Pediatrics

A nationwide cohort study found an association between a woman’s use of hormonal contraceptives and a small increased risk of nonlymphoid leukemia in her offspring.

copyright Thinkstock

Maternal use of hormonal contraception either during pregnancy or in the 3 months beforehand was associated with a 46% higher risk of any leukemia in the children (P = .011), compared with no use, Marie Hargreave, PhD, of the Danish Cancer Society Research Center and her coauthors reported in Lancet Oncology.

The study of 1,185,157 children born between 1996 and 2014 included data from the Danish Cancer Registry and Danish National Prescription Registry and followed children for a median of 9.3 years.

Use during pregnancy was associated with a 78% higher risk of any leukemia in the offspring (P = .070), and contraception use that stopped more than 3 months before pregnancy was associated with a 25% higher risk of any leukemia (P = .039).

The researchers estimated that maternal use of hormonal contraceptives up to and including during pregnancy would have resulted in about one additional case of leukemia per 47,170 children; in other words, 25 additional cases of leukemia in Denmark from contraceptive use from 1996 to 2014.

The increased risk appeared to be limited to nonlymphoid leukemia only. The risk with recent use was more than twofold higher (HR, 2.17), compared with nonuse, and use during pregnancy was associated with a nearly fourfold increase in the risk of leukemia (HR, 3.87).

“Sex hormones are considered to be potent carcinogens, and the causal association between in-utero exposure to the oestrogen analogue diethylstilbestrol and subsequent risk for adenocarcinoma of the vagina is firmly established,” Dr. Hargreave and her colleagues wrote. “The mechanism by which maternal use of hormones increases cancer risk in children is, however, still not clear.”

Recent use of combined oral contraceptive products was associated with a more than twofold increased risk of nonlymphoid leukemia in offspring, compared with no use. However progestin-only oral contraceptives and emergency contraception did not appear to increase in the risk of lymphoid or nonlymphoid leukemia.

The association was strongest in children aged 6-10 years, which the authors suggested was likely because the incidence of nonlymphoid leukemia increases after the age of 6 years.

While acknowledging that the small increase in leukemia risk was not a major safety concern for hormonal contraceptives, the authors commented that the results suggested the intrauterine hormonal environment could be a direction for research into the causes of leukemia.

The study was supported by the Danish Cancer Research Foundation and other foundations. One author reported grants from the sponsoring foundations and another author reported speaking fees from Jazz Pharmaceuticals and Shire Pharmaceuticals.

SOURCE: Hargreave M et al. Lancet Oncol. 2018 Sep 6. doi: 10.1016/S1470-2045(18)30479-0.
 

A nationwide cohort study found an association between a woman’s use of hormonal contraceptives and a small increased risk of nonlymphoid leukemia in her offspring.

copyright Thinkstock

Maternal use of hormonal contraception either during pregnancy or in the 3 months beforehand was associated with a 46% higher risk of any leukemia in the children (P = .011), compared with no use, Marie Hargreave, PhD, of the Danish Cancer Society Research Center and her coauthors reported in Lancet Oncology.

The study of 1,185,157 children born between 1996 and 2014 included data from the Danish Cancer Registry and Danish National Prescription Registry and followed children for a median of 9.3 years.

Use during pregnancy was associated with a 78% higher risk of any leukemia in the offspring (P = .070), and contraception use that stopped more than 3 months before pregnancy was associated with a 25% higher risk of any leukemia (P = .039).

The researchers estimated that maternal use of hormonal contraceptives up to and including during pregnancy would have resulted in about one additional case of leukemia per 47,170 children; in other words, 25 additional cases of leukemia in Denmark from contraceptive use from 1996 to 2014.

The increased risk appeared to be limited to nonlymphoid leukemia only. The risk with recent use was more than twofold higher (HR, 2.17), compared with nonuse, and use during pregnancy was associated with a nearly fourfold increase in the risk of leukemia (HR, 3.87).

“Sex hormones are considered to be potent carcinogens, and the causal association between in-utero exposure to the oestrogen analogue diethylstilbestrol and subsequent risk for adenocarcinoma of the vagina is firmly established,” Dr. Hargreave and her colleagues wrote. “The mechanism by which maternal use of hormones increases cancer risk in children is, however, still not clear.”

Recent use of combined oral contraceptive products was associated with a more than twofold increased risk of nonlymphoid leukemia in offspring, compared with no use. However progestin-only oral contraceptives and emergency contraception did not appear to increase in the risk of lymphoid or nonlymphoid leukemia.

The association was strongest in children aged 6-10 years, which the authors suggested was likely because the incidence of nonlymphoid leukemia increases after the age of 6 years.

While acknowledging that the small increase in leukemia risk was not a major safety concern for hormonal contraceptives, the authors commented that the results suggested the intrauterine hormonal environment could be a direction for research into the causes of leukemia.

The study was supported by the Danish Cancer Research Foundation and other foundations. One author reported grants from the sponsoring foundations and another author reported speaking fees from Jazz Pharmaceuticals and Shire Pharmaceuticals.

SOURCE: Hargreave M et al. Lancet Oncol. 2018 Sep 6. doi: 10.1016/S1470-2045(18)30479-0.
 

A nationwide cohort study found an association between a woman’s use of hormonal contraceptives and a small increased risk of nonlymphoid leukemia in her offspring.

copyright Thinkstock

Maternal use of hormonal contraception either during pregnancy or in the 3 months beforehand was associated with a 46% higher risk of any leukemia in the children (P = .011), compared with no use, Marie Hargreave, PhD, of the Danish Cancer Society Research Center and her coauthors reported in Lancet Oncology.

The study of 1,185,157 children born between 1996 and 2014 included data from the Danish Cancer Registry and Danish National Prescription Registry and followed children for a median of 9.3 years.

Use during pregnancy was associated with a 78% higher risk of any leukemia in the offspring (P = .070), and contraception use that stopped more than 3 months before pregnancy was associated with a 25% higher risk of any leukemia (P = .039).

The researchers estimated that maternal use of hormonal contraceptives up to and including during pregnancy would have resulted in about one additional case of leukemia per 47,170 children; in other words, 25 additional cases of leukemia in Denmark from contraceptive use from 1996 to 2014.

The increased risk appeared to be limited to nonlymphoid leukemia only. The risk with recent use was more than twofold higher (HR, 2.17), compared with nonuse, and use during pregnancy was associated with a nearly fourfold increase in the risk of leukemia (HR, 3.87).

“Sex hormones are considered to be potent carcinogens, and the causal association between in-utero exposure to the oestrogen analogue diethylstilbestrol and subsequent risk for adenocarcinoma of the vagina is firmly established,” Dr. Hargreave and her colleagues wrote. “The mechanism by which maternal use of hormones increases cancer risk in children is, however, still not clear.”

Recent use of combined oral contraceptive products was associated with a more than twofold increased risk of nonlymphoid leukemia in offspring, compared with no use. However progestin-only oral contraceptives and emergency contraception did not appear to increase in the risk of lymphoid or nonlymphoid leukemia.

The association was strongest in children aged 6-10 years, which the authors suggested was likely because the incidence of nonlymphoid leukemia increases after the age of 6 years.

While acknowledging that the small increase in leukemia risk was not a major safety concern for hormonal contraceptives, the authors commented that the results suggested the intrauterine hormonal environment could be a direction for research into the causes of leukemia.

The study was supported by the Danish Cancer Research Foundation and other foundations. One author reported grants from the sponsoring foundations and another author reported speaking fees from Jazz Pharmaceuticals and Shire Pharmaceuticals.

SOURCE: Hargreave M et al. Lancet Oncol. 2018 Sep 6. doi: 10.1016/S1470-2045(18)30479-0.
 

Hispanic pediatric patients undergoing treatment for acute lymphoblastic leukemia (ALL) had a risk of methotrexate toxicity that was more than twice that of non-Hispanic whites, according to results of a prospective multicenter study.

Methotrexate toxicity often led to treatment modification or delays, which may have increased relapse risk in the Hispanic patients, according to investigator Michael E. Scheurer, PhD, MPH, of Baylor College of Medicine, Houston, and his colleagues.

“We had observed that our Hispanic patients tended to experience neurotoxicity more often than other groups, but we were surprised to see the magnitude of the difference,” Dr. Scheurer said in statement.

The study, described in Clinical Cancer Research, involved 280 patients with newly diagnosed ALL enrolled at one of three major U.S. pediatric cancer treatment centers. Nearly half of the patients (48.2%) were Hispanic, and approximately 86% had a diagnosis of pre B-cell leukemia.

The patients, who had a mean age of 8.4 years at diagnosis, were treated with modern ALL protocols and were followed from diagnosis to the start of maintenance/continuation therapy.

Methotrexate toxicity was seen in 39 patients at the time of the analysis. Of those patients, 29 (74.4%) were Hispanic, Dr. Scheurer and his coauthors reported.

Compared with non-Hispanic whites, Hispanics had a high risk of methotrexate neurotoxicity, even after the researchers accounted for age, sex, ALL risk stratification, and other factors (adjusted hazard ratio, 2.43; 95% confidence interval, 1.06-5.58).

Among nine patients who experienced a second neurotoxic event, all were Hispanic.

Patients who had neurotoxicity received an average of 2.25 fewer doses of intrathecal methotrexate, and slightly lower intravenous methotrexate doses. About three-quarters of the patients experiencing methotrexate toxicity received leucovorin after intrathecal methotrexate, according to the investigators, who noted that leucovorin may interact with methotrexate and reduce efficacy.

“These findings may help us better understand what factors contribute to poorer survival among Hispanic patients with ALL,” wrote Dr. Scheurer and his coauthors.

Relapse occurred in 15.4% of patients with neurotoxicity (6 of 39 patients), and in 2.1% of patients with no neurotoxicity (13 of 241 patients).

Taken together, the findings add to the growing body of evidence that Hispanics and other minority pediatric patients with ALL experience “significant disparities” in treatment outcomes, according to the investigators.

That body of evidence includes several recent cases series that suggest Hispanic patients with ALL have a high prevalence of methotrexate neurotoxicity.

It remains unclear why Hispanic patients would have a higher risk of methotrexate toxicity, and that must be explored in future studies, the investigators said.

The research team is currently investigating biomarkers that may help identify patients at risk of methotrexate toxicity up front. “If we can identify these at-risk patients, we can potentially employ strategies to either fully prevent or mitigate these toxicities,” Dr. Scheurer said in a statement.

The research was supported by the National Institutes of Health and Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, a St. Baldrick’s Foundation Consortium Research Grant. The researchers reported having no potential conflicts of interest.

SOURCE: Taylor OA et al. Clin Cancer Res. 2018 Sep 11. doi: 10.1158/1078-0432.CCR-18-0939.

Hispanic pediatric patients undergoing treatment for acute lymphoblastic leukemia (ALL) had a risk of methotrexate toxicity that was more than twice that of non-Hispanic whites, according to results of a prospective multicenter study.

Methotrexate toxicity often led to treatment modification or delays, which may have increased relapse risk in the Hispanic patients, according to investigator Michael E. Scheurer, PhD, MPH, of Baylor College of Medicine, Houston, and his colleagues.

“We had observed that our Hispanic patients tended to experience neurotoxicity more often than other groups, but we were surprised to see the magnitude of the difference,” Dr. Scheurer said in statement.

The study, described in Clinical Cancer Research, involved 280 patients with newly diagnosed ALL enrolled at one of three major U.S. pediatric cancer treatment centers. Nearly half of the patients (48.2%) were Hispanic, and approximately 86% had a diagnosis of pre B-cell leukemia.

The patients, who had a mean age of 8.4 years at diagnosis, were treated with modern ALL protocols and were followed from diagnosis to the start of maintenance/continuation therapy.

Methotrexate toxicity was seen in 39 patients at the time of the analysis. Of those patients, 29 (74.4%) were Hispanic, Dr. Scheurer and his coauthors reported.

Compared with non-Hispanic whites, Hispanics had a high risk of methotrexate neurotoxicity, even after the researchers accounted for age, sex, ALL risk stratification, and other factors (adjusted hazard ratio, 2.43; 95% confidence interval, 1.06-5.58).

Among nine patients who experienced a second neurotoxic event, all were Hispanic.

Patients who had neurotoxicity received an average of 2.25 fewer doses of intrathecal methotrexate, and slightly lower intravenous methotrexate doses. About three-quarters of the patients experiencing methotrexate toxicity received leucovorin after intrathecal methotrexate, according to the investigators, who noted that leucovorin may interact with methotrexate and reduce efficacy.

“These findings may help us better understand what factors contribute to poorer survival among Hispanic patients with ALL,” wrote Dr. Scheurer and his coauthors.

Relapse occurred in 15.4% of patients with neurotoxicity (6 of 39 patients), and in 2.1% of patients with no neurotoxicity (13 of 241 patients).

Taken together, the findings add to the growing body of evidence that Hispanics and other minority pediatric patients with ALL experience “significant disparities” in treatment outcomes, according to the investigators.

That body of evidence includes several recent cases series that suggest Hispanic patients with ALL have a high prevalence of methotrexate neurotoxicity.

It remains unclear why Hispanic patients would have a higher risk of methotrexate toxicity, and that must be explored in future studies, the investigators said.

The research team is currently investigating biomarkers that may help identify patients at risk of methotrexate toxicity up front. “If we can identify these at-risk patients, we can potentially employ strategies to either fully prevent or mitigate these toxicities,” Dr. Scheurer said in a statement.

The research was supported by the National Institutes of Health and Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, a St. Baldrick’s Foundation Consortium Research Grant. The researchers reported having no potential conflicts of interest.

SOURCE: Taylor OA et al. Clin Cancer Res. 2018 Sep 11. doi: 10.1158/1078-0432.CCR-18-0939.

Hispanic pediatric patients undergoing treatment for acute lymphoblastic leukemia (ALL) had a risk of methotrexate toxicity that was more than twice that of non-Hispanic whites, according to results of a prospective multicenter study.

Methotrexate toxicity often led to treatment modification or delays, which may have increased relapse risk in the Hispanic patients, according to investigator Michael E. Scheurer, PhD, MPH, of Baylor College of Medicine, Houston, and his colleagues.

“We had observed that our Hispanic patients tended to experience neurotoxicity more often than other groups, but we were surprised to see the magnitude of the difference,” Dr. Scheurer said in statement.

The study, described in Clinical Cancer Research, involved 280 patients with newly diagnosed ALL enrolled at one of three major U.S. pediatric cancer treatment centers. Nearly half of the patients (48.2%) were Hispanic, and approximately 86% had a diagnosis of pre B-cell leukemia.

The patients, who had a mean age of 8.4 years at diagnosis, were treated with modern ALL protocols and were followed from diagnosis to the start of maintenance/continuation therapy.

Methotrexate toxicity was seen in 39 patients at the time of the analysis. Of those patients, 29 (74.4%) were Hispanic, Dr. Scheurer and his coauthors reported.

Compared with non-Hispanic whites, Hispanics had a high risk of methotrexate neurotoxicity, even after the researchers accounted for age, sex, ALL risk stratification, and other factors (adjusted hazard ratio, 2.43; 95% confidence interval, 1.06-5.58).

Among nine patients who experienced a second neurotoxic event, all were Hispanic.

Patients who had neurotoxicity received an average of 2.25 fewer doses of intrathecal methotrexate, and slightly lower intravenous methotrexate doses. About three-quarters of the patients experiencing methotrexate toxicity received leucovorin after intrathecal methotrexate, according to the investigators, who noted that leucovorin may interact with methotrexate and reduce efficacy.

“These findings may help us better understand what factors contribute to poorer survival among Hispanic patients with ALL,” wrote Dr. Scheurer and his coauthors.

Relapse occurred in 15.4% of patients with neurotoxicity (6 of 39 patients), and in 2.1% of patients with no neurotoxicity (13 of 241 patients).

Taken together, the findings add to the growing body of evidence that Hispanics and other minority pediatric patients with ALL experience “significant disparities” in treatment outcomes, according to the investigators.

That body of evidence includes several recent cases series that suggest Hispanic patients with ALL have a high prevalence of methotrexate neurotoxicity.

It remains unclear why Hispanic patients would have a higher risk of methotrexate toxicity, and that must be explored in future studies, the investigators said.

The research team is currently investigating biomarkers that may help identify patients at risk of methotrexate toxicity up front. “If we can identify these at-risk patients, we can potentially employ strategies to either fully prevent or mitigate these toxicities,” Dr. Scheurer said in a statement.

The research was supported by the National Institutes of Health and Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, a St. Baldrick’s Foundation Consortium Research Grant. The researchers reported having no potential conflicts of interest.

SOURCE: Taylor OA et al. Clin Cancer Res. 2018 Sep 11. doi: 10.1158/1078-0432.CCR-18-0939.

Just over half of female to male transgender adolescents have reported attempting suicide, according to a study published in Pediatrics.

Russell B. Toomey, PhD, of the University of Arizona, Tucson, and his associates performed an analysis of data from the Profiles of Student Life: Attitudes and Behaviors survey. Data was collected from June 2012 to May 2015 and included 120,617 adolescents aged 11-19 years. A total of 202 adolescents identified as male to female transgender, 175 identified as female to male transgender, 344 identified as nonbinary transgender, 1,052 identified as questioning, 60,973 identified as female, and 57,871 identified as male.

Male adolescents were least likely to attempt suicide, with 10% reporting at least one attempt, followed by those identifying as female (18%), questioning (28%), male to female transgender (30%), nonbinary transgender (42%), and female to male transgender (51%). All groups were significantly more likely to attempt suicide, compared with male adolescents.

Compared with transgender adolescents who identified as heterosexual only, identifying as non-heterosexual was associated with an increased risk of attempting suicide, except in nonbinary transgender adolescents. There was no association of increased risk of attempting suicide in transgender adolescents based on ethnicity, parental education levels, age, or urbanicity, except parent education level appeared to be a protective factor for questioning adolescents.

“These results should be used to inform suicide prevention and intervention policy and programs that are aimed at reducing ongoing gender identity–related disparities in suicide behavior as well as ongoing research in which authors seek to better understand for whom and why suicide behavior risk exists,” the authors concluded.

The study was supported by the American Foundation for Suicide Prevention and the National Institute of Minority Health and Health Disparities. The authors had no relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Toomey RB et al. Pediatrics. 2018 Sept 11. doi: 10.1542/peds.2017-4218.

Just over half of female to male transgender adolescents have reported attempting suicide, according to a study published in Pediatrics.

Russell B. Toomey, PhD, of the University of Arizona, Tucson, and his associates performed an analysis of data from the Profiles of Student Life: Attitudes and Behaviors survey. Data was collected from June 2012 to May 2015 and included 120,617 adolescents aged 11-19 years. A total of 202 adolescents identified as male to female transgender, 175 identified as female to male transgender, 344 identified as nonbinary transgender, 1,052 identified as questioning, 60,973 identified as female, and 57,871 identified as male.

Male adolescents were least likely to attempt suicide, with 10% reporting at least one attempt, followed by those identifying as female (18%), questioning (28%), male to female transgender (30%), nonbinary transgender (42%), and female to male transgender (51%). All groups were significantly more likely to attempt suicide, compared with male adolescents.

Compared with transgender adolescents who identified as heterosexual only, identifying as non-heterosexual was associated with an increased risk of attempting suicide, except in nonbinary transgender adolescents. There was no association of increased risk of attempting suicide in transgender adolescents based on ethnicity, parental education levels, age, or urbanicity, except parent education level appeared to be a protective factor for questioning adolescents.

“These results should be used to inform suicide prevention and intervention policy and programs that are aimed at reducing ongoing gender identity–related disparities in suicide behavior as well as ongoing research in which authors seek to better understand for whom and why suicide behavior risk exists,” the authors concluded.

The study was supported by the American Foundation for Suicide Prevention and the National Institute of Minority Health and Health Disparities. The authors had no relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Toomey RB et al. Pediatrics. 2018 Sept 11. doi: 10.1542/peds.2017-4218.

Just over half of female to male transgender adolescents have reported attempting suicide, according to a study published in Pediatrics.

Russell B. Toomey, PhD, of the University of Arizona, Tucson, and his associates performed an analysis of data from the Profiles of Student Life: Attitudes and Behaviors survey. Data was collected from June 2012 to May 2015 and included 120,617 adolescents aged 11-19 years. A total of 202 adolescents identified as male to female transgender, 175 identified as female to male transgender, 344 identified as nonbinary transgender, 1,052 identified as questioning, 60,973 identified as female, and 57,871 identified as male.

Male adolescents were least likely to attempt suicide, with 10% reporting at least one attempt, followed by those identifying as female (18%), questioning (28%), male to female transgender (30%), nonbinary transgender (42%), and female to male transgender (51%). All groups were significantly more likely to attempt suicide, compared with male adolescents.

Compared with transgender adolescents who identified as heterosexual only, identifying as non-heterosexual was associated with an increased risk of attempting suicide, except in nonbinary transgender adolescents. There was no association of increased risk of attempting suicide in transgender adolescents based on ethnicity, parental education levels, age, or urbanicity, except parent education level appeared to be a protective factor for questioning adolescents.

“These results should be used to inform suicide prevention and intervention policy and programs that are aimed at reducing ongoing gender identity–related disparities in suicide behavior as well as ongoing research in which authors seek to better understand for whom and why suicide behavior risk exists,” the authors concluded.

The study was supported by the American Foundation for Suicide Prevention and the National Institute of Minority Health and Health Disparities. The authors had no relevant financial disclosures.

lfranki@mdedge.com

SOURCE: Toomey RB et al. Pediatrics. 2018 Sept 11. doi: 10.1542/peds.2017-4218.

The prevalence of pediatric asthma is lowest in Oregon and highest in Alabama, according to estimates from the American Lung Association.

Oregon’s rate comes in at 557 per 10,000 population under the age of 18 years, just ahead of Montana at 574 per 10,000 and Iowa at 577. The prevalence of pediatric asthma in Alabama is 1,315 per 10,000, with North Carolina (1,149), Connecticut (1,107), Hawaii (1,026), and New York (1,005) joining it as members of the over-1,000 club. (MDedge News used the ALA’s estimates for persons under age 18 years with asthma in each state and Census Bureau estimates for population to calculate an unadjusted rate for each state.)

The ALA analysis was based on data from the Behavioral Risk Factor Behavioral System surveys for 2016 (31 states), 2015 (District of Columbia, Louisiana, New Hampshire, Texas), 2014 (Alabama, Maryland, North Carolina, Tennessee, West Virginia), 2012 (North Dakota and Wyoming), and 2011 (Iowa). National data were used for eight states (Alaska, Arkansas, Colorado, Delaware, Idaho, South Carolina, South Dakota, Virginia) that had no data available.

rfranki@mdedge.com

The prevalence of pediatric asthma is lowest in Oregon and highest in Alabama, according to estimates from the American Lung Association.

Oregon’s rate comes in at 557 per 10,000 population under the age of 18 years, just ahead of Montana at 574 per 10,000 and Iowa at 577. The prevalence of pediatric asthma in Alabama is 1,315 per 10,000, with North Carolina (1,149), Connecticut (1,107), Hawaii (1,026), and New York (1,005) joining it as members of the over-1,000 club. (MDedge News used the ALA’s estimates for persons under age 18 years with asthma in each state and Census Bureau estimates for population to calculate an unadjusted rate for each state.)

The ALA analysis was based on data from the Behavioral Risk Factor Behavioral System surveys for 2016 (31 states), 2015 (District of Columbia, Louisiana, New Hampshire, Texas), 2014 (Alabama, Maryland, North Carolina, Tennessee, West Virginia), 2012 (North Dakota and Wyoming), and 2011 (Iowa). National data were used for eight states (Alaska, Arkansas, Colorado, Delaware, Idaho, South Carolina, South Dakota, Virginia) that had no data available.

rfranki@mdedge.com

The prevalence of pediatric asthma is lowest in Oregon and highest in Alabama, according to estimates from the American Lung Association.

Oregon’s rate comes in at 557 per 10,000 population under the age of 18 years, just ahead of Montana at 574 per 10,000 and Iowa at 577. The prevalence of pediatric asthma in Alabama is 1,315 per 10,000, with North Carolina (1,149), Connecticut (1,107), Hawaii (1,026), and New York (1,005) joining it as members of the over-1,000 club. (MDedge News used the ALA’s estimates for persons under age 18 years with asthma in each state and Census Bureau estimates for population to calculate an unadjusted rate for each state.)

The ALA analysis was based on data from the Behavioral Risk Factor Behavioral System surveys for 2016 (31 states), 2015 (District of Columbia, Louisiana, New Hampshire, Texas), 2014 (Alabama, Maryland, North Carolina, Tennessee, West Virginia), 2012 (North Dakota and Wyoming), and 2011 (Iowa). National data were used for eight states (Alaska, Arkansas, Colorado, Delaware, Idaho, South Carolina, South Dakota, Virginia) that had no data available.

rfranki@mdedge.com

Nearly all newborns who received an acellular pertussis-only vaccine at birth showed titers for pertussis and no difference in adverse events, compared with a group receiving only the hepatitis B vaccine, a randomized clinical trial from Australia has found.

copyright Jacopo Werther/Wikimedia Commons/Creative Commons Attribution 2.0

“These results indicate that a birth dose of aP vaccine is immunogenic in newborns and significantly narrows the immunity gap between birth and 14 days after receipt of DTaP at 6 or 8 weeks of age, marking the critical period when infants are most vulnerable to severe pertussis infection,” reported Nicholas Wood, PhD, of the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases in New South Wales, Australia, and his colleagues.

“Administration of the acellular pertussis vaccine at birth has the potential to reduce severe morbidity from Bordetella pertussis infection in the first 3 months of life, especially for infants of mothers who have not received a pertussis vaccine during pregnancy,” the researchers concluded in JAMA Pediatrics.

The researchers enrolled 417 infants from Sydney, Melbourne, Adelaide, and Perth between June 2010 and March 2013 and randomized them to receive either the hepatitis B vaccine alone (n = 205) or the hepatitis B vaccine with a monovalent acellular pertussis vaccine (n = 212) within the first 5 days after birth. The randomization was stratified for mothers’ receipt of the Tdap before pregnancy.

The Centers for Disease Control and Prevention currently recommends all newborns receive the hepatitis B vaccine shortly after birth and that pregnant women receive the Tdap vaccine during each pregnancy. There is not currently a monovalent acellular pertussis vaccine licensed in the United States.

The study infants then received the hexavalent DTaP-Hib-hep B-polio vaccine and the 10-valent pneumococcal conjugate vaccine at 6 weeks, 4 months, and 6 months.

The primary outcome was detectable levels of IgG antibody to pertussis toxin and pertactin at 10 weeks old.

Of the 206 infants receiving the pertussis vaccine at birth, 93% had detectable antibodies to pertussis toxin and pertactin at 10 weeks, compared with 51% of the 193 infants who received only the hepatitis B shot (P less than .001). Geometric mean concentration for pertussis toxin IgG also was four times higher in infants who received the pertussis vaccine at birth.

Adverse events were similar in the two groups both at birth and at 32 weeks, demonstrating that the pertussis birth dose is safe and tolerable.

“More important, in this study, the prevalence of fever after receipt of the birth dose, which can mistakenly be associated with potential sepsis and result in additional investigations in the neonatal period, was similar in both the group that received the aP vaccine at birth and the control group,” the authors reported.

A remaining question is the potential impact of maternal antibodies on protection from pertussis.

“The presence of maternal pertussis antibodies at birth can negatively affect postprimary responses to pertussis, diphtheria, and diphtheria-related CRM197 conjugate vaccines with a variety of infant immunization schedules and vaccines,” the authors noted. “The clinical significance of reductions in pertussis antibody related to maternal interference will require ongoing clinical evaluation, because there are no accepted serologic correlates of protection.”

The research was funded by a Australian National Health and Medical Research Council (NHMRC) grant, and several authors received NHMRC grants. One author also was supported by a Murdoch Children’s Research Institute Career Development Award. GlaxoSmithKline provided the vaccine and conducted the serologic assays. The authors reported having no conflicts of interest.

SOURCE: Wood N et al, JAMA Pediatr. 2018 Sep 10. doi: 10.1001/jamapediatrics.2018.2349.

Nearly all newborns who received an acellular pertussis-only vaccine at birth showed titers for pertussis and no difference in adverse events, compared with a group receiving only the hepatitis B vaccine, a randomized clinical trial from Australia has found.

copyright Jacopo Werther/Wikimedia Commons/Creative Commons Attribution 2.0

“These results indicate that a birth dose of aP vaccine is immunogenic in newborns and significantly narrows the immunity gap between birth and 14 days after receipt of DTaP at 6 or 8 weeks of age, marking the critical period when infants are most vulnerable to severe pertussis infection,” reported Nicholas Wood, PhD, of the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases in New South Wales, Australia, and his colleagues.

“Administration of the acellular pertussis vaccine at birth has the potential to reduce severe morbidity from Bordetella pertussis infection in the first 3 months of life, especially for infants of mothers who have not received a pertussis vaccine during pregnancy,” the researchers concluded in JAMA Pediatrics.

The researchers enrolled 417 infants from Sydney, Melbourne, Adelaide, and Perth between June 2010 and March 2013 and randomized them to receive either the hepatitis B vaccine alone (n = 205) or the hepatitis B vaccine with a monovalent acellular pertussis vaccine (n = 212) within the first 5 days after birth. The randomization was stratified for mothers’ receipt of the Tdap before pregnancy.

The Centers for Disease Control and Prevention currently recommends all newborns receive the hepatitis B vaccine shortly after birth and that pregnant women receive the Tdap vaccine during each pregnancy. There is not currently a monovalent acellular pertussis vaccine licensed in the United States.

The study infants then received the hexavalent DTaP-Hib-hep B-polio vaccine and the 10-valent pneumococcal conjugate vaccine at 6 weeks, 4 months, and 6 months.

The primary outcome was detectable levels of IgG antibody to pertussis toxin and pertactin at 10 weeks old.

Of the 206 infants receiving the pertussis vaccine at birth, 93% had detectable antibodies to pertussis toxin and pertactin at 10 weeks, compared with 51% of the 193 infants who received only the hepatitis B shot (P less than .001). Geometric mean concentration for pertussis toxin IgG also was four times higher in infants who received the pertussis vaccine at birth.

Adverse events were similar in the two groups both at birth and at 32 weeks, demonstrating that the pertussis birth dose is safe and tolerable.

“More important, in this study, the prevalence of fever after receipt of the birth dose, which can mistakenly be associated with potential sepsis and result in additional investigations in the neonatal period, was similar in both the group that received the aP vaccine at birth and the control group,” the authors reported.

A remaining question is the potential impact of maternal antibodies on protection from pertussis.

“The presence of maternal pertussis antibodies at birth can negatively affect postprimary responses to pertussis, diphtheria, and diphtheria-related CRM197 conjugate vaccines with a variety of infant immunization schedules and vaccines,” the authors noted. “The clinical significance of reductions in pertussis antibody related to maternal interference will require ongoing clinical evaluation, because there are no accepted serologic correlates of protection.”

The research was funded by a Australian National Health and Medical Research Council (NHMRC) grant, and several authors received NHMRC grants. One author also was supported by a Murdoch Children’s Research Institute Career Development Award. GlaxoSmithKline provided the vaccine and conducted the serologic assays. The authors reported having no conflicts of interest.

SOURCE: Wood N et al, JAMA Pediatr. 2018 Sep 10. doi: 10.1001/jamapediatrics.2018.2349.

Nearly all newborns who received an acellular pertussis-only vaccine at birth showed titers for pertussis and no difference in adverse events, compared with a group receiving only the hepatitis B vaccine, a randomized clinical trial from Australia has found.

copyright Jacopo Werther/Wikimedia Commons/Creative Commons Attribution 2.0

“These results indicate that a birth dose of aP vaccine is immunogenic in newborns and significantly narrows the immunity gap between birth and 14 days after receipt of DTaP at 6 or 8 weeks of age, marking the critical period when infants are most vulnerable to severe pertussis infection,” reported Nicholas Wood, PhD, of the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases in New South Wales, Australia, and his colleagues.

“Administration of the acellular pertussis vaccine at birth has the potential to reduce severe morbidity from Bordetella pertussis infection in the first 3 months of life, especially for infants of mothers who have not received a pertussis vaccine during pregnancy,” the researchers concluded in JAMA Pediatrics.

The researchers enrolled 417 infants from Sydney, Melbourne, Adelaide, and Perth between June 2010 and March 2013 and randomized them to receive either the hepatitis B vaccine alone (n = 205) or the hepatitis B vaccine with a monovalent acellular pertussis vaccine (n = 212) within the first 5 days after birth. The randomization was stratified for mothers’ receipt of the Tdap before pregnancy.

The Centers for Disease Control and Prevention currently recommends all newborns receive the hepatitis B vaccine shortly after birth and that pregnant women receive the Tdap vaccine during each pregnancy. There is not currently a monovalent acellular pertussis vaccine licensed in the United States.

The study infants then received the hexavalent DTaP-Hib-hep B-polio vaccine and the 10-valent pneumococcal conjugate vaccine at 6 weeks, 4 months, and 6 months.

The primary outcome was detectable levels of IgG antibody to pertussis toxin and pertactin at 10 weeks old.

Of the 206 infants receiving the pertussis vaccine at birth, 93% had detectable antibodies to pertussis toxin and pertactin at 10 weeks, compared with 51% of the 193 infants who received only the hepatitis B shot (P less than .001). Geometric mean concentration for pertussis toxin IgG also was four times higher in infants who received the pertussis vaccine at birth.

Adverse events were similar in the two groups both at birth and at 32 weeks, demonstrating that the pertussis birth dose is safe and tolerable.

“More important, in this study, the prevalence of fever after receipt of the birth dose, which can mistakenly be associated with potential sepsis and result in additional investigations in the neonatal period, was similar in both the group that received the aP vaccine at birth and the control group,” the authors reported.

A remaining question is the potential impact of maternal antibodies on protection from pertussis.

“The presence of maternal pertussis antibodies at birth can negatively affect postprimary responses to pertussis, diphtheria, and diphtheria-related CRM197 conjugate vaccines with a variety of infant immunization schedules and vaccines,” the authors noted. “The clinical significance of reductions in pertussis antibody related to maternal interference will require ongoing clinical evaluation, because there are no accepted serologic correlates of protection.”

The research was funded by a Australian National Health and Medical Research Council (NHMRC) grant, and several authors received NHMRC grants. One author also was supported by a Murdoch Children’s Research Institute Career Development Award. GlaxoSmithKline provided the vaccine and conducted the serologic assays. The authors reported having no conflicts of interest.

SOURCE: Wood N et al, JAMA Pediatr. 2018 Sep 10. doi: 10.1001/jamapediatrics.2018.2349.

Youths with opioid use disorder (OUD) are more likely to remain in care if they receive medications to treat the condition, but very few are receiving them, results of a retrospective cohort study suggest.

Hailshadow/iStock/Getty Images

Prescribing buprenorphine, naltrexone, or methadone soon after an OUD diagnosis in this study was associated with increased retention in care for adolescents and young adults.

However, medications were provided to just 1 in 4 youths overall in the study, and only 1 in 21 adolescents, according to Scott E. Hadland, MD, MPH, MS, of Grayken Center for Addiction and Department of Pediatrics, Boston Medical Center, and coinvestigators.

These findings highlight a crucial need to improve care of youths with opioid use disorder (OUD) and enhance retention in treatment, Dr. Hadland and coauthors said in JAMA Pediatrics.

“As deaths from overdose increase among U.S. youths, it is vital that clinicians, researchers, and policy makers ensure that access to evidence-based OUD medications for young people remains a national priority,” they said. Their study, based on Medicaid enrollment and claims data from 11 states, included 4,837 youths aged 13-22 years with a diagnosis of OUD. The median age at diagnosis was 20 years, and 2,752 of the youths were female.

Timely buprenorphine, naltrexone, or methadone were received by just 34 out of 728 adolescents (4.7%) and 1,105 out of 4,109 young adults (27%). Most received buprenorphine (82%), while 12% got naltrexone and 6% got methadone. Treatment was considered timely if received within 3 months, and most patients received this treatment within 1 month.

Youths who received timely OUD medications were more likely to be retained in addiction treatment, the investigators found. Median retention in care was 67 days for youths who received behavioral health services only, compared with 123 days for those who received buprenorphine, 150 days for naltrexone, and 324 days for methadone.

Youths receiving buprenorphine were 42% less likely to discontinue addiction treatment, compared with those receiving behavioral services only, while those receiving naltrexone were 46% less likely to discontinue, and those receiving methadone were 68% less likely to discontinue.

Similarly, median duration of behavioral health services was longer for youths who received OUD medications versus those who did not, they added.

Retention in care is critical to successful addiction treatment, according to Dr. Hadland and coauthors.“Even when patients do not reduce their substance use, individuals engaged and retained in care can receive harm-reduction services and treatment of comorbid medical and psychiatric conditions.”

The benefit of that approach is affirmed by results of a recent meta-analysis in adults showing that staying in treatment was associated with reduced all-cause mortality and mortality from overdose, they said.

Dr. Hadland and coauthors reported no conflicts of interest related to the study. Researchers were supported by grants from the National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA), a grant from the NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Thrasher Research Fund Early Career Award, and the Academic Pediatric Association Young Investigator Award.
 

SOURCE: Hadland SE, et al. JAMA Pediatr. 2018 Sep 10. doi:10.1001/jamapediatrics.2018.2143.

Youths with opioid use disorder (OUD) are more likely to remain in care if they receive medications to treat the condition, but very few are receiving them, results of a retrospective cohort study suggest.

Hailshadow/iStock/Getty Images

Prescribing buprenorphine, naltrexone, or methadone soon after an OUD diagnosis in this study was associated with increased retention in care for adolescents and young adults.

However, medications were provided to just 1 in 4 youths overall in the study, and only 1 in 21 adolescents, according to Scott E. Hadland, MD, MPH, MS, of Grayken Center for Addiction and Department of Pediatrics, Boston Medical Center, and coinvestigators.

These findings highlight a crucial need to improve care of youths with opioid use disorder (OUD) and enhance retention in treatment, Dr. Hadland and coauthors said in JAMA Pediatrics.

“As deaths from overdose increase among U.S. youths, it is vital that clinicians, researchers, and policy makers ensure that access to evidence-based OUD medications for young people remains a national priority,” they said. Their study, based on Medicaid enrollment and claims data from 11 states, included 4,837 youths aged 13-22 years with a diagnosis of OUD. The median age at diagnosis was 20 years, and 2,752 of the youths were female.

Timely buprenorphine, naltrexone, or methadone were received by just 34 out of 728 adolescents (4.7%) and 1,105 out of 4,109 young adults (27%). Most received buprenorphine (82%), while 12% got naltrexone and 6% got methadone. Treatment was considered timely if received within 3 months, and most patients received this treatment within 1 month.

Youths who received timely OUD medications were more likely to be retained in addiction treatment, the investigators found. Median retention in care was 67 days for youths who received behavioral health services only, compared with 123 days for those who received buprenorphine, 150 days for naltrexone, and 324 days for methadone.

Youths receiving buprenorphine were 42% less likely to discontinue addiction treatment, compared with those receiving behavioral services only, while those receiving naltrexone were 46% less likely to discontinue, and those receiving methadone were 68% less likely to discontinue.

Similarly, median duration of behavioral health services was longer for youths who received OUD medications versus those who did not, they added.

Retention in care is critical to successful addiction treatment, according to Dr. Hadland and coauthors.“Even when patients do not reduce their substance use, individuals engaged and retained in care can receive harm-reduction services and treatment of comorbid medical and psychiatric conditions.”

The benefit of that approach is affirmed by results of a recent meta-analysis in adults showing that staying in treatment was associated with reduced all-cause mortality and mortality from overdose, they said.

Dr. Hadland and coauthors reported no conflicts of interest related to the study. Researchers were supported by grants from the National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA), a grant from the NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Thrasher Research Fund Early Career Award, and the Academic Pediatric Association Young Investigator Award.
 

SOURCE: Hadland SE, et al. JAMA Pediatr. 2018 Sep 10. doi:10.1001/jamapediatrics.2018.2143.

Youths with opioid use disorder (OUD) are more likely to remain in care if they receive medications to treat the condition, but very few are receiving them, results of a retrospective cohort study suggest.

Hailshadow/iStock/Getty Images

Prescribing buprenorphine, naltrexone, or methadone soon after an OUD diagnosis in this study was associated with increased retention in care for adolescents and young adults.

However, medications were provided to just 1 in 4 youths overall in the study, and only 1 in 21 adolescents, according to Scott E. Hadland, MD, MPH, MS, of Grayken Center for Addiction and Department of Pediatrics, Boston Medical Center, and coinvestigators.

These findings highlight a crucial need to improve care of youths with opioid use disorder (OUD) and enhance retention in treatment, Dr. Hadland and coauthors said in JAMA Pediatrics.

“As deaths from overdose increase among U.S. youths, it is vital that clinicians, researchers, and policy makers ensure that access to evidence-based OUD medications for young people remains a national priority,” they said. Their study, based on Medicaid enrollment and claims data from 11 states, included 4,837 youths aged 13-22 years with a diagnosis of OUD. The median age at diagnosis was 20 years, and 2,752 of the youths were female.

Timely buprenorphine, naltrexone, or methadone were received by just 34 out of 728 adolescents (4.7%) and 1,105 out of 4,109 young adults (27%). Most received buprenorphine (82%), while 12% got naltrexone and 6% got methadone. Treatment was considered timely if received within 3 months, and most patients received this treatment within 1 month.

Youths who received timely OUD medications were more likely to be retained in addiction treatment, the investigators found. Median retention in care was 67 days for youths who received behavioral health services only, compared with 123 days for those who received buprenorphine, 150 days for naltrexone, and 324 days for methadone.

Youths receiving buprenorphine were 42% less likely to discontinue addiction treatment, compared with those receiving behavioral services only, while those receiving naltrexone were 46% less likely to discontinue, and those receiving methadone were 68% less likely to discontinue.

Similarly, median duration of behavioral health services was longer for youths who received OUD medications versus those who did not, they added.

Retention in care is critical to successful addiction treatment, according to Dr. Hadland and coauthors.“Even when patients do not reduce their substance use, individuals engaged and retained in care can receive harm-reduction services and treatment of comorbid medical and psychiatric conditions.”

The benefit of that approach is affirmed by results of a recent meta-analysis in adults showing that staying in treatment was associated with reduced all-cause mortality and mortality from overdose, they said.

Dr. Hadland and coauthors reported no conflicts of interest related to the study. Researchers were supported by grants from the National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA), a grant from the NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Thrasher Research Fund Early Career Award, and the Academic Pediatric Association Young Investigator Award.
 

SOURCE: Hadland SE, et al. JAMA Pediatr. 2018 Sep 10. doi:10.1001/jamapediatrics.2018.2143.

ATLANTA – Everyone has to be on the same page when it comes to anorexia nervosa in a community hospital, according to pediatric hospitalists at Moses H. Cone Memorial Hospital in Greensboro, N.C.

M. Alexander Otto/MDedge News

Anorexia cases used to be rare there. When one came in, “everyone was anxious because we just didn’t know quite what to do,” said Suresh Nagappan, MD, a pediatrician and member of the teaching faculty at the hospital. Parents would hear one thing from one provider, something else from the next, and leave angry and confused. “Basically, it was a mess. We needed to standardize it,” he added.

So Dr. Nagappan and his colleagues created guidelines for treating patients with eating disorders about 3 years ago. “It was meeting after meeting for months, but well worth it,” he said at Pediatric Hospital Medicine.

Word of the hospital’s newfound expertise in anorexia has spread since then, and now it’s not unusual for Moses H. Cone to handle a few cases a week.

The pediatric hospitalist team has come to realize that, first and foremost, patients and families need to know why they are there; it’s about medical stabilization, not treating the eating disorder. That comes after discharge. Families need help sometimes to understand that it’s not a quick fix.

To make things clear, there’s strict criteria now for admission, based on American Academy of Pediatrics guidance. The main trigger is being under 75% of ideal body weight, but patients must also have systolic blood pressure below 90 mm Hg and other worrisome signs. “Sometimes, it feels like we’re splitting hairs” on who gets admitted, “but if we don’t have strict criteria on admission, we don’t have an end goal for discharge,” said pediatrician Maggie S. Hall, MD, also on the Moses H. Cone teaching faculty.

As for treatment, “food is medicine, and it’s not negotiable. We make that clear to everyone on day 1. If patients don’t eat their actual meal, they have 20 minutes to drink a supplement. If they can’t do that, they get a nasogastric tube,” Dr. Nagappan said. The tube is pulled after each meal, so that it remains an incentive to eat.

The team start patients with 1,600 calories a day and increase the intake by 200-250 calories a day. The goal is for a patient to gain 100-200 grams per day. Patients pick out what they want to eat with the help of a dietitian. When meals set off overwhelming anxiety, the Moses H. Cone team has learned that benzodiazepines can help.

Ironically, the initiation of regular meals is the most dangerous time for patients. As anorexic bodies switch from catabolic to anabolic metabolism, electrolytes can drop to dangerously low levels, causing arrhythmias, heart failure, and death. In general, “the reason these kids die is cardiac,” Dr. Nagappan said at the meeting, sponsored by the Society of Hospital Medicine, the AAP, and the Academic Pediatric Association.

Refeeding syndrome, as it’s known, is clinically significant in perhaps 6% of patients. The risk goes up if they are below 70% of their ideal body weight; have a prolonged QTc interval; or begin treatment with low phosphorous, magnesium, or potassium.

M. Alexander Otto/MDedge News

To counter the threat, electrolytes are measured twice a day at Moses H. Cone during the first week of treatment, and ECGs are taken daily for the first few days. “One thing to be really careful about is when you notice their heart rate beginning to creep up during rest. That can be a sign of developing cardiomyopathy; it’s an indication for us to get echocardiograms,” Dr. Hall said.

The Moses H. Cone team like to include families in meal times – it’s been shown to help – but family members need to be coached beforehand. They can’t be punitive. Mealtime talk has to be positive, and can’t focus on eating. Parents often need help handling their own anger and guilt before trying to eat with their child. Progress has to be monitored, but Dr. Nagappan cautioned that “you have to be really careful about how you get weights”; it should always be in the morning after the first void. Urine needs to be checked to make sure patients aren’t water loading.

Staff should be neutral about weight results, and keep them to themselves. Even something as benign as “good job” can be a problem. “You don’t want these patients focused on their weight. You want them focused on getting better and eating and taking it step by step,” he said.

The presenters had no disclosures to report.

aotto@mdedge.com

ATLANTA – Everyone has to be on the same page when it comes to anorexia nervosa in a community hospital, according to pediatric hospitalists at Moses H. Cone Memorial Hospital in Greensboro, N.C.

M. Alexander Otto/MDedge News

Anorexia cases used to be rare there. When one came in, “everyone was anxious because we just didn’t know quite what to do,” said Suresh Nagappan, MD, a pediatrician and member of the teaching faculty at the hospital. Parents would hear one thing from one provider, something else from the next, and leave angry and confused. “Basically, it was a mess. We needed to standardize it,” he added.

So Dr. Nagappan and his colleagues created guidelines for treating patients with eating disorders about 3 years ago. “It was meeting after meeting for months, but well worth it,” he said at Pediatric Hospital Medicine.

Word of the hospital’s newfound expertise in anorexia has spread since then, and now it’s not unusual for Moses H. Cone to handle a few cases a week.

The pediatric hospitalist team has come to realize that, first and foremost, patients and families need to know why they are there; it’s about medical stabilization, not treating the eating disorder. That comes after discharge. Families need help sometimes to understand that it’s not a quick fix.

To make things clear, there’s strict criteria now for admission, based on American Academy of Pediatrics guidance. The main trigger is being under 75% of ideal body weight, but patients must also have systolic blood pressure below 90 mm Hg and other worrisome signs. “Sometimes, it feels like we’re splitting hairs” on who gets admitted, “but if we don’t have strict criteria on admission, we don’t have an end goal for discharge,” said pediatrician Maggie S. Hall, MD, also on the Moses H. Cone teaching faculty.

As for treatment, “food is medicine, and it’s not negotiable. We make that clear to everyone on day 1. If patients don’t eat their actual meal, they have 20 minutes to drink a supplement. If they can’t do that, they get a nasogastric tube,” Dr. Nagappan said. The tube is pulled after each meal, so that it remains an incentive to eat.

The team start patients with 1,600 calories a day and increase the intake by 200-250 calories a day. The goal is for a patient to gain 100-200 grams per day. Patients pick out what they want to eat with the help of a dietitian. When meals set off overwhelming anxiety, the Moses H. Cone team has learned that benzodiazepines can help.

Ironically, the initiation of regular meals is the most dangerous time for patients. As anorexic bodies switch from catabolic to anabolic metabolism, electrolytes can drop to dangerously low levels, causing arrhythmias, heart failure, and death. In general, “the reason these kids die is cardiac,” Dr. Nagappan said at the meeting, sponsored by the Society of Hospital Medicine, the AAP, and the Academic Pediatric Association.

Refeeding syndrome, as it’s known, is clinically significant in perhaps 6% of patients. The risk goes up if they are below 70% of their ideal body weight; have a prolonged QTc interval; or begin treatment with low phosphorous, magnesium, or potassium.

M. Alexander Otto/MDedge News

To counter the threat, electrolytes are measured twice a day at Moses H. Cone during the first week of treatment, and ECGs are taken daily for the first few days. “One thing to be really careful about is when you notice their heart rate beginning to creep up during rest. That can be a sign of developing cardiomyopathy; it’s an indication for us to get echocardiograms,” Dr. Hall said.

The Moses H. Cone team like to include families in meal times – it’s been shown to help – but family members need to be coached beforehand. They can’t be punitive. Mealtime talk has to be positive, and can’t focus on eating. Parents often need help handling their own anger and guilt before trying to eat with their child. Progress has to be monitored, but Dr. Nagappan cautioned that “you have to be really careful about how you get weights”; it should always be in the morning after the first void. Urine needs to be checked to make sure patients aren’t water loading.

Staff should be neutral about weight results, and keep them to themselves. Even something as benign as “good job” can be a problem. “You don’t want these patients focused on their weight. You want them focused on getting better and eating and taking it step by step,” he said.

The presenters had no disclosures to report.

aotto@mdedge.com

ATLANTA – Everyone has to be on the same page when it comes to anorexia nervosa in a community hospital, according to pediatric hospitalists at Moses H. Cone Memorial Hospital in Greensboro, N.C.

M. Alexander Otto/MDedge News

Anorexia cases used to be rare there. When one came in, “everyone was anxious because we just didn’t know quite what to do,” said Suresh Nagappan, MD, a pediatrician and member of the teaching faculty at the hospital. Parents would hear one thing from one provider, something else from the next, and leave angry and confused. “Basically, it was a mess. We needed to standardize it,” he added.

So Dr. Nagappan and his colleagues created guidelines for treating patients with eating disorders about 3 years ago. “It was meeting after meeting for months, but well worth it,” he said at Pediatric Hospital Medicine.

Word of the hospital’s newfound expertise in anorexia has spread since then, and now it’s not unusual for Moses H. Cone to handle a few cases a week.

The pediatric hospitalist team has come to realize that, first and foremost, patients and families need to know why they are there; it’s about medical stabilization, not treating the eating disorder. That comes after discharge. Families need help sometimes to understand that it’s not a quick fix.

To make things clear, there’s strict criteria now for admission, based on American Academy of Pediatrics guidance. The main trigger is being under 75% of ideal body weight, but patients must also have systolic blood pressure below 90 mm Hg and other worrisome signs. “Sometimes, it feels like we’re splitting hairs” on who gets admitted, “but if we don’t have strict criteria on admission, we don’t have an end goal for discharge,” said pediatrician Maggie S. Hall, MD, also on the Moses H. Cone teaching faculty.

As for treatment, “food is medicine, and it’s not negotiable. We make that clear to everyone on day 1. If patients don’t eat their actual meal, they have 20 minutes to drink a supplement. If they can’t do that, they get a nasogastric tube,” Dr. Nagappan said. The tube is pulled after each meal, so that it remains an incentive to eat.

The team start patients with 1,600 calories a day and increase the intake by 200-250 calories a day. The goal is for a patient to gain 100-200 grams per day. Patients pick out what they want to eat with the help of a dietitian. When meals set off overwhelming anxiety, the Moses H. Cone team has learned that benzodiazepines can help.

Ironically, the initiation of regular meals is the most dangerous time for patients. As anorexic bodies switch from catabolic to anabolic metabolism, electrolytes can drop to dangerously low levels, causing arrhythmias, heart failure, and death. In general, “the reason these kids die is cardiac,” Dr. Nagappan said at the meeting, sponsored by the Society of Hospital Medicine, the AAP, and the Academic Pediatric Association.

Refeeding syndrome, as it’s known, is clinically significant in perhaps 6% of patients. The risk goes up if they are below 70% of their ideal body weight; have a prolonged QTc interval; or begin treatment with low phosphorous, magnesium, or potassium.

M. Alexander Otto/MDedge News

To counter the threat, electrolytes are measured twice a day at Moses H. Cone during the first week of treatment, and ECGs are taken daily for the first few days. “One thing to be really careful about is when you notice their heart rate beginning to creep up during rest. That can be a sign of developing cardiomyopathy; it’s an indication for us to get echocardiograms,” Dr. Hall said.

The Moses H. Cone team like to include families in meal times – it’s been shown to help – but family members need to be coached beforehand. They can’t be punitive. Mealtime talk has to be positive, and can’t focus on eating. Parents often need help handling their own anger and guilt before trying to eat with their child. Progress has to be monitored, but Dr. Nagappan cautioned that “you have to be really careful about how you get weights”; it should always be in the morning after the first void. Urine needs to be checked to make sure patients aren’t water loading.

Staff should be neutral about weight results, and keep them to themselves. Even something as benign as “good job” can be a problem. “You don’t want these patients focused on their weight. You want them focused on getting better and eating and taking it step by step,” he said.

The presenters had no disclosures to report.

aotto@mdedge.com

LAKE TAHOE, CALIF. – Mosaicism makes everything in genetics more challenging, but it also enables researchers to understand how genes and cell pathways work in cancer and during human development, Leslie G. Biesecker, MD said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Biesecker, senior investigator and head of the clinical genomics section of the National Human Genome Research Institute’s Medical Genomics and Metabolic Genetics Branch, discussed mosaicism and a number of overgrowth syndromes that he and his associates have been studying that have clinical relevance for pediatric dermatologists. He noted that mosaicism can affect any tissue, anywhere, in any pattern. “If an affected cell cannot survive gametogenesis, fertilization, or survive early development, this generates Happle-type mosaicism,” explained Dr. Biesecker, who is trained in pediatrics and in clinical and molecular genetics.

“This is characterized by patchy manifestations, and no parent-to-child transmission or recurrence. You must always be careful here, though, because Mother Nature does what she wants to. Mosaic mutations can happen more than once, but it’s a very unlikely outcome. Happle-type mosaicism is also characterized by discordant monozygotic twins,” he noted.

The prototype for Happle-type mosaicism is Proteus syndrome, formerly known as Elephant Man disease, which is caused by a mutation in the AKT1 gene. Patients with Proteus syndrome undergo severe, relentless overgrowth, and about 25% of them die during childhood. “If you see one of these patients, you have a serious clinical problem on your hands,” he said. “There is enormous individual variability, but it is ultra rare.”

Dermatologic lesions that are characteristic of Proteus syndrome include cerebriform connective tissue nevus, which typically presents on the hands and feet. “A wide range of vascular malformations have also been associated with this, even patients with arteriovenous malformations,” Dr. Biesecker said. “They are a serious problem.” Linear verrucous epidermal nevus is another characteristic lesion of Proteus syndrome. It can present in a number of ways and in various body sites. “The natural history of these lesions is important,” he commented. “Over time, are they stable, or do they spread and expand over time? These lesions do not ever spontaneously regress. This does enable molecular diagnosis, but don’t bother sampling their blood, because it will be negative. You have to have a biopsy sample.”

Overgrowth syndromes that do not meet criteria for Proteus syndrome fall into a category known as PIK3CA-related overgrowth spectrum, which Dr. Biesecker characterized as “a bunch of clinical designations all caused by the same underlying somatic mutation in a gene called PIK3CA. There is an enormous variability in these patients, ranging from those who have profound overgrowth, including malformations, truncal overgrowth, and vascular malformations, and digital overgrowth in all sorts of patterns. We designate this as PIK3CA-related overgrowth spectrum (PROS), because we can’t clinically separate these things from one another.”

These conditions include what used to be called CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal/spinal anomalies), facial infiltrating lipomatosis, and megalencephaly-capillary malformation syndrome. PROS is about 100 times more common than Proteus syndrome. “There are no rational boundaries to distinguish these entities,” Dr. Biesecker said. “They are rationalized under a combined clinical-molecular PROS framework, meaning that the molecular diagnosis is absolutely key to correctly diagnosing these patients.”

In this way, mosaicism challenges the traditional concept of diagnosing overgrowth disorders. “What we thought were separate disorders are in fact many manifestations of a single disorder,” he continued. “When I was doing my genetics training, we were taught that it would turn out that there was one gene for every disease, and one disease for every gene. That is completely wrong; it’s much more complicated than that. Mosaicism is also important for us as biologists, because it gives us a window into biology we otherwise would not see. Without a mosaicism, Proteus syndrome cannot exist biologically. So if I want to understand that gene product, I have to study patients who are mosaics. Mosaicism can happen in any tissue, whether it’s visible or not.”

Dr. Biesecker, who has been elected to serve as president of the American Society of Human Genetics for 2019, noted that most of the gene mutations that cause overgrowth disorders are the same ones implicated in cancer. “It makes sense, because cancer is a disorder of uncontrolled proliferation and differentiation,” he said. “These overgrowth disorders are similar but less severe manifestations of the same problem. It turns out that these mosaic patients are single gene model systems of cancer biology.” Therefore, when a drug company develops an anti-cancer drug, he continued, it also can be useful for PROS or Proteus syndrome. It’s much easier to inhibit a protein that’s overactive than it is to replace the activity of a gene that has lost its function.

But in PROS and Proteus, “we have very different treatment objectives than oncologists do,” he said. “Our goal is to reduce the signaling caused by these mutations; we do not want to kill the cells. Some of my patients with these disorders have pretty close to 50% of cells in their body carrying these mutations. If I were thinking like an oncologist, the oncologist wants to kill cancer cells; that’s their objective. If I were to kill all of the mutant cells in my patients, I’m certain that would kill them.”

One promising development is the investigational oral agent ARQ 092, which is an inhibitor of AKT1. Dr. Biesecker and his colleagues at the NIH have been working to figure out what dosing should be used in humans based on mouse data, lab data, and data from cancer patients. They started with about one-twelvth the dose that oncologists use. After treating the first patient with overgrowth syndrome, on day 15 that person’s AKT1 level dropped to about 20% of normal, while on day 75 it moved to around 60% of normal. “We are right in that zone where we want to drive the activity of that protein to about half of what it should be,” Dr. Biesecker said. He and his colleagues also have observed regression of lesions in a patient with cerebriform connective tissue nevus who was treated with ARQ 092. “We’ve never seen this before.”

Dr. Biesecker disclosed that he is a member of the Illumina medical ethics board. He has received royalties from Genentech and in-kind research support from ArQule and Pfizer.

dbrunk@mdedge.com

 

LAKE TAHOE, CALIF. – Mosaicism makes everything in genetics more challenging, but it also enables researchers to understand how genes and cell pathways work in cancer and during human development, Leslie G. Biesecker, MD said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Biesecker, senior investigator and head of the clinical genomics section of the National Human Genome Research Institute’s Medical Genomics and Metabolic Genetics Branch, discussed mosaicism and a number of overgrowth syndromes that he and his associates have been studying that have clinical relevance for pediatric dermatologists. He noted that mosaicism can affect any tissue, anywhere, in any pattern. “If an affected cell cannot survive gametogenesis, fertilization, or survive early development, this generates Happle-type mosaicism,” explained Dr. Biesecker, who is trained in pediatrics and in clinical and molecular genetics.

“This is characterized by patchy manifestations, and no parent-to-child transmission or recurrence. You must always be careful here, though, because Mother Nature does what she wants to. Mosaic mutations can happen more than once, but it’s a very unlikely outcome. Happle-type mosaicism is also characterized by discordant monozygotic twins,” he noted.

The prototype for Happle-type mosaicism is Proteus syndrome, formerly known as Elephant Man disease, which is caused by a mutation in the AKT1 gene. Patients with Proteus syndrome undergo severe, relentless overgrowth, and about 25% of them die during childhood. “If you see one of these patients, you have a serious clinical problem on your hands,” he said. “There is enormous individual variability, but it is ultra rare.”

Dermatologic lesions that are characteristic of Proteus syndrome include cerebriform connective tissue nevus, which typically presents on the hands and feet. “A wide range of vascular malformations have also been associated with this, even patients with arteriovenous malformations,” Dr. Biesecker said. “They are a serious problem.” Linear verrucous epidermal nevus is another characteristic lesion of Proteus syndrome. It can present in a number of ways and in various body sites. “The natural history of these lesions is important,” he commented. “Over time, are they stable, or do they spread and expand over time? These lesions do not ever spontaneously regress. This does enable molecular diagnosis, but don’t bother sampling their blood, because it will be negative. You have to have a biopsy sample.”

Overgrowth syndromes that do not meet criteria for Proteus syndrome fall into a category known as PIK3CA-related overgrowth spectrum, which Dr. Biesecker characterized as “a bunch of clinical designations all caused by the same underlying somatic mutation in a gene called PIK3CA. There is an enormous variability in these patients, ranging from those who have profound overgrowth, including malformations, truncal overgrowth, and vascular malformations, and digital overgrowth in all sorts of patterns. We designate this as PIK3CA-related overgrowth spectrum (PROS), because we can’t clinically separate these things from one another.”

These conditions include what used to be called CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal/spinal anomalies), facial infiltrating lipomatosis, and megalencephaly-capillary malformation syndrome. PROS is about 100 times more common than Proteus syndrome. “There are no rational boundaries to distinguish these entities,” Dr. Biesecker said. “They are rationalized under a combined clinical-molecular PROS framework, meaning that the molecular diagnosis is absolutely key to correctly diagnosing these patients.”

In this way, mosaicism challenges the traditional concept of diagnosing overgrowth disorders. “What we thought were separate disorders are in fact many manifestations of a single disorder,” he continued. “When I was doing my genetics training, we were taught that it would turn out that there was one gene for every disease, and one disease for every gene. That is completely wrong; it’s much more complicated than that. Mosaicism is also important for us as biologists, because it gives us a window into biology we otherwise would not see. Without a mosaicism, Proteus syndrome cannot exist biologically. So if I want to understand that gene product, I have to study patients who are mosaics. Mosaicism can happen in any tissue, whether it’s visible or not.”

Dr. Biesecker, who has been elected to serve as president of the American Society of Human Genetics for 2019, noted that most of the gene mutations that cause overgrowth disorders are the same ones implicated in cancer. “It makes sense, because cancer is a disorder of uncontrolled proliferation and differentiation,” he said. “These overgrowth disorders are similar but less severe manifestations of the same problem. It turns out that these mosaic patients are single gene model systems of cancer biology.” Therefore, when a drug company develops an anti-cancer drug, he continued, it also can be useful for PROS or Proteus syndrome. It’s much easier to inhibit a protein that’s overactive than it is to replace the activity of a gene that has lost its function.

But in PROS and Proteus, “we have very different treatment objectives than oncologists do,” he said. “Our goal is to reduce the signaling caused by these mutations; we do not want to kill the cells. Some of my patients with these disorders have pretty close to 50% of cells in their body carrying these mutations. If I were thinking like an oncologist, the oncologist wants to kill cancer cells; that’s their objective. If I were to kill all of the mutant cells in my patients, I’m certain that would kill them.”

One promising development is the investigational oral agent ARQ 092, which is an inhibitor of AKT1. Dr. Biesecker and his colleagues at the NIH have been working to figure out what dosing should be used in humans based on mouse data, lab data, and data from cancer patients. They started with about one-twelvth the dose that oncologists use. After treating the first patient with overgrowth syndrome, on day 15 that person’s AKT1 level dropped to about 20% of normal, while on day 75 it moved to around 60% of normal. “We are right in that zone where we want to drive the activity of that protein to about half of what it should be,” Dr. Biesecker said. He and his colleagues also have observed regression of lesions in a patient with cerebriform connective tissue nevus who was treated with ARQ 092. “We’ve never seen this before.”

Dr. Biesecker disclosed that he is a member of the Illumina medical ethics board. He has received royalties from Genentech and in-kind research support from ArQule and Pfizer.

dbrunk@mdedge.com

 

LAKE TAHOE, CALIF. – Mosaicism makes everything in genetics more challenging, but it also enables researchers to understand how genes and cell pathways work in cancer and during human development, Leslie G. Biesecker, MD said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Biesecker, senior investigator and head of the clinical genomics section of the National Human Genome Research Institute’s Medical Genomics and Metabolic Genetics Branch, discussed mosaicism and a number of overgrowth syndromes that he and his associates have been studying that have clinical relevance for pediatric dermatologists. He noted that mosaicism can affect any tissue, anywhere, in any pattern. “If an affected cell cannot survive gametogenesis, fertilization, or survive early development, this generates Happle-type mosaicism,” explained Dr. Biesecker, who is trained in pediatrics and in clinical and molecular genetics.

“This is characterized by patchy manifestations, and no parent-to-child transmission or recurrence. You must always be careful here, though, because Mother Nature does what she wants to. Mosaic mutations can happen more than once, but it’s a very unlikely outcome. Happle-type mosaicism is also characterized by discordant monozygotic twins,” he noted.

The prototype for Happle-type mosaicism is Proteus syndrome, formerly known as Elephant Man disease, which is caused by a mutation in the AKT1 gene. Patients with Proteus syndrome undergo severe, relentless overgrowth, and about 25% of them die during childhood. “If you see one of these patients, you have a serious clinical problem on your hands,” he said. “There is enormous individual variability, but it is ultra rare.”

Dermatologic lesions that are characteristic of Proteus syndrome include cerebriform connective tissue nevus, which typically presents on the hands and feet. “A wide range of vascular malformations have also been associated with this, even patients with arteriovenous malformations,” Dr. Biesecker said. “They are a serious problem.” Linear verrucous epidermal nevus is another characteristic lesion of Proteus syndrome. It can present in a number of ways and in various body sites. “The natural history of these lesions is important,” he commented. “Over time, are they stable, or do they spread and expand over time? These lesions do not ever spontaneously regress. This does enable molecular diagnosis, but don’t bother sampling their blood, because it will be negative. You have to have a biopsy sample.”

Overgrowth syndromes that do not meet criteria for Proteus syndrome fall into a category known as PIK3CA-related overgrowth spectrum, which Dr. Biesecker characterized as “a bunch of clinical designations all caused by the same underlying somatic mutation in a gene called PIK3CA. There is an enormous variability in these patients, ranging from those who have profound overgrowth, including malformations, truncal overgrowth, and vascular malformations, and digital overgrowth in all sorts of patterns. We designate this as PIK3CA-related overgrowth spectrum (PROS), because we can’t clinically separate these things from one another.”

These conditions include what used to be called CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal/spinal anomalies), facial infiltrating lipomatosis, and megalencephaly-capillary malformation syndrome. PROS is about 100 times more common than Proteus syndrome. “There are no rational boundaries to distinguish these entities,” Dr. Biesecker said. “They are rationalized under a combined clinical-molecular PROS framework, meaning that the molecular diagnosis is absolutely key to correctly diagnosing these patients.”

In this way, mosaicism challenges the traditional concept of diagnosing overgrowth disorders. “What we thought were separate disorders are in fact many manifestations of a single disorder,” he continued. “When I was doing my genetics training, we were taught that it would turn out that there was one gene for every disease, and one disease for every gene. That is completely wrong; it’s much more complicated than that. Mosaicism is also important for us as biologists, because it gives us a window into biology we otherwise would not see. Without a mosaicism, Proteus syndrome cannot exist biologically. So if I want to understand that gene product, I have to study patients who are mosaics. Mosaicism can happen in any tissue, whether it’s visible or not.”

Dr. Biesecker, who has been elected to serve as president of the American Society of Human Genetics for 2019, noted that most of the gene mutations that cause overgrowth disorders are the same ones implicated in cancer. “It makes sense, because cancer is a disorder of uncontrolled proliferation and differentiation,” he said. “These overgrowth disorders are similar but less severe manifestations of the same problem. It turns out that these mosaic patients are single gene model systems of cancer biology.” Therefore, when a drug company develops an anti-cancer drug, he continued, it also can be useful for PROS or Proteus syndrome. It’s much easier to inhibit a protein that’s overactive than it is to replace the activity of a gene that has lost its function.

But in PROS and Proteus, “we have very different treatment objectives than oncologists do,” he said. “Our goal is to reduce the signaling caused by these mutations; we do not want to kill the cells. Some of my patients with these disorders have pretty close to 50% of cells in their body carrying these mutations. If I were thinking like an oncologist, the oncologist wants to kill cancer cells; that’s their objective. If I were to kill all of the mutant cells in my patients, I’m certain that would kill them.”

One promising development is the investigational oral agent ARQ 092, which is an inhibitor of AKT1. Dr. Biesecker and his colleagues at the NIH have been working to figure out what dosing should be used in humans based on mouse data, lab data, and data from cancer patients. They started with about one-twelvth the dose that oncologists use. After treating the first patient with overgrowth syndrome, on day 15 that person’s AKT1 level dropped to about 20% of normal, while on day 75 it moved to around 60% of normal. “We are right in that zone where we want to drive the activity of that protein to about half of what it should be,” Dr. Biesecker said. He and his colleagues also have observed regression of lesions in a patient with cerebriform connective tissue nevus who was treated with ARQ 092. “We’ve never seen this before.”

Dr. Biesecker disclosed that he is a member of the Illumina medical ethics board. He has received royalties from Genentech and in-kind research support from ArQule and Pfizer.

dbrunk@mdedge.com

 

LAKE TAHOE, CALIF. – Strong associations exist between intestinal dysbiosis and a wide variety of gut and systemic diseases, according to Mark A. Underwood, MD.

Doug Brunk/MDedge News

“Antibiotic exposure changes the composition of the intestinal microbiota,” he said at the annual meeting of the Society for Pediatric Dermatology. “That clearly causes both antibiotic-associated diarrhea and Clostridium difficile colitis. The bigger question is, is it possible that intestinal dysbiosis is related to a whole bunch of other systemic diseases? In other words, does an insult during a critical window of development cause changes in the intestinal microbiota that can lead to systemic diseases in the brain, the lung, the liver, or the immune system?”

According Dr. Underwood, a pediatrician who is chief of the division of neonatology at the University of California, Davis, the prevalence of dysbiosis is increasing worldwide, particularly in developed countries, where Bifidobacteria are decreasing and Enterobacteriaceae are increasing. “Those changes are associated with gut permeability and alterations in both local and systemic inflammation, and the risk for a number of diseases, including atopic dermatitis,” he said. Key reasons for the increasing prevalence of dysbiosis, he continued, include the use of antibiotics, cesarean section delivery, formula feeding, changes in hygiene that alter the intestinal biota, the high-fat, high-sugar Western diet, and a loss of vertical and horizontal transmission over generations.

In an effort to evaluate the association between early childhood antibiotic use with allergic diseases in later childhood, Japanese researchers followed 1,200 infants to the age of 5 years (Ann Allergy Asthma Immunol. 2017;119:54-8). They found that antibiotic exposure within the first 2 years of life was associated with an increased risk of asthma (adjusted odds ratio 1.72), allergic rhinitis (adjusted OR 1.65), and atopic dermatitis (adjusted OR 1.40). In a more recent, smaller prospective study, 436 Dutch infants were followed to 1 year of age (Pediatr Allergy Immunol. 2018;29[2]:151-8). The researchers found that antibiotic exposure within the first week of life was associated with allergic sensitization (adjusted OR 3.26), colic (adjusted OR 1.66), and wheezing (adjusted OR 1.56).

In a study of 44 term infants with a family history of allergy, changes in the fecal microbiota, especially colonization with Ruminococcus gnavus, preceded the onset of allergic symptoms (Gastroenterol. 2018;154[1]:154-67). The same researchers observed similar findings in an animal model.

One potential mechanism by which intestinal dysbiosis causes systemic disease is stimulation of toll-like receptor 4 (TLR4), “which is a receptor on a variety of mucosal cells that senses the presence of a microbial pathogen-associated patterns, particularly those of Gram-negative Enterobacteriaceae,” Dr. Underwood explained. Other potential mechanisms include increased intestinal permeability, an increase in the pH and decreases in short-chain fatty acids within the gut lumen, and a loss of intraluminal hypoxia. “Think of the colon as an anaerobic chamber,” he said. “The colon lumen should be very low in oxygen. It should be dominated by obligate anaerobes.”

Efforts to prevent or treat dysbiosis-related diseases include the use of probiotics and fecal transplantation. A recent Cochrane review of 8,672 patients found “moderate certainty evidence” that probiotics are effective for preventing C. difficile-associated diarrhea. The analysis included 31 randomized, controlled trials of adults who were treated either with a probiotic or with a placebo. When pooled, the risk ratio was 0.40, which represented a significant protection. In addition, a summary of 7 randomized controlled trials and 30 case series suggests that fecal microbial transplantation is superior to vancomycin for adults with recurrent C. difficile colitis (relative risk 0.23) (Aliment Pharmacol Ther. 2017;46[5]:470-93).

To date, the effect of giving probiotics to pregnant women who have a family history of allergy is less clear. One pooled analysis of such studies put the overall risk ratio at 0.74 (Mil Med. 2014;179[6]:580-92). “While I think the jury’s still out on how to best prevent atopic dermatitis in these families, it looks like there is some potential benefit in treating these moms during pregnancy with probiotics and treating the infant during the first few months of life,” Dr. Underwood said. The most effective were mixtures including one or more Lactobacillus species or L. rhamnosus, mixtures including one or more Bifidobacterium species, or B. lactis by itself. The use of probiotics also has been found to prevent necrotizing enterocolitis, sepsis, and death in premature infants (Semin Pediatr Surg. 2018;27[1]:39-46).

Dr. Underwood disclosed that he has received honoraria from Abbott and that he was a member of the scientific review board for Avexegen. He also chaired the data safety and monitoring board for Infant Bacterial Therapeutics and has received support from Evolve BioSystems to perform a clinical trial.

dbrunk@mdedge.com

LAKE TAHOE, CALIF. – Strong associations exist between intestinal dysbiosis and a wide variety of gut and systemic diseases, according to Mark A. Underwood, MD.

Doug Brunk/MDedge News

“Antibiotic exposure changes the composition of the intestinal microbiota,” he said at the annual meeting of the Society for Pediatric Dermatology. “That clearly causes both antibiotic-associated diarrhea and Clostridium difficile colitis. The bigger question is, is it possible that intestinal dysbiosis is related to a whole bunch of other systemic diseases? In other words, does an insult during a critical window of development cause changes in the intestinal microbiota that can lead to systemic diseases in the brain, the lung, the liver, or the immune system?”

According Dr. Underwood, a pediatrician who is chief of the division of neonatology at the University of California, Davis, the prevalence of dysbiosis is increasing worldwide, particularly in developed countries, where Bifidobacteria are decreasing and Enterobacteriaceae are increasing. “Those changes are associated with gut permeability and alterations in both local and systemic inflammation, and the risk for a number of diseases, including atopic dermatitis,” he said. Key reasons for the increasing prevalence of dysbiosis, he continued, include the use of antibiotics, cesarean section delivery, formula feeding, changes in hygiene that alter the intestinal biota, the high-fat, high-sugar Western diet, and a loss of vertical and horizontal transmission over generations.

In an effort to evaluate the association between early childhood antibiotic use with allergic diseases in later childhood, Japanese researchers followed 1,200 infants to the age of 5 years (Ann Allergy Asthma Immunol. 2017;119:54-8). They found that antibiotic exposure within the first 2 years of life was associated with an increased risk of asthma (adjusted odds ratio 1.72), allergic rhinitis (adjusted OR 1.65), and atopic dermatitis (adjusted OR 1.40). In a more recent, smaller prospective study, 436 Dutch infants were followed to 1 year of age (Pediatr Allergy Immunol. 2018;29[2]:151-8). The researchers found that antibiotic exposure within the first week of life was associated with allergic sensitization (adjusted OR 3.26), colic (adjusted OR 1.66), and wheezing (adjusted OR 1.56).

In a study of 44 term infants with a family history of allergy, changes in the fecal microbiota, especially colonization with Ruminococcus gnavus, preceded the onset of allergic symptoms (Gastroenterol. 2018;154[1]:154-67). The same researchers observed similar findings in an animal model.

One potential mechanism by which intestinal dysbiosis causes systemic disease is stimulation of toll-like receptor 4 (TLR4), “which is a receptor on a variety of mucosal cells that senses the presence of a microbial pathogen-associated patterns, particularly those of Gram-negative Enterobacteriaceae,” Dr. Underwood explained. Other potential mechanisms include increased intestinal permeability, an increase in the pH and decreases in short-chain fatty acids within the gut lumen, and a loss of intraluminal hypoxia. “Think of the colon as an anaerobic chamber,” he said. “The colon lumen should be very low in oxygen. It should be dominated by obligate anaerobes.”

Efforts to prevent or treat dysbiosis-related diseases include the use of probiotics and fecal transplantation. A recent Cochrane review of 8,672 patients found “moderate certainty evidence” that probiotics are effective for preventing C. difficile-associated diarrhea. The analysis included 31 randomized, controlled trials of adults who were treated either with a probiotic or with a placebo. When pooled, the risk ratio was 0.40, which represented a significant protection. In addition, a summary of 7 randomized controlled trials and 30 case series suggests that fecal microbial transplantation is superior to vancomycin for adults with recurrent C. difficile colitis (relative risk 0.23) (Aliment Pharmacol Ther. 2017;46[5]:470-93).

To date, the effect of giving probiotics to pregnant women who have a family history of allergy is less clear. One pooled analysis of such studies put the overall risk ratio at 0.74 (Mil Med. 2014;179[6]:580-92). “While I think the jury’s still out on how to best prevent atopic dermatitis in these families, it looks like there is some potential benefit in treating these moms during pregnancy with probiotics and treating the infant during the first few months of life,” Dr. Underwood said. The most effective were mixtures including one or more Lactobacillus species or L. rhamnosus, mixtures including one or more Bifidobacterium species, or B. lactis by itself. The use of probiotics also has been found to prevent necrotizing enterocolitis, sepsis, and death in premature infants (Semin Pediatr Surg. 2018;27[1]:39-46).

Dr. Underwood disclosed that he has received honoraria from Abbott and that he was a member of the scientific review board for Avexegen. He also chaired the data safety and monitoring board for Infant Bacterial Therapeutics and has received support from Evolve BioSystems to perform a clinical trial.

dbrunk@mdedge.com

LAKE TAHOE, CALIF. – Strong associations exist between intestinal dysbiosis and a wide variety of gut and systemic diseases, according to Mark A. Underwood, MD.

Doug Brunk/MDedge News

“Antibiotic exposure changes the composition of the intestinal microbiota,” he said at the annual meeting of the Society for Pediatric Dermatology. “That clearly causes both antibiotic-associated diarrhea and Clostridium difficile colitis. The bigger question is, is it possible that intestinal dysbiosis is related to a whole bunch of other systemic diseases? In other words, does an insult during a critical window of development cause changes in the intestinal microbiota that can lead to systemic diseases in the brain, the lung, the liver, or the immune system?”

According Dr. Underwood, a pediatrician who is chief of the division of neonatology at the University of California, Davis, the prevalence of dysbiosis is increasing worldwide, particularly in developed countries, where Bifidobacteria are decreasing and Enterobacteriaceae are increasing. “Those changes are associated with gut permeability and alterations in both local and systemic inflammation, and the risk for a number of diseases, including atopic dermatitis,” he said. Key reasons for the increasing prevalence of dysbiosis, he continued, include the use of antibiotics, cesarean section delivery, formula feeding, changes in hygiene that alter the intestinal biota, the high-fat, high-sugar Western diet, and a loss of vertical and horizontal transmission over generations.

In an effort to evaluate the association between early childhood antibiotic use with allergic diseases in later childhood, Japanese researchers followed 1,200 infants to the age of 5 years (Ann Allergy Asthma Immunol. 2017;119:54-8). They found that antibiotic exposure within the first 2 years of life was associated with an increased risk of asthma (adjusted odds ratio 1.72), allergic rhinitis (adjusted OR 1.65), and atopic dermatitis (adjusted OR 1.40). In a more recent, smaller prospective study, 436 Dutch infants were followed to 1 year of age (Pediatr Allergy Immunol. 2018;29[2]:151-8). The researchers found that antibiotic exposure within the first week of life was associated with allergic sensitization (adjusted OR 3.26), colic (adjusted OR 1.66), and wheezing (adjusted OR 1.56).

In a study of 44 term infants with a family history of allergy, changes in the fecal microbiota, especially colonization with Ruminococcus gnavus, preceded the onset of allergic symptoms (Gastroenterol. 2018;154[1]:154-67). The same researchers observed similar findings in an animal model.

One potential mechanism by which intestinal dysbiosis causes systemic disease is stimulation of toll-like receptor 4 (TLR4), “which is a receptor on a variety of mucosal cells that senses the presence of a microbial pathogen-associated patterns, particularly those of Gram-negative Enterobacteriaceae,” Dr. Underwood explained. Other potential mechanisms include increased intestinal permeability, an increase in the pH and decreases in short-chain fatty acids within the gut lumen, and a loss of intraluminal hypoxia. “Think of the colon as an anaerobic chamber,” he said. “The colon lumen should be very low in oxygen. It should be dominated by obligate anaerobes.”

Efforts to prevent or treat dysbiosis-related diseases include the use of probiotics and fecal transplantation. A recent Cochrane review of 8,672 patients found “moderate certainty evidence” that probiotics are effective for preventing C. difficile-associated diarrhea. The analysis included 31 randomized, controlled trials of adults who were treated either with a probiotic or with a placebo. When pooled, the risk ratio was 0.40, which represented a significant protection. In addition, a summary of 7 randomized controlled trials and 30 case series suggests that fecal microbial transplantation is superior to vancomycin for adults with recurrent C. difficile colitis (relative risk 0.23) (Aliment Pharmacol Ther. 2017;46[5]:470-93).

To date, the effect of giving probiotics to pregnant women who have a family history of allergy is less clear. One pooled analysis of such studies put the overall risk ratio at 0.74 (Mil Med. 2014;179[6]:580-92). “While I think the jury’s still out on how to best prevent atopic dermatitis in these families, it looks like there is some potential benefit in treating these moms during pregnancy with probiotics and treating the infant during the first few months of life,” Dr. Underwood said. The most effective were mixtures including one or more Lactobacillus species or L. rhamnosus, mixtures including one or more Bifidobacterium species, or B. lactis by itself. The use of probiotics also has been found to prevent necrotizing enterocolitis, sepsis, and death in premature infants (Semin Pediatr Surg. 2018;27[1]:39-46).

Dr. Underwood disclosed that he has received honoraria from Abbott and that he was a member of the scientific review board for Avexegen. He also chaired the data safety and monitoring board for Infant Bacterial Therapeutics and has received support from Evolve BioSystems to perform a clinical trial.

dbrunk@mdedge.com

CHICAGO – Though research shows that nail fungus occurs in just 0.3% of pediatric patients in the United States, that’s not what Sheila Friedlander, MD, is seeing in her southern California practice, where it’s not uncommon to see children whose nails, toe nails in particular, have fungal involvement.

fotokostic/iStock/Getty Images

“I know I started out telling you fungus isn’t that common in children … but you do need to think about it,” said Dr. Friedlander during a nail-focused session at the annual summer meeting of the American Academy of Dermatology. Dr. Friedlander, professor of dermatology and pediatrics at the University of California San Diego and Rady Children’s Hospital, said that she suspects that more participation in organized sports at a young age may be contributing to the increase, with occlusive sports footwear replacing bare feet or sandals for more hours of the day, presenting more opportunities for toenail trauma in sports such as soccer.

When making the clinical call about a nail problem, bear in mind that the younger the child, the less likely a nail problem is fungal, Dr. Friedlander noted. “Little children are much less likely than older children to have nail fungus. Pediatric nails are thinner, and they are faster growing, with better blood supply to the matrix.”

And if frank onychomadesis is observed, think about the time of year, and ask about recent fevers and rashes, because coxsackievirus may be the culprit. “Be not afraid, and look everywhere if the nail is confusing to you,” she said. In all ages, the diagnosis is primarily clinical, “but I culture them, I ‘PAS’ [periodic acid-Schiff stain] them, too. If you do both, you’ll increase your yield,” Dr. Friedlander said, adding, “the beauty of PAS is you can use it to give your families an answer very soon.”

Once you’ve established that fungus is to blame for a nail problem, there’s a conundrum: There are no Food and Drug Administration-approved therapies, either topical or systemic, for pediatric onychomycosis, Dr. Friedlander said. She, along with coauthors and first author Aditya Gupta, MD, of Mediprobe Research, London, Ontario, Canada, recently published an article reviewing the safety and efficacy of antifungal agents in this age group (Pediatr Dermatol. 2018 Jun 26. doi: 10.1111/pde.13561).

Reviewing information available in the United States and Canada, Dr. Friedlander and her coauthors came up with three topical and four oral options for children, along with recommendations for dosage and duration.

In response to an audience question about the use of topical antifungal treatment for nail involvement, Dr. Friedlander responded, “I think topicals would be great for kids, but it’s for kids where there is no nail matrix involvement. Also, cost is a problem. Nobody will cover it. But some families are willing to do this to avoid systemic therapy,” and if the family budget can accommodate a topical choice, it’s a logical option, she said, noting that partial reimbursement via a coupon system is available from some pharmaceutical companies.

Where appropriate, ciclopirox 8%, efinaconazole 10%, and tavaborole 5% can each be considered. Dr. Friedlander cited one study she coauthored, which reported that 70% of pediatric participants with nonmatrix onychomycosis saw effective treatment, with a 71% mycological cure rate (P = .03), after 32 weeks of treatment with ciclopirox lacquer versus vehicle (Pediatr Dermatol. 2013 May-Jun;30[3]:316-22).

Systemic therapies – which, when studied, have been given at tinea capitis doses – could include griseofulvin, terbinafine, itraconazole, and fluconazole.

In terms of oral options, Dr. Friedlander said, griseofulvin has some practical limitations. While prolonged treatment is required in any case, terbinafine may produce results in about 3 months, whereas griseofulvin may require up to 9 months of therapy. “I always try to use terbinafine … griseofulvin takes a year and a day,” she said.

She also shared some tips to improve pediatric adherence with oral antifungals: “You can tell parents to crush terbinafine tablets and mix in peanut butter or applesauce to improve adherence. Griseofulvin can be flavored by the pharmacy, but volumes are big with griseofulvin, so it’s a challenge to get kids to take it all,” she said.

Dr. Friedlander reported that she had no relevant financial disclosures.

koakes@mdedge.com



 

CHICAGO – Though research shows that nail fungus occurs in just 0.3% of pediatric patients in the United States, that’s not what Sheila Friedlander, MD, is seeing in her southern California practice, where it’s not uncommon to see children whose nails, toe nails in particular, have fungal involvement.

fotokostic/iStock/Getty Images

“I know I started out telling you fungus isn’t that common in children … but you do need to think about it,” said Dr. Friedlander during a nail-focused session at the annual summer meeting of the American Academy of Dermatology. Dr. Friedlander, professor of dermatology and pediatrics at the University of California San Diego and Rady Children’s Hospital, said that she suspects that more participation in organized sports at a young age may be contributing to the increase, with occlusive sports footwear replacing bare feet or sandals for more hours of the day, presenting more opportunities for toenail trauma in sports such as soccer.

When making the clinical call about a nail problem, bear in mind that the younger the child, the less likely a nail problem is fungal, Dr. Friedlander noted. “Little children are much less likely than older children to have nail fungus. Pediatric nails are thinner, and they are faster growing, with better blood supply to the matrix.”

And if frank onychomadesis is observed, think about the time of year, and ask about recent fevers and rashes, because coxsackievirus may be the culprit. “Be not afraid, and look everywhere if the nail is confusing to you,” she said. In all ages, the diagnosis is primarily clinical, “but I culture them, I ‘PAS’ [periodic acid-Schiff stain] them, too. If you do both, you’ll increase your yield,” Dr. Friedlander said, adding, “the beauty of PAS is you can use it to give your families an answer very soon.”

Once you’ve established that fungus is to blame for a nail problem, there’s a conundrum: There are no Food and Drug Administration-approved therapies, either topical or systemic, for pediatric onychomycosis, Dr. Friedlander said. She, along with coauthors and first author Aditya Gupta, MD, of Mediprobe Research, London, Ontario, Canada, recently published an article reviewing the safety and efficacy of antifungal agents in this age group (Pediatr Dermatol. 2018 Jun 26. doi: 10.1111/pde.13561).

Reviewing information available in the United States and Canada, Dr. Friedlander and her coauthors came up with three topical and four oral options for children, along with recommendations for dosage and duration.

In response to an audience question about the use of topical antifungal treatment for nail involvement, Dr. Friedlander responded, “I think topicals would be great for kids, but it’s for kids where there is no nail matrix involvement. Also, cost is a problem. Nobody will cover it. But some families are willing to do this to avoid systemic therapy,” and if the family budget can accommodate a topical choice, it’s a logical option, she said, noting that partial reimbursement via a coupon system is available from some pharmaceutical companies.

Where appropriate, ciclopirox 8%, efinaconazole 10%, and tavaborole 5% can each be considered. Dr. Friedlander cited one study she coauthored, which reported that 70% of pediatric participants with nonmatrix onychomycosis saw effective treatment, with a 71% mycological cure rate (P = .03), after 32 weeks of treatment with ciclopirox lacquer versus vehicle (Pediatr Dermatol. 2013 May-Jun;30[3]:316-22).

Systemic therapies – which, when studied, have been given at tinea capitis doses – could include griseofulvin, terbinafine, itraconazole, and fluconazole.

In terms of oral options, Dr. Friedlander said, griseofulvin has some practical limitations. While prolonged treatment is required in any case, terbinafine may produce results in about 3 months, whereas griseofulvin may require up to 9 months of therapy. “I always try to use terbinafine … griseofulvin takes a year and a day,” she said.

She also shared some tips to improve pediatric adherence with oral antifungals: “You can tell parents to crush terbinafine tablets and mix in peanut butter or applesauce to improve adherence. Griseofulvin can be flavored by the pharmacy, but volumes are big with griseofulvin, so it’s a challenge to get kids to take it all,” she said.

Dr. Friedlander reported that she had no relevant financial disclosures.

koakes@mdedge.com



 

CHICAGO – Though research shows that nail fungus occurs in just 0.3% of pediatric patients in the United States, that’s not what Sheila Friedlander, MD, is seeing in her southern California practice, where it’s not uncommon to see children whose nails, toe nails in particular, have fungal involvement.

fotokostic/iStock/Getty Images

“I know I started out telling you fungus isn’t that common in children … but you do need to think about it,” said Dr. Friedlander during a nail-focused session at the annual summer meeting of the American Academy of Dermatology. Dr. Friedlander, professor of dermatology and pediatrics at the University of California San Diego and Rady Children’s Hospital, said that she suspects that more participation in organized sports at a young age may be contributing to the increase, with occlusive sports footwear replacing bare feet or sandals for more hours of the day, presenting more opportunities for toenail trauma in sports such as soccer.

When making the clinical call about a nail problem, bear in mind that the younger the child, the less likely a nail problem is fungal, Dr. Friedlander noted. “Little children are much less likely than older children to have nail fungus. Pediatric nails are thinner, and they are faster growing, with better blood supply to the matrix.”

And if frank onychomadesis is observed, think about the time of year, and ask about recent fevers and rashes, because coxsackievirus may be the culprit. “Be not afraid, and look everywhere if the nail is confusing to you,” she said. In all ages, the diagnosis is primarily clinical, “but I culture them, I ‘PAS’ [periodic acid-Schiff stain] them, too. If you do both, you’ll increase your yield,” Dr. Friedlander said, adding, “the beauty of PAS is you can use it to give your families an answer very soon.”

Once you’ve established that fungus is to blame for a nail problem, there’s a conundrum: There are no Food and Drug Administration-approved therapies, either topical or systemic, for pediatric onychomycosis, Dr. Friedlander said. She, along with coauthors and first author Aditya Gupta, MD, of Mediprobe Research, London, Ontario, Canada, recently published an article reviewing the safety and efficacy of antifungal agents in this age group (Pediatr Dermatol. 2018 Jun 26. doi: 10.1111/pde.13561).

Reviewing information available in the United States and Canada, Dr. Friedlander and her coauthors came up with three topical and four oral options for children, along with recommendations for dosage and duration.

In response to an audience question about the use of topical antifungal treatment for nail involvement, Dr. Friedlander responded, “I think topicals would be great for kids, but it’s for kids where there is no nail matrix involvement. Also, cost is a problem. Nobody will cover it. But some families are willing to do this to avoid systemic therapy,” and if the family budget can accommodate a topical choice, it’s a logical option, she said, noting that partial reimbursement via a coupon system is available from some pharmaceutical companies.

Where appropriate, ciclopirox 8%, efinaconazole 10%, and tavaborole 5% can each be considered. Dr. Friedlander cited one study she coauthored, which reported that 70% of pediatric participants with nonmatrix onychomycosis saw effective treatment, with a 71% mycological cure rate (P = .03), after 32 weeks of treatment with ciclopirox lacquer versus vehicle (Pediatr Dermatol. 2013 May-Jun;30[3]:316-22).

Systemic therapies – which, when studied, have been given at tinea capitis doses – could include griseofulvin, terbinafine, itraconazole, and fluconazole.

In terms of oral options, Dr. Friedlander said, griseofulvin has some practical limitations. While prolonged treatment is required in any case, terbinafine may produce results in about 3 months, whereas griseofulvin may require up to 9 months of therapy. “I always try to use terbinafine … griseofulvin takes a year and a day,” she said.

She also shared some tips to improve pediatric adherence with oral antifungals: “You can tell parents to crush terbinafine tablets and mix in peanut butter or applesauce to improve adherence. Griseofulvin can be flavored by the pharmacy, but volumes are big with griseofulvin, so it’s a challenge to get kids to take it all,” she said.

Dr. Friedlander reported that she had no relevant financial disclosures.

koakes@mdedge.com