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AHA: Consider obesity as CVD risk factor in children
The American Heart Association has included obesity and severe obesity in its updated scientific statement outlining risk factors and considerations for cardiovascular risk reduction in high-risk pediatric patients.
The scientific statement is an update to a 2006 American Heart Association (AHA) statement, adding details about obesity as an at-risk condition and severe obesity as a moderate-risk condition. Other additions include classifying type 2 diabetes as a high-risk condition and expanding on new risk factors for cardiovascular disease (CVD) among patients who received treatment for childhood cancer.
The AHA said the statement is aimed at pediatric cardiologists, primary care physicians, and subspecialists who care for at-risk pediatric patients, as well as providers who will care for these patients as they transition to adult life.
Obesity
In the AHA scientific statement, Sarah de Ferranti, MD, MPH, of Boston Children’s Hospital, chair of the writing group, and her colleagues, highlighted a 2016 study that identified a twofold to threefold higher risk of CVD-related mortality among patients who were overweight or obese, compared with patients of normal weight (Diabetes Care. 2016 Nov;39[11]:1996-2003).
Patients with obesity and severe obesity are at increased risk of aortic or coronary fatty streaks, dyslipidemia, high blood pressure, hyperglycemia, and insulin resistance, as well as inflammatory and oxidative stress, the AHA writing group noted.
They estimated that approximately 6% of U.S. children aged 2-19 years old are considered severely obese.
After identifying patients with obesity, the writing group said, a “multimodal and graduated approach to treatment” for these patients is generally warranted, with a focus on dietary and lifestyle changes, and use of pharmacotherapy and bariatric surgery if indicated.
However, the authors said therapeutic life change modification “is limited in severe obesity because of small effect size and difficulty with sustainability,” while use of pharmacotherapy for treatment of pediatric obesity remains understudied and medications such as orlistat and metformin offer only modest weight loss.
Bariatric surgery, “the only treatment for severe pediatric obesity consistently associated with clinically meaningful and durable weight loss,” is not consistently offered to patients under 12 years old, they added.
Diabetes
The AHA statement also addresses risks from type 1 (T1D) and type 2 diabetes (T2D). Children with T1D and T2D are at increased risk for dyslipidemia, hypertension, microalbuminuria, and obesity. Annual screening for these patients is indicated, and cardiovascular risk factor reduction can be achieved by managing hyperglycemia, controlling weight gain as a result of medication, and implementing therapeutic lifestyle changes, when possible.
Childhood cancer
As survival rates from childhood cancer have improved, there is a need to address the increased risk of cardiovascular-related mortality (estimated at 8-10 times higher than the general population) as well as cancer relapse, according to the writing group.
Among patients recruited to the Childhood Cancer Survivor Study, there was a 9-fold increase in cerebrovascular accident, 10-fold increased risk of coronary artery disease, and 15-fold increase in heart failure for childhood cancer survivors, compared with their siblings who were cancer free.
Cancer treatments such as radiation exposure are linked to increased rates of myocardial infarction, heart failure, valvular abnormalities, and pericardial disease at a twofold to sixfold higher rate when administered at a greater than 1,500 centigray dose, compared to cancer survivors who did not receive radiation, the authors wrote.
Anthracycline treatment is associated with a dose-dependent increase in the risk of dilated cardiomyopathy, while hematopoietic stem cell transplantation may increase the risk of CVD-related mortality from heart failure, cerebrovascular accident, cardiomyopathy, coronary artery disease, and rhythm disorders.
In treating childhood cancer survivors for CVD risk factors, “a low threshold should be used when considering the initiation of pharmacological agents because of the high risk of these youth,” and standard pharmacotherapies can be used, the authors said. “Treatment of cardiovascular risk factors should consider the cancer therapies the patient has received previously.”
In the AHA statement, Dr. de Ferranti and her colleagues also outlined epidemiology, screening, and treatment data for other cardiovascular risk factors such as familial hypercholesterolemia, Lipoprotein(a), hypertension, chronic kidney disease, congenital heart disease, Kawasaki disease, and heart transplantation.
Some members of the writing group reported research grants from Amgen, Sanofi, the Wisconsin Partnership Program, and the National Institutes of Health. One author reported unpaid consultancies with Novo Nordisk, Orexigen, and Vivus.
SOURCE: de Ferranti SD et al. Circulation. 2019 Feb 25. doi: 10.1161/CIR.0000000000000618.
The American Heart Association has included obesity and severe obesity in its updated scientific statement outlining risk factors and considerations for cardiovascular risk reduction in high-risk pediatric patients.
The scientific statement is an update to a 2006 American Heart Association (AHA) statement, adding details about obesity as an at-risk condition and severe obesity as a moderate-risk condition. Other additions include classifying type 2 diabetes as a high-risk condition and expanding on new risk factors for cardiovascular disease (CVD) among patients who received treatment for childhood cancer.
The AHA said the statement is aimed at pediatric cardiologists, primary care physicians, and subspecialists who care for at-risk pediatric patients, as well as providers who will care for these patients as they transition to adult life.
Obesity
In the AHA scientific statement, Sarah de Ferranti, MD, MPH, of Boston Children’s Hospital, chair of the writing group, and her colleagues, highlighted a 2016 study that identified a twofold to threefold higher risk of CVD-related mortality among patients who were overweight or obese, compared with patients of normal weight (Diabetes Care. 2016 Nov;39[11]:1996-2003).
Patients with obesity and severe obesity are at increased risk of aortic or coronary fatty streaks, dyslipidemia, high blood pressure, hyperglycemia, and insulin resistance, as well as inflammatory and oxidative stress, the AHA writing group noted.
They estimated that approximately 6% of U.S. children aged 2-19 years old are considered severely obese.
After identifying patients with obesity, the writing group said, a “multimodal and graduated approach to treatment” for these patients is generally warranted, with a focus on dietary and lifestyle changes, and use of pharmacotherapy and bariatric surgery if indicated.
However, the authors said therapeutic life change modification “is limited in severe obesity because of small effect size and difficulty with sustainability,” while use of pharmacotherapy for treatment of pediatric obesity remains understudied and medications such as orlistat and metformin offer only modest weight loss.
Bariatric surgery, “the only treatment for severe pediatric obesity consistently associated with clinically meaningful and durable weight loss,” is not consistently offered to patients under 12 years old, they added.
Diabetes
The AHA statement also addresses risks from type 1 (T1D) and type 2 diabetes (T2D). Children with T1D and T2D are at increased risk for dyslipidemia, hypertension, microalbuminuria, and obesity. Annual screening for these patients is indicated, and cardiovascular risk factor reduction can be achieved by managing hyperglycemia, controlling weight gain as a result of medication, and implementing therapeutic lifestyle changes, when possible.
Childhood cancer
As survival rates from childhood cancer have improved, there is a need to address the increased risk of cardiovascular-related mortality (estimated at 8-10 times higher than the general population) as well as cancer relapse, according to the writing group.
Among patients recruited to the Childhood Cancer Survivor Study, there was a 9-fold increase in cerebrovascular accident, 10-fold increased risk of coronary artery disease, and 15-fold increase in heart failure for childhood cancer survivors, compared with their siblings who were cancer free.
Cancer treatments such as radiation exposure are linked to increased rates of myocardial infarction, heart failure, valvular abnormalities, and pericardial disease at a twofold to sixfold higher rate when administered at a greater than 1,500 centigray dose, compared to cancer survivors who did not receive radiation, the authors wrote.
Anthracycline treatment is associated with a dose-dependent increase in the risk of dilated cardiomyopathy, while hematopoietic stem cell transplantation may increase the risk of CVD-related mortality from heart failure, cerebrovascular accident, cardiomyopathy, coronary artery disease, and rhythm disorders.
In treating childhood cancer survivors for CVD risk factors, “a low threshold should be used when considering the initiation of pharmacological agents because of the high risk of these youth,” and standard pharmacotherapies can be used, the authors said. “Treatment of cardiovascular risk factors should consider the cancer therapies the patient has received previously.”
In the AHA statement, Dr. de Ferranti and her colleagues also outlined epidemiology, screening, and treatment data for other cardiovascular risk factors such as familial hypercholesterolemia, Lipoprotein(a), hypertension, chronic kidney disease, congenital heart disease, Kawasaki disease, and heart transplantation.
Some members of the writing group reported research grants from Amgen, Sanofi, the Wisconsin Partnership Program, and the National Institutes of Health. One author reported unpaid consultancies with Novo Nordisk, Orexigen, and Vivus.
SOURCE: de Ferranti SD et al. Circulation. 2019 Feb 25. doi: 10.1161/CIR.0000000000000618.
The American Heart Association has included obesity and severe obesity in its updated scientific statement outlining risk factors and considerations for cardiovascular risk reduction in high-risk pediatric patients.
The scientific statement is an update to a 2006 American Heart Association (AHA) statement, adding details about obesity as an at-risk condition and severe obesity as a moderate-risk condition. Other additions include classifying type 2 diabetes as a high-risk condition and expanding on new risk factors for cardiovascular disease (CVD) among patients who received treatment for childhood cancer.
The AHA said the statement is aimed at pediatric cardiologists, primary care physicians, and subspecialists who care for at-risk pediatric patients, as well as providers who will care for these patients as they transition to adult life.
Obesity
In the AHA scientific statement, Sarah de Ferranti, MD, MPH, of Boston Children’s Hospital, chair of the writing group, and her colleagues, highlighted a 2016 study that identified a twofold to threefold higher risk of CVD-related mortality among patients who were overweight or obese, compared with patients of normal weight (Diabetes Care. 2016 Nov;39[11]:1996-2003).
Patients with obesity and severe obesity are at increased risk of aortic or coronary fatty streaks, dyslipidemia, high blood pressure, hyperglycemia, and insulin resistance, as well as inflammatory and oxidative stress, the AHA writing group noted.
They estimated that approximately 6% of U.S. children aged 2-19 years old are considered severely obese.
After identifying patients with obesity, the writing group said, a “multimodal and graduated approach to treatment” for these patients is generally warranted, with a focus on dietary and lifestyle changes, and use of pharmacotherapy and bariatric surgery if indicated.
However, the authors said therapeutic life change modification “is limited in severe obesity because of small effect size and difficulty with sustainability,” while use of pharmacotherapy for treatment of pediatric obesity remains understudied and medications such as orlistat and metformin offer only modest weight loss.
Bariatric surgery, “the only treatment for severe pediatric obesity consistently associated with clinically meaningful and durable weight loss,” is not consistently offered to patients under 12 years old, they added.
Diabetes
The AHA statement also addresses risks from type 1 (T1D) and type 2 diabetes (T2D). Children with T1D and T2D are at increased risk for dyslipidemia, hypertension, microalbuminuria, and obesity. Annual screening for these patients is indicated, and cardiovascular risk factor reduction can be achieved by managing hyperglycemia, controlling weight gain as a result of medication, and implementing therapeutic lifestyle changes, when possible.
Childhood cancer
As survival rates from childhood cancer have improved, there is a need to address the increased risk of cardiovascular-related mortality (estimated at 8-10 times higher than the general population) as well as cancer relapse, according to the writing group.
Among patients recruited to the Childhood Cancer Survivor Study, there was a 9-fold increase in cerebrovascular accident, 10-fold increased risk of coronary artery disease, and 15-fold increase in heart failure for childhood cancer survivors, compared with their siblings who were cancer free.
Cancer treatments such as radiation exposure are linked to increased rates of myocardial infarction, heart failure, valvular abnormalities, and pericardial disease at a twofold to sixfold higher rate when administered at a greater than 1,500 centigray dose, compared to cancer survivors who did not receive radiation, the authors wrote.
Anthracycline treatment is associated with a dose-dependent increase in the risk of dilated cardiomyopathy, while hematopoietic stem cell transplantation may increase the risk of CVD-related mortality from heart failure, cerebrovascular accident, cardiomyopathy, coronary artery disease, and rhythm disorders.
In treating childhood cancer survivors for CVD risk factors, “a low threshold should be used when considering the initiation of pharmacological agents because of the high risk of these youth,” and standard pharmacotherapies can be used, the authors said. “Treatment of cardiovascular risk factors should consider the cancer therapies the patient has received previously.”
In the AHA statement, Dr. de Ferranti and her colleagues also outlined epidemiology, screening, and treatment data for other cardiovascular risk factors such as familial hypercholesterolemia, Lipoprotein(a), hypertension, chronic kidney disease, congenital heart disease, Kawasaki disease, and heart transplantation.
Some members of the writing group reported research grants from Amgen, Sanofi, the Wisconsin Partnership Program, and the National Institutes of Health. One author reported unpaid consultancies with Novo Nordisk, Orexigen, and Vivus.
SOURCE: de Ferranti SD et al. Circulation. 2019 Feb 25. doi: 10.1161/CIR.0000000000000618.
FROM CIRCULATION
Induction at 41 weeks may cut perinatal complications for low-risk pregnancies
Inducing labor at 41 weeks’ gestation for women with low-risk pregnancies was associated with a 1.4% lower risk of adverse perinatal outcomes, compared with expectant management until 42 weeks, according to results from a randomized, controlled noninferiority trial.
“As with every intervention in the natural birth process, the decision to induce labour must be made with caution, as the expected benefits should outweigh possible adverse effects for both mother and child,” wrote Judit K.J. Keulen, of the department of obstetrics and gynecology at Amsterdam University Medical Center, and her colleagues. “The results of our study should be used to inform women approaching a gestational age of 41 weeks, so they can weigh the respective outcomes and decide whether to be induced at 41 weeks or to continue pregnancy until 42 weeks.”
Ms. Keulen and her colleagues randomized 1,801 women from 123 primary care midwifery practices and 45 hospitals across the Netherlands to receive induction (n = 900) at 41 weeks or expectant management (n = 901) at 42 weeks between 2012 and 2016. The investigators used a composite of perinatal mortality measures, which included Apgar score less than 7 at 5 minutes, arterial pH less than 7.05, meconium aspiration syndrome, neonatal ICU admission, intracranial hemorrhage, and/or brachial plexus injury.
Overall, there were 15 adverse perinatal outcomes in the induction group (1.7%) and 28 adverse outcomes in the expectant management group (3.1%; absolute risk difference, −1.4%). A lower number of infants (n = 11; 1.2%) in the induction group had an Apgar score less than 7 at 5 minutes, compared with infants (n = 23; 2.6%) in the expectant management group (relative risk, 0.48), and there were zero infants and 3 infants (RR, 0.3%) in the induction and expectant management groups, respectively, who had an Apgar score less than 4 at 5 minutes.
Three (0.3%) infants in the induction group and 8 (0.9%) infants in the expectant management group were admitted to the NICU (RR, 0.38). There was one (0.1%) case of fetal death in the induction group and two (0.2%) cases in the expectant management group, but there were no neonatal deaths in either group. With regard to composite adverse maternal outcomes, there were no significant differences between the induction group (n = 122; 14%) and the expectant management group (n = 102; 11%) and both groups had the same number of cesarean sections (n = 97; 11%).
The investigators noted several limitations, such as the noninferiority study design, use of composite adverse perinatal outcome, and lack of stratification by parity that led to an imbalance between the induction and expectant management groups.
“If the composite outcome is interpreted straightforwardly, there is a small benefit of induction at 41 weeks that could justify standard induction at 41 weeks,” Ms. Keulen and colleagues wrote.
“It could be argued, however, that a change of policy to earlier induction, concerning roughly one-fifth of all women with a singleton pregnancy, is too rigorous in light of the relatively low incidence of perinatal mortality, gestational age associated NICU admission, and Apgar score less than 4 at 5 minutes as indicator for encephalopathy,” they added. “This could justify expectant management if women want to avoid induction.”
This study was supported by a grant from the Netherlands Organisation for Health Research and Development ZonMw. Dr. Ben Willem Mol reported a practitioner fellowship with the National Health and Medical Research Council and is a consultant for ObsEva, Merck, and Guerbet. The other authors reported no relevant conflicts of interest.
SOURCE: Keulen JKJ et al. BMJ. 2019 Feb 20. doi: 10.1136/bmj.l344.
In the United States, the current guidelines state that you should consider induction of labor between 41 0/7 and 41 6/7 weeks of gestation and recommend induction between 42 0/7 and 42 6/7 weeks. This study demonstrates that there is a high rate of spontaneous labor among women who are managed with expectant management. Of the women randomized to the expectant management group, only 19% had not gone into labor by 42 weeks and thus, ultimately required induction.
In addition, there is only a 2-day difference in the gestational age of delivery between the induction and expectant management groups. The difference of 2 days does not change the rate of cesarean section or meconium aspiration system. There was a decrease in the rate of the composite neonatal outcome with induction which was mainly related to Apgar less than 7 at 5 minutes. Other significant neonatal outcomes were very rare in the study population (3 vs. 8 neonatal ICU admissions and 0 vs. 2 meconium aspiration).
However, arterial pH, a common marker of adverse neonatal outcomes, was not collected in 70% of the individuals enrolled this study. The rare rate of neonatal complications may reflect the relatively homogenous (about 86% white) and healthy population (about 11% of body mass index greater than or equal to 30).
Further, the lack of difference must be looked at with some caution as the rate of cesarean sections in the study population (11%) is much lower than the cesarean section rate in the United States of 32%. The absolute number of neonates with meconium aspiration system is very low in the study (0.2% for expectant management and none with induction). Previous studies on this subject have demonstrated rates 10-fold higher than in this current study.
In a related editorial, Kenyon et al. are correct in noting that by excluding Apgar scores, the composite adverse neonatal outcome loses its statistical significance (BMJ 2019 Feb 20. doi: 10.1136/bmj.l681). But, the study did not routinely collect arterial pH, which could be an objective measure of neonatal acidemia; thus, Apgar less than 7 at 5 minutes has to remain, as it is associated with neonatal acidemia. Induction should be part of the decision making for patients who are approaching post term. While an induction may alter a birth experience, some individuals opt for this method as evident by 616 individuals who refused enrollment because they desired induction at 41 weeks or the 87 individuals in the expectant management group who desired induction prior to 42 weeks. Thus, this study allows the clinician to provide counseling about the patient’s desires for management of their pregnancy with more information about neonatal outcomes with both expectant management and induction.
This trial, as well as the ARRIVE trial, have studied the effects of induction on a composite neonatal outcome. Both studies note statistical significance with the composite outcome but secondary to rare outcomes, statistical significance is not demonstrated when you look at each individual outcome. The study by Keulen et al. may help guide clinicians in counseling patients about the timing of their induction at late term. In the low-risk patient, these findings may help guide in the timing of induction.
Sarah D. Crimmins, DO, is an assistant professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland, Baltimore, and specializes in maternal-fetal medicine. She was asked to comment on the article by Keulen et al. Dr. Crimmins reported having no conflicts of interest.
In the United States, the current guidelines state that you should consider induction of labor between 41 0/7 and 41 6/7 weeks of gestation and recommend induction between 42 0/7 and 42 6/7 weeks. This study demonstrates that there is a high rate of spontaneous labor among women who are managed with expectant management. Of the women randomized to the expectant management group, only 19% had not gone into labor by 42 weeks and thus, ultimately required induction.
In addition, there is only a 2-day difference in the gestational age of delivery between the induction and expectant management groups. The difference of 2 days does not change the rate of cesarean section or meconium aspiration system. There was a decrease in the rate of the composite neonatal outcome with induction which was mainly related to Apgar less than 7 at 5 minutes. Other significant neonatal outcomes were very rare in the study population (3 vs. 8 neonatal ICU admissions and 0 vs. 2 meconium aspiration).
However, arterial pH, a common marker of adverse neonatal outcomes, was not collected in 70% of the individuals enrolled this study. The rare rate of neonatal complications may reflect the relatively homogenous (about 86% white) and healthy population (about 11% of body mass index greater than or equal to 30).
Further, the lack of difference must be looked at with some caution as the rate of cesarean sections in the study population (11%) is much lower than the cesarean section rate in the United States of 32%. The absolute number of neonates with meconium aspiration system is very low in the study (0.2% for expectant management and none with induction). Previous studies on this subject have demonstrated rates 10-fold higher than in this current study.
In a related editorial, Kenyon et al. are correct in noting that by excluding Apgar scores, the composite adverse neonatal outcome loses its statistical significance (BMJ 2019 Feb 20. doi: 10.1136/bmj.l681). But, the study did not routinely collect arterial pH, which could be an objective measure of neonatal acidemia; thus, Apgar less than 7 at 5 minutes has to remain, as it is associated with neonatal acidemia. Induction should be part of the decision making for patients who are approaching post term. While an induction may alter a birth experience, some individuals opt for this method as evident by 616 individuals who refused enrollment because they desired induction at 41 weeks or the 87 individuals in the expectant management group who desired induction prior to 42 weeks. Thus, this study allows the clinician to provide counseling about the patient’s desires for management of their pregnancy with more information about neonatal outcomes with both expectant management and induction.
This trial, as well as the ARRIVE trial, have studied the effects of induction on a composite neonatal outcome. Both studies note statistical significance with the composite outcome but secondary to rare outcomes, statistical significance is not demonstrated when you look at each individual outcome. The study by Keulen et al. may help guide clinicians in counseling patients about the timing of their induction at late term. In the low-risk patient, these findings may help guide in the timing of induction.
Sarah D. Crimmins, DO, is an assistant professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland, Baltimore, and specializes in maternal-fetal medicine. She was asked to comment on the article by Keulen et al. Dr. Crimmins reported having no conflicts of interest.
In the United States, the current guidelines state that you should consider induction of labor between 41 0/7 and 41 6/7 weeks of gestation and recommend induction between 42 0/7 and 42 6/7 weeks. This study demonstrates that there is a high rate of spontaneous labor among women who are managed with expectant management. Of the women randomized to the expectant management group, only 19% had not gone into labor by 42 weeks and thus, ultimately required induction.
In addition, there is only a 2-day difference in the gestational age of delivery between the induction and expectant management groups. The difference of 2 days does not change the rate of cesarean section or meconium aspiration system. There was a decrease in the rate of the composite neonatal outcome with induction which was mainly related to Apgar less than 7 at 5 minutes. Other significant neonatal outcomes were very rare in the study population (3 vs. 8 neonatal ICU admissions and 0 vs. 2 meconium aspiration).
However, arterial pH, a common marker of adverse neonatal outcomes, was not collected in 70% of the individuals enrolled this study. The rare rate of neonatal complications may reflect the relatively homogenous (about 86% white) and healthy population (about 11% of body mass index greater than or equal to 30).
Further, the lack of difference must be looked at with some caution as the rate of cesarean sections in the study population (11%) is much lower than the cesarean section rate in the United States of 32%. The absolute number of neonates with meconium aspiration system is very low in the study (0.2% for expectant management and none with induction). Previous studies on this subject have demonstrated rates 10-fold higher than in this current study.
In a related editorial, Kenyon et al. are correct in noting that by excluding Apgar scores, the composite adverse neonatal outcome loses its statistical significance (BMJ 2019 Feb 20. doi: 10.1136/bmj.l681). But, the study did not routinely collect arterial pH, which could be an objective measure of neonatal acidemia; thus, Apgar less than 7 at 5 minutes has to remain, as it is associated with neonatal acidemia. Induction should be part of the decision making for patients who are approaching post term. While an induction may alter a birth experience, some individuals opt for this method as evident by 616 individuals who refused enrollment because they desired induction at 41 weeks or the 87 individuals in the expectant management group who desired induction prior to 42 weeks. Thus, this study allows the clinician to provide counseling about the patient’s desires for management of their pregnancy with more information about neonatal outcomes with both expectant management and induction.
This trial, as well as the ARRIVE trial, have studied the effects of induction on a composite neonatal outcome. Both studies note statistical significance with the composite outcome but secondary to rare outcomes, statistical significance is not demonstrated when you look at each individual outcome. The study by Keulen et al. may help guide clinicians in counseling patients about the timing of their induction at late term. In the low-risk patient, these findings may help guide in the timing of induction.
Sarah D. Crimmins, DO, is an assistant professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland, Baltimore, and specializes in maternal-fetal medicine. She was asked to comment on the article by Keulen et al. Dr. Crimmins reported having no conflicts of interest.
Inducing labor at 41 weeks’ gestation for women with low-risk pregnancies was associated with a 1.4% lower risk of adverse perinatal outcomes, compared with expectant management until 42 weeks, according to results from a randomized, controlled noninferiority trial.
“As with every intervention in the natural birth process, the decision to induce labour must be made with caution, as the expected benefits should outweigh possible adverse effects for both mother and child,” wrote Judit K.J. Keulen, of the department of obstetrics and gynecology at Amsterdam University Medical Center, and her colleagues. “The results of our study should be used to inform women approaching a gestational age of 41 weeks, so they can weigh the respective outcomes and decide whether to be induced at 41 weeks or to continue pregnancy until 42 weeks.”
Ms. Keulen and her colleagues randomized 1,801 women from 123 primary care midwifery practices and 45 hospitals across the Netherlands to receive induction (n = 900) at 41 weeks or expectant management (n = 901) at 42 weeks between 2012 and 2016. The investigators used a composite of perinatal mortality measures, which included Apgar score less than 7 at 5 minutes, arterial pH less than 7.05, meconium aspiration syndrome, neonatal ICU admission, intracranial hemorrhage, and/or brachial plexus injury.
Overall, there were 15 adverse perinatal outcomes in the induction group (1.7%) and 28 adverse outcomes in the expectant management group (3.1%; absolute risk difference, −1.4%). A lower number of infants (n = 11; 1.2%) in the induction group had an Apgar score less than 7 at 5 minutes, compared with infants (n = 23; 2.6%) in the expectant management group (relative risk, 0.48), and there were zero infants and 3 infants (RR, 0.3%) in the induction and expectant management groups, respectively, who had an Apgar score less than 4 at 5 minutes.
Three (0.3%) infants in the induction group and 8 (0.9%) infants in the expectant management group were admitted to the NICU (RR, 0.38). There was one (0.1%) case of fetal death in the induction group and two (0.2%) cases in the expectant management group, but there were no neonatal deaths in either group. With regard to composite adverse maternal outcomes, there were no significant differences between the induction group (n = 122; 14%) and the expectant management group (n = 102; 11%) and both groups had the same number of cesarean sections (n = 97; 11%).
The investigators noted several limitations, such as the noninferiority study design, use of composite adverse perinatal outcome, and lack of stratification by parity that led to an imbalance between the induction and expectant management groups.
“If the composite outcome is interpreted straightforwardly, there is a small benefit of induction at 41 weeks that could justify standard induction at 41 weeks,” Ms. Keulen and colleagues wrote.
“It could be argued, however, that a change of policy to earlier induction, concerning roughly one-fifth of all women with a singleton pregnancy, is too rigorous in light of the relatively low incidence of perinatal mortality, gestational age associated NICU admission, and Apgar score less than 4 at 5 minutes as indicator for encephalopathy,” they added. “This could justify expectant management if women want to avoid induction.”
This study was supported by a grant from the Netherlands Organisation for Health Research and Development ZonMw. Dr. Ben Willem Mol reported a practitioner fellowship with the National Health and Medical Research Council and is a consultant for ObsEva, Merck, and Guerbet. The other authors reported no relevant conflicts of interest.
SOURCE: Keulen JKJ et al. BMJ. 2019 Feb 20. doi: 10.1136/bmj.l344.
Inducing labor at 41 weeks’ gestation for women with low-risk pregnancies was associated with a 1.4% lower risk of adverse perinatal outcomes, compared with expectant management until 42 weeks, according to results from a randomized, controlled noninferiority trial.
“As with every intervention in the natural birth process, the decision to induce labour must be made with caution, as the expected benefits should outweigh possible adverse effects for both mother and child,” wrote Judit K.J. Keulen, of the department of obstetrics and gynecology at Amsterdam University Medical Center, and her colleagues. “The results of our study should be used to inform women approaching a gestational age of 41 weeks, so they can weigh the respective outcomes and decide whether to be induced at 41 weeks or to continue pregnancy until 42 weeks.”
Ms. Keulen and her colleagues randomized 1,801 women from 123 primary care midwifery practices and 45 hospitals across the Netherlands to receive induction (n = 900) at 41 weeks or expectant management (n = 901) at 42 weeks between 2012 and 2016. The investigators used a composite of perinatal mortality measures, which included Apgar score less than 7 at 5 minutes, arterial pH less than 7.05, meconium aspiration syndrome, neonatal ICU admission, intracranial hemorrhage, and/or brachial plexus injury.
Overall, there were 15 adverse perinatal outcomes in the induction group (1.7%) and 28 adverse outcomes in the expectant management group (3.1%; absolute risk difference, −1.4%). A lower number of infants (n = 11; 1.2%) in the induction group had an Apgar score less than 7 at 5 minutes, compared with infants (n = 23; 2.6%) in the expectant management group (relative risk, 0.48), and there were zero infants and 3 infants (RR, 0.3%) in the induction and expectant management groups, respectively, who had an Apgar score less than 4 at 5 minutes.
Three (0.3%) infants in the induction group and 8 (0.9%) infants in the expectant management group were admitted to the NICU (RR, 0.38). There was one (0.1%) case of fetal death in the induction group and two (0.2%) cases in the expectant management group, but there were no neonatal deaths in either group. With regard to composite adverse maternal outcomes, there were no significant differences between the induction group (n = 122; 14%) and the expectant management group (n = 102; 11%) and both groups had the same number of cesarean sections (n = 97; 11%).
The investigators noted several limitations, such as the noninferiority study design, use of composite adverse perinatal outcome, and lack of stratification by parity that led to an imbalance between the induction and expectant management groups.
“If the composite outcome is interpreted straightforwardly, there is a small benefit of induction at 41 weeks that could justify standard induction at 41 weeks,” Ms. Keulen and colleagues wrote.
“It could be argued, however, that a change of policy to earlier induction, concerning roughly one-fifth of all women with a singleton pregnancy, is too rigorous in light of the relatively low incidence of perinatal mortality, gestational age associated NICU admission, and Apgar score less than 4 at 5 minutes as indicator for encephalopathy,” they added. “This could justify expectant management if women want to avoid induction.”
This study was supported by a grant from the Netherlands Organisation for Health Research and Development ZonMw. Dr. Ben Willem Mol reported a practitioner fellowship with the National Health and Medical Research Council and is a consultant for ObsEva, Merck, and Guerbet. The other authors reported no relevant conflicts of interest.
SOURCE: Keulen JKJ et al. BMJ. 2019 Feb 20. doi: 10.1136/bmj.l344.
FROM BMJ
AAD, NPF release two joint guidelines on treatment, management of psoriasis
The .
These guidelines are the first of two papers to be published in the Journal of the American Academy of Dermatology (JAAD), with four more guidelines on psoriasis to be published later this year in JAAD on phototherapy, topical therapy, nonbiologic systemic medications, and treatment of pediatric patients.
The guideline on biologics updates the 2008 AAD guidelines on psoriasis. In an interview, Alan Menter, MD, cochair of the guidelines work group and lead author of the biologics paper, said the guidelines for biologics were needed because of major advances with the availability of new biologics over the last decade. For example, three tumor necrosis factor–alpha (TNF-alpha) inhibitors were available in 2008, but that number has increased to 10 biologics and now includes agents such as those targeting interleukin (IL)-12/IL-23, IL-17 and IL-23.
In addition, the new guidelines from AAD were developed to represent improvements in the management of patients with moderate to severe psoriasis as well as the relationship between psoriasis and related comorbidities.
“Major advances in new biologic drugs [are] now available to patients, plus [there have been] significant advances in our understanding of comorbid conditions,” such as cardiovascular comorbidities, said Dr. Menter, chairman of the division of dermatology, Baylor University Medical Center, and clinical professor of dermatology, University of Texas, both in Dallas.
The working group for each set of guidelines consisted of dermatologists, patient representatives, a cardiologist, and a rheumatologist. The biologic guidelines working group analyzed studies published between January 2008 and December 2018 and issued a series of recommendations based on published evidence for the effectiveness, adverse events, and switching for Food and Drug Administration–approved TNF-alpha inhibitors (etanercept, infliximab, adalimumab, certolizumab, and TNF-alpha biosimilars); IL-12/IL-23 inhibitors (ustekinumab); IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab); and IL-23 inhibitors (guselkumab and tildrakizumab, and risankizumab, which is still under FDA review) for monotherapy or combination therapy in patients with moderate to severe psoriasis.
The biologic guidelines noted that, while FDA-approved biologics were deemed safe overall for patients with moderate to severe psoriasis, dermatologists should recognize the adverse effects of these therapies, monitor for infections, and counsel their patients against modifying or discontinuing therapy without first consulting a dermatologist. In general, the working group noted that failure with one biologic does not necessarily mean that a patient will experience failure with a different biologic, even among TNF-alpha and IL-12/IL-23 inhibitors. However, reduced efficacy for a patient receiving a specific TNF-alpha inhibitor may predict reduced efficacy when switching to a different TNF-alpha inhibitor, they said.
In the psoriasis comorbidity guideline, the working group examined the therapeutic interventions for psoriasis-related comorbidities such as psoriatic arthritis (PsA), cardiovascular disease, metabolic syndrome, and inflammatory bowel disease. They also provided recommendations on the effect of psoriasis on mental health, quality of life, and lifestyle choices such as smoking and alcohol use.
With respect to cardiovascular disease, the dermatologist should ensure that patients are aware of the association between risk factors for cardiovascular disease and psoriasis, and that they undergo screening for these risk factors, consider lifestyle changes to reduce risk of cardiovascular disease, and consult with cardiologists and primary care providers based on individual risk, the guideline states. The working group recommended that patients with psoriasis undergo screening for hypertension, diabetes, and hyperlipidemia based on national guidelines, with more frequent screening recommended for patients with psoriasis greater than 10% body surface area or who are eligible for systemic or phototherapy.
In both the biologic and the comorbidity guidelines, the working groups stressed the importance of patient education and the role of the dermatologist in educating patients so that shared decision-making can occur. They noted that education was related to improved quality of life for these patients.
“Both the comorbidities guidelines and the biologic guidelines will help educate the psoriasis population with input from dermatologists in clinical practices,” Dr. Menter said.
However, both working groups noted there are still significant gaps in research, such as the effects of treatment combinations for new biologics and the lack of biomarkers that would identify which biologics are best suited for individual psoriasis patients.
There is also little known about the complex relationship between psoriasis and its comorbidities, and how psoriasis treatment can potentially prevent future disease. To ensure treatment of psoriasis-related comorbidities, dermatologists should consider psoriasis as a systemic disease with multiple comorbidities and interact with primary care doctors, cardiologists, and other providers involved in the care of the patients, Dr. Menter said.
There were no specific funding sources reported for the guidelines. Several authors reported relationships with industry, including pharmaceutical companies with drugs and products involving psoriasis, during the development of the guidelines. If a potential conflict was noted, the working group member recused himself or herself from discussion and drafting of recommendations, according to the paper. Dr. Menter’s disclosure includes serving as a consultant, speaker, investigator, and adviser, and receiving honoraria, from multiple pharmaceutical companies.
SOURCE: Menter A et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.057. Elmets CA et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.058.
The .
These guidelines are the first of two papers to be published in the Journal of the American Academy of Dermatology (JAAD), with four more guidelines on psoriasis to be published later this year in JAAD on phototherapy, topical therapy, nonbiologic systemic medications, and treatment of pediatric patients.
The guideline on biologics updates the 2008 AAD guidelines on psoriasis. In an interview, Alan Menter, MD, cochair of the guidelines work group and lead author of the biologics paper, said the guidelines for biologics were needed because of major advances with the availability of new biologics over the last decade. For example, three tumor necrosis factor–alpha (TNF-alpha) inhibitors were available in 2008, but that number has increased to 10 biologics and now includes agents such as those targeting interleukin (IL)-12/IL-23, IL-17 and IL-23.
In addition, the new guidelines from AAD were developed to represent improvements in the management of patients with moderate to severe psoriasis as well as the relationship between psoriasis and related comorbidities.
“Major advances in new biologic drugs [are] now available to patients, plus [there have been] significant advances in our understanding of comorbid conditions,” such as cardiovascular comorbidities, said Dr. Menter, chairman of the division of dermatology, Baylor University Medical Center, and clinical professor of dermatology, University of Texas, both in Dallas.
The working group for each set of guidelines consisted of dermatologists, patient representatives, a cardiologist, and a rheumatologist. The biologic guidelines working group analyzed studies published between January 2008 and December 2018 and issued a series of recommendations based on published evidence for the effectiveness, adverse events, and switching for Food and Drug Administration–approved TNF-alpha inhibitors (etanercept, infliximab, adalimumab, certolizumab, and TNF-alpha biosimilars); IL-12/IL-23 inhibitors (ustekinumab); IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab); and IL-23 inhibitors (guselkumab and tildrakizumab, and risankizumab, which is still under FDA review) for monotherapy or combination therapy in patients with moderate to severe psoriasis.
The biologic guidelines noted that, while FDA-approved biologics were deemed safe overall for patients with moderate to severe psoriasis, dermatologists should recognize the adverse effects of these therapies, monitor for infections, and counsel their patients against modifying or discontinuing therapy without first consulting a dermatologist. In general, the working group noted that failure with one biologic does not necessarily mean that a patient will experience failure with a different biologic, even among TNF-alpha and IL-12/IL-23 inhibitors. However, reduced efficacy for a patient receiving a specific TNF-alpha inhibitor may predict reduced efficacy when switching to a different TNF-alpha inhibitor, they said.
In the psoriasis comorbidity guideline, the working group examined the therapeutic interventions for psoriasis-related comorbidities such as psoriatic arthritis (PsA), cardiovascular disease, metabolic syndrome, and inflammatory bowel disease. They also provided recommendations on the effect of psoriasis on mental health, quality of life, and lifestyle choices such as smoking and alcohol use.
With respect to cardiovascular disease, the dermatologist should ensure that patients are aware of the association between risk factors for cardiovascular disease and psoriasis, and that they undergo screening for these risk factors, consider lifestyle changes to reduce risk of cardiovascular disease, and consult with cardiologists and primary care providers based on individual risk, the guideline states. The working group recommended that patients with psoriasis undergo screening for hypertension, diabetes, and hyperlipidemia based on national guidelines, with more frequent screening recommended for patients with psoriasis greater than 10% body surface area or who are eligible for systemic or phototherapy.
In both the biologic and the comorbidity guidelines, the working groups stressed the importance of patient education and the role of the dermatologist in educating patients so that shared decision-making can occur. They noted that education was related to improved quality of life for these patients.
“Both the comorbidities guidelines and the biologic guidelines will help educate the psoriasis population with input from dermatologists in clinical practices,” Dr. Menter said.
However, both working groups noted there are still significant gaps in research, such as the effects of treatment combinations for new biologics and the lack of biomarkers that would identify which biologics are best suited for individual psoriasis patients.
There is also little known about the complex relationship between psoriasis and its comorbidities, and how psoriasis treatment can potentially prevent future disease. To ensure treatment of psoriasis-related comorbidities, dermatologists should consider psoriasis as a systemic disease with multiple comorbidities and interact with primary care doctors, cardiologists, and other providers involved in the care of the patients, Dr. Menter said.
There were no specific funding sources reported for the guidelines. Several authors reported relationships with industry, including pharmaceutical companies with drugs and products involving psoriasis, during the development of the guidelines. If a potential conflict was noted, the working group member recused himself or herself from discussion and drafting of recommendations, according to the paper. Dr. Menter’s disclosure includes serving as a consultant, speaker, investigator, and adviser, and receiving honoraria, from multiple pharmaceutical companies.
SOURCE: Menter A et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.057. Elmets CA et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.058.
The .
These guidelines are the first of two papers to be published in the Journal of the American Academy of Dermatology (JAAD), with four more guidelines on psoriasis to be published later this year in JAAD on phototherapy, topical therapy, nonbiologic systemic medications, and treatment of pediatric patients.
The guideline on biologics updates the 2008 AAD guidelines on psoriasis. In an interview, Alan Menter, MD, cochair of the guidelines work group and lead author of the biologics paper, said the guidelines for biologics were needed because of major advances with the availability of new biologics over the last decade. For example, three tumor necrosis factor–alpha (TNF-alpha) inhibitors were available in 2008, but that number has increased to 10 biologics and now includes agents such as those targeting interleukin (IL)-12/IL-23, IL-17 and IL-23.
In addition, the new guidelines from AAD were developed to represent improvements in the management of patients with moderate to severe psoriasis as well as the relationship between psoriasis and related comorbidities.
“Major advances in new biologic drugs [are] now available to patients, plus [there have been] significant advances in our understanding of comorbid conditions,” such as cardiovascular comorbidities, said Dr. Menter, chairman of the division of dermatology, Baylor University Medical Center, and clinical professor of dermatology, University of Texas, both in Dallas.
The working group for each set of guidelines consisted of dermatologists, patient representatives, a cardiologist, and a rheumatologist. The biologic guidelines working group analyzed studies published between January 2008 and December 2018 and issued a series of recommendations based on published evidence for the effectiveness, adverse events, and switching for Food and Drug Administration–approved TNF-alpha inhibitors (etanercept, infliximab, adalimumab, certolizumab, and TNF-alpha biosimilars); IL-12/IL-23 inhibitors (ustekinumab); IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab); and IL-23 inhibitors (guselkumab and tildrakizumab, and risankizumab, which is still under FDA review) for monotherapy or combination therapy in patients with moderate to severe psoriasis.
The biologic guidelines noted that, while FDA-approved biologics were deemed safe overall for patients with moderate to severe psoriasis, dermatologists should recognize the adverse effects of these therapies, monitor for infections, and counsel their patients against modifying or discontinuing therapy without first consulting a dermatologist. In general, the working group noted that failure with one biologic does not necessarily mean that a patient will experience failure with a different biologic, even among TNF-alpha and IL-12/IL-23 inhibitors. However, reduced efficacy for a patient receiving a specific TNF-alpha inhibitor may predict reduced efficacy when switching to a different TNF-alpha inhibitor, they said.
In the psoriasis comorbidity guideline, the working group examined the therapeutic interventions for psoriasis-related comorbidities such as psoriatic arthritis (PsA), cardiovascular disease, metabolic syndrome, and inflammatory bowel disease. They also provided recommendations on the effect of psoriasis on mental health, quality of life, and lifestyle choices such as smoking and alcohol use.
With respect to cardiovascular disease, the dermatologist should ensure that patients are aware of the association between risk factors for cardiovascular disease and psoriasis, and that they undergo screening for these risk factors, consider lifestyle changes to reduce risk of cardiovascular disease, and consult with cardiologists and primary care providers based on individual risk, the guideline states. The working group recommended that patients with psoriasis undergo screening for hypertension, diabetes, and hyperlipidemia based on national guidelines, with more frequent screening recommended for patients with psoriasis greater than 10% body surface area or who are eligible for systemic or phototherapy.
In both the biologic and the comorbidity guidelines, the working groups stressed the importance of patient education and the role of the dermatologist in educating patients so that shared decision-making can occur. They noted that education was related to improved quality of life for these patients.
“Both the comorbidities guidelines and the biologic guidelines will help educate the psoriasis population with input from dermatologists in clinical practices,” Dr. Menter said.
However, both working groups noted there are still significant gaps in research, such as the effects of treatment combinations for new biologics and the lack of biomarkers that would identify which biologics are best suited for individual psoriasis patients.
There is also little known about the complex relationship between psoriasis and its comorbidities, and how psoriasis treatment can potentially prevent future disease. To ensure treatment of psoriasis-related comorbidities, dermatologists should consider psoriasis as a systemic disease with multiple comorbidities and interact with primary care doctors, cardiologists, and other providers involved in the care of the patients, Dr. Menter said.
There were no specific funding sources reported for the guidelines. Several authors reported relationships with industry, including pharmaceutical companies with drugs and products involving psoriasis, during the development of the guidelines. If a potential conflict was noted, the working group member recused himself or herself from discussion and drafting of recommendations, according to the paper. Dr. Menter’s disclosure includes serving as a consultant, speaker, investigator, and adviser, and receiving honoraria, from multiple pharmaceutical companies.
SOURCE: Menter A et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.057. Elmets CA et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.058.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Hormone therapy in transgender individuals may up risk of CV events
when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.
“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.
They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*
Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).
The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.
There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).
The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).
In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.
The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.
The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.
The study had no specific funding, and the authors reported no relevant conflicts of interest.
SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584
*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate.
when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.
“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.
They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*
Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).
The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.
There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).
The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).
In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.
The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.
The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.
The study had no specific funding, and the authors reported no relevant conflicts of interest.
SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584
*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate.
when compared with the general population, according to a study that analyzed medical records of more than 6,000 patients.
“In light of our results, we urge both physicians and transgender individuals to be aware of this increased cardiovascular risk,” first author Nienke M. Nota, MD, said in a press release for the study, which was published online Feb. 18 in Circulation. “It may be helpful to reduce risk factors by stopping smoking, exercising, eating a healthy diet, and losing weight, if needed, before starting therapy, and clinicians should continue to evaluate patients on an ongoing basis thereafter.”Dr. Nota and her colleagues at the Amsterdam University Medical Center analyzed the risk of cardiovascular events by comparing the medical records of 6,793 individuals, including only patients who received hormone therapy at their center or affiliate. They did not include those who had discontinued hormone therapy for an extended period or had alternated female and male sex hormones.
They defined transmen as indiviuals assigned female sex at birth but who had male gender identity, and transwomen as those assigned male sex at birth but with female gender identity.*
Researchers analyzed 2,517 transwomen (median age 30 years) and 1,358 transmen (median age 23 years) who received hormone therapy (defined as estrogen with and without androgen-suppressors for transwomen and testosterone for transmen) at the center gender’s clinic between 1972 and 2015. These records were compared with those of cisgender women and men (individuals whose gender identity matches their assigned birth gender).
The mean follow-up duration was 9.07 years for transwomen and 8.10 years for transmen. The researchers compared observed cases of stroke, myocardial infarction (MI), and venous thromboembolism (VTE) with expected cases using cisgender reference women and men. There were 29 stroke events, 30 MIs, and 73 VTE events for transwomen and 6 stroke, 11 MIs, and 2 VTE events for transmen.
There was a greater risk of stroke for transwomen, compared with cisgender women (standardized incidence ratio [SIR] = 2.42) and cisgender men (1.80), and a significantly greater risk of VTE, compared with cisgender women (5.52) and cisgender men (4.55).
The rate of MI was also significantly higher in transwomen, compared with cisgender women (2.64) and in transmen compared with cisgender women (3.69).
In a subgroup analysis, the researchers found ethinylestradiol use prior to 2001 did not significantly change the incident rate of cardiovascular events, but noted there was a lower rate of VTE when transwomen who began hormone therapy prior to 2001 were excluded from the analysis.
The researchers noted that hormone therapy may increase the risk of cardiovascular events in transgender individuals, in part, due to hormone therapy’s effect on cardiovascular risk factors such as lipid levels. Although a previous study analyzed the risk of cardiovascular events in transwomen and transmen, the researchers said that study could not conclude there was an increased risk of cardiovascular events for transmen.
The researchers said the results may be limited by study design, and their analysis of medical records could not account for potential confounders such as psychosocial stressors and smoking, as well as the decreasing risk of cardiovascular events over the period of the study, and assessing cardiovascular events differently than reference studies used.
The study had no specific funding, and the authors reported no relevant conflicts of interest.
SOURCE: Nota NM et al. Circulation. 2019 Feb 18. doi: 10.1161/CIRCULATIONAHA.118.038584
*Correction 2/25/2019: An earlier version of this story incorrectly defined transwomen and transmen. The definitions are now accurate.
FROM CIRCULATION
TNFi use may not affect joint replacement rates for RA patients
Patients with rheumatoid arthritis using tumor necrosis factor inhibitors do not appear to have a lower rate of joint replacement when compared with patients taking conventional synthetic disease-modifying antirheumatic drugs, according to an analysis of data in the British Society for Rheumatology Biologics Register for RA.
Although there was not a general protective effect, patients with rheumatoid arthritis (RA) who were 60 years or older had a 40% reduction in total hip replacement (THR) when using tumor necrosis factor inhibitors (TNFi), according to first author Samuel Hawley from the Nuffield Department of Orthopaedics in the Rheumatology and Musculoskeletal Sciences at the University of Oxford (England) and his colleagues.
“While a reduction in THR amongst older TNFi users offers some support for biologics playing a role in reducing need for joint replacement, it must also be noted that the lack of an overall protective effect is suggestive that other factors apart from TNFi are likely to be involved in the ... downward population trends in joint replacement rates in RA,” Mr. Hawley and his colleagues wrote in their report published in the journal Rheumatology.
The researchers analyzed prospectively collected data on 11,202 RA patients from the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) from 2001-2016 who were using TNFi (n = 9,558) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; n = 1,644). Patients had a median disease duration of 11.0 years in the TNFi group and 10.8 years in the csDMARD group. TNFi and csDMARD users were matched based on their propensity to receive treatment, and researchers used a Cox regression analysis to compare the rates of total knee replacement (TKR), THR, and other joint replacement. The researchers utilized each csDMARD user a median of three times (interquartile range, one to six) in the comparisons.
The incidence rate for THR was 5.22/1,000 person-years for TNFi users and 6.30/1,000 person-years for csDMARD users, while the incidence rate for TKR was 8.89/1,000 person-years for TNFi users and 8.09/1,000 person-years for csDMARD users. Mr. Hawley and his colleagues found no association between TNFi use and THR when compared with csDMARD users (adjusted pooled hazard ratio, 0.86; 95% confidence interval, 0.60-1.22; P = .39) based on 589 THRs during follow-up. There was also no association between the incidence of TKR and TNFi use when compared with csDMARD users (adjusted pooled HR, 1.11; 95% CI, 0.84-1.47; P = .46) based on 846 TKRs during follow-up. When the researchers examined 336 other joint replacements performed during follow-up, there was also no significant difference in incidence between TNFi and csDMARD users (HR, 1.15; 95% CI, 0.75-1.77).
For patients 60 years or older, TNFi use was associated with a 40% reduction in THR incidence (HR, 0.60; 95% CI, 0.41-0.87; P = .008), but not in TKR incidence. However, younger patients using TNFi did not have a reduced incidence of THR, and there were no associations between TNFi use and incidence of TKR or other joint replacements.
“It could be that the relatively long disease duration at our baseline meant there was greater potential for prevention of joint destruction at the hip over knee, although details of differential natural history of RA disease at these two joints are not well established,” the researchers wrote. “It is also very difficult to disentangle the impact of TNFi on improved function and overall quality of life and how this may have mediated effects on longer-term progression of joint damage, potentially differentially at the knee and hip.”
The researchers said the study was limited by the potential for residual confounding by indication, and the long disease duration of patients means that the results would not be generalizable to patients with early RA. In addition, underreporting of joint replacement could create bias because the registry information is a combination of physician-reported and self-reported incidences, they added.
This study was funded by an award from the National Institute for Health Research (NIHR) and support from the Oxford NIHR Biomedical Research Unit. Four authors disclosed financial relationships with industry, including many companies marketing biologics for RA. Other authors reported no relevant conflicts of interest.
SOURCE: Hawley S et al. Rheumatology. 2019 Jan 10. doi: 10.1093/rheumatology/key424.
The arrival and widespread use of tumor necrosis factor inhibitors (TNFi) in the late 1990s has “created a perception of causality” that led many to believe that TNFi use was associated with decreased rates of joint replacement. However, the decline in total hip arthroplasties (THAs), total knee arthroplasties (TKAs), and other joint replacements is likely because of a confluence of factors, Susan M. Goodman, MD, and Anne R. Bass, MD, wrote in an editorial accompanying the report by Hawley et al. (Rheumatology. 2019 Jan 10. doi: 10.1093/rheumatology/kez022).
Although Hawley et al. attempted to mitigate confounding in their study by using a propensity score when comparing TNFi and conventional synthetic disease-modifying antirheumatic drug (csDMARD) users, there was a preference for physicians prescribing biologics at a rate of 87% versus 13%, and the biologic preference was associated with disease severity, which is “a strong driver of the need for surgery.” In addition, in patients 60 years or older for whom TNFi reduced indications for joint replacement, “[t]he differential effect of TNFi use on THA utilization in the elderly is especially curious because a previous study by the same authors demonstrated that TKA, but not THA, rates were impacted by introduction of NICE guidance in 2002.”
The authors also noted clinicians should exercise caution in extrapolating the results of Hawley et al. because the effects of biologic treatment in patients with a long disease duration, such as in this study, may not be generalizable to most RA patients.
Dr. Goodman and Dr. Bass are rheumatologists and professors of clinical medicine at Cornell University and the Hospital for Special Surgery, both in New York. Dr. Goodman disclosed financial relationships with Novartis and UCB outside the scope of this work.
The arrival and widespread use of tumor necrosis factor inhibitors (TNFi) in the late 1990s has “created a perception of causality” that led many to believe that TNFi use was associated with decreased rates of joint replacement. However, the decline in total hip arthroplasties (THAs), total knee arthroplasties (TKAs), and other joint replacements is likely because of a confluence of factors, Susan M. Goodman, MD, and Anne R. Bass, MD, wrote in an editorial accompanying the report by Hawley et al. (Rheumatology. 2019 Jan 10. doi: 10.1093/rheumatology/kez022).
Although Hawley et al. attempted to mitigate confounding in their study by using a propensity score when comparing TNFi and conventional synthetic disease-modifying antirheumatic drug (csDMARD) users, there was a preference for physicians prescribing biologics at a rate of 87% versus 13%, and the biologic preference was associated with disease severity, which is “a strong driver of the need for surgery.” In addition, in patients 60 years or older for whom TNFi reduced indications for joint replacement, “[t]he differential effect of TNFi use on THA utilization in the elderly is especially curious because a previous study by the same authors demonstrated that TKA, but not THA, rates were impacted by introduction of NICE guidance in 2002.”
The authors also noted clinicians should exercise caution in extrapolating the results of Hawley et al. because the effects of biologic treatment in patients with a long disease duration, such as in this study, may not be generalizable to most RA patients.
Dr. Goodman and Dr. Bass are rheumatologists and professors of clinical medicine at Cornell University and the Hospital for Special Surgery, both in New York. Dr. Goodman disclosed financial relationships with Novartis and UCB outside the scope of this work.
The arrival and widespread use of tumor necrosis factor inhibitors (TNFi) in the late 1990s has “created a perception of causality” that led many to believe that TNFi use was associated with decreased rates of joint replacement. However, the decline in total hip arthroplasties (THAs), total knee arthroplasties (TKAs), and other joint replacements is likely because of a confluence of factors, Susan M. Goodman, MD, and Anne R. Bass, MD, wrote in an editorial accompanying the report by Hawley et al. (Rheumatology. 2019 Jan 10. doi: 10.1093/rheumatology/kez022).
Although Hawley et al. attempted to mitigate confounding in their study by using a propensity score when comparing TNFi and conventional synthetic disease-modifying antirheumatic drug (csDMARD) users, there was a preference for physicians prescribing biologics at a rate of 87% versus 13%, and the biologic preference was associated with disease severity, which is “a strong driver of the need for surgery.” In addition, in patients 60 years or older for whom TNFi reduced indications for joint replacement, “[t]he differential effect of TNFi use on THA utilization in the elderly is especially curious because a previous study by the same authors demonstrated that TKA, but not THA, rates were impacted by introduction of NICE guidance in 2002.”
The authors also noted clinicians should exercise caution in extrapolating the results of Hawley et al. because the effects of biologic treatment in patients with a long disease duration, such as in this study, may not be generalizable to most RA patients.
Dr. Goodman and Dr. Bass are rheumatologists and professors of clinical medicine at Cornell University and the Hospital for Special Surgery, both in New York. Dr. Goodman disclosed financial relationships with Novartis and UCB outside the scope of this work.
Patients with rheumatoid arthritis using tumor necrosis factor inhibitors do not appear to have a lower rate of joint replacement when compared with patients taking conventional synthetic disease-modifying antirheumatic drugs, according to an analysis of data in the British Society for Rheumatology Biologics Register for RA.
Although there was not a general protective effect, patients with rheumatoid arthritis (RA) who were 60 years or older had a 40% reduction in total hip replacement (THR) when using tumor necrosis factor inhibitors (TNFi), according to first author Samuel Hawley from the Nuffield Department of Orthopaedics in the Rheumatology and Musculoskeletal Sciences at the University of Oxford (England) and his colleagues.
“While a reduction in THR amongst older TNFi users offers some support for biologics playing a role in reducing need for joint replacement, it must also be noted that the lack of an overall protective effect is suggestive that other factors apart from TNFi are likely to be involved in the ... downward population trends in joint replacement rates in RA,” Mr. Hawley and his colleagues wrote in their report published in the journal Rheumatology.
The researchers analyzed prospectively collected data on 11,202 RA patients from the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) from 2001-2016 who were using TNFi (n = 9,558) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; n = 1,644). Patients had a median disease duration of 11.0 years in the TNFi group and 10.8 years in the csDMARD group. TNFi and csDMARD users were matched based on their propensity to receive treatment, and researchers used a Cox regression analysis to compare the rates of total knee replacement (TKR), THR, and other joint replacement. The researchers utilized each csDMARD user a median of three times (interquartile range, one to six) in the comparisons.
The incidence rate for THR was 5.22/1,000 person-years for TNFi users and 6.30/1,000 person-years for csDMARD users, while the incidence rate for TKR was 8.89/1,000 person-years for TNFi users and 8.09/1,000 person-years for csDMARD users. Mr. Hawley and his colleagues found no association between TNFi use and THR when compared with csDMARD users (adjusted pooled hazard ratio, 0.86; 95% confidence interval, 0.60-1.22; P = .39) based on 589 THRs during follow-up. There was also no association between the incidence of TKR and TNFi use when compared with csDMARD users (adjusted pooled HR, 1.11; 95% CI, 0.84-1.47; P = .46) based on 846 TKRs during follow-up. When the researchers examined 336 other joint replacements performed during follow-up, there was also no significant difference in incidence between TNFi and csDMARD users (HR, 1.15; 95% CI, 0.75-1.77).
For patients 60 years or older, TNFi use was associated with a 40% reduction in THR incidence (HR, 0.60; 95% CI, 0.41-0.87; P = .008), but not in TKR incidence. However, younger patients using TNFi did not have a reduced incidence of THR, and there were no associations between TNFi use and incidence of TKR or other joint replacements.
“It could be that the relatively long disease duration at our baseline meant there was greater potential for prevention of joint destruction at the hip over knee, although details of differential natural history of RA disease at these two joints are not well established,” the researchers wrote. “It is also very difficult to disentangle the impact of TNFi on improved function and overall quality of life and how this may have mediated effects on longer-term progression of joint damage, potentially differentially at the knee and hip.”
The researchers said the study was limited by the potential for residual confounding by indication, and the long disease duration of patients means that the results would not be generalizable to patients with early RA. In addition, underreporting of joint replacement could create bias because the registry information is a combination of physician-reported and self-reported incidences, they added.
This study was funded by an award from the National Institute for Health Research (NIHR) and support from the Oxford NIHR Biomedical Research Unit. Four authors disclosed financial relationships with industry, including many companies marketing biologics for RA. Other authors reported no relevant conflicts of interest.
SOURCE: Hawley S et al. Rheumatology. 2019 Jan 10. doi: 10.1093/rheumatology/key424.
Patients with rheumatoid arthritis using tumor necrosis factor inhibitors do not appear to have a lower rate of joint replacement when compared with patients taking conventional synthetic disease-modifying antirheumatic drugs, according to an analysis of data in the British Society for Rheumatology Biologics Register for RA.
Although there was not a general protective effect, patients with rheumatoid arthritis (RA) who were 60 years or older had a 40% reduction in total hip replacement (THR) when using tumor necrosis factor inhibitors (TNFi), according to first author Samuel Hawley from the Nuffield Department of Orthopaedics in the Rheumatology and Musculoskeletal Sciences at the University of Oxford (England) and his colleagues.
“While a reduction in THR amongst older TNFi users offers some support for biologics playing a role in reducing need for joint replacement, it must also be noted that the lack of an overall protective effect is suggestive that other factors apart from TNFi are likely to be involved in the ... downward population trends in joint replacement rates in RA,” Mr. Hawley and his colleagues wrote in their report published in the journal Rheumatology.
The researchers analyzed prospectively collected data on 11,202 RA patients from the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) from 2001-2016 who were using TNFi (n = 9,558) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; n = 1,644). Patients had a median disease duration of 11.0 years in the TNFi group and 10.8 years in the csDMARD group. TNFi and csDMARD users were matched based on their propensity to receive treatment, and researchers used a Cox regression analysis to compare the rates of total knee replacement (TKR), THR, and other joint replacement. The researchers utilized each csDMARD user a median of three times (interquartile range, one to six) in the comparisons.
The incidence rate for THR was 5.22/1,000 person-years for TNFi users and 6.30/1,000 person-years for csDMARD users, while the incidence rate for TKR was 8.89/1,000 person-years for TNFi users and 8.09/1,000 person-years for csDMARD users. Mr. Hawley and his colleagues found no association between TNFi use and THR when compared with csDMARD users (adjusted pooled hazard ratio, 0.86; 95% confidence interval, 0.60-1.22; P = .39) based on 589 THRs during follow-up. There was also no association between the incidence of TKR and TNFi use when compared with csDMARD users (adjusted pooled HR, 1.11; 95% CI, 0.84-1.47; P = .46) based on 846 TKRs during follow-up. When the researchers examined 336 other joint replacements performed during follow-up, there was also no significant difference in incidence between TNFi and csDMARD users (HR, 1.15; 95% CI, 0.75-1.77).
For patients 60 years or older, TNFi use was associated with a 40% reduction in THR incidence (HR, 0.60; 95% CI, 0.41-0.87; P = .008), but not in TKR incidence. However, younger patients using TNFi did not have a reduced incidence of THR, and there were no associations between TNFi use and incidence of TKR or other joint replacements.
“It could be that the relatively long disease duration at our baseline meant there was greater potential for prevention of joint destruction at the hip over knee, although details of differential natural history of RA disease at these two joints are not well established,” the researchers wrote. “It is also very difficult to disentangle the impact of TNFi on improved function and overall quality of life and how this may have mediated effects on longer-term progression of joint damage, potentially differentially at the knee and hip.”
The researchers said the study was limited by the potential for residual confounding by indication, and the long disease duration of patients means that the results would not be generalizable to patients with early RA. In addition, underreporting of joint replacement could create bias because the registry information is a combination of physician-reported and self-reported incidences, they added.
This study was funded by an award from the National Institute for Health Research (NIHR) and support from the Oxford NIHR Biomedical Research Unit. Four authors disclosed financial relationships with industry, including many companies marketing biologics for RA. Other authors reported no relevant conflicts of interest.
SOURCE: Hawley S et al. Rheumatology. 2019 Jan 10. doi: 10.1093/rheumatology/key424.
FROM RHEUMATOLOGY
Key clinical point: The rate of joint replacement did not differ among patients with RA using conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or tumor necrosis factor inhibitors (TNFis).
Major finding: There was no association between TNFi use and total hip replacement when compared with csDMARD users based on an adjusted pooled hazard ratio of 0.86 (95% confidence interval, 0.60-1.22), but patients older than 60 years using TNFi had a significantly greater reduction in total hip replacement.
Study details: An observational study of 11,202 prospectively collected RA patients in the British Society for Rheumatology Biologics Register for RA.
Disclosures: This study was funded by an award from the National Institute for Health Research (NIHR) and support from the Oxford NIHR Biomedical Research Unit. Four authors disclosed financial relationships with industry, including many companies marketing biologics for RA. Other authors reported no relevant conflicts of interest.
Source: Hawley S et al. Rheumatology. 2019 Jan 10. doi: 10.1093/rheumatology/key424.
In California, opioids most often prescribed in low-income, mostly white areas
There is a higher prevalence of opioid prescribing and opioid-related overdose deaths concentrated in regions with mostly low-income, white residents, compared with regions with high income and the lowest proportion of white residents, according to a new analysis of data on people living in California.
The findings of this study provide further evidence that the opioid epidemic affects a large proportion of low-income white communities (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6721).
“Whereas most epidemics predominate within social minority groups and previous US drug epidemics have typically been concentrated in nonwhite communities, Joseph Friedman, MPH, from the University of California, Los Angeles, and his colleagues wrote in their study. “Our analysis suggests that, at least in California, an important determinant of this phenomenon may be that white individuals have a higher level of exposure than nonwhite individuals to opioid prescriptions on a per capita basis through the health care system.”
Mr. Friedman and his colleagues analyzed 29.7 million prescription drug records from California’s Controlled Substance Utilization Review and Evaluation System in and examined the prevalence of opioids, benzodiazepines, and stimulants by race, ethnicity, and income level in 1,760 zip codes during 2011-2015. The researchers estimated the prevalence of opioid prescriptions in each zip code by calculating the number of people per zip code receiving an opioid prescription divided by the population of the zip code during each year.
Overall, 23.6% of California residents received at least one opioid prescription each year of the study. The researchers found 44.2% of individuals in zip codes with the lowest income but highest proportion of white residents and 16.1% of individuals in areas with the highest income and lowest proportion of white residents had received a minimum of one opioid prescription each year. The prevalence of stimulant prescriptions was 3.8% in zip codes with high income, and a high proportion of white population, compared with a prevalence of 0.6% in areas with low income and a low proportion of white residents. The researchers noted there was no association between income and benzodiazepine prescription, but the prevalence of benzodiazepine prescriptions was 15.7% in zip codes with the highest proportion of white residents, compared with 7.0% in zip codes with a low proportion of white residents.
During the same time period, there were 9,534 opioid overdose deaths in California from causes such as fentanyl, synthetic opioids, and prescription opioids. “Overdose deaths were highly concentrated in lower-income and mostly white areas,” Mr. Friedman and his colleagues wrote. “We observed an approximate 10-fold difference in overdose rates across the race/ethnicity–income gradient in California.”
Although the number of opioids prescribed each year has decreased since 2012, in a research letter published in the same issue noted that the rate of prescribing is still higher than it was in 1999 (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6989). The authors also pointed out increases in the duration of opioid prescriptions and wide regional variations in opioid prescribing rates.
In their study, Gery P. Guy Jr., PhD, and his colleagues used data from the IQVIA Xponent database from approximately 50,400 retail pharmacies and discovered the average morphine milligram equivalent (MME) per capita had decreased from 641.4 MME per capita in 2015 to 512.6 MME per capita in 2017 (20.1%). The number of opioid prescriptions also decreased from 6.7 per 100 persons in 2015 to 5.0 per 100 persons in 2017 (25.3%). However, during 2015-2017, the average duration of opioid prescriptions increased from 17.7 days to 18.3 days (3.4%), while the median duration increased during the same time from 15.0 days to 20.0 days (33.3%).
While 74.7% of counties reduced the number of opioids prescribed during 2015-2017 and there also were reductions in the rate of high-dose prescribing (76.6%) and overall prescribing rates (74.7%), Dr. Guy of the Centers for Disease Control and Prevention and his colleagues found “substantial variation” in 2017 prescription rates at the county level, with opioids prescribed at 1,061.0 MME per capita at the highest quartile, compared with 182.8 MME per capita at the lowest quartile.
“Recent reductions could be related to policies and strategies aimed at reducing inappropriate prescribing, increased awareness of the risks associated with opioids, and release of the CDC Guideline for Prescribing Opioids for Chronic Pain–United States, 2016,” Dr. Guy and his colleagues noted.
In an additional article published in the same JAMA Internal Medicine issue, Bennett Allen, a research associate at the New York City Department of Health and Mental Hygiene and his colleagues examined the rate of opioid overdose deaths for non-Hispanic white, non-Hispanic black, Hispanic, and undefined other races in New York (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7700). They identified 1,487 deaths in 2017, which included 556 white (37.0%), 421 black (28.0%), 455 Hispanic (31.0%), and 55 undefined (4.0%) opioid overdose deaths. There was a higher rate of fentanyl and/or heroin overdose deaths from younger (aged 15-34 years) white New Yorkers (22.2/100,000 persons; 95% confidence interval, 19.0-25.5), compared with younger black New Yorkers (5.8/100,000; 95% CI, 4.0-8.2) and Hispanic (9.7/100,000; 95% CI, 7.6-12.1).
Among older residents (aged 55-84 years), Mr. Allen and his colleagues found higher rates of fentanyl and/or heroin overdose for black New Yorkers (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with older white New Yorkers (9.4/100,000 persons; 95% CI, 7.3-11.8), as well as significantly higher rates of cocaine overdose (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with white (5.1/100,000 persons; 95% CI, 3.6-7.0) and Hispanic residents (11.8/100,000 persons; 95% CI, 8.9-15.4).
“The distinct age distribution and drug involvement of overdose deaths among New York City blacks, Latinos, and whites, along with complementary evidence about drug use trajectories, highlight the need for heterogeneous approaches to treatment and the equitable allocation of treatment and health care resources to reach diverse populations at risk of overdose,” Mr. Allen and his colleagues wrote.
Dr. Schriger reported support from Korein Foundation for his time working on the study by Friedman et al. The other authors reported no conflicts of interest.
The results published by Friedman et al. are a reminder that we can use regional prescribing trends to identify communities most susceptible to the opioid epidemic and give them the resources they need to combat opioid addiction, Vice Adm. Jerome M. Adams, MD, MPH, and Adm. Brett P. Giroir, MD, wrote in a related editorial.
“Discussion of overdose risks and coprescribing of naloxone must become routine if we are to make opioid prescribing safer,” the authors wrote.
Physicians also can help respond to the opioid epidemic outside of prescribing by promoting evidence-based nonopioid and nonpharmaceutical pain treatments, screening their patients for OUD and OUD risks, and acknowledging “that the problem cannot be solved by medical interventions alone.” Individual, environmental, and societal factors also contribute to the opioid epidemic, and physicians are uniquely suited to spearhead efforts aimed at addressing comprehensive opioid misuse.
“Physicians stand out as natural leaders to help solve the crises because of the depth of their knowledge, immediacy of their contact with patients, and relatively high level of respect their profession enjoys,” Dr. Adams and Dr. Giroir wrote. “We thereby call on our nation’s doctors to embrace their roles in the clinic and beyond to help educate communities, bring together stakeholders, and be part of the cultural change to support people living free from addiction.”
Dr. Adams is the 20th surgeon general of the United States at the U.S. Public Health Service and HHS; Dr. Giroir is the 16th U.S. assistant secretary for health at the U.S. Public Health Service and HHS. They reported no relevant conflicts of interest. Their invited commentary accompanied the three related articles in the publication (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7934 ).
The results published by Friedman et al. are a reminder that we can use regional prescribing trends to identify communities most susceptible to the opioid epidemic and give them the resources they need to combat opioid addiction, Vice Adm. Jerome M. Adams, MD, MPH, and Adm. Brett P. Giroir, MD, wrote in a related editorial.
“Discussion of overdose risks and coprescribing of naloxone must become routine if we are to make opioid prescribing safer,” the authors wrote.
Physicians also can help respond to the opioid epidemic outside of prescribing by promoting evidence-based nonopioid and nonpharmaceutical pain treatments, screening their patients for OUD and OUD risks, and acknowledging “that the problem cannot be solved by medical interventions alone.” Individual, environmental, and societal factors also contribute to the opioid epidemic, and physicians are uniquely suited to spearhead efforts aimed at addressing comprehensive opioid misuse.
“Physicians stand out as natural leaders to help solve the crises because of the depth of their knowledge, immediacy of their contact with patients, and relatively high level of respect their profession enjoys,” Dr. Adams and Dr. Giroir wrote. “We thereby call on our nation’s doctors to embrace their roles in the clinic and beyond to help educate communities, bring together stakeholders, and be part of the cultural change to support people living free from addiction.”
Dr. Adams is the 20th surgeon general of the United States at the U.S. Public Health Service and HHS; Dr. Giroir is the 16th U.S. assistant secretary for health at the U.S. Public Health Service and HHS. They reported no relevant conflicts of interest. Their invited commentary accompanied the three related articles in the publication (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7934 ).
The results published by Friedman et al. are a reminder that we can use regional prescribing trends to identify communities most susceptible to the opioid epidemic and give them the resources they need to combat opioid addiction, Vice Adm. Jerome M. Adams, MD, MPH, and Adm. Brett P. Giroir, MD, wrote in a related editorial.
“Discussion of overdose risks and coprescribing of naloxone must become routine if we are to make opioid prescribing safer,” the authors wrote.
Physicians also can help respond to the opioid epidemic outside of prescribing by promoting evidence-based nonopioid and nonpharmaceutical pain treatments, screening their patients for OUD and OUD risks, and acknowledging “that the problem cannot be solved by medical interventions alone.” Individual, environmental, and societal factors also contribute to the opioid epidemic, and physicians are uniquely suited to spearhead efforts aimed at addressing comprehensive opioid misuse.
“Physicians stand out as natural leaders to help solve the crises because of the depth of their knowledge, immediacy of their contact with patients, and relatively high level of respect their profession enjoys,” Dr. Adams and Dr. Giroir wrote. “We thereby call on our nation’s doctors to embrace their roles in the clinic and beyond to help educate communities, bring together stakeholders, and be part of the cultural change to support people living free from addiction.”
Dr. Adams is the 20th surgeon general of the United States at the U.S. Public Health Service and HHS; Dr. Giroir is the 16th U.S. assistant secretary for health at the U.S. Public Health Service and HHS. They reported no relevant conflicts of interest. Their invited commentary accompanied the three related articles in the publication (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7934 ).
There is a higher prevalence of opioid prescribing and opioid-related overdose deaths concentrated in regions with mostly low-income, white residents, compared with regions with high income and the lowest proportion of white residents, according to a new analysis of data on people living in California.
The findings of this study provide further evidence that the opioid epidemic affects a large proportion of low-income white communities (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6721).
“Whereas most epidemics predominate within social minority groups and previous US drug epidemics have typically been concentrated in nonwhite communities, Joseph Friedman, MPH, from the University of California, Los Angeles, and his colleagues wrote in their study. “Our analysis suggests that, at least in California, an important determinant of this phenomenon may be that white individuals have a higher level of exposure than nonwhite individuals to opioid prescriptions on a per capita basis through the health care system.”
Mr. Friedman and his colleagues analyzed 29.7 million prescription drug records from California’s Controlled Substance Utilization Review and Evaluation System in and examined the prevalence of opioids, benzodiazepines, and stimulants by race, ethnicity, and income level in 1,760 zip codes during 2011-2015. The researchers estimated the prevalence of opioid prescriptions in each zip code by calculating the number of people per zip code receiving an opioid prescription divided by the population of the zip code during each year.
Overall, 23.6% of California residents received at least one opioid prescription each year of the study. The researchers found 44.2% of individuals in zip codes with the lowest income but highest proportion of white residents and 16.1% of individuals in areas with the highest income and lowest proportion of white residents had received a minimum of one opioid prescription each year. The prevalence of stimulant prescriptions was 3.8% in zip codes with high income, and a high proportion of white population, compared with a prevalence of 0.6% in areas with low income and a low proportion of white residents. The researchers noted there was no association between income and benzodiazepine prescription, but the prevalence of benzodiazepine prescriptions was 15.7% in zip codes with the highest proportion of white residents, compared with 7.0% in zip codes with a low proportion of white residents.
During the same time period, there were 9,534 opioid overdose deaths in California from causes such as fentanyl, synthetic opioids, and prescription opioids. “Overdose deaths were highly concentrated in lower-income and mostly white areas,” Mr. Friedman and his colleagues wrote. “We observed an approximate 10-fold difference in overdose rates across the race/ethnicity–income gradient in California.”
Although the number of opioids prescribed each year has decreased since 2012, in a research letter published in the same issue noted that the rate of prescribing is still higher than it was in 1999 (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6989). The authors also pointed out increases in the duration of opioid prescriptions and wide regional variations in opioid prescribing rates.
In their study, Gery P. Guy Jr., PhD, and his colleagues used data from the IQVIA Xponent database from approximately 50,400 retail pharmacies and discovered the average morphine milligram equivalent (MME) per capita had decreased from 641.4 MME per capita in 2015 to 512.6 MME per capita in 2017 (20.1%). The number of opioid prescriptions also decreased from 6.7 per 100 persons in 2015 to 5.0 per 100 persons in 2017 (25.3%). However, during 2015-2017, the average duration of opioid prescriptions increased from 17.7 days to 18.3 days (3.4%), while the median duration increased during the same time from 15.0 days to 20.0 days (33.3%).
While 74.7% of counties reduced the number of opioids prescribed during 2015-2017 and there also were reductions in the rate of high-dose prescribing (76.6%) and overall prescribing rates (74.7%), Dr. Guy of the Centers for Disease Control and Prevention and his colleagues found “substantial variation” in 2017 prescription rates at the county level, with opioids prescribed at 1,061.0 MME per capita at the highest quartile, compared with 182.8 MME per capita at the lowest quartile.
“Recent reductions could be related to policies and strategies aimed at reducing inappropriate prescribing, increased awareness of the risks associated with opioids, and release of the CDC Guideline for Prescribing Opioids for Chronic Pain–United States, 2016,” Dr. Guy and his colleagues noted.
In an additional article published in the same JAMA Internal Medicine issue, Bennett Allen, a research associate at the New York City Department of Health and Mental Hygiene and his colleagues examined the rate of opioid overdose deaths for non-Hispanic white, non-Hispanic black, Hispanic, and undefined other races in New York (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7700). They identified 1,487 deaths in 2017, which included 556 white (37.0%), 421 black (28.0%), 455 Hispanic (31.0%), and 55 undefined (4.0%) opioid overdose deaths. There was a higher rate of fentanyl and/or heroin overdose deaths from younger (aged 15-34 years) white New Yorkers (22.2/100,000 persons; 95% confidence interval, 19.0-25.5), compared with younger black New Yorkers (5.8/100,000; 95% CI, 4.0-8.2) and Hispanic (9.7/100,000; 95% CI, 7.6-12.1).
Among older residents (aged 55-84 years), Mr. Allen and his colleagues found higher rates of fentanyl and/or heroin overdose for black New Yorkers (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with older white New Yorkers (9.4/100,000 persons; 95% CI, 7.3-11.8), as well as significantly higher rates of cocaine overdose (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with white (5.1/100,000 persons; 95% CI, 3.6-7.0) and Hispanic residents (11.8/100,000 persons; 95% CI, 8.9-15.4).
“The distinct age distribution and drug involvement of overdose deaths among New York City blacks, Latinos, and whites, along with complementary evidence about drug use trajectories, highlight the need for heterogeneous approaches to treatment and the equitable allocation of treatment and health care resources to reach diverse populations at risk of overdose,” Mr. Allen and his colleagues wrote.
Dr. Schriger reported support from Korein Foundation for his time working on the study by Friedman et al. The other authors reported no conflicts of interest.
There is a higher prevalence of opioid prescribing and opioid-related overdose deaths concentrated in regions with mostly low-income, white residents, compared with regions with high income and the lowest proportion of white residents, according to a new analysis of data on people living in California.
The findings of this study provide further evidence that the opioid epidemic affects a large proportion of low-income white communities (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6721).
“Whereas most epidemics predominate within social minority groups and previous US drug epidemics have typically been concentrated in nonwhite communities, Joseph Friedman, MPH, from the University of California, Los Angeles, and his colleagues wrote in their study. “Our analysis suggests that, at least in California, an important determinant of this phenomenon may be that white individuals have a higher level of exposure than nonwhite individuals to opioid prescriptions on a per capita basis through the health care system.”
Mr. Friedman and his colleagues analyzed 29.7 million prescription drug records from California’s Controlled Substance Utilization Review and Evaluation System in and examined the prevalence of opioids, benzodiazepines, and stimulants by race, ethnicity, and income level in 1,760 zip codes during 2011-2015. The researchers estimated the prevalence of opioid prescriptions in each zip code by calculating the number of people per zip code receiving an opioid prescription divided by the population of the zip code during each year.
Overall, 23.6% of California residents received at least one opioid prescription each year of the study. The researchers found 44.2% of individuals in zip codes with the lowest income but highest proportion of white residents and 16.1% of individuals in areas with the highest income and lowest proportion of white residents had received a minimum of one opioid prescription each year. The prevalence of stimulant prescriptions was 3.8% in zip codes with high income, and a high proportion of white population, compared with a prevalence of 0.6% in areas with low income and a low proportion of white residents. The researchers noted there was no association between income and benzodiazepine prescription, but the prevalence of benzodiazepine prescriptions was 15.7% in zip codes with the highest proportion of white residents, compared with 7.0% in zip codes with a low proportion of white residents.
During the same time period, there were 9,534 opioid overdose deaths in California from causes such as fentanyl, synthetic opioids, and prescription opioids. “Overdose deaths were highly concentrated in lower-income and mostly white areas,” Mr. Friedman and his colleagues wrote. “We observed an approximate 10-fold difference in overdose rates across the race/ethnicity–income gradient in California.”
Although the number of opioids prescribed each year has decreased since 2012, in a research letter published in the same issue noted that the rate of prescribing is still higher than it was in 1999 (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.6989). The authors also pointed out increases in the duration of opioid prescriptions and wide regional variations in opioid prescribing rates.
In their study, Gery P. Guy Jr., PhD, and his colleagues used data from the IQVIA Xponent database from approximately 50,400 retail pharmacies and discovered the average morphine milligram equivalent (MME) per capita had decreased from 641.4 MME per capita in 2015 to 512.6 MME per capita in 2017 (20.1%). The number of opioid prescriptions also decreased from 6.7 per 100 persons in 2015 to 5.0 per 100 persons in 2017 (25.3%). However, during 2015-2017, the average duration of opioid prescriptions increased from 17.7 days to 18.3 days (3.4%), while the median duration increased during the same time from 15.0 days to 20.0 days (33.3%).
While 74.7% of counties reduced the number of opioids prescribed during 2015-2017 and there also were reductions in the rate of high-dose prescribing (76.6%) and overall prescribing rates (74.7%), Dr. Guy of the Centers for Disease Control and Prevention and his colleagues found “substantial variation” in 2017 prescription rates at the county level, with opioids prescribed at 1,061.0 MME per capita at the highest quartile, compared with 182.8 MME per capita at the lowest quartile.
“Recent reductions could be related to policies and strategies aimed at reducing inappropriate prescribing, increased awareness of the risks associated with opioids, and release of the CDC Guideline for Prescribing Opioids for Chronic Pain–United States, 2016,” Dr. Guy and his colleagues noted.
In an additional article published in the same JAMA Internal Medicine issue, Bennett Allen, a research associate at the New York City Department of Health and Mental Hygiene and his colleagues examined the rate of opioid overdose deaths for non-Hispanic white, non-Hispanic black, Hispanic, and undefined other races in New York (JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7700). They identified 1,487 deaths in 2017, which included 556 white (37.0%), 421 black (28.0%), 455 Hispanic (31.0%), and 55 undefined (4.0%) opioid overdose deaths. There was a higher rate of fentanyl and/or heroin overdose deaths from younger (aged 15-34 years) white New Yorkers (22.2/100,000 persons; 95% confidence interval, 19.0-25.5), compared with younger black New Yorkers (5.8/100,000; 95% CI, 4.0-8.2) and Hispanic (9.7/100,000; 95% CI, 7.6-12.1).
Among older residents (aged 55-84 years), Mr. Allen and his colleagues found higher rates of fentanyl and/or heroin overdose for black New Yorkers (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with older white New Yorkers (9.4/100,000 persons; 95% CI, 7.3-11.8), as well as significantly higher rates of cocaine overdose (25.4/100,000 persons; 95% CI, 20.9-30.0), compared with white (5.1/100,000 persons; 95% CI, 3.6-7.0) and Hispanic residents (11.8/100,000 persons; 95% CI, 8.9-15.4).
“The distinct age distribution and drug involvement of overdose deaths among New York City blacks, Latinos, and whites, along with complementary evidence about drug use trajectories, highlight the need for heterogeneous approaches to treatment and the equitable allocation of treatment and health care resources to reach diverse populations at risk of overdose,” Mr. Allen and his colleagues wrote.
Dr. Schriger reported support from Korein Foundation for his time working on the study by Friedman et al. The other authors reported no conflicts of interest.
FROM JAMA INTERNAL MEDICINE
Key clinical point: The most common users of opioids according to prescription drug records are residents of mostly low-income, white neighborhoods.
Major finding: Compared with 23.6% of all Californians, 44.2% of individuals in zip codes containing mostly low-income, white residents had at least one opioid prescription each year, compared with 16.1% of individuals in high-income zip codes with the lowest population of white residents.
Study details: An analysis of 29.7 million opioid prescription drug records by race and income in California during 2011-2015.
Disclosures: Dr. Schriger reported support from the Korein Foundation for his time working on the study by Friedman et al. The other authors from Friedman et al. reported no conflicts of interest.
Most pregnant women want guidance on prenatal whole-genome sequencing
according to results from a survey published in Obstetrics & Gynecology.
Nearly half said they would want clear guidance from clinicians before undergoing the noninvasive procedure.
“Prenatal whole-genome sequencing offers significantly more fetal information than women can currently receive, and it is not surprising that, when faced with a tremendous range of information, many women want recommendations from their clinicians,” Haley K. Sullivan from the National Institutes of Health Clinical Center and National Human Genome Research Institute and colleagues wrote. “Our data suggest that most women prefer a directive interaction with their clinician when deciding what types of genetic information to receive from prenatal whole-genome sequencing.”
Research coordinators from the Inova Translational Medicine Institute offered 805 pregnant women a survey on their preferences for prenatal whole-genome sequencing between June and August 2017; of these, 553 women answered (69% response rate). The women responded to questions about what type of information they would like to receive if they were to undergo prenatal whole-genome sequencing and what role a clinician would preferably play in the decision-making process. The researchers divided the survey into sections based on actionability, severity, prevalence, and age of onset.
According to the survey results, 90% of respondents wanted information on serious treatable childhood-onset diseases from prenatal whole-genome sequencing results, while 40% said they did not want to receive results based on nonmedical traits such as eye color, height, or athletic ability.
With regard to clinician role, 45% of women said they wanted all options presented with clear recommendations from a clinician on which tests to order, 26% wanted all options presented but with a joint decision-making process, 13% wanted all options presented but independent decision making, and 11% wanted the clear recommendation from clinicians alone.
The respondents said the most common reason for wanting to undergo prenatal whole-genome sequencing was to prepare “financially, medically, or psychologically” for a child with special needs, the researchers said.
“This represents a departure from the current state of genetic counseling, where nondirectiveness is a central tenet, and is contrary to the 45% of ob.gyns. who said in a previous survey that they should not be at all directive when counseling patients on prenatal whole-genome sequencing,” the authors wrote. “Given this clear patient desire for guidance, there is a vital opportunity for the American College of Obstetricians and Gynecologists to provide leadership and recommendations as prenatal whole-genome sequencing is adopted into clinical practice.”
Limitations in the study include asking the respondents to make hypothetical decisions, using examples to describe genetic conditions that might have skewed decision making; asking women to pick only one reason for wanting the sequencing information from a list of predetermined options, when many reasons may be important to them; social desirability bias in the responses, if women are reluctant to pick a choice they perceive as less socially acceptable; and a potential systematic difference between women who were and were not enrolled as survey participants. The respondents also were from the Northern Virginia area, which may not be generalizable to a national population of patients, the researchers said.
This study was supported by the Intramural Research Program of the National Human Genome Research Institute and the Clinical Center Department of Bioethics, National Institutes of Health. The authors reported no relevant conflicts of interest.
SOURCE: Sullivan HK et al. Obstet Gynecol. 2019 Mar. doi: 10.1097/AOG.0000000000003121.
according to results from a survey published in Obstetrics & Gynecology.
Nearly half said they would want clear guidance from clinicians before undergoing the noninvasive procedure.
“Prenatal whole-genome sequencing offers significantly more fetal information than women can currently receive, and it is not surprising that, when faced with a tremendous range of information, many women want recommendations from their clinicians,” Haley K. Sullivan from the National Institutes of Health Clinical Center and National Human Genome Research Institute and colleagues wrote. “Our data suggest that most women prefer a directive interaction with their clinician when deciding what types of genetic information to receive from prenatal whole-genome sequencing.”
Research coordinators from the Inova Translational Medicine Institute offered 805 pregnant women a survey on their preferences for prenatal whole-genome sequencing between June and August 2017; of these, 553 women answered (69% response rate). The women responded to questions about what type of information they would like to receive if they were to undergo prenatal whole-genome sequencing and what role a clinician would preferably play in the decision-making process. The researchers divided the survey into sections based on actionability, severity, prevalence, and age of onset.
According to the survey results, 90% of respondents wanted information on serious treatable childhood-onset diseases from prenatal whole-genome sequencing results, while 40% said they did not want to receive results based on nonmedical traits such as eye color, height, or athletic ability.
With regard to clinician role, 45% of women said they wanted all options presented with clear recommendations from a clinician on which tests to order, 26% wanted all options presented but with a joint decision-making process, 13% wanted all options presented but independent decision making, and 11% wanted the clear recommendation from clinicians alone.
The respondents said the most common reason for wanting to undergo prenatal whole-genome sequencing was to prepare “financially, medically, or psychologically” for a child with special needs, the researchers said.
“This represents a departure from the current state of genetic counseling, where nondirectiveness is a central tenet, and is contrary to the 45% of ob.gyns. who said in a previous survey that they should not be at all directive when counseling patients on prenatal whole-genome sequencing,” the authors wrote. “Given this clear patient desire for guidance, there is a vital opportunity for the American College of Obstetricians and Gynecologists to provide leadership and recommendations as prenatal whole-genome sequencing is adopted into clinical practice.”
Limitations in the study include asking the respondents to make hypothetical decisions, using examples to describe genetic conditions that might have skewed decision making; asking women to pick only one reason for wanting the sequencing information from a list of predetermined options, when many reasons may be important to them; social desirability bias in the responses, if women are reluctant to pick a choice they perceive as less socially acceptable; and a potential systematic difference between women who were and were not enrolled as survey participants. The respondents also were from the Northern Virginia area, which may not be generalizable to a national population of patients, the researchers said.
This study was supported by the Intramural Research Program of the National Human Genome Research Institute and the Clinical Center Department of Bioethics, National Institutes of Health. The authors reported no relevant conflicts of interest.
SOURCE: Sullivan HK et al. Obstet Gynecol. 2019 Mar. doi: 10.1097/AOG.0000000000003121.
according to results from a survey published in Obstetrics & Gynecology.
Nearly half said they would want clear guidance from clinicians before undergoing the noninvasive procedure.
“Prenatal whole-genome sequencing offers significantly more fetal information than women can currently receive, and it is not surprising that, when faced with a tremendous range of information, many women want recommendations from their clinicians,” Haley K. Sullivan from the National Institutes of Health Clinical Center and National Human Genome Research Institute and colleagues wrote. “Our data suggest that most women prefer a directive interaction with their clinician when deciding what types of genetic information to receive from prenatal whole-genome sequencing.”
Research coordinators from the Inova Translational Medicine Institute offered 805 pregnant women a survey on their preferences for prenatal whole-genome sequencing between June and August 2017; of these, 553 women answered (69% response rate). The women responded to questions about what type of information they would like to receive if they were to undergo prenatal whole-genome sequencing and what role a clinician would preferably play in the decision-making process. The researchers divided the survey into sections based on actionability, severity, prevalence, and age of onset.
According to the survey results, 90% of respondents wanted information on serious treatable childhood-onset diseases from prenatal whole-genome sequencing results, while 40% said they did not want to receive results based on nonmedical traits such as eye color, height, or athletic ability.
With regard to clinician role, 45% of women said they wanted all options presented with clear recommendations from a clinician on which tests to order, 26% wanted all options presented but with a joint decision-making process, 13% wanted all options presented but independent decision making, and 11% wanted the clear recommendation from clinicians alone.
The respondents said the most common reason for wanting to undergo prenatal whole-genome sequencing was to prepare “financially, medically, or psychologically” for a child with special needs, the researchers said.
“This represents a departure from the current state of genetic counseling, where nondirectiveness is a central tenet, and is contrary to the 45% of ob.gyns. who said in a previous survey that they should not be at all directive when counseling patients on prenatal whole-genome sequencing,” the authors wrote. “Given this clear patient desire for guidance, there is a vital opportunity for the American College of Obstetricians and Gynecologists to provide leadership and recommendations as prenatal whole-genome sequencing is adopted into clinical practice.”
Limitations in the study include asking the respondents to make hypothetical decisions, using examples to describe genetic conditions that might have skewed decision making; asking women to pick only one reason for wanting the sequencing information from a list of predetermined options, when many reasons may be important to them; social desirability bias in the responses, if women are reluctant to pick a choice they perceive as less socially acceptable; and a potential systematic difference between women who were and were not enrolled as survey participants. The respondents also were from the Northern Virginia area, which may not be generalizable to a national population of patients, the researchers said.
This study was supported by the Intramural Research Program of the National Human Genome Research Institute and the Clinical Center Department of Bioethics, National Institutes of Health. The authors reported no relevant conflicts of interest.
SOURCE: Sullivan HK et al. Obstet Gynecol. 2019 Mar. doi: 10.1097/AOG.0000000000003121.
FROM OBSTETRICS & GYNECOLOGY
Key clinical point: A majority of pregnant women surveyed said they wanted information on childhood-onset genetic diseases, with almost half wanting clear clinical recommendations before deciding to undergo noninvasive prenatal whole-genome sequencing.
Major finding: Of the respondents, 90% said they wanted information on serious treatable childhood-onset conditions.
Study details: A survey of 553 pregnant women coordinated by the Inova Translational Medicine Institute.
Disclosures: This study was supported by the Intramural Research Program of the National Human Genome Research Institute and the Clinical Center Department of Bioethics, National Institutes of Health. The authors reported no relevant conflicts of interest.
Source: Sullivan HK et al. Obstet Gynecol. 2019 Mar. doi: 10.1097/AOG.0000000000003121.
Statins cut vascular events in elderly patients
Statin therapy appears to reduce the risk of major vascular events for patients of all age groups, but there is less evidence that older patients with evidence of occlusive vascular disease benefit from the treatment, according to a recent meta-analysis of 28 trials from the Cholesterol Treatment Trialists’ Collaboration published in The Lancet.
Statins are “useful and affordable drug[s] that reduce heart attacks and strokes in older patients. Until now there has been an evidence gap and we wanted to look at their efficacy and safety in older people,” Jordan Fulcher, BSc (Med), MBBS, from the Cholesterol Treatment Trialists’ (CTT) Collaboration and the University of Sydney stated in a press release. “Our analysis indicates that major cardiovascular events were reduced by about a fifth, per mmol/L lower LDL cholesterol, by statin therapy across all age groups. Despite previous concerns, we found no adverse effect on cancer or nonvascular mortality in any age group.”
The researchers examined 186,854 participants from 28 CTT trials undergoing statin therapy, of whom 14,483 (8%) were older than 75 years. Patients were divided into six groups based on age and examined the risk of major cardiovascular events such as stroke, coronary revascularization and major coronary events, as well as the incidence of cancer and vascular mortality.
Among all age groups, there was a significant reduction in major vascular events, with a 21% proportional per 1.0-mmol/L reduction in LDL cholesterol (risk ratio, 0.79; 95% confidence interval, 0.77-0.81) among patients receiving statin therapy or a more intensive statin regimen, and there was a 24% proportional reduction (RR, 0.76; 95% CI, 0.73-0.79) of major coronary events per 1.0-mmol/L reduction in LDL cholesterol, with older age resulting in a lower proportional reduction of major coronary events (P = .009). The researchers also found a proportional reduction of coronary revascularization procedures by 25% (RR, 0.75; 95% CI, 0.73-0.78) and stroke by 16% (RR, 0.84; 95% CI, 0.80-0.89) among patients of any age group receiving statin therapy or more intensive statin regimen, with no significant differences between age groups.
There was a 12% proportional reduction in vascular mortality per 1.0-mmol/L reduction in LDL cholesterol (RR, 0.88; 95% CI, 0.85-0.91), but this statistic did not remain significant after the researchers excluded four trials that included patients with heart failure or who were receiving renal dialysis. After excluding these trials from the overall analysis, the researchers found the smaller proportional reductions persisted for older patients for major coronary events (P = .01) but was no longer significant for major vascular events.
The researchers noted their study was limited by the highly selected patient population, low percentage of patients older than 75 years, including trials with efficacy endpoints where some nonserious adverse events may not have been recorded, and not including some trials in the meta-analysis if they were not part of the CTT.
This study was funded by Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation. The authors have reported personal fees, grants, and consulting fees from Abbott, Aegerion, Amgen, Arisaph, AstraZeneca, Bayer, Beckmann, Berlin-Chemie, Boehringer Ingelheim, Daiichi Sankyo, Dalcor, DuPont, Esperion, GlaxoSmithKline, ISIS Pharmaceuticals, Kowa, Mylan, Pfizer, Roche, Sanofi, Singulex, The Medicines Company, and Vatera Capital, as well as the British Heart Foundation, Cancer Research UK, National Institute for Health Research Oxford Biomedical Research Centre, Medical Research Council, Nuffield Department of Population Health, Weill Cornell Medicine, and UK Biobank.
SOURCE: Fulcher J et al. Lancet. 2019;393:407-15.
Statin therapy is often discontinued for older patients who have concomitant disease or other considerations, but it should still be considered in older patients when the benefits outweigh the risks, Bernard M.Y. Cheung, PhD, and Karen S.L. Lam, MD, wrote in a related editorial.
“Even if the relative risk reduction in people older than 75 years is less than expected, statin therapy might still be justified by a high baseline cardiovascular risk, which is usually present in older people,” they said.
One explanation for the decreased relative risk reduction among older patients from the results by Fulcher et al. in the Cholesterol Treatment Trialists’ (CTT) Collaboration trial could have been the inclusion of older patients with cardiac and renal failure, and treating patients with lower cardiac risk or lowering LDL cholesterol in patients at risk of cardiovascular events can help prevent major vascular events later.
Ultimately, no drug is harmless and the risk and benefits must be weighed before making a decision to use statins with older patients just as they would in any other patient population. “The challenge for the health-care profession and the media is to convey risks and benefits in ways that patients can understand, enabling them to make an informed choice,” the authors wrote.
Dr. Cheung and Dr. Lam are from the department of medicine at Queen Mary Hospital, University of Hong Kong in Hong Kong Special Administrative Region, China. They had no relevant disclosures.
Statin therapy is often discontinued for older patients who have concomitant disease or other considerations, but it should still be considered in older patients when the benefits outweigh the risks, Bernard M.Y. Cheung, PhD, and Karen S.L. Lam, MD, wrote in a related editorial.
“Even if the relative risk reduction in people older than 75 years is less than expected, statin therapy might still be justified by a high baseline cardiovascular risk, which is usually present in older people,” they said.
One explanation for the decreased relative risk reduction among older patients from the results by Fulcher et al. in the Cholesterol Treatment Trialists’ (CTT) Collaboration trial could have been the inclusion of older patients with cardiac and renal failure, and treating patients with lower cardiac risk or lowering LDL cholesterol in patients at risk of cardiovascular events can help prevent major vascular events later.
Ultimately, no drug is harmless and the risk and benefits must be weighed before making a decision to use statins with older patients just as they would in any other patient population. “The challenge for the health-care profession and the media is to convey risks and benefits in ways that patients can understand, enabling them to make an informed choice,” the authors wrote.
Dr. Cheung and Dr. Lam are from the department of medicine at Queen Mary Hospital, University of Hong Kong in Hong Kong Special Administrative Region, China. They had no relevant disclosures.
Statin therapy is often discontinued for older patients who have concomitant disease or other considerations, but it should still be considered in older patients when the benefits outweigh the risks, Bernard M.Y. Cheung, PhD, and Karen S.L. Lam, MD, wrote in a related editorial.
“Even if the relative risk reduction in people older than 75 years is less than expected, statin therapy might still be justified by a high baseline cardiovascular risk, which is usually present in older people,” they said.
One explanation for the decreased relative risk reduction among older patients from the results by Fulcher et al. in the Cholesterol Treatment Trialists’ (CTT) Collaboration trial could have been the inclusion of older patients with cardiac and renal failure, and treating patients with lower cardiac risk or lowering LDL cholesterol in patients at risk of cardiovascular events can help prevent major vascular events later.
Ultimately, no drug is harmless and the risk and benefits must be weighed before making a decision to use statins with older patients just as they would in any other patient population. “The challenge for the health-care profession and the media is to convey risks and benefits in ways that patients can understand, enabling them to make an informed choice,” the authors wrote.
Dr. Cheung and Dr. Lam are from the department of medicine at Queen Mary Hospital, University of Hong Kong in Hong Kong Special Administrative Region, China. They had no relevant disclosures.
Statin therapy appears to reduce the risk of major vascular events for patients of all age groups, but there is less evidence that older patients with evidence of occlusive vascular disease benefit from the treatment, according to a recent meta-analysis of 28 trials from the Cholesterol Treatment Trialists’ Collaboration published in The Lancet.
Statins are “useful and affordable drug[s] that reduce heart attacks and strokes in older patients. Until now there has been an evidence gap and we wanted to look at their efficacy and safety in older people,” Jordan Fulcher, BSc (Med), MBBS, from the Cholesterol Treatment Trialists’ (CTT) Collaboration and the University of Sydney stated in a press release. “Our analysis indicates that major cardiovascular events were reduced by about a fifth, per mmol/L lower LDL cholesterol, by statin therapy across all age groups. Despite previous concerns, we found no adverse effect on cancer or nonvascular mortality in any age group.”
The researchers examined 186,854 participants from 28 CTT trials undergoing statin therapy, of whom 14,483 (8%) were older than 75 years. Patients were divided into six groups based on age and examined the risk of major cardiovascular events such as stroke, coronary revascularization and major coronary events, as well as the incidence of cancer and vascular mortality.
Among all age groups, there was a significant reduction in major vascular events, with a 21% proportional per 1.0-mmol/L reduction in LDL cholesterol (risk ratio, 0.79; 95% confidence interval, 0.77-0.81) among patients receiving statin therapy or a more intensive statin regimen, and there was a 24% proportional reduction (RR, 0.76; 95% CI, 0.73-0.79) of major coronary events per 1.0-mmol/L reduction in LDL cholesterol, with older age resulting in a lower proportional reduction of major coronary events (P = .009). The researchers also found a proportional reduction of coronary revascularization procedures by 25% (RR, 0.75; 95% CI, 0.73-0.78) and stroke by 16% (RR, 0.84; 95% CI, 0.80-0.89) among patients of any age group receiving statin therapy or more intensive statin regimen, with no significant differences between age groups.
There was a 12% proportional reduction in vascular mortality per 1.0-mmol/L reduction in LDL cholesterol (RR, 0.88; 95% CI, 0.85-0.91), but this statistic did not remain significant after the researchers excluded four trials that included patients with heart failure or who were receiving renal dialysis. After excluding these trials from the overall analysis, the researchers found the smaller proportional reductions persisted for older patients for major coronary events (P = .01) but was no longer significant for major vascular events.
The researchers noted their study was limited by the highly selected patient population, low percentage of patients older than 75 years, including trials with efficacy endpoints where some nonserious adverse events may not have been recorded, and not including some trials in the meta-analysis if they were not part of the CTT.
This study was funded by Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation. The authors have reported personal fees, grants, and consulting fees from Abbott, Aegerion, Amgen, Arisaph, AstraZeneca, Bayer, Beckmann, Berlin-Chemie, Boehringer Ingelheim, Daiichi Sankyo, Dalcor, DuPont, Esperion, GlaxoSmithKline, ISIS Pharmaceuticals, Kowa, Mylan, Pfizer, Roche, Sanofi, Singulex, The Medicines Company, and Vatera Capital, as well as the British Heart Foundation, Cancer Research UK, National Institute for Health Research Oxford Biomedical Research Centre, Medical Research Council, Nuffield Department of Population Health, Weill Cornell Medicine, and UK Biobank.
SOURCE: Fulcher J et al. Lancet. 2019;393:407-15.
Statin therapy appears to reduce the risk of major vascular events for patients of all age groups, but there is less evidence that older patients with evidence of occlusive vascular disease benefit from the treatment, according to a recent meta-analysis of 28 trials from the Cholesterol Treatment Trialists’ Collaboration published in The Lancet.
Statins are “useful and affordable drug[s] that reduce heart attacks and strokes in older patients. Until now there has been an evidence gap and we wanted to look at their efficacy and safety in older people,” Jordan Fulcher, BSc (Med), MBBS, from the Cholesterol Treatment Trialists’ (CTT) Collaboration and the University of Sydney stated in a press release. “Our analysis indicates that major cardiovascular events were reduced by about a fifth, per mmol/L lower LDL cholesterol, by statin therapy across all age groups. Despite previous concerns, we found no adverse effect on cancer or nonvascular mortality in any age group.”
The researchers examined 186,854 participants from 28 CTT trials undergoing statin therapy, of whom 14,483 (8%) were older than 75 years. Patients were divided into six groups based on age and examined the risk of major cardiovascular events such as stroke, coronary revascularization and major coronary events, as well as the incidence of cancer and vascular mortality.
Among all age groups, there was a significant reduction in major vascular events, with a 21% proportional per 1.0-mmol/L reduction in LDL cholesterol (risk ratio, 0.79; 95% confidence interval, 0.77-0.81) among patients receiving statin therapy or a more intensive statin regimen, and there was a 24% proportional reduction (RR, 0.76; 95% CI, 0.73-0.79) of major coronary events per 1.0-mmol/L reduction in LDL cholesterol, with older age resulting in a lower proportional reduction of major coronary events (P = .009). The researchers also found a proportional reduction of coronary revascularization procedures by 25% (RR, 0.75; 95% CI, 0.73-0.78) and stroke by 16% (RR, 0.84; 95% CI, 0.80-0.89) among patients of any age group receiving statin therapy or more intensive statin regimen, with no significant differences between age groups.
There was a 12% proportional reduction in vascular mortality per 1.0-mmol/L reduction in LDL cholesterol (RR, 0.88; 95% CI, 0.85-0.91), but this statistic did not remain significant after the researchers excluded four trials that included patients with heart failure or who were receiving renal dialysis. After excluding these trials from the overall analysis, the researchers found the smaller proportional reductions persisted for older patients for major coronary events (P = .01) but was no longer significant for major vascular events.
The researchers noted their study was limited by the highly selected patient population, low percentage of patients older than 75 years, including trials with efficacy endpoints where some nonserious adverse events may not have been recorded, and not including some trials in the meta-analysis if they were not part of the CTT.
This study was funded by Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation. The authors have reported personal fees, grants, and consulting fees from Abbott, Aegerion, Amgen, Arisaph, AstraZeneca, Bayer, Beckmann, Berlin-Chemie, Boehringer Ingelheim, Daiichi Sankyo, Dalcor, DuPont, Esperion, GlaxoSmithKline, ISIS Pharmaceuticals, Kowa, Mylan, Pfizer, Roche, Sanofi, Singulex, The Medicines Company, and Vatera Capital, as well as the British Heart Foundation, Cancer Research UK, National Institute for Health Research Oxford Biomedical Research Centre, Medical Research Council, Nuffield Department of Population Health, Weill Cornell Medicine, and UK Biobank.
SOURCE: Fulcher J et al. Lancet. 2019;393:407-15.
FROM THE LANCET
Key clinical point: but patients older than 75 years with occlusive vascular disease have a smaller reduction in major coronary events.
Major finding: Major vascular coronary events were reduced by 24% (risk ratio, 0.76; 95% confidence interval, 0.73-0.79) with a decrease in the reduction of coronary events among patients older than 75 years. Study details: A meta-analysis of 28 trials with 186,854 individuals undergoing statin therapy from the Cholesterol Treatment Trialists’ Collaboration.
Disclosures: This study was funded by Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation. The authors have reported personal fees, grants, and consulting fees from Abbott, Aegerion, Amgen, Arisaph, AstraZeneca, Bayer, Beckmann, Berlin-Chemie, Boehringer Ingelheim, Daiichi Sankyo, Dalcor, DuPont, Esperion, GlaxoSmithKline, ISIS Pharmaceuticals, Kowa, Mylan, Pfizer, Roche, Sanofi, Singulex, The Medicines Company, and Vatera Capital, as well as the British Heart Foundation, Cancer Research UK, National Institute for Health Research Oxford Biomedical Research Centre, Medical Research Council, Nuffield Department of Population Health, Weill Cornell Medicine, and UK Biobank.
Source: Fulcher J et al. Lancet. 2019;393:407-15.
Automated office BP readings best routine measures
Automated office blood pressure readings appear to be more accurate than routine office readings and BP readings in research settings, according to a recent systematic review and meta-analysis.
Based on the evidence, automated office BP (AOBP) readings should now be the preferred method of reading a patient’s BP in clinical practice despite initial reluctance to incorporate this technique over other methods, the researchers wrote in JAMA Internal Medicine.
“The existing evidence supports the use of AOBP to screen patients for possible hypertension in clinical practice, especially if one takes into account the white coat effect associated with current manual or oscillometric techniques for office BP measurement,” wrote Michael Roerecke, PhD, of the University of Toronto, and his colleagues.
Dr. Roerecke and his colleagues identified 31 articles with 9,279 participants (4,736 men, 4,543 women) where AOBP was compared with another method of BP reading, such as awake ambulatory, routine office, and research BP readings. The AOBP reading was performed with a fully automated oscillometric sphygmomanometer with the patient resting in a quiet area.
The researchers found systolic AOBP of 130 mm Hg was associated with significantly higher readings from routine office (mean difference, 14.5 mm Hg) or research BP readings (7.0 mm Hg), while participants had similar AOBP and awake ambulatory BP readings (0.3 mm Hg). All differences were statistically significant (P less than .001).
“If AOBP is to be used in clinical practice, readings must closely adhere to the procedures used in the AOBP studies in this meta-analysis, including multiple BP readings recorded with a fully automated oscillometric sphygmomanometer while the patient rests alone in a quiet place,” the researchers wrote.
Potential limitations of the study were the large statistical heterogeneity of the sample, though the researchers noted little clinical heterogeneity, and that most studies measured AOBP and awake ambulatory BP on the same day to limit differences in timing.
The authors reported no relevant conflicts of interest.
SOURCE: Roerecke M et al. JAMA Intern Med. 2019 Feb 4. doi: 10.1001/jamainternmed.2018.6551.
Automated office blood pressure readings appear to be more accurate than routine office readings and BP readings in research settings, according to a recent systematic review and meta-analysis.
Based on the evidence, automated office BP (AOBP) readings should now be the preferred method of reading a patient’s BP in clinical practice despite initial reluctance to incorporate this technique over other methods, the researchers wrote in JAMA Internal Medicine.
“The existing evidence supports the use of AOBP to screen patients for possible hypertension in clinical practice, especially if one takes into account the white coat effect associated with current manual or oscillometric techniques for office BP measurement,” wrote Michael Roerecke, PhD, of the University of Toronto, and his colleagues.
Dr. Roerecke and his colleagues identified 31 articles with 9,279 participants (4,736 men, 4,543 women) where AOBP was compared with another method of BP reading, such as awake ambulatory, routine office, and research BP readings. The AOBP reading was performed with a fully automated oscillometric sphygmomanometer with the patient resting in a quiet area.
The researchers found systolic AOBP of 130 mm Hg was associated with significantly higher readings from routine office (mean difference, 14.5 mm Hg) or research BP readings (7.0 mm Hg), while participants had similar AOBP and awake ambulatory BP readings (0.3 mm Hg). All differences were statistically significant (P less than .001).
“If AOBP is to be used in clinical practice, readings must closely adhere to the procedures used in the AOBP studies in this meta-analysis, including multiple BP readings recorded with a fully automated oscillometric sphygmomanometer while the patient rests alone in a quiet place,” the researchers wrote.
Potential limitations of the study were the large statistical heterogeneity of the sample, though the researchers noted little clinical heterogeneity, and that most studies measured AOBP and awake ambulatory BP on the same day to limit differences in timing.
The authors reported no relevant conflicts of interest.
SOURCE: Roerecke M et al. JAMA Intern Med. 2019 Feb 4. doi: 10.1001/jamainternmed.2018.6551.
Automated office blood pressure readings appear to be more accurate than routine office readings and BP readings in research settings, according to a recent systematic review and meta-analysis.
Based on the evidence, automated office BP (AOBP) readings should now be the preferred method of reading a patient’s BP in clinical practice despite initial reluctance to incorporate this technique over other methods, the researchers wrote in JAMA Internal Medicine.
“The existing evidence supports the use of AOBP to screen patients for possible hypertension in clinical practice, especially if one takes into account the white coat effect associated with current manual or oscillometric techniques for office BP measurement,” wrote Michael Roerecke, PhD, of the University of Toronto, and his colleagues.
Dr. Roerecke and his colleagues identified 31 articles with 9,279 participants (4,736 men, 4,543 women) where AOBP was compared with another method of BP reading, such as awake ambulatory, routine office, and research BP readings. The AOBP reading was performed with a fully automated oscillometric sphygmomanometer with the patient resting in a quiet area.
The researchers found systolic AOBP of 130 mm Hg was associated with significantly higher readings from routine office (mean difference, 14.5 mm Hg) or research BP readings (7.0 mm Hg), while participants had similar AOBP and awake ambulatory BP readings (0.3 mm Hg). All differences were statistically significant (P less than .001).
“If AOBP is to be used in clinical practice, readings must closely adhere to the procedures used in the AOBP studies in this meta-analysis, including multiple BP readings recorded with a fully automated oscillometric sphygmomanometer while the patient rests alone in a quiet place,” the researchers wrote.
Potential limitations of the study were the large statistical heterogeneity of the sample, though the researchers noted little clinical heterogeneity, and that most studies measured AOBP and awake ambulatory BP on the same day to limit differences in timing.
The authors reported no relevant conflicts of interest.
SOURCE: Roerecke M et al. JAMA Intern Med. 2019 Feb 4. doi: 10.1001/jamainternmed.2018.6551.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Automated office BP readings are lower than those taken in routine office or research settings and are similar to awake ambulatory BP readings.
Major finding: The mean difference between automated office BP readings was 14.5 mm Hg, compared with routine office systolic BP, and 7.0 mm Hg, compared with research systolic BP readings.
Study details: A systematic review and meta-analysis of 31 articles with 9,279 patients comparing automated office BP readings with awake ambulatory, routine office, and research BP readings.
Disclosures: The authors reported no relevant conflicts of interest.
Source: Roerecke M et al. JAMA Intern Med. 2019 Feb 4. doi: 10.1001/jamainternmed.2018.6551.
Insulin may be toxic to the placenta in early pregnancy
, according to findings from an experimental in vitro study published in Fertility and Sterility.
“Collectively these results demonstrate that insulin itself may be directly toxic to the early human placenta but that metformin can prevent these deleterious effects,” wrote Mario Vega, MD, of Columbia University Fertility Center, New York, and his colleagues. “If confirmed in animal and human studies, this would indicate that screening and treatment for insulin resistance should focus on hyperinsulinemia.”
Dr. Vega and his colleagues cultivated trophoblast cells from three healthy women scheduled for manual vacuum aspiration during the first trimester of pregnancy to study the effects of insulin exposure alone, while trophoblast cells were cultured from a different set of women for the insulin and metformin follow-up experiments. The researchers tested each experiment against a control group of cultivated lung fibroblast cells. Insulin was measured in doses of 0.2 nmol, 1 nmol, and 5 nmol, while metformin was measured at 10 micromol. The primary outcome measures examined were gamma-H2AX for DNA damage, cell proliferation assay for cell survival, and cleaved caspase-3 for apoptosis.
Within 48 hours, the cultures showed DNA damage and induction of apoptosis when exposed to 1 nmol of insulin, but researchers said pretreatment with metformin prevented these effects. Exposing cells to metformin after insulin reduced but did not eliminate the effects of insulin.
The researchers noted the study is limited because the effects of insulin and metformin have not been examined in vivo, and it is not known at what level insulin causes damage. In addition, they suggested downregulation of genes in trophoblasts caused by insulin could cause apoptosis and DNA damage to trophoblast cells.
“Although studies performed on kidney and colon cells suggest that one possible mechanism of action for insulin-mediated genotoxicity is through AKT activation of mitochondria and subsequent reactive oxygen species production, the exact mechanism is poorly understood,” Dr. Vega and colleagues said. “Future studies will be necessary to determine variability among subjects, as well as mechanisms of action through which insulin exerts its cytotoxicity and genotoxicity.”
This study was funded by a grant from the National Institutes of Health Human Placenta Project. The authors reported no relevant financial disclosures.
SOURCE: Vega M et al. Fertil Steril. 2019. doi: 10.1016/j.fertnstert.2018.11.032.
, according to findings from an experimental in vitro study published in Fertility and Sterility.
“Collectively these results demonstrate that insulin itself may be directly toxic to the early human placenta but that metformin can prevent these deleterious effects,” wrote Mario Vega, MD, of Columbia University Fertility Center, New York, and his colleagues. “If confirmed in animal and human studies, this would indicate that screening and treatment for insulin resistance should focus on hyperinsulinemia.”
Dr. Vega and his colleagues cultivated trophoblast cells from three healthy women scheduled for manual vacuum aspiration during the first trimester of pregnancy to study the effects of insulin exposure alone, while trophoblast cells were cultured from a different set of women for the insulin and metformin follow-up experiments. The researchers tested each experiment against a control group of cultivated lung fibroblast cells. Insulin was measured in doses of 0.2 nmol, 1 nmol, and 5 nmol, while metformin was measured at 10 micromol. The primary outcome measures examined were gamma-H2AX for DNA damage, cell proliferation assay for cell survival, and cleaved caspase-3 for apoptosis.
Within 48 hours, the cultures showed DNA damage and induction of apoptosis when exposed to 1 nmol of insulin, but researchers said pretreatment with metformin prevented these effects. Exposing cells to metformin after insulin reduced but did not eliminate the effects of insulin.
The researchers noted the study is limited because the effects of insulin and metformin have not been examined in vivo, and it is not known at what level insulin causes damage. In addition, they suggested downregulation of genes in trophoblasts caused by insulin could cause apoptosis and DNA damage to trophoblast cells.
“Although studies performed on kidney and colon cells suggest that one possible mechanism of action for insulin-mediated genotoxicity is through AKT activation of mitochondria and subsequent reactive oxygen species production, the exact mechanism is poorly understood,” Dr. Vega and colleagues said. “Future studies will be necessary to determine variability among subjects, as well as mechanisms of action through which insulin exerts its cytotoxicity and genotoxicity.”
This study was funded by a grant from the National Institutes of Health Human Placenta Project. The authors reported no relevant financial disclosures.
SOURCE: Vega M et al. Fertil Steril. 2019. doi: 10.1016/j.fertnstert.2018.11.032.
, according to findings from an experimental in vitro study published in Fertility and Sterility.
“Collectively these results demonstrate that insulin itself may be directly toxic to the early human placenta but that metformin can prevent these deleterious effects,” wrote Mario Vega, MD, of Columbia University Fertility Center, New York, and his colleagues. “If confirmed in animal and human studies, this would indicate that screening and treatment for insulin resistance should focus on hyperinsulinemia.”
Dr. Vega and his colleagues cultivated trophoblast cells from three healthy women scheduled for manual vacuum aspiration during the first trimester of pregnancy to study the effects of insulin exposure alone, while trophoblast cells were cultured from a different set of women for the insulin and metformin follow-up experiments. The researchers tested each experiment against a control group of cultivated lung fibroblast cells. Insulin was measured in doses of 0.2 nmol, 1 nmol, and 5 nmol, while metformin was measured at 10 micromol. The primary outcome measures examined were gamma-H2AX for DNA damage, cell proliferation assay for cell survival, and cleaved caspase-3 for apoptosis.
Within 48 hours, the cultures showed DNA damage and induction of apoptosis when exposed to 1 nmol of insulin, but researchers said pretreatment with metformin prevented these effects. Exposing cells to metformin after insulin reduced but did not eliminate the effects of insulin.
The researchers noted the study is limited because the effects of insulin and metformin have not been examined in vivo, and it is not known at what level insulin causes damage. In addition, they suggested downregulation of genes in trophoblasts caused by insulin could cause apoptosis and DNA damage to trophoblast cells.
“Although studies performed on kidney and colon cells suggest that one possible mechanism of action for insulin-mediated genotoxicity is through AKT activation of mitochondria and subsequent reactive oxygen species production, the exact mechanism is poorly understood,” Dr. Vega and colleagues said. “Future studies will be necessary to determine variability among subjects, as well as mechanisms of action through which insulin exerts its cytotoxicity and genotoxicity.”
This study was funded by a grant from the National Institutes of Health Human Placenta Project. The authors reported no relevant financial disclosures.
SOURCE: Vega M et al. Fertil Steril. 2019. doi: 10.1016/j.fertnstert.2018.11.032.
FROM FERTILITY & STERILITY
Key clinical point: Trophoblasts cultured during the first trimester of pregnancy exposed to insulin were more likely to have increased apoptosis, DNA damage, and decreased cell survival, while pretreatment with metformin prior to exposure with insulin prevented these effects.
Major finding: DNA damage and rate of apoptosis increased in trophoblast cells exposed to 1 nmol of insulin, and cell survival decreased, compared with primary lung fibroblast cells; treating the cells with metformin prior to exposure with insulin resulted in prevention of these effects.
Study details: An experimental in vitro study of first trimester trophoblast cells exposed to insulin and metformin.
Disclosures: This study was funded by a grant from the National Institutes of Health Human Placenta Project. The authors reported they had no relevant financial disclosures.
Source: Vega M et al. Fertil Steril. 2019. doi: 10.1016/j.fertnstert.2018.11.032.