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Diet low in free sugars shows promise for adolescent NAFLD
after 8 weeks, compared with boys on a usual diet.
“Because of growing evidence implicating dietary sugars in NAFLD, well-controlled studies in children with NAFLD are needed to inform clinical practice and public policy,” wrote Jeffrey B. Schwimmer, MD, of the University of California, San Diego, La Jolla, and colleagues in JAMA.
The researchers randomized 40 boys aged 11-16 years with active NAFLD to a diet low in free sugars or their usual diet. The intervention diet involved personalized menu planning and provision of meals for the boys’ entire households that were designed to restrict free sugar intake to less than 3% of daily calories. Adherence to the diet was assessed by twice-weekly phone calls.
In the intervention group, hepatic steatosis decreased from an average of 25% at baseline to 17% after 8 weeks, compared with a change from 21% to 20% in the control group. The adjusted mean difference at 8 weeks was −6.23%, which was statistically significant (P less than .001).
The average age of the participants was 13 years, 95% were Hispanic. All 40 completed the study, and 18 of the 20 boys in the intervention group reported less than 3% of calories from free sugar during the study period. No adverse events were reported related to study participation.
The results were limited by several factors, including the small sample size and homogeneous population. In addition, neither hepatic steatosis or serum alanine aminotransferase (ALT) levels decreased enough to enter the normal range, the researchers noted. The findings, though preliminary, support the value of reducing free sugars, including glucose, fructose, and sucrose, to help manage NAFLD in adolescents, and “further research is required to assess long-term and clinical outcomes,” they said.
The study was supported by grants from multiple foundations and organizations, including the Nutrition Science Initiative, the University of California, San Diego, the National Institutes of Health, Children’s Healthcare of Atlanta and Emory University Pediatric Biostatistics Core, and the Georgia Clinical and Translational Science Alliance. Dr. Schwimmer reported receiving research support from Galmed and Intercept.
SOURCE: Schwimmer JB et al. JAMA. 2019;321(3):256-265.
after 8 weeks, compared with boys on a usual diet.
“Because of growing evidence implicating dietary sugars in NAFLD, well-controlled studies in children with NAFLD are needed to inform clinical practice and public policy,” wrote Jeffrey B. Schwimmer, MD, of the University of California, San Diego, La Jolla, and colleagues in JAMA.
The researchers randomized 40 boys aged 11-16 years with active NAFLD to a diet low in free sugars or their usual diet. The intervention diet involved personalized menu planning and provision of meals for the boys’ entire households that were designed to restrict free sugar intake to less than 3% of daily calories. Adherence to the diet was assessed by twice-weekly phone calls.
In the intervention group, hepatic steatosis decreased from an average of 25% at baseline to 17% after 8 weeks, compared with a change from 21% to 20% in the control group. The adjusted mean difference at 8 weeks was −6.23%, which was statistically significant (P less than .001).
The average age of the participants was 13 years, 95% were Hispanic. All 40 completed the study, and 18 of the 20 boys in the intervention group reported less than 3% of calories from free sugar during the study period. No adverse events were reported related to study participation.
The results were limited by several factors, including the small sample size and homogeneous population. In addition, neither hepatic steatosis or serum alanine aminotransferase (ALT) levels decreased enough to enter the normal range, the researchers noted. The findings, though preliminary, support the value of reducing free sugars, including glucose, fructose, and sucrose, to help manage NAFLD in adolescents, and “further research is required to assess long-term and clinical outcomes,” they said.
The study was supported by grants from multiple foundations and organizations, including the Nutrition Science Initiative, the University of California, San Diego, the National Institutes of Health, Children’s Healthcare of Atlanta and Emory University Pediatric Biostatistics Core, and the Georgia Clinical and Translational Science Alliance. Dr. Schwimmer reported receiving research support from Galmed and Intercept.
SOURCE: Schwimmer JB et al. JAMA. 2019;321(3):256-265.
after 8 weeks, compared with boys on a usual diet.
“Because of growing evidence implicating dietary sugars in NAFLD, well-controlled studies in children with NAFLD are needed to inform clinical practice and public policy,” wrote Jeffrey B. Schwimmer, MD, of the University of California, San Diego, La Jolla, and colleagues in JAMA.
The researchers randomized 40 boys aged 11-16 years with active NAFLD to a diet low in free sugars or their usual diet. The intervention diet involved personalized menu planning and provision of meals for the boys’ entire households that were designed to restrict free sugar intake to less than 3% of daily calories. Adherence to the diet was assessed by twice-weekly phone calls.
In the intervention group, hepatic steatosis decreased from an average of 25% at baseline to 17% after 8 weeks, compared with a change from 21% to 20% in the control group. The adjusted mean difference at 8 weeks was −6.23%, which was statistically significant (P less than .001).
The average age of the participants was 13 years, 95% were Hispanic. All 40 completed the study, and 18 of the 20 boys in the intervention group reported less than 3% of calories from free sugar during the study period. No adverse events were reported related to study participation.
The results were limited by several factors, including the small sample size and homogeneous population. In addition, neither hepatic steatosis or serum alanine aminotransferase (ALT) levels decreased enough to enter the normal range, the researchers noted. The findings, though preliminary, support the value of reducing free sugars, including glucose, fructose, and sucrose, to help manage NAFLD in adolescents, and “further research is required to assess long-term and clinical outcomes,” they said.
The study was supported by grants from multiple foundations and organizations, including the Nutrition Science Initiative, the University of California, San Diego, the National Institutes of Health, Children’s Healthcare of Atlanta and Emory University Pediatric Biostatistics Core, and the Georgia Clinical and Translational Science Alliance. Dr. Schwimmer reported receiving research support from Galmed and Intercept.
SOURCE: Schwimmer JB et al. JAMA. 2019;321(3):256-265.
FROM JAMA
Key clinical point: After 8 weeks, adolescent boys on a diet low in free sugars showed significant improvement in hepatic steatosis, compared with those on a usual diet.
Major finding: Hepatic steatosis decreased from an average of 25% at baseline to 17% after 8 weeks in the modified diet group, compared with a decrease from 21% to 20% in the usual diet group.
Study details: The data come from an open-label, randomized trial of 40 adolescent boys aged 11 to 16 years with active NAFLD.
Disclosures: The study was supported by grants from multiple foundations and organizations, including the Nutrition Science Initiative, the University of California, San Diego, the National Institutes of Health, Children’s Healthcare of Atlanta and Emory University Pediatric Biostatistics Core, and the Georgia Clinical and Translational Science Alliance. Dr. Schwimmer reported receiving research support from Galmed and Intercept.
Source: Schwimmer JB et al. JAMA. 2019;321(3):256-265.
Any mental disorder increases risk for all mental disorders
Diagnosis of any mental disorder significantly increased the risk for all other mental disorders, based on data from a population-based cohort study of almost 6 million individuals followed for nearly 84 million person-years.
Comorbidity among mental disorders has been acknowledged, but comprehensive data on comorbidities across all subsets of disease and a comprehensive risk assessment has been lacking, wrote Oleguer Plana-Ripoll, PhD, of Aarhus University in Denmark, and his colleagues.
In a study published in JAMA Psychiatry, the researchers included all individuals born in Denmark between Jan. 1, 1900, and Dec. 31, 2015, who were living in Denmark between Jan. 1, 2000, and Dec. 31, 2016. They used national health registries to identify mental disorders, and diagnoses were based on the International Statistical Classification of Diseases and Related Health Problems. The study population included 2,958,293 men and 2,982,485 women with an average age of 32 years at the start of the follow-up period; participants were followed for a total of 83.9 million person-years. Mental disorders were categorized in groups, and groups were paired for risk assessment.
Overall, the risk of developing all other mental disorders increased with the diagnosis of one mental disorder, most prominently in the first year after diagnosis, but the risk persisted for at least 15 years. In one model controlling for age, calendar time, and sex, hazard ratios ranged from 2.0 for prior intellectual disabilities paired with later eating disorders to 48.6 for prior developmental disorders paired with later intellectual disabilities.
The large sample size allowed for focus on absolute risk and the study was accompanied by an interactive website (http://www.nbepi.com) that allows clinicians (and potentially patients) to monitor possible emerging mental health comorbidities.
As one example of absolute risk assessment, the researchers determined that 40% of men and 50% of women diagnosed with a mood disorder before age 20 years would develop an incident neurotic disorder as defined by the 10th revision of the International Statistical Classification of Diseases and Related Health Problems within the next 15 years. “The provision of absolute risk estimates may facilitate the clinical translation of our findings, and lay the groundwork for future studies related to personalized medicine and the primary prevention of comorbidity,” Dr. Plana-Ripoll and his colleagues wrote.
The researchers acknowledged the study’s limitation of comorbidities to pairs of disorders versus three or more, the use of groups of disorders rather than specific disorders, and the limitation to mental disorders treated in secondary care settings. However, and the comprehensive nature of the analysis will provide an important foundation for future research,” they said.
The research was supported by the Danish National Research Foundation. Dr. Plana-Ripoll had no financial conflicts to disclose. Some coauthors disclosed grants from the National Institutes of Health, Novo Nordisk Foundation, and the European Research Council, and some coauthors disclosed financial relationships with Sanofi Aventis, Johnson & Johnson, Sage Pharmaceuticals, Shire, and Takeda.
SOURCE: Plana-Ripoll O et al. JAMA Psychiatry. 2019 Jan 16. doi: 10.1001/jamapsychiatry.2018.3658.
The study’s large, population-based sample supports the findings of pervasive and bidirectional comorbidity across all areas of psychopathology, Steven E. Hyman, MD, wrote in an accompanying editorial.
“As the authors recognize, this bidirectionality provides new evidence for the sharing of risk architecture across mental disorders,” Dr. Hyman said.
Dr. Hyman added that the data from the study, available via website for access by clinicians and patients, represent an important public health contribution by providing insight into factors that might increase risk for comorbid mental health conditions. However, the data must be interpreted and used with caution, he said, and users must be “educated not to interpret this type of probabilistic information in an excessively pessimistic and fatalistic manner – an issue that is not unique to this risk predictor,” he said.
Dr. Hyman added that, although the findings support theories on the shared factor models for pathogenesis of mental disorders, new classification proposals and research into the genetics of mental disorders are in the early stages. “Indeed, if research is to advance the laudable desire of the authors to contribute to prevention of new incident diagnoses, Plana-Rapoll et al. have helped their cause by pointing out that we must make diagnoses in a new way,” he said (JAMA Psychiatry. 2019 Jan 16. doi: 10.1001/jamapsychiatry.2018.4269).
Dr. Hyman is affiliated with the Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard in Cambridge, Mass. He disclosed personal fees for serving on the scientific advisory boards of Janssen, BlackThorn Therapeutics, and F-Prime Capital Partners, and personal fees for serving on the board of directors of Voyager Therapeutics and Q-State Biosciences.
The study’s large, population-based sample supports the findings of pervasive and bidirectional comorbidity across all areas of psychopathology, Steven E. Hyman, MD, wrote in an accompanying editorial.
“As the authors recognize, this bidirectionality provides new evidence for the sharing of risk architecture across mental disorders,” Dr. Hyman said.
Dr. Hyman added that the data from the study, available via website for access by clinicians and patients, represent an important public health contribution by providing insight into factors that might increase risk for comorbid mental health conditions. However, the data must be interpreted and used with caution, he said, and users must be “educated not to interpret this type of probabilistic information in an excessively pessimistic and fatalistic manner – an issue that is not unique to this risk predictor,” he said.
Dr. Hyman added that, although the findings support theories on the shared factor models for pathogenesis of mental disorders, new classification proposals and research into the genetics of mental disorders are in the early stages. “Indeed, if research is to advance the laudable desire of the authors to contribute to prevention of new incident diagnoses, Plana-Rapoll et al. have helped their cause by pointing out that we must make diagnoses in a new way,” he said (JAMA Psychiatry. 2019 Jan 16. doi: 10.1001/jamapsychiatry.2018.4269).
Dr. Hyman is affiliated with the Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard in Cambridge, Mass. He disclosed personal fees for serving on the scientific advisory boards of Janssen, BlackThorn Therapeutics, and F-Prime Capital Partners, and personal fees for serving on the board of directors of Voyager Therapeutics and Q-State Biosciences.
The study’s large, population-based sample supports the findings of pervasive and bidirectional comorbidity across all areas of psychopathology, Steven E. Hyman, MD, wrote in an accompanying editorial.
“As the authors recognize, this bidirectionality provides new evidence for the sharing of risk architecture across mental disorders,” Dr. Hyman said.
Dr. Hyman added that the data from the study, available via website for access by clinicians and patients, represent an important public health contribution by providing insight into factors that might increase risk for comorbid mental health conditions. However, the data must be interpreted and used with caution, he said, and users must be “educated not to interpret this type of probabilistic information in an excessively pessimistic and fatalistic manner – an issue that is not unique to this risk predictor,” he said.
Dr. Hyman added that, although the findings support theories on the shared factor models for pathogenesis of mental disorders, new classification proposals and research into the genetics of mental disorders are in the early stages. “Indeed, if research is to advance the laudable desire of the authors to contribute to prevention of new incident diagnoses, Plana-Rapoll et al. have helped their cause by pointing out that we must make diagnoses in a new way,” he said (JAMA Psychiatry. 2019 Jan 16. doi: 10.1001/jamapsychiatry.2018.4269).
Dr. Hyman is affiliated with the Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard in Cambridge, Mass. He disclosed personal fees for serving on the scientific advisory boards of Janssen, BlackThorn Therapeutics, and F-Prime Capital Partners, and personal fees for serving on the board of directors of Voyager Therapeutics and Q-State Biosciences.
Diagnosis of any mental disorder significantly increased the risk for all other mental disorders, based on data from a population-based cohort study of almost 6 million individuals followed for nearly 84 million person-years.
Comorbidity among mental disorders has been acknowledged, but comprehensive data on comorbidities across all subsets of disease and a comprehensive risk assessment has been lacking, wrote Oleguer Plana-Ripoll, PhD, of Aarhus University in Denmark, and his colleagues.
In a study published in JAMA Psychiatry, the researchers included all individuals born in Denmark between Jan. 1, 1900, and Dec. 31, 2015, who were living in Denmark between Jan. 1, 2000, and Dec. 31, 2016. They used national health registries to identify mental disorders, and diagnoses were based on the International Statistical Classification of Diseases and Related Health Problems. The study population included 2,958,293 men and 2,982,485 women with an average age of 32 years at the start of the follow-up period; participants were followed for a total of 83.9 million person-years. Mental disorders were categorized in groups, and groups were paired for risk assessment.
Overall, the risk of developing all other mental disorders increased with the diagnosis of one mental disorder, most prominently in the first year after diagnosis, but the risk persisted for at least 15 years. In one model controlling for age, calendar time, and sex, hazard ratios ranged from 2.0 for prior intellectual disabilities paired with later eating disorders to 48.6 for prior developmental disorders paired with later intellectual disabilities.
The large sample size allowed for focus on absolute risk and the study was accompanied by an interactive website (http://www.nbepi.com) that allows clinicians (and potentially patients) to monitor possible emerging mental health comorbidities.
As one example of absolute risk assessment, the researchers determined that 40% of men and 50% of women diagnosed with a mood disorder before age 20 years would develop an incident neurotic disorder as defined by the 10th revision of the International Statistical Classification of Diseases and Related Health Problems within the next 15 years. “The provision of absolute risk estimates may facilitate the clinical translation of our findings, and lay the groundwork for future studies related to personalized medicine and the primary prevention of comorbidity,” Dr. Plana-Ripoll and his colleagues wrote.
The researchers acknowledged the study’s limitation of comorbidities to pairs of disorders versus three or more, the use of groups of disorders rather than specific disorders, and the limitation to mental disorders treated in secondary care settings. However, and the comprehensive nature of the analysis will provide an important foundation for future research,” they said.
The research was supported by the Danish National Research Foundation. Dr. Plana-Ripoll had no financial conflicts to disclose. Some coauthors disclosed grants from the National Institutes of Health, Novo Nordisk Foundation, and the European Research Council, and some coauthors disclosed financial relationships with Sanofi Aventis, Johnson & Johnson, Sage Pharmaceuticals, Shire, and Takeda.
SOURCE: Plana-Ripoll O et al. JAMA Psychiatry. 2019 Jan 16. doi: 10.1001/jamapsychiatry.2018.3658.
Diagnosis of any mental disorder significantly increased the risk for all other mental disorders, based on data from a population-based cohort study of almost 6 million individuals followed for nearly 84 million person-years.
Comorbidity among mental disorders has been acknowledged, but comprehensive data on comorbidities across all subsets of disease and a comprehensive risk assessment has been lacking, wrote Oleguer Plana-Ripoll, PhD, of Aarhus University in Denmark, and his colleagues.
In a study published in JAMA Psychiatry, the researchers included all individuals born in Denmark between Jan. 1, 1900, and Dec. 31, 2015, who were living in Denmark between Jan. 1, 2000, and Dec. 31, 2016. They used national health registries to identify mental disorders, and diagnoses were based on the International Statistical Classification of Diseases and Related Health Problems. The study population included 2,958,293 men and 2,982,485 women with an average age of 32 years at the start of the follow-up period; participants were followed for a total of 83.9 million person-years. Mental disorders were categorized in groups, and groups were paired for risk assessment.
Overall, the risk of developing all other mental disorders increased with the diagnosis of one mental disorder, most prominently in the first year after diagnosis, but the risk persisted for at least 15 years. In one model controlling for age, calendar time, and sex, hazard ratios ranged from 2.0 for prior intellectual disabilities paired with later eating disorders to 48.6 for prior developmental disorders paired with later intellectual disabilities.
The large sample size allowed for focus on absolute risk and the study was accompanied by an interactive website (http://www.nbepi.com) that allows clinicians (and potentially patients) to monitor possible emerging mental health comorbidities.
As one example of absolute risk assessment, the researchers determined that 40% of men and 50% of women diagnosed with a mood disorder before age 20 years would develop an incident neurotic disorder as defined by the 10th revision of the International Statistical Classification of Diseases and Related Health Problems within the next 15 years. “The provision of absolute risk estimates may facilitate the clinical translation of our findings, and lay the groundwork for future studies related to personalized medicine and the primary prevention of comorbidity,” Dr. Plana-Ripoll and his colleagues wrote.
The researchers acknowledged the study’s limitation of comorbidities to pairs of disorders versus three or more, the use of groups of disorders rather than specific disorders, and the limitation to mental disorders treated in secondary care settings. However, and the comprehensive nature of the analysis will provide an important foundation for future research,” they said.
The research was supported by the Danish National Research Foundation. Dr. Plana-Ripoll had no financial conflicts to disclose. Some coauthors disclosed grants from the National Institutes of Health, Novo Nordisk Foundation, and the European Research Council, and some coauthors disclosed financial relationships with Sanofi Aventis, Johnson & Johnson, Sage Pharmaceuticals, Shire, and Takeda.
SOURCE: Plana-Ripoll O et al. JAMA Psychiatry. 2019 Jan 16. doi: 10.1001/jamapsychiatry.2018.3658.
FROM JAMA PSYCHIATRY
Key clinical point: Comorbid mental disorders are common across all domains of psychopathology.
Major finding: Hazard ratios for comorbid mental disorders after one disorder ranged from 2.0 to 48.6.
Study details: The data come from a population-based cohort study of 5,940,778 individuals.
Disclosures: The research was supported by the Danish National Research Foundation. Dr. Plana-Ripoll had no financial conflicts to disclose. Several coauthors disclosed grants from the National Institutes of Health, Novo Nordisk Foundation, and the European Research Council, and some coauthors disclosed financial relationships with Sanofi Aventis, Johnson & Johnson, Sage Pharmaceuticals, Shire, and Takeda.
Source: Plana-Ripoll O et al. JAMA Psychiatry. 2019 Jan 16. doi: 10.1001/jamapsychiatry.2018.3658.
Delayed first contraception use raises unwanted pregnancy risk
Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.
Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.
“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.
In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.
Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.
When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.
No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.
The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.
The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.
SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.
Despite a declining teen birth rate in the last several decades, the United States has the highest teen birth rate among industrialized nations. While many factors play into this rate, we know that, in many European countries with low teen birth rates, adolescents often initiate contraceptive methods before their sexual debut. As we often tell teenagers, they can become pregnant the “first time,” which makes initiating contraception early – and preferably before sexual debut – an important strategy to preventing unplanned pregnancy.
This study identifies the trends over time in the initiation of contraception in relationship to sexual debut and examines its effects on unplanned teen pregnancy. Understanding these trends can help clinicians more effectively target teen pregnancy.
I was pleasantly surprised to see that rates of timely contraceptive initiation have increased since 1970. Sadly, this rise is largely because of condom use. Use of effective forms of contraception – especially long-acting reversible forms of contraception (LARC), such as the IUD or the etonogestrel rod – still remain low at the time of sexual debut. While we continue to encourage LARCs as first line for pregnancy prevention, many patients are not getting the message about these highly effective, safe methods. Unsurprisingly, there are significant differences based on race/ethnicity and socioeconomic status on timely initiation of contraceptive methods, especially highly effective methods. This supports prior research which has shown significant barriers in access to contraception to these groups, which leads to higher rates of unplanned pregnancies.
Dr. Kelly Curran, MD, specializes in adolescent medicine at the University of Oklahoma, Oklahoma City. She is a member of the Pediatric News editorial advisory board and was asked to comment on the study by Murray Horwitz et al. Dr. Curran had no relevant financial disclosures.
Despite a declining teen birth rate in the last several decades, the United States has the highest teen birth rate among industrialized nations. While many factors play into this rate, we know that, in many European countries with low teen birth rates, adolescents often initiate contraceptive methods before their sexual debut. As we often tell teenagers, they can become pregnant the “first time,” which makes initiating contraception early – and preferably before sexual debut – an important strategy to preventing unplanned pregnancy.
This study identifies the trends over time in the initiation of contraception in relationship to sexual debut and examines its effects on unplanned teen pregnancy. Understanding these trends can help clinicians more effectively target teen pregnancy.
I was pleasantly surprised to see that rates of timely contraceptive initiation have increased since 1970. Sadly, this rise is largely because of condom use. Use of effective forms of contraception – especially long-acting reversible forms of contraception (LARC), such as the IUD or the etonogestrel rod – still remain low at the time of sexual debut. While we continue to encourage LARCs as first line for pregnancy prevention, many patients are not getting the message about these highly effective, safe methods. Unsurprisingly, there are significant differences based on race/ethnicity and socioeconomic status on timely initiation of contraceptive methods, especially highly effective methods. This supports prior research which has shown significant barriers in access to contraception to these groups, which leads to higher rates of unplanned pregnancies.
Dr. Kelly Curran, MD, specializes in adolescent medicine at the University of Oklahoma, Oklahoma City. She is a member of the Pediatric News editorial advisory board and was asked to comment on the study by Murray Horwitz et al. Dr. Curran had no relevant financial disclosures.
Despite a declining teen birth rate in the last several decades, the United States has the highest teen birth rate among industrialized nations. While many factors play into this rate, we know that, in many European countries with low teen birth rates, adolescents often initiate contraceptive methods before their sexual debut. As we often tell teenagers, they can become pregnant the “first time,” which makes initiating contraception early – and preferably before sexual debut – an important strategy to preventing unplanned pregnancy.
This study identifies the trends over time in the initiation of contraception in relationship to sexual debut and examines its effects on unplanned teen pregnancy. Understanding these trends can help clinicians more effectively target teen pregnancy.
I was pleasantly surprised to see that rates of timely contraceptive initiation have increased since 1970. Sadly, this rise is largely because of condom use. Use of effective forms of contraception – especially long-acting reversible forms of contraception (LARC), such as the IUD or the etonogestrel rod – still remain low at the time of sexual debut. While we continue to encourage LARCs as first line for pregnancy prevention, many patients are not getting the message about these highly effective, safe methods. Unsurprisingly, there are significant differences based on race/ethnicity and socioeconomic status on timely initiation of contraceptive methods, especially highly effective methods. This supports prior research which has shown significant barriers in access to contraception to these groups, which leads to higher rates of unplanned pregnancies.
Dr. Kelly Curran, MD, specializes in adolescent medicine at the University of Oklahoma, Oklahoma City. She is a member of the Pediatric News editorial advisory board and was asked to comment on the study by Murray Horwitz et al. Dr. Curran had no relevant financial disclosures.
Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.
Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.
“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.
In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.
Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.
When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.
No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.
The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.
The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.
SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.
Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.
Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.
“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.
In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.
Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.
When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.
No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.
The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.
The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.
SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.
FROM PEDIATRICS
Key clinical point: Women who delayed using contraception were significantly more likely to become pregnant within 3 months of starting sexual activity than were those who had initiated contraception use, especially black, Hispanic, and low-income women.
Major finding: Unwanted pregnancy within 3 months of sexual debut was 3.7 times more likely in women who delayed initial contraception use, compared with those who had timely initiation.
Study details: The data come from a cross-sectional study including 26,359 women with sexual debuts between 1970 and 2014.
Disclosures: The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.
Source: Horwitz M et al. Pediatrics. 2019;143(2):e20182463.
Back pain persists in one in five patients
according to data from a population-based study of more than 12,000 adults in Canada.
“Given that back pain [BP] is often recurrent, it is important to understand the course of back pain over time as this can provide additional insights on risk factors for nonfavorable outcomes,” wrote Mayilee Canizares, PhD, and her colleagues at the University Health Network’s Krembil Research Institute in Toronto.
In a longitudinal study published in Arthritis Care & Research, the investigators followed 12,782 adults from 1994 to 2011. The study population was a representative sample of the Canadian population via the National Population Health Survey, which collected data every 2 years for a total of nine cycles of data. They included people aged 15 years or older in 1994-1995 who had at least three cycles of data from baseline onward.
Over the 16-year study period, 46% of the participants reported at least one episode of back pain. Of these, 18% were identified as persistent, 28% as developing, 21% as recovering, and 33% as occasional.
“A major finding from this study is the negative impact of persistent BP on a range of health-related outcomes, including health care use, after adjustments for sociodemographic, behavior-related factors, and comorbidities,” the researchers wrote.
They examined several sociodemographic variables, including age, gender, educational level, and household income, as well as behavior-related variables including physical activity, work activity, smoking status, and obesity. The average age of the participants at baseline was 39 years; 51% were female.
Individuals who reported any back pain were more likely than those with no back pain to be overweight or obese, to smoke, to engage in moderate to heavy physical activity each day, and to have chronic conditions, including arthritis, depression, high blood pressure, and migraine.
Overall, individuals with persistent or developing BP had more pain, disability, health care visits, and medication use, compared with those in the recovery and occasional BP groups. However, individuals in the recovery group showed increased use of opioids and antidepressants over time as well, suggesting a need for long-term monitoring of back pain patients.
The trend in general disability was greatest for individuals in the persistent group followed by the developing group, recovery group, and occasional BP group.
The study findings were limited by several factors, including the use of self-reports, potential selection bias, and the inability to differentiate the specific types of back pain, the researchers noted. However, the results support and extend data from previous studies and provide clinical implications for understanding back pain.
The researchers concluded that “the different trajectory patterns potentially represent subgroups in the population that may require different interventions. In light of the trend of marked worsening outcomes, particularly for the persistent and developing groups, studies are needed to determine the nature of these groups.”
The authors reported no relevant financial conflicts.
SOURCE: Canizares M et al. Arthritis Care Res. 2019 Jan 14. doi: 10.1002/acr.23811.
according to data from a population-based study of more than 12,000 adults in Canada.
“Given that back pain [BP] is often recurrent, it is important to understand the course of back pain over time as this can provide additional insights on risk factors for nonfavorable outcomes,” wrote Mayilee Canizares, PhD, and her colleagues at the University Health Network’s Krembil Research Institute in Toronto.
In a longitudinal study published in Arthritis Care & Research, the investigators followed 12,782 adults from 1994 to 2011. The study population was a representative sample of the Canadian population via the National Population Health Survey, which collected data every 2 years for a total of nine cycles of data. They included people aged 15 years or older in 1994-1995 who had at least three cycles of data from baseline onward.
Over the 16-year study period, 46% of the participants reported at least one episode of back pain. Of these, 18% were identified as persistent, 28% as developing, 21% as recovering, and 33% as occasional.
“A major finding from this study is the negative impact of persistent BP on a range of health-related outcomes, including health care use, after adjustments for sociodemographic, behavior-related factors, and comorbidities,” the researchers wrote.
They examined several sociodemographic variables, including age, gender, educational level, and household income, as well as behavior-related variables including physical activity, work activity, smoking status, and obesity. The average age of the participants at baseline was 39 years; 51% were female.
Individuals who reported any back pain were more likely than those with no back pain to be overweight or obese, to smoke, to engage in moderate to heavy physical activity each day, and to have chronic conditions, including arthritis, depression, high blood pressure, and migraine.
Overall, individuals with persistent or developing BP had more pain, disability, health care visits, and medication use, compared with those in the recovery and occasional BP groups. However, individuals in the recovery group showed increased use of opioids and antidepressants over time as well, suggesting a need for long-term monitoring of back pain patients.
The trend in general disability was greatest for individuals in the persistent group followed by the developing group, recovery group, and occasional BP group.
The study findings were limited by several factors, including the use of self-reports, potential selection bias, and the inability to differentiate the specific types of back pain, the researchers noted. However, the results support and extend data from previous studies and provide clinical implications for understanding back pain.
The researchers concluded that “the different trajectory patterns potentially represent subgroups in the population that may require different interventions. In light of the trend of marked worsening outcomes, particularly for the persistent and developing groups, studies are needed to determine the nature of these groups.”
The authors reported no relevant financial conflicts.
SOURCE: Canizares M et al. Arthritis Care Res. 2019 Jan 14. doi: 10.1002/acr.23811.
according to data from a population-based study of more than 12,000 adults in Canada.
“Given that back pain [BP] is often recurrent, it is important to understand the course of back pain over time as this can provide additional insights on risk factors for nonfavorable outcomes,” wrote Mayilee Canizares, PhD, and her colleagues at the University Health Network’s Krembil Research Institute in Toronto.
In a longitudinal study published in Arthritis Care & Research, the investigators followed 12,782 adults from 1994 to 2011. The study population was a representative sample of the Canadian population via the National Population Health Survey, which collected data every 2 years for a total of nine cycles of data. They included people aged 15 years or older in 1994-1995 who had at least three cycles of data from baseline onward.
Over the 16-year study period, 46% of the participants reported at least one episode of back pain. Of these, 18% were identified as persistent, 28% as developing, 21% as recovering, and 33% as occasional.
“A major finding from this study is the negative impact of persistent BP on a range of health-related outcomes, including health care use, after adjustments for sociodemographic, behavior-related factors, and comorbidities,” the researchers wrote.
They examined several sociodemographic variables, including age, gender, educational level, and household income, as well as behavior-related variables including physical activity, work activity, smoking status, and obesity. The average age of the participants at baseline was 39 years; 51% were female.
Individuals who reported any back pain were more likely than those with no back pain to be overweight or obese, to smoke, to engage in moderate to heavy physical activity each day, and to have chronic conditions, including arthritis, depression, high blood pressure, and migraine.
Overall, individuals with persistent or developing BP had more pain, disability, health care visits, and medication use, compared with those in the recovery and occasional BP groups. However, individuals in the recovery group showed increased use of opioids and antidepressants over time as well, suggesting a need for long-term monitoring of back pain patients.
The trend in general disability was greatest for individuals in the persistent group followed by the developing group, recovery group, and occasional BP group.
The study findings were limited by several factors, including the use of self-reports, potential selection bias, and the inability to differentiate the specific types of back pain, the researchers noted. However, the results support and extend data from previous studies and provide clinical implications for understanding back pain.
The researchers concluded that “the different trajectory patterns potentially represent subgroups in the population that may require different interventions. In light of the trend of marked worsening outcomes, particularly for the persistent and developing groups, studies are needed to determine the nature of these groups.”
The authors reported no relevant financial conflicts.
SOURCE: Canizares M et al. Arthritis Care Res. 2019 Jan 14. doi: 10.1002/acr.23811.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Back pain is a common health problem, and one in five Canadian adults reported persistent back pain.
Major finding: Approximately half (46%) of Canadian adults reported some type of back pain over a 16-year period.
Study details: The data come from a population-based study of 12,782 adults followed from 1994 to 2011.
Disclosures: The authors reported no relevant financial conflicts.
Source: Canizares M et al. Arthritis Care Res. 2019 Jan 14. doi: 10.1002/acr.23811.
Novel atopic dermatitis cream shows promise in phase 2 study
Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.
“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.
In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.
After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.
In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.
The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.
The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.
The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.
However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.
AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.
SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.
Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.
“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.
In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.
After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.
In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.
The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.
The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.
The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.
However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.
AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.
SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.
Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.
“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.
In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.
After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.
In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.
The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.
The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.
The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.
However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.
AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.
SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.
FROM THE BRITISH JOURNAL OF DERMATOLOGY
Key clinical point: Significantly more atopic dermatitis patients improved when treated with PAC-14028 cream, compared with those treated with a placebo vehicle.
Major finding: After 8 weeks, 58% of patients given the 1.0 cream achieved scores of 0 or 1 on the Investigator’s Global Assessment scale, compared with 15% for placebo patients.
Study details: The data come from a phase 2b randomized, double-blind trial including 194 atopic dermatitis patients.
Disclosures: AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.
Source: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.
Treprostinil improves function for complex PAH patients
Treatment with , a study based on data from 105 adults has shown.
Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.
The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.
Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.
The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.
In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.
Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.
The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.
The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
Treatment with , a study based on data from 105 adults has shown.
Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.
The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.
Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.
The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.
In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.
Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.
The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.
The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
Treatment with , a study based on data from 105 adults has shown.
Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.
The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.
Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.
The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.
In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.
Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.
The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.
The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
FROM THE LANCET RESPIRATORY MEDICINE
Key clinical point: Treprostinil is a safe and effective nonsurgical treatment option for severe CTEPH patients.
Major finding: After 24 weeks, 6-minute walk distance improved by 44.98 m from baseline in the high-dose group compared with an increase of 4.29 m from baseline in the low-dose group.
Study details: The data come from a randomized trial of 105 adults with confirmed CTEPH.
Disclosures: The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
Source: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
Knee pathologies, including multiple meniscal tears, predict accelerated OA
Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.
The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.
“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.
The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.
Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.
Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.
Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.
At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.
Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.
Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).
“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.
The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.
“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.
“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.
The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.
SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.
Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.
The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.
“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.
The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.
Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.
Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.
Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.
At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.
Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.
Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).
“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.
The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.
“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.
“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.
The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.
SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.
Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.
The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.
“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.
The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.
Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.
Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.
Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.
At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.
Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.
Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).
“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.
The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.
“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.
“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.
The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.
SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: One year before the knee OA index visit, more than 75% of patients with accelerated knee OA had meniscal damage in at least two regions.
Study details: The data come from 375 adults with typical knee OA, accelerated knee OA, or no knee OA in the longitudinal Osteoarthritis Initiative cohort study.
Disclosures: The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.
Source: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.
Prenatal valproate exposure raises ADHD risk
Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.
Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.
The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.
Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.
A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.
The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.
“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.
However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.
The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
The data from the current study differ from a recent meta-analysis of five studies that did not find a statistically significant increase in ADHD risk in children associated with prenatal valproate exposure, Kimford J. Meador, MD, wrote in an accompanying editorial (JAMA Network Open. 2019;2[1]:e186603. doi: 10.1001/jamanetworkopen.2018.6603).
“The discrepancy between the present study and the prior meta-analysis might be due to the meta-analysis using different analytical approaches and examining studies with smaller sample sizes, higher attrition rates, shorter follow-ups, and cohort differences,” Dr. Meador said. “Nevertheless, the findings by Christensen et al. are consistent with multiple studies demonstrating adverse neurodevelopmental effects associated with fetal valproate exposure.”
Given the potential risks associated with valproate exposure not only for behavior problems such as ADHD but also for congenital malformations and other cognitive and behavioral issues in children, women of childbearing age who are using valproate or considering a prescription should be counseled for informed consent, Dr. Meador said.
Dr. Meador advocated additional research on the impact of antiepileptic drugs during pregnancy and risk assessment strategies, including “a national reporting system for congenital malformations, routine preclinical testing of all new antiseizure medications for neurodevelopmental effects, monitoring of antiseizure medication prescription practices for women of childbearing age to determine whether emerging knowledge is being appropriately applied, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms of anatomical and behavioral teratogenesis from antiseizure medications.”
Dr. Meador is affiliated with the department of neurology and neurological sciences at Stanford (Calif.) University. He disclosed research support from the National Institutes of Health and Sunovion, and travel support from UCB. The Epilepsy Study Consortium pays Stanford University for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB, and Vivus.
The data from the current study differ from a recent meta-analysis of five studies that did not find a statistically significant increase in ADHD risk in children associated with prenatal valproate exposure, Kimford J. Meador, MD, wrote in an accompanying editorial (JAMA Network Open. 2019;2[1]:e186603. doi: 10.1001/jamanetworkopen.2018.6603).
“The discrepancy between the present study and the prior meta-analysis might be due to the meta-analysis using different analytical approaches and examining studies with smaller sample sizes, higher attrition rates, shorter follow-ups, and cohort differences,” Dr. Meador said. “Nevertheless, the findings by Christensen et al. are consistent with multiple studies demonstrating adverse neurodevelopmental effects associated with fetal valproate exposure.”
Given the potential risks associated with valproate exposure not only for behavior problems such as ADHD but also for congenital malformations and other cognitive and behavioral issues in children, women of childbearing age who are using valproate or considering a prescription should be counseled for informed consent, Dr. Meador said.
Dr. Meador advocated additional research on the impact of antiepileptic drugs during pregnancy and risk assessment strategies, including “a national reporting system for congenital malformations, routine preclinical testing of all new antiseizure medications for neurodevelopmental effects, monitoring of antiseizure medication prescription practices for women of childbearing age to determine whether emerging knowledge is being appropriately applied, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms of anatomical and behavioral teratogenesis from antiseizure medications.”
Dr. Meador is affiliated with the department of neurology and neurological sciences at Stanford (Calif.) University. He disclosed research support from the National Institutes of Health and Sunovion, and travel support from UCB. The Epilepsy Study Consortium pays Stanford University for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB, and Vivus.
The data from the current study differ from a recent meta-analysis of five studies that did not find a statistically significant increase in ADHD risk in children associated with prenatal valproate exposure, Kimford J. Meador, MD, wrote in an accompanying editorial (JAMA Network Open. 2019;2[1]:e186603. doi: 10.1001/jamanetworkopen.2018.6603).
“The discrepancy between the present study and the prior meta-analysis might be due to the meta-analysis using different analytical approaches and examining studies with smaller sample sizes, higher attrition rates, shorter follow-ups, and cohort differences,” Dr. Meador said. “Nevertheless, the findings by Christensen et al. are consistent with multiple studies demonstrating adverse neurodevelopmental effects associated with fetal valproate exposure.”
Given the potential risks associated with valproate exposure not only for behavior problems such as ADHD but also for congenital malformations and other cognitive and behavioral issues in children, women of childbearing age who are using valproate or considering a prescription should be counseled for informed consent, Dr. Meador said.
Dr. Meador advocated additional research on the impact of antiepileptic drugs during pregnancy and risk assessment strategies, including “a national reporting system for congenital malformations, routine preclinical testing of all new antiseizure medications for neurodevelopmental effects, monitoring of antiseizure medication prescription practices for women of childbearing age to determine whether emerging knowledge is being appropriately applied, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms of anatomical and behavioral teratogenesis from antiseizure medications.”
Dr. Meador is affiliated with the department of neurology and neurological sciences at Stanford (Calif.) University. He disclosed research support from the National Institutes of Health and Sunovion, and travel support from UCB. The Epilepsy Study Consortium pays Stanford University for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB, and Vivus.
Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.
Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.
The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.
Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.
A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.
The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.
“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.
However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.
The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.
Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.
The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.
Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.
A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.
The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.
“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.
However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.
The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
FROM JAMA NETWORK OPEN
Key clinical point:
Major finding: The children whose mothers used valproate between 90 days before conception and birth had a 48% increased risk of ADHD compared with children whose mothers did not use valproate.
Study details: The data come from a population-based cohort study of 913,302 children in Denmark.
Disclosures: The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
Source: SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
Biomarkers predict asthma/COPD risk in 9/11 first responders
Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.
Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.
In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.
In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).
In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.
The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.
However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.
The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.
SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.
Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.
Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.
In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.
In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).
In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.
The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.
However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.
The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.
SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.
Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.
Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.
In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.
In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).
In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.
The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.
However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.
The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.
SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.
FROM CHEST
Key clinical point: Firefighters exposed to toxins at the World Trade Center on 9/11 who demonstrated elevated blood eosinophils and IL-4 levels were at increased risk for subsequent asthma/chronic obstructive pulmonary disease overlap.
Major finding: Increased eosinophils (300 cells/mcL or higher) was significantly associated with asthma/chronic obstructive pulmonary disease overlap (hazard ratio, 1.85).
Study details: The data come from 2,137 firefighters exposed to toxins at the World Trade Center in New York on 9/11.
Disclosures: The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.
Source: Singh A et al. CHEST. 2018 Dec; 154;1301-10.
Aspirin appears underused to prevent preeclampsia in SLE patients
Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.
Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.
The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).
Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.
The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.
Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.
“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.
The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.
The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.
SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.
Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.
Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.
The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).
Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.
The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.
Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.
“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.
The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.
The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.
SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.
Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.
Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.
The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).
Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.
The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.
Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.
“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.
The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.
The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.
SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: Aspirin use was low among pregnant systemic lupus erythematosus patients despite risk factors for preeclampsia.
Major finding: Approximately 25% of women with systemic lupus erythematosus took aspirin during pregnancy.
Study details: The data come from a prospective study of 300 women and 475 pregnancies.
Disclosures: The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.
Source: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.