had significantly higher FVC at 7 and 13 years, while ACOS participants had significantly lower FVC at 45 years,” the researchers said.
“There was no evidence of effect modification by childhood lung infections, childhood asthma, maternal asthma, maternal smoking, or paternal smoking during childhood on the associations between childhood lung and the disease groups,” they noted.
The study was limited by its “relatively small sample sizes for the ACOS and COPD alone groups” and the absence of post-BD spirometry at 7 years, they added.
The researchers concluded that “screening of lung function in school-aged children may provide an opportunity to detect children likely to have ongoing poorer lung health, such as those with lung function below the lower limit of normal,” and that “[multifaceted] intervention strategies could then be implemented to reduce the burden of COPD and ACOS in adulthood.”
“I suspect that genetics may play a big role in the results, and there is increasing interest in learning how genetics are involved in COPD. A better understanding of the risk factors for lower lung function in children may also provide targets of intervention. The groups with ACOS and COPD have higher rates of maternal smoking, and while this study determined that the association between childhood low lung function and development of COPD and ACOS is independent of maternal smoking, maternal smoking still seems like a good area to target,” she said in an interview.
It would also be interesting to further study the first quartile of patients, she added. “The clinical disease for this quartile of patients covers a wide range of severities. I would be interested in dividing this group up further and learning the outcomes of their lung function and development of COPD and ACOS.”
Using inhaled corticosteroids and other medications for maintenance control, reducing and monitoring impairment, educating patients and patients’ guardians on triggers, avoiding triggers, and having an action plan for changing therapy based on symptoms or measured flows are ways to aggressively treat such conditions, said Dr. Gartman, assistant professor of medicine at Brown University, Providence, R.I*. He cited avoiding exposure to smoke, environmental pollutants, and living near highways, for those with low childhood function, as interventions that might prevent people with low lung function from later developing COPD.
Dr. Gartman added that differences between the availability of medication for children with asthma today and at the time of the study may mean there are differences between the children with low lung function in the study and those children who have low function today. A population of children with low lung function now may be experiencing relatively less asthma and more chronic lung disorders brought on by prematurity or cystic fibrosis, he noted. “As such, identification of poor function in today’s young children may carry with it a significantly different set of interventions and challenges,” Dr. Gartman said.
While asthma in children is better controlled now than it was at the time of the study, because the researchers did not provide any information about the asthma control of the study participants, “it [is] hard for me to say if better asthma drugs in those children would have made a difference in long-term outcomes of COPD and ACOS as an adult,” Dr. Swaminathan noted.
“The best thing we currently can do for children with low lung function is try and determine the underlying cause and treat any active diseases [such as asthma] that we can. This study reminds us of the need to keep searching for causes of low lung function that may be reversible,” she said.
The investigators recommended future research to understand the risk factors for lower lung function in children. They called for studies that address “the risk factors over adulthood that interact with lower lung function to increase the risk of rapid lung function decline.”
The study was supported by a National Health and Medical Research Council of Australia research grant, the University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, the Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, GlaxoSmithKline, and John L Hopper. Five authors were supported by the research grant; the others reported no conflicts. Dr. Swaminathan and Dr. Gartman had no disclosures.
*This story was updated March 16, 2017, with Dr. Gartman's full affiliation.
FROM AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Surveillance
A few weeks ago I received an email from a pediatrician thanking me for supporting her decision to quit work so that she could be home when her teenage son came home from school. She felt that by being home during her son’s adolescence, not only had she provided him a secure base but she also had helped protect him from a drug-dominated culture that permeated the community where they lived. While I hadn’t touched on it in my column, “Perfect Attendance” (Pediatric News, March 2017), this pediatrician’s experience highlights another benefit of a parental presence during those potentially stormy adolescent years.
In a recent article in the New York Times (“Teenagers Do Dumb Things, but There Are Ways to Limit Recklessness,” by Lisa Damour, March 8, 2017), Dr. Laurence Steinberg, a psychology professor at Temple University, is quoted as saying that “the context in which kids grow up must matter a great deal, and that recklessness isn’t the inevitable byproduct of the period’s biology.”
As writer Lisa Damour cogently states in her article, “For teenagers to find trouble, temptation must meet opportunity.”
Here in Brunswick, high school students finish their school day at 2:10 pm. If the student doesn’t play on a sports team and even if his or her home is at the end of the longest bus route, he or she is going to be home before 3 p.m. ... probably unsupervised. And stuff happens.
Although I may have been unsupervised, I was – or at least I believed that I was – always under constant surveillance. In the 1950s and 1960s, the population of Pleasantville, N.Y. was 5,000 and my mother had me convinced that she knew 4,000 of them. She recounted enough little things she had heard to make me believe that I was being watched by 8,000 eyes. She and the other mothers in town were masters of information sharing long before anyone had heard of networking.
These were not helicopter mothers hovering over every shady corner of our lives. They were simply concerned parents and fellow citizens going about their daily business who were not afraid to say something if they saw something. My mother’s apparent omniscience was a powerful deterrent to my adolescent recklessness. Only after I could afford to buy a car did I feel I could escape her surveillance network. And even then I wasn’t always sure.
The Internet has opened opportunities for mischief that are several orders of magnitude greater than the ones my friends and I sought to exploit in the 1950s and 1960s. However, parents today do have tools with which they can create a surveillance network to protect adolescents from their biologically predetermined urges. They simply need to have to courage to use them and not be afraid to say something if they see something.
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.
A few weeks ago I received an email from a pediatrician thanking me for supporting her decision to quit work so that she could be home when her teenage son came home from school. She felt that by being home during her son’s adolescence, not only had she provided him a secure base but she also had helped protect him from a drug-dominated culture that permeated the community where they lived. While I hadn’t touched on it in my column, “Perfect Attendance” (Pediatric News, March 2017), this pediatrician’s experience highlights another benefit of a parental presence during those potentially stormy adolescent years.
In a recent article in the New York Times (“Teenagers Do Dumb Things, but There Are Ways to Limit Recklessness,” by Lisa Damour, March 8, 2017), Dr. Laurence Steinberg, a psychology professor at Temple University, is quoted as saying that “the context in which kids grow up must matter a great deal, and that recklessness isn’t the inevitable byproduct of the period’s biology.”
As writer Lisa Damour cogently states in her article, “For teenagers to find trouble, temptation must meet opportunity.”
Here in Brunswick, high school students finish their school day at 2:10 pm. If the student doesn’t play on a sports team and even if his or her home is at the end of the longest bus route, he or she is going to be home before 3 p.m. ... probably unsupervised. And stuff happens.
Although I may have been unsupervised, I was – or at least I believed that I was – always under constant surveillance. In the 1950s and 1960s, the population of Pleasantville, N.Y. was 5,000 and my mother had me convinced that she knew 4,000 of them. She recounted enough little things she had heard to make me believe that I was being watched by 8,000 eyes. She and the other mothers in town were masters of information sharing long before anyone had heard of networking.
These were not helicopter mothers hovering over every shady corner of our lives. They were simply concerned parents and fellow citizens going about their daily business who were not afraid to say something if they saw something. My mother’s apparent omniscience was a powerful deterrent to my adolescent recklessness. Only after I could afford to buy a car did I feel I could escape her surveillance network. And even then I wasn’t always sure.
The Internet has opened opportunities for mischief that are several orders of magnitude greater than the ones my friends and I sought to exploit in the 1950s and 1960s. However, parents today do have tools with which they can create a surveillance network to protect adolescents from their biologically predetermined urges. They simply need to have to courage to use them and not be afraid to say something if they see something.
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.
A few weeks ago I received an email from a pediatrician thanking me for supporting her decision to quit work so that she could be home when her teenage son came home from school. She felt that by being home during her son’s adolescence, not only had she provided him a secure base but she also had helped protect him from a drug-dominated culture that permeated the community where they lived. While I hadn’t touched on it in my column, “Perfect Attendance” (Pediatric News, March 2017), this pediatrician’s experience highlights another benefit of a parental presence during those potentially stormy adolescent years.
In a recent article in the New York Times (“Teenagers Do Dumb Things, but There Are Ways to Limit Recklessness,” by Lisa Damour, March 8, 2017), Dr. Laurence Steinberg, a psychology professor at Temple University, is quoted as saying that “the context in which kids grow up must matter a great deal, and that recklessness isn’t the inevitable byproduct of the period’s biology.”
As writer Lisa Damour cogently states in her article, “For teenagers to find trouble, temptation must meet opportunity.”
Here in Brunswick, high school students finish their school day at 2:10 pm. If the student doesn’t play on a sports team and even if his or her home is at the end of the longest bus route, he or she is going to be home before 3 p.m. ... probably unsupervised. And stuff happens.
Although I may have been unsupervised, I was – or at least I believed that I was – always under constant surveillance. In the 1950s and 1960s, the population of Pleasantville, N.Y. was 5,000 and my mother had me convinced that she knew 4,000 of them. She recounted enough little things she had heard to make me believe that I was being watched by 8,000 eyes. She and the other mothers in town were masters of information sharing long before anyone had heard of networking.
These were not helicopter mothers hovering over every shady corner of our lives. They were simply concerned parents and fellow citizens going about their daily business who were not afraid to say something if they saw something. My mother’s apparent omniscience was a powerful deterrent to my adolescent recklessness. Only after I could afford to buy a car did I feel I could escape her surveillance network. And even then I wasn’t always sure.
The Internet has opened opportunities for mischief that are several orders of magnitude greater than the ones my friends and I sought to exploit in the 1950s and 1960s. However, parents today do have tools with which they can create a surveillance network to protect adolescents from their biologically predetermined urges. They simply need to have to courage to use them and not be afraid to say something if they see something.
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.
Steroids During Late Preterm Labor? Better Later Than Never
A 21-year-old G1P0 at 35 weeks, 2 days of gestation presents to labor and delivery reporting a “gush of clear fluid.” On exam, you confirm she has preterm rupture of membranes. She is contracting every three minutes and has a cervix dilated to 3 cm. Is there any neonatal benefit to using corticosteroids in this late preterm period?
Approximately 12% of all births in the United States are the result of preterm labor, and 8% take place in the late preterm period, defined as 34 to 36 weeks’ gestation.2,3 To reduce risk for neonatal death and respiratory complications, both the American College of Obstetricians and Gynecologists and the National Institutes of Health recommend a course of corticosteroids between 24 and 34 weeks’ gestation for women at increased risk for preterm delivery.2,4 Due to a lack of evidence from RCTs on the benefit of corticosteroids in late preterm labor, there are no recommendations to extend this period.5 However, multiple studies have shown that babies born during the late preterm period have more neonatal complications than term newborns.6-8
A retrospective chart review of more than 130,000 live births found that newborns who were delivered between 34 and 36 weeks had higher rates of respiratory distress than those delivered at 39 weeks (ventilator use dropped from 3.3% at 34 weeks to 0.3% at 39 weeks, and transient tachypnea decreased from 2.4% at 34 weeks to 0.4% at 39 weeks).6 Another retrospective review of more than 230,000 newborns, 19,000 of whom were born in the late preterm period, revealed that more neonates born between 34 and 36 weeks’ gestation had respiratory distress syndrome than neonates delivered at 39 weeks (10.5% at 34 weeks, 6% at 35 weeks, 2.8% at 36 weeks vs 0.3% at 39 weeks).8
STUDY SUMMARY
Late preterm newborns breathe better with antenatal betamethasone
This RCT examined the effectiveness of betamethasone in preventing neonatal respiratory complications for 2,831 women at high probability of preterm delivery between 34 weeks and 36 weeks, 6 days of gestation. “High probability of preterm delivery” was defined as preterm labor with intact membranes and at least 3 cm dilation or 75% cervical effacement; spontaneous rupture of membranes; or anticipated preterm delivery for any other indication either through induction or cesarean section between 24 hours and seven days after the planned randomization.
Patients were randomly assigned to receive two intramuscular injections (12 mg each) of either betamethasone or placebo, 24 hours apart. The two doses were successfully given in 60% of the betamethasone group and 59% of the placebo group. In 95% of the cases in which the second dose was not given, it was because delivery occurred within 24 hours of the first dose.
The primary outcome was the need for respiratory support within 72 hours of birth, defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least two consecutive hours, supplemental oxygen for at least four continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation.
The median length of time from enrollment to delivery was 31 to 33 hours, and 31.4% underwent cesarean delivery. In the intention-to-treat analysis, the primary outcome was significantly lower in the betamethasone group than in the placebo group (11.6% vs 14.4%; relative risk [RR], 0.80; number needed to treat [NNT], 35). Secondary outcomes (severe complications, representing a composite of the use of CPAP or high-flow nasal cannula for at least 12 continuous hours, supplemental oxygen for at least 24 continuous hours, ECMO, mechanical ventilation, stillbirth, or neonatal death within 72 hours after delivery) were also lower in the betamethasone group (8.1% vs 12.1%; RR, 0.67; NNT, 25). The betamethasone group also had a lower risk for transient tachypnea of the newborn (6.7% vs 9.9%; RR, 0.68).
There were no significant differences in the occurrence of maternal chorioamnionitis or endometritis between the groups. Hypoglycemia in the newborn occurred more in the betamethasone group (24% vs 15%; RR, 1.6; number needed to harm [NNH], 11). The betamethasone group had two neonatal deaths: one from septic shock, and the other from a structural cardiac anomaly and arrhythmia.
WHAT’S NEW
Betamethasone effective even in the late, late preterm period
This study demonstrated an improvement in neonatal respiratory outcomes when betamethasone versus placebo was used in the late preterm period. The findings were similar to those from the Antenatal Steroids for Term Elective Caesarean Section Research Team.9 Their trial showed a reduction in respiratory complications in term neonates delivered via elective cesarean section to mothers who received antenatal betamethasone (NNT, 37, to prevent admission to a special care nursery with respiratory distress). The findings were also consistent with those of a recent meta-analysis evaluating the occurrence of respiratory complications with the use of antenatal betamethasone in women expected to deliver in the late preterm period or with a planned cesarean delivery at ≥ 37 weeks’ gestation.10
CAVEATS
Neonates may develop hypoglycemia
The authors of the study reported an increased risk for hypoglycemia in the neonates receiving antenatal betamethasone. The long-term implications of this are unclear, however, given that there was a reduction in intermediate care nursery and neonatal ICU stays that were three days or longer in the betamethasone group. There was also no difference in hospital length of stay between the two groups. Additionally, it’s unclear if there are any long-term neonatal complications of betamethasone use in the late preterm period.
CHALLENGES TO IMPLEMENTATION
Challenges are negligible
There are minimal challenges to implementing this strategy, as betamethasone is routinely used for preterm labor and is readily available on labor and delivery units.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2017;66(2):104-106.
1. Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; NICHD Maternal–Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374:1311-1320.
2. Practice Bulletin No. 159 Summary: Management of Preterm Labor. Obstet Gynecol. 2016;127:190-191.
3. Martin JA, Hamilton BE, Osterman MJ, et al. Births: final data for 2013. Natl Vital Stat Rep. 2015;64:1-65.
4. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994;12:1-24.
5. Society for Maternal-Fetal Medicine (SMFM) Publications Committee. Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. Am J Obstet Gynecol. 2016;215:B13-B15.
6. McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol. 2008;111:35-41.
7. Yoder BA, Gordon MC, Barth WH Jr. Late-preterm birth: does the changing obstetric paradigm alter the epidemiology of respiratory complications? Obstet Gynecol. 2008;111:814-822.
8. Consortium on Safe Labor, Hibbard JU, Wilkins I, Sun L, et al. Respiratory morbidity in late preterm births. JAMA. 2010;304:419-425.
9. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ. 2005;331:662.
10. Saccone G, Berghella V. Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. BMJ. 2016;355:i5044.
A 21-year-old G1P0 at 35 weeks, 2 days of gestation presents to labor and delivery reporting a “gush of clear fluid.” On exam, you confirm she has preterm rupture of membranes. She is contracting every three minutes and has a cervix dilated to 3 cm. Is there any neonatal benefit to using corticosteroids in this late preterm period?
Approximately 12% of all births in the United States are the result of preterm labor, and 8% take place in the late preterm period, defined as 34 to 36 weeks’ gestation.2,3 To reduce risk for neonatal death and respiratory complications, both the American College of Obstetricians and Gynecologists and the National Institutes of Health recommend a course of corticosteroids between 24 and 34 weeks’ gestation for women at increased risk for preterm delivery.2,4 Due to a lack of evidence from RCTs on the benefit of corticosteroids in late preterm labor, there are no recommendations to extend this period.5 However, multiple studies have shown that babies born during the late preterm period have more neonatal complications than term newborns.6-8
A retrospective chart review of more than 130,000 live births found that newborns who were delivered between 34 and 36 weeks had higher rates of respiratory distress than those delivered at 39 weeks (ventilator use dropped from 3.3% at 34 weeks to 0.3% at 39 weeks, and transient tachypnea decreased from 2.4% at 34 weeks to 0.4% at 39 weeks).6 Another retrospective review of more than 230,000 newborns, 19,000 of whom were born in the late preterm period, revealed that more neonates born between 34 and 36 weeks’ gestation had respiratory distress syndrome than neonates delivered at 39 weeks (10.5% at 34 weeks, 6% at 35 weeks, 2.8% at 36 weeks vs 0.3% at 39 weeks).8
STUDY SUMMARY
Late preterm newborns breathe better with antenatal betamethasone
This RCT examined the effectiveness of betamethasone in preventing neonatal respiratory complications for 2,831 women at high probability of preterm delivery between 34 weeks and 36 weeks, 6 days of gestation. “High probability of preterm delivery” was defined as preterm labor with intact membranes and at least 3 cm dilation or 75% cervical effacement; spontaneous rupture of membranes; or anticipated preterm delivery for any other indication either through induction or cesarean section between 24 hours and seven days after the planned randomization.
Patients were randomly assigned to receive two intramuscular injections (12 mg each) of either betamethasone or placebo, 24 hours apart. The two doses were successfully given in 60% of the betamethasone group and 59% of the placebo group. In 95% of the cases in which the second dose was not given, it was because delivery occurred within 24 hours of the first dose.
The primary outcome was the need for respiratory support within 72 hours of birth, defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least two consecutive hours, supplemental oxygen for at least four continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation.
The median length of time from enrollment to delivery was 31 to 33 hours, and 31.4% underwent cesarean delivery. In the intention-to-treat analysis, the primary outcome was significantly lower in the betamethasone group than in the placebo group (11.6% vs 14.4%; relative risk [RR], 0.80; number needed to treat [NNT], 35). Secondary outcomes (severe complications, representing a composite of the use of CPAP or high-flow nasal cannula for at least 12 continuous hours, supplemental oxygen for at least 24 continuous hours, ECMO, mechanical ventilation, stillbirth, or neonatal death within 72 hours after delivery) were also lower in the betamethasone group (8.1% vs 12.1%; RR, 0.67; NNT, 25). The betamethasone group also had a lower risk for transient tachypnea of the newborn (6.7% vs 9.9%; RR, 0.68).
There were no significant differences in the occurrence of maternal chorioamnionitis or endometritis between the groups. Hypoglycemia in the newborn occurred more in the betamethasone group (24% vs 15%; RR, 1.6; number needed to harm [NNH], 11). The betamethasone group had two neonatal deaths: one from septic shock, and the other from a structural cardiac anomaly and arrhythmia.
WHAT’S NEW
Betamethasone effective even in the late, late preterm period
This study demonstrated an improvement in neonatal respiratory outcomes when betamethasone versus placebo was used in the late preterm period. The findings were similar to those from the Antenatal Steroids for Term Elective Caesarean Section Research Team.9 Their trial showed a reduction in respiratory complications in term neonates delivered via elective cesarean section to mothers who received antenatal betamethasone (NNT, 37, to prevent admission to a special care nursery with respiratory distress). The findings were also consistent with those of a recent meta-analysis evaluating the occurrence of respiratory complications with the use of antenatal betamethasone in women expected to deliver in the late preterm period or with a planned cesarean delivery at ≥ 37 weeks’ gestation.10
CAVEATS
Neonates may develop hypoglycemia
The authors of the study reported an increased risk for hypoglycemia in the neonates receiving antenatal betamethasone. The long-term implications of this are unclear, however, given that there was a reduction in intermediate care nursery and neonatal ICU stays that were three days or longer in the betamethasone group. There was also no difference in hospital length of stay between the two groups. Additionally, it’s unclear if there are any long-term neonatal complications of betamethasone use in the late preterm period.
CHALLENGES TO IMPLEMENTATION
Challenges are negligible
There are minimal challenges to implementing this strategy, as betamethasone is routinely used for preterm labor and is readily available on labor and delivery units.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2017;66(2):104-106.
A 21-year-old G1P0 at 35 weeks, 2 days of gestation presents to labor and delivery reporting a “gush of clear fluid.” On exam, you confirm she has preterm rupture of membranes. She is contracting every three minutes and has a cervix dilated to 3 cm. Is there any neonatal benefit to using corticosteroids in this late preterm period?
Approximately 12% of all births in the United States are the result of preterm labor, and 8% take place in the late preterm period, defined as 34 to 36 weeks’ gestation.2,3 To reduce risk for neonatal death and respiratory complications, both the American College of Obstetricians and Gynecologists and the National Institutes of Health recommend a course of corticosteroids between 24 and 34 weeks’ gestation for women at increased risk for preterm delivery.2,4 Due to a lack of evidence from RCTs on the benefit of corticosteroids in late preterm labor, there are no recommendations to extend this period.5 However, multiple studies have shown that babies born during the late preterm period have more neonatal complications than term newborns.6-8
A retrospective chart review of more than 130,000 live births found that newborns who were delivered between 34 and 36 weeks had higher rates of respiratory distress than those delivered at 39 weeks (ventilator use dropped from 3.3% at 34 weeks to 0.3% at 39 weeks, and transient tachypnea decreased from 2.4% at 34 weeks to 0.4% at 39 weeks).6 Another retrospective review of more than 230,000 newborns, 19,000 of whom were born in the late preterm period, revealed that more neonates born between 34 and 36 weeks’ gestation had respiratory distress syndrome than neonates delivered at 39 weeks (10.5% at 34 weeks, 6% at 35 weeks, 2.8% at 36 weeks vs 0.3% at 39 weeks).8
STUDY SUMMARY
Late preterm newborns breathe better with antenatal betamethasone
This RCT examined the effectiveness of betamethasone in preventing neonatal respiratory complications for 2,831 women at high probability of preterm delivery between 34 weeks and 36 weeks, 6 days of gestation. “High probability of preterm delivery” was defined as preterm labor with intact membranes and at least 3 cm dilation or 75% cervical effacement; spontaneous rupture of membranes; or anticipated preterm delivery for any other indication either through induction or cesarean section between 24 hours and seven days after the planned randomization.
Patients were randomly assigned to receive two intramuscular injections (12 mg each) of either betamethasone or placebo, 24 hours apart. The two doses were successfully given in 60% of the betamethasone group and 59% of the placebo group. In 95% of the cases in which the second dose was not given, it was because delivery occurred within 24 hours of the first dose.
The primary outcome was the need for respiratory support within 72 hours of birth, defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least two consecutive hours, supplemental oxygen for at least four continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation.
The median length of time from enrollment to delivery was 31 to 33 hours, and 31.4% underwent cesarean delivery. In the intention-to-treat analysis, the primary outcome was significantly lower in the betamethasone group than in the placebo group (11.6% vs 14.4%; relative risk [RR], 0.80; number needed to treat [NNT], 35). Secondary outcomes (severe complications, representing a composite of the use of CPAP or high-flow nasal cannula for at least 12 continuous hours, supplemental oxygen for at least 24 continuous hours, ECMO, mechanical ventilation, stillbirth, or neonatal death within 72 hours after delivery) were also lower in the betamethasone group (8.1% vs 12.1%; RR, 0.67; NNT, 25). The betamethasone group also had a lower risk for transient tachypnea of the newborn (6.7% vs 9.9%; RR, 0.68).
There were no significant differences in the occurrence of maternal chorioamnionitis or endometritis between the groups. Hypoglycemia in the newborn occurred more in the betamethasone group (24% vs 15%; RR, 1.6; number needed to harm [NNH], 11). The betamethasone group had two neonatal deaths: one from septic shock, and the other from a structural cardiac anomaly and arrhythmia.
WHAT’S NEW
Betamethasone effective even in the late, late preterm period
This study demonstrated an improvement in neonatal respiratory outcomes when betamethasone versus placebo was used in the late preterm period. The findings were similar to those from the Antenatal Steroids for Term Elective Caesarean Section Research Team.9 Their trial showed a reduction in respiratory complications in term neonates delivered via elective cesarean section to mothers who received antenatal betamethasone (NNT, 37, to prevent admission to a special care nursery with respiratory distress). The findings were also consistent with those of a recent meta-analysis evaluating the occurrence of respiratory complications with the use of antenatal betamethasone in women expected to deliver in the late preterm period or with a planned cesarean delivery at ≥ 37 weeks’ gestation.10
CAVEATS
Neonates may develop hypoglycemia
The authors of the study reported an increased risk for hypoglycemia in the neonates receiving antenatal betamethasone. The long-term implications of this are unclear, however, given that there was a reduction in intermediate care nursery and neonatal ICU stays that were three days or longer in the betamethasone group. There was also no difference in hospital length of stay between the two groups. Additionally, it’s unclear if there are any long-term neonatal complications of betamethasone use in the late preterm period.
CHALLENGES TO IMPLEMENTATION
Challenges are negligible
There are minimal challenges to implementing this strategy, as betamethasone is routinely used for preterm labor and is readily available on labor and delivery units.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2017;66(2):104-106.
1. Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; NICHD Maternal–Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374:1311-1320.
2. Practice Bulletin No. 159 Summary: Management of Preterm Labor. Obstet Gynecol. 2016;127:190-191.
3. Martin JA, Hamilton BE, Osterman MJ, et al. Births: final data for 2013. Natl Vital Stat Rep. 2015;64:1-65.
4. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994;12:1-24.
5. Society for Maternal-Fetal Medicine (SMFM) Publications Committee. Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. Am J Obstet Gynecol. 2016;215:B13-B15.
6. McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol. 2008;111:35-41.
7. Yoder BA, Gordon MC, Barth WH Jr. Late-preterm birth: does the changing obstetric paradigm alter the epidemiology of respiratory complications? Obstet Gynecol. 2008;111:814-822.
8. Consortium on Safe Labor, Hibbard JU, Wilkins I, Sun L, et al. Respiratory morbidity in late preterm births. JAMA. 2010;304:419-425.
9. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ. 2005;331:662.
10. Saccone G, Berghella V. Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. BMJ. 2016;355:i5044.
1. Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; NICHD Maternal–Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374:1311-1320.
2. Practice Bulletin No. 159 Summary: Management of Preterm Labor. Obstet Gynecol. 2016;127:190-191.
3. Martin JA, Hamilton BE, Osterman MJ, et al. Births: final data for 2013. Natl Vital Stat Rep. 2015;64:1-65.
4. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994;12:1-24.
5. Society for Maternal-Fetal Medicine (SMFM) Publications Committee. Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. Am J Obstet Gynecol. 2016;215:B13-B15.
6. McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol. 2008;111:35-41.
7. Yoder BA, Gordon MC, Barth WH Jr. Late-preterm birth: does the changing obstetric paradigm alter the epidemiology of respiratory complications? Obstet Gynecol. 2008;111:814-822.
8. Consortium on Safe Labor, Hibbard JU, Wilkins I, Sun L, et al. Respiratory morbidity in late preterm births. JAMA. 2010;304:419-425.
9. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ. 2005;331:662.
10. Saccone G, Berghella V. Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. BMJ. 2016;355:i5044.
Pneumococcal conjugate vaccine beats Streptococcus pneumoniae bacteremia
Routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) reduced the incidence of Streptococcus pneumoniae bacteremia by 95% from a time period before to a time period after the vaccine was implemented, based on a review of more than 57,000 blood cultures from children aged 3-36 months.
Kaiser Permanente implemented universal immunization with PCV13 in June 2010. “Initial trends through 2012 demonstrated continued decline in pneumococcal infections, with the biggest impact in children less than 5 years old,” wrote Tara Greenhow, MD, of Kaiser Permanente Northern California, San Francisco, and her colleagues.
Overall, the incidence of S. pneumoniae bacteremia declined from 74.5 per 100,000 children during the period before PCV7 (1998-1999) to 3.5 per 100,000 children during a period after routine use of PCV13 (2013-2014). The annual number of bacteremia cases from any cause dropped by 78% between these two time periods.
As bacteremia caused by pneumococci decreased, 77% of cases in the post-PCV13 time period were caused by Escherichia coli, Salmonella spp., and Staphylococcus aureus. “A total of 76% of bacteremia occurred with a source, including 34% urinary tract infections, 17% gastroenteritis, 8% pneumonias, 8% osteomyelitis, 6% skin and soft tissue infections, and 3% other,” Dr. Greenhow and her associates reported.
The large population of the Kaiser Permanente system supports the accuracy of the now rare incidence of bacteremia in young children, the researchers noted. However, “because bacteremia in the post-PCV13 era is more likely to occur with a source, a focused examination should be performed and appropriate studies should be obtained at the time of a blood culture collection,” they said.
Routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) reduced the incidence of Streptococcus pneumoniae bacteremia by 95% from a time period before to a time period after the vaccine was implemented, based on a review of more than 57,000 blood cultures from children aged 3-36 months.
Kaiser Permanente implemented universal immunization with PCV13 in June 2010. “Initial trends through 2012 demonstrated continued decline in pneumococcal infections, with the biggest impact in children less than 5 years old,” wrote Tara Greenhow, MD, of Kaiser Permanente Northern California, San Francisco, and her colleagues.
Overall, the incidence of S. pneumoniae bacteremia declined from 74.5 per 100,000 children during the period before PCV7 (1998-1999) to 3.5 per 100,000 children during a period after routine use of PCV13 (2013-2014). The annual number of bacteremia cases from any cause dropped by 78% between these two time periods.
As bacteremia caused by pneumococci decreased, 77% of cases in the post-PCV13 time period were caused by Escherichia coli, Salmonella spp., and Staphylococcus aureus. “A total of 76% of bacteremia occurred with a source, including 34% urinary tract infections, 17% gastroenteritis, 8% pneumonias, 8% osteomyelitis, 6% skin and soft tissue infections, and 3% other,” Dr. Greenhow and her associates reported.
The large population of the Kaiser Permanente system supports the accuracy of the now rare incidence of bacteremia in young children, the researchers noted. However, “because bacteremia in the post-PCV13 era is more likely to occur with a source, a focused examination should be performed and appropriate studies should be obtained at the time of a blood culture collection,” they said.
Routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) reduced the incidence of Streptococcus pneumoniae bacteremia by 95% from a time period before to a time period after the vaccine was implemented, based on a review of more than 57,000 blood cultures from children aged 3-36 months.
Kaiser Permanente implemented universal immunization with PCV13 in June 2010. “Initial trends through 2012 demonstrated continued decline in pneumococcal infections, with the biggest impact in children less than 5 years old,” wrote Tara Greenhow, MD, of Kaiser Permanente Northern California, San Francisco, and her colleagues.
Overall, the incidence of S. pneumoniae bacteremia declined from 74.5 per 100,000 children during the period before PCV7 (1998-1999) to 3.5 per 100,000 children during a period after routine use of PCV13 (2013-2014). The annual number of bacteremia cases from any cause dropped by 78% between these two time periods.
As bacteremia caused by pneumococci decreased, 77% of cases in the post-PCV13 time period were caused by Escherichia coli, Salmonella spp., and Staphylococcus aureus. “A total of 76% of bacteremia occurred with a source, including 34% urinary tract infections, 17% gastroenteritis, 8% pneumonias, 8% osteomyelitis, 6% skin and soft tissue infections, and 3% other,” Dr. Greenhow and her associates reported.
The large population of the Kaiser Permanente system supports the accuracy of the now rare incidence of bacteremia in young children, the researchers noted. However, “because bacteremia in the post-PCV13 era is more likely to occur with a source, a focused examination should be performed and appropriate studies should be obtained at the time of a blood culture collection,” they said.
FROM PEDIATRICS
STD testing in youth hindered by confidentiality concerns
Adolescents and young adults on their parents’ health insurance plan are less likely to receive sexual preventive health care, such as sexual risk assessments and testing for sexually transmitted disease, a study found.
Further, teen girls (aged 15-17 years), were more than twice as likely to be tested for chlamydia if they met with their provider alone than if they did not, researchers found.
“Confidentiality issues, including concerns that parents might find out, might be barriers to the use of STD [sexually transmitted disease] services among some subpopulations,” Jami S. Leichliter, PhD, and colleagues at the Centers for Disease Control and Prevention wrote. “Public health efforts to reduce these confidentiality concerns might be useful,” such as providers meeting privately for at least part of an appointment with an adolescent (MMWR. 2017 Mar 10;66[9]:237-41).
The researchers examined data collected from the 2013-2015 National Survey of Family Growth regarding sexual and reproductive health care experiences and behaviors of youth with sexual experience, specifically teens aged 15-17 and young adults aged 18-25 who were on their parents’ health plan. Sexual experience refers to having ever had vaginal, anal, or oral sex with any partner.
Overall, 12.7% of these youth avoided seeking care for sexual and reproductive health because they worried their parents could find out. For those aged 15-17 years, the rate was even higher, at 22.6%.
These concerns were also reflected in the overall prevalence of chlamydia screenings: Just 17.1% of young women who worried about confidentiality had been screened for chlamydia, compared with 38.7% of young women who did not report that concern.
The researchers also compared teens aged 15-17 who had and had not received a sexual risk assessment, which includes being asked by a provider about their (or their partners’) sexual orientation, number of sexual partners, condom use, and types of sex. Among teens who met with a provider alone in the past year, 71.1% reported receiving a sexual risk assessment, compared with about 36.6% who did not meet privately with a provider.
Similarly, 34.0% of teen girls (aged 15-17 years) who saw their provider alone were tested for chlamydia, compared with 14.9% who never met with their provider alone. Slightly more teen boys (13.6%) received STD testing if they met with their provider alone than if they didn’t (9.5%), but this difference did not reach statistical significance.
The study was funded by the Centers for Disease Control and Prevention. The authors did not report any disclosures.
Adolescents and young adults on their parents’ health insurance plan are less likely to receive sexual preventive health care, such as sexual risk assessments and testing for sexually transmitted disease, a study found.
Further, teen girls (aged 15-17 years), were more than twice as likely to be tested for chlamydia if they met with their provider alone than if they did not, researchers found.
“Confidentiality issues, including concerns that parents might find out, might be barriers to the use of STD [sexually transmitted disease] services among some subpopulations,” Jami S. Leichliter, PhD, and colleagues at the Centers for Disease Control and Prevention wrote. “Public health efforts to reduce these confidentiality concerns might be useful,” such as providers meeting privately for at least part of an appointment with an adolescent (MMWR. 2017 Mar 10;66[9]:237-41).
The researchers examined data collected from the 2013-2015 National Survey of Family Growth regarding sexual and reproductive health care experiences and behaviors of youth with sexual experience, specifically teens aged 15-17 and young adults aged 18-25 who were on their parents’ health plan. Sexual experience refers to having ever had vaginal, anal, or oral sex with any partner.
Overall, 12.7% of these youth avoided seeking care for sexual and reproductive health because they worried their parents could find out. For those aged 15-17 years, the rate was even higher, at 22.6%.
These concerns were also reflected in the overall prevalence of chlamydia screenings: Just 17.1% of young women who worried about confidentiality had been screened for chlamydia, compared with 38.7% of young women who did not report that concern.
The researchers also compared teens aged 15-17 who had and had not received a sexual risk assessment, which includes being asked by a provider about their (or their partners’) sexual orientation, number of sexual partners, condom use, and types of sex. Among teens who met with a provider alone in the past year, 71.1% reported receiving a sexual risk assessment, compared with about 36.6% who did not meet privately with a provider.
Similarly, 34.0% of teen girls (aged 15-17 years) who saw their provider alone were tested for chlamydia, compared with 14.9% who never met with their provider alone. Slightly more teen boys (13.6%) received STD testing if they met with their provider alone than if they didn’t (9.5%), but this difference did not reach statistical significance.
The study was funded by the Centers for Disease Control and Prevention. The authors did not report any disclosures.
Adolescents and young adults on their parents’ health insurance plan are less likely to receive sexual preventive health care, such as sexual risk assessments and testing for sexually transmitted disease, a study found.
Further, teen girls (aged 15-17 years), were more than twice as likely to be tested for chlamydia if they met with their provider alone than if they did not, researchers found.
“Confidentiality issues, including concerns that parents might find out, might be barriers to the use of STD [sexually transmitted disease] services among some subpopulations,” Jami S. Leichliter, PhD, and colleagues at the Centers for Disease Control and Prevention wrote. “Public health efforts to reduce these confidentiality concerns might be useful,” such as providers meeting privately for at least part of an appointment with an adolescent (MMWR. 2017 Mar 10;66[9]:237-41).
The researchers examined data collected from the 2013-2015 National Survey of Family Growth regarding sexual and reproductive health care experiences and behaviors of youth with sexual experience, specifically teens aged 15-17 and young adults aged 18-25 who were on their parents’ health plan. Sexual experience refers to having ever had vaginal, anal, or oral sex with any partner.
Overall, 12.7% of these youth avoided seeking care for sexual and reproductive health because they worried their parents could find out. For those aged 15-17 years, the rate was even higher, at 22.6%.
These concerns were also reflected in the overall prevalence of chlamydia screenings: Just 17.1% of young women who worried about confidentiality had been screened for chlamydia, compared with 38.7% of young women who did not report that concern.
The researchers also compared teens aged 15-17 who had and had not received a sexual risk assessment, which includes being asked by a provider about their (or their partners’) sexual orientation, number of sexual partners, condom use, and types of sex. Among teens who met with a provider alone in the past year, 71.1% reported receiving a sexual risk assessment, compared with about 36.6% who did not meet privately with a provider.
Similarly, 34.0% of teen girls (aged 15-17 years) who saw their provider alone were tested for chlamydia, compared with 14.9% who never met with their provider alone. Slightly more teen boys (13.6%) received STD testing if they met with their provider alone than if they didn’t (9.5%), but this difference did not reach statistical significance.
The study was funded by the Centers for Disease Control and Prevention. The authors did not report any disclosures.
FROM MMWR
Key clinical point:
Major finding: Overall, 12.7% of sexually experienced youths (aged 15-25 years) who were on their parents’ health plan would not seek sexual and reproductive health care because of confidentiality concerns.
Data source: Responses from sexually experienced youth aged 15-25 years provided during the 2013-2015 U.S. National Survey of Family Growth.
Disclosures: The study was funded by the Centers for Disease Control and Prevention. The authors did not report any disclosures.
Oral immunotherapy induced wheat allergy tolerance
ATLANTA – Oral immunotherapy with wheat gluten flour decreased wheat reactions in some allergic patients, according to a trial reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
Wheat allergy is fairly common in young children; most people outgrow it. For some, though, it remains a dangerous problem, especially because wheat is almost impossible to avoid, said senior investigator Hugh Sampson, MD, the Kurt Hirschhorn Professor of Pediatrics at the Icahn School of Medicine at Mount Sinai and director of the Jaffe Food Allergy Institute at Mount Sinai Hospital, New York.
For example, one of the study subjects stopped for a bite on the way to the clinic. “He thought he ate a wheat-free breakfast but ended up arriving with anaphylaxis,” the physician said.
Gluten is the protein-rich allergenic part of wheat; using gluten flour instead of regular flour allowed for smaller, more convenient doses. It was sprinkled over applesauce and other foods. Twelve of the 23 gluten flour subjects (52%), but no one in the placebo group, tolerated a challenge of 4,443 mg at 1 year.
Next, placebo subjects were started on their own gluten flour regimen, but they shot for a higher maximum dose of 3,870 mg/day. The original gluten group stayed on their dose, a maximum of 1,445 mg/day.
The higher dose was more effective at 2-year follow-up; 7 of 23 patients (30%) in the 1,445-mg group tolerated a challenge of 7,443 mg at 2 years, versus 12 of 21 patients (57%) in the 3,870-mg group.
Just over 10% of the doses triggered adverse reactions. Most of the reactions were mild – itching in the throat or mouth, nausea, and the like – but epinephrine was needed after 0.05% of the doses. The adverse reaction rate was similar to that with other forms of oral immunotherapy, and there were no statistically significant differences in the number of reactions between the low- and high-dose gluten groups.
For anyone who reads the study and thinks about running to the grocery store for gluten flour, Dr. Sampson cautioned against it. There’s no Food and Drug Administration–approved product, and, more importantly, “you can run into [serious medical] problems” if, for instance, immunotherapy triggers anaphylaxis with too much exercise afterward.
The study “has nothing to do with” the kind of gluten intolerance that’s led to an explosion in gluten-free products in recent years, he said. “Our study was directed at IgE-mediated reactions. Celiac disease has a very different mechanism.”
Also, only a few people remained tolerant after being backed off wheat immunotherapy for a couple of months. There’s no such thing as a cure for food allergies at this point.
“We are trying to get people into remission. Nobody yet has demonstrated that you can make a permanent change in somebody [who] is hypersensitive, even to a bee sting,” Dr. Sampson said.
The study results are big enough to protect wheat-allergic people from accidental exposure. In the case of the study subject who reacted to wheat in his breakfast, he probably reacted to far less than 7,443 mg of wheat protein – about the amount in a plate of pasta – before immunotherapy. No one with a wheat allergy is intentionally going to order something like that, Dr. Sampson said.
The next step is industry funding for a larger trial. “These studies are expensive, and we hope somebody will take up the torch. We have to get industry involved,” he said.
Private philanthropies funded the work. Dr. Sampson is chief scientific officer for DBV Technologies, a company developing a patch for peanut allergies.
ATLANTA – Oral immunotherapy with wheat gluten flour decreased wheat reactions in some allergic patients, according to a trial reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
Wheat allergy is fairly common in young children; most people outgrow it. For some, though, it remains a dangerous problem, especially because wheat is almost impossible to avoid, said senior investigator Hugh Sampson, MD, the Kurt Hirschhorn Professor of Pediatrics at the Icahn School of Medicine at Mount Sinai and director of the Jaffe Food Allergy Institute at Mount Sinai Hospital, New York.
For example, one of the study subjects stopped for a bite on the way to the clinic. “He thought he ate a wheat-free breakfast but ended up arriving with anaphylaxis,” the physician said.
Gluten is the protein-rich allergenic part of wheat; using gluten flour instead of regular flour allowed for smaller, more convenient doses. It was sprinkled over applesauce and other foods. Twelve of the 23 gluten flour subjects (52%), but no one in the placebo group, tolerated a challenge of 4,443 mg at 1 year.
Next, placebo subjects were started on their own gluten flour regimen, but they shot for a higher maximum dose of 3,870 mg/day. The original gluten group stayed on their dose, a maximum of 1,445 mg/day.
The higher dose was more effective at 2-year follow-up; 7 of 23 patients (30%) in the 1,445-mg group tolerated a challenge of 7,443 mg at 2 years, versus 12 of 21 patients (57%) in the 3,870-mg group.
Just over 10% of the doses triggered adverse reactions. Most of the reactions were mild – itching in the throat or mouth, nausea, and the like – but epinephrine was needed after 0.05% of the doses. The adverse reaction rate was similar to that with other forms of oral immunotherapy, and there were no statistically significant differences in the number of reactions between the low- and high-dose gluten groups.
For anyone who reads the study and thinks about running to the grocery store for gluten flour, Dr. Sampson cautioned against it. There’s no Food and Drug Administration–approved product, and, more importantly, “you can run into [serious medical] problems” if, for instance, immunotherapy triggers anaphylaxis with too much exercise afterward.
The study “has nothing to do with” the kind of gluten intolerance that’s led to an explosion in gluten-free products in recent years, he said. “Our study was directed at IgE-mediated reactions. Celiac disease has a very different mechanism.”
Also, only a few people remained tolerant after being backed off wheat immunotherapy for a couple of months. There’s no such thing as a cure for food allergies at this point.
“We are trying to get people into remission. Nobody yet has demonstrated that you can make a permanent change in somebody [who] is hypersensitive, even to a bee sting,” Dr. Sampson said.
The study results are big enough to protect wheat-allergic people from accidental exposure. In the case of the study subject who reacted to wheat in his breakfast, he probably reacted to far less than 7,443 mg of wheat protein – about the amount in a plate of pasta – before immunotherapy. No one with a wheat allergy is intentionally going to order something like that, Dr. Sampson said.
The next step is industry funding for a larger trial. “These studies are expensive, and we hope somebody will take up the torch. We have to get industry involved,” he said.
Private philanthropies funded the work. Dr. Sampson is chief scientific officer for DBV Technologies, a company developing a patch for peanut allergies.
ATLANTA – Oral immunotherapy with wheat gluten flour decreased wheat reactions in some allergic patients, according to a trial reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
Wheat allergy is fairly common in young children; most people outgrow it. For some, though, it remains a dangerous problem, especially because wheat is almost impossible to avoid, said senior investigator Hugh Sampson, MD, the Kurt Hirschhorn Professor of Pediatrics at the Icahn School of Medicine at Mount Sinai and director of the Jaffe Food Allergy Institute at Mount Sinai Hospital, New York.
For example, one of the study subjects stopped for a bite on the way to the clinic. “He thought he ate a wheat-free breakfast but ended up arriving with anaphylaxis,” the physician said.
Gluten is the protein-rich allergenic part of wheat; using gluten flour instead of regular flour allowed for smaller, more convenient doses. It was sprinkled over applesauce and other foods. Twelve of the 23 gluten flour subjects (52%), but no one in the placebo group, tolerated a challenge of 4,443 mg at 1 year.
Next, placebo subjects were started on their own gluten flour regimen, but they shot for a higher maximum dose of 3,870 mg/day. The original gluten group stayed on their dose, a maximum of 1,445 mg/day.
The higher dose was more effective at 2-year follow-up; 7 of 23 patients (30%) in the 1,445-mg group tolerated a challenge of 7,443 mg at 2 years, versus 12 of 21 patients (57%) in the 3,870-mg group.
Just over 10% of the doses triggered adverse reactions. Most of the reactions were mild – itching in the throat or mouth, nausea, and the like – but epinephrine was needed after 0.05% of the doses. The adverse reaction rate was similar to that with other forms of oral immunotherapy, and there were no statistically significant differences in the number of reactions between the low- and high-dose gluten groups.
For anyone who reads the study and thinks about running to the grocery store for gluten flour, Dr. Sampson cautioned against it. There’s no Food and Drug Administration–approved product, and, more importantly, “you can run into [serious medical] problems” if, for instance, immunotherapy triggers anaphylaxis with too much exercise afterward.
The study “has nothing to do with” the kind of gluten intolerance that’s led to an explosion in gluten-free products in recent years, he said. “Our study was directed at IgE-mediated reactions. Celiac disease has a very different mechanism.”
Also, only a few people remained tolerant after being backed off wheat immunotherapy for a couple of months. There’s no such thing as a cure for food allergies at this point.
“We are trying to get people into remission. Nobody yet has demonstrated that you can make a permanent change in somebody [who] is hypersensitive, even to a bee sting,” Dr. Sampson said.
The study results are big enough to protect wheat-allergic people from accidental exposure. In the case of the study subject who reacted to wheat in his breakfast, he probably reacted to far less than 7,443 mg of wheat protein – about the amount in a plate of pasta – before immunotherapy. No one with a wheat allergy is intentionally going to order something like that, Dr. Sampson said.
The next step is industry funding for a larger trial. “These studies are expensive, and we hope somebody will take up the torch. We have to get industry involved,” he said.
Private philanthropies funded the work. Dr. Sampson is chief scientific officer for DBV Technologies, a company developing a patch for peanut allergies.
AT 2017 AAAAI ANNUAL MEETING
Key clinical point:
Major finding: Twelve of the 23 gluten flour subjects (52%), but no one in the placebo group, tolerated a challenge dose of 4,443 mg at 1 year.
Data source: A randomized trial of 46 wheat-allergic patients.
Disclosures: Private philanthropies funded the work. The senior investigator is chief scientific officer for DBV Technologies, a company developing a patch for peanut allergies.
Synthetic cannabinoid use linked to multiple risk factors
An estimated 1 in 10 high school students uses synthetic cannabinoids, which are linked to multiple other risk behaviors, and use is more likely among students with depressive symptoms, marijuana use, and alcohol use, investigators in two studies reported.
Synthetic cannabinoids are structurally similar to delta-9-tetrahydrocannabinol, but they may be more potent, with adverse health effects not seen with natural tetrahydrocannabinol in marijuana. These synthetic products are accessible to teens online, in convenience stores, and in smoke shops. Past research has suggested that adolescents aren’t aware of the possible negative effects of these products, such as tachycardia, hypertension, lethargy, nausea, vomiting, irritability, chest pain, hallucinations, confusion, and vertigo.
“Overall, we observed that ever use of synthetic cannabinoids was associated with the majority of health risk behaviors included in our study and that those associations tended to be more pronounced for ever use of synthetic cannabinoids than for ever use of marijuana only, particularly for substance use behaviors and sexual risk behaviors,” they wrote (Pediatrics. 2017 March 13. doi: 10.1542/peds.2016-2675).
Dr. Clayton’s team analyzed data from 15,624 students in grades 9-12 from the cross-sectional 2015 Youth Risk Behavior Survey, including all 50 states and Washington. The questions asked about use of marijuana, synthetic cannabinoids, or both. The question about synthetic cannabinoids included reference to street names of the drug, such as K2, Spice, fake weed, King Kong, Yucatan Fire, Skunk, or Moon Rocks. Another three dozen questions asked about risk behaviors related to substance use, violence and injury, mental health, and sexual health.
The results revealed that 29% of students had ever used only marijuana and 9% had ever used synthetic cannabinoids. Most of the students, 61%, had never used either. Although 23% of marijuana users had used synthetic cannabinoids, nearly all (98%) of the cannabinoids users had used marijuana.
Compared with those who had used only marijuana, adolescents who had ever used synthetic cannabinoids were considerably more likely to engage in substance use (adjusted prevalence ratio [aPR] = 4.85 for current alcohol use; aPR =151.90 for ever use of heroin) or sexual risk behaviors (had sexual intercourse with four or more persons during their life; aPR = 6.20). They also were more than twice as likely to have tried marijuana before age 13 years (aPR = 2.35) and were more likely to have used marijuana at least once in the past month (aPR = 1.36) and to have used marijuana 20 or more times in the past month (aPR = 1.88).
“Youth may progress from marijuana use only to the use of synthetic cannabinoids for a variety of reasons, such as ease of access, perception of safety, and ability to be undetected by many drug tests,” Dr. Clayton and her associates wrote.
The second study found similar associations between marijuana use and later use of synthetic cannabinoids. Andrew L. Ninnemann of the University of Missouri–Columbia, and his associates collected data twice over a 12-month period from 964 high school students at seven public schools in Southeast Texas (Pediatrics. 2017 March 13. doi: 10.1542/peds.2016-3009), to examine the relationship of synthetic cannabinoid use with anxiety, depression, impulsivity, and marijuana use.
The first assessment occurred in spring of 2011 and the second in spring of 2012. Most respondents (response rate, 62%) were sophomores (73%) or juniors (24%), with only 1% each of freshmen and seniors; 1% reported “other.” The sample included 31% African American students, 29% white students, 28% Hispanic students, and 12% of other ethnicities.
Males were more likely than females to use synthetic cannabinoids, and African American students were less likely to use them than teens of other ethnicities. Depression at baseline predicted use of synthetic cannabinoids a year later (adjusted odds ratio [aOR] = 1.42, P = .04), as did alcohol use (aOR = 1.85, P = .02), marijuana use (aOR = 2.47, P less than .001), and synthetic cannabinoid use at baseline (aOR = 2.36, P less than .001).
Students also were more likely to use marijuana at follow-up if they had used alcohol (aOR = 1.96, P less than .001) or marijuana (aOR = 4.52, P less than .001) at baseline. However, neither demographic variables nor anxiety, impulsivity, synthetic cannabinoid use, or other drug use significantly predicted marijuana use 1 year later.
Mr. Ninnemann’s study also found a slightly higher prevalence of synthetic cannabinoid use at baseline than the Clayton study did, with 13% of the Texas sample reporting use.
“The substantial risks associated with even a single episode of synthetic cannabinoid use emphasize the critical importance of identifying and targeting potential risk factors,” Mr. Ninnemann and his coauthors wrote. “Our findings indicate that prevention and intervention efforts may benefit from targeting depressive symptoms and alcohol and marijuana use to potentially reduce adolescent use of synthetic cannabinoids.”
Dr. Clayton and her colleagues mentioned a past study finding that 50% of elementary schools, 33% of middle schools, and 13% of high schools do not require instruction on alcohol or other drug use prevention. The U.S. trend of cannabis legalization also introduces uncertainty, the investigators noted.
“It is unclear what impact the legalization of marijuana will have on the use of synthetic cannabinoids,” Dr. Clayton’s team wrote. The evidence is contradictory on the likelihood of teens trying marijuana in these environments, but “there is a concern that if marijuana use increases, the use of synthetic marijuana may also increase,” they noted.
The Clayton study did not have external funding. The Ninnemann study received funding from the National Science Foundation, the National Institute of Child Health and Human Development, and the National Institute of Justice. The authors of both studies reported that they had no disclosures.
Synthetic cannabinoids are made in a lab to have marijuanalike properties, but often have more short-term medical and behavioral toxicities. We at the University of Florida McKnight Brain Institute in Gainesville have studied bath salts and synthetics in the laboratory, but there have been few human studies. The current studies by Clayton et al. and Ninnemann et al., following shortly after the American Academy of Pediatrics warning about the effects of cannabis smoking in adolescents (Pediatrics. 2017 10.1542/peds.2016-4069), are a grim reminder that adolescence is a period of extreme vulnerability to drugs of abuse. Synthetic cannabinoids, as addiction specialists will attest, produce some signs and symptoms of cannabis intoxication, but often with more acute problems, with greater intensity, and of longer duration. In the current two studies, it is clear that the reported consequences of synthetic cannabinoids are greater in terms of risk behaviors and depression than in marijuana smokers.
Mark S. Gold, MD, is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. He also is chairman of the scientific advisory boards for RiverMend Health, Atlanta.
Synthetic cannabinoids are made in a lab to have marijuanalike properties, but often have more short-term medical and behavioral toxicities. We at the University of Florida McKnight Brain Institute in Gainesville have studied bath salts and synthetics in the laboratory, but there have been few human studies. The current studies by Clayton et al. and Ninnemann et al., following shortly after the American Academy of Pediatrics warning about the effects of cannabis smoking in adolescents (Pediatrics. 2017 10.1542/peds.2016-4069), are a grim reminder that adolescence is a period of extreme vulnerability to drugs of abuse. Synthetic cannabinoids, as addiction specialists will attest, produce some signs and symptoms of cannabis intoxication, but often with more acute problems, with greater intensity, and of longer duration. In the current two studies, it is clear that the reported consequences of synthetic cannabinoids are greater in terms of risk behaviors and depression than in marijuana smokers.
Mark S. Gold, MD, is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. He also is chairman of the scientific advisory boards for RiverMend Health, Atlanta.
Synthetic cannabinoids are made in a lab to have marijuanalike properties, but often have more short-term medical and behavioral toxicities. We at the University of Florida McKnight Brain Institute in Gainesville have studied bath salts and synthetics in the laboratory, but there have been few human studies. The current studies by Clayton et al. and Ninnemann et al., following shortly after the American Academy of Pediatrics warning about the effects of cannabis smoking in adolescents (Pediatrics. 2017 10.1542/peds.2016-4069), are a grim reminder that adolescence is a period of extreme vulnerability to drugs of abuse. Synthetic cannabinoids, as addiction specialists will attest, produce some signs and symptoms of cannabis intoxication, but often with more acute problems, with greater intensity, and of longer duration. In the current two studies, it is clear that the reported consequences of synthetic cannabinoids are greater in terms of risk behaviors and depression than in marijuana smokers.
Mark S. Gold, MD, is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. He also is chairman of the scientific advisory boards for RiverMend Health, Atlanta.
An estimated 1 in 10 high school students uses synthetic cannabinoids, which are linked to multiple other risk behaviors, and use is more likely among students with depressive symptoms, marijuana use, and alcohol use, investigators in two studies reported.
Synthetic cannabinoids are structurally similar to delta-9-tetrahydrocannabinol, but they may be more potent, with adverse health effects not seen with natural tetrahydrocannabinol in marijuana. These synthetic products are accessible to teens online, in convenience stores, and in smoke shops. Past research has suggested that adolescents aren’t aware of the possible negative effects of these products, such as tachycardia, hypertension, lethargy, nausea, vomiting, irritability, chest pain, hallucinations, confusion, and vertigo.
“Overall, we observed that ever use of synthetic cannabinoids was associated with the majority of health risk behaviors included in our study and that those associations tended to be more pronounced for ever use of synthetic cannabinoids than for ever use of marijuana only, particularly for substance use behaviors and sexual risk behaviors,” they wrote (Pediatrics. 2017 March 13. doi: 10.1542/peds.2016-2675).
Dr. Clayton’s team analyzed data from 15,624 students in grades 9-12 from the cross-sectional 2015 Youth Risk Behavior Survey, including all 50 states and Washington. The questions asked about use of marijuana, synthetic cannabinoids, or both. The question about synthetic cannabinoids included reference to street names of the drug, such as K2, Spice, fake weed, King Kong, Yucatan Fire, Skunk, or Moon Rocks. Another three dozen questions asked about risk behaviors related to substance use, violence and injury, mental health, and sexual health.
The results revealed that 29% of students had ever used only marijuana and 9% had ever used synthetic cannabinoids. Most of the students, 61%, had never used either. Although 23% of marijuana users had used synthetic cannabinoids, nearly all (98%) of the cannabinoids users had used marijuana.
Compared with those who had used only marijuana, adolescents who had ever used synthetic cannabinoids were considerably more likely to engage in substance use (adjusted prevalence ratio [aPR] = 4.85 for current alcohol use; aPR =151.90 for ever use of heroin) or sexual risk behaviors (had sexual intercourse with four or more persons during their life; aPR = 6.20). They also were more than twice as likely to have tried marijuana before age 13 years (aPR = 2.35) and were more likely to have used marijuana at least once in the past month (aPR = 1.36) and to have used marijuana 20 or more times in the past month (aPR = 1.88).
“Youth may progress from marijuana use only to the use of synthetic cannabinoids for a variety of reasons, such as ease of access, perception of safety, and ability to be undetected by many drug tests,” Dr. Clayton and her associates wrote.
The second study found similar associations between marijuana use and later use of synthetic cannabinoids. Andrew L. Ninnemann of the University of Missouri–Columbia, and his associates collected data twice over a 12-month period from 964 high school students at seven public schools in Southeast Texas (Pediatrics. 2017 March 13. doi: 10.1542/peds.2016-3009), to examine the relationship of synthetic cannabinoid use with anxiety, depression, impulsivity, and marijuana use.
The first assessment occurred in spring of 2011 and the second in spring of 2012. Most respondents (response rate, 62%) were sophomores (73%) or juniors (24%), with only 1% each of freshmen and seniors; 1% reported “other.” The sample included 31% African American students, 29% white students, 28% Hispanic students, and 12% of other ethnicities.
Males were more likely than females to use synthetic cannabinoids, and African American students were less likely to use them than teens of other ethnicities. Depression at baseline predicted use of synthetic cannabinoids a year later (adjusted odds ratio [aOR] = 1.42, P = .04), as did alcohol use (aOR = 1.85, P = .02), marijuana use (aOR = 2.47, P less than .001), and synthetic cannabinoid use at baseline (aOR = 2.36, P less than .001).
Students also were more likely to use marijuana at follow-up if they had used alcohol (aOR = 1.96, P less than .001) or marijuana (aOR = 4.52, P less than .001) at baseline. However, neither demographic variables nor anxiety, impulsivity, synthetic cannabinoid use, or other drug use significantly predicted marijuana use 1 year later.
Mr. Ninnemann’s study also found a slightly higher prevalence of synthetic cannabinoid use at baseline than the Clayton study did, with 13% of the Texas sample reporting use.
“The substantial risks associated with even a single episode of synthetic cannabinoid use emphasize the critical importance of identifying and targeting potential risk factors,” Mr. Ninnemann and his coauthors wrote. “Our findings indicate that prevention and intervention efforts may benefit from targeting depressive symptoms and alcohol and marijuana use to potentially reduce adolescent use of synthetic cannabinoids.”
Dr. Clayton and her colleagues mentioned a past study finding that 50% of elementary schools, 33% of middle schools, and 13% of high schools do not require instruction on alcohol or other drug use prevention. The U.S. trend of cannabis legalization also introduces uncertainty, the investigators noted.
“It is unclear what impact the legalization of marijuana will have on the use of synthetic cannabinoids,” Dr. Clayton’s team wrote. The evidence is contradictory on the likelihood of teens trying marijuana in these environments, but “there is a concern that if marijuana use increases, the use of synthetic marijuana may also increase,” they noted.
The Clayton study did not have external funding. The Ninnemann study received funding from the National Science Foundation, the National Institute of Child Health and Human Development, and the National Institute of Justice. The authors of both studies reported that they had no disclosures.
An estimated 1 in 10 high school students uses synthetic cannabinoids, which are linked to multiple other risk behaviors, and use is more likely among students with depressive symptoms, marijuana use, and alcohol use, investigators in two studies reported.
Synthetic cannabinoids are structurally similar to delta-9-tetrahydrocannabinol, but they may be more potent, with adverse health effects not seen with natural tetrahydrocannabinol in marijuana. These synthetic products are accessible to teens online, in convenience stores, and in smoke shops. Past research has suggested that adolescents aren’t aware of the possible negative effects of these products, such as tachycardia, hypertension, lethargy, nausea, vomiting, irritability, chest pain, hallucinations, confusion, and vertigo.
“Overall, we observed that ever use of synthetic cannabinoids was associated with the majority of health risk behaviors included in our study and that those associations tended to be more pronounced for ever use of synthetic cannabinoids than for ever use of marijuana only, particularly for substance use behaviors and sexual risk behaviors,” they wrote (Pediatrics. 2017 March 13. doi: 10.1542/peds.2016-2675).
Dr. Clayton’s team analyzed data from 15,624 students in grades 9-12 from the cross-sectional 2015 Youth Risk Behavior Survey, including all 50 states and Washington. The questions asked about use of marijuana, synthetic cannabinoids, or both. The question about synthetic cannabinoids included reference to street names of the drug, such as K2, Spice, fake weed, King Kong, Yucatan Fire, Skunk, or Moon Rocks. Another three dozen questions asked about risk behaviors related to substance use, violence and injury, mental health, and sexual health.
The results revealed that 29% of students had ever used only marijuana and 9% had ever used synthetic cannabinoids. Most of the students, 61%, had never used either. Although 23% of marijuana users had used synthetic cannabinoids, nearly all (98%) of the cannabinoids users had used marijuana.
Compared with those who had used only marijuana, adolescents who had ever used synthetic cannabinoids were considerably more likely to engage in substance use (adjusted prevalence ratio [aPR] = 4.85 for current alcohol use; aPR =151.90 for ever use of heroin) or sexual risk behaviors (had sexual intercourse with four or more persons during their life; aPR = 6.20). They also were more than twice as likely to have tried marijuana before age 13 years (aPR = 2.35) and were more likely to have used marijuana at least once in the past month (aPR = 1.36) and to have used marijuana 20 or more times in the past month (aPR = 1.88).
“Youth may progress from marijuana use only to the use of synthetic cannabinoids for a variety of reasons, such as ease of access, perception of safety, and ability to be undetected by many drug tests,” Dr. Clayton and her associates wrote.
The second study found similar associations between marijuana use and later use of synthetic cannabinoids. Andrew L. Ninnemann of the University of Missouri–Columbia, and his associates collected data twice over a 12-month period from 964 high school students at seven public schools in Southeast Texas (Pediatrics. 2017 March 13. doi: 10.1542/peds.2016-3009), to examine the relationship of synthetic cannabinoid use with anxiety, depression, impulsivity, and marijuana use.
The first assessment occurred in spring of 2011 and the second in spring of 2012. Most respondents (response rate, 62%) were sophomores (73%) or juniors (24%), with only 1% each of freshmen and seniors; 1% reported “other.” The sample included 31% African American students, 29% white students, 28% Hispanic students, and 12% of other ethnicities.
Males were more likely than females to use synthetic cannabinoids, and African American students were less likely to use them than teens of other ethnicities. Depression at baseline predicted use of synthetic cannabinoids a year later (adjusted odds ratio [aOR] = 1.42, P = .04), as did alcohol use (aOR = 1.85, P = .02), marijuana use (aOR = 2.47, P less than .001), and synthetic cannabinoid use at baseline (aOR = 2.36, P less than .001).
Students also were more likely to use marijuana at follow-up if they had used alcohol (aOR = 1.96, P less than .001) or marijuana (aOR = 4.52, P less than .001) at baseline. However, neither demographic variables nor anxiety, impulsivity, synthetic cannabinoid use, or other drug use significantly predicted marijuana use 1 year later.
Mr. Ninnemann’s study also found a slightly higher prevalence of synthetic cannabinoid use at baseline than the Clayton study did, with 13% of the Texas sample reporting use.
“The substantial risks associated with even a single episode of synthetic cannabinoid use emphasize the critical importance of identifying and targeting potential risk factors,” Mr. Ninnemann and his coauthors wrote. “Our findings indicate that prevention and intervention efforts may benefit from targeting depressive symptoms and alcohol and marijuana use to potentially reduce adolescent use of synthetic cannabinoids.”
Dr. Clayton and her colleagues mentioned a past study finding that 50% of elementary schools, 33% of middle schools, and 13% of high schools do not require instruction on alcohol or other drug use prevention. The U.S. trend of cannabis legalization also introduces uncertainty, the investigators noted.
“It is unclear what impact the legalization of marijuana will have on the use of synthetic cannabinoids,” Dr. Clayton’s team wrote. The evidence is contradictory on the likelihood of teens trying marijuana in these environments, but “there is a concern that if marijuana use increases, the use of synthetic marijuana may also increase,” they noted.
The Clayton study did not have external funding. The Ninnemann study received funding from the National Science Foundation, the National Institute of Child Health and Human Development, and the National Institute of Justice. The authors of both studies reported that they had no disclosures.
FROM PEDIATRICS
Key clinical point: Results of two studies found that 9%-13% of high school students have used synthetic cannabinoids.
Major finding: Depression, alcohol use, and marijuana use increase the likelihood of adolescents’ use of synthetic cannabinoids, which increases the risk of multiple substance use and risky sexual behavior.
Data source: Two studies, one surveying 15,624 high school students nationwide and one surveying 964 Texas public high school students twice over a period of 1 year.
Disclosures: The Clayton study had no external funding. The Ninnemann study received funding from the National Science Foundation, the National Institute of Child Health and Human Development, and the National Institute of Justice. The authors of both studies reported that they had no disclosures.
Esophageal variceal bleeding, portal hypertension tied to recurrent pediatric GI bleeds
Readmission to the hospital after acute GI bleeding in children is most often associated with an initial diagnosis of portal hypertension or esophageal variceal hemorrhage, based on data from a retrospective study of 9,902 patients.
Rebleeding in adults may be predicted by endoscopic characteristics of the bleeding source in some cases, but “there is still a considerable subgroup of children admitted with acute gastrointestinal bleeding and not endoscoped but in whom we do not have any measure to predict rebleeding including after discharge,” Thomas M. Attard, MD, Children’s Mercy Hospital, Kansas City, Mo., and his colleagues said.
The study included children aged 1-21 years with upper or indeterminate GI bleeding who were discharged from 49 pediatric hospitals between January 1, 2007 and September 30, 2015. Overall, 1,460 children (16%) were readmitted at least once within 30 days, with 72 readmitted twice and an average of 10 days’ time to readmission.
Readmission for recurrent bleeding was most frequently associated with an initial diagnosis of portal hypertension (20%) or esophageal variceal hemorrhage (20%). Children who had undergone endoscopy (odds ratio, 0.77) or Meckel’s scan (OR, 0.51) on initial admission were least likely to require readmission.
Children with one or two complex chronic conditions were almost twice as likely to be readmitted than were those with no complex chronic conditions, and a longer initial hospital stay and early treatment with proton pump inhibitors were associated with increased likelihood of readmission. “These may be indicative of more medically frail patients and greater severity of initial illness, respectively,” the researchers said. They found no association between increased risk of readmission and demographic factors including age, sex, race, and urban vs. rural residence (J Pediatr. 2017 Feb. doi: 10.1016/j.jpeds.2017.01.044).
Readmission to the hospital after acute GI bleeding in children is most often associated with an initial diagnosis of portal hypertension or esophageal variceal hemorrhage, based on data from a retrospective study of 9,902 patients.
Rebleeding in adults may be predicted by endoscopic characteristics of the bleeding source in some cases, but “there is still a considerable subgroup of children admitted with acute gastrointestinal bleeding and not endoscoped but in whom we do not have any measure to predict rebleeding including after discharge,” Thomas M. Attard, MD, Children’s Mercy Hospital, Kansas City, Mo., and his colleagues said.
The study included children aged 1-21 years with upper or indeterminate GI bleeding who were discharged from 49 pediatric hospitals between January 1, 2007 and September 30, 2015. Overall, 1,460 children (16%) were readmitted at least once within 30 days, with 72 readmitted twice and an average of 10 days’ time to readmission.
Readmission for recurrent bleeding was most frequently associated with an initial diagnosis of portal hypertension (20%) or esophageal variceal hemorrhage (20%). Children who had undergone endoscopy (odds ratio, 0.77) or Meckel’s scan (OR, 0.51) on initial admission were least likely to require readmission.
Children with one or two complex chronic conditions were almost twice as likely to be readmitted than were those with no complex chronic conditions, and a longer initial hospital stay and early treatment with proton pump inhibitors were associated with increased likelihood of readmission. “These may be indicative of more medically frail patients and greater severity of initial illness, respectively,” the researchers said. They found no association between increased risk of readmission and demographic factors including age, sex, race, and urban vs. rural residence (J Pediatr. 2017 Feb. doi: 10.1016/j.jpeds.2017.01.044).
Readmission to the hospital after acute GI bleeding in children is most often associated with an initial diagnosis of portal hypertension or esophageal variceal hemorrhage, based on data from a retrospective study of 9,902 patients.
Rebleeding in adults may be predicted by endoscopic characteristics of the bleeding source in some cases, but “there is still a considerable subgroup of children admitted with acute gastrointestinal bleeding and not endoscoped but in whom we do not have any measure to predict rebleeding including after discharge,” Thomas M. Attard, MD, Children’s Mercy Hospital, Kansas City, Mo., and his colleagues said.
The study included children aged 1-21 years with upper or indeterminate GI bleeding who were discharged from 49 pediatric hospitals between January 1, 2007 and September 30, 2015. Overall, 1,460 children (16%) were readmitted at least once within 30 days, with 72 readmitted twice and an average of 10 days’ time to readmission.
Readmission for recurrent bleeding was most frequently associated with an initial diagnosis of portal hypertension (20%) or esophageal variceal hemorrhage (20%). Children who had undergone endoscopy (odds ratio, 0.77) or Meckel’s scan (OR, 0.51) on initial admission were least likely to require readmission.
Children with one or two complex chronic conditions were almost twice as likely to be readmitted than were those with no complex chronic conditions, and a longer initial hospital stay and early treatment with proton pump inhibitors were associated with increased likelihood of readmission. “These may be indicative of more medically frail patients and greater severity of initial illness, respectively,” the researchers said. They found no association between increased risk of readmission and demographic factors including age, sex, race, and urban vs. rural residence (J Pediatr. 2017 Feb. doi: 10.1016/j.jpeds.2017.01.044).
FROM THE JOURNAL OF PEDIATRICS
AKI seen in 64% of children hospitalized with diabetic ketoacidosis
A high proportion of children with type 1 diabetes who are hospitalized for diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), according to results from a study.
Researchers reviewing records from a Canadian hospital found that in a cohort of 165 children hospitalized for DKA during a 5-year period (2008-2013), 64% developed the complication. Severe forms of AKI (stage 2 or 3) were common, representing 45% and 20%, respectively, of children with AKI. Two patients in the cohort required dialysis.
“We hypothesized that, because DKA is associated with both volume depletion and conservative fluid administration upon presentation, these children are potentially at high risk for AKI, above the level of risk expected by the rare reported cases in the literature,” Dr. Hursh and his colleagues wrote (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0020).
The investigators found that lower serum bicarbonate levels and elevated heart rates were indeed associated with increased risk of severe AKI. Serum bicarbonate level of less than 10 mEq/L was associated with a fivefold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio, 5.22; 95% confidence interval, 1.35-20.22). Each increase of 5 bpm in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39).
Dr. Hursh and his colleagues defined AKI using serum creatinine values. As baseline values prior to hospital admission were not available, the researchers used estimated normal value ranges from published studies, choosing a glomerular filtration rate of 120 mL/min per 1.73 m2 as a standard baseline value. Urine output was not used as a measure because of inconsistent records.
Of particular concern was that more than 40% of patients with AKI “did not have documented resolution of AKI prior to discharge or arrangements for follow-up in the nephrology clinic. Of note, the final AKI stage was severe for 50% of these children,” the researchers wrote in their analysis.
The findings suggest that clinicians “should consider AKI as a frequent complication that accompanies pediatric DKA and should be especially alert to its presence in severe presentations of DKA,” they said. AKI is underrecognized “both because of a lack of awareness of AKI as a complication of DKA and because the serum creatinine level in pediatric patients must be interpreted in the context of the child’s age and height. It is crucial to develop or have in place systems that identify and monitor abnormal markers of renal function in this population.”
The researchers acknowledged as limitations of their study its retrospective design, the absence of baseline serum creatinine values, and the lack of urine output data for use in AKI severity grading. And prospective longitudinal studies, they wrote, “are needed to assess the effect of these AKI episodes on the trajectory of renal disease in children with diabetes.”
The researchers reported no outside funding or relevant financial disclosures.
With the lack of targeted therapies to prevent AKI or decrease its associated consequences, supportive care is the mainstay of treatment and focuses on fluid and electrolyte management, nutrition, prevention of further injury through close attention to medication dosing, and, when needed, renal replacement therapy. At first glance, these findings may not appear to be overly surprising or significant; children with volume depletion have decreased renal blood flow, leading to AKI, which corrects with fluid administration. However, the authors appropriately suggest that this issue is not a simple one and that fluid management should be carefully considered in these patients. Because of severe hyperglycemia and derangements in serum sodium concentration, children with DKA are at risk of potentially catastrophic cerebral edema, leading to recommendations for cautious administration of fluids in this high-risk population.
These findings may lead clinicians and investigators to question established practices related to aggressive fluid administration in the sickest children. While awaiting more research to determine the sweet spot for fluid management in children with AKI, it seems reasonable to give fluids to patients with AKI secondary to volume depletion while quickly shifting to more restrictive strategies in those who do not respond to volume and have decreasing urine output. This may be especially important for children with DKA, as conservative fluid management may decrease central nervous system complications.
We commend the authors for exploring AKI in a novel pediatric population, expanding our knowledge on whom kidney function should be more diligently examined, providing insights on relevant fluid strategies, and increasing awareness for a group of patients who may benefit from closer long-term nephrology follow-up.
Benjamin L. Laskin, MD , is at the Children’s Hospital of Philadelphia, and Jens Goebel, MD , is at Children’s Hospital Colorado, Aurora. Dr. Laskin’s and Dr. Goebel’s comments are excerpted from an editorial accompanying the study by Hursh et al. (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0009). Dr Laskin is supported by a National Institutes of Health grant. The editorialists had no other relevant financial disclosures.
With the lack of targeted therapies to prevent AKI or decrease its associated consequences, supportive care is the mainstay of treatment and focuses on fluid and electrolyte management, nutrition, prevention of further injury through close attention to medication dosing, and, when needed, renal replacement therapy. At first glance, these findings may not appear to be overly surprising or significant; children with volume depletion have decreased renal blood flow, leading to AKI, which corrects with fluid administration. However, the authors appropriately suggest that this issue is not a simple one and that fluid management should be carefully considered in these patients. Because of severe hyperglycemia and derangements in serum sodium concentration, children with DKA are at risk of potentially catastrophic cerebral edema, leading to recommendations for cautious administration of fluids in this high-risk population.
These findings may lead clinicians and investigators to question established practices related to aggressive fluid administration in the sickest children. While awaiting more research to determine the sweet spot for fluid management in children with AKI, it seems reasonable to give fluids to patients with AKI secondary to volume depletion while quickly shifting to more restrictive strategies in those who do not respond to volume and have decreasing urine output. This may be especially important for children with DKA, as conservative fluid management may decrease central nervous system complications.
We commend the authors for exploring AKI in a novel pediatric population, expanding our knowledge on whom kidney function should be more diligently examined, providing insights on relevant fluid strategies, and increasing awareness for a group of patients who may benefit from closer long-term nephrology follow-up.
Benjamin L. Laskin, MD , is at the Children’s Hospital of Philadelphia, and Jens Goebel, MD , is at Children’s Hospital Colorado, Aurora. Dr. Laskin’s and Dr. Goebel’s comments are excerpted from an editorial accompanying the study by Hursh et al. (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0009). Dr Laskin is supported by a National Institutes of Health grant. The editorialists had no other relevant financial disclosures.
With the lack of targeted therapies to prevent AKI or decrease its associated consequences, supportive care is the mainstay of treatment and focuses on fluid and electrolyte management, nutrition, prevention of further injury through close attention to medication dosing, and, when needed, renal replacement therapy. At first glance, these findings may not appear to be overly surprising or significant; children with volume depletion have decreased renal blood flow, leading to AKI, which corrects with fluid administration. However, the authors appropriately suggest that this issue is not a simple one and that fluid management should be carefully considered in these patients. Because of severe hyperglycemia and derangements in serum sodium concentration, children with DKA are at risk of potentially catastrophic cerebral edema, leading to recommendations for cautious administration of fluids in this high-risk population.
These findings may lead clinicians and investigators to question established practices related to aggressive fluid administration in the sickest children. While awaiting more research to determine the sweet spot for fluid management in children with AKI, it seems reasonable to give fluids to patients with AKI secondary to volume depletion while quickly shifting to more restrictive strategies in those who do not respond to volume and have decreasing urine output. This may be especially important for children with DKA, as conservative fluid management may decrease central nervous system complications.
We commend the authors for exploring AKI in a novel pediatric population, expanding our knowledge on whom kidney function should be more diligently examined, providing insights on relevant fluid strategies, and increasing awareness for a group of patients who may benefit from closer long-term nephrology follow-up.
Benjamin L. Laskin, MD , is at the Children’s Hospital of Philadelphia, and Jens Goebel, MD , is at Children’s Hospital Colorado, Aurora. Dr. Laskin’s and Dr. Goebel’s comments are excerpted from an editorial accompanying the study by Hursh et al. (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0009). Dr Laskin is supported by a National Institutes of Health grant. The editorialists had no other relevant financial disclosures.
A high proportion of children with type 1 diabetes who are hospitalized for diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), according to results from a study.
Researchers reviewing records from a Canadian hospital found that in a cohort of 165 children hospitalized for DKA during a 5-year period (2008-2013), 64% developed the complication. Severe forms of AKI (stage 2 or 3) were common, representing 45% and 20%, respectively, of children with AKI. Two patients in the cohort required dialysis.
“We hypothesized that, because DKA is associated with both volume depletion and conservative fluid administration upon presentation, these children are potentially at high risk for AKI, above the level of risk expected by the rare reported cases in the literature,” Dr. Hursh and his colleagues wrote (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0020).
The investigators found that lower serum bicarbonate levels and elevated heart rates were indeed associated with increased risk of severe AKI. Serum bicarbonate level of less than 10 mEq/L was associated with a fivefold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio, 5.22; 95% confidence interval, 1.35-20.22). Each increase of 5 bpm in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39).
Dr. Hursh and his colleagues defined AKI using serum creatinine values. As baseline values prior to hospital admission were not available, the researchers used estimated normal value ranges from published studies, choosing a glomerular filtration rate of 120 mL/min per 1.73 m2 as a standard baseline value. Urine output was not used as a measure because of inconsistent records.
Of particular concern was that more than 40% of patients with AKI “did not have documented resolution of AKI prior to discharge or arrangements for follow-up in the nephrology clinic. Of note, the final AKI stage was severe for 50% of these children,” the researchers wrote in their analysis.
The findings suggest that clinicians “should consider AKI as a frequent complication that accompanies pediatric DKA and should be especially alert to its presence in severe presentations of DKA,” they said. AKI is underrecognized “both because of a lack of awareness of AKI as a complication of DKA and because the serum creatinine level in pediatric patients must be interpreted in the context of the child’s age and height. It is crucial to develop or have in place systems that identify and monitor abnormal markers of renal function in this population.”
The researchers acknowledged as limitations of their study its retrospective design, the absence of baseline serum creatinine values, and the lack of urine output data for use in AKI severity grading. And prospective longitudinal studies, they wrote, “are needed to assess the effect of these AKI episodes on the trajectory of renal disease in children with diabetes.”
The researchers reported no outside funding or relevant financial disclosures.
A high proportion of children with type 1 diabetes who are hospitalized for diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), according to results from a study.
Researchers reviewing records from a Canadian hospital found that in a cohort of 165 children hospitalized for DKA during a 5-year period (2008-2013), 64% developed the complication. Severe forms of AKI (stage 2 or 3) were common, representing 45% and 20%, respectively, of children with AKI. Two patients in the cohort required dialysis.
“We hypothesized that, because DKA is associated with both volume depletion and conservative fluid administration upon presentation, these children are potentially at high risk for AKI, above the level of risk expected by the rare reported cases in the literature,” Dr. Hursh and his colleagues wrote (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0020).
The investigators found that lower serum bicarbonate levels and elevated heart rates were indeed associated with increased risk of severe AKI. Serum bicarbonate level of less than 10 mEq/L was associated with a fivefold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio, 5.22; 95% confidence interval, 1.35-20.22). Each increase of 5 bpm in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39).
Dr. Hursh and his colleagues defined AKI using serum creatinine values. As baseline values prior to hospital admission were not available, the researchers used estimated normal value ranges from published studies, choosing a glomerular filtration rate of 120 mL/min per 1.73 m2 as a standard baseline value. Urine output was not used as a measure because of inconsistent records.
Of particular concern was that more than 40% of patients with AKI “did not have documented resolution of AKI prior to discharge or arrangements for follow-up in the nephrology clinic. Of note, the final AKI stage was severe for 50% of these children,” the researchers wrote in their analysis.
The findings suggest that clinicians “should consider AKI as a frequent complication that accompanies pediatric DKA and should be especially alert to its presence in severe presentations of DKA,” they said. AKI is underrecognized “both because of a lack of awareness of AKI as a complication of DKA and because the serum creatinine level in pediatric patients must be interpreted in the context of the child’s age and height. It is crucial to develop or have in place systems that identify and monitor abnormal markers of renal function in this population.”
The researchers acknowledged as limitations of their study its retrospective design, the absence of baseline serum creatinine values, and the lack of urine output data for use in AKI severity grading. And prospective longitudinal studies, they wrote, “are needed to assess the effect of these AKI episodes on the trajectory of renal disease in children with diabetes.”
The researchers reported no outside funding or relevant financial disclosures.
FROM JAMA PEDIATRICS
Key clinical point: Acute kidney injury may occur in up to two-thirds of children hospitalized for diabetic ketoacidosis.
Major finding: In a cohort of 165 children hospitalized with DKA, 64% developed AKI. Of these, 45% had stage 2 AKI and 20% had stage 3.
Data source: A retrospective single-site cohort study of records from 165 children with DKA hospitalized from 2008 to 2013.
Disclosures: The researchers disclosed no outside funding or relevant financial conflicts of interest.